Federal Practitioner

Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.

“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
 

Kidney disease in younger patients also linked to poorer outcomes

The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m², which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).

As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

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

Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.

“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
 

Kidney disease in younger patients also linked to poorer outcomes

The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m², which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).

As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

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

Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.

“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
 

Kidney disease in younger patients also linked to poorer outcomes

The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m², which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).

As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

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

Among those with type 2 diabetes, women receive some cardioprotective treatments less often than men, according to a post hoc analysis of data from the REWIND trial, conducted in nearly 10,000 adults from 24 countries.

At study entry, significantly fewer women received a statin, at 73%, or daily aspirin, at 44%, compared with men, who had treatment rates of 81% and 58%, respectively, Giulia Ferrannini, MD, reported at the annual meeting of the European Association for the Study of Diabetes.

The data also show that significantly fewer women received treatment with an ACE inhibitor or angiotensin-receptor blocker (ARB), at 80%, than men, at 83%, although the absolute between-group difference was modest. Rates of a fourth metric of appropriate treatment, receipt of antihypertensive medications if systolic blood pressure was at least 130 mm Hg, were nearly identical among women and men.
 

Cardiovascular risk in women “less well managed”

“This is confirmation that women are less well managed than men when it comes to cardiovascular risk, especially if they have [type 2] diabetes,” Dr. Ferrannini said in an interview.

Similar observations have been documented before, including in a report in 2019.

The treatment disparity by sex among the 9901 women and men with type 2 diabetes enrolled in REWIND is particularly striking because in clinical trials “patients are generally better managed than in the real world,” Dr. Ferrannini noted. “Despite this, the pattern of disadvantage to women was still evident,” she added.

“In cardiovascular protection the gender issue is preponderant. Women are less well treated,” she said.

REWIND is the cardiovascular outcomes trial for the once-weekly injectable glucagonlike peptide–1 receptor agonist dulaglutide (Trulicity, Lilly) in patients with type 2 diabetes.

The primary results, reported at the 2019 scientific sessions of the American Diabetes Association and simultaneously published in The Lancet, showed dulaglutide significantly reduced major adverse cardiovascular events (MACE) by 12%, compared with placebo. The study ran at about 300 centers worldwide, including many U.S. and Canadian sites, and 46% of enrolled patients were women.

But despite undertreatment, women had significantly better outcomes in terms of MACE, the primary endpoint, during a median 5.4 years of follow-up compared with men. After adjustment for sex, other baseline characteristics, and study-treatment assignment, women had a significant 27% lower composite rate of nonfatal MI, nonfatal stroke, or death from either cardiovascular or unknown causes, compared with men, said Dr. Ferrannini, a researcher at the Karolinska Institute in Stockholm.

The analysis by sex also showed that women had a significant outcome advantage, compared with men, for three of the four components of the combined MACE outcome: nonfatal MI, cardiovascular death, and all-cause death, as well as for the outcome of hospitalization for heart failure, which was not part of the composite MACE outcome. The only MACE outcome component that showed no significant between-group difference was nonfatal stroke, which had roughly equal incidence rates among women and men.
 

Women had half the prevalence of CVD at baseline

The results also showed that the women with type 2 diabetes enrolled in REWIND had a prevalence of existing cardiovascular disease of 20%, which was half the rate of men at study entry, at 41%. However, the between-sex differences in the primary outcome, as well as each of the individual cardiovascular disease outcomes, didn’t change based on whether or not patients had a history of cardiovascular disease at baseline.

Only one outcome showed a between-sex difference linked to prevalent cardiovascular disease at study entry, the rate of all-cause mortality, which was not significantly different between men and women with a history of cardiovascular disease, but was 39% lower in women compared with men without such a history.

“The good news is that, at baseline and after 2 years, the majority of participants were meeting the relevant treatment targets regardless of sex,” commented Peter Novodvorsky, MUDr, a diabetes researcher at the University of Sheffield (England), who chaired the session during which Dr. Ferrannini presented her findings.
 

A role for geography, or selection bias?

The new analyses did not examine whether the overall pattern of undertreatment of women differed among each of the 24 participating countries, or by region of the world.

“We have to assume that these results reflect current [routine] practice” in the 24 countries that contributed patients to the trial, noted Dr. Novodvorsky.

There is also “the well-known issue of selection bias” in randomized trials. The current findings raise the question of whether the women willing to take part in the trial somehow differed from the men, he suggested.

Dr. Ferrannini added: “Even if we do observe a gender difference in management, if the majority of women with type 2 diabetes are appropriately treated, this ‘restores’ their cardiovascular risk advantage, compared with men, with the exception of stroke.”

The main hypothesis generated by the post hoc analysis of REWIND is that “women with diabetes have better outcomes than men if they are treated properly,” she stressed, noting that this “would have to be tested in a trial designed to ascertain gender differences.”

REWIND was sponsored by Eli Lilly. Dr. Ferrannini has reported no relevant financial relationships.

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

Among those with type 2 diabetes, women receive some cardioprotective treatments less often than men, according to a post hoc analysis of data from the REWIND trial, conducted in nearly 10,000 adults from 24 countries.

At study entry, significantly fewer women received a statin, at 73%, or daily aspirin, at 44%, compared with men, who had treatment rates of 81% and 58%, respectively, Giulia Ferrannini, MD, reported at the annual meeting of the European Association for the Study of Diabetes.

The data also show that significantly fewer women received treatment with an ACE inhibitor or angiotensin-receptor blocker (ARB), at 80%, than men, at 83%, although the absolute between-group difference was modest. Rates of a fourth metric of appropriate treatment, receipt of antihypertensive medications if systolic blood pressure was at least 130 mm Hg, were nearly identical among women and men.
 

Cardiovascular risk in women “less well managed”

“This is confirmation that women are less well managed than men when it comes to cardiovascular risk, especially if they have [type 2] diabetes,” Dr. Ferrannini said in an interview.

Similar observations have been documented before, including in a report in 2019.

The treatment disparity by sex among the 9901 women and men with type 2 diabetes enrolled in REWIND is particularly striking because in clinical trials “patients are generally better managed than in the real world,” Dr. Ferrannini noted. “Despite this, the pattern of disadvantage to women was still evident,” she added.

“In cardiovascular protection the gender issue is preponderant. Women are less well treated,” she said.

REWIND is the cardiovascular outcomes trial for the once-weekly injectable glucagonlike peptide–1 receptor agonist dulaglutide (Trulicity, Lilly) in patients with type 2 diabetes.

The primary results, reported at the 2019 scientific sessions of the American Diabetes Association and simultaneously published in The Lancet, showed dulaglutide significantly reduced major adverse cardiovascular events (MACE) by 12%, compared with placebo. The study ran at about 300 centers worldwide, including many U.S. and Canadian sites, and 46% of enrolled patients were women.

But despite undertreatment, women had significantly better outcomes in terms of MACE, the primary endpoint, during a median 5.4 years of follow-up compared with men. After adjustment for sex, other baseline characteristics, and study-treatment assignment, women had a significant 27% lower composite rate of nonfatal MI, nonfatal stroke, or death from either cardiovascular or unknown causes, compared with men, said Dr. Ferrannini, a researcher at the Karolinska Institute in Stockholm.

The analysis by sex also showed that women had a significant outcome advantage, compared with men, for three of the four components of the combined MACE outcome: nonfatal MI, cardiovascular death, and all-cause death, as well as for the outcome of hospitalization for heart failure, which was not part of the composite MACE outcome. The only MACE outcome component that showed no significant between-group difference was nonfatal stroke, which had roughly equal incidence rates among women and men.
 

Women had half the prevalence of CVD at baseline

The results also showed that the women with type 2 diabetes enrolled in REWIND had a prevalence of existing cardiovascular disease of 20%, which was half the rate of men at study entry, at 41%. However, the between-sex differences in the primary outcome, as well as each of the individual cardiovascular disease outcomes, didn’t change based on whether or not patients had a history of cardiovascular disease at baseline.

Only one outcome showed a between-sex difference linked to prevalent cardiovascular disease at study entry, the rate of all-cause mortality, which was not significantly different between men and women with a history of cardiovascular disease, but was 39% lower in women compared with men without such a history.

“The good news is that, at baseline and after 2 years, the majority of participants were meeting the relevant treatment targets regardless of sex,” commented Peter Novodvorsky, MUDr, a diabetes researcher at the University of Sheffield (England), who chaired the session during which Dr. Ferrannini presented her findings.
 

A role for geography, or selection bias?

The new analyses did not examine whether the overall pattern of undertreatment of women differed among each of the 24 participating countries, or by region of the world.

“We have to assume that these results reflect current [routine] practice” in the 24 countries that contributed patients to the trial, noted Dr. Novodvorsky.

