CHICAGO – Many physicians still hold beliefs despite the existence of clear evidence that they are incorrect, said a presenter at the annual meeting of the American College of Physicians.

These long-held pieces of dogma – or “medical myths” – were engraved during training or early in the careers of many physicians, and are difficult to overcome, noted Douglas Paauw, MD, professor of medicine at the University of Washington, Seattle.

“I think that myths persist because medical professionals get taught one way in training, given a ‘truth’ or ‘This is the way we do it,’ and then do not ever rethink, ‘Is it true?’ ” he said in an interview. “Studies pop up to question conventional wisdom, but unless the studies get highly publicized, they aren’t noticed.”

During his presentation, Dr. Paauw discussed three of what he considers to be some of the some of the medical myths that are in greatest need of being dispelled.
 

Shellfish allergy and radiocontrast

A myth persists that people with a shellfish allergy could have an allergic reaction when a contrast agent is used for a scan, he said.

This belief arose, because fish and shellfish contain iodine, and allergic reactions to seafood are fairly common, and contrast agents contain iodine, too, Dr. Paauw said.

The belief is widespread, with 65% of radiologists and 88.9% of interventional cardiologists saying they ask about seafood or shellfish allergies before administering contrast. And a third of radiologists and 50% of cardiologists said they would withhold contrast media or recommend a premedication for patients with such an allergy.

But the belief makes no sense, Dr. Pauuw said. Iodine is present in many other foods, including milk and bread, and allergies to shellfish are because of parvalbumin protein and tropomyosins, not iodine.
 

Colonoscopy dogma

It’s been long believed that people need to be on a clear, liquid diet for 1 or 2 days and need to drink a bowel-prep liquid before a colonoscopy, noted Dr. Paauw.

But the evidence shows this isn’t necessary, he said.

A 2020 study found that a low-residual diet, allowing foods such as meat, eggs, dairy, and bread, were comparable to the clear liquid diet in terms of bowel prep and detection of polyps during the exam. The patients on the low-residual diet had less nausea, less vomiting, and less hunger, and expressed more willingness to have a repeat colonoscopy.

“Let them eat,” Dr. Paauw said in his presentation.
 

Metronidazole and alcohol

There is a belief that patients shouldn’t drink alcohol if they are taking metronidazole, because of concerns about nausea, vomiting, flushing and other symptoms – also known as a disulfiramlike reaction, Dr. Paauw explained.

Case reports have been published, but the cases were presented as though a metronidazole-ethanol reaction was an established fact, and the authors didn’t provide evidence to justify this, Dr. Paauw said.

But it’s been shown in rat models that metronidazole can increase levels of acetaldehyde, the trigger of symptoms, in the colon, but not in the blood. And in a small placebo-controlled, randomized trial, six people were given metronidazole and ethanol and, after regular blood testing, no difference was seen in acetaldehyde blood levels, vital signs, or symptoms.

The Centers for Disease Control and Prevention has said that avoiding alcohol while taking metronidazole is unnecessary, said Dr. Paauw.
 

Sinus headaches

Contrary to common belief, headaches thought to be “sinus headaches” are usually migraine headaches, Dr. Paauw said.

In one study, 2,991 patients with six headaches in the previous 6 months were self-diagnosed or were physician-diagnosed with sinus headaches. But 88% of these headaches met the International Headache Society criteria for migraine headache.

Dr. Paauw said he hopes that clinicians reconsider the evidence regularly when deciding how to treat their patients, and not rely on bits of dogma.

“They stay with us,” he said, “and sometimes there are other ways to do it.”

Shien Tze, MD, an internist in Fargo, N,D,, said that patients sometimes also hold misconceptions, based on outdated dogma, that he needs to dispel.

“I try to convince them that this is a myth that is not based on evidence, not based on science,” he said. “I think it depends on the way you say it. If you say it in a calm, firm, not wishy-washy way, the patients believe you.”

Dr. Paauw reported no relevant financial disclosures. He serves on the editorial advisory board of Internal Medicine News, and he contributes “Myth of the Month” and “Pearl of the Month” columns to this publication.

CHICAGO – Many physicians still hold beliefs despite the existence of clear evidence that they are incorrect, said a presenter at the annual meeting of the American College of Physicians.

These long-held pieces of dogma – or “medical myths” – were engraved during training or early in the careers of many physicians, and are difficult to overcome, noted Douglas Paauw, MD, professor of medicine at the University of Washington, Seattle.

“I think that myths persist because medical professionals get taught one way in training, given a ‘truth’ or ‘This is the way we do it,’ and then do not ever rethink, ‘Is it true?’ ” he said in an interview. “Studies pop up to question conventional wisdom, but unless the studies get highly publicized, they aren’t noticed.”

During his presentation, Dr. Paauw discussed three of what he considers to be some of the some of the medical myths that are in greatest need of being dispelled.
 

Shellfish allergy and radiocontrast

A myth persists that people with a shellfish allergy could have an allergic reaction when a contrast agent is used for a scan, he said.

This belief arose, because fish and shellfish contain iodine, and allergic reactions to seafood are fairly common, and contrast agents contain iodine, too, Dr. Paauw said.

The belief is widespread, with 65% of radiologists and 88.9% of interventional cardiologists saying they ask about seafood or shellfish allergies before administering contrast. And a third of radiologists and 50% of cardiologists said they would withhold contrast media or recommend a premedication for patients with such an allergy.

But the belief makes no sense, Dr. Pauuw said. Iodine is present in many other foods, including milk and bread, and allergies to shellfish are because of parvalbumin protein and tropomyosins, not iodine.
 

Colonoscopy dogma

It’s been long believed that people need to be on a clear, liquid diet for 1 or 2 days and need to drink a bowel-prep liquid before a colonoscopy, noted Dr. Paauw.

But the evidence shows this isn’t necessary, he said.

A 2020 study found that a low-residual diet, allowing foods such as meat, eggs, dairy, and bread, were comparable to the clear liquid diet in terms of bowel prep and detection of polyps during the exam. The patients on the low-residual diet had less nausea, less vomiting, and less hunger, and expressed more willingness to have a repeat colonoscopy.

“Let them eat,” Dr. Paauw said in his presentation.
 

Metronidazole and alcohol

There is a belief that patients shouldn’t drink alcohol if they are taking metronidazole, because of concerns about nausea, vomiting, flushing and other symptoms – also known as a disulfiramlike reaction, Dr. Paauw explained.

Case reports have been published, but the cases were presented as though a metronidazole-ethanol reaction was an established fact, and the authors didn’t provide evidence to justify this, Dr. Paauw said.

But it’s been shown in rat models that metronidazole can increase levels of acetaldehyde, the trigger of symptoms, in the colon, but not in the blood. And in a small placebo-controlled, randomized trial, six people were given metronidazole and ethanol and, after regular blood testing, no difference was seen in acetaldehyde blood levels, vital signs, or symptoms.

The Centers for Disease Control and Prevention has said that avoiding alcohol while taking metronidazole is unnecessary, said Dr. Paauw.
 

Sinus headaches

Contrary to common belief, headaches thought to be “sinus headaches” are usually migraine headaches, Dr. Paauw said.

In one study, 2,991 patients with six headaches in the previous 6 months were self-diagnosed or were physician-diagnosed with sinus headaches. But 88% of these headaches met the International Headache Society criteria for migraine headache.

