Federal Practitioner

If there’s one public health message Americans have heard loud and clear, it’s this one:

Move more.

Take more steps.

Spend more time doing physical activity – at least 150 minutes a week, according to the latest guidelines.

But hearing the message doesn’t mean we act on it. A whopping 25% of Americans don’t get any physical activity beyond what they do in their job, according to a CDC survey.

A new study suggests a different approach: You don’t have to do more. Just do what you’re already doing, but with a little more effort.

The study, which was published in the European Heart Journal, builds on growing evidence that suggests exercise intensity matters just as much as the amount. So, something as simple as turning a leisurely stroll into a brisk walk can, over time, lead to significant reductions in your risk of cardiovascular disease. No additional moves, steps, or minutes needed.
 

Step it up

Researchers at Cambridge University and the University of Leicester in England looked at data from 88,000 middle-aged adults who wore an activity tracking device for 7 days.

The devices tracked both the total amount of activity they did and the intensity of that movement – that is, how fast they walked or how hard they pushed themselves.

The researchers then calculated their physical activity energy expenditure (the number of calories they burned when they were up and moving) and the percentage that came from moderate to vigorous physical activity.

What’s the difference?

• Physical activity means any and every movement you do throughout the day. Mostly it’s mundane tasks like shopping, walking to the mailbox, playing with your dog, or cooking.
• Moderate-intensity physical activity includes things you do at a faster pace. Maybe you’re walking for exercise, doing yard work or household chores, or running late and just trying to get somewhere faster. You’re breathing a little harder and possibly working up a sweat.
• Vigorous-intensity physical activity is usually an exercise session – a run, a strenuous hike, a tough workout in the gym. It can also be an exhausting chore like shoveling snow, which feels like a workout. You’re definitely breathing harder, and you’re probably working up a sweat, even in the middle of winter.

Over the next 6 to 7 years, there were 4,000 new cases of cardiovascular disease among the people in the study.

Those who got at least 20% of their physical activity energy expenditure from moderate to vigorous activities had significantly less risk of heart disease, compared with those whose higher-effort activities were about 10%.

That was true even for those whose total activity was relatively low. As long as higher-effort activities reached 20% of their total, they were 14% less likely to be diagnosed with a heart condition.

And for those with relatively high activity levels, there was little extra benefit if their moderate and vigorous activities remained around 10%.

That finding surprised Paddy Dempsey, PhD, a medical research scientist at Cambridge and the study’s lead author. But it also makes sense.

“People can improve their cardiorespiratory fitness to a greater degree with higher-intensity activity,” he says. “More intensity will stress the system and lead to greater adaptation.”

The key is an increase in the amount of oxygen your heart and lungs can provide your muscles during exercise, a measure known as VO_2max.

Raising your VO_2max is the best way to reduce your risk of early death, especially death from heart disease. Simply moving up from the lowest conditioning category to a higher one will cut your risk of dying in any given year by as much as 60%.
 

Making strides

The study builds on previous research that shows the benefits of moving faster.

Walking faster will naturally increase your stride length, another predictor of longevity and future health. A review study published in 2021 found that older adults who took shorter steps were 26% more likely to have a disability, 34% more likely to have a major adverse event (like an injury that leads to a loss of independence), and 69% more likely to die over the next several years.
 

Quality versus quantity

We’ve focused so far on the quality of your physical activity – moving faster, taking longer strides.

But there’s still a lot to be said for movement quantity.

“It would be a mistake to say volume doesn’t matter,” Dr. Dempsey cautions.

A 2022 study in the journal The Lancet found that the risk of dying during a given period decreases with each increase in daily steps. The protective effect peaks at about 6,000 to 8,000 steps a day for adults 60 and over, and at 8,000 to 10,000 steps for those under 60.

“The relative value of the quality and quantity of exercise are very specific to a person’s goals,” says Chhanda Dutta, PhD, chief of the Clinical Gerontology Branch at the National Institute on Aging. “If performance is the goal, quality matters at least as much as quantity.”

Dr. Dempsey agrees that it’s not a cage match between two. Every step you take is a step in the right direction.

“People can choose or gravitate to an approach that works best for them,” he says. “It’s also helpful to think about where some everyday activities can be punctuated with intensity,” which could be as simple as walking faster when possible.

What matters most is that you choose something, Dr. Dutta says. “You have more to risk by not exercising.”

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

If there’s one public health message Americans have heard loud and clear, it’s this one:

Move more.

Take more steps.

Spend more time doing physical activity – at least 150 minutes a week, according to the latest guidelines.

But hearing the message doesn’t mean we act on it. A whopping 25% of Americans don’t get any physical activity beyond what they do in their job, according to a CDC survey.

A new study suggests a different approach: You don’t have to do more. Just do what you’re already doing, but with a little more effort.

The study, which was published in the European Heart Journal, builds on growing evidence that suggests exercise intensity matters just as much as the amount. So, something as simple as turning a leisurely stroll into a brisk walk can, over time, lead to significant reductions in your risk of cardiovascular disease. No additional moves, steps, or minutes needed.
 

Step it up

Researchers at Cambridge University and the University of Leicester in England looked at data from 88,000 middle-aged adults who wore an activity tracking device for 7 days.

The devices tracked both the total amount of activity they did and the intensity of that movement – that is, how fast they walked or how hard they pushed themselves.

The researchers then calculated their physical activity energy expenditure (the number of calories they burned when they were up and moving) and the percentage that came from moderate to vigorous physical activity.

What’s the difference?

• Physical activity means any and every movement you do throughout the day. Mostly it’s mundane tasks like shopping, walking to the mailbox, playing with your dog, or cooking.
• Moderate-intensity physical activity includes things you do at a faster pace. Maybe you’re walking for exercise, doing yard work or household chores, or running late and just trying to get somewhere faster. You’re breathing a little harder and possibly working up a sweat.
• Vigorous-intensity physical activity is usually an exercise session – a run, a strenuous hike, a tough workout in the gym. It can also be an exhausting chore like shoveling snow, which feels like a workout. You’re definitely breathing harder, and you’re probably working up a sweat, even in the middle of winter.

Over the next 6 to 7 years, there were 4,000 new cases of cardiovascular disease among the people in the study.

Those who got at least 20% of their physical activity energy expenditure from moderate to vigorous activities had significantly less risk of heart disease, compared with those whose higher-effort activities were about 10%.

That was true even for those whose total activity was relatively low. As long as higher-effort activities reached 20% of their total, they were 14% less likely to be diagnosed with a heart condition.

And for those with relatively high activity levels, there was little extra benefit if their moderate and vigorous activities remained around 10%.

That finding surprised Paddy Dempsey, PhD, a medical research scientist at Cambridge and the study’s lead author. But it also makes sense.

“People can improve their cardiorespiratory fitness to a greater degree with higher-intensity activity,” he says. “More intensity will stress the system and lead to greater adaptation.”

The key is an increase in the amount of oxygen your heart and lungs can provide your muscles during exercise, a measure known as VO_2max.

Raising your VO_2max is the best way to reduce your risk of early death, especially death from heart disease. Simply moving up from the lowest conditioning category to a higher one will cut your risk of dying in any given year by as much as 60%.
 

Making strides

The study builds on previous research that shows the benefits of moving faster.

Walking faster will naturally increase your stride length, another predictor of longevity and future health. A review study published in 2021 found that older adults who took shorter steps were 26% more likely to have a disability, 34% more likely to have a major adverse event (like an injury that leads to a loss of independence), and 69% more likely to die over the next several years.
 

Quality versus quantity

We’ve focused so far on the quality of your physical activity – moving faster, taking longer strides.

But there’s still a lot to be said for movement quantity.

“It would be a mistake to say volume doesn’t matter,” Dr. Dempsey cautions.

A 2022 study in the journal The Lancet found that the risk of dying during a given period decreases with each increase in daily steps. The protective effect peaks at about 6,000 to 8,000 steps a day for adults 60 and over, and at 8,000 to 10,000 steps for those under 60.

“The relative value of the quality and quantity of exercise are very specific to a person’s goals,” says Chhanda Dutta, PhD, chief of the Clinical Gerontology Branch at the National Institute on Aging. “If performance is the goal, quality matters at least as much as quantity.”

Dr. Dempsey agrees that it’s not a cage match between two. Every step you take is a step in the right direction.

“People can choose or gravitate to an approach that works best for them,” he says. “It’s also helpful to think about where some everyday activities can be punctuated with intensity,” which could be as simple as walking faster when possible.

What matters most is that you choose something, Dr. Dutta says. “You have more to risk by not exercising.”

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

If there’s one public health message Americans have heard loud and clear, it’s this one:

Move more.

Take more steps.

Spend more time doing physical activity – at least 150 minutes a week, according to the latest guidelines.

But hearing the message doesn’t mean we act on it. A whopping 25% of Americans don’t get any physical activity beyond what they do in their job, according to a CDC survey.

A new study suggests a different approach: You don’t have to do more. Just do what you’re already doing, but with a little more effort.

The study, which was published in the European Heart Journal, builds on growing evidence that suggests exercise intensity matters just as much as the amount. So, something as simple as turning a leisurely stroll into a brisk walk can, over time, lead to significant reductions in your risk of cardiovascular disease. No additional moves, steps, or minutes needed.
 

Step it up

Researchers at Cambridge University and the University of Leicester in England looked at data from 88,000 middle-aged adults who wore an activity tracking device for 7 days.

The devices tracked both the total amount of activity they did and the intensity of that movement – that is, how fast they walked or how hard they pushed themselves.

The researchers then calculated their physical activity energy expenditure (the number of calories they burned when they were up and moving) and the percentage that came from moderate to vigorous physical activity.

What’s the difference?