There is also “the well-known issue of selection bias” in randomized trials. The current findings raise the question of whether the women willing to take part in the trial somehow differed from the men, he suggested.

Dr. Ferrannini added: “Even if we do observe a gender difference in management, if the majority of women with type 2 diabetes are appropriately treated, this ‘restores’ their cardiovascular risk advantage, compared with men, with the exception of stroke.”

The main hypothesis generated by the post hoc analysis of REWIND is that “women with diabetes have better outcomes than men if they are treated properly,” she stressed, noting that this “would have to be tested in a trial designed to ascertain gender differences.”

REWIND was sponsored by Eli Lilly. Dr. Ferrannini has reported no relevant financial relationships.

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

Among those with type 2 diabetes, women receive some cardioprotective treatments less often than men, according to a post hoc analysis of data from the REWIND trial, conducted in nearly 10,000 adults from 24 countries.

At study entry, significantly fewer women received a statin, at 73%, or daily aspirin, at 44%, compared with men, who had treatment rates of 81% and 58%, respectively, Giulia Ferrannini, MD, reported at the annual meeting of the European Association for the Study of Diabetes.

The data also show that significantly fewer women received treatment with an ACE inhibitor or angiotensin-receptor blocker (ARB), at 80%, than men, at 83%, although the absolute between-group difference was modest. Rates of a fourth metric of appropriate treatment, receipt of antihypertensive medications if systolic blood pressure was at least 130 mm Hg, were nearly identical among women and men.
 

Cardiovascular risk in women “less well managed”

“This is confirmation that women are less well managed than men when it comes to cardiovascular risk, especially if they have [type 2] diabetes,” Dr. Ferrannini said in an interview.

Similar observations have been documented before, including in a report in 2019.

The treatment disparity by sex among the 9901 women and men with type 2 diabetes enrolled in REWIND is particularly striking because in clinical trials “patients are generally better managed than in the real world,” Dr. Ferrannini noted. “Despite this, the pattern of disadvantage to women was still evident,” she added.

“In cardiovascular protection the gender issue is preponderant. Women are less well treated,” she said.

REWIND is the cardiovascular outcomes trial for the once-weekly injectable glucagonlike peptide–1 receptor agonist dulaglutide (Trulicity, Lilly) in patients with type 2 diabetes.

The primary results, reported at the 2019 scientific sessions of the American Diabetes Association and simultaneously published in The Lancet, showed dulaglutide significantly reduced major adverse cardiovascular events (MACE) by 12%, compared with placebo. The study ran at about 300 centers worldwide, including many U.S. and Canadian sites, and 46% of enrolled patients were women.

But despite undertreatment, women had significantly better outcomes in terms of MACE, the primary endpoint, during a median 5.4 years of follow-up compared with men. After adjustment for sex, other baseline characteristics, and study-treatment assignment, women had a significant 27% lower composite rate of nonfatal MI, nonfatal stroke, or death from either cardiovascular or unknown causes, compared with men, said Dr. Ferrannini, a researcher at the Karolinska Institute in Stockholm.

The analysis by sex also showed that women had a significant outcome advantage, compared with men, for three of the four components of the combined MACE outcome: nonfatal MI, cardiovascular death, and all-cause death, as well as for the outcome of hospitalization for heart failure, which was not part of the composite MACE outcome. The only MACE outcome component that showed no significant between-group difference was nonfatal stroke, which had roughly equal incidence rates among women and men.
 

Women had half the prevalence of CVD at baseline

The results also showed that the women with type 2 diabetes enrolled in REWIND had a prevalence of existing cardiovascular disease of 20%, which was half the rate of men at study entry, at 41%. However, the between-sex differences in the primary outcome, as well as each of the individual cardiovascular disease outcomes, didn’t change based on whether or not patients had a history of cardiovascular disease at baseline.

Only one outcome showed a between-sex difference linked to prevalent cardiovascular disease at study entry, the rate of all-cause mortality, which was not significantly different between men and women with a history of cardiovascular disease, but was 39% lower in women compared with men without such a history.

“The good news is that, at baseline and after 2 years, the majority of participants were meeting the relevant treatment targets regardless of sex,” commented Peter Novodvorsky, MUDr, a diabetes researcher at the University of Sheffield (England), who chaired the session during which Dr. Ferrannini presented her findings.
 

A role for geography, or selection bias?

The new analyses did not examine whether the overall pattern of undertreatment of women differed among each of the 24 participating countries, or by region of the world.

“We have to assume that these results reflect current [routine] practice” in the 24 countries that contributed patients to the trial, noted Dr. Novodvorsky.

There is also “the well-known issue of selection bias” in randomized trials. The current findings raise the question of whether the women willing to take part in the trial somehow differed from the men, he suggested.

Dr. Ferrannini added: “Even if we do observe a gender difference in management, if the majority of women with type 2 diabetes are appropriately treated, this ‘restores’ their cardiovascular risk advantage, compared with men, with the exception of stroke.”

The main hypothesis generated by the post hoc analysis of REWIND is that “women with diabetes have better outcomes than men if they are treated properly,” she stressed, noting that this “would have to be tested in a trial designed to ascertain gender differences.”

REWIND was sponsored by Eli Lilly. Dr. Ferrannini has reported no relevant financial relationships.

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

Smokers are 80% more likely to be admitted to the hospital with COVID-19 than nonsmokers, according to an Oxford (England) University–led study.

Observational data was analyzed alongside hospital coronavirus test data and UK Biobank genetic information for the first time, and the findings are published in Thorax.

The data cover 421,469 people overall. Of these, 3.2% took a polymerase chain reaction swab test, 0.4% of these tested positive, 0.2% of them required hospitalization for COVID-19, and 0.1% of them died because of COVID-19.

When it came to smoking status, 59% had never smoked, 37% were ex-smokers, and 3% were current smokers.

Current smokers were 80% more likely to be admitted to hospital, and significantly more likely to die from COVID-19, than nonsmokers.
 

Time to quit

Heavy smokers who smoked more than 20 cigarettes a day were 6.11 times more likely to die from COVID-19 than people who had never smoked.

Analysis also showed those with a genetic predisposition to being smokers had a 45% higher infection risk, and 60% higher hospitalization risk.

The authors wrote: “Overall, the congruence of observational analyses indicating associations with recent smoking behaviors and [Mendelian randomization] analyses indicating associations with lifelong predisposition to smoking and smoking heaviness support a causal effect of smoking on COVID-19 severity.”

In a linked podcast, lead researcher Dr. Ashley Clift, said: “Our results strongly suggest that smoking is related to your risk of getting severe COVID, and just as smoking affects your risk of heart disease, different cancers, and all those other conditions we know smoking is linked to, it appears that it’s the same for COVID. So now might be as good a time as any to quit cigarettes and quit smoking.”

These results contrast with previous studies that have suggested a protective effect of smoking against COVID-19. In a linked editorial,  Anthony Laverty, PhD, and Christopher Millet, PhD, Imperial College London, wrote: “The idea that tobacco smoking may protect against COVID-19 was always an improbable one.”

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

Smokers are 80% more likely to be admitted to the hospital with COVID-19 than nonsmokers, according to an Oxford (England) University–led study.

Observational data was analyzed alongside hospital coronavirus test data and UK Biobank genetic information for the first time, and the findings are published in Thorax.

The data cover 421,469 people overall. Of these, 3.2% took a polymerase chain reaction swab test, 0.4% of these tested positive, 0.2% of them required hospitalization for COVID-19, and 0.1% of them died because of COVID-19.

When it came to smoking status, 59% had never smoked, 37% were ex-smokers, and 3% were current smokers.

Current smokers were 80% more likely to be admitted to hospital, and significantly more likely to die from COVID-19, than nonsmokers.
 

Time to quit

Heavy smokers who smoked more than 20 cigarettes a day were 6.11 times more likely to die from COVID-19 than people who had never smoked.

Analysis also showed those with a genetic predisposition to being smokers had a 45% higher infection risk, and 60% higher hospitalization risk.

The authors wrote: “Overall, the congruence of observational analyses indicating associations with recent smoking behaviors and [Mendelian randomization] analyses indicating associations with lifelong predisposition to smoking and smoking heaviness support a causal effect of smoking on COVID-19 severity.”

In a linked podcast, lead researcher Dr. Ashley Clift, said: “Our results strongly suggest that smoking is related to your risk of getting severe COVID, and just as smoking affects your risk of heart disease, different cancers, and all those other conditions we know smoking is linked to, it appears that it’s the same for COVID. So now might be as good a time as any to quit cigarettes and quit smoking.”

These results contrast with previous studies that have suggested a protective effect of smoking against COVID-19. In a linked editorial,  Anthony Laverty, PhD, and Christopher Millet, PhD, Imperial College London, wrote: “The idea that tobacco smoking may protect against COVID-19 was always an improbable one.”

