MDedge Endocrinology

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

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

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

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

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

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

As COVID-19 cases surge and vaccinations lag, health authorities continue to seek additional ways to mitigate the spread of the novel coronavirus.

Now, a modeling study estimates that more than half of transmissions come from pre-, never-, and asymptomatic individuals, indicating that symptom-based screening will have little effect on spread.

Courtesy NIAID

The analysis

Based on data from several COVID-19 studies from last year, the CDC’s analytical model assumes at baseline that infectiousness peaks at the median point of symptom onset, and that 30% of infected individuals never develop symptoms but are nevertheless 75% as infectious as those who develop overt symptoms.

The investigators then model multiple scenarios of transmission based pre- and never-symptomatic individuals, assuming different incubation and infectious periods, and varying numbers of days from point of infection to symptom onset.

When combined, the models predicts that 59% of all transmission would come from asymptomatic transmission – 35% from presymptomatic individuals and 24% from never-symptomatic individuals.

The findings complement those of an earlier CDC analysis, according to the authors.

The overall proportion of transmission from presymptomatic and never-symptomatic individuals is key to identifying mitigation measures that may be able to control SARS-CoV-2, the authors stated.

For example, they explain, if the infection reproduction number (R) in a particular setting is 2.0, a reduction in transmission of at least 50% is needed in order to reduce R to below 1.0. “Given that in some settings R is likely much greater than 2 and more than half of transmissions may come from individuals who are asymptomatic at the time of transmission, effective control must mitigate transmission risk from people without symptoms,” they wrote.

The authors acknowledge that the study applies a simplistic model to a complex and evolving phenomenon, and that the exact proportions of presymptomatic and never-symptomatic transmission and the incubation periods are not known. They also note symptoms and transmissions appear to vary across different population groups, with older individuals more likely than younger persons to experience symptoms, according to previous studies.

“Assume that everyone is potentially infected”

Other experts agree that expanded testing of asymptomatic individuals is important. “Screening for fever and isolation of symptomatic individuals is a common-sense approach to help prevent spread, but these measures are by no means adequate since it’s been clearly documented that individuals who are either asymptomatic or presymptomatic can still spread the virus,” said Brett Williams, MD, an infectious disease specialist and assistant professor of medicine at Rush University in Chicago. 

“As we saw with the White House Rose Garden superspreader outbreak, testing does not reliably exclude infection either because the tested individual has not yet become positive or the test is falsely negative,” Dr. Williams, who was not involved in the CDC study, said in an interview. He further noted that when prevalence is as high as it currently is in the United States, the rate of false negatives will be high because a large proportion of those screened will be unknowingly infected.

At his center, all visitors and staff are screened with a temperature probe on entry, and since the earliest days of the pandemic, universal masking has been required. “Nationally there have been many instances of hospital break room outbreaks because of staff eating lunch together, and these outbreaks also demonstrate the incompleteness of symptomatic isolation,” Dr. Williams said.

For his part, virologist Frank Esper, MD, a pediatric infectious disease specialist at the Cleveland Clinic, said that while it’s been understood for some time that many infected people will not exhibit symptoms, “the question that remains is just how infectious are they?”

Dr. Esper’s takeaway from the modeling study is not so much that we need more screening of possibly exposed but asymptomatic people, but rather testing symptomatic people and tracing their contacts is not enough.

“We need to continue to assume that everyone is potentially infected whether they know it or not. And even though we have ramped up our testing to a much greater capacity than in the first wave, we need to continue to wear masks and socially distance because just identifying people who are sick and isolating or quarantining them is not going to be enough to contain the pandemic.”

And although assumption-based modeling is helpful, it cannot tell us “how many asymptomatic people are actually infected,” said Dr. Esper, who was not involved in the CDC study.

Dr. Esper also pointed out that the study estimates are based on data from early Chinese studies, but the virus has since changed. The new, more transmissible strain in the United States and elsewhere may involve not only more infections but also a longer presymptomatic stage. “So the CDC study may actually undershoot asymptomatic infections,” he said. 

He also agreed with the authors that when it comes to infection, not all humans are equal. “Older people tend to be more symptomatic and become symptomatic more quickly so the asymptomatic rate is not the same across board from young people age 20 to older people.”

The bottom line, said David. A. Hirschwerk, MD, an infectious disease specialist at Northwell Health in Manhasset, N.Y., is that these data support the maintenance of protective measures we’ve been taking over the past months. “They support the concept that asymptomatic people are a significant source of transmission and that we need to adhere to mask wearing and social distancing, particularly indoors,” Dr. Hirschwerk, who was not involved in the analysis, said in an interview. “More testing would be better but it has to be fast and it has to be efficient, and there are a lot of challenges to overcome.”

The study was done as part of the CDC’s coronavirus disease 2019 response and was supported solely by federal base and response funding. The authors and commentators have disclosed no relevant financial relationships.

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

As COVID-19 cases surge and vaccinations lag, health authorities continue to seek additional ways to mitigate the spread of the novel coronavirus.

Now, a modeling study estimates that more than half of transmissions come from pre-, never-, and asymptomatic individuals, indicating that symptom-based screening will have little effect on spread.

Courtesy NIAID

The analysis

Based on data from several COVID-19 studies from last year, the CDC’s analytical model assumes at baseline that infectiousness peaks at the median point of symptom onset, and that 30% of infected individuals never develop symptoms but are nevertheless 75% as infectious as those who develop overt symptoms.

The investigators then model multiple scenarios of transmission based pre- and never-symptomatic individuals, assuming different incubation and infectious periods, and varying numbers of days from point of infection to symptom onset.

When combined, the models predicts that 59% of all transmission would come from asymptomatic transmission – 35% from presymptomatic individuals and 24% from never-symptomatic individuals.

The findings complement those of an earlier CDC analysis, according to the authors.

The overall proportion of transmission from presymptomatic and never-symptomatic individuals is key to identifying mitigation measures that may be able to control SARS-CoV-2, the authors stated.

For example, they explain, if the infection reproduction number (R) in a particular setting is 2.0, a reduction in transmission of at least 50% is needed in order to reduce R to below 1.0. “Given that in some settings R is likely much greater than 2 and more than half of transmissions may come from individuals who are asymptomatic at the time of transmission, effective control must mitigate transmission risk from people without symptoms,” they wrote.

The authors acknowledge that the study applies a simplistic model to a complex and evolving phenomenon, and that the exact proportions of presymptomatic and never-symptomatic transmission and the incubation periods are not known. They also note symptoms and transmissions appear to vary across different population groups, with older individuals more likely than younger persons to experience symptoms, according to previous studies.

“Assume that everyone is potentially infected”

Other experts agree that expanded testing of asymptomatic individuals is important. “Screening for fever and isolation of symptomatic individuals is a common-sense approach to help prevent spread, but these measures are by no means adequate since it’s been clearly documented that individuals who are either asymptomatic or presymptomatic can still spread the virus,” said Brett Williams, MD, an infectious disease specialist and assistant professor of medicine at Rush University in Chicago. 

“As we saw with the White House Rose Garden superspreader outbreak, testing does not reliably exclude infection either because the tested individual has not yet become positive or the test is falsely negative,” Dr. Williams, who was not involved in the CDC study, said in an interview. He further noted that when prevalence is as high as it currently is in the United States, the rate of false negatives will be high because a large proportion of those screened will be unknowingly infected.

At his center, all visitors and staff are screened with a temperature probe on entry, and since the earliest days of the pandemic, universal masking has been required. “Nationally there have been many instances of hospital break room outbreaks because of staff eating lunch together, and these outbreaks also demonstrate the incompleteness of symptomatic isolation,” Dr. Williams said.

For his part, virologist Frank Esper, MD, a pediatric infectious disease specialist at the Cleveland Clinic, said that while it’s been understood for some time that many infected people will not exhibit symptoms, “the question that remains is just how infectious are they?”

Dr. Esper’s takeaway from the modeling study is not so much that we need more screening of possibly exposed but asymptomatic people, but rather testing symptomatic people and tracing their contacts is not enough.

“We need to continue to assume that everyone is potentially infected whether they know it or not. And even though we have ramped up our testing to a much greater capacity than in the first wave, we need to continue to wear masks and socially distance because just identifying people who are sick and isolating or quarantining them is not going to be enough to contain the pandemic.”

And although assumption-based modeling is helpful, it cannot tell us “how many asymptomatic people are actually infected,” said Dr. Esper, who was not involved in the CDC study.

Dr. Esper also pointed out that the study estimates are based on data from early Chinese studies, but the virus has since changed. The new, more transmissible strain in the United States and elsewhere may involve not only more infections but also a longer presymptomatic stage. “So the CDC study may actually undershoot asymptomatic infections,” he said. 

He also agreed with the authors that when it comes to infection, not all humans are equal. “Older people tend to be more symptomatic and become symptomatic more quickly so the asymptomatic rate is not the same across board from young people age 20 to older people.”

The bottom line, said David. A. Hirschwerk, MD, an infectious disease specialist at Northwell Health in Manhasset, N.Y., is that these data support the maintenance of protective measures we’ve been taking over the past months. “They support the concept that asymptomatic people are a significant source of transmission and that we need to adhere to mask wearing and social distancing, particularly indoors,” Dr. Hirschwerk, who was not involved in the analysis, said in an interview. “More testing would be better but it has to be fast and it has to be efficient, and there are a lot of challenges to overcome.”

The study was done as part of the CDC’s coronavirus disease 2019 response and was supported solely by federal base and response funding. The authors and commentators have disclosed no relevant financial relationships.

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

As COVID-19 cases surge and vaccinations lag, health authorities continue to seek additional ways to mitigate the spread of the novel coronavirus.

Now, a modeling study estimates that more than half of transmissions come from pre-, never-, and asymptomatic individuals, indicating that symptom-based screening will have little effect on spread.

Courtesy NIAID

The analysis

Based on data from several COVID-19 studies from last year, the CDC’s analytical model assumes at baseline that infectiousness peaks at the median point of symptom onset, and that 30% of infected individuals never develop symptoms but are nevertheless 75% as infectious as those who develop overt symptoms.

The investigators then model multiple scenarios of transmission based pre- and never-symptomatic individuals, assuming different incubation and infectious periods, and varying numbers of days from point of infection to symptom onset.

When combined, the models predicts that 59% of all transmission would come from asymptomatic transmission – 35% from presymptomatic individuals and 24% from never-symptomatic individuals.

The findings complement those of an earlier CDC analysis, according to the authors.

The overall proportion of transmission from presymptomatic and never-symptomatic individuals is key to identifying mitigation measures that may be able to control SARS-CoV-2, the authors stated.

For example, they explain, if the infection reproduction number (R) in a particular setting is 2.0, a reduction in transmission of at least 50% is needed in order to reduce R to below 1.0. “Given that in some settings R is likely much greater than 2 and more than half of transmissions may come from individuals who are asymptomatic at the time of transmission, effective control must mitigate transmission risk from people without symptoms,” they wrote.

The authors acknowledge that the study applies a simplistic model to a complex and evolving phenomenon, and that the exact proportions of presymptomatic and never-symptomatic transmission and the incubation periods are not known. They also note symptoms and transmissions appear to vary across different population groups, with older individuals more likely than younger persons to experience symptoms, according to previous studies.