Dr. Paauw said he hopes that clinicians reconsider the evidence regularly when deciding how to treat their patients, and not rely on bits of dogma.

“They stay with us,” he said, “and sometimes there are other ways to do it.”

Shien Tze, MD, an internist in Fargo, N,D,, said that patients sometimes also hold misconceptions, based on outdated dogma, that he needs to dispel.

“I try to convince them that this is a myth that is not based on evidence, not based on science,” he said. “I think it depends on the way you say it. If you say it in a calm, firm, not wishy-washy way, the patients believe you.”

Dr. Paauw reported no relevant financial disclosures. He serves on the editorial advisory board of Internal Medicine News, and he contributes “Myth of the Month” and “Pearl of the Month” columns to this publication.

CHICAGO – Many physicians still hold beliefs despite the existence of clear evidence that they are incorrect, said a presenter at the annual meeting of the American College of Physicians.

These long-held pieces of dogma – or “medical myths” – were engraved during training or early in the careers of many physicians, and are difficult to overcome, noted Douglas Paauw, MD, professor of medicine at the University of Washington, Seattle.

“I think that myths persist because medical professionals get taught one way in training, given a ‘truth’ or ‘This is the way we do it,’ and then do not ever rethink, ‘Is it true?’ ” he said in an interview. “Studies pop up to question conventional wisdom, but unless the studies get highly publicized, they aren’t noticed.”

During his presentation, Dr. Paauw discussed three of what he considers to be some of the some of the medical myths that are in greatest need of being dispelled.
 

Shellfish allergy and radiocontrast

A myth persists that people with a shellfish allergy could have an allergic reaction when a contrast agent is used for a scan, he said.

This belief arose, because fish and shellfish contain iodine, and allergic reactions to seafood are fairly common, and contrast agents contain iodine, too, Dr. Paauw said.

The belief is widespread, with 65% of radiologists and 88.9% of interventional cardiologists saying they ask about seafood or shellfish allergies before administering contrast. And a third of radiologists and 50% of cardiologists said they would withhold contrast media or recommend a premedication for patients with such an allergy.

But the belief makes no sense, Dr. Pauuw said. Iodine is present in many other foods, including milk and bread, and allergies to shellfish are because of parvalbumin protein and tropomyosins, not iodine.
 

Colonoscopy dogma

It’s been long believed that people need to be on a clear, liquid diet for 1 or 2 days and need to drink a bowel-prep liquid before a colonoscopy, noted Dr. Paauw.

But the evidence shows this isn’t necessary, he said.

A 2020 study found that a low-residual diet, allowing foods such as meat, eggs, dairy, and bread, were comparable to the clear liquid diet in terms of bowel prep and detection of polyps during the exam. The patients on the low-residual diet had less nausea, less vomiting, and less hunger, and expressed more willingness to have a repeat colonoscopy.

“Let them eat,” Dr. Paauw said in his presentation.
 

Metronidazole and alcohol

There is a belief that patients shouldn’t drink alcohol if they are taking metronidazole, because of concerns about nausea, vomiting, flushing and other symptoms – also known as a disulfiramlike reaction, Dr. Paauw explained.

Case reports have been published, but the cases were presented as though a metronidazole-ethanol reaction was an established fact, and the authors didn’t provide evidence to justify this, Dr. Paauw said.

But it’s been shown in rat models that metronidazole can increase levels of acetaldehyde, the trigger of symptoms, in the colon, but not in the blood. And in a small placebo-controlled, randomized trial, six people were given metronidazole and ethanol and, after regular blood testing, no difference was seen in acetaldehyde blood levels, vital signs, or symptoms.

The Centers for Disease Control and Prevention has said that avoiding alcohol while taking metronidazole is unnecessary, said Dr. Paauw.
 

Sinus headaches

Contrary to common belief, headaches thought to be “sinus headaches” are usually migraine headaches, Dr. Paauw said.

In one study, 2,991 patients with six headaches in the previous 6 months were self-diagnosed or were physician-diagnosed with sinus headaches. But 88% of these headaches met the International Headache Society criteria for migraine headache.

Dr. Paauw said he hopes that clinicians reconsider the evidence regularly when deciding how to treat their patients, and not rely on bits of dogma.

“They stay with us,” he said, “and sometimes there are other ways to do it.”

Shien Tze, MD, an internist in Fargo, N,D,, said that patients sometimes also hold misconceptions, based on outdated dogma, that he needs to dispel.

“I try to convince them that this is a myth that is not based on evidence, not based on science,” he said. “I think it depends on the way you say it. If you say it in a calm, firm, not wishy-washy way, the patients believe you.”

Dr. Paauw reported no relevant financial disclosures. He serves on the editorial advisory board of Internal Medicine News, and he contributes “Myth of the Month” and “Pearl of the Month” columns to this publication.

In an updated clinical practice guideline, the American Society of Clinical Oncology has named the Breast Cancer Index (BCI) as the only genomic test that should be used to guide extended endocrine therapy decisions for women with early-stage, hormone receptor–positive breast cancer. The update applies to women who are node negative or have one to three positive nodes treated with 5 years of endocrine therapy and no sign of recurrence.

The update was published in the Journal of Clinical Oncology. It also gives more specific details on how to apply other, previously recommended, genomic tests to guide treatment choices.

More than half of breast cancer deaths occur after 5 years of tamoxifen therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP)- B14 trial, published in 2001, showed no benefit to extending tamoxifen therapy to 10 years, but other studies have produced mixed results.

Extended endocrine therapy may reduce the risk of recurrence, but significant side effects can impact quality of life, including osteoporosis, bone fractures, and joint pain. The uncertain benefits of extended endocrine therapy, combined with its side effects and impact on quality of life, has generated interest in genomic tests to identify patients most likely to benefit.

The BCI analyzes 11 genes from the tumor and delivers two results: the likelihood of recurrence 5-10 years after diagnosis, and whether a total of 10 years of endocrine therapy are likely to provide a survival benefit.

The 21-gene prognostic and predictive assay Oncotype DX Breast Recurrence Score, the 70-gene signature test Mammaprint, the 12-gene risk score EndoPredict, levels of Ki67 expression, and immunohistochemistry are also recommended for guiding decisions on endocrine therapy. The update included additional guidance on specific situations that each can be used. However, their usefulness for predicting recurrence at 5-10 years is unproven.

“The clinical decision to either extend or end adjuvant endocrine therapy after 5 years is a challenging decision for healthcare providers and their patients,” Mark Pegram, MD, said in a press release. He is chief medical consultant for breast oncology at Biotheranostics, a subsidiary of Hologic. “There is an extensive body of clinical evidence consistently proving the utility of BCI, and its addition to major oncology clinical guidelines like those from ASCO further underscores the test’s potential in clinical decision-making regarding extended adjuvant endocrine therapy.”

The practice update cited five previous studies showing the ability of BCI to predict benefit from extending endocrine therapy: From 5 years of tamoxifen to 5 more years of tamoxifen; from 5 years of tamoxifen to 5 years of an aromatase inhibitor, and from 5 years of an AI to another 5 years of a drug from the same class. Most of the trials included patients who were node negative or had one to three positive nodes, so there is limited evidence supporting BCI in patients with more than three positive lymph nodes. The recommendation also applies only to postmenopausal women, as the trials included fewer premenopausal and perimenopausal women.

Several of the guideline authors reported conflicts of interest with numerous sources.