• Physical activity means any and every movement you do throughout the day. Mostly it’s mundane tasks like shopping, walking to the mailbox, playing with your dog, or cooking.
• Moderate-intensity physical activity includes things you do at a faster pace. Maybe you’re walking for exercise, doing yard work or household chores, or running late and just trying to get somewhere faster. You’re breathing a little harder and possibly working up a sweat.
• Vigorous-intensity physical activity is usually an exercise session – a run, a strenuous hike, a tough workout in the gym. It can also be an exhausting chore like shoveling snow, which feels like a workout. You’re definitely breathing harder, and you’re probably working up a sweat, even in the middle of winter.

Over the next 6 to 7 years, there were 4,000 new cases of cardiovascular disease among the people in the study.

Those who got at least 20% of their physical activity energy expenditure from moderate to vigorous activities had significantly less risk of heart disease, compared with those whose higher-effort activities were about 10%.

That was true even for those whose total activity was relatively low. As long as higher-effort activities reached 20% of their total, they were 14% less likely to be diagnosed with a heart condition.

And for those with relatively high activity levels, there was little extra benefit if their moderate and vigorous activities remained around 10%.

That finding surprised Paddy Dempsey, PhD, a medical research scientist at Cambridge and the study’s lead author. But it also makes sense.

“People can improve their cardiorespiratory fitness to a greater degree with higher-intensity activity,” he says. “More intensity will stress the system and lead to greater adaptation.”

The key is an increase in the amount of oxygen your heart and lungs can provide your muscles during exercise, a measure known as VO_2max.

Raising your VO_2max is the best way to reduce your risk of early death, especially death from heart disease. Simply moving up from the lowest conditioning category to a higher one will cut your risk of dying in any given year by as much as 60%.
 

Making strides

The study builds on previous research that shows the benefits of moving faster.

Walking faster will naturally increase your stride length, another predictor of longevity and future health. A review study published in 2021 found that older adults who took shorter steps were 26% more likely to have a disability, 34% more likely to have a major adverse event (like an injury that leads to a loss of independence), and 69% more likely to die over the next several years.
 

Quality versus quantity

We’ve focused so far on the quality of your physical activity – moving faster, taking longer strides.

But there’s still a lot to be said for movement quantity.

“It would be a mistake to say volume doesn’t matter,” Dr. Dempsey cautions.

A 2022 study in the journal The Lancet found that the risk of dying during a given period decreases with each increase in daily steps. The protective effect peaks at about 6,000 to 8,000 steps a day for adults 60 and over, and at 8,000 to 10,000 steps for those under 60.

“The relative value of the quality and quantity of exercise are very specific to a person’s goals,” says Chhanda Dutta, PhD, chief of the Clinical Gerontology Branch at the National Institute on Aging. “If performance is the goal, quality matters at least as much as quantity.”

Dr. Dempsey agrees that it’s not a cage match between two. Every step you take is a step in the right direction.

“People can choose or gravitate to an approach that works best for them,” he says. “It’s also helpful to think about where some everyday activities can be punctuated with intensity,” which could be as simple as walking faster when possible.

What matters most is that you choose something, Dr. Dutta says. “You have more to risk by not exercising.”

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

The Food and Drug Administration has announced it will not approve the investigational drug poziotinib (Spectrum Pharmaceuticals) for the treatment of certain patients with non–small cell lung cancer (NSCLC).

The clinical data the company submitted were deemed insufficient for approval, and additional data including a randomized clinical trial would be needed, the agency said.

The move is not a surprise, as the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 against approval when it met to discuss the drug in September, as reported at the time by this news organization.

Poziotinib was developed for patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations, which occur in about 2% of patients with NSCLC.

Poziotinib is a potent oral pan-HER tyrosine kinase inhibitor with activity in patients with these mutations. Clinical data from the ZENITH20 Trial reported last year showed an overall response rate of 43.8%, and the drug was described as showing “clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.”

“We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed,” commented Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals. 

However, following multiple interactions with the FDA, “we have made the strategic decision to immediately deprioritize the poziotinib program,” he said. The change is effective immediately, and the company is now in the process of reducing its R&D workforce by approximately 75%.
 

Drug development criticized

At the ODAC meeting, several panelists were openly critical of the approach Spectrum took in developing the drug. The FDA’s top cancer official, Richard Pazdur, MD, characterized Spectrum’s work as “poor drug development” and likened it to “building a house on quicksand.”

The FDA panel detailed several ways they felt that the poziotinib application fell short of the benchmarks needed for accelerated approval.

To win such a speedy clearance, a company needs to show that a drug provides a meaningful therapeutic benefit over existing treatments. The panel argued that, so far, poziotinib appears to be inferior to a product already available for HER2-mutant NSCLC, trastuzumab deruxtecan (Enhertu), which received accelerated approval in August.

The FDA staff contrasted a reported overall response rate for poziotinib, which was estimated at 28% (from data discussed at the meeting), with the overall response rate for trastuzumab deruxtecan, which is 58%.

Harpreet Singh, MD, a director in the FDA’s oncology division, asked the panel to consider what they would do as a physician treating a patient with this mutation, given the choices that are now available.

“That’s something we’re asking the committee to consider … to think about the context of what’s available to you in the clinic,” Dr. Singh said.

Dr. Singh said she expected that patients and physicians would prefer a drug such as trastuzumab deruxtecan, which has a more established record, regardless of the fact that treatment with poziotinib is more convenient because it is given as a tablet.

Dr. Singh and other staff also raised concerns about side effects of poziotinib, including diarrhea, as well as difficulty determining the right dose.

Katherine Scilla, MD, one of the nine ODAC panelists to vote “no,” echoed these views. Although Dr. Scilla, an oncologist at the University of Maryland, Baltimore, sympathized with the need for options for people with this rare form of lung cancer, she was not persuaded by the data on poziotinib that were presented to support accelerated approval.

“I’m not sure that this represents a meaningful therapeutic benefit over other agents,” she said at the time. 

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

The Food and Drug Administration has announced it will not approve the investigational drug poziotinib (Spectrum Pharmaceuticals) for the treatment of certain patients with non–small cell lung cancer (NSCLC).

The clinical data the company submitted were deemed insufficient for approval, and additional data including a randomized clinical trial would be needed, the agency said.

The move is not a surprise, as the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 against approval when it met to discuss the drug in September, as reported at the time by this news organization.

Poziotinib was developed for patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations, which occur in about 2% of patients with NSCLC.

Poziotinib is a potent oral pan-HER tyrosine kinase inhibitor with activity in patients with these mutations. Clinical data from the ZENITH20 Trial reported last year showed an overall response rate of 43.8%, and the drug was described as showing “clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.”

“We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed,” commented Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals. 

However, following multiple interactions with the FDA, “we have made the strategic decision to immediately deprioritize the poziotinib program,” he said. The change is effective immediately, and the company is now in the process of reducing its R&D workforce by approximately 75%.
 

Drug development criticized

At the ODAC meeting, several panelists were openly critical of the approach Spectrum took in developing the drug. The FDA’s top cancer official, Richard Pazdur, MD, characterized Spectrum’s work as “poor drug development” and likened it to “building a house on quicksand.”

The FDA panel detailed several ways they felt that the poziotinib application fell short of the benchmarks needed for accelerated approval.

To win such a speedy clearance, a company needs to show that a drug provides a meaningful therapeutic benefit over existing treatments. The panel argued that, so far, poziotinib appears to be inferior to a product already available for HER2-mutant NSCLC, trastuzumab deruxtecan (Enhertu), which received accelerated approval in August.

The FDA staff contrasted a reported overall response rate for poziotinib, which was estimated at 28% (from data discussed at the meeting), with the overall response rate for trastuzumab deruxtecan, which is 58%.

Harpreet Singh, MD, a director in the FDA’s oncology division, asked the panel to consider what they would do as a physician treating a patient with this mutation, given the choices that are now available.

“That’s something we’re asking the committee to consider … to think about the context of what’s available to you in the clinic,” Dr. Singh said.

Dr. Singh said she expected that patients and physicians would prefer a drug such as trastuzumab deruxtecan, which has a more established record, regardless of the fact that treatment with poziotinib is more convenient because it is given as a tablet.

Dr. Singh and other staff also raised concerns about side effects of poziotinib, including diarrhea, as well as difficulty determining the right dose.

Katherine Scilla, MD, one of the nine ODAC panelists to vote “no,” echoed these views. Although Dr. Scilla, an oncologist at the University of Maryland, Baltimore, sympathized with the need for options for people with this rare form of lung cancer, she was not persuaded by the data on poziotinib that were presented to support accelerated approval.

“I’m not sure that this represents a meaningful therapeutic benefit over other agents,” she said at the time. 

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

The Food and Drug Administration has announced it will not approve the investigational drug poziotinib (Spectrum Pharmaceuticals) for the treatment of certain patients with non–small cell lung cancer (NSCLC).

The clinical data the company submitted were deemed insufficient for approval, and additional data including a randomized clinical trial would be needed, the agency said.

The move is not a surprise, as the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 against approval when it met to discuss the drug in September, as reported at the time by this news organization.

Poziotinib was developed for patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations, which occur in about 2% of patients with NSCLC.

Poziotinib is a potent oral pan-HER tyrosine kinase inhibitor with activity in patients with these mutations. Clinical data from the ZENITH20 Trial reported last year showed an overall response rate of 43.8%, and the drug was described as showing “clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.”

“We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed,” commented Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals. 

However, following multiple interactions with the FDA, “we have made the strategic decision to immediately deprioritize the poziotinib program,” he said. The change is effective immediately, and the company is now in the process of reducing its R&D workforce by approximately 75%.
 

Drug development criticized

At the ODAC meeting, several panelists were openly critical of the approach Spectrum took in developing the drug. The FDA’s top cancer official, Richard Pazdur, MD, characterized Spectrum’s work as “poor drug development” and likened it to “building a house on quicksand.”

The FDA panel detailed several ways they felt that the poziotinib application fell short of the benchmarks needed for accelerated approval.

To win such a speedy clearance, a company needs to show that a drug provides a meaningful therapeutic benefit over existing treatments. The panel argued that, so far, poziotinib appears to be inferior to a product already available for HER2-mutant NSCLC, trastuzumab deruxtecan (Enhertu), which received accelerated approval in August.