“Assume that everyone is potentially infected”

Other experts agree that expanded testing of asymptomatic individuals is important. “Screening for fever and isolation of symptomatic individuals is a common-sense approach to help prevent spread, but these measures are by no means adequate since it’s been clearly documented that individuals who are either asymptomatic or presymptomatic can still spread the virus,” said Brett Williams, MD, an infectious disease specialist and assistant professor of medicine at Rush University in Chicago. 

“As we saw with the White House Rose Garden superspreader outbreak, testing does not reliably exclude infection either because the tested individual has not yet become positive or the test is falsely negative,” Dr. Williams, who was not involved in the CDC study, said in an interview. He further noted that when prevalence is as high as it currently is in the United States, the rate of false negatives will be high because a large proportion of those screened will be unknowingly infected.

At his center, all visitors and staff are screened with a temperature probe on entry, and since the earliest days of the pandemic, universal masking has been required. “Nationally there have been many instances of hospital break room outbreaks because of staff eating lunch together, and these outbreaks also demonstrate the incompleteness of symptomatic isolation,” Dr. Williams said.

For his part, virologist Frank Esper, MD, a pediatric infectious disease specialist at the Cleveland Clinic, said that while it’s been understood for some time that many infected people will not exhibit symptoms, “the question that remains is just how infectious are they?”

Dr. Esper’s takeaway from the modeling study is not so much that we need more screening of possibly exposed but asymptomatic people, but rather testing symptomatic people and tracing their contacts is not enough.

“We need to continue to assume that everyone is potentially infected whether they know it or not. And even though we have ramped up our testing to a much greater capacity than in the first wave, we need to continue to wear masks and socially distance because just identifying people who are sick and isolating or quarantining them is not going to be enough to contain the pandemic.”

And although assumption-based modeling is helpful, it cannot tell us “how many asymptomatic people are actually infected,” said Dr. Esper, who was not involved in the CDC study.

Dr. Esper also pointed out that the study estimates are based on data from early Chinese studies, but the virus has since changed. The new, more transmissible strain in the United States and elsewhere may involve not only more infections but also a longer presymptomatic stage. “So the CDC study may actually undershoot asymptomatic infections,” he said. 

He also agreed with the authors that when it comes to infection, not all humans are equal. “Older people tend to be more symptomatic and become symptomatic more quickly so the asymptomatic rate is not the same across board from young people age 20 to older people.”

The bottom line, said David. A. Hirschwerk, MD, an infectious disease specialist at Northwell Health in Manhasset, N.Y., is that these data support the maintenance of protective measures we’ve been taking over the past months. “They support the concept that asymptomatic people are a significant source of transmission and that we need to adhere to mask wearing and social distancing, particularly indoors,” Dr. Hirschwerk, who was not involved in the analysis, said in an interview. “More testing would be better but it has to be fast and it has to be efficient, and there are a lot of challenges to overcome.”

The study was done as part of the CDC’s coronavirus disease 2019 response and was supported solely by federal base and response funding. The authors and commentators have disclosed no relevant financial relationships.

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

For too long, eating disorders have been considered a disease that afflicted mostly affluent white teenage girls, but there really is no type for eating disorders, said Laurie L. Hornberger, MD, MPH, lead author of a new clinical report on eating disorders in children and adolescents prepared by the American Academy of Pediatrics Committee on Adolescence.

FatCamera/E+

In a separate interview with Pediatric News, Dr. Hornberger, associate professor of pediatrics, University of Missouri–Kansas City, explained that eating disorders occur across the spectrum of races, ethnicities, sexes, and socioeconomic statuses, so “getting caught up in that stereotype can cause you to overlook kids with significant problems.” Pediatricians are on the front line in identifying and referring eating disorders for treatment, which is crucial to earlier detection, intervention, and better outcomes, she said.

“Once you become familiar with the signs and symptoms of EDs [eating disorders] and actively start screening for them, you realize how common they are,” she noted, adding that pediatricians should be inquiring routinely about body image, attempts at weight management and what was involved in that weight management. Efforts to restrict calories, limit food choices/groups, exercise excessively, force vomiting, abuse laxatives, etc., are all signs. If the child/adolescent experiences guilt with eating, feels the need to compensate for their eating with exercise or purging, is preoccupied with thoughts of food or calorie counting, feels he/she has lost control of their eating, or experiences uncontrollable binges where they are unable to stop eating despite feeling full and wanting to stop, these are all further evidence of an eating disorder, she added.

There are also physical clues to alert pediatricians. Abrupt or sharp increases or decreases in weight, as measured in growth charts, should be monitored and questioned, Dr. Hornberger cautioned. Physicians should be careful to hold compliments on weight loss until learning how the weight loss was achieved. “Vital signs, such as a resting bradycardia and orthostatic tachycardia, can reflect malnutrition, as can other physical findings. Although lab screening is frequently normal, it should not, by itself, rule out an [eating disorder]. Pediatricians should also be aware of the signs and symptoms of medical instability in an [eating disorder] patient that warrant hospitalization for renourishment,” she explained.
 

Number of eating disorders increased in 2020

Current pandemic conditions have shown an uptick in the number of referrals and long wait lists for eating disorder centers, noted Dr. Hornberger. Having a formal eating disorder treatment program nearby is a luxury not all communities have, so being able to call upon primary care pediatricians to be an active part of a treatment team, which ideally includes a mental health provider and dietitian, both experienced in eating disorders, is pretty important. In coordination with the team, pediatricians are responsible for monitoring physical recovery and remaining alert for signs of struggle to recover and the need for a higher level of care.

In a separate interview with Pediatric News, Margaret Thew, DNP, FNP-BC, medical director of adolescent medicine at the Medical College of Wisconsin, Milwaukee, observed, “COVID-19 has created a surge of children and adolescents struggling with eating disorders. Eating disorder numbers have been associated with social media promoting the avoidance of COVID-19–related weight gain and influencers promoting thin body image. The abrupt end of face-to-face learning, sports participation, and generalized anxiety have further influenced mental health and disordered eating behaviors. Early in the pandemic, the true impact on the psychosocial well-being of children and teens was not known. We are only now seeing the impact months into this pandemic. The timeliness of the American Association of Pediatrics guidelines on the identification and management of children and teens presenting with an eating disorder is pivotal to recognition and treatment,” she said.

“I applaud the AAP for presenting timely guidelines on the evaluation and management of eating disorders for the general pediatrician, yet feel the authors fell short in recognizing the challenges of mitigating management of an eating disorder,” Ms. Thew added.

“Treatment of disordered eating requires all parties to accept the diagnosis and no longer support unhealthy eating patterns. The environment rationalizing the disordered eating may require changes to reduce behaviors and improve nutrition,” she cautioned.
 

New guidelines offer a range of diagnostic and treatment resources

In preparing the current report, the authors included the most recent definitions of eating disorders outlined in the “Diagnostic and Statistical Manual of Mental Disorders,” 5th Edition (DSM-5). Special attention was paid to four classifications of eating disorders in particular – anorexia nervosa (AN), avoidant/restrictive food intake disorder (ARFID); binge-eating disorder (BED); and bulimia nervosa (BN) – because so many disorders are subclassified under these.

Beyond providing a list of comprehensive definitions, the guidance reviews prevalence data for eating disorders, and provides detailed screening, assessment, and laboratory evaluation guidelines. Medical complications, including psychological, neurologic, dermatologic, dental and/or oral, cardiovascular, gastrointestinal, renal and electrolyte, and endocrine effects are discussed in detail as are treatment principles, financial considerations, and prognosis. Besides the important prevention and advocacy roles the authors identify for pediatricians, the guidelines highlight four key areas where pediatricians play a key role in the screening and management of eating disorders, as touched on previously by the guidance authors in this article.

In a separate AAP press release, Margo Lane, MD, coauthor of the report, noted, “As pediatricians, there is much we can also do outside the clinic to advocate for our patients, through legislation and policy that support services, including medical care, nutritional intervention, mental health treatment, and care coordination.” Physicians can also play an important role in reprograming familial and societal attitudes and behaviors by encouraging more positive language that deemphasizes weight and embraces and celebrates kids of all shapes and sizes, added Dr. Lane.

Dr. Hornberger and colleagues as well as Ms. Thew had no conflicts of interest and no relevant financial disclosures.

SOURCE: Pediatrics. 2021;147(1):e2020040279. doi: 10.1542/peds.2020-040279.

For too long, eating disorders have been considered a disease that afflicted mostly affluent white teenage girls, but there really is no type for eating disorders, said Laurie L. Hornberger, MD, MPH, lead author of a new clinical report on eating disorders in children and adolescents prepared by the American Academy of Pediatrics Committee on Adolescence.

FatCamera/E+

In a separate interview with Pediatric News, Dr. Hornberger, associate professor of pediatrics, University of Missouri–Kansas City, explained that eating disorders occur across the spectrum of races, ethnicities, sexes, and socioeconomic statuses, so “getting caught up in that stereotype can cause you to overlook kids with significant problems.” Pediatricians are on the front line in identifying and referring eating disorders for treatment, which is crucial to earlier detection, intervention, and better outcomes, she said.

“Once you become familiar with the signs and symptoms of EDs [eating disorders] and actively start screening for them, you realize how common they are,” she noted, adding that pediatricians should be inquiring routinely about body image, attempts at weight management and what was involved in that weight management. Efforts to restrict calories, limit food choices/groups, exercise excessively, force vomiting, abuse laxatives, etc., are all signs. If the child/adolescent experiences guilt with eating, feels the need to compensate for their eating with exercise or purging, is preoccupied with thoughts of food or calorie counting, feels he/she has lost control of their eating, or experiences uncontrollable binges where they are unable to stop eating despite feeling full and wanting to stop, these are all further evidence of an eating disorder, she added.

There are also physical clues to alert pediatricians. Abrupt or sharp increases or decreases in weight, as measured in growth charts, should be monitored and questioned, Dr. Hornberger cautioned. Physicians should be careful to hold compliments on weight loss until learning how the weight loss was achieved. “Vital signs, such as a resting bradycardia and orthostatic tachycardia, can reflect malnutrition, as can other physical findings. Although lab screening is frequently normal, it should not, by itself, rule out an [eating disorder]. Pediatricians should also be aware of the signs and symptoms of medical instability in an [eating disorder] patient that warrant hospitalization for renourishment,” she explained.
 

Number of eating disorders increased in 2020

Current pandemic conditions have shown an uptick in the number of referrals and long wait lists for eating disorder centers, noted Dr. Hornberger. Having a formal eating disorder treatment program nearby is a luxury not all communities have, so being able to call upon primary care pediatricians to be an active part of a treatment team, which ideally includes a mental health provider and dietitian, both experienced in eating disorders, is pretty important. In coordination with the team, pediatricians are responsible for monitoring physical recovery and remaining alert for signs of struggle to recover and the need for a higher level of care.

In a separate interview with Pediatric News, Margaret Thew, DNP, FNP-BC, medical director of adolescent medicine at the Medical College of Wisconsin, Milwaukee, observed, “COVID-19 has created a surge of children and adolescents struggling with eating disorders. Eating disorder numbers have been associated with social media promoting the avoidance of COVID-19–related weight gain and influencers promoting thin body image. The abrupt end of face-to-face learning, sports participation, and generalized anxiety have further influenced mental health and disordered eating behaviors. Early in the pandemic, the true impact on the psychosocial well-being of children and teens was not known. We are only now seeing the impact months into this pandemic. The timeliness of the American Association of Pediatrics guidelines on the identification and management of children and teens presenting with an eating disorder is pivotal to recognition and treatment,” she said.