In an updated clinical practice guideline, the American Society of Clinical Oncology has named the Breast Cancer Index (BCI) as the only genomic test that should be used to guide extended endocrine therapy decisions for women with early-stage, hormone receptor–positive breast cancer. The update applies to women who are node negative or have one to three positive nodes treated with 5 years of endocrine therapy and no sign of recurrence.

The update was published in the Journal of Clinical Oncology. It also gives more specific details on how to apply other, previously recommended, genomic tests to guide treatment choices.

More than half of breast cancer deaths occur after 5 years of tamoxifen therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP)- B14 trial, published in 2001, showed no benefit to extending tamoxifen therapy to 10 years, but other studies have produced mixed results.

Extended endocrine therapy may reduce the risk of recurrence, but significant side effects can impact quality of life, including osteoporosis, bone fractures, and joint pain. The uncertain benefits of extended endocrine therapy, combined with its side effects and impact on quality of life, has generated interest in genomic tests to identify patients most likely to benefit.

The BCI analyzes 11 genes from the tumor and delivers two results: the likelihood of recurrence 5-10 years after diagnosis, and whether a total of 10 years of endocrine therapy are likely to provide a survival benefit.

The 21-gene prognostic and predictive assay Oncotype DX Breast Recurrence Score, the 70-gene signature test Mammaprint, the 12-gene risk score EndoPredict, levels of Ki67 expression, and immunohistochemistry are also recommended for guiding decisions on endocrine therapy. The update included additional guidance on specific situations that each can be used. However, their usefulness for predicting recurrence at 5-10 years is unproven.

“The clinical decision to either extend or end adjuvant endocrine therapy after 5 years is a challenging decision for healthcare providers and their patients,” Mark Pegram, MD, said in a press release. He is chief medical consultant for breast oncology at Biotheranostics, a subsidiary of Hologic. “There is an extensive body of clinical evidence consistently proving the utility of BCI, and its addition to major oncology clinical guidelines like those from ASCO further underscores the test’s potential in clinical decision-making regarding extended adjuvant endocrine therapy.”

The practice update cited five previous studies showing the ability of BCI to predict benefit from extending endocrine therapy: From 5 years of tamoxifen to 5 more years of tamoxifen; from 5 years of tamoxifen to 5 years of an aromatase inhibitor, and from 5 years of an AI to another 5 years of a drug from the same class. Most of the trials included patients who were node negative or had one to three positive nodes, so there is limited evidence supporting BCI in patients with more than three positive lymph nodes. The recommendation also applies only to postmenopausal women, as the trials included fewer premenopausal and perimenopausal women.

Several of the guideline authors reported conflicts of interest with numerous sources.

In an updated clinical practice guideline, the American Society of Clinical Oncology has named the Breast Cancer Index (BCI) as the only genomic test that should be used to guide extended endocrine therapy decisions for women with early-stage, hormone receptor–positive breast cancer. The update applies to women who are node negative or have one to three positive nodes treated with 5 years of endocrine therapy and no sign of recurrence.

The update was published in the Journal of Clinical Oncology. It also gives more specific details on how to apply other, previously recommended, genomic tests to guide treatment choices.

More than half of breast cancer deaths occur after 5 years of tamoxifen therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP)- B14 trial, published in 2001, showed no benefit to extending tamoxifen therapy to 10 years, but other studies have produced mixed results.

Extended endocrine therapy may reduce the risk of recurrence, but significant side effects can impact quality of life, including osteoporosis, bone fractures, and joint pain. The uncertain benefits of extended endocrine therapy, combined with its side effects and impact on quality of life, has generated interest in genomic tests to identify patients most likely to benefit.

The BCI analyzes 11 genes from the tumor and delivers two results: the likelihood of recurrence 5-10 years after diagnosis, and whether a total of 10 years of endocrine therapy are likely to provide a survival benefit.

The 21-gene prognostic and predictive assay Oncotype DX Breast Recurrence Score, the 70-gene signature test Mammaprint, the 12-gene risk score EndoPredict, levels of Ki67 expression, and immunohistochemistry are also recommended for guiding decisions on endocrine therapy. The update included additional guidance on specific situations that each can be used. However, their usefulness for predicting recurrence at 5-10 years is unproven.

“The clinical decision to either extend or end adjuvant endocrine therapy after 5 years is a challenging decision for healthcare providers and their patients,” Mark Pegram, MD, said in a press release. He is chief medical consultant for breast oncology at Biotheranostics, a subsidiary of Hologic. “There is an extensive body of clinical evidence consistently proving the utility of BCI, and its addition to major oncology clinical guidelines like those from ASCO further underscores the test’s potential in clinical decision-making regarding extended adjuvant endocrine therapy.”

The practice update cited five previous studies showing the ability of BCI to predict benefit from extending endocrine therapy: From 5 years of tamoxifen to 5 more years of tamoxifen; from 5 years of tamoxifen to 5 years of an aromatase inhibitor, and from 5 years of an AI to another 5 years of a drug from the same class. Most of the trials included patients who were node negative or had one to three positive nodes, so there is limited evidence supporting BCI in patients with more than three positive lymph nodes. The recommendation also applies only to postmenopausal women, as the trials included fewer premenopausal and perimenopausal women.

Several of the guideline authors reported conflicts of interest with numerous sources.

The Food and Drug Administration is limiting who can receive the Johnson & Johnson COVID-19 vaccine because of concerns about the risk of a rare blood clotting condition.

In a statement issued May 5, the FDA said the J&J vaccine should only be given to people 18 and older who don’t have access to other vaccines or for whom other vaccines are not clinically appropriate. People 18 and older can also get the J&J vaccine if they choose to because they wouldn’t otherwise receive any vaccine, the FDA said.

The FDA statement was similar to the recommendation made in December by a Centers for Disease Control and Prevention committee of experts.

The FDA said the decision was made after more information was shared about the occurrence of a rare blood clotting condition, thrombosis with thrombocytopenia syndrome (TTS), 1 or 2 weeks after people received the J&J vaccine. The finding “warrants limiting the authorized use of the vaccine,” the FDA said.

“We recognize that the Janssen COVID-19 vaccine still has a role in the current pandemic response in the United States and across the global community,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the statement.

“Our action reflects our updated analysis of the risk of TTS following administration of this vaccine and limits the use of the vaccine to certain individuals.”

The CDC says 16.9 million people are fully vaccinated with the J&J vaccine, compared with 76.5 million with Moderna and 126.3 million with Pfizer.

Through March 18, the CDC and FDA have detected 60 confirmed cases of TTS, including 9 fatal cases, ABC News reported.

The J&J vaccine was granted emergency authorization in February 2021. Health authorities hoped it would help spread vaccines across the nation because it only required one initial dose and didn’t need to be stored at extremely cold temperatures, unlike the two-dose Pfizer and Moderna vaccines.

But 2 months after authorization, the government paused its use for 10 days because of reports of TTS. In December 2021, the CDC’s Advisory Committee on Immunization Practices said the Pfizer and Moderna vaccines were preferred over J&J because J&J carried the rare risk of blood clots and bleeding in the brain.

The FDA said the cause of the blood clotting is not known. But the “known and potential benefits of the vaccine” outweigh the risks for those people now allowed to receive it, the FDA said.