The FDA staff contrasted a reported overall response rate for poziotinib, which was estimated at 28% (from data discussed at the meeting), with the overall response rate for trastuzumab deruxtecan, which is 58%.

Harpreet Singh, MD, a director in the FDA’s oncology division, asked the panel to consider what they would do as a physician treating a patient with this mutation, given the choices that are now available.

“That’s something we’re asking the committee to consider … to think about the context of what’s available to you in the clinic,” Dr. Singh said.

Dr. Singh said she expected that patients and physicians would prefer a drug such as trastuzumab deruxtecan, which has a more established record, regardless of the fact that treatment with poziotinib is more convenient because it is given as a tablet.

Dr. Singh and other staff also raised concerns about side effects of poziotinib, including diarrhea, as well as difficulty determining the right dose.

Katherine Scilla, MD, one of the nine ODAC panelists to vote “no,” echoed these views. Although Dr. Scilla, an oncologist at the University of Maryland, Baltimore, sympathized with the need for options for people with this rare form of lung cancer, she was not persuaded by the data on poziotinib that were presented to support accelerated approval.

“I’m not sure that this represents a meaningful therapeutic benefit over other agents,” she said at the time. 

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

CHICAGO – Discovering lung cancer early with annual low-dose computed tomography greatly improves long-term survival rates to 80%, findings from a 20-year international study indicate.

Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.

The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.

Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
 

Participants’ 20-year survival rate 80%

Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.

Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.

For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).

No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.

These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.

At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.

Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.

When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.

“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.

“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
 

Findings “very promising”

Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.

“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.

“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.

Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.

So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.

“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.

Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.

Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.

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

CHICAGO – Discovering lung cancer early with annual low-dose computed tomography greatly improves long-term survival rates to 80%, findings from a 20-year international study indicate.

Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.

The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.

Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
 

Participants’ 20-year survival rate 80%

Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.

Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.

For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).

No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.

These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.

At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.

Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.

When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.

“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.

“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
 

Findings “very promising”

Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.

“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.

“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.

Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.

So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.

“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.

Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.

Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.

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

CHICAGO – Discovering lung cancer early with annual low-dose computed tomography greatly improves long-term survival rates to 80%, findings from a 20-year international study indicate.

Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.

The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.

Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
 

Participants’ 20-year survival rate 80%

Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.

Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.

For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).

No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.

These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.

At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.

Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.

When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.

“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.

“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
 

Findings “very promising”

Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.

“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.

“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.

Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.

So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.

“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.

Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.

Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.

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

Atezolizumab (Tecentriq) is no longer approved in the United States for use in certain patients with bladder or urinary tract cancer.

The drug is an anti–PD-L1 inhibitor immunotherapy, and continues to be approved for use in lung and liver cancer and melanoma.

The manufacturer, Genentech, announced that it was voluntarily withdrawing the U.S. indication for atezolizumab that covered its use in adults with locally advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

The company said that it made the decision after consultation with the Food and Drug Administration.

“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development.

Atezolizumab had been granted an accelerated approval for this indication back in 2016, based on response rate data from the IMvigor210 trial.

The company was obliged to conduct a follow-up trial to show clinical benefit, and launched IMvigor130, which it described as “the designated postmarketing requirement to convert the accelerated approval to regular approval.”

The bladder cancer indication for atezolizumab was discussed (alongside several other indications for different immunotherapy drugs) at a historic 3-day meeting of the FDA’s oncologic Drugs Advisory Committee in April 2021. At the time, ODAC voted 10-1 in favor of maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

Genentech has now said that this trial “did not meet the coprimary endpoint of overall survival for atezolizumab plus chemotherapy compared with chemotherapy alone” when used for the first-line treatment of patients with previously untreated advanced bladder cancer.

These data will be presented at an upcoming medical meeting, the company added.

“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Dr. Garraway commented.

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

Atezolizumab (Tecentriq) is no longer approved in the United States for use in certain patients with bladder or urinary tract cancer.

The drug is an anti–PD-L1 inhibitor immunotherapy, and continues to be approved for use in lung and liver cancer and melanoma.

The manufacturer, Genentech, announced that it was voluntarily withdrawing the U.S. indication for atezolizumab that covered its use in adults with locally advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

The company said that it made the decision after consultation with the Food and Drug Administration.

“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development.

Atezolizumab had been granted an accelerated approval for this indication back in 2016, based on response rate data from the IMvigor210 trial.

The company was obliged to conduct a follow-up trial to show clinical benefit, and launched IMvigor130, which it described as “the designated postmarketing requirement to convert the accelerated approval to regular approval.”

The bladder cancer indication for atezolizumab was discussed (alongside several other indications for different immunotherapy drugs) at a historic 3-day meeting of the FDA’s oncologic Drugs Advisory Committee in April 2021. At the time, ODAC voted 10-1 in favor of maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

Genentech has now said that this trial “did not meet the coprimary endpoint of overall survival for atezolizumab plus chemotherapy compared with chemotherapy alone” when used for the first-line treatment of patients with previously untreated advanced bladder cancer.

These data will be presented at an upcoming medical meeting, the company added.

“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Dr. Garraway commented.

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

Atezolizumab (Tecentriq) is no longer approved in the United States for use in certain patients with bladder or urinary tract cancer.

The drug is an anti–PD-L1 inhibitor immunotherapy, and continues to be approved for use in lung and liver cancer and melanoma.

The manufacturer, Genentech, announced that it was voluntarily withdrawing the U.S. indication for atezolizumab that covered its use in adults with locally advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

The company said that it made the decision after consultation with the Food and Drug Administration.

“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development.

Atezolizumab had been granted an accelerated approval for this indication back in 2016, based on response rate data from the IMvigor210 trial.

The company was obliged to conduct a follow-up trial to show clinical benefit, and launched IMvigor130, which it described as “the designated postmarketing requirement to convert the accelerated approval to regular approval.”

The bladder cancer indication for atezolizumab was discussed (alongside several other indications for different immunotherapy drugs) at a historic 3-day meeting of the FDA’s oncologic Drugs Advisory Committee in April 2021. At the time, ODAC voted 10-1 in favor of maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

Genentech has now said that this trial “did not meet the coprimary endpoint of overall survival for atezolizumab plus chemotherapy compared with chemotherapy alone” when used for the first-line treatment of patients with previously untreated advanced bladder cancer.

These data will be presented at an upcoming medical meeting, the company added.

“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Dr. Garraway commented.

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

The Food and Drug Administration has approved the first fecal microbiota product to prevent recurrence of Clostridioides difficile infection (CDI) in people aged 18 years and older.

Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.

“Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing approval.

As the first FDA-approved fecal microbiota product, this approval “represents an important milestone, as it provides an additional approved option to prevent recurrent CDI,” Dr. Marks added.

A panel of FDA advisors recommended approval of Rebyota in September.

The application for Rebyota received priority review and had orphan drug and breakthrough therapy designation.
 

A vicious cycle

Treatment options for recurrent CDI are limited. It’s been estimated that up to one-third of CDI cases recur, and people who suffer a recurrent bout of CDI are at a significantly higher risk for further infections.

Following the first recurrence, up to two-thirds of patients may experience a subsequent recurrence. Antibiotics used to treat CDI may contribute to a cycle of recurrence by altering the gut flora. The administration of fecal microbiota helps restore the gut flora to prevent further episodes of CDI.

Rebyota is a microbiota-based live biotherapeutic prepared from human stool collected from prescreened, qualified donors. It comes prepackaged in a single dose that is administered rectally.

The safety and efficacy of Rebyota were assessed in five clinical trials with more than 1,000 participants, the company notes in a press release.

In one trial, following a standard course of antibiotics, a one-time treatment with Rebyota was successful for three-quarters of participants at 8 weeks.

The treatment also prevented additional bouts; 84% of these initial responders remaining free of CDI at 6 months.

Two-thirds of participants reported treatment-emergent adverse events. Most events were mild to moderate in severity. Diarrhea and abdominal pain were the most common.

The data, from the ongoing PUNCH CD3-OLS study, were presented in October at the annual meeting of the American College of Gastroenterology and were published simultaneously in the journal Drugs.

“This is a positive adjunct to our current therapies for C. difficile in terms of trying to knock it out once a standard course of antibiotics has been administered,” Lisa Malter, MD, a gastroenterologist and professor of medicine at New York University Langone Health, said in an interview.

Dr. Malter acknowledged that because it’s delivered rectally, there could be “some hesitation” on the patient’s part to undergo the therapy.

However, C. difficile can be “excruciating” for patients, and they “may be more than willing to take [this agent] because it gets them feeling better,” Dr. Malter said.

Full prescribing information for Rebyota is available online.

Dr. Malter reported no relevant financial relationships.

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

The Food and Drug Administration has approved the first fecal microbiota product to prevent recurrence of Clostridioides difficile infection (CDI) in people aged 18 years and older.

Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.

“Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing approval.

As the first FDA-approved fecal microbiota product, this approval “represents an important milestone, as it provides an additional approved option to prevent recurrent CDI,” Dr. Marks added.

A panel of FDA advisors recommended approval of Rebyota in September.

The application for Rebyota received priority review and had orphan drug and breakthrough therapy designation.
 

A vicious cycle

Treatment options for recurrent CDI are limited. It’s been estimated that up to one-third of CDI cases recur, and people who suffer a recurrent bout of CDI are at a significantly higher risk for further infections.

Following the first recurrence, up to two-thirds of patients may experience a subsequent recurrence. Antibiotics used to treat CDI may contribute to a cycle of recurrence by altering the gut flora. The administration of fecal microbiota helps restore the gut flora to prevent further episodes of CDI.

Rebyota is a microbiota-based live biotherapeutic prepared from human stool collected from prescreened, qualified donors. It comes prepackaged in a single dose that is administered rectally.

The safety and efficacy of Rebyota were assessed in five clinical trials with more than 1,000 participants, the company notes in a press release.