“I applaud the AAP for presenting timely guidelines on the evaluation and management of eating disorders for the general pediatrician, yet feel the authors fell short in recognizing the challenges of mitigating management of an eating disorder,” Ms. Thew added.

“Treatment of disordered eating requires all parties to accept the diagnosis and no longer support unhealthy eating patterns. The environment rationalizing the disordered eating may require changes to reduce behaviors and improve nutrition,” she cautioned.
 

New guidelines offer a range of diagnostic and treatment resources

In preparing the current report, the authors included the most recent definitions of eating disorders outlined in the “Diagnostic and Statistical Manual of Mental Disorders,” 5th Edition (DSM-5). Special attention was paid to four classifications of eating disorders in particular – anorexia nervosa (AN), avoidant/restrictive food intake disorder (ARFID); binge-eating disorder (BED); and bulimia nervosa (BN) – because so many disorders are subclassified under these.

Beyond providing a list of comprehensive definitions, the guidance reviews prevalence data for eating disorders, and provides detailed screening, assessment, and laboratory evaluation guidelines. Medical complications, including psychological, neurologic, dermatologic, dental and/or oral, cardiovascular, gastrointestinal, renal and electrolyte, and endocrine effects are discussed in detail as are treatment principles, financial considerations, and prognosis. Besides the important prevention and advocacy roles the authors identify for pediatricians, the guidelines highlight four key areas where pediatricians play a key role in the screening and management of eating disorders, as touched on previously by the guidance authors in this article.

In a separate AAP press release, Margo Lane, MD, coauthor of the report, noted, “As pediatricians, there is much we can also do outside the clinic to advocate for our patients, through legislation and policy that support services, including medical care, nutritional intervention, mental health treatment, and care coordination.” Physicians can also play an important role in reprograming familial and societal attitudes and behaviors by encouraging more positive language that deemphasizes weight and embraces and celebrates kids of all shapes and sizes, added Dr. Lane.

Dr. Hornberger and colleagues as well as Ms. Thew had no conflicts of interest and no relevant financial disclosures.

SOURCE: Pediatrics. 2021;147(1):e2020040279. doi: 10.1542/peds.2020-040279.

For too long, eating disorders have been considered a disease that afflicted mostly affluent white teenage girls, but there really is no type for eating disorders, said Laurie L. Hornberger, MD, MPH, lead author of a new clinical report on eating disorders in children and adolescents prepared by the American Academy of Pediatrics Committee on Adolescence.

FatCamera/E+

In a separate interview with Pediatric News, Dr. Hornberger, associate professor of pediatrics, University of Missouri–Kansas City, explained that eating disorders occur across the spectrum of races, ethnicities, sexes, and socioeconomic statuses, so “getting caught up in that stereotype can cause you to overlook kids with significant problems.” Pediatricians are on the front line in identifying and referring eating disorders for treatment, which is crucial to earlier detection, intervention, and better outcomes, she said.

“Once you become familiar with the signs and symptoms of EDs [eating disorders] and actively start screening for them, you realize how common they are,” she noted, adding that pediatricians should be inquiring routinely about body image, attempts at weight management and what was involved in that weight management. Efforts to restrict calories, limit food choices/groups, exercise excessively, force vomiting, abuse laxatives, etc., are all signs. If the child/adolescent experiences guilt with eating, feels the need to compensate for their eating with exercise or purging, is preoccupied with thoughts of food or calorie counting, feels he/she has lost control of their eating, or experiences uncontrollable binges where they are unable to stop eating despite feeling full and wanting to stop, these are all further evidence of an eating disorder, she added.

There are also physical clues to alert pediatricians. Abrupt or sharp increases or decreases in weight, as measured in growth charts, should be monitored and questioned, Dr. Hornberger cautioned. Physicians should be careful to hold compliments on weight loss until learning how the weight loss was achieved. “Vital signs, such as a resting bradycardia and orthostatic tachycardia, can reflect malnutrition, as can other physical findings. Although lab screening is frequently normal, it should not, by itself, rule out an [eating disorder]. Pediatricians should also be aware of the signs and symptoms of medical instability in an [eating disorder] patient that warrant hospitalization for renourishment,” she explained.
 

Number of eating disorders increased in 2020

Current pandemic conditions have shown an uptick in the number of referrals and long wait lists for eating disorder centers, noted Dr. Hornberger. Having a formal eating disorder treatment program nearby is a luxury not all communities have, so being able to call upon primary care pediatricians to be an active part of a treatment team, which ideally includes a mental health provider and dietitian, both experienced in eating disorders, is pretty important. In coordination with the team, pediatricians are responsible for monitoring physical recovery and remaining alert for signs of struggle to recover and the need for a higher level of care.

In a separate interview with Pediatric News, Margaret Thew, DNP, FNP-BC, medical director of adolescent medicine at the Medical College of Wisconsin, Milwaukee, observed, “COVID-19 has created a surge of children and adolescents struggling with eating disorders. Eating disorder numbers have been associated with social media promoting the avoidance of COVID-19–related weight gain and influencers promoting thin body image. The abrupt end of face-to-face learning, sports participation, and generalized anxiety have further influenced mental health and disordered eating behaviors. Early in the pandemic, the true impact on the psychosocial well-being of children and teens was not known. We are only now seeing the impact months into this pandemic. The timeliness of the American Association of Pediatrics guidelines on the identification and management of children and teens presenting with an eating disorder is pivotal to recognition and treatment,” she said.

“I applaud the AAP for presenting timely guidelines on the evaluation and management of eating disorders for the general pediatrician, yet feel the authors fell short in recognizing the challenges of mitigating management of an eating disorder,” Ms. Thew added.

“Treatment of disordered eating requires all parties to accept the diagnosis and no longer support unhealthy eating patterns. The environment rationalizing the disordered eating may require changes to reduce behaviors and improve nutrition,” she cautioned.
 

New guidelines offer a range of diagnostic and treatment resources

In preparing the current report, the authors included the most recent definitions of eating disorders outlined in the “Diagnostic and Statistical Manual of Mental Disorders,” 5th Edition (DSM-5). Special attention was paid to four classifications of eating disorders in particular – anorexia nervosa (AN), avoidant/restrictive food intake disorder (ARFID); binge-eating disorder (BED); and bulimia nervosa (BN) – because so many disorders are subclassified under these.

Beyond providing a list of comprehensive definitions, the guidance reviews prevalence data for eating disorders, and provides detailed screening, assessment, and laboratory evaluation guidelines. Medical complications, including psychological, neurologic, dermatologic, dental and/or oral, cardiovascular, gastrointestinal, renal and electrolyte, and endocrine effects are discussed in detail as are treatment principles, financial considerations, and prognosis. Besides the important prevention and advocacy roles the authors identify for pediatricians, the guidelines highlight four key areas where pediatricians play a key role in the screening and management of eating disorders, as touched on previously by the guidance authors in this article.

In a separate AAP press release, Margo Lane, MD, coauthor of the report, noted, “As pediatricians, there is much we can also do outside the clinic to advocate for our patients, through legislation and policy that support services, including medical care, nutritional intervention, mental health treatment, and care coordination.” Physicians can also play an important role in reprograming familial and societal attitudes and behaviors by encouraging more positive language that deemphasizes weight and embraces and celebrates kids of all shapes and sizes, added Dr. Lane.

Dr. Hornberger and colleagues as well as Ms. Thew had no conflicts of interest and no relevant financial disclosures.

SOURCE: Pediatrics. 2021;147(1):e2020040279. doi: 10.1542/peds.2020-040279.

Health care providers should be ready to treat rare cases of anaphylaxis following administration of COVID-19 vaccines, federal medical officials have urged. The officials also stressed the importance of continuing vaccinations, despite reports of the rare side effect.

There have been 29 cases of anaphylaxis to date following administration of a COVID-19 vaccine, officials from the Centers for Disease Control and Prevention said in a call with reporters on Jan. 6.

The severe allergic reaction, which appears to be rare, can happen with either the Pfizer-BioNTech vaccine or the rival Moderna product. The Food and Drug Administration granted emergency use authorizations for these two vaccines in December.

Even with the cases seen to date, the COVID-19 vaccines remain a “good value proposition,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization, said in the call.

There have been about 11.1 cases of anaphylaxis per million doses with the Pfizer-BioNTech COVID-19 vaccine, which is higher than the estimated 1.3 cases per million doses with influenza vaccines, she said. But the low risk of anaphylaxis must be balanced against the threat of COVID-19, which currently claims about 2,000 lives a day in the United States, she said. In addition, many people are reporting long-term complications with COVID-19 even if they recover.

Kept in context, the data on anaphylaxis should not scare people away from getting a COVID-19 vaccine, she added.

“Their risk from COVID and poor outcomes is still more than the risk of a severe outcome from the vaccine,” Dr. Messonnier said. “And fortunately, we know how to treat anaphylaxis.”

Dr. Messonnier urged health care workers administering COVID-19 vaccines to be prepared.

“Anybody administering vaccines needs not just to have the EpiPen available, but frankly, to know how to use it,” Dr. Messonnier said.
 

MMWR details

The CDC on Jan. 6 also provided an update on anaphylaxis in Morbidity and Mortality Weekly Report (MMWR).

The information included in the report was based on cases reported with the Pfizer-BioNTech vaccine – the first to get emergency use authorization from the FDA. On the call with reporters, CDC officials confirmed there have been additional reports since then and anaphylaxis has been reported with both the Pfizer-BioNTech and Moderna vaccines. CDC officials said they could not give a breakdown of how many cases were linked to each of these products at this time.

Between Dec. 14 and 23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine. Most reactions – 71% – occurred within 15 minutes of vaccination.

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

Health care providers should be ready to treat rare cases of anaphylaxis following administration of COVID-19 vaccines, federal medical officials have urged. The officials also stressed the importance of continuing vaccinations, despite reports of the rare side effect.

There have been 29 cases of anaphylaxis to date following administration of a COVID-19 vaccine, officials from the Centers for Disease Control and Prevention said in a call with reporters on Jan. 6.

The severe allergic reaction, which appears to be rare, can happen with either the Pfizer-BioNTech vaccine or the rival Moderna product. The Food and Drug Administration granted emergency use authorizations for these two vaccines in December.

Even with the cases seen to date, the COVID-19 vaccines remain a “good value proposition,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization, said in the call.

There have been about 11.1 cases of anaphylaxis per million doses with the Pfizer-BioNTech COVID-19 vaccine, which is higher than the estimated 1.3 cases per million doses with influenza vaccines, she said. But the low risk of anaphylaxis must be balanced against the threat of COVID-19, which currently claims about 2,000 lives a day in the United States, she said. In addition, many people are reporting long-term complications with COVID-19 even if they recover.

Kept in context, the data on anaphylaxis should not scare people away from getting a COVID-19 vaccine, she added.

“Their risk from COVID and poor outcomes is still more than the risk of a severe outcome from the vaccine,” Dr. Messonnier said. “And fortunately, we know how to treat anaphylaxis.”

Dr. Messonnier urged health care workers administering COVID-19 vaccines to be prepared.