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

The Food and Drug Administration is limiting who can receive the Johnson & Johnson COVID-19 vaccine because of concerns about the risk of a rare blood clotting condition.

In a statement issued May 5, the FDA said the J&J vaccine should only be given to people 18 and older who don’t have access to other vaccines or for whom other vaccines are not clinically appropriate. People 18 and older can also get the J&J vaccine if they choose to because they wouldn’t otherwise receive any vaccine, the FDA said.

The FDA statement was similar to the recommendation made in December by a Centers for Disease Control and Prevention committee of experts.

The FDA said the decision was made after more information was shared about the occurrence of a rare blood clotting condition, thrombosis with thrombocytopenia syndrome (TTS), 1 or 2 weeks after people received the J&J vaccine. The finding “warrants limiting the authorized use of the vaccine,” the FDA said.

“We recognize that the Janssen COVID-19 vaccine still has a role in the current pandemic response in the United States and across the global community,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the statement.

“Our action reflects our updated analysis of the risk of TTS following administration of this vaccine and limits the use of the vaccine to certain individuals.”

The CDC says 16.9 million people are fully vaccinated with the J&J vaccine, compared with 76.5 million with Moderna and 126.3 million with Pfizer.

Through March 18, the CDC and FDA have detected 60 confirmed cases of TTS, including 9 fatal cases, ABC News reported.

The J&J vaccine was granted emergency authorization in February 2021. Health authorities hoped it would help spread vaccines across the nation because it only required one initial dose and didn’t need to be stored at extremely cold temperatures, unlike the two-dose Pfizer and Moderna vaccines.

But 2 months after authorization, the government paused its use for 10 days because of reports of TTS. In December 2021, the CDC’s Advisory Committee on Immunization Practices said the Pfizer and Moderna vaccines were preferred over J&J because J&J carried the rare risk of blood clots and bleeding in the brain.

The FDA said the cause of the blood clotting is not known. But the “known and potential benefits of the vaccine” outweigh the risks for those people now allowed to receive it, the FDA said.

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

The Food and Drug Administration is limiting who can receive the Johnson & Johnson COVID-19 vaccine because of concerns about the risk of a rare blood clotting condition.

In a statement issued May 5, the FDA said the J&J vaccine should only be given to people 18 and older who don’t have access to other vaccines or for whom other vaccines are not clinically appropriate. People 18 and older can also get the J&J vaccine if they choose to because they wouldn’t otherwise receive any vaccine, the FDA said.

The FDA statement was similar to the recommendation made in December by a Centers for Disease Control and Prevention committee of experts.

The FDA said the decision was made after more information was shared about the occurrence of a rare blood clotting condition, thrombosis with thrombocytopenia syndrome (TTS), 1 or 2 weeks after people received the J&J vaccine. The finding “warrants limiting the authorized use of the vaccine,” the FDA said.

“We recognize that the Janssen COVID-19 vaccine still has a role in the current pandemic response in the United States and across the global community,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the statement.

“Our action reflects our updated analysis of the risk of TTS following administration of this vaccine and limits the use of the vaccine to certain individuals.”

The CDC says 16.9 million people are fully vaccinated with the J&J vaccine, compared with 76.5 million with Moderna and 126.3 million with Pfizer.

Through March 18, the CDC and FDA have detected 60 confirmed cases of TTS, including 9 fatal cases, ABC News reported.

The J&J vaccine was granted emergency authorization in February 2021. Health authorities hoped it would help spread vaccines across the nation because it only required one initial dose and didn’t need to be stored at extremely cold temperatures, unlike the two-dose Pfizer and Moderna vaccines.

But 2 months after authorization, the government paused its use for 10 days because of reports of TTS. In December 2021, the CDC’s Advisory Committee on Immunization Practices said the Pfizer and Moderna vaccines were preferred over J&J because J&J carried the rare risk of blood clots and bleeding in the brain.

The FDA said the cause of the blood clotting is not known. But the “known and potential benefits of the vaccine” outweigh the risks for those people now allowed to receive it, the FDA said.

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

A few weeks ago I talked about my evening practice of doing jigsaw puzzles to relax, as a pleasant alternative to surfing the Internet.

Last week my daughter moved home from college for the summer. It’s been several years since she and I last did puzzles together, and I’d forgotten how much she likes them.

So now each night we sit there, either side by side or across the table from each other, each quietly working on some little portion of the same jigsaw. Very little is said, but it’s still the same bonding time I’ve always cherished.

But I notice things I’d never thought of.

I always start a puzzle like I thought most people do: Pick out the flat edge pieces to build the outside frame, then work inward from there.

But she doesn’t. Once the box is opened and pieces dumped out, she starts sorting them by patterns and colors, and begins there. The edges don’t get her attention at all as she begins. She assembles like-pieces and gradually expands from there.

Why?

I mean, I’m a neurologist. Brains are my business. So why are our thought patterns on the same task so different?

I have no clue.

This is part of the mystery of the brain. Why different ones, although anatomically similar, can function so differently in how they approach and solve the same problem.

I can’t blame this on who she learned from. We’ve been doing puzzles together since she was little. Think about it – do you even remember someone teaching you to do jigsaw puzzles at some point? Neither do I. I assume a family member or schoolteacher showed me a basic one at some point, and how the pieces fit together, but that’s a guess.

So I sit there working on my section and watch her doing hers, and the neurologist turns the whole thing over. Does she have more neurons and/or glia in whatever the “puzzle solving” portion of her brain (I assume part of visual memory and spatial relationships) is? Or do I? Like so much of neurology this should have a structural answer – I think.

It reminds me of how little we still know. And it bugs me.

Has anyone done PET scans while people work on jigsaw puzzles? I checked PubMed and couldn’t find anything. I doubt it due to the logistics of having someone do one inside a scanner. Searching Google with the same question only gets me ads for customized jigsaws of pets.

So I made the leap to doing a jigsaw puzzle on an iPad while in a PET machine. But even then, how do I know I’d be testing the same functions? The touchscreen is similar, but not the same, as doing a real jigsaw. (In my opinion real puzzles are preferable to iPad ones, except when traveling).

At the end of the day it’s a mystery I don’t know the answer to, probably never will, and realistically shouldn’t think too much about.

Because this summer the real meaning of the puzzle isn’t the jigsaw itself. It’s the young woman sitting next to me working on it.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A few weeks ago I talked about my evening practice of doing jigsaw puzzles to relax, as a pleasant alternative to surfing the Internet.

Last week my daughter moved home from college for the summer. It’s been several years since she and I last did puzzles together, and I’d forgotten how much she likes them.

So now each night we sit there, either side by side or across the table from each other, each quietly working on some little portion of the same jigsaw. Very little is said, but it’s still the same bonding time I’ve always cherished.

But I notice things I’d never thought of.

I always start a puzzle like I thought most people do: Pick out the flat edge pieces to build the outside frame, then work inward from there.

But she doesn’t. Once the box is opened and pieces dumped out, she starts sorting them by patterns and colors, and begins there. The edges don’t get her attention at all as she begins. She assembles like-pieces and gradually expands from there.

Why?

I mean, I’m a neurologist. Brains are my business. So why are our thought patterns on the same task so different?

I have no clue.

This is part of the mystery of the brain. Why different ones, although anatomically similar, can function so differently in how they approach and solve the same problem.