In one trial, following a standard course of antibiotics, a one-time treatment with Rebyota was successful for three-quarters of participants at 8 weeks.

The treatment also prevented additional bouts; 84% of these initial responders remaining free of CDI at 6 months.

Two-thirds of participants reported treatment-emergent adverse events. Most events were mild to moderate in severity. Diarrhea and abdominal pain were the most common.

The data, from the ongoing PUNCH CD3-OLS study, were presented in October at the annual meeting of the American College of Gastroenterology and were published simultaneously in the journal Drugs.

“This is a positive adjunct to our current therapies for C. difficile in terms of trying to knock it out once a standard course of antibiotics has been administered,” Lisa Malter, MD, a gastroenterologist and professor of medicine at New York University Langone Health, said in an interview.

Dr. Malter acknowledged that because it’s delivered rectally, there could be “some hesitation” on the patient’s part to undergo the therapy.

However, C. difficile can be “excruciating” for patients, and they “may be more than willing to take [this agent] because it gets them feeling better,” Dr. Malter said.

Full prescribing information for Rebyota is available online.

Dr. Malter reported no relevant financial relationships.

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

The Food and Drug Administration has approved the first fecal microbiota product to prevent recurrence of Clostridioides difficile infection (CDI) in people aged 18 years and older.

Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.

“Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing approval.

As the first FDA-approved fecal microbiota product, this approval “represents an important milestone, as it provides an additional approved option to prevent recurrent CDI,” Dr. Marks added.

A panel of FDA advisors recommended approval of Rebyota in September.

The application for Rebyota received priority review and had orphan drug and breakthrough therapy designation.
 

A vicious cycle

Treatment options for recurrent CDI are limited. It’s been estimated that up to one-third of CDI cases recur, and people who suffer a recurrent bout of CDI are at a significantly higher risk for further infections.

Following the first recurrence, up to two-thirds of patients may experience a subsequent recurrence. Antibiotics used to treat CDI may contribute to a cycle of recurrence by altering the gut flora. The administration of fecal microbiota helps restore the gut flora to prevent further episodes of CDI.

Rebyota is a microbiota-based live biotherapeutic prepared from human stool collected from prescreened, qualified donors. It comes prepackaged in a single dose that is administered rectally.

The safety and efficacy of Rebyota were assessed in five clinical trials with more than 1,000 participants, the company notes in a press release.

In one trial, following a standard course of antibiotics, a one-time treatment with Rebyota was successful for three-quarters of participants at 8 weeks.

The treatment also prevented additional bouts; 84% of these initial responders remaining free of CDI at 6 months.

Two-thirds of participants reported treatment-emergent adverse events. Most events were mild to moderate in severity. Diarrhea and abdominal pain were the most common.

The data, from the ongoing PUNCH CD3-OLS study, were presented in October at the annual meeting of the American College of Gastroenterology and were published simultaneously in the journal Drugs.

“This is a positive adjunct to our current therapies for C. difficile in terms of trying to knock it out once a standard course of antibiotics has been administered,” Lisa Malter, MD, a gastroenterologist and professor of medicine at New York University Langone Health, said in an interview.

Dr. Malter acknowledged that because it’s delivered rectally, there could be “some hesitation” on the patient’s part to undergo the therapy.

However, C. difficile can be “excruciating” for patients, and they “may be more than willing to take [this agent] because it gets them feeling better,” Dr. Malter said.

Full prescribing information for Rebyota is available online.

Dr. Malter reported no relevant financial relationships.

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

Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug.

Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.
 

Kim Kardashian and Elon Musk

In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.

Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not prediabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.

As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.

This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.

“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”

A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.
 

At last, an effective weight-loss drug

Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.

The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.

“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”
 

More demand than supply

As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January. 

“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Dr. Apovian says. “These are people who are going to die, and you’re taking it away just for cosmetic weight loss. That is deplorable.”

In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.
 

The price of access

With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it. 

“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Dr. Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.

It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.

Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death.

“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Dr. Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”

Unpleasant side effects

Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea.

“The way we counteract that is to start very slowly at a low dose of these medications,” Dr. Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”

Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”

With a BMI over 30, Ms. Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week.

It turns out, that’s too much, too fast. Dr. Apovian and Dr. Velazquez say their patients lose more like 2 pounds each week, with careful monitoring. 

By early December, Ms. Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.

“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.”

Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.
 

More than just weight loss

Even though Ms. Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.

“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”

Dr. Apovian and Dr. Velazquez say their patients regularly discover similar things.

“Obesity is not a disease of willpower. Medications are not the easy way out,” Dr. Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”

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

Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug.

Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.
 

Kim Kardashian and Elon Musk

In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.

Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not prediabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.

As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.

This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.

“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”

A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.
 

At last, an effective weight-loss drug

Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.

The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.

“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”
 

More demand than supply

As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January. 

“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Dr. Apovian says. “These are people who are going to die, and you’re taking it away just for cosmetic weight loss. That is deplorable.”

In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.
 

The price of access

With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it. 

“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Dr. Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.

It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.

Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death.

“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Dr. Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”

Unpleasant side effects

Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea.

“The way we counteract that is to start very slowly at a low dose of these medications,” Dr. Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”

Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”

With a BMI over 30, Ms. Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week.

It turns out, that’s too much, too fast. Dr. Apovian and Dr. Velazquez say their patients lose more like 2 pounds each week, with careful monitoring. 

By early December, Ms. Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.

“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.”

Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.
 

More than just weight loss

Even though Ms. Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.

“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”

Dr. Apovian and Dr. Velazquez say their patients regularly discover similar things.

“Obesity is not a disease of willpower. Medications are not the easy way out,” Dr. Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”

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

Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug.

Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.
 

Kim Kardashian and Elon Musk

In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.

Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not prediabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.

As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.

This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.

“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”

A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.
 

At last, an effective weight-loss drug

Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.

The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.

“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”
 

More demand than supply

As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January. 

“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Dr. Apovian says. “These are people who are going to die, and you’re taking it away just for cosmetic weight loss. That is deplorable.”

In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.
 

The price of access

With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it. 

“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Dr. Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.

It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.

Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death.

“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Dr. Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”

Unpleasant side effects

Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea.

“The way we counteract that is to start very slowly at a low dose of these medications,” Dr. Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”

Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”

With a BMI over 30, Ms. Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week.

It turns out, that’s too much, too fast. Dr. Apovian and Dr. Velazquez say their patients lose more like 2 pounds each week, with careful monitoring. 

By early December, Ms. Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.

“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.”

Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.
 

More than just weight loss

Even though Ms. Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.

“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”

Dr. Apovian and Dr. Velazquez say their patients regularly discover similar things.

“Obesity is not a disease of willpower. Medications are not the easy way out,” Dr. Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”

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

Low energy–density diets that are based either on potatoes or beans similarly reduced insulin resistance in adults with poor blood glucose control, according to a controlled feeding study in 36 individuals.

PxHere

Potatoes have gotten a bad rap for their high glycemic index, but they have little fat and a low energy density, wrote the study investigators. In fact, “cooling of gelatinized potatoes generates appreciable levels of slowly digested starch (resistant starch type 3) and substantially lowers the blood glucose response that potatoes elicit.”

“There is a view that potatoes are a less healthy plant food, but there is very little empirical data from randomized trials to support this view,” senior investigator John P. Kirwan, PhD, said in an interview.

Dry beans and peas (known as pulses) also contain resistant starch that improves insulin sensitivity and glucose tolerance, and multiple studies support pulses as part of a low-glycemic diet to improve glucose control in adults, the researchers explained, but because the density of food often guides how much people eat, they hypothesized that potatoes could substitute for beans and provide similar glucose control benefits.

In a study published in the Journal of Medicinal Food, the researchers randomized 36 adults aged 18-60 years with insulin resistance to 8 weeks of a low energy–density diet (1 kcal/g) high in either potatoes or beans. The baseline body mass index ranged from 25 to 40 kg/m². Insulin resistance was defined using the homeostatic model assessment of insulin resistance (HOMA-IR) with a score greater than 2.

The controlled diet consisted of 50%-55% carbohydrates, 30%-35% fats, and 15%-20% protein. Each meal in the potato group included a side of potatoes, and each meal in the bean group included a side of beans.

The primary outcome was the mean change in blood glucose concentration; the researchers also assessed weight loss.

A total of 14 individuals in the potato group and 17 in the bean group completed the study; but data from the 18 individuals in each group were included in an intent-to-treat analysis.

Among study completers, HOMA-IR in the bean group showed an average decrease of 1.4 from baseline (P = .02 ); a similar decrease of 1.3 occurred in the potato group (P < .05) with no significant difference between the two diets.

Overall compliance with both diets was roughly 88%. Body weight reductions were similar in both groups and significantly reduced from baseline over the study period, with average reductions in intent-to-treat analysis of 5.82 kg in the potato group and 4.0 kg in the bean group. BMI also was significantly reduced from baseline in both potato and bean groups (2.04 kg/m² and 1.35 kg/m², respectively). Although baseline differences were not significant, “BMI at baseline was higher and the reduction in response to the treatment was significantly greater in the potato diet compared with the bean diet,” the researchers noted. The effect on blood glucose response was not significantly different between the two groups or from baseline, they said.

The findings were limited by several factors including the small size, relatively short study period, and controlled nature of the study diet, the researchers noted. “The addition of a typical Western diet would have enhanced our understanding of the effect of low energy–dense diets on metabolic outcomes,” they noted in their discussion.

However, both diets led to a reduction in body weight, and the low energy density of both potato and bean diets promoted weight loss without affecting appetite or requiring calorie restriction, the researchers explained. Therefore, “this weight loss if sustained over time could have a substantial impact on body weight,” they said.

“We hypothesized that there would be equivalence between the potato and bean diet and this hypothesis proved to be correct,” said Dr. Kirwan, of the Pennington Biomedical Research Center, Baton Rouge, La., in an interview.

The take-home message for clinicians is that, though small, the study was very well-controlled, Dr. Kirwan emphasized. “Clinicians ought to consider the health benefits of the potato when it is cooked and served appropriately.”