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

Smokers are 80% more likely to be admitted to the hospital with COVID-19 than nonsmokers, according to an Oxford (England) University–led study.

Observational data was analyzed alongside hospital coronavirus test data and UK Biobank genetic information for the first time, and the findings are published in Thorax.

The data cover 421,469 people overall. Of these, 3.2% took a polymerase chain reaction swab test, 0.4% of these tested positive, 0.2% of them required hospitalization for COVID-19, and 0.1% of them died because of COVID-19.

When it came to smoking status, 59% had never smoked, 37% were ex-smokers, and 3% were current smokers.

Current smokers were 80% more likely to be admitted to hospital, and significantly more likely to die from COVID-19, than nonsmokers.
 

Time to quit

Heavy smokers who smoked more than 20 cigarettes a day were 6.11 times more likely to die from COVID-19 than people who had never smoked.

Analysis also showed those with a genetic predisposition to being smokers had a 45% higher infection risk, and 60% higher hospitalization risk.

The authors wrote: “Overall, the congruence of observational analyses indicating associations with recent smoking behaviors and [Mendelian randomization] analyses indicating associations with lifelong predisposition to smoking and smoking heaviness support a causal effect of smoking on COVID-19 severity.”

In a linked podcast, lead researcher Dr. Ashley Clift, said: “Our results strongly suggest that smoking is related to your risk of getting severe COVID, and just as smoking affects your risk of heart disease, different cancers, and all those other conditions we know smoking is linked to, it appears that it’s the same for COVID. So now might be as good a time as any to quit cigarettes and quit smoking.”

These results contrast with previous studies that have suggested a protective effect of smoking against COVID-19. In a linked editorial,  Anthony Laverty, PhD, and Christopher Millet, PhD, Imperial College London, wrote: “The idea that tobacco smoking may protect against COVID-19 was always an improbable one.”

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

Avanos medical to pay $22 million to resolve criminal charge for fraudulent misbranding of PPE

A U.S.-based multinational medical device corporation will pay more than $22 million to resolve a criminal charge regarding fraudulent misbranding of their surgical gowns.

Avanos Medical Inc, which as its U.S. headquarters in Alpharetta, Georgia, is charged with one count of introducing misbranded surgical gowns into interstate commerce with the intent to defraud and mislead.

According to the Department of Justice, the company knowingly falsely labeled its MicroCool surgical gowns as providing AAMI Level 4 protection (the highest level) against fluid and virus penetration. Under the standards set by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), the highest protection level for surgical gowns is reserved for gowns intended to be used in surgeries and other high-risk medical procedures on patients suspected of having infectious diseases.

Avanos admitted to selling hundreds of thousands of MicroCool gowns that were falsely labeled as AAMI Level 4 between late 2014 and early 2015, as well as directly lying to customers about the gowns’ protective capacities. In total, Avanos sold almost $9 million of misbranded MicroCool gowns.

“The last thing health care workers should have to worry about is whether their personal protective equipment lives up to manufacturers’ claims,” said Acting U.S. Attorney Prerak Shah for the Northern District of Texas. “Misbranded PPE can pose serious risks to medical professionals and patients alike.”
 

Company pays $38.75 million to settle allegations of knowingly selling defective devices 

Medical device manufacturers Alere and Alere San Diego (collectively, Alere) have agreed to pay almost $39 million to resolve allegations that they violated the False Claims Act by billing, and causing others to bill, the Medicare program for defective rapid point-of-care testing devices. 

From 2008 to 2016, the Department of Justice alleges, Alere knowingly sold defective INRatio blood coagulation monitors used by Medicare beneficiaries who were taking anticoagulants. The software algorithms in the monitors contained a material defect, which Alere had found in their research, to cause inaccurate readings. Blood coagulation monitoring is essential for the safety of these patients, enabling them to maintain a safe dosage of their medications. Taking too much of an anticoagulant can cause major bleeding, while taking too little can cause blood clots that lead to strokes. 

While Alere was aware that these devices were linked to over a dozen deaths and hundreds of injuries, the company continued to conceal the defect and billed Medicare for the devices.

In 2016, the product was taken off the market at the request of the FDA.
 

Mass. doctor, wife charged in international money laundering, fraud scheme

Massachusetts psychiatrist Rahim Shafa, MD, and his wife and office manager, Nahid Tormosi Shafa, are charged in connection to an international money laundering scheme involving importing illegal and misbranded drugs. 

Through Shafa’s company, Novel Psychopharmacology, the two allegedly filed false and fraudulent Medicare reimbursement claims from 2016-2019, then deposited the money in their bank accounts, according to federal officials. From 2008-2018, the couple also engaged in an international money laundering scheme to purchase naltrexone pellet implants, disulfiram pellet implants, and injections from Hong Kong that were not approved by the FDA. According to officials, they falsified shipping documents, disguising the naltrexone pellet implants as “plastic beads in plastic tubes” to receive the drugs. They then offered to sell these drugs to patients of Novel Psychopharmacology. 

Rahim Shafa was indicted on conspiracies of international money laundering, health care fraud, and defrauding the United States, as well as illegally importing merchandise and purposely delivering misbranded drugs. His wife was indicted on one count each of health care fraud conspiracy and international money laundering conspiracy.
 

Jury convicts medical equipment company owners of $27 million fraud

A federal jury in Texas convicted the owners of two durable medical equipment (DME) companies linked to a scheme to defraud Medicare.

Leah Hagen, 49, and Michael Hagen, 54, were convicted of one count of conspiracy to defraud the United States and to pay and receive health care kickbacks and one count of conspiracy to commit money laundering. The defendants owned and operated Metro DME Supply and Ortho Pain Solutions. 

Ms. Hagen and Mr. Hagen paid a fixed rate per DME item in exchange for prescriptions and paperwork completed by telemedicine doctors that were used to submit false claims to Medicare, which totaled about $59 million. They were paid $27 million, and wired millions to their personal bank accounts. The defendants paid illegal bribes and kickbacks and wired money to their co-conspirator’s call center in the Philippines that provided signed doctor’s orders for orthotic braces. 

At trial, evidence showed emails between Leah and Michael Hagen and their co-conspirators outlining a per-product pricing structure for orthotic braces, but not disclosing their agreement as one for marketing and other services.

At sentencing, the Hagens each face a maximum sentence of 25 years in prison.

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

Avanos medical to pay $22 million to resolve criminal charge for fraudulent misbranding of PPE

A U.S.-based multinational medical device corporation will pay more than $22 million to resolve a criminal charge regarding fraudulent misbranding of their surgical gowns.

Avanos Medical Inc, which as its U.S. headquarters in Alpharetta, Georgia, is charged with one count of introducing misbranded surgical gowns into interstate commerce with the intent to defraud and mislead.

According to the Department of Justice, the company knowingly falsely labeled its MicroCool surgical gowns as providing AAMI Level 4 protection (the highest level) against fluid and virus penetration. Under the standards set by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), the highest protection level for surgical gowns is reserved for gowns intended to be used in surgeries and other high-risk medical procedures on patients suspected of having infectious diseases.

Avanos admitted to selling hundreds of thousands of MicroCool gowns that were falsely labeled as AAMI Level 4 between late 2014 and early 2015, as well as directly lying to customers about the gowns’ protective capacities. In total, Avanos sold almost $9 million of misbranded MicroCool gowns.

“The last thing health care workers should have to worry about is whether their personal protective equipment lives up to manufacturers’ claims,” said Acting U.S. Attorney Prerak Shah for the Northern District of Texas. “Misbranded PPE can pose serious risks to medical professionals and patients alike.”
 

Company pays $38.75 million to settle allegations of knowingly selling defective devices 

Medical device manufacturers Alere and Alere San Diego (collectively, Alere) have agreed to pay almost $39 million to resolve allegations that they violated the False Claims Act by billing, and causing others to bill, the Medicare program for defective rapid point-of-care testing devices. 

From 2008 to 2016, the Department of Justice alleges, Alere knowingly sold defective INRatio blood coagulation monitors used by Medicare beneficiaries who were taking anticoagulants. The software algorithms in the monitors contained a material defect, which Alere had found in their research, to cause inaccurate readings. Blood coagulation monitoring is essential for the safety of these patients, enabling them to maintain a safe dosage of their medications. Taking too much of an anticoagulant can cause major bleeding, while taking too little can cause blood clots that lead to strokes. 

While Alere was aware that these devices were linked to over a dozen deaths and hundreds of injuries, the company continued to conceal the defect and billed Medicare for the devices.

In 2016, the product was taken off the market at the request of the FDA.
 