I can’t blame this on who she learned from. We’ve been doing puzzles together since she was little. Think about it – do you even remember someone teaching you to do jigsaw puzzles at some point? Neither do I. I assume a family member or schoolteacher showed me a basic one at some point, and how the pieces fit together, but that’s a guess.

So I sit there working on my section and watch her doing hers, and the neurologist turns the whole thing over. Does she have more neurons and/or glia in whatever the “puzzle solving” portion of her brain (I assume part of visual memory and spatial relationships) is? Or do I? Like so much of neurology this should have a structural answer – I think.

It reminds me of how little we still know. And it bugs me.

Has anyone done PET scans while people work on jigsaw puzzles? I checked PubMed and couldn’t find anything. I doubt it due to the logistics of having someone do one inside a scanner. Searching Google with the same question only gets me ads for customized jigsaws of pets.

So I made the leap to doing a jigsaw puzzle on an iPad while in a PET machine. But even then, how do I know I’d be testing the same functions? The touchscreen is similar, but not the same, as doing a real jigsaw. (In my opinion real puzzles are preferable to iPad ones, except when traveling).

At the end of the day it’s a mystery I don’t know the answer to, probably never will, and realistically shouldn’t think too much about.

Because this summer the real meaning of the puzzle isn’t the jigsaw itself. It’s the young woman sitting next to me working on it.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A few weeks ago I talked about my evening practice of doing jigsaw puzzles to relax, as a pleasant alternative to surfing the Internet.

Last week my daughter moved home from college for the summer. It’s been several years since she and I last did puzzles together, and I’d forgotten how much she likes them.

So now each night we sit there, either side by side or across the table from each other, each quietly working on some little portion of the same jigsaw. Very little is said, but it’s still the same bonding time I’ve always cherished.

But I notice things I’d never thought of.

I always start a puzzle like I thought most people do: Pick out the flat edge pieces to build the outside frame, then work inward from there.

But she doesn’t. Once the box is opened and pieces dumped out, she starts sorting them by patterns and colors, and begins there. The edges don’t get her attention at all as she begins. She assembles like-pieces and gradually expands from there.

Why?

I mean, I’m a neurologist. Brains are my business. So why are our thought patterns on the same task so different?

I have no clue.

This is part of the mystery of the brain. Why different ones, although anatomically similar, can function so differently in how they approach and solve the same problem.

I can’t blame this on who she learned from. We’ve been doing puzzles together since she was little. Think about it – do you even remember someone teaching you to do jigsaw puzzles at some point? Neither do I. I assume a family member or schoolteacher showed me a basic one at some point, and how the pieces fit together, but that’s a guess.

So I sit there working on my section and watch her doing hers, and the neurologist turns the whole thing over. Does she have more neurons and/or glia in whatever the “puzzle solving” portion of her brain (I assume part of visual memory and spatial relationships) is? Or do I? Like so much of neurology this should have a structural answer – I think.

It reminds me of how little we still know. And it bugs me.

Has anyone done PET scans while people work on jigsaw puzzles? I checked PubMed and couldn’t find anything. I doubt it due to the logistics of having someone do one inside a scanner. Searching Google with the same question only gets me ads for customized jigsaws of pets.

So I made the leap to doing a jigsaw puzzle on an iPad while in a PET machine. But even then, how do I know I’d be testing the same functions? The touchscreen is similar, but not the same, as doing a real jigsaw. (In my opinion real puzzles are preferable to iPad ones, except when traveling).

At the end of the day it’s a mystery I don’t know the answer to, probably never will, and realistically shouldn’t think too much about.

Because this summer the real meaning of the puzzle isn’t the jigsaw itself. It’s the young woman sitting next to me working on it.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Researchers in Scotland have developed a risk calculator using a large electronic health records database that has shown a high reliability in predicting the risk of death for patients hospitalized for chronic occlusive pulmonary disease (COPD), providing another potential tool for improving postdischarge survival in these patients.

In a study published online in the journal Pharmacological Research, Pierpalo Pellicori, MD, and colleagues reported that a few variables, including prescriptions and laboratory data in routine EHRs, could help predict a patient’s risk of dying within 90 days after a hospital stay for COPD. Dr. Pellicori is a clinical cardiologist and research fellow at the Robertson Center for Biostatistics at the University of Glasgow.

“Identification of patients at high risk is valuable information for multidisciplinary teams,” Dr. Pellicori said in a written comment. “It allows the most vulnerable patients to be highlighted and prioritized for consideration of optimized value-based care, and for anticipatory care plan discussions.”

The retrospective cohort study analyzed EHR records of 17,973 patients who had an unplanned hospitalization for COPD in the Glasgow area from 2011 to 2017. The risk calculator model achieved a potential accuracy of 80%.

The study noted that, while a number of models have been developed to calculate the risk of exacerbations, inpatient death and prognosis in patients hospitalized for COPD, most of those models were based on cohorts of 1000 patients or less.

“Older age, male sex, and a longer hospital stay were important predictors of mortality in patients with COPD,” Dr. Pellicori said. “We also found that use of commonly prescribed medications such as digoxin identify patients with COPD more likely to die, perhaps because many have underlying heart failure, a highly prevalent but frequently missed diagnosis.”

He noted that heart failure and COPD share many risk factors, signs, and symptoms, such as smoking history, peripheral edema, and breathlessness. “Distinguishing between COPD and heart failure can be difficult, but is very important, as appropriate treatment for heart failure can improve a patient’s quality of life and survival substantially in many cases.”

The study also found that routinely collected and inexpensive blood markers – such as hemoglobin, neutrophil/lymphocyte ratio, serum chloride, urea, creatinine, and albumin – can also improve predictability of outcomes.

For example, the study found a linear increase in mortality of blood hemoglobin concentration less than 14 g/dL, but higher levels posed no greater risk. Higher white blood cell and neutrophil counts and lower lymphocyte and eosinophil counts were associated with a worse prognosis.

The study also found a linear increase in mortality with serum sodium less than 140 mmol/L or serum chloride less than 105 mmol/L –  but that higher concentrations of each were associated with a worse outcome.

“Interestingly,” Pellicori added, “social deprivation was not associated with mortality in this cohort.”

The final predictive model included age, sex, length of stay, and just nine other variables. “The model can be applied easily in clinical practice, even if electronic records are not available, because there are only 12 variables,” Dr. Pellicori said. “These could easily be entered manually into the risk calculator that we provide.”

“What is notable about this risk calculator is that it uses some of the techniques of machine learning, although it’s not specifically machine learning,” Angel Coz, MD, a pulmonologist at the Cleveland Clinic Respiratory Institute, said in an interview. “But it’s a retrospective data analysis, and actually by doing that it may catch some factors that we may not have necessarily paid attention to on a regular basis.”

While he called it a “well-done study,” Dr. Coz cautioned that “we have to be conservative in how to interpret and apply this because it is retrospective,” adding that future research should also use a prospective cohort.

For future consideration, Dr. Pellicori said that, while EHRs provide a “rich source” of data for such risk calculators, systems differ greatly across hospitals and health care systems and don’t link easily.

Future research would focus on validating the model in other large national datasets and seeing if machine learning can improve its predictability, Dr. Pellicori said. “Whether such models can provide a real-time, refined risk assessment for all patients in both primary or secondary care settings and improve the efficacy, efficiency, and quality of health care is our long-term goal.”

Dr. Pellicori and Dr. Coz disclosed no relevant financial relationships.