“Anybody administering vaccines needs not just to have the EpiPen available, but frankly, to know how to use it,” Dr. Messonnier said.
 

MMWR details

The CDC on Jan. 6 also provided an update on anaphylaxis in Morbidity and Mortality Weekly Report (MMWR).

The information included in the report was based on cases reported with the Pfizer-BioNTech vaccine – the first to get emergency use authorization from the FDA. On the call with reporters, CDC officials confirmed there have been additional reports since then and anaphylaxis has been reported with both the Pfizer-BioNTech and Moderna vaccines. CDC officials said they could not give a breakdown of how many cases were linked to each of these products at this time.

Between Dec. 14 and 23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine. Most reactions – 71% – occurred within 15 minutes of vaccination.

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

Health care providers should be ready to treat rare cases of anaphylaxis following administration of COVID-19 vaccines, federal medical officials have urged. The officials also stressed the importance of continuing vaccinations, despite reports of the rare side effect.

There have been 29 cases of anaphylaxis to date following administration of a COVID-19 vaccine, officials from the Centers for Disease Control and Prevention said in a call with reporters on Jan. 6.

The severe allergic reaction, which appears to be rare, can happen with either the Pfizer-BioNTech vaccine or the rival Moderna product. The Food and Drug Administration granted emergency use authorizations for these two vaccines in December.

Even with the cases seen to date, the COVID-19 vaccines remain a “good value proposition,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization, said in the call.

There have been about 11.1 cases of anaphylaxis per million doses with the Pfizer-BioNTech COVID-19 vaccine, which is higher than the estimated 1.3 cases per million doses with influenza vaccines, she said. But the low risk of anaphylaxis must be balanced against the threat of COVID-19, which currently claims about 2,000 lives a day in the United States, she said. In addition, many people are reporting long-term complications with COVID-19 even if they recover.

Kept in context, the data on anaphylaxis should not scare people away from getting a COVID-19 vaccine, she added.

“Their risk from COVID and poor outcomes is still more than the risk of a severe outcome from the vaccine,” Dr. Messonnier said. “And fortunately, we know how to treat anaphylaxis.”

Dr. Messonnier urged health care workers administering COVID-19 vaccines to be prepared.

“Anybody administering vaccines needs not just to have the EpiPen available, but frankly, to know how to use it,” Dr. Messonnier said.
 

MMWR details

The CDC on Jan. 6 also provided an update on anaphylaxis in Morbidity and Mortality Weekly Report (MMWR).

The information included in the report was based on cases reported with the Pfizer-BioNTech vaccine – the first to get emergency use authorization from the FDA. On the call with reporters, CDC officials confirmed there have been additional reports since then and anaphylaxis has been reported with both the Pfizer-BioNTech and Moderna vaccines. CDC officials said they could not give a breakdown of how many cases were linked to each of these products at this time.

Between Dec. 14 and 23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine. Most reactions – 71% – occurred within 15 minutes of vaccination.

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

Saliva spit tests stack up well against the gold standard for molecular COVID-19 tests – the back-of-the-nose deep swab – without the discomfort and induced coughing or sneezing of the test taker, updated guidelines indicate.

In a press briefing on Jan. 6, the Infectious Diseases Society of America explained the findings of an expert panel that reviewed the literature since the IDSA released its first guidelines in May.

The panel found that saliva tests were especially effective if the test included instructions to cough or clear the throat before spitting into the tube, said panel chair Kimberly E. Hanson, MD, MHS, of University of Utah Health, Salt Lake City.
 

Throat swab alone less effective

Using a throat swab alone was less effective and missed more cases than the other methods, she said.

The IDSA has updated its recommendation: A saliva test or swabs from either the middle or front of the nose front are preferred to a throat swab alone.

A combination of saliva and swabs from the front and middle of the nose and throat together “looked pretty much equivalent” to the gold-standard deep swab, the panel found.

She acknowledged, however, that multiple swabs exacerbate already challenging supply issues.

Saliva samples do come with challenges, Dr. Hanson noted. A laboratory must validate that its systems can handle the stickier material. And asking a patient to cough necessitates more personal protective equipment for the health care professional.

Each center will have to tailor the specimen type it chooses, based on what resources it has available and the setting – whether in a hospital or a drive-through operation, for instance, she said.
 

Rapid testing vs. standard

Panel member Angela M. Caliendo, MD, PhD, of Brown University, Providence, R.I., said the panel preferred rapid polymerase chain reaction tests and standard, laboratory-based PCR tests over a rapid isothermal test.

The panel defined rapid tests as those for which results are available within an hour after a test provider has the specimen in hand. They excluded home tests for this category.

The only rapid isothermal test that had enough data on which to issue a recommendation was the ID NOW test (Abbott Labs), she noted. 

Rapid PCR tests performed just as well as the standard laboratory-based tests, she said, with a high sensitivity of “97% on average and a very high specificity.”

But the rapid isothermal test had an average sensitivity of only about 80%, compared with the lab-based PCR test, Dr. Caliendo said, yielding a substantial number of false-negative results.

Testing centers will have to weigh the considerable advantages of having results in 15 minutes with a rapid isothermal test and being able to educate positive patients about immediate isolation against the potential for false negatives, which could send positive patients home thinking they don’t have the virus – and thus potentially spreading the disease.

And if a clinician gets a negative result with the rapid isothermal test, but has a strong suspicion the person has COVID or lives in an area with high prevalence, a backup test with a rapid PCR or laboratory-based test should be administered.

“You will miss a certain percentage of people using this rapid isothermal test,” she said.

However, Dr. Caliendo said, if the only available option is the isothermal test, “you should definitely use it because it’s certainly better than not testing at all.”

On a positive note, she said, all the varieties of tests have high specificity, so “you’re not going to see a lot of false-positive results.”

The guidelines back in May didn’t make recommendations on rapid tests, she said, because there weren’t enough data in the literature.

Dr. Caliendo noted that most of the available data were for symptomatic patients, but there are some data that show the amount of virus in the respiratory tract is similar for people with and without symptoms. The panel, therefore, expects that the performance of the various assays would be similar whether or not a person had symptoms.
 

Testing the immunocompromised

Dr. Hanson said the original recommendation in May was to do molecular testing for asymptomatic people who were awaiting a transplant or were waiting to start immunosuppressive therapy for cancer or an autoimmune disease. Now the current guidelines “make no recommendation for or against screening” in those cases.

Dr. Hanson added that the panel feels that patients awaiting bone marrow and solid organ transplants should have the testing because of the high risks that will result if patients have contracted the virus.

But for those with cancer or an autoimmune disease, the panel decided to leave it up to each physician to assess individual risk and determine whether the patient should be tested.
 

Home testing

The IDSA guidelines didn’t weigh in on home testing because the products are so new and studies so far have included fewer than 200 patients. But Dr. Caliendo said they clearly perform better earlier in the disease phase – the first 5-7 days – when the amount of the virus is higher.

Dr. Hanson and Dr. Caliendo also fielded a question about what the new virus variant, first discovered in the United Kingdom and now spreading to other countries (including the United States) means for diagnostic testing.

“So far we think with the majority of tests that are [emergency use] authorized, it doesn’t look like this new variant should really affect test performance,” Dr. Hanson said.

The variant has differences in the spike gene, and many of the current tests detect and identify SARS-CoV-2 without the spike gene so they wouldn’t be affected, she added.

Dr. Caliendo agreed: “I think the vast majority of our tests should be in good shape.”

Dr. Hanson and Dr. Caliendo disclosed no relevant financial relationships.

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

Saliva spit tests stack up well against the gold standard for molecular COVID-19 tests – the back-of-the-nose deep swab – without the discomfort and induced coughing or sneezing of the test taker, updated guidelines indicate.

In a press briefing on Jan. 6, the Infectious Diseases Society of America explained the findings of an expert panel that reviewed the literature since the IDSA released its first guidelines in May.

The panel found that saliva tests were especially effective if the test included instructions to cough or clear the throat before spitting into the tube, said panel chair Kimberly E. Hanson, MD, MHS, of University of Utah Health, Salt Lake City.
 

Throat swab alone less effective

Using a throat swab alone was less effective and missed more cases than the other methods, she said.

The IDSA has updated its recommendation: A saliva test or swabs from either the middle or front of the nose front are preferred to a throat swab alone.

A combination of saliva and swabs from the front and middle of the nose and throat together “looked pretty much equivalent” to the gold-standard deep swab, the panel found.

She acknowledged, however, that multiple swabs exacerbate already challenging supply issues.

Saliva samples do come with challenges, Dr. Hanson noted. A laboratory must validate that its systems can handle the stickier material. And asking a patient to cough necessitates more personal protective equipment for the health care professional.

Each center will have to tailor the specimen type it chooses, based on what resources it has available and the setting – whether in a hospital or a drive-through operation, for instance, she said.
 

Rapid testing vs. standard

Panel member Angela M. Caliendo, MD, PhD, of Brown University, Providence, R.I., said the panel preferred rapid polymerase chain reaction tests and standard, laboratory-based PCR tests over a rapid isothermal test.

The panel defined rapid tests as those for which results are available within an hour after a test provider has the specimen in hand. They excluded home tests for this category.

The only rapid isothermal test that had enough data on which to issue a recommendation was the ID NOW test (Abbott Labs), she noted. 

Rapid PCR tests performed just as well as the standard laboratory-based tests, she said, with a high sensitivity of “97% on average and a very high specificity.”

But the rapid isothermal test had an average sensitivity of only about 80%, compared with the lab-based PCR test, Dr. Caliendo said, yielding a substantial number of false-negative results.

Testing centers will have to weigh the considerable advantages of having results in 15 minutes with a rapid isothermal test and being able to educate positive patients about immediate isolation against the potential for false negatives, which could send positive patients home thinking they don’t have the virus – and thus potentially spreading the disease.

And if a clinician gets a negative result with the rapid isothermal test, but has a strong suspicion the person has COVID or lives in an area with high prevalence, a backup test with a rapid PCR or laboratory-based test should be administered.

“You will miss a certain percentage of people using this rapid isothermal test,” she said.

However, Dr. Caliendo said, if the only available option is the isothermal test, “you should definitely use it because it’s certainly better than not testing at all.”

On a positive note, she said, all the varieties of tests have high specificity, so “you’re not going to see a lot of false-positive results.”

The guidelines back in May didn’t make recommendations on rapid tests, she said, because there weren’t enough data in the literature.

Dr. Caliendo noted that most of the available data were for symptomatic patients, but there are some data that show the amount of virus in the respiratory tract is similar for people with and without symptoms. The panel, therefore, expects that the performance of the various assays would be similar whether or not a person had symptoms.
 

Testing the immunocompromised

Dr. Hanson said the original recommendation in May was to do molecular testing for asymptomatic people who were awaiting a transplant or were waiting to start immunosuppressive therapy for cancer or an autoimmune disease. Now the current guidelines “make no recommendation for or against screening” in those cases.

Dr. Hanson added that the panel feels that patients awaiting bone marrow and solid organ transplants should have the testing because of the high risks that will result if patients have contracted the virus.

But for those with cancer or an autoimmune disease, the panel decided to leave it up to each physician to assess individual risk and determine whether the patient should be tested.
 