Looking ahead, larger randomized controlled trials with additional control arms, longer time of at least 12 weeks, and different patient populations are needed, Dr. Kirwan added.
 

Findings mitigate food myths

The debate continues about whether there are foods that are “good” or “evil;” or foods that one “should not eat” or “should eat,” said Amy Rothberg, MD, associate professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, in an interview.

“This study dispels the myth that incorporating a small portion of potato into the diet (although these are not potatoes that are fried, or are topped with cheese, bacon, sour cream, etc.) results in deleterious metabolic outcomes when compared to a diet that is comprised of beans (pulses) as part of a low energy–dense diet,” she explained.

“The diet in both groups was of low energy density, which has been shown to result in fewer calories consumed, weight loss, and improvement in insulin resistance,” so the similarity in results was not so surprising, said Dr. Rothberg.  

For the clinical takeaway, Dr. Rothberg agreed with the study authors: “Clinicians may counsel their patients that they can still consume a small potato (with the caveat above regarding cooking methods and toppings) as part of a balanced meal so long as they are keeping their overall calories low and not exceeding their metabolic requirements based on body weight/BMI,” she said.

As for additional research, studies with a longer time frame and a larger and more diverse study population are needed, including populations with common insulin resistance comorbidities such as type 2 diabetes, fatty liver disease, and cardiovascular disease, Dr. Rothberg noted.
 

Consumer considerations, with caveats

The key message for consumers is that, “based on this very small study of short duration, consuming a small portion of potato as part of an overall balanced, low-energy diet did not produce adverse effects on glucose or insulin when compared to a diet of pulses known to have favorable effects on glucose and insulin,” Dr. Rothberg told this news organization. However, “consumers should note that, although the results from this small study are encouraging, it would be premature to extrapolate the findings from this study to other populations,” she said. Also, keep in mind that the study was supported in part by the Alliance for Potato Research, although the authors stated that none of the funders (Alliance for Potato Research and Education and the National Institutes of Health) had any role in the design, analysis, or writing of the article, she added.

The study was supported in part by the Alliance for Potato Research and Education and the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The researchers and Dr. Rothberg had no financial conflicts to disclose.

Low energy–density diets that are based either on potatoes or beans similarly reduced insulin resistance in adults with poor blood glucose control, according to a controlled feeding study in 36 individuals.

PxHere

Potatoes have gotten a bad rap for their high glycemic index, but they have little fat and a low energy density, wrote the study investigators. In fact, “cooling of gelatinized potatoes generates appreciable levels of slowly digested starch (resistant starch type 3) and substantially lowers the blood glucose response that potatoes elicit.”

“There is a view that potatoes are a less healthy plant food, but there is very little empirical data from randomized trials to support this view,” senior investigator John P. Kirwan, PhD, said in an interview.

Dry beans and peas (known as pulses) also contain resistant starch that improves insulin sensitivity and glucose tolerance, and multiple studies support pulses as part of a low-glycemic diet to improve glucose control in adults, the researchers explained, but because the density of food often guides how much people eat, they hypothesized that potatoes could substitute for beans and provide similar glucose control benefits.

In a study published in the Journal of Medicinal Food, the researchers randomized 36 adults aged 18-60 years with insulin resistance to 8 weeks of a low energy–density diet (1 kcal/g) high in either potatoes or beans. The baseline body mass index ranged from 25 to 40 kg/m². Insulin resistance was defined using the homeostatic model assessment of insulin resistance (HOMA-IR) with a score greater than 2.

The controlled diet consisted of 50%-55% carbohydrates, 30%-35% fats, and 15%-20% protein. Each meal in the potato group included a side of potatoes, and each meal in the bean group included a side of beans.

The primary outcome was the mean change in blood glucose concentration; the researchers also assessed weight loss.

A total of 14 individuals in the potato group and 17 in the bean group completed the study; but data from the 18 individuals in each group were included in an intent-to-treat analysis.

Among study completers, HOMA-IR in the bean group showed an average decrease of 1.4 from baseline (P = .02 ); a similar decrease of 1.3 occurred in the potato group (P < .05) with no significant difference between the two diets.

Overall compliance with both diets was roughly 88%. Body weight reductions were similar in both groups and significantly reduced from baseline over the study period, with average reductions in intent-to-treat analysis of 5.82 kg in the potato group and 4.0 kg in the bean group. BMI also was significantly reduced from baseline in both potato and bean groups (2.04 kg/m² and 1.35 kg/m², respectively). Although baseline differences were not significant, “BMI at baseline was higher and the reduction in response to the treatment was significantly greater in the potato diet compared with the bean diet,” the researchers noted. The effect on blood glucose response was not significantly different between the two groups or from baseline, they said.

The findings were limited by several factors including the small size, relatively short study period, and controlled nature of the study diet, the researchers noted. “The addition of a typical Western diet would have enhanced our understanding of the effect of low energy–dense diets on metabolic outcomes,” they noted in their discussion.

However, both diets led to a reduction in body weight, and the low energy density of both potato and bean diets promoted weight loss without affecting appetite or requiring calorie restriction, the researchers explained. Therefore, “this weight loss if sustained over time could have a substantial impact on body weight,” they said.

“We hypothesized that there would be equivalence between the potato and bean diet and this hypothesis proved to be correct,” said Dr. Kirwan, of the Pennington Biomedical Research Center, Baton Rouge, La., in an interview.

The take-home message for clinicians is that, though small, the study was very well-controlled, Dr. Kirwan emphasized. “Clinicians ought to consider the health benefits of the potato when it is cooked and served appropriately.”

Looking ahead, larger randomized controlled trials with additional control arms, longer time of at least 12 weeks, and different patient populations are needed, Dr. Kirwan added.
 

Findings mitigate food myths

The debate continues about whether there are foods that are “good” or “evil;” or foods that one “should not eat” or “should eat,” said Amy Rothberg, MD, associate professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, in an interview.

“This study dispels the myth that incorporating a small portion of potato into the diet (although these are not potatoes that are fried, or are topped with cheese, bacon, sour cream, etc.) results in deleterious metabolic outcomes when compared to a diet that is comprised of beans (pulses) as part of a low energy–dense diet,” she explained.

“The diet in both groups was of low energy density, which has been shown to result in fewer calories consumed, weight loss, and improvement in insulin resistance,” so the similarity in results was not so surprising, said Dr. Rothberg.  

For the clinical takeaway, Dr. Rothberg agreed with the study authors: “Clinicians may counsel their patients that they can still consume a small potato (with the caveat above regarding cooking methods and toppings) as part of a balanced meal so long as they are keeping their overall calories low and not exceeding their metabolic requirements based on body weight/BMI,” she said.

As for additional research, studies with a longer time frame and a larger and more diverse study population are needed, including populations with common insulin resistance comorbidities such as type 2 diabetes, fatty liver disease, and cardiovascular disease, Dr. Rothberg noted.
 

Consumer considerations, with caveats

The key message for consumers is that, “based on this very small study of short duration, consuming a small portion of potato as part of an overall balanced, low-energy diet did not produce adverse effects on glucose or insulin when compared to a diet of pulses known to have favorable effects on glucose and insulin,” Dr. Rothberg told this news organization. However, “consumers should note that, although the results from this small study are encouraging, it would be premature to extrapolate the findings from this study to other populations,” she said. Also, keep in mind that the study was supported in part by the Alliance for Potato Research, although the authors stated that none of the funders (Alliance for Potato Research and Education and the National Institutes of Health) had any role in the design, analysis, or writing of the article, she added.

The study was supported in part by the Alliance for Potato Research and Education and the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The researchers and Dr. Rothberg had no financial conflicts to disclose.

Low energy–density diets that are based either on potatoes or beans similarly reduced insulin resistance in adults with poor blood glucose control, according to a controlled feeding study in 36 individuals.

PxHere

Potatoes have gotten a bad rap for their high glycemic index, but they have little fat and a low energy density, wrote the study investigators. In fact, “cooling of gelatinized potatoes generates appreciable levels of slowly digested starch (resistant starch type 3) and substantially lowers the blood glucose response that potatoes elicit.”

“There is a view that potatoes are a less healthy plant food, but there is very little empirical data from randomized trials to support this view,” senior investigator John P. Kirwan, PhD, said in an interview.

Dry beans and peas (known as pulses) also contain resistant starch that improves insulin sensitivity and glucose tolerance, and multiple studies support pulses as part of a low-glycemic diet to improve glucose control in adults, the researchers explained, but because the density of food often guides how much people eat, they hypothesized that potatoes could substitute for beans and provide similar glucose control benefits.

In a study published in the Journal of Medicinal Food, the researchers randomized 36 adults aged 18-60 years with insulin resistance to 8 weeks of a low energy–density diet (1 kcal/g) high in either potatoes or beans. The baseline body mass index ranged from 25 to 40 kg/m². Insulin resistance was defined using the homeostatic model assessment of insulin resistance (HOMA-IR) with a score greater than 2.

The controlled diet consisted of 50%-55% carbohydrates, 30%-35% fats, and 15%-20% protein. Each meal in the potato group included a side of potatoes, and each meal in the bean group included a side of beans.

The primary outcome was the mean change in blood glucose concentration; the researchers also assessed weight loss.

A total of 14 individuals in the potato group and 17 in the bean group completed the study; but data from the 18 individuals in each group were included in an intent-to-treat analysis.

Among study completers, HOMA-IR in the bean group showed an average decrease of 1.4 from baseline (P = .02 ); a similar decrease of 1.3 occurred in the potato group (P < .05) with no significant difference between the two diets.

Overall compliance with both diets was roughly 88%. Body weight reductions were similar in both groups and significantly reduced from baseline over the study period, with average reductions in intent-to-treat analysis of 5.82 kg in the potato group and 4.0 kg in the bean group. BMI also was significantly reduced from baseline in both potato and bean groups (2.04 kg/m² and 1.35 kg/m², respectively). Although baseline differences were not significant, “BMI at baseline was higher and the reduction in response to the treatment was significantly greater in the potato diet compared with the bean diet,” the researchers noted. The effect on blood glucose response was not significantly different between the two groups or from baseline, they said.