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

Researchers in Scotland have developed a risk calculator using a large electronic health records database that has shown a high reliability in predicting the risk of death for patients hospitalized for chronic occlusive pulmonary disease (COPD), providing another potential tool for improving postdischarge survival in these patients.

In a study published online in the journal Pharmacological Research, Pierpalo Pellicori, MD, and colleagues reported that a few variables, including prescriptions and laboratory data in routine EHRs, could help predict a patient’s risk of dying within 90 days after a hospital stay for COPD. Dr. Pellicori is a clinical cardiologist and research fellow at the Robertson Center for Biostatistics at the University of Glasgow.

“Identification of patients at high risk is valuable information for multidisciplinary teams,” Dr. Pellicori said in a written comment. “It allows the most vulnerable patients to be highlighted and prioritized for consideration of optimized value-based care, and for anticipatory care plan discussions.”

The retrospective cohort study analyzed EHR records of 17,973 patients who had an unplanned hospitalization for COPD in the Glasgow area from 2011 to 2017. The risk calculator model achieved a potential accuracy of 80%.

The study noted that, while a number of models have been developed to calculate the risk of exacerbations, inpatient death and prognosis in patients hospitalized for COPD, most of those models were based on cohorts of 1000 patients or less.

“Older age, male sex, and a longer hospital stay were important predictors of mortality in patients with COPD,” Dr. Pellicori said. “We also found that use of commonly prescribed medications such as digoxin identify patients with COPD more likely to die, perhaps because many have underlying heart failure, a highly prevalent but frequently missed diagnosis.”

He noted that heart failure and COPD share many risk factors, signs, and symptoms, such as smoking history, peripheral edema, and breathlessness. “Distinguishing between COPD and heart failure can be difficult, but is very important, as appropriate treatment for heart failure can improve a patient’s quality of life and survival substantially in many cases.”

The study also found that routinely collected and inexpensive blood markers – such as hemoglobin, neutrophil/lymphocyte ratio, serum chloride, urea, creatinine, and albumin – can also improve predictability of outcomes.

For example, the study found a linear increase in mortality of blood hemoglobin concentration less than 14 g/dL, but higher levels posed no greater risk. Higher white blood cell and neutrophil counts and lower lymphocyte and eosinophil counts were associated with a worse prognosis.

The study also found a linear increase in mortality with serum sodium less than 140 mmol/L or serum chloride less than 105 mmol/L –  but that higher concentrations of each were associated with a worse outcome.

“Interestingly,” Pellicori added, “social deprivation was not associated with mortality in this cohort.”

The final predictive model included age, sex, length of stay, and just nine other variables. “The model can be applied easily in clinical practice, even if electronic records are not available, because there are only 12 variables,” Dr. Pellicori said. “These could easily be entered manually into the risk calculator that we provide.”

“What is notable about this risk calculator is that it uses some of the techniques of machine learning, although it’s not specifically machine learning,” Angel Coz, MD, a pulmonologist at the Cleveland Clinic Respiratory Institute, said in an interview. “But it’s a retrospective data analysis, and actually by doing that it may catch some factors that we may not have necessarily paid attention to on a regular basis.”

While he called it a “well-done study,” Dr. Coz cautioned that “we have to be conservative in how to interpret and apply this because it is retrospective,” adding that future research should also use a prospective cohort.

For future consideration, Dr. Pellicori said that, while EHRs provide a “rich source” of data for such risk calculators, systems differ greatly across hospitals and health care systems and don’t link easily.

Future research would focus on validating the model in other large national datasets and seeing if machine learning can improve its predictability, Dr. Pellicori said. “Whether such models can provide a real-time, refined risk assessment for all patients in both primary or secondary care settings and improve the efficacy, efficiency, and quality of health care is our long-term goal.”

Dr. Pellicori and Dr. Coz disclosed no relevant financial relationships.

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

Researchers in Scotland have developed a risk calculator using a large electronic health records database that has shown a high reliability in predicting the risk of death for patients hospitalized for chronic occlusive pulmonary disease (COPD), providing another potential tool for improving postdischarge survival in these patients.

In a study published online in the journal Pharmacological Research, Pierpalo Pellicori, MD, and colleagues reported that a few variables, including prescriptions and laboratory data in routine EHRs, could help predict a patient’s risk of dying within 90 days after a hospital stay for COPD. Dr. Pellicori is a clinical cardiologist and research fellow at the Robertson Center for Biostatistics at the University of Glasgow.

“Identification of patients at high risk is valuable information for multidisciplinary teams,” Dr. Pellicori said in a written comment. “It allows the most vulnerable patients to be highlighted and prioritized for consideration of optimized value-based care, and for anticipatory care plan discussions.”

The retrospective cohort study analyzed EHR records of 17,973 patients who had an unplanned hospitalization for COPD in the Glasgow area from 2011 to 2017. The risk calculator model achieved a potential accuracy of 80%.

The study noted that, while a number of models have been developed to calculate the risk of exacerbations, inpatient death and prognosis in patients hospitalized for COPD, most of those models were based on cohorts of 1000 patients or less.

“Older age, male sex, and a longer hospital stay were important predictors of mortality in patients with COPD,” Dr. Pellicori said. “We also found that use of commonly prescribed medications such as digoxin identify patients with COPD more likely to die, perhaps because many have underlying heart failure, a highly prevalent but frequently missed diagnosis.”

He noted that heart failure and COPD share many risk factors, signs, and symptoms, such as smoking history, peripheral edema, and breathlessness. “Distinguishing between COPD and heart failure can be difficult, but is very important, as appropriate treatment for heart failure can improve a patient’s quality of life and survival substantially in many cases.”

The study also found that routinely collected and inexpensive blood markers – such as hemoglobin, neutrophil/lymphocyte ratio, serum chloride, urea, creatinine, and albumin – can also improve predictability of outcomes.

For example, the study found a linear increase in mortality of blood hemoglobin concentration less than 14 g/dL, but higher levels posed no greater risk. Higher white blood cell and neutrophil counts and lower lymphocyte and eosinophil counts were associated with a worse prognosis.

The study also found a linear increase in mortality with serum sodium less than 140 mmol/L or serum chloride less than 105 mmol/L –  but that higher concentrations of each were associated with a worse outcome.

“Interestingly,” Pellicori added, “social deprivation was not associated with mortality in this cohort.”

The final predictive model included age, sex, length of stay, and just nine other variables. “The model can be applied easily in clinical practice, even if electronic records are not available, because there are only 12 variables,” Dr. Pellicori said. “These could easily be entered manually into the risk calculator that we provide.”

“What is notable about this risk calculator is that it uses some of the techniques of machine learning, although it’s not specifically machine learning,” Angel Coz, MD, a pulmonologist at the Cleveland Clinic Respiratory Institute, said in an interview. “But it’s a retrospective data analysis, and actually by doing that it may catch some factors that we may not have necessarily paid attention to on a regular basis.”

While he called it a “well-done study,” Dr. Coz cautioned that “we have to be conservative in how to interpret and apply this because it is retrospective,” adding that future research should also use a prospective cohort.

For future consideration, Dr. Pellicori said that, while EHRs provide a “rich source” of data for such risk calculators, systems differ greatly across hospitals and health care systems and don’t link easily.

Future research would focus on validating the model in other large national datasets and seeing if machine learning can improve its predictability, Dr. Pellicori said. “Whether such models can provide a real-time, refined risk assessment for all patients in both primary or secondary care settings and improve the efficacy, efficiency, and quality of health care is our long-term goal.”