Home testing

The IDSA guidelines didn’t weigh in on home testing because the products are so new and studies so far have included fewer than 200 patients. But Dr. Caliendo said they clearly perform better earlier in the disease phase – the first 5-7 days – when the amount of the virus is higher.

Dr. Hanson and Dr. Caliendo also fielded a question about what the new virus variant, first discovered in the United Kingdom and now spreading to other countries (including the United States) means for diagnostic testing.

“So far we think with the majority of tests that are [emergency use] authorized, it doesn’t look like this new variant should really affect test performance,” Dr. Hanson said.

The variant has differences in the spike gene, and many of the current tests detect and identify SARS-CoV-2 without the spike gene so they wouldn’t be affected, she added.

Dr. Caliendo agreed: “I think the vast majority of our tests should be in good shape.”

Dr. Hanson and Dr. Caliendo disclosed no relevant financial relationships.

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

Saliva spit tests stack up well against the gold standard for molecular COVID-19 tests – the back-of-the-nose deep swab – without the discomfort and induced coughing or sneezing of the test taker, updated guidelines indicate.

In a press briefing on Jan. 6, the Infectious Diseases Society of America explained the findings of an expert panel that reviewed the literature since the IDSA released its first guidelines in May.

The panel found that saliva tests were especially effective if the test included instructions to cough or clear the throat before spitting into the tube, said panel chair Kimberly E. Hanson, MD, MHS, of University of Utah Health, Salt Lake City.
 

Throat swab alone less effective

Using a throat swab alone was less effective and missed more cases than the other methods, she said.

The IDSA has updated its recommendation: A saliva test or swabs from either the middle or front of the nose front are preferred to a throat swab alone.

A combination of saliva and swabs from the front and middle of the nose and throat together “looked pretty much equivalent” to the gold-standard deep swab, the panel found.

She acknowledged, however, that multiple swabs exacerbate already challenging supply issues.

Saliva samples do come with challenges, Dr. Hanson noted. A laboratory must validate that its systems can handle the stickier material. And asking a patient to cough necessitates more personal protective equipment for the health care professional.

Each center will have to tailor the specimen type it chooses, based on what resources it has available and the setting – whether in a hospital or a drive-through operation, for instance, she said.
 

Rapid testing vs. standard

Panel member Angela M. Caliendo, MD, PhD, of Brown University, Providence, R.I., said the panel preferred rapid polymerase chain reaction tests and standard, laboratory-based PCR tests over a rapid isothermal test.

The panel defined rapid tests as those for which results are available within an hour after a test provider has the specimen in hand. They excluded home tests for this category.

The only rapid isothermal test that had enough data on which to issue a recommendation was the ID NOW test (Abbott Labs), she noted. 

Rapid PCR tests performed just as well as the standard laboratory-based tests, she said, with a high sensitivity of “97% on average and a very high specificity.”

But the rapid isothermal test had an average sensitivity of only about 80%, compared with the lab-based PCR test, Dr. Caliendo said, yielding a substantial number of false-negative results.

Testing centers will have to weigh the considerable advantages of having results in 15 minutes with a rapid isothermal test and being able to educate positive patients about immediate isolation against the potential for false negatives, which could send positive patients home thinking they don’t have the virus – and thus potentially spreading the disease.

And if a clinician gets a negative result with the rapid isothermal test, but has a strong suspicion the person has COVID or lives in an area with high prevalence, a backup test with a rapid PCR or laboratory-based test should be administered.

“You will miss a certain percentage of people using this rapid isothermal test,” she said.

However, Dr. Caliendo said, if the only available option is the isothermal test, “you should definitely use it because it’s certainly better than not testing at all.”

On a positive note, she said, all the varieties of tests have high specificity, so “you’re not going to see a lot of false-positive results.”

The guidelines back in May didn’t make recommendations on rapid tests, she said, because there weren’t enough data in the literature.

Dr. Caliendo noted that most of the available data were for symptomatic patients, but there are some data that show the amount of virus in the respiratory tract is similar for people with and without symptoms. The panel, therefore, expects that the performance of the various assays would be similar whether or not a person had symptoms.
 

Testing the immunocompromised

Dr. Hanson said the original recommendation in May was to do molecular testing for asymptomatic people who were awaiting a transplant or were waiting to start immunosuppressive therapy for cancer or an autoimmune disease. Now the current guidelines “make no recommendation for or against screening” in those cases.

Dr. Hanson added that the panel feels that patients awaiting bone marrow and solid organ transplants should have the testing because of the high risks that will result if patients have contracted the virus.

But for those with cancer or an autoimmune disease, the panel decided to leave it up to each physician to assess individual risk and determine whether the patient should be tested.
 

Home testing

The IDSA guidelines didn’t weigh in on home testing because the products are so new and studies so far have included fewer than 200 patients. But Dr. Caliendo said they clearly perform better earlier in the disease phase – the first 5-7 days – when the amount of the virus is higher.

Dr. Hanson and Dr. Caliendo also fielded a question about what the new virus variant, first discovered in the United Kingdom and now spreading to other countries (including the United States) means for diagnostic testing.

“So far we think with the majority of tests that are [emergency use] authorized, it doesn’t look like this new variant should really affect test performance,” Dr. Hanson said.

The variant has differences in the spike gene, and many of the current tests detect and identify SARS-CoV-2 without the spike gene so they wouldn’t be affected, she added.

Dr. Caliendo agreed: “I think the vast majority of our tests should be in good shape.”

Dr. Hanson and Dr. Caliendo disclosed no relevant financial relationships.

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

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Obese women may benefit from a higher dose of magnesium sulfate to protect against preeclampsia, based on data from a randomized trial.

Pharmacokinetic models have shown that, “in women who received a 4-g intravenous loading dose followed by a 2-g/h IV maintenance dose, obese women took approximately twice as long as women of mean body weight in the sample to achieve these previously accepted therapeutic serum magnesium concentrations,” which suggests the need for alternate dosing based on body mass index, wrote Kathleen F. Brookfield, MD, of Oregon Health & Science University, Portland, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers randomized 37 women aged 15-45 years with a BMI of 35 kg/m² or higher who were at least 32 weeks’ gestation to receive the standard Zuspan regimen of magnesium sulfate (4 g intravenous loading dose, followed by a 1-g/hour infusion) or to higher dosing (6 g IV loading dose, followed by a 2-g/hour infusion).
 

Higher dose increases effectiveness

Serum magnesium concentrations were measured at baseline, and after administration of magnesium sulfate at 1 hour, 4 hours, and delivery; the primary outcome was the proportion of women with subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration.

After 4 hours, the average magnesium sulfate concentrations were significantly higher for women in the high-dose group vs. the standard group (4.41 mg/dL vs. 3.53 mg/dL). In addition, 100% of women in the standard group had subtherapeutic serum magnesium concentrations compared with 63% of the high-dose group.

No significant differences in maternal side effects or neonatal outcomes occurred between the groups. However, rates of nausea and flushing were higher in the higher dose group, compared with the standard group (10.5% vs. 5.5% and 5.2% vs. 0%, respectively).

The study findings were limited by several factors including the lack of statistical power to evaluate clinical outcomes and lack of generalizability to extremely obese patients, as well as to settings in which the higher-dose regimen is already the standard treatment, the researchers noted. However, the results were strengthened by the use of prospective pharmacokinetic data to determine dosing.

The researchers also noted that the study was not powered to examine preeclampsia as an outcome “and there is no evidence to date to suggest women in the United States with higher BMIs are more likely to experience eclampsia,” they said. “Therefore, we caution against universally applying the study findings to obese women without also considering the potential for increased toxicity with higher dosing regimens,” they added.

Current results may not affect practice

The study objectives are unclear, as they do not change the dosing for magnesium sulfate already in use, said Baha M. Sibai, MD, of the University of Texas Health Science Center at Houston, in an interview.

Dr. Sibai said he was not surprised by the findings. “This information has been known for almost 30 years as to serum levels with different dosing irrespective of BMI,” he said. Based on current evidence, Dr. Sibai advised clinicians “not to change your practice, since there are no therapeutic levels for preventing seizures.” In fact, “the largest trial that included 10,000 women showed no difference in the rate of eclampsia between 4 grams loading with 1 g/hour [magnesium sulfate] and 6 g loading and 2 g/hour,” he explained.

Future research should focus on different outcomes, said Dr. Sibai. “The outcome should be eclampsia and not serum levels. This requires studying over 6,000 women,” he emphasized.

The study was supported by the National Institutes of Health Loan Repayment Program and a Mission Support Award from Oregon Health & Science University to Dr. Brookfield and by the Oregon Clinical & Translational Research Institute grant. Dr. Brookfield also disclosed funding from the World Health Organization. Dr. Sibai had no financial conflicts to disclose.

SOURCE: Brookfield KF et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004137.

Obese women may benefit from a higher dose of magnesium sulfate to protect against preeclampsia, based on data from a randomized trial.

Pharmacokinetic models have shown that, “in women who received a 4-g intravenous loading dose followed by a 2-g/h IV maintenance dose, obese women took approximately twice as long as women of mean body weight in the sample to achieve these previously accepted therapeutic serum magnesium concentrations,” which suggests the need for alternate dosing based on body mass index, wrote Kathleen F. Brookfield, MD, of Oregon Health & Science University, Portland, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers randomized 37 women aged 15-45 years with a BMI of 35 kg/m² or higher who were at least 32 weeks’ gestation to receive the standard Zuspan regimen of magnesium sulfate (4 g intravenous loading dose, followed by a 1-g/hour infusion) or to higher dosing (6 g IV loading dose, followed by a 2-g/hour infusion).
 

Higher dose increases effectiveness

Serum magnesium concentrations were measured at baseline, and after administration of magnesium sulfate at 1 hour, 4 hours, and delivery; the primary outcome was the proportion of women with subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration.

After 4 hours, the average magnesium sulfate concentrations were significantly higher for women in the high-dose group vs. the standard group (4.41 mg/dL vs. 3.53 mg/dL). In addition, 100% of women in the standard group had subtherapeutic serum magnesium concentrations compared with 63% of the high-dose group.

No significant differences in maternal side effects or neonatal outcomes occurred between the groups. However, rates of nausea and flushing were higher in the higher dose group, compared with the standard group (10.5% vs. 5.5% and 5.2% vs. 0%, respectively).

The study findings were limited by several factors including the lack of statistical power to evaluate clinical outcomes and lack of generalizability to extremely obese patients, as well as to settings in which the higher-dose regimen is already the standard treatment, the researchers noted. However, the results were strengthened by the use of prospective pharmacokinetic data to determine dosing.

The researchers also noted that the study was not powered to examine preeclampsia as an outcome “and there is no evidence to date to suggest women in the United States with higher BMIs are more likely to experience eclampsia,” they said. “Therefore, we caution against universally applying the study findings to obese women without also considering the potential for increased toxicity with higher dosing regimens,” they added.

Current results may not affect practice

The study objectives are unclear, as they do not change the dosing for magnesium sulfate already in use, said Baha M. Sibai, MD, of the University of Texas Health Science Center at Houston, in an interview.

Dr. Sibai said he was not surprised by the findings. “This information has been known for almost 30 years as to serum levels with different dosing irrespective of BMI,” he said. Based on current evidence, Dr. Sibai advised clinicians “not to change your practice, since there are no therapeutic levels for preventing seizures.” In fact, “the largest trial that included 10,000 women showed no difference in the rate of eclampsia between 4 grams loading with 1 g/hour [magnesium sulfate] and 6 g loading and 2 g/hour,” he explained.