Mass. doctor, wife charged in international money laundering, fraud scheme

Massachusetts psychiatrist Rahim Shafa, MD, and his wife and office manager, Nahid Tormosi Shafa, are charged in connection to an international money laundering scheme involving importing illegal and misbranded drugs. 

Through Shafa’s company, Novel Psychopharmacology, the two allegedly filed false and fraudulent Medicare reimbursement claims from 2016-2019, then deposited the money in their bank accounts, according to federal officials. From 2008-2018, the couple also engaged in an international money laundering scheme to purchase naltrexone pellet implants, disulfiram pellet implants, and injections from Hong Kong that were not approved by the FDA. According to officials, they falsified shipping documents, disguising the naltrexone pellet implants as “plastic beads in plastic tubes” to receive the drugs. They then offered to sell these drugs to patients of Novel Psychopharmacology. 

Rahim Shafa was indicted on conspiracies of international money laundering, health care fraud, and defrauding the United States, as well as illegally importing merchandise and purposely delivering misbranded drugs. His wife was indicted on one count each of health care fraud conspiracy and international money laundering conspiracy.
 

Jury convicts medical equipment company owners of $27 million fraud

A federal jury in Texas convicted the owners of two durable medical equipment (DME) companies linked to a scheme to defraud Medicare.

Leah Hagen, 49, and Michael Hagen, 54, were convicted of one count of conspiracy to defraud the United States and to pay and receive health care kickbacks and one count of conspiracy to commit money laundering. The defendants owned and operated Metro DME Supply and Ortho Pain Solutions. 

Ms. Hagen and Mr. Hagen paid a fixed rate per DME item in exchange for prescriptions and paperwork completed by telemedicine doctors that were used to submit false claims to Medicare, which totaled about $59 million. They were paid $27 million, and wired millions to their personal bank accounts. The defendants paid illegal bribes and kickbacks and wired money to their co-conspirator’s call center in the Philippines that provided signed doctor’s orders for orthotic braces. 

At trial, evidence showed emails between Leah and Michael Hagen and their co-conspirators outlining a per-product pricing structure for orthotic braces, but not disclosing their agreement as one for marketing and other services.

At sentencing, the Hagens each face a maximum sentence of 25 years in prison.

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

Avanos medical to pay $22 million to resolve criminal charge for fraudulent misbranding of PPE

A U.S.-based multinational medical device corporation will pay more than $22 million to resolve a criminal charge regarding fraudulent misbranding of their surgical gowns.

Avanos Medical Inc, which as its U.S. headquarters in Alpharetta, Georgia, is charged with one count of introducing misbranded surgical gowns into interstate commerce with the intent to defraud and mislead.

According to the Department of Justice, the company knowingly falsely labeled its MicroCool surgical gowns as providing AAMI Level 4 protection (the highest level) against fluid and virus penetration. Under the standards set by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), the highest protection level for surgical gowns is reserved for gowns intended to be used in surgeries and other high-risk medical procedures on patients suspected of having infectious diseases.

Avanos admitted to selling hundreds of thousands of MicroCool gowns that were falsely labeled as AAMI Level 4 between late 2014 and early 2015, as well as directly lying to customers about the gowns’ protective capacities. In total, Avanos sold almost $9 million of misbranded MicroCool gowns.

“The last thing health care workers should have to worry about is whether their personal protective equipment lives up to manufacturers’ claims,” said Acting U.S. Attorney Prerak Shah for the Northern District of Texas. “Misbranded PPE can pose serious risks to medical professionals and patients alike.”
 

Company pays $38.75 million to settle allegations of knowingly selling defective devices 

Medical device manufacturers Alere and Alere San Diego (collectively, Alere) have agreed to pay almost $39 million to resolve allegations that they violated the False Claims Act by billing, and causing others to bill, the Medicare program for defective rapid point-of-care testing devices. 

From 2008 to 2016, the Department of Justice alleges, Alere knowingly sold defective INRatio blood coagulation monitors used by Medicare beneficiaries who were taking anticoagulants. The software algorithms in the monitors contained a material defect, which Alere had found in their research, to cause inaccurate readings. Blood coagulation monitoring is essential for the safety of these patients, enabling them to maintain a safe dosage of their medications. Taking too much of an anticoagulant can cause major bleeding, while taking too little can cause blood clots that lead to strokes. 

While Alere was aware that these devices were linked to over a dozen deaths and hundreds of injuries, the company continued to conceal the defect and billed Medicare for the devices.

In 2016, the product was taken off the market at the request of the FDA.
 

Mass. doctor, wife charged in international money laundering, fraud scheme

Massachusetts psychiatrist Rahim Shafa, MD, and his wife and office manager, Nahid Tormosi Shafa, are charged in connection to an international money laundering scheme involving importing illegal and misbranded drugs. 

Through Shafa’s company, Novel Psychopharmacology, the two allegedly filed false and fraudulent Medicare reimbursement claims from 2016-2019, then deposited the money in their bank accounts, according to federal officials. From 2008-2018, the couple also engaged in an international money laundering scheme to purchase naltrexone pellet implants, disulfiram pellet implants, and injections from Hong Kong that were not approved by the FDA. According to officials, they falsified shipping documents, disguising the naltrexone pellet implants as “plastic beads in plastic tubes” to receive the drugs. They then offered to sell these drugs to patients of Novel Psychopharmacology. 

Rahim Shafa was indicted on conspiracies of international money laundering, health care fraud, and defrauding the United States, as well as illegally importing merchandise and purposely delivering misbranded drugs. His wife was indicted on one count each of health care fraud conspiracy and international money laundering conspiracy.
 

Jury convicts medical equipment company owners of $27 million fraud

A federal jury in Texas convicted the owners of two durable medical equipment (DME) companies linked to a scheme to defraud Medicare.

Leah Hagen, 49, and Michael Hagen, 54, were convicted of one count of conspiracy to defraud the United States and to pay and receive health care kickbacks and one count of conspiracy to commit money laundering. The defendants owned and operated Metro DME Supply and Ortho Pain Solutions. 

Ms. Hagen and Mr. Hagen paid a fixed rate per DME item in exchange for prescriptions and paperwork completed by telemedicine doctors that were used to submit false claims to Medicare, which totaled about $59 million. They were paid $27 million, and wired millions to their personal bank accounts. The defendants paid illegal bribes and kickbacks and wired money to their co-conspirator’s call center in the Philippines that provided signed doctor’s orders for orthotic braces. 

At trial, evidence showed emails between Leah and Michael Hagen and their co-conspirators outlining a per-product pricing structure for orthotic braces, but not disclosing their agreement as one for marketing and other services.

At sentencing, the Hagens each face a maximum sentence of 25 years in prison.

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

A common inert ingredient may be the culprit behind the rare allergic reactions reported among individuals who have received mRNA COVID-19 vaccines, according to investigators at a large regional health center that was among the first to administer the shots.

Blood samples from 10 of 11 individuals with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of both the Pfizer and Moderna mRNA  vaccines, according to a report in JAMA Network Open.

In total, only 22 individuals had suspected allergic reactions out of nearly 39,000 mRNA COVID-19 vaccine doses administered, the investigators reported, noting that the reactions were generally mild and all fully resolved.

Those findings should be reassuring to individuals who are reticent to sign up for a COVID-19 vaccine because of fear of an allergic reaction, said study senior author Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

“We’re hoping that this word will get out and then that the companies could also think about making vaccines that have other products in them that don’t include polyethylene glycol,” Dr. Nadeau said in an interview.

PEG is a compound used in many products, including pharmaceuticals, cosmetics, and food. In the mRNA COVID-19 vaccines, PEG serves to stabilize the lipid nanoparticles that help protect and transport mRNA. However, its use in this setting has been linked to allergic reactions in this and previous studies.

No immunoglobulin E (IgE) antibodies to PEG were detected among the 22 individuals with suspected allergic reactions to mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. That suggests non-IgE mediated allergic reactions to PEG may be implicated for the majority of cases, Dr. Nadeau said.

This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic response is behind the suspected allergic reactions that are occurring after mRNA COVID-19 vaccine, said Aleena Banerji, MD, associate professor at Harvard Medical School, Boston, and clinical director of the Drug Allergy Program at Massachusetts General Hospital.

“We need to further understand the mechanism of these reactions, but what we know is that IGE mediated allergy to excipients like PEG is probably not the main cause,” Dr. Banerji, who was not involved in the study, said in an interview.

In a recent research letter published in JAMA Internal Medicine, Dr. Banerji and coauthors reported that all individuals with immediate suspected allergic reactions to mRNA COVID-19 vaccine went on to tolerate the second dose, with mild symptoms reported in the minority of patients (32 out of 159, or about 20%).