The findings were limited by several factors including the small size, relatively short study period, and controlled nature of the study diet, the researchers noted. “The addition of a typical Western diet would have enhanced our understanding of the effect of low energy–dense diets on metabolic outcomes,” they noted in their discussion.

However, both diets led to a reduction in body weight, and the low energy density of both potato and bean diets promoted weight loss without affecting appetite or requiring calorie restriction, the researchers explained. Therefore, “this weight loss if sustained over time could have a substantial impact on body weight,” they said.

“We hypothesized that there would be equivalence between the potato and bean diet and this hypothesis proved to be correct,” said Dr. Kirwan, of the Pennington Biomedical Research Center, Baton Rouge, La., in an interview.

The take-home message for clinicians is that, though small, the study was very well-controlled, Dr. Kirwan emphasized. “Clinicians ought to consider the health benefits of the potato when it is cooked and served appropriately.”

Looking ahead, larger randomized controlled trials with additional control arms, longer time of at least 12 weeks, and different patient populations are needed, Dr. Kirwan added.
 

Findings mitigate food myths

The debate continues about whether there are foods that are “good” or “evil;” or foods that one “should not eat” or “should eat,” said Amy Rothberg, MD, associate professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, in an interview.

“This study dispels the myth that incorporating a small portion of potato into the diet (although these are not potatoes that are fried, or are topped with cheese, bacon, sour cream, etc.) results in deleterious metabolic outcomes when compared to a diet that is comprised of beans (pulses) as part of a low energy–dense diet,” she explained.

“The diet in both groups was of low energy density, which has been shown to result in fewer calories consumed, weight loss, and improvement in insulin resistance,” so the similarity in results was not so surprising, said Dr. Rothberg.  

For the clinical takeaway, Dr. Rothberg agreed with the study authors: “Clinicians may counsel their patients that they can still consume a small potato (with the caveat above regarding cooking methods and toppings) as part of a balanced meal so long as they are keeping their overall calories low and not exceeding their metabolic requirements based on body weight/BMI,” she said.

As for additional research, studies with a longer time frame and a larger and more diverse study population are needed, including populations with common insulin resistance comorbidities such as type 2 diabetes, fatty liver disease, and cardiovascular disease, Dr. Rothberg noted.
 

Consumer considerations, with caveats

The key message for consumers is that, “based on this very small study of short duration, consuming a small portion of potato as part of an overall balanced, low-energy diet did not produce adverse effects on glucose or insulin when compared to a diet of pulses known to have favorable effects on glucose and insulin,” Dr. Rothberg told this news organization. However, “consumers should note that, although the results from this small study are encouraging, it would be premature to extrapolate the findings from this study to other populations,” she said. Also, keep in mind that the study was supported in part by the Alliance for Potato Research, although the authors stated that none of the funders (Alliance for Potato Research and Education and the National Institutes of Health) had any role in the design, analysis, or writing of the article, she added.

The study was supported in part by the Alliance for Potato Research and Education and the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The researchers and Dr. Rothberg had no financial conflicts to disclose.

Among high-risk early breast cancer patients, a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from a phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.

“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.

“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.

The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.

Among high-risk early breast cancer patients, a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from a phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.

“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.

“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.

The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.

Among high-risk early breast cancer patients, a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from a phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.

“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.

“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.

The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.

A striking characteristic of COVID-19 is that the severity of clinical outcomes is remarkably variable. Establishing a prognosis for individuals infected with COVID-19 remains a challenge.

Since the start of the COVID-19 pandemic, the heterogeneity of individuals who progress toward severe disease or death, along with the fact that individuals directly exposed to the virus do not necessarily become sick, supports the hypothesis that genetic risk or protective factors are at play.

In an interview with this news organization, Mayana Zatz, PhD, head professor of genetics and coordinator of the Human Genome and Stem Cell Study Center at the University of São Paulo, explained: “The first case that caught my eye was the case of my neighbors, a couple. He presented COVID-19 symptoms, but his wife, who took care of him, had absolutely no symptoms. I thought that it was strange, but we received 3,000 emails from people saying, ‘This happened to me, too.’”

Reports in the media about seven pairs of monozygotic (MZ) twins who died from COVID-19 within days of one another in Brazil also stood out, said the researcher.

Twin studies are important for investigating the contribution of genetics vs. that of the environment in the susceptibility or resistance to infectious diseases, as well as their pathology. Dr. Zatz’s team analyzed the case of a 31-year-old Brazilian MZ twin brother pair who presented simultaneously with severe COVID-19 and the need for oxygen support, despite their age and good health conditions. Curiously, they were admitted and intubated on the same day, but neither of the twins knew about the other’s situation; they found out only when they were extubated.

The study was carried out at the USP with the collaboration of the State University of São Paulo. The authors mapped the genetic profile (by sequencing the genome responsible for coding proteins, or whole-exome sequencing) and the immune cell profile to evaluate innate and adaptive immunity.

The MZ twin brothers shared the same two rare genetic mutations, which may be associated with their increased risk of developing severe COVID-19. However, since these variants were not studied at the protein or functional level, their pathogenicity has yet to be determined. The twins also had [human leukocyte antigen (HLA)] alleles associated with severe COVID-19, which are important candidates for the mechanisms of innate and adaptive immunity and susceptibility to COVID-19 infection and manifestation.

But one particular oddity stood out to the researchers: One of the brothers required longer hospitalization, and only he reported symptoms of long COVID.

In the authors’ eyes, even though the patients shared genetic mutations potentially associated with the risk of developing severe COVID-19, the differences in clinical progression emphasize that, beyond genetic risk factors, continuous exposure to pathogens over a lifetime and other environmental factors mean that each individual’s immune response is unique, even in twins.

“There is no doubt that genetics contribute to the severity of COVID-19, and environmental factors sometimes give us the opportunity to study the disease, too. Such [is the case with] MZ twins who have genetic similarities, even with changes that take place over a lifetime,” José Eduardo Krieger, MD, PhD, professor of molecular medicine at the University of São Paulo Medical School (FMUSP), told this news organization. “Examining MZ twins is a strategy that may help, but, with n = 2, luck really needs to be on your side to get straight to the problem. You need to combine [these findings] with other studies to solve this conundrum,” said Dr. Krieger, who did not take part in the research.
 

Large cohorts

Genomic and computer resources allow for the study of large sets of data from thousands of individuals. In each of those sets of data, the signal offered by thousands of markers distributed throughout the genome can be studied. This is the possibility offered by various genomic studies of large cohorts of patients with different clinical manifestations.

“Researchers examine thousands of genetic variants throughout the genome from a large sample of individuals and have the chance, for example, to identify genetic variants that are more prevalent in patients who have presented with severe disease than in those who presented with milder disease,” said Dr. Krieger. “These associations highlight a chromosome region in which one or more genes explain, at least in part, the differences observed.”

Genomewide association studies have identified some genetic variants that indicate severity of COVID-19, with potential impact on the virus entering the cell, the immune response, or the development of cytokine storms.

One of these studies, COVID-19 Host Genetics Initiative (COVID-19 HGI), is an international, open-science collaboration for sharing scientific methods and resources with research groups across the world, with the goal of robustly mapping the host genetic determinants of SARS-CoV-2 infection and the severity of the resulting COVID-19 disease. At the start of 2021, the COVID-19 HGI combined genetic data from 49,562 cases and 2 million controls from 46 studies in 19 countries. A total of 853 samples from the BRACOVID study were included in the meta-analysis. The endeavor enabled the identification of 13 genomewide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19.

The BRACOVID study, in which Dr. Krieger participates, aims to identify host genetic factors that determine the severity of COVID-19. It is currently the largest project of its kind in Latin America. An article provides the analysis of the first 5,233 participants in the BRACOVID study, who were recruited in São Paulo. Of these participants, 3,533 had been infected with COVID-19 and hospitalized at either the Heart Institute or the Central Institute of the FMUSP General Hospital. The remaining 1,700 made up the control group, which included health care professionals and members of the general population. The controls were recruited through serology assays or PCR tests for SARS-CoV-2.

The researchers discovered a region of chromosome 1 that could play a role in modulating immune response and that could lead to an increase in the likelihood of hospitalization across a wide range of COVID-19 risk factors. This region of chromosome 1 was observed only in Brazilians with a strong European ancestry; however, this finding had not been mentioned in previous studies, suggesting that it could harbor a risk allele specific to the Brazilian population.

The study also confirmed most, but not all, of the regions recorded in the literature, which may be significant in identifying factors determining severity that are specific to a given population.

Including information from the BRACOVID study, other studies have enhanced the knowledge on affected organs. Combined data from 14,000 patients from nine countries evaluated a region of a single chromosome and found that carriers of a certain allele had a higher probability of experiencing various COVID-19 complications, such as severe respiratory failure, venous thromboembolism, and liver damage. The risk was even higher for individuals aged 60 years and over.
 

Discordant couples

Smaller sample sizes of underrepresented populations also provide relevant data for genomic studies. Dr. Zatz’s team carried out genomic studies on smaller groups, comparing serodiscordant couples (where one was infected and symptomatic while the partner remained asymptomatic and seronegative despite sharing the same bedroom during the infection). Their research found genetic variants related to immune response that were associated with susceptibility to infection and progression to severe COVID-19. 

The team also went on to study a group of patients older than 90 years who recovered from COVID-19 with mild symptoms or who remained asymptomatic following a positive test for SARS-CoV-2. They compared these patients with a sample of elderly patients from the same city (São Paulo), sampled before the current pandemic. The researchers identified a genetic variant related to mucin production. “In individuals with mild COVID-19, the degradation of these mucins would be more efficient,” said Dr. Zatz. It is possible for this variant to interfere not only with the production of mucus, but also in its composition, as there is an exchange of amino acids in the protein.

“We continued the study by comparing the extremes, i.e., those in their 90s with mild COVID-19 and younger patients with severe COVID-19, including several who died,” said Dr. Zatz.
 