Future research should focus on different outcomes, said Dr. Sibai. “The outcome should be eclampsia and not serum levels. This requires studying over 6,000 women,” he emphasized.

The study was supported by the National Institutes of Health Loan Repayment Program and a Mission Support Award from Oregon Health & Science University to Dr. Brookfield and by the Oregon Clinical & Translational Research Institute grant. Dr. Brookfield also disclosed funding from the World Health Organization. Dr. Sibai had no financial conflicts to disclose.

SOURCE: Brookfield KF et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004137.

Obese women may benefit from a higher dose of magnesium sulfate to protect against preeclampsia, based on data from a randomized trial.

Pharmacokinetic models have shown that, “in women who received a 4-g intravenous loading dose followed by a 2-g/h IV maintenance dose, obese women took approximately twice as long as women of mean body weight in the sample to achieve these previously accepted therapeutic serum magnesium concentrations,” which suggests the need for alternate dosing based on body mass index, wrote Kathleen F. Brookfield, MD, of Oregon Health & Science University, Portland, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers randomized 37 women aged 15-45 years with a BMI of 35 kg/m² or higher who were at least 32 weeks’ gestation to receive the standard Zuspan regimen of magnesium sulfate (4 g intravenous loading dose, followed by a 1-g/hour infusion) or to higher dosing (6 g IV loading dose, followed by a 2-g/hour infusion).
 

Higher dose increases effectiveness

Serum magnesium concentrations were measured at baseline, and after administration of magnesium sulfate at 1 hour, 4 hours, and delivery; the primary outcome was the proportion of women with subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration.

After 4 hours, the average magnesium sulfate concentrations were significantly higher for women in the high-dose group vs. the standard group (4.41 mg/dL vs. 3.53 mg/dL). In addition, 100% of women in the standard group had subtherapeutic serum magnesium concentrations compared with 63% of the high-dose group.

No significant differences in maternal side effects or neonatal outcomes occurred between the groups. However, rates of nausea and flushing were higher in the higher dose group, compared with the standard group (10.5% vs. 5.5% and 5.2% vs. 0%, respectively).

The study findings were limited by several factors including the lack of statistical power to evaluate clinical outcomes and lack of generalizability to extremely obese patients, as well as to settings in which the higher-dose regimen is already the standard treatment, the researchers noted. However, the results were strengthened by the use of prospective pharmacokinetic data to determine dosing.

The researchers also noted that the study was not powered to examine preeclampsia as an outcome “and there is no evidence to date to suggest women in the United States with higher BMIs are more likely to experience eclampsia,” they said. “Therefore, we caution against universally applying the study findings to obese women without also considering the potential for increased toxicity with higher dosing regimens,” they added.

Current results may not affect practice

The study objectives are unclear, as they do not change the dosing for magnesium sulfate already in use, said Baha M. Sibai, MD, of the University of Texas Health Science Center at Houston, in an interview.

Dr. Sibai said he was not surprised by the findings. “This information has been known for almost 30 years as to serum levels with different dosing irrespective of BMI,” he said. Based on current evidence, Dr. Sibai advised clinicians “not to change your practice, since there are no therapeutic levels for preventing seizures.” In fact, “the largest trial that included 10,000 women showed no difference in the rate of eclampsia between 4 grams loading with 1 g/hour [magnesium sulfate] and 6 g loading and 2 g/hour,” he explained.

Future research should focus on different outcomes, said Dr. Sibai. “The outcome should be eclampsia and not serum levels. This requires studying over 6,000 women,” he emphasized.

The study was supported by the National Institutes of Health Loan Repayment Program and a Mission Support Award from Oregon Health & Science University to Dr. Brookfield and by the Oregon Clinical & Translational Research Institute grant. Dr. Brookfield also disclosed funding from the World Health Organization. Dr. Sibai had no financial conflicts to disclose.

SOURCE: Brookfield KF et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004137.

Incorporating gender-nonconforming patients into practice can seem like a daunting task at first. However, obstetricians/gynecologists, midwives, and other advanced women’s health care practitioners can provide quality care for both transgender men and women. Basic preventative services such as routine health and cancer screening and testing for sexually transmitted infections does not require specialized training in transgender health. In fact, administration of hormonal therapy and some surgical interventions are well within the scope of practice of the general obstetrician/gynecologist, as long as the provider has undergone appropriate training to achieve expertise. For example, organizations such as the World Professional Association for Transgender Health (WPATH) not only provides standards of care regarding the treatment of transgender individuals, but they also have training and educational opportunities targeted at providers who wish to become certified in more advanced care of the transgender patient. If an obstetrician/gynecologist is interested in prescribing hormone therapy, seeking further training within the field is a must.

It is important to remember that the process by which transgender individuals express their gender is a spectrum. Not all patients who identify as transgender will seek hormone therapy or surgical procedures. However, even if a provider has not undergone more specific training to administer hormone therapy, it is still very important to have a basic understanding of the hormones, routes of administration, and side effects.

While cross-sex hormone therapy does differ in practice, compared with hormone replacement therapy in cisgender counterparts, the principles are relatively similar. Testosterone therapy is the mainstay treatment for transgender men who desire medical transition.^1,2 The overall goal of therapy is to achieve testosterone levels within the cisgender male physiologic range (300-1000 ng/dL). While the most common route of administration is subcutaneous or intramuscular injections in weekly, biweekly, or quarterly intervals, other routes may include daily transdermal patches and gels or oral formulations.1 Within the first few months of use, patients will notice signs of masculinization such as increased facial and body hair, increased muscle mass, increased libido, and amenorrhea. Other changes include male-pattern hair loss, clitoromegaly, redistribution of fat, voice deepening, and mood changes.¹

Hormone therapy for transgender women is a bit more complicated as estrogen alone will often not achieve feminizing characteristics that are satisfying for patients.³ Estrogen therapy can include oral formulations of 17-beta estradiol or conjugated estrogens, although the latter is typically avoided because of the marked increase in thromboembolic events. Estrogens can also be administered in sublingual, intramuscular, or transdermal forms. Antiandrogens are often required to help decrease endogenous testosterone levels to cisgender female levels (30-100 ng/dL).³ Spironolactone is most commonly prescribed as an adjunct to estrogen therapy. Finasteride and GnRH agonists like leuprolide acetate can also be added if spironolactone is not effective or not tolerated by the patient. Feminizing effects of estrogen can take several months and most commonly include decreased spontaneous erections, decreased libido, breast growth, redistribution of fat to the waist and hips, decreased skin oiliness, and softening of the skin.³

Overall, hormone therapy for both transgender men and women is considered effective, safe, and well tolerated.⁴ Monitoring is typically performed every 3 months within the first year after initiating hormone therapy, and then continued every 6-12 months thereafter. Routine screening for all organs and tissues present (e.g. prostate, breast) should be undertaken.³ While this simply highlights the therapy and surveillance for patients, it is important to remember that many transgender men and women will see an obstetrician/gynecologist at some interval during their transition. Ultimately, it is paramount that we as obstetricians/gynecologists have a basic understanding of the treatments available so we can provide our patients with competent and compassionate care.
 

Dr. Brandt is an obstetrician/gynecologist and a plastic surgeon at Reading Hospital/Tower Health System in West Reading, Pa., where she has developed a gender-affirming medical and surgical clinic for ob.gyn. residents and plastic surgeon fellows.

References

1. World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 7th version. Accessed 10/15/20.

2. Joint meeting of the International Society of Endocrinology and the Endocrine Society 2014; ICE/ENDO 2014, Paper 14354. Accessed 01/08/16.

3. Qian R, Safer JD. Hormone treatment for the adult transgender patient, in “Comprehensive Care of the Transgender Patient,” 1st ed. Philadelphia: Elsevier, 2020, pp. 34-6.

4. Weinand JD and Safer JD. Hormone therapy in transgender adults is safe with provider supervision: A review of hormone therapy sequelae for transgender individuals. J Clin Transl Endocrinol. 2015;2(2):55-60.
 

Incorporating gender-nonconforming patients into practice can seem like a daunting task at first. However, obstetricians/gynecologists, midwives, and other advanced women’s health care practitioners can provide quality care for both transgender men and women. Basic preventative services such as routine health and cancer screening and testing for sexually transmitted infections does not require specialized training in transgender health. In fact, administration of hormonal therapy and some surgical interventions are well within the scope of practice of the general obstetrician/gynecologist, as long as the provider has undergone appropriate training to achieve expertise. For example, organizations such as the World Professional Association for Transgender Health (WPATH) not only provides standards of care regarding the treatment of transgender individuals, but they also have training and educational opportunities targeted at providers who wish to become certified in more advanced care of the transgender patient. If an obstetrician/gynecologist is interested in prescribing hormone therapy, seeking further training within the field is a must.

It is important to remember that the process by which transgender individuals express their gender is a spectrum. Not all patients who identify as transgender will seek hormone therapy or surgical procedures. However, even if a provider has not undergone more specific training to administer hormone therapy, it is still very important to have a basic understanding of the hormones, routes of administration, and side effects.

While cross-sex hormone therapy does differ in practice, compared with hormone replacement therapy in cisgender counterparts, the principles are relatively similar. Testosterone therapy is the mainstay treatment for transgender men who desire medical transition.^1,2 The overall goal of therapy is to achieve testosterone levels within the cisgender male physiologic range (300-1000 ng/dL). While the most common route of administration is subcutaneous or intramuscular injections in weekly, biweekly, or quarterly intervals, other routes may include daily transdermal patches and gels or oral formulations.1 Within the first few months of use, patients will notice signs of masculinization such as increased facial and body hair, increased muscle mass, increased libido, and amenorrhea. Other changes include male-pattern hair loss, clitoromegaly, redistribution of fat, voice deepening, and mood changes.¹

Hormone therapy for transgender women is a bit more complicated as estrogen alone will often not achieve feminizing characteristics that are satisfying for patients.³ Estrogen therapy can include oral formulations of 17-beta estradiol or conjugated estrogens, although the latter is typically avoided because of the marked increase in thromboembolic events. Estrogens can also be administered in sublingual, intramuscular, or transdermal forms. Antiandrogens are often required to help decrease endogenous testosterone levels to cisgender female levels (30-100 ng/dL).³ Spironolactone is most commonly prescribed as an adjunct to estrogen therapy. Finasteride and GnRH agonists like leuprolide acetate can also be added if spironolactone is not effective or not tolerated by the patient. Feminizing effects of estrogen can take several months and most commonly include decreased spontaneous erections, decreased libido, breast growth, redistribution of fat to the waist and hips, decreased skin oiliness, and softening of the skin.³

Overall, hormone therapy for both transgender men and women is considered effective, safe, and well tolerated.⁴ Monitoring is typically performed every 3 months within the first year after initiating hormone therapy, and then continued every 6-12 months thereafter. Routine screening for all organs and tissues present (e.g. prostate, breast) should be undertaken.³ While this simply highlights the therapy and surveillance for patients, it is important to remember that many transgender men and women will see an obstetrician/gynecologist at some interval during their transition. Ultimately, it is paramount that we as obstetricians/gynecologists have a basic understanding of the treatments available so we can provide our patients with competent and compassionate care.
 