“Again, that is very consistent with not having an IgE-mediated allergy, so it seems to all be fitting with that picture,” Dr. Banerji said.

The case series by Dr. Nadeau and coauthors was based on review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most mRNA vaccine recipients were Stanford-affiliated health care workers, according to the report.

Among recipients of those doses, they identified 148 individuals who had anaphylaxis-related ICD-10 codes recorded over the same time period. In a review of medical records, investigators pinpointed 22 individuals as having suspected allergy and invited them to participate in follow-up allergy testing.

A total of 11 individuals underwent skin prick testing, but none of them tested positive to PEG or to polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients tested positive to the same mRNA vaccine they had previously received, according to the report.

Those same 11 individuals also underwent basophil activation testing (BAT). In contrast to the skin testing results, BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for their administered vaccine in all 11 cases, the report shows.

High levels of IgG to PEG were identified in blood samples of individuals with an allergy to the vaccine. Investigators said it’s possible that the BAT results were activated due to IgG via complement activation–related pseudoallergy, or CARPA, as has been hypothesized by some other investigators.

The negative skin prick testing results for PEG, which contrast with the positive BAT results to PEG, suggest that the former may not be appropriate for use as a predictive marker of potential vaccine allergy, according to Dr. Nadeau.

“The take-home message for doctors is to be careful,” she said. “Don’t assume that just because the person skin-tests negative to PEG or to the vaccine itself that you’re out of the woods, because the skin test would be often negative in those scenarios.”

The study was supported by a grants from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation. Dr. Nadeau reports numerous conflicts with various sources in the industry. Dr. Banerji has disclosed no relevant financial relationships.

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

A common inert ingredient may be the culprit behind the rare allergic reactions reported among individuals who have received mRNA COVID-19 vaccines, according to investigators at a large regional health center that was among the first to administer the shots.

Blood samples from 10 of 11 individuals with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of both the Pfizer and Moderna mRNA  vaccines, according to a report in JAMA Network Open.

In total, only 22 individuals had suspected allergic reactions out of nearly 39,000 mRNA COVID-19 vaccine doses administered, the investigators reported, noting that the reactions were generally mild and all fully resolved.

Those findings should be reassuring to individuals who are reticent to sign up for a COVID-19 vaccine because of fear of an allergic reaction, said study senior author Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

“We’re hoping that this word will get out and then that the companies could also think about making vaccines that have other products in them that don’t include polyethylene glycol,” Dr. Nadeau said in an interview.

PEG is a compound used in many products, including pharmaceuticals, cosmetics, and food. In the mRNA COVID-19 vaccines, PEG serves to stabilize the lipid nanoparticles that help protect and transport mRNA. However, its use in this setting has been linked to allergic reactions in this and previous studies.

No immunoglobulin E (IgE) antibodies to PEG were detected among the 22 individuals with suspected allergic reactions to mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. That suggests non-IgE mediated allergic reactions to PEG may be implicated for the majority of cases, Dr. Nadeau said.

This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic response is behind the suspected allergic reactions that are occurring after mRNA COVID-19 vaccine, said Aleena Banerji, MD, associate professor at Harvard Medical School, Boston, and clinical director of the Drug Allergy Program at Massachusetts General Hospital.

“We need to further understand the mechanism of these reactions, but what we know is that IGE mediated allergy to excipients like PEG is probably not the main cause,” Dr. Banerji, who was not involved in the study, said in an interview.

In a recent research letter published in JAMA Internal Medicine, Dr. Banerji and coauthors reported that all individuals with immediate suspected allergic reactions to mRNA COVID-19 vaccine went on to tolerate the second dose, with mild symptoms reported in the minority of patients (32 out of 159, or about 20%).

“Again, that is very consistent with not having an IgE-mediated allergy, so it seems to all be fitting with that picture,” Dr. Banerji said.

The case series by Dr. Nadeau and coauthors was based on review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most mRNA vaccine recipients were Stanford-affiliated health care workers, according to the report.

Among recipients of those doses, they identified 148 individuals who had anaphylaxis-related ICD-10 codes recorded over the same time period. In a review of medical records, investigators pinpointed 22 individuals as having suspected allergy and invited them to participate in follow-up allergy testing.

A total of 11 individuals underwent skin prick testing, but none of them tested positive to PEG or to polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients tested positive to the same mRNA vaccine they had previously received, according to the report.

Those same 11 individuals also underwent basophil activation testing (BAT). In contrast to the skin testing results, BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for their administered vaccine in all 11 cases, the report shows.

High levels of IgG to PEG were identified in blood samples of individuals with an allergy to the vaccine. Investigators said it’s possible that the BAT results were activated due to IgG via complement activation–related pseudoallergy, or CARPA, as has been hypothesized by some other investigators.

The negative skin prick testing results for PEG, which contrast with the positive BAT results to PEG, suggest that the former may not be appropriate for use as a predictive marker of potential vaccine allergy, according to Dr. Nadeau.

“The take-home message for doctors is to be careful,” she said. “Don’t assume that just because the person skin-tests negative to PEG or to the vaccine itself that you’re out of the woods, because the skin test would be often negative in those scenarios.”

The study was supported by a grants from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation. Dr. Nadeau reports numerous conflicts with various sources in the industry. Dr. Banerji has disclosed no relevant financial relationships.

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

A common inert ingredient may be the culprit behind the rare allergic reactions reported among individuals who have received mRNA COVID-19 vaccines, according to investigators at a large regional health center that was among the first to administer the shots.

Blood samples from 10 of 11 individuals with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of both the Pfizer and Moderna mRNA  vaccines, according to a report in JAMA Network Open.

In total, only 22 individuals had suspected allergic reactions out of nearly 39,000 mRNA COVID-19 vaccine doses administered, the investigators reported, noting that the reactions were generally mild and all fully resolved.

Those findings should be reassuring to individuals who are reticent to sign up for a COVID-19 vaccine because of fear of an allergic reaction, said study senior author Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

“We’re hoping that this word will get out and then that the companies could also think about making vaccines that have other products in them that don’t include polyethylene glycol,” Dr. Nadeau said in an interview.

PEG is a compound used in many products, including pharmaceuticals, cosmetics, and food. In the mRNA COVID-19 vaccines, PEG serves to stabilize the lipid nanoparticles that help protect and transport mRNA. However, its use in this setting has been linked to allergic reactions in this and previous studies.

No immunoglobulin E (IgE) antibodies to PEG were detected among the 22 individuals with suspected allergic reactions to mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. That suggests non-IgE mediated allergic reactions to PEG may be implicated for the majority of cases, Dr. Nadeau said.

This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic response is behind the suspected allergic reactions that are occurring after mRNA COVID-19 vaccine, said Aleena Banerji, MD, associate professor at Harvard Medical School, Boston, and clinical director of the Drug Allergy Program at Massachusetts General Hospital.

“We need to further understand the mechanism of these reactions, but what we know is that IGE mediated allergy to excipients like PEG is probably not the main cause,” Dr. Banerji, who was not involved in the study, said in an interview.

In a recent research letter published in JAMA Internal Medicine, Dr. Banerji and coauthors reported that all individuals with immediate suspected allergic reactions to mRNA COVID-19 vaccine went on to tolerate the second dose, with mild symptoms reported in the minority of patients (32 out of 159, or about 20%).

“Again, that is very consistent with not having an IgE-mediated allergy, so it seems to all be fitting with that picture,” Dr. Banerji said.

The case series by Dr. Nadeau and coauthors was based on review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most mRNA vaccine recipients were Stanford-affiliated health care workers, according to the report.

Among recipients of those doses, they identified 148 individuals who had anaphylaxis-related ICD-10 codes recorded over the same time period. In a review of medical records, investigators pinpointed 22 individuals as having suspected allergy and invited them to participate in follow-up allergy testing.

A total of 11 individuals underwent skin prick testing, but none of them tested positive to PEG or to polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients tested positive to the same mRNA vaccine they had previously received, according to the report.

Those same 11 individuals also underwent basophil activation testing (BAT). In contrast to the skin testing results, BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for their administered vaccine in all 11 cases, the report shows.

High levels of IgG to PEG were identified in blood samples of individuals with an allergy to the vaccine. Investigators said it’s possible that the BAT results were activated due to IgG via complement activation–related pseudoallergy, or CARPA, as has been hypothesized by some other investigators.

The negative skin prick testing results for PEG, which contrast with the positive BAT results to PEG, suggest that the former may not be appropriate for use as a predictive marker of potential vaccine allergy, according to Dr. Nadeau.

“The take-home message for doctors is to be careful,” she said. “Don’t assume that just because the person skin-tests negative to PEG or to the vaccine itself that you’re out of the woods, because the skin test would be often negative in those scenarios.”