Dr. Pellicori and Dr. Coz disclosed no relevant financial relationships.

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

New research from 10 countries around the globe, including 1,164 participants from the United Kingdom, presented at this year’s European Congress on Obesity shows that nearly one-quarter (24%) of adolescents living with obesity (ALwO) do not know they have obesity.

“The impact of obesity – in children and adults – on individuals, society, and our health care systems should not be underestimated,” said lead author Professor Jason C.G. Halford, PhD, C.Psychol, AFBPS, head of the school of psychology, University of Leeds (England), and president of the European Association for the Study of Obesity.

The new findings come from the ACTION teens global survey study, a quantitative survey-based study that collected data in 10 countries (Australia, Colombia, Italy, Korea, Mexico, Saudi Arabia, Spain, Taiwan, Turkey, and the United Kingdom) and included ALwO, their caregivers, and health care professionals (HCPs) who had direct, recent experience of clinical obesity management in adolescents.

Included in the survey were:

• 5,275 ALwO aged 12-17 years with current body mass index–for-age (based on self-reported sex, age, height, and weight) in the top 5% (≥95th percentile) for age and sex.
• 5,389 caregivers aged 25 years and over, who were the parent or legal guardian of an ALwO who lived in the same household at least 50% of the time and were involved in their ALwO’s health care decisions.
• 2,323 HCP, primary care physicians, pediatricians, or other specialists, who had been in clinical practice for at least 2 years, spent at least 50% of their time in direct patient care, and treated at least 10 ALwO in a typical month

An online panel, telephone calls, and in-person meetings were utilized to survey participants on a wide range of topics, including attitudes towards obesity and its impact, number of weight-loss attempts, and motivations/barriers to weight loss.
 

Many believe losing weight is their sole responsibility

The authors reported that around 9 out of 10 (89%) HCPs indicated that obesity has a strong impact on a person’s overall health and wellbeing. Fewer ALwO and caregivers, however, had similar views about this (72% and 67% respectively). In addition, the authors said that “most participants thought obesity was at least as, or more, impactful than heart disease, cancer, or diabetes.”

Despite many ALwO not recognizing being obese, most surveyed (85%) were worried about the impact of their weight on their future health, with two-thirds (65%) feeling it was their sole responsibility to deal with their excess weight. This compared to 37% of caregivers and around one in four HCPs (27%) feeling that losing weight was solely the ALwO’s responsibility.

Study coauthor Vicki Mooney, chairwoman of the Irish Coalition for People Living with Obesity and executive director of the European Coalition for People living with Obesity, said: “It is hard to fathom the pressure for these teenagers, especially as two-thirds believe it is their sole responsibility to lose weight, with many of their parents/caregivers struggling to know how to best care for their child.”
 

Teenagers unable to speak to parents about losing weight

Many ALwO said they struggled to talk to those closest to them about their weight, with 1 in 3 saying they couldn’t talk to either parent about their weight, and alarmingly 1 in 10 feeling they couldn’t talk to anyone about their weight. However, around one in three could talk to their doctor, and 74% said that they trusted the advice of a HCP about weight management.

Ms. Mooney said: “The results show us teenagers want to lose weight and improve their health, however, one in three teenagers feel unable to speak to their parents about it and many revert to social media for guidance.”

When it came to sources of information YouTube (34%), social media (28%), family and friends (25%), search engines (25%), and doctors (24%) were the most popular.
 

Motivation, barriers, and attempts

Weight-loss attempts by ALwO appeared to be underestimated by HCPs, the authors explained, while caregivers tended to underestimate both the impact of obesity on health and wellbeing, and ALwO’s weight-loss attempts.

Efforts had been made to try and lose weight in the past year by more than half (58%) of ALwO, with three-quarters (75%) being somewhat/very likely to attempt to lose weight in the next 6 months. However, fewer (41%) caregivers reported that their ‘linked’ ALwO attempted weight loss over the past year or that their ALwO was somewhat/very likely (63%) to attempt to lose weight in the next 6 months. Amongst HCPs, only about two out of five (38%) responded that their ALwO patients had made a serious weight loss attempt in the past year.

Motivation is a key component of successful weight reduction and wanting to be more fit/in better shape (40%), not being happy with their weight (37%), and wanting to feel more confident (35%) were the most common motivators for ALwO, and also the most common motivators reported by caregivers for their ALwO. For HCPs, though, things were somewhat different, with the top three motivators they reported for ALwO to lose weight were wanting the have more confidence/self-esteem (69%), improved social life and popularity (69%), and wanting to look like peers their age (65%).

The top three barriers to losing weight reported by ALwO and by caregivers for their ALwO were not being able to control hunger (38%), lack of motivation (34%), and enjoying eating unhealthy food (32%). For HCPs, the top three barriers they reported for ALwO losing weight were unhealthy eating habits (93%), lack of exercise (92%), and enjoying eating unhealthy food (91%).

“Key motivations and barriers for weight loss were not aligned between ALwO and HCPs,” said the authors. They pointed out that these disconnects may “negatively impact the level of support and effectiveness” of obesity care ALwO receive from caregivers and HCPs.

Prof. Halford said: “There is urgent need for governments and society to recognize and treat obesity as a disease, so that more teens can get the right support to help them live happier and healthier lives.”

The conference posters have yet to be published in a journal but were peer reviewed by the ECO selection committee.

The studies were sponsored by Novo Nordisk A/S.

A version of this article first appeared on Univadis.

New research from 10 countries around the globe, including 1,164 participants from the United Kingdom, presented at this year’s European Congress on Obesity shows that nearly one-quarter (24%) of adolescents living with obesity (ALwO) do not know they have obesity.

“The impact of obesity – in children and adults – on individuals, society, and our health care systems should not be underestimated,” said lead author Professor Jason C.G. Halford, PhD, C.Psychol, AFBPS, head of the school of psychology, University of Leeds (England), and president of the European Association for the Study of Obesity.

The new findings come from the ACTION teens global survey study, a quantitative survey-based study that collected data in 10 countries (Australia, Colombia, Italy, Korea, Mexico, Saudi Arabia, Spain, Taiwan, Turkey, and the United Kingdom) and included ALwO, their caregivers, and health care professionals (HCPs) who had direct, recent experience of clinical obesity management in adolescents.

Included in the survey were:

• 5,275 ALwO aged 12-17 years with current body mass index–for-age (based on self-reported sex, age, height, and weight) in the top 5% (≥95th percentile) for age and sex.
• 5,389 caregivers aged 25 years and over, who were the parent or legal guardian of an ALwO who lived in the same household at least 50% of the time and were involved in their ALwO’s health care decisions.
• 2,323 HCP, primary care physicians, pediatricians, or other specialists, who had been in clinical practice for at least 2 years, spent at least 50% of their time in direct patient care, and treated at least 10 ALwO in a typical month

An online panel, telephone calls, and in-person meetings were utilized to survey participants on a wide range of topics, including attitudes towards obesity and its impact, number of weight-loss attempts, and motivations/barriers to weight loss.
 

Many believe losing weight is their sole responsibility

The authors reported that around 9 out of 10 (89%) HCPs indicated that obesity has a strong impact on a person’s overall health and wellbeing. Fewer ALwO and caregivers, however, had similar views about this (72% and 67% respectively). In addition, the authors said that “most participants thought obesity was at least as, or more, impactful than heart disease, cancer, or diabetes.”