More personalized medicine

The specialists agreed that a genetic test to predict COVID-19 severity is still a long way away. The genetic component is too little understood to enable the evaluation of individual risk. It has been possible to identify several important areas but, as Dr. Krieger pointed out, a variant identified in a certain chromosome interval may not be just one gene. There may be various candidate genes, or there may be a regulatory sequence for a distant gene. Furthermore, there are regions with genes that make sense as moderators of COVID-19 severity, because they regulate an inflammatory or immunologic reaction, but evidence is still lacking.

Reaching the molecular mechanism would, in future, allow a medicine to be chosen for a given patient, as already happens with other diseases. It also could enable the discovery of new medicines following as-yet-unexplored lines of research. Dr. Zatz also considers the possibility of genetic therapy.

Even with the knowledge of human genetics, one part of the equation is missing: viral genetics. “Many of the individuals who were resistant to the Delta variant were later affected by Omicron,” she pointed out.
 

Significance of Brazil

“We have an infinite amount of genomic data worldwide, but the vast majority originates from White Americans of European origin,” said Dr. Krieger. Moreover, genomic associations of COVID-19 severity discovered in the Chinese population were not significant in the European population. Besides underscoring the importance of collaborating with international studies, this situation supports scientists’ interest in carrying out genetic studies within Brazil, he added.

“In the genomic study of the Brazilian population, we found 2 million variants that were not present in the European populations,” said Dr. Zatz.

Dr. Krieger mentioned a technical advantage that Brazil has. “Having been colonized by different ethnic groups and mixed many generations ago, Brazil has a population with a unique genetic structure; the recombinations are different. When preparing the samples, the regions break differently.” This factor could help to separate, in a candidate region, the gene that is significant from those that might not be.

In general, severe COVID-19 would be a complex phenomenon involving several genes and interactions with environmental factors. The Brazilian studies tried to find a factor that was unique to Brazil, but the significance of the differences remained unclear. “We found some signs that were specific to our population,” concluded Dr. Krieger. “But the reason that more people in Brazil died as a result of COVID-19 was not genetic,” he added.

Dr. Zatz and Dr. Krieger reported no conflicts of interest. This article was translated from the Medscape Portuguese edition.

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

A striking characteristic of COVID-19 is that the severity of clinical outcomes is remarkably variable. Establishing a prognosis for individuals infected with COVID-19 remains a challenge.

Since the start of the COVID-19 pandemic, the heterogeneity of individuals who progress toward severe disease or death, along with the fact that individuals directly exposed to the virus do not necessarily become sick, supports the hypothesis that genetic risk or protective factors are at play.

In an interview with this news organization, Mayana Zatz, PhD, head professor of genetics and coordinator of the Human Genome and Stem Cell Study Center at the University of São Paulo, explained: “The first case that caught my eye was the case of my neighbors, a couple. He presented COVID-19 symptoms, but his wife, who took care of him, had absolutely no symptoms. I thought that it was strange, but we received 3,000 emails from people saying, ‘This happened to me, too.’”

Reports in the media about seven pairs of monozygotic (MZ) twins who died from COVID-19 within days of one another in Brazil also stood out, said the researcher.

Twin studies are important for investigating the contribution of genetics vs. that of the environment in the susceptibility or resistance to infectious diseases, as well as their pathology. Dr. Zatz’s team analyzed the case of a 31-year-old Brazilian MZ twin brother pair who presented simultaneously with severe COVID-19 and the need for oxygen support, despite their age and good health conditions. Curiously, they were admitted and intubated on the same day, but neither of the twins knew about the other’s situation; they found out only when they were extubated.

The study was carried out at the USP with the collaboration of the State University of São Paulo. The authors mapped the genetic profile (by sequencing the genome responsible for coding proteins, or whole-exome sequencing) and the immune cell profile to evaluate innate and adaptive immunity.

The MZ twin brothers shared the same two rare genetic mutations, which may be associated with their increased risk of developing severe COVID-19. However, since these variants were not studied at the protein or functional level, their pathogenicity has yet to be determined. The twins also had [human leukocyte antigen (HLA)] alleles associated with severe COVID-19, which are important candidates for the mechanisms of innate and adaptive immunity and susceptibility to COVID-19 infection and manifestation.

But one particular oddity stood out to the researchers: One of the brothers required longer hospitalization, and only he reported symptoms of long COVID.

In the authors’ eyes, even though the patients shared genetic mutations potentially associated with the risk of developing severe COVID-19, the differences in clinical progression emphasize that, beyond genetic risk factors, continuous exposure to pathogens over a lifetime and other environmental factors mean that each individual’s immune response is unique, even in twins.

“There is no doubt that genetics contribute to the severity of COVID-19, and environmental factors sometimes give us the opportunity to study the disease, too. Such [is the case with] MZ twins who have genetic similarities, even with changes that take place over a lifetime,” José Eduardo Krieger, MD, PhD, professor of molecular medicine at the University of São Paulo Medical School (FMUSP), told this news organization. “Examining MZ twins is a strategy that may help, but, with n = 2, luck really needs to be on your side to get straight to the problem. You need to combine [these findings] with other studies to solve this conundrum,” said Dr. Krieger, who did not take part in the research.
 

Large cohorts

Genomic and computer resources allow for the study of large sets of data from thousands of individuals. In each of those sets of data, the signal offered by thousands of markers distributed throughout the genome can be studied. This is the possibility offered by various genomic studies of large cohorts of patients with different clinical manifestations.

“Researchers examine thousands of genetic variants throughout the genome from a large sample of individuals and have the chance, for example, to identify genetic variants that are more prevalent in patients who have presented with severe disease than in those who presented with milder disease,” said Dr. Krieger. “These associations highlight a chromosome region in which one or more genes explain, at least in part, the differences observed.”

Genomewide association studies have identified some genetic variants that indicate severity of COVID-19, with potential impact on the virus entering the cell, the immune response, or the development of cytokine storms.

One of these studies, COVID-19 Host Genetics Initiative (COVID-19 HGI), is an international, open-science collaboration for sharing scientific methods and resources with research groups across the world, with the goal of robustly mapping the host genetic determinants of SARS-CoV-2 infection and the severity of the resulting COVID-19 disease. At the start of 2021, the COVID-19 HGI combined genetic data from 49,562 cases and 2 million controls from 46 studies in 19 countries. A total of 853 samples from the BRACOVID study were included in the meta-analysis. The endeavor enabled the identification of 13 genomewide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19.

The BRACOVID study, in which Dr. Krieger participates, aims to identify host genetic factors that determine the severity of COVID-19. It is currently the largest project of its kind in Latin America. An article provides the analysis of the first 5,233 participants in the BRACOVID study, who were recruited in São Paulo. Of these participants, 3,533 had been infected with COVID-19 and hospitalized at either the Heart Institute or the Central Institute of the FMUSP General Hospital. The remaining 1,700 made up the control group, which included health care professionals and members of the general population. The controls were recruited through serology assays or PCR tests for SARS-CoV-2.

The researchers discovered a region of chromosome 1 that could play a role in modulating immune response and that could lead to an increase in the likelihood of hospitalization across a wide range of COVID-19 risk factors. This region of chromosome 1 was observed only in Brazilians with a strong European ancestry; however, this finding had not been mentioned in previous studies, suggesting that it could harbor a risk allele specific to the Brazilian population.

The study also confirmed most, but not all, of the regions recorded in the literature, which may be significant in identifying factors determining severity that are specific to a given population.

Including information from the BRACOVID study, other studies have enhanced the knowledge on affected organs. Combined data from 14,000 patients from nine countries evaluated a region of a single chromosome and found that carriers of a certain allele had a higher probability of experiencing various COVID-19 complications, such as severe respiratory failure, venous thromboembolism, and liver damage. The risk was even higher for individuals aged 60 years and over.
 

Discordant couples

Smaller sample sizes of underrepresented populations also provide relevant data for genomic studies. Dr. Zatz’s team carried out genomic studies on smaller groups, comparing serodiscordant couples (where one was infected and symptomatic while the partner remained asymptomatic and seronegative despite sharing the same bedroom during the infection). Their research found genetic variants related to immune response that were associated with susceptibility to infection and progression to severe COVID-19. 

The team also went on to study a group of patients older than 90 years who recovered from COVID-19 with mild symptoms or who remained asymptomatic following a positive test for SARS-CoV-2. They compared these patients with a sample of elderly patients from the same city (São Paulo), sampled before the current pandemic. The researchers identified a genetic variant related to mucin production. “In individuals with mild COVID-19, the degradation of these mucins would be more efficient,” said Dr. Zatz. It is possible for this variant to interfere not only with the production of mucus, but also in its composition, as there is an exchange of amino acids in the protein.

“We continued the study by comparing the extremes, i.e., those in their 90s with mild COVID-19 and younger patients with severe COVID-19, including several who died,” said Dr. Zatz.
 

More personalized medicine

The specialists agreed that a genetic test to predict COVID-19 severity is still a long way away. The genetic component is too little understood to enable the evaluation of individual risk. It has been possible to identify several important areas but, as Dr. Krieger pointed out, a variant identified in a certain chromosome interval may not be just one gene. There may be various candidate genes, or there may be a regulatory sequence for a distant gene. Furthermore, there are regions with genes that make sense as moderators of COVID-19 severity, because they regulate an inflammatory or immunologic reaction, but evidence is still lacking.

Reaching the molecular mechanism would, in future, allow a medicine to be chosen for a given patient, as already happens with other diseases. It also could enable the discovery of new medicines following as-yet-unexplored lines of research. Dr. Zatz also considers the possibility of genetic therapy.

Even with the knowledge of human genetics, one part of the equation is missing: viral genetics. “Many of the individuals who were resistant to the Delta variant were later affected by Omicron,” she pointed out.
 