The study was supported by a grants from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation. Dr. Nadeau reports numerous conflicts with various sources in the industry. Dr. Banerji has disclosed no relevant financial relationships.

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

The US Department of Veterans Affairs (VA) has issued a new policy statement to help ensure that active-duty service members who were discharged for their sexual orientation under the Don’t Ask, Don’t Tell policy will be able to receive full VA benefits.

“[A] great injustice was remedied and a tremendous weight was finally lifted off the shoulders of tens of thousands of dedicated American service members,” President Biden said on September 20 as the country commemorated the 10th anniversary of the repeal of “Don’t Ask, Don’t Tell,” the policy that barred lesbian, gay, bisexual, transgender, and queer (LGBTQ+) service members from serving openly.

Prior to DADT, if active-duty service members spoke out about their sexual orientation, they ran the risk of being hounded, shunned, in some cases assaulted, and discharged. If they kept it a secret, they felt they were living a lie, unable to be their whole selves. More than 100,000 were discharged because of their sexual orientation or gender identity.

Although Don’t Ask, Don’t Tell was a “compromise” law that purposed to protect them, LGBTQ+ service members were still at risk for harassment and abuse. Nor did the law protect them from discharge. Some 14,000 LGBTQ+ service members were discharged while DADT was in effect. And those who received “other than honorable” (OTH) discharges could be excluded from receiving services and benefits.

The 2011 repeal followed a “hard-fought battle,” said a release from the Human Rights Campaign, which led a coalition of members, supporters, elected officials, 70+ organizations, and 20,000 veterans to get the law overturned. HRC staff coordinated grassroots efforts and sent 19 million e-mails to members and supporters, in turn generating an “unprecedented” 625,000 e-mails and 50,000 handwritten letters to members of Congress.

After the repeal, the VA began the long process of inclusion for LGBTQ+ veterans. “At VA, we continuously work not only to meet the needs of LGBTQ+ veterans, but also to address ongoing issues that LGBTQ+ veterans face as a result of the military’s decades-long official policy of homophobia and transphobia,” Kayla Williams, assistant secretary for public affairs in VA’s Office of Public and Intergovernmental Affairs wrote in the Secretary’s blog.

The VA “recognizes that the trauma caused by the military’s decades-long policy of discrimination against LGBTQ+ people cannot be undone in a few short months,” she continued, but the Biden administration and Secretary McDonough are “taking the steps necessary to begin addressing the pain that such policies have created.”

President Biden, in his remarks, noted that as a US Senator, he had supported allowing service members to serve openly and, as Vice President, championed the repeal. He said, “I am honored to be Commander-in-Chief of the strongest and most inclusive military in our nation’s history. Today, our military doesn’t just welcome LGBTQ+ service members—it is led at the highest levels by brave LGBTQ+ veterans, including Under Secretary of the Air Force Gina Ortiz Jones and Assistant Secretary of Defense for Readiness Shawn Skelly, who served under Don’t Ask, Don’t Tell. I was gratified to appoint the first openly gay Senate-confirmed Cabinet member, Secretary Pete Buttigieg, a lieutenant in the U.S. Navy Reserve and Afghanistan veteran who joined the military under the Don’t Ask, Don’t Tell policy. And during my first week in office, I proudly delivered on my pledge to repeal the discriminatory ban on open service by patriotic transgender service members.”

In early September, Rep. Chris Pappas (D-NH), a member of the House Veterans Affairs Committee and Co-Chair of the Equality Caucus, reintroduced the SERVE (Securing the Rights our Veterans Earned) Act. The act, which is co-sponsored by Reps. Mike Levin (D-CA), Kathleen Rice (D-NY), Anthony Brown (D-MD), and Jackie Speier (D-CA), would ensure LGBTQ+ veterans who received an OTH or Entry-Level Separation discharge solely due to sexual orientation or gender identity are afforded the VA benefits they rightfully earned, including access to VA healthcare, and education, burial and memorial services, and home loans. The act includes veterans who were issued “blue discharges” during World War II and veterans discharged under former President Trump’s ban on transgender service members. The legislation has been endorsed by the Congressional LGBTQ+ Equality Caucus and is supported by more than 45 representatives.

There are processes for those veterans through which they can have their discharge papers and separation statuses reviewed and modified, Pappas said in a release, but “it can take months for the changes to take effect, and many of these veterans do not even realize they are eligible.”

Earlier this year, Veterans Affairs Secretary Denis McDonough made it a priority to ensure that LGBTQ+ veterans have the same level of access to VA care and services that all other veterans have. Among other things, he established a task force to examine how VA policies hinder or prohibit access to care and services and remove barriers that transgender veterans face in accessing gender-affirming care.

The VA is also taking steps, Williams noted, to clarify VA policy for veterans who were given OTH discharges based on homosexual conduct, gender identity or HIV status. Under this newly issued guidance, VA adjudicators shall find that all discharged service members whose separation was due to sexual orientation, gender identity or HIV status are considered “Veterans” who may be eligible for VA benefits, like VR&E, home loan guaranty, compensation and pension, health care, homeless program and/or burial benefits, so long as the record does not implicate a statutory or regulatory bar to benefits.

The policy statement does not represent a change in law, as veterans who were discharged under DADT alone have been generally eligible for benefits under current statute and regulation. However, it reiterates what constitutes eligibility for benefits under law. In addition, every Character of Discharge case that is initially considered for denial will also get a second look before that action is taken.

“Given that large numbers of LGBTQ+ veterans who were affected by previous homophobic and transphobic policies have not applied for a discharge upgrade due to the perception that the process could be onerous,” Williams wrote, “we are hopeful that this policy statement encourages more of them to contact VA to determine their eligibility for care and services.”

Today, according to the Human Right Campaign, nearly 6.1% of US military personnel self-identify as LGBTQ. Williams, herself a bisexual veteran, said she chose to present as straight during the push to repeal DADT. “I could talk credibly about how the lack of sufficient Arabic linguists harmed our effectiveness downrange, and my own identity seemed irrelevant. It took many years for me to shed the toxic legacy of having served under DADT and come back out of the closet; I’m proud to recognize this anniversary as my authentic self.”

The US Department of Veterans Affairs (VA) has issued a new policy statement to help ensure that active-duty service members who were discharged for their sexual orientation under the Don’t Ask, Don’t Tell policy will be able to receive full VA benefits.

“[A] great injustice was remedied and a tremendous weight was finally lifted off the shoulders of tens of thousands of dedicated American service members,” President Biden said on September 20 as the country commemorated the 10th anniversary of the repeal of “Don’t Ask, Don’t Tell,” the policy that barred lesbian, gay, bisexual, transgender, and queer (LGBTQ+) service members from serving openly.

Prior to DADT, if active-duty service members spoke out about their sexual orientation, they ran the risk of being hounded, shunned, in some cases assaulted, and discharged. If they kept it a secret, they felt they were living a lie, unable to be their whole selves. More than 100,000 were discharged because of their sexual orientation or gender identity.

Although Don’t Ask, Don’t Tell was a “compromise” law that purposed to protect them, LGBTQ+ service members were still at risk for harassment and abuse. Nor did the law protect them from discharge. Some 14,000 LGBTQ+ service members were discharged while DADT was in effect. And those who received “other than honorable” (OTH) discharges could be excluded from receiving services and benefits.

The 2011 repeal followed a “hard-fought battle,” said a release from the Human Rights Campaign, which led a coalition of members, supporters, elected officials, 70+ organizations, and 20,000 veterans to get the law overturned. HRC staff coordinated grassroots efforts and sent 19 million e-mails to members and supporters, in turn generating an “unprecedented” 625,000 e-mails and 50,000 handwritten letters to members of Congress.

After the repeal, the VA began the long process of inclusion for LGBTQ+ veterans. “At VA, we continuously work not only to meet the needs of LGBTQ+ veterans, but also to address ongoing issues that LGBTQ+ veterans face as a result of the military’s decades-long official policy of homophobia and transphobia,” Kayla Williams, assistant secretary for public affairs in VA’s Office of Public and Intergovernmental Affairs wrote in the Secretary’s blog.

The VA “recognizes that the trauma caused by the military’s decades-long policy of discrimination against LGBTQ+ people cannot be undone in a few short months,” she continued, but the Biden administration and Secretary McDonough are “taking the steps necessary to begin addressing the pain that such policies have created.”