Dr. Brandt is an obstetrician/gynecologist and a plastic surgeon at Reading Hospital/Tower Health System in West Reading, Pa., where she has developed a gender-affirming medical and surgical clinic for ob.gyn. residents and plastic surgeon fellows.

References

1. World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 7th version. Accessed 10/15/20.

2. Joint meeting of the International Society of Endocrinology and the Endocrine Society 2014; ICE/ENDO 2014, Paper 14354. Accessed 01/08/16.

3. Qian R, Safer JD. Hormone treatment for the adult transgender patient, in “Comprehensive Care of the Transgender Patient,” 1st ed. Philadelphia: Elsevier, 2020, pp. 34-6.

4. Weinand JD and Safer JD. Hormone therapy in transgender adults is safe with provider supervision: A review of hormone therapy sequelae for transgender individuals. J Clin Transl Endocrinol. 2015;2(2):55-60.
 

Incorporating gender-nonconforming patients into practice can seem like a daunting task at first. However, obstetricians/gynecologists, midwives, and other advanced women’s health care practitioners can provide quality care for both transgender men and women. Basic preventative services such as routine health and cancer screening and testing for sexually transmitted infections does not require specialized training in transgender health. In fact, administration of hormonal therapy and some surgical interventions are well within the scope of practice of the general obstetrician/gynecologist, as long as the provider has undergone appropriate training to achieve expertise. For example, organizations such as the World Professional Association for Transgender Health (WPATH) not only provides standards of care regarding the treatment of transgender individuals, but they also have training and educational opportunities targeted at providers who wish to become certified in more advanced care of the transgender patient. If an obstetrician/gynecologist is interested in prescribing hormone therapy, seeking further training within the field is a must.

It is important to remember that the process by which transgender individuals express their gender is a spectrum. Not all patients who identify as transgender will seek hormone therapy or surgical procedures. However, even if a provider has not undergone more specific training to administer hormone therapy, it is still very important to have a basic understanding of the hormones, routes of administration, and side effects.

While cross-sex hormone therapy does differ in practice, compared with hormone replacement therapy in cisgender counterparts, the principles are relatively similar. Testosterone therapy is the mainstay treatment for transgender men who desire medical transition.^1,2 The overall goal of therapy is to achieve testosterone levels within the cisgender male physiologic range (300-1000 ng/dL). While the most common route of administration is subcutaneous or intramuscular injections in weekly, biweekly, or quarterly intervals, other routes may include daily transdermal patches and gels or oral formulations.1 Within the first few months of use, patients will notice signs of masculinization such as increased facial and body hair, increased muscle mass, increased libido, and amenorrhea. Other changes include male-pattern hair loss, clitoromegaly, redistribution of fat, voice deepening, and mood changes.¹

Hormone therapy for transgender women is a bit more complicated as estrogen alone will often not achieve feminizing characteristics that are satisfying for patients.³ Estrogen therapy can include oral formulations of 17-beta estradiol or conjugated estrogens, although the latter is typically avoided because of the marked increase in thromboembolic events. Estrogens can also be administered in sublingual, intramuscular, or transdermal forms. Antiandrogens are often required to help decrease endogenous testosterone levels to cisgender female levels (30-100 ng/dL).³ Spironolactone is most commonly prescribed as an adjunct to estrogen therapy. Finasteride and GnRH agonists like leuprolide acetate can also be added if spironolactone is not effective or not tolerated by the patient. Feminizing effects of estrogen can take several months and most commonly include decreased spontaneous erections, decreased libido, breast growth, redistribution of fat to the waist and hips, decreased skin oiliness, and softening of the skin.³

Overall, hormone therapy for both transgender men and women is considered effective, safe, and well tolerated.⁴ Monitoring is typically performed every 3 months within the first year after initiating hormone therapy, and then continued every 6-12 months thereafter. Routine screening for all organs and tissues present (e.g. prostate, breast) should be undertaken.³ While this simply highlights the therapy and surveillance for patients, it is important to remember that many transgender men and women will see an obstetrician/gynecologist at some interval during their transition. Ultimately, it is paramount that we as obstetricians/gynecologists have a basic understanding of the treatments available so we can provide our patients with competent and compassionate care.
 

Dr. Brandt is an obstetrician/gynecologist and a plastic surgeon at Reading Hospital/Tower Health System in West Reading, Pa., where she has developed a gender-affirming medical and surgical clinic for ob.gyn. residents and plastic surgeon fellows.

References

1. World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 7th version. Accessed 10/15/20.

2. Joint meeting of the International Society of Endocrinology and the Endocrine Society 2014; ICE/ENDO 2014, Paper 14354. Accessed 01/08/16.

3. Qian R, Safer JD. Hormone treatment for the adult transgender patient, in “Comprehensive Care of the Transgender Patient,” 1st ed. Philadelphia: Elsevier, 2020, pp. 34-6.

4. Weinand JD and Safer JD. Hormone therapy in transgender adults is safe with provider supervision: A review of hormone therapy sequelae for transgender individuals. J Clin Transl Endocrinol. 2015;2(2):55-60.
 

In reproductive medicine, there are few, if any, more pressing concerns from our patients than the biological clock, i.e., ovarian aging. While addressing this issue with women can be challenging, particularly for those who are anxious regarding their advanced maternal age, gynecologists must possess a thorough understanding of available diagnostic testing. This article will review the various methods to assess ovarian age and appropriate clinical management.

Ovarian reserve tests

Ovarian reserve represents the quality and quantity of oocytes. The former is defined by the woman’s chronologic age, which is the greatest predictor of fertility. From a peak monthly fecundity rate at age 30 of approximately 20%, the slow and steady decline of fertility ensues. Quantity represents the number of oocytes remaining from the original cohort.

Ovarian reserve is most provocatively gauged by the follicle response to gonadotropin stimulation, typically during an in vitro fertilization (IVF) cycle.

Several biomarkers have been used to assess ovarian age. These include FSH, estradiol, and inhibin B. In general, these tests are more specific than sensitive, i.e., “normal” results do not necessarily exclude decreased ovarian reserve. But as a screening tool for decreased ovarian reserve, the most important factor is the positive predictive value (PPV). Statistically, in a population of women at low risk for decreased ovarian reserve, the PPV will be low despite sensitivity and specificity.

While inhibin B is a more direct and earlier reflection of ovarian function produced by granulose cells, assays lacked consistent results and a standardized cut-off value. FSH is the last biomarker to be affected by decreased ovarian reserve so elevations reflect more “end-stage” ovarian aging.

Additional tests for decreased ovarian reserve include antral follicle count (AFC) and the clomiphene citrate challenge test (CCCT). AFC is determined by using transvaginal ultrasound to count the number of follicular cysts in the 2- to 9-mm range. While AFC can be performed on any day of the cycle, the ovary is most optimally measured on menses because of less cystic activity. A combined AFC of 3-6 is considered severe decreased ovarian reserve. The CCCT involves prescribing clomiphene citrate 100 mg daily from cycle day 5-9 to measure FSH on cycle days 3 and 10. An FSH level greater than 10 IU/L or any elevation in FSH following CCCT is considered decreased ovarian reserve.

FSH had been the standard but levels may dramatically change monthly, making testing only valuable if it is elevated. Consequently, antimüllerian hormone (AMH) and AFC are considered the most useful tools to determine decreased ovarian reserve because of less variability. The other distinct advantage is the ability to obtain AMH any day in the menstrual cycle. Recently, in women undergoing IVF, AMH was superior to FSH in predicting live birth, particularly when their values were discordant (J Ovarian Res. 2018;11:60). While there is no established consensus, the ideal interval for repeating AMH appears to be approximately 3 months (Obstet Gynecol 2016;127:65S-6S).
 

AMH

AMH is expressed in the embryo at 8 weeks by the Sertoli cells of the testis causing the female reproductive internal system (müllerian) to regress. Without AMH expression, the müllerian system remains and the male (woffian duct system) regresses. The discovery of AMH production by the granulosa cells of the ovary launched a new era in the evaluation and management of infertile women. First reported in Fertility & Sterility in 2002 as a much earlier potential marker of ovarian aging, low levels of AMH predict a lower number of eggs in IVF.

AMH levels are produced in the embryo at 36 weeks’ gestation and increase up to the age of 24.5 years, decreasing thereafter. AMH reflects primordial (early) follicles that are FSH independent. The median AMH level decreases per year according to age groups are: 0.25 ng/mL in ages 26-30; 0.2 ng/mL in ages 31-36 years; and 0.1 ng/mL above age 36. (PLOS ONE 2015 doi: 10.1371/journal.pone.0125216).

AMH has also been studied as a potential biomarker to diagnose PCOS. While many women with PCOS have elevated AMH levels (typically greater than 3 ng/mL), there is no consensus on an AMH value that would be a criterion.

Many women, particularly those electing to defer fertility, express interest in obtaining their AMH level to consider planned oocyte cryopreservation, AKA, social egg freezing. While it is possible the results of AMH screening may compel women to electively freeze their eggs, extensive counseling on the implications and pitfalls of AMH levels is essential. Further, AMH cannot be used to accurately predict menopause.
 

Predicting outcomes

No biomarker is necessarily predictive of pregnancy but more a gauge of gonadotropin dosage to induce multifollicular development. AMH is a great predictor of oocyte yield with IVF (J Assist Reprod Genet. 2009;26[7]:383-9). However, in women older than 35 undergoing IVF, low AMH levels have been shown to reduce pregnancy rates (J Hum Reprod Sci. 2017;10:24–30). During IVF cycle attempts, an ultra-low AMH (≤0.4) resulted in high cancellation rates, reduced the number of oocytes retrieved and embryos developed, and lowered pregnancy rates in women of advanced reproductive age.

Alternatively, a study of 750 women who were not infertile and were actively trying to conceive demonstrated no difference in natural pregnancy rates in women aged 30-44 irrespective of AMH levels (JAMA. 2017;318[14]:1367-76).

A special consideration is for cancer patients who are status postgonadotoxic chemotherapy. Their oocyte attrition can be accelerated and AMH levels can become profoundly low. In those patients, current data suggest there is a modest recovery of postchemotherapy AMH levels up to 1 year. Further, oocyte yield following stimulation may be higher than expected despite a poor AMH level.
 

Conclusion

Ovarian aging is currently best measured by combining chronologic age, AFC, and AMH. There is no current evidence that AMH levels should be used to exclude patients from undergoing IVF or to recommend egg donation. Random screening of AMH levels in a low-risk population for decreased ovarian reserve may result in unnecessary alarm.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

In reproductive medicine, there are few, if any, more pressing concerns from our patients than the biological clock, i.e., ovarian aging. While addressing this issue with women can be challenging, particularly for those who are anxious regarding their advanced maternal age, gynecologists must possess a thorough understanding of available diagnostic testing. This article will review the various methods to assess ovarian age and appropriate clinical management.

Ovarian reserve tests

Ovarian reserve represents the quality and quantity of oocytes. The former is defined by the woman’s chronologic age, which is the greatest predictor of fertility. From a peak monthly fecundity rate at age 30 of approximately 20%, the slow and steady decline of fertility ensues. Quantity represents the number of oocytes remaining from the original cohort.