Significance of Brazil

“We have an infinite amount of genomic data worldwide, but the vast majority originates from White Americans of European origin,” said Dr. Krieger. Moreover, genomic associations of COVID-19 severity discovered in the Chinese population were not significant in the European population. Besides underscoring the importance of collaborating with international studies, this situation supports scientists’ interest in carrying out genetic studies within Brazil, he added.

“In the genomic study of the Brazilian population, we found 2 million variants that were not present in the European populations,” said Dr. Zatz.

Dr. Krieger mentioned a technical advantage that Brazil has. “Having been colonized by different ethnic groups and mixed many generations ago, Brazil has a population with a unique genetic structure; the recombinations are different. When preparing the samples, the regions break differently.” This factor could help to separate, in a candidate region, the gene that is significant from those that might not be.

In general, severe COVID-19 would be a complex phenomenon involving several genes and interactions with environmental factors. The Brazilian studies tried to find a factor that was unique to Brazil, but the significance of the differences remained unclear. “We found some signs that were specific to our population,” concluded Dr. Krieger. “But the reason that more people in Brazil died as a result of COVID-19 was not genetic,” he added.

Dr. Zatz and Dr. Krieger reported no conflicts of interest. This article was translated from the Medscape Portuguese edition.

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

A striking characteristic of COVID-19 is that the severity of clinical outcomes is remarkably variable. Establishing a prognosis for individuals infected with COVID-19 remains a challenge.

Since the start of the COVID-19 pandemic, the heterogeneity of individuals who progress toward severe disease or death, along with the fact that individuals directly exposed to the virus do not necessarily become sick, supports the hypothesis that genetic risk or protective factors are at play.

In an interview with this news organization, Mayana Zatz, PhD, head professor of genetics and coordinator of the Human Genome and Stem Cell Study Center at the University of São Paulo, explained: “The first case that caught my eye was the case of my neighbors, a couple. He presented COVID-19 symptoms, but his wife, who took care of him, had absolutely no symptoms. I thought that it was strange, but we received 3,000 emails from people saying, ‘This happened to me, too.’”

Reports in the media about seven pairs of monozygotic (MZ) twins who died from COVID-19 within days of one another in Brazil also stood out, said the researcher.

Twin studies are important for investigating the contribution of genetics vs. that of the environment in the susceptibility or resistance to infectious diseases, as well as their pathology. Dr. Zatz’s team analyzed the case of a 31-year-old Brazilian MZ twin brother pair who presented simultaneously with severe COVID-19 and the need for oxygen support, despite their age and good health conditions. Curiously, they were admitted and intubated on the same day, but neither of the twins knew about the other’s situation; they found out only when they were extubated.

The study was carried out at the USP with the collaboration of the State University of São Paulo. The authors mapped the genetic profile (by sequencing the genome responsible for coding proteins, or whole-exome sequencing) and the immune cell profile to evaluate innate and adaptive immunity.

The MZ twin brothers shared the same two rare genetic mutations, which may be associated with their increased risk of developing severe COVID-19. However, since these variants were not studied at the protein or functional level, their pathogenicity has yet to be determined. The twins also had [human leukocyte antigen (HLA)] alleles associated with severe COVID-19, which are important candidates for the mechanisms of innate and adaptive immunity and susceptibility to COVID-19 infection and manifestation.

But one particular oddity stood out to the researchers: One of the brothers required longer hospitalization, and only he reported symptoms of long COVID.

In the authors’ eyes, even though the patients shared genetic mutations potentially associated with the risk of developing severe COVID-19, the differences in clinical progression emphasize that, beyond genetic risk factors, continuous exposure to pathogens over a lifetime and other environmental factors mean that each individual’s immune response is unique, even in twins.

“There is no doubt that genetics contribute to the severity of COVID-19, and environmental factors sometimes give us the opportunity to study the disease, too. Such [is the case with] MZ twins who have genetic similarities, even with changes that take place over a lifetime,” José Eduardo Krieger, MD, PhD, professor of molecular medicine at the University of São Paulo Medical School (FMUSP), told this news organization. “Examining MZ twins is a strategy that may help, but, with n = 2, luck really needs to be on your side to get straight to the problem. You need to combine [these findings] with other studies to solve this conundrum,” said Dr. Krieger, who did not take part in the research.
 

Large cohorts

Genomic and computer resources allow for the study of large sets of data from thousands of individuals. In each of those sets of data, the signal offered by thousands of markers distributed throughout the genome can be studied. This is the possibility offered by various genomic studies of large cohorts of patients with different clinical manifestations.

“Researchers examine thousands of genetic variants throughout the genome from a large sample of individuals and have the chance, for example, to identify genetic variants that are more prevalent in patients who have presented with severe disease than in those who presented with milder disease,” said Dr. Krieger. “These associations highlight a chromosome region in which one or more genes explain, at least in part, the differences observed.”

Genomewide association studies have identified some genetic variants that indicate severity of COVID-19, with potential impact on the virus entering the cell, the immune response, or the development of cytokine storms.

One of these studies, COVID-19 Host Genetics Initiative (COVID-19 HGI), is an international, open-science collaboration for sharing scientific methods and resources with research groups across the world, with the goal of robustly mapping the host genetic determinants of SARS-CoV-2 infection and the severity of the resulting COVID-19 disease. At the start of 2021, the COVID-19 HGI combined genetic data from 49,562 cases and 2 million controls from 46 studies in 19 countries. A total of 853 samples from the BRACOVID study were included in the meta-analysis. The endeavor enabled the identification of 13 genomewide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19.

The BRACOVID study, in which Dr. Krieger participates, aims to identify host genetic factors that determine the severity of COVID-19. It is currently the largest project of its kind in Latin America. An article provides the analysis of the first 5,233 participants in the BRACOVID study, who were recruited in São Paulo. Of these participants, 3,533 had been infected with COVID-19 and hospitalized at either the Heart Institute or the Central Institute of the FMUSP General Hospital. The remaining 1,700 made up the control group, which included health care professionals and members of the general population. The controls were recruited through serology assays or PCR tests for SARS-CoV-2.

The researchers discovered a region of chromosome 1 that could play a role in modulating immune response and that could lead to an increase in the likelihood of hospitalization across a wide range of COVID-19 risk factors. This region of chromosome 1 was observed only in Brazilians with a strong European ancestry; however, this finding had not been mentioned in previous studies, suggesting that it could harbor a risk allele specific to the Brazilian population.

The study also confirmed most, but not all, of the regions recorded in the literature, which may be significant in identifying factors determining severity that are specific to a given population.

Including information from the BRACOVID study, other studies have enhanced the knowledge on affected organs. Combined data from 14,000 patients from nine countries evaluated a region of a single chromosome and found that carriers of a certain allele had a higher probability of experiencing various COVID-19 complications, such as severe respiratory failure, venous thromboembolism, and liver damage. The risk was even higher for individuals aged 60 years and over.
 

Discordant couples

Smaller sample sizes of underrepresented populations also provide relevant data for genomic studies. Dr. Zatz’s team carried out genomic studies on smaller groups, comparing serodiscordant couples (where one was infected and symptomatic while the partner remained asymptomatic and seronegative despite sharing the same bedroom during the infection). Their research found genetic variants related to immune response that were associated with susceptibility to infection and progression to severe COVID-19. 

The team also went on to study a group of patients older than 90 years who recovered from COVID-19 with mild symptoms or who remained asymptomatic following a positive test for SARS-CoV-2. They compared these patients with a sample of elderly patients from the same city (São Paulo), sampled before the current pandemic. The researchers identified a genetic variant related to mucin production. “In individuals with mild COVID-19, the degradation of these mucins would be more efficient,” said Dr. Zatz. It is possible for this variant to interfere not only with the production of mucus, but also in its composition, as there is an exchange of amino acids in the protein.

“We continued the study by comparing the extremes, i.e., those in their 90s with mild COVID-19 and younger patients with severe COVID-19, including several who died,” said Dr. Zatz.
 

More personalized medicine

The specialists agreed that a genetic test to predict COVID-19 severity is still a long way away. The genetic component is too little understood to enable the evaluation of individual risk. It has been possible to identify several important areas but, as Dr. Krieger pointed out, a variant identified in a certain chromosome interval may not be just one gene. There may be various candidate genes, or there may be a regulatory sequence for a distant gene. Furthermore, there are regions with genes that make sense as moderators of COVID-19 severity, because they regulate an inflammatory or immunologic reaction, but evidence is still lacking.

Reaching the molecular mechanism would, in future, allow a medicine to be chosen for a given patient, as already happens with other diseases. It also could enable the discovery of new medicines following as-yet-unexplored lines of research. Dr. Zatz also considers the possibility of genetic therapy.

Even with the knowledge of human genetics, one part of the equation is missing: viral genetics. “Many of the individuals who were resistant to the Delta variant were later affected by Omicron,” she pointed out.
 

Significance of Brazil

“We have an infinite amount of genomic data worldwide, but the vast majority originates from White Americans of European origin,” said Dr. Krieger. Moreover, genomic associations of COVID-19 severity discovered in the Chinese population were not significant in the European population. Besides underscoring the importance of collaborating with international studies, this situation supports scientists’ interest in carrying out genetic studies within Brazil, he added.

“In the genomic study of the Brazilian population, we found 2 million variants that were not present in the European populations,” said Dr. Zatz.

Dr. Krieger mentioned a technical advantage that Brazil has. “Having been colonized by different ethnic groups and mixed many generations ago, Brazil has a population with a unique genetic structure; the recombinations are different. When preparing the samples, the regions break differently.” This factor could help to separate, in a candidate region, the gene that is significant from those that might not be.

In general, severe COVID-19 would be a complex phenomenon involving several genes and interactions with environmental factors. The Brazilian studies tried to find a factor that was unique to Brazil, but the significance of the differences remained unclear. “We found some signs that were specific to our population,” concluded Dr. Krieger. “But the reason that more people in Brazil died as a result of COVID-19 was not genetic,” he added.

Dr. Zatz and Dr. Krieger reported no conflicts of interest. This article was translated from the Medscape Portuguese edition.

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