President Biden, in his remarks, noted that as a US Senator, he had supported allowing service members to serve openly and, as Vice President, championed the repeal. He said, “I am honored to be Commander-in-Chief of the strongest and most inclusive military in our nation’s history. Today, our military doesn’t just welcome LGBTQ+ service members—it is led at the highest levels by brave LGBTQ+ veterans, including Under Secretary of the Air Force Gina Ortiz Jones and Assistant Secretary of Defense for Readiness Shawn Skelly, who served under Don’t Ask, Don’t Tell. I was gratified to appoint the first openly gay Senate-confirmed Cabinet member, Secretary Pete Buttigieg, a lieutenant in the U.S. Navy Reserve and Afghanistan veteran who joined the military under the Don’t Ask, Don’t Tell policy. And during my first week in office, I proudly delivered on my pledge to repeal the discriminatory ban on open service by patriotic transgender service members.”

In early September, Rep. Chris Pappas (D-NH), a member of the House Veterans Affairs Committee and Co-Chair of the Equality Caucus, reintroduced the SERVE (Securing the Rights our Veterans Earned) Act. The act, which is co-sponsored by Reps. Mike Levin (D-CA), Kathleen Rice (D-NY), Anthony Brown (D-MD), and Jackie Speier (D-CA), would ensure LGBTQ+ veterans who received an OTH or Entry-Level Separation discharge solely due to sexual orientation or gender identity are afforded the VA benefits they rightfully earned, including access to VA healthcare, and education, burial and memorial services, and home loans. The act includes veterans who were issued “blue discharges” during World War II and veterans discharged under former President Trump’s ban on transgender service members. The legislation has been endorsed by the Congressional LGBTQ+ Equality Caucus and is supported by more than 45 representatives.

There are processes for those veterans through which they can have their discharge papers and separation statuses reviewed and modified, Pappas said in a release, but “it can take months for the changes to take effect, and many of these veterans do not even realize they are eligible.”

Earlier this year, Veterans Affairs Secretary Denis McDonough made it a priority to ensure that LGBTQ+ veterans have the same level of access to VA care and services that all other veterans have. Among other things, he established a task force to examine how VA policies hinder or prohibit access to care and services and remove barriers that transgender veterans face in accessing gender-affirming care.

The VA is also taking steps, Williams noted, to clarify VA policy for veterans who were given OTH discharges based on homosexual conduct, gender identity or HIV status. Under this newly issued guidance, VA adjudicators shall find that all discharged service members whose separation was due to sexual orientation, gender identity or HIV status are considered “Veterans” who may be eligible for VA benefits, like VR&E, home loan guaranty, compensation and pension, health care, homeless program and/or burial benefits, so long as the record does not implicate a statutory or regulatory bar to benefits.

The policy statement does not represent a change in law, as veterans who were discharged under DADT alone have been generally eligible for benefits under current statute and regulation. However, it reiterates what constitutes eligibility for benefits under law. In addition, every Character of Discharge case that is initially considered for denial will also get a second look before that action is taken.

“Given that large numbers of LGBTQ+ veterans who were affected by previous homophobic and transphobic policies have not applied for a discharge upgrade due to the perception that the process could be onerous,” Williams wrote, “we are hopeful that this policy statement encourages more of them to contact VA to determine their eligibility for care and services.”

Today, according to the Human Right Campaign, nearly 6.1% of US military personnel self-identify as LGBTQ. Williams, herself a bisexual veteran, said she chose to present as straight during the push to repeal DADT. “I could talk credibly about how the lack of sufficient Arabic linguists harmed our effectiveness downrange, and my own identity seemed irrelevant. It took many years for me to shed the toxic legacy of having served under DADT and come back out of the closet; I’m proud to recognize this anniversary as my authentic self.”

The US Department of Veterans Affairs (VA) has issued a new policy statement to help ensure that active-duty service members who were discharged for their sexual orientation under the Don’t Ask, Don’t Tell policy will be able to receive full VA benefits.

“[A] great injustice was remedied and a tremendous weight was finally lifted off the shoulders of tens of thousands of dedicated American service members,” President Biden said on September 20 as the country commemorated the 10th anniversary of the repeal of “Don’t Ask, Don’t Tell,” the policy that barred lesbian, gay, bisexual, transgender, and queer (LGBTQ+) service members from serving openly.

Prior to DADT, if active-duty service members spoke out about their sexual orientation, they ran the risk of being hounded, shunned, in some cases assaulted, and discharged. If they kept it a secret, they felt they were living a lie, unable to be their whole selves. More than 100,000 were discharged because of their sexual orientation or gender identity.

Although Don’t Ask, Don’t Tell was a “compromise” law that purposed to protect them, LGBTQ+ service members were still at risk for harassment and abuse. Nor did the law protect them from discharge. Some 14,000 LGBTQ+ service members were discharged while DADT was in effect. And those who received “other than honorable” (OTH) discharges could be excluded from receiving services and benefits.

The 2011 repeal followed a “hard-fought battle,” said a release from the Human Rights Campaign, which led a coalition of members, supporters, elected officials, 70+ organizations, and 20,000 veterans to get the law overturned. HRC staff coordinated grassroots efforts and sent 19 million e-mails to members and supporters, in turn generating an “unprecedented” 625,000 e-mails and 50,000 handwritten letters to members of Congress.

After the repeal, the VA began the long process of inclusion for LGBTQ+ veterans. “At VA, we continuously work not only to meet the needs of LGBTQ+ veterans, but also to address ongoing issues that LGBTQ+ veterans face as a result of the military’s decades-long official policy of homophobia and transphobia,” Kayla Williams, assistant secretary for public affairs in VA’s Office of Public and Intergovernmental Affairs wrote in the Secretary’s blog.

The VA “recognizes that the trauma caused by the military’s decades-long policy of discrimination against LGBTQ+ people cannot be undone in a few short months,” she continued, but the Biden administration and Secretary McDonough are “taking the steps necessary to begin addressing the pain that such policies have created.”

President Biden, in his remarks, noted that as a US Senator, he had supported allowing service members to serve openly and, as Vice President, championed the repeal. He said, “I am honored to be Commander-in-Chief of the strongest and most inclusive military in our nation’s history. Today, our military doesn’t just welcome LGBTQ+ service members—it is led at the highest levels by brave LGBTQ+ veterans, including Under Secretary of the Air Force Gina Ortiz Jones and Assistant Secretary of Defense for Readiness Shawn Skelly, who served under Don’t Ask, Don’t Tell. I was gratified to appoint the first openly gay Senate-confirmed Cabinet member, Secretary Pete Buttigieg, a lieutenant in the U.S. Navy Reserve and Afghanistan veteran who joined the military under the Don’t Ask, Don’t Tell policy. And during my first week in office, I proudly delivered on my pledge to repeal the discriminatory ban on open service by patriotic transgender service members.”

In early September, Rep. Chris Pappas (D-NH), a member of the House Veterans Affairs Committee and Co-Chair of the Equality Caucus, reintroduced the SERVE (Securing the Rights our Veterans Earned) Act. The act, which is co-sponsored by Reps. Mike Levin (D-CA), Kathleen Rice (D-NY), Anthony Brown (D-MD), and Jackie Speier (D-CA), would ensure LGBTQ+ veterans who received an OTH or Entry-Level Separation discharge solely due to sexual orientation or gender identity are afforded the VA benefits they rightfully earned, including access to VA healthcare, and education, burial and memorial services, and home loans. The act includes veterans who were issued “blue discharges” during World War II and veterans discharged under former President Trump’s ban on transgender service members. The legislation has been endorsed by the Congressional LGBTQ+ Equality Caucus and is supported by more than 45 representatives.

There are processes for those veterans through which they can have their discharge papers and separation statuses reviewed and modified, Pappas said in a release, but “it can take months for the changes to take effect, and many of these veterans do not even realize they are eligible.”

Earlier this year, Veterans Affairs Secretary Denis McDonough made it a priority to ensure that LGBTQ+ veterans have the same level of access to VA care and services that all other veterans have. Among other things, he established a task force to examine how VA policies hinder or prohibit access to care and services and remove barriers that transgender veterans face in accessing gender-affirming care.

The VA is also taking steps, Williams noted, to clarify VA policy for veterans who were given OTH discharges based on homosexual conduct, gender identity or HIV status. Under this newly issued guidance, VA adjudicators shall find that all discharged service members whose separation was due to sexual orientation, gender identity or HIV status are considered “Veterans” who may be eligible for VA benefits, like VR&E, home loan guaranty, compensation and pension, health care, homeless program and/or burial benefits, so long as the record does not implicate a statutory or regulatory bar to benefits.

The policy statement does not represent a change in law, as veterans who were discharged under DADT alone have been generally eligible for benefits under current statute and regulation. However, it reiterates what constitutes eligibility for benefits under law. In addition, every Character of Discharge case that is initially considered for denial will also get a second look before that action is taken.

“Given that large numbers of LGBTQ+ veterans who were affected by previous homophobic and transphobic policies have not applied for a discharge upgrade due to the perception that the process could be onerous,” Williams wrote, “we are hopeful that this policy statement encourages more of them to contact VA to determine their eligibility for care and services.”