Ovarian reserve is most provocatively gauged by the follicle response to gonadotropin stimulation, typically during an in vitro fertilization (IVF) cycle.

Several biomarkers have been used to assess ovarian age. These include FSH, estradiol, and inhibin B. In general, these tests are more specific than sensitive, i.e., “normal” results do not necessarily exclude decreased ovarian reserve. But as a screening tool for decreased ovarian reserve, the most important factor is the positive predictive value (PPV). Statistically, in a population of women at low risk for decreased ovarian reserve, the PPV will be low despite sensitivity and specificity.

While inhibin B is a more direct and earlier reflection of ovarian function produced by granulose cells, assays lacked consistent results and a standardized cut-off value. FSH is the last biomarker to be affected by decreased ovarian reserve so elevations reflect more “end-stage” ovarian aging.

Additional tests for decreased ovarian reserve include antral follicle count (AFC) and the clomiphene citrate challenge test (CCCT). AFC is determined by using transvaginal ultrasound to count the number of follicular cysts in the 2- to 9-mm range. While AFC can be performed on any day of the cycle, the ovary is most optimally measured on menses because of less cystic activity. A combined AFC of 3-6 is considered severe decreased ovarian reserve. The CCCT involves prescribing clomiphene citrate 100 mg daily from cycle day 5-9 to measure FSH on cycle days 3 and 10. An FSH level greater than 10 IU/L or any elevation in FSH following CCCT is considered decreased ovarian reserve.

FSH had been the standard but levels may dramatically change monthly, making testing only valuable if it is elevated. Consequently, antimüllerian hormone (AMH) and AFC are considered the most useful tools to determine decreased ovarian reserve because of less variability. The other distinct advantage is the ability to obtain AMH any day in the menstrual cycle. Recently, in women undergoing IVF, AMH was superior to FSH in predicting live birth, particularly when their values were discordant (J Ovarian Res. 2018;11:60). While there is no established consensus, the ideal interval for repeating AMH appears to be approximately 3 months (Obstet Gynecol 2016;127:65S-6S).
 

AMH

AMH is expressed in the embryo at 8 weeks by the Sertoli cells of the testis causing the female reproductive internal system (müllerian) to regress. Without AMH expression, the müllerian system remains and the male (woffian duct system) regresses. The discovery of AMH production by the granulosa cells of the ovary launched a new era in the evaluation and management of infertile women. First reported in Fertility & Sterility in 2002 as a much earlier potential marker of ovarian aging, low levels of AMH predict a lower number of eggs in IVF.

AMH levels are produced in the embryo at 36 weeks’ gestation and increase up to the age of 24.5 years, decreasing thereafter. AMH reflects primordial (early) follicles that are FSH independent. The median AMH level decreases per year according to age groups are: 0.25 ng/mL in ages 26-30; 0.2 ng/mL in ages 31-36 years; and 0.1 ng/mL above age 36. (PLOS ONE 2015 doi: 10.1371/journal.pone.0125216).

AMH has also been studied as a potential biomarker to diagnose PCOS. While many women with PCOS have elevated AMH levels (typically greater than 3 ng/mL), there is no consensus on an AMH value that would be a criterion.

Many women, particularly those electing to defer fertility, express interest in obtaining their AMH level to consider planned oocyte cryopreservation, AKA, social egg freezing. While it is possible the results of AMH screening may compel women to electively freeze their eggs, extensive counseling on the implications and pitfalls of AMH levels is essential. Further, AMH cannot be used to accurately predict menopause.
 

Predicting outcomes

No biomarker is necessarily predictive of pregnancy but more a gauge of gonadotropin dosage to induce multifollicular development. AMH is a great predictor of oocyte yield with IVF (J Assist Reprod Genet. 2009;26[7]:383-9). However, in women older than 35 undergoing IVF, low AMH levels have been shown to reduce pregnancy rates (J Hum Reprod Sci. 2017;10:24–30). During IVF cycle attempts, an ultra-low AMH (≤0.4) resulted in high cancellation rates, reduced the number of oocytes retrieved and embryos developed, and lowered pregnancy rates in women of advanced reproductive age.

Alternatively, a study of 750 women who were not infertile and were actively trying to conceive demonstrated no difference in natural pregnancy rates in women aged 30-44 irrespective of AMH levels (JAMA. 2017;318[14]:1367-76).

A special consideration is for cancer patients who are status postgonadotoxic chemotherapy. Their oocyte attrition can be accelerated and AMH levels can become profoundly low. In those patients, current data suggest there is a modest recovery of postchemotherapy AMH levels up to 1 year. Further, oocyte yield following stimulation may be higher than expected despite a poor AMH level.
 

Conclusion

Ovarian aging is currently best measured by combining chronologic age, AFC, and AMH. There is no current evidence that AMH levels should be used to exclude patients from undergoing IVF or to recommend egg donation. Random screening of AMH levels in a low-risk population for decreased ovarian reserve may result in unnecessary alarm.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

In reproductive medicine, there are few, if any, more pressing concerns from our patients than the biological clock, i.e., ovarian aging. While addressing this issue with women can be challenging, particularly for those who are anxious regarding their advanced maternal age, gynecologists must possess a thorough understanding of available diagnostic testing. This article will review the various methods to assess ovarian age and appropriate clinical management.

Ovarian reserve tests

Ovarian reserve represents the quality and quantity of oocytes. The former is defined by the woman’s chronologic age, which is the greatest predictor of fertility. From a peak monthly fecundity rate at age 30 of approximately 20%, the slow and steady decline of fertility ensues. Quantity represents the number of oocytes remaining from the original cohort.

Ovarian reserve is most provocatively gauged by the follicle response to gonadotropin stimulation, typically during an in vitro fertilization (IVF) cycle.

Several biomarkers have been used to assess ovarian age. These include FSH, estradiol, and inhibin B. In general, these tests are more specific than sensitive, i.e., “normal” results do not necessarily exclude decreased ovarian reserve. But as a screening tool for decreased ovarian reserve, the most important factor is the positive predictive value (PPV). Statistically, in a population of women at low risk for decreased ovarian reserve, the PPV will be low despite sensitivity and specificity.

While inhibin B is a more direct and earlier reflection of ovarian function produced by granulose cells, assays lacked consistent results and a standardized cut-off value. FSH is the last biomarker to be affected by decreased ovarian reserve so elevations reflect more “end-stage” ovarian aging.

Additional tests for decreased ovarian reserve include antral follicle count (AFC) and the clomiphene citrate challenge test (CCCT). AFC is determined by using transvaginal ultrasound to count the number of follicular cysts in the 2- to 9-mm range. While AFC can be performed on any day of the cycle, the ovary is most optimally measured on menses because of less cystic activity. A combined AFC of 3-6 is considered severe decreased ovarian reserve. The CCCT involves prescribing clomiphene citrate 100 mg daily from cycle day 5-9 to measure FSH on cycle days 3 and 10. An FSH level greater than 10 IU/L or any elevation in FSH following CCCT is considered decreased ovarian reserve.

FSH had been the standard but levels may dramatically change monthly, making testing only valuable if it is elevated. Consequently, antimüllerian hormone (AMH) and AFC are considered the most useful tools to determine decreased ovarian reserve because of less variability. The other distinct advantage is the ability to obtain AMH any day in the menstrual cycle. Recently, in women undergoing IVF, AMH was superior to FSH in predicting live birth, particularly when their values were discordant (J Ovarian Res. 2018;11:60). While there is no established consensus, the ideal interval for repeating AMH appears to be approximately 3 months (Obstet Gynecol 2016;127:65S-6S).
 

AMH

AMH is expressed in the embryo at 8 weeks by the Sertoli cells of the testis causing the female reproductive internal system (müllerian) to regress. Without AMH expression, the müllerian system remains and the male (woffian duct system) regresses. The discovery of AMH production by the granulosa cells of the ovary launched a new era in the evaluation and management of infertile women. First reported in Fertility & Sterility in 2002 as a much earlier potential marker of ovarian aging, low levels of AMH predict a lower number of eggs in IVF.

AMH levels are produced in the embryo at 36 weeks’ gestation and increase up to the age of 24.5 years, decreasing thereafter. AMH reflects primordial (early) follicles that are FSH independent. The median AMH level decreases per year according to age groups are: 0.25 ng/mL in ages 26-30; 0.2 ng/mL in ages 31-36 years; and 0.1 ng/mL above age 36. (PLOS ONE 2015 doi: 10.1371/journal.pone.0125216).

AMH has also been studied as a potential biomarker to diagnose PCOS. While many women with PCOS have elevated AMH levels (typically greater than 3 ng/mL), there is no consensus on an AMH value that would be a criterion.

Many women, particularly those electing to defer fertility, express interest in obtaining their AMH level to consider planned oocyte cryopreservation, AKA, social egg freezing. While it is possible the results of AMH screening may compel women to electively freeze their eggs, extensive counseling on the implications and pitfalls of AMH levels is essential. Further, AMH cannot be used to accurately predict menopause.
 

Predicting outcomes

No biomarker is necessarily predictive of pregnancy but more a gauge of gonadotropin dosage to induce multifollicular development. AMH is a great predictor of oocyte yield with IVF (J Assist Reprod Genet. 2009;26[7]:383-9). However, in women older than 35 undergoing IVF, low AMH levels have been shown to reduce pregnancy rates (J Hum Reprod Sci. 2017;10:24–30). During IVF cycle attempts, an ultra-low AMH (≤0.4) resulted in high cancellation rates, reduced the number of oocytes retrieved and embryos developed, and lowered pregnancy rates in women of advanced reproductive age.

Alternatively, a study of 750 women who were not infertile and were actively trying to conceive demonstrated no difference in natural pregnancy rates in women aged 30-44 irrespective of AMH levels (JAMA. 2017;318[14]:1367-76).

A special consideration is for cancer patients who are status postgonadotoxic chemotherapy. Their oocyte attrition can be accelerated and AMH levels can become profoundly low. In those patients, current data suggest there is a modest recovery of postchemotherapy AMH levels up to 1 year. Further, oocyte yield following stimulation may be higher than expected despite a poor AMH level.
 

Conclusion

Ovarian aging is currently best measured by combining chronologic age, AFC, and AMH. There is no current evidence that AMH levels should be used to exclude patients from undergoing IVF or to recommend egg donation. Random screening of AMH levels in a low-risk population for decreased ovarian reserve may result in unnecessary alarm.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.

In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.

High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.

The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.

Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.

A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.

As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.

Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
 

Where’s the food?

There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.

Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.

The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.

Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.

UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.

Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.

The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).

High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.

In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.

During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
 

The more UPF, the higher the risk for CVD, death

The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.

Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).

High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.

Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.

Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.

The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.

“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.

“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.

“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.

The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.

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

Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.

In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.

High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.

The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.

Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.

A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.

As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.

Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
 

Where’s the food?

There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.

Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.

The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.

Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.

UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.

Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.

The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).

High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.

In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.

During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
 

The more UPF, the higher the risk for CVD, death

The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.

Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).

High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.

Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.

Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.

The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.

“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.

“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.

“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.

The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.

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

Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.

In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.

High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.

The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.

Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.

A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.

As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.

Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
 

Where’s the food?

There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.

Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.

The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.

Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.

UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.

Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.

The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).

High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.

In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.

During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
 

The more UPF, the higher the risk for CVD, death

The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.

Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).

High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.

Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.

Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.

The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.

“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.

“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.

“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.

The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.

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