Today, according to the Human Right Campaign, nearly 6.1% of US military personnel self-identify as LGBTQ. Williams, herself a bisexual veteran, said she chose to present as straight during the push to repeal DADT. “I could talk credibly about how the lack of sufficient Arabic linguists harmed our effectiveness downrange, and my own identity seemed irrelevant. It took many years for me to shed the toxic legacy of having served under DADT and come back out of the closet; I’m proud to recognize this anniversary as my authentic self.”

Foregoing chemotherapy in favor of cancer immunotherapy (CIT) alone for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and high programmed death–ligand 1 (PD-L1) expression did not impact survival outcomes in a retrospective cohort of U.S. patients – except in a subgroup of nonsmokers.

Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).

However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.

She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.

Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.

The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.

“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.

The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.

Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.

Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.

For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.

The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.

“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.

Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.

Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.

This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.

[email protected]

Foregoing chemotherapy in favor of cancer immunotherapy (CIT) alone for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and high programmed death–ligand 1 (PD-L1) expression did not impact survival outcomes in a retrospective cohort of U.S. patients – except in a subgroup of nonsmokers.

Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).

However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.

She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.

Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.

The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.

“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.

The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.

Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.

Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.

For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.

The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.

“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.

Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.

Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.

This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.

[email protected]

Foregoing chemotherapy in favor of cancer immunotherapy (CIT) alone for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and high programmed death–ligand 1 (PD-L1) expression did not impact survival outcomes in a retrospective cohort of U.S. patients – except in a subgroup of nonsmokers.

Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).

However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.

She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.

Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.

The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.

“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.

The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.

Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.

Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.

For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.

The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.

“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.

Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.

Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.

This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.

[email protected]

The U.S. Drug Enforcement Administration has issued a public safety alert over an “alarming” increase in fake prescription pills laced with the synthetic opioid fentanyl or the stimulant methamphetamine.

“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in the alert.

“Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. DEA is focusing resources on taking down the violent drug traffickers causing the greatest harm and posing the greatest threat to the safety and health of Americans,” Ms. Milgram said.

Criminal drug networks are mass-producing fake fentanyl- and methamphetamine-laced pills and deceptively marketing them as legitimate prescription pills, the DEA warns.

These lethal counterfeit pills are made to look like legitimate prescription opioid medications such as oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), and alprazolam (Xanax); or stimulants like amphetamines (Adderall).

The agency has seized fake pills in every U.S. state. More than 9.5 million fake pills have been seized so far this year – more than the last 2 years combined.

The number of seized counterfeit pills with fentanyl has jumped nearly 430% since 2019. DEA lab tests reveal that two out of every five pills with fentanyl contain a potentially lethal dose.

These deadly pills are widely accessible and often sold on social media and e-commerce platforms – making them available to anyone with a smartphone, including minors, the DEA warns.

More than 93,000 people died of a drug overdose in the United States last year, according to federal statistics, and fentanyl is the primary driver of this alarming increase in overdose deaths, the DEA says.

The agency has launched a “One Pill Can Kill” public awareness campaign to educate the public of the dangers of counterfeit pills purchased outside of a licensed pharmacy. These pills are “illegal, dangerous, and potentially lethal,” the DEA warns.

This alert does not apply to legitimate pharmaceutical medications prescribed by doctors and dispensed by licensed pharmacists, the DEA says.

“The legitimate prescription supply chain is not impacted. Anyone filling a prescription at a licensed pharmacy can be confident that the medications they receive are safe when taken as directed by a medical professional,” the agency says.

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

The U.S. Drug Enforcement Administration has issued a public safety alert over an “alarming” increase in fake prescription pills laced with the synthetic opioid fentanyl or the stimulant methamphetamine.

“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in the alert.

“Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. DEA is focusing resources on taking down the violent drug traffickers causing the greatest harm and posing the greatest threat to the safety and health of Americans,” Ms. Milgram said.

Criminal drug networks are mass-producing fake fentanyl- and methamphetamine-laced pills and deceptively marketing them as legitimate prescription pills, the DEA warns.

These lethal counterfeit pills are made to look like legitimate prescription opioid medications such as oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), and alprazolam (Xanax); or stimulants like amphetamines (Adderall).

The agency has seized fake pills in every U.S. state. More than 9.5 million fake pills have been seized so far this year – more than the last 2 years combined.

The number of seized counterfeit pills with fentanyl has jumped nearly 430% since 2019. DEA lab tests reveal that two out of every five pills with fentanyl contain a potentially lethal dose.

These deadly pills are widely accessible and often sold on social media and e-commerce platforms – making them available to anyone with a smartphone, including minors, the DEA warns.

More than 93,000 people died of a drug overdose in the United States last year, according to federal statistics, and fentanyl is the primary driver of this alarming increase in overdose deaths, the DEA says.

The agency has launched a “One Pill Can Kill” public awareness campaign to educate the public of the dangers of counterfeit pills purchased outside of a licensed pharmacy. These pills are “illegal, dangerous, and potentially lethal,” the DEA warns.

This alert does not apply to legitimate pharmaceutical medications prescribed by doctors and dispensed by licensed pharmacists, the DEA says.

“The legitimate prescription supply chain is not impacted. Anyone filling a prescription at a licensed pharmacy can be confident that the medications they receive are safe when taken as directed by a medical professional,” the agency says.

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

The U.S. Drug Enforcement Administration has issued a public safety alert over an “alarming” increase in fake prescription pills laced with the synthetic opioid fentanyl or the stimulant methamphetamine.

“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in the alert.

“Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. DEA is focusing resources on taking down the violent drug traffickers causing the greatest harm and posing the greatest threat to the safety and health of Americans,” Ms. Milgram said.

Criminal drug networks are mass-producing fake fentanyl- and methamphetamine-laced pills and deceptively marketing them as legitimate prescription pills, the DEA warns.

These lethal counterfeit pills are made to look like legitimate prescription opioid medications such as oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), and alprazolam (Xanax); or stimulants like amphetamines (Adderall).

The agency has seized fake pills in every U.S. state. More than 9.5 million fake pills have been seized so far this year – more than the last 2 years combined.

The number of seized counterfeit pills with fentanyl has jumped nearly 430% since 2019. DEA lab tests reveal that two out of every five pills with fentanyl contain a potentially lethal dose.

These deadly pills are widely accessible and often sold on social media and e-commerce platforms – making them available to anyone with a smartphone, including minors, the DEA warns.

More than 93,000 people died of a drug overdose in the United States last year, according to federal statistics, and fentanyl is the primary driver of this alarming increase in overdose deaths, the DEA says.

The agency has launched a “One Pill Can Kill” public awareness campaign to educate the public of the dangers of counterfeit pills purchased outside of a licensed pharmacy. These pills are “illegal, dangerous, and potentially lethal,” the DEA warns.

This alert does not apply to legitimate pharmaceutical medications prescribed by doctors and dispensed by licensed pharmacists, the DEA says.

“The legitimate prescription supply chain is not impacted. Anyone filling a prescription at a licensed pharmacy can be confident that the medications they receive are safe when taken as directed by a medical professional,” the agency says.

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

Physical activity, long recommended by health experts to reduce risk for obesity, heart disease, type 2 diabetes, high blood pressure, hypercholesterolemia, and other cardiovascular disease risk factors, is also associated with increases in the amount of calcium deposited in the coronary arteries, new observational data suggest.

In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.

“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.

This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.

“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.

The study is published online September 20 in Heart.

The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.

In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.

“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.

The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.

At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.

Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).

On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.  

Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.

At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).

Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.

A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.

The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.

Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.

“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.

“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.

“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.

Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”

“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.

The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.

“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.

Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.

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

Physical activity, long recommended by health experts to reduce risk for obesity, heart disease, type 2 diabetes, high blood pressure, hypercholesterolemia, and other cardiovascular disease risk factors, is also associated with increases in the amount of calcium deposited in the coronary arteries, new observational data suggest.

In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.

“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.

This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.

“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.

The study is published online September 20 in Heart.

The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.

In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.

“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.

The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.

At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.

Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).

On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.  

Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.

At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).

Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.

A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.

The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.

Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.

“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.

“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.

“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.

Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”

“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.

The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.

“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.

Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.

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

Physical activity, long recommended by health experts to reduce risk for obesity, heart disease, type 2 diabetes, high blood pressure, hypercholesterolemia, and other cardiovascular disease risk factors, is also associated with increases in the amount of calcium deposited in the coronary arteries, new observational data suggest.

In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.

“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.

This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.

“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.

The study is published online September 20 in Heart.

The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.

In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.

“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.

The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.

At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.

Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).

On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.  

Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.

At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).

Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.

A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.

The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.

Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.

“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.

“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.

“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.

Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”

“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.

The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.

“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.

Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.

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