Despite many ALwO not recognizing being obese, most surveyed (85%) were worried about the impact of their weight on their future health, with two-thirds (65%) feeling it was their sole responsibility to deal with their excess weight. This compared to 37% of caregivers and around one in four HCPs (27%) feeling that losing weight was solely the ALwO’s responsibility.

Study coauthor Vicki Mooney, chairwoman of the Irish Coalition for People Living with Obesity and executive director of the European Coalition for People living with Obesity, said: “It is hard to fathom the pressure for these teenagers, especially as two-thirds believe it is their sole responsibility to lose weight, with many of their parents/caregivers struggling to know how to best care for their child.”
 

Teenagers unable to speak to parents about losing weight

Many ALwO said they struggled to talk to those closest to them about their weight, with 1 in 3 saying they couldn’t talk to either parent about their weight, and alarmingly 1 in 10 feeling they couldn’t talk to anyone about their weight. However, around one in three could talk to their doctor, and 74% said that they trusted the advice of a HCP about weight management.

Ms. Mooney said: “The results show us teenagers want to lose weight and improve their health, however, one in three teenagers feel unable to speak to their parents about it and many revert to social media for guidance.”

When it came to sources of information YouTube (34%), social media (28%), family and friends (25%), search engines (25%), and doctors (24%) were the most popular.
 

Motivation, barriers, and attempts

Weight-loss attempts by ALwO appeared to be underestimated by HCPs, the authors explained, while caregivers tended to underestimate both the impact of obesity on health and wellbeing, and ALwO’s weight-loss attempts.

Efforts had been made to try and lose weight in the past year by more than half (58%) of ALwO, with three-quarters (75%) being somewhat/very likely to attempt to lose weight in the next 6 months. However, fewer (41%) caregivers reported that their ‘linked’ ALwO attempted weight loss over the past year or that their ALwO was somewhat/very likely (63%) to attempt to lose weight in the next 6 months. Amongst HCPs, only about two out of five (38%) responded that their ALwO patients had made a serious weight loss attempt in the past year.

Motivation is a key component of successful weight reduction and wanting to be more fit/in better shape (40%), not being happy with their weight (37%), and wanting to feel more confident (35%) were the most common motivators for ALwO, and also the most common motivators reported by caregivers for their ALwO. For HCPs, though, things were somewhat different, with the top three motivators they reported for ALwO to lose weight were wanting the have more confidence/self-esteem (69%), improved social life and popularity (69%), and wanting to look like peers their age (65%).

The top three barriers to losing weight reported by ALwO and by caregivers for their ALwO were not being able to control hunger (38%), lack of motivation (34%), and enjoying eating unhealthy food (32%). For HCPs, the top three barriers they reported for ALwO losing weight were unhealthy eating habits (93%), lack of exercise (92%), and enjoying eating unhealthy food (91%).

“Key motivations and barriers for weight loss were not aligned between ALwO and HCPs,” said the authors. They pointed out that these disconnects may “negatively impact the level of support and effectiveness” of obesity care ALwO receive from caregivers and HCPs.

Prof. Halford said: “There is urgent need for governments and society to recognize and treat obesity as a disease, so that more teens can get the right support to help them live happier and healthier lives.”

The conference posters have yet to be published in a journal but were peer reviewed by the ECO selection committee.

The studies were sponsored by Novo Nordisk A/S.

A version of this article first appeared on Univadis.

New research from 10 countries around the globe, including 1,164 participants from the United Kingdom, presented at this year’s European Congress on Obesity shows that nearly one-quarter (24%) of adolescents living with obesity (ALwO) do not know they have obesity.

“The impact of obesity – in children and adults – on individuals, society, and our health care systems should not be underestimated,” said lead author Professor Jason C.G. Halford, PhD, C.Psychol, AFBPS, head of the school of psychology, University of Leeds (England), and president of the European Association for the Study of Obesity.

The new findings come from the ACTION teens global survey study, a quantitative survey-based study that collected data in 10 countries (Australia, Colombia, Italy, Korea, Mexico, Saudi Arabia, Spain, Taiwan, Turkey, and the United Kingdom) and included ALwO, their caregivers, and health care professionals (HCPs) who had direct, recent experience of clinical obesity management in adolescents.

Included in the survey were:

• 5,275 ALwO aged 12-17 years with current body mass index–for-age (based on self-reported sex, age, height, and weight) in the top 5% (≥95th percentile) for age and sex.
• 5,389 caregivers aged 25 years and over, who were the parent or legal guardian of an ALwO who lived in the same household at least 50% of the time and were involved in their ALwO’s health care decisions.
• 2,323 HCP, primary care physicians, pediatricians, or other specialists, who had been in clinical practice for at least 2 years, spent at least 50% of their time in direct patient care, and treated at least 10 ALwO in a typical month

An online panel, telephone calls, and in-person meetings were utilized to survey participants on a wide range of topics, including attitudes towards obesity and its impact, number of weight-loss attempts, and motivations/barriers to weight loss.
 

Many believe losing weight is their sole responsibility

The authors reported that around 9 out of 10 (89%) HCPs indicated that obesity has a strong impact on a person’s overall health and wellbeing. Fewer ALwO and caregivers, however, had similar views about this (72% and 67% respectively). In addition, the authors said that “most participants thought obesity was at least as, or more, impactful than heart disease, cancer, or diabetes.”

Despite many ALwO not recognizing being obese, most surveyed (85%) were worried about the impact of their weight on their future health, with two-thirds (65%) feeling it was their sole responsibility to deal with their excess weight. This compared to 37% of caregivers and around one in four HCPs (27%) feeling that losing weight was solely the ALwO’s responsibility.

Study coauthor Vicki Mooney, chairwoman of the Irish Coalition for People Living with Obesity and executive director of the European Coalition for People living with Obesity, said: “It is hard to fathom the pressure for these teenagers, especially as two-thirds believe it is their sole responsibility to lose weight, with many of their parents/caregivers struggling to know how to best care for their child.”
 

Teenagers unable to speak to parents about losing weight

Many ALwO said they struggled to talk to those closest to them about their weight, with 1 in 3 saying they couldn’t talk to either parent about their weight, and alarmingly 1 in 10 feeling they couldn’t talk to anyone about their weight. However, around one in three could talk to their doctor, and 74% said that they trusted the advice of a HCP about weight management.

Ms. Mooney said: “The results show us teenagers want to lose weight and improve their health, however, one in three teenagers feel unable to speak to their parents about it and many revert to social media for guidance.”

When it came to sources of information YouTube (34%), social media (28%), family and friends (25%), search engines (25%), and doctors (24%) were the most popular.
 

Motivation, barriers, and attempts

Weight-loss attempts by ALwO appeared to be underestimated by HCPs, the authors explained, while caregivers tended to underestimate both the impact of obesity on health and wellbeing, and ALwO’s weight-loss attempts.

Efforts had been made to try and lose weight in the past year by more than half (58%) of ALwO, with three-quarters (75%) being somewhat/very likely to attempt to lose weight in the next 6 months. However, fewer (41%) caregivers reported that their ‘linked’ ALwO attempted weight loss over the past year or that their ALwO was somewhat/very likely (63%) to attempt to lose weight in the next 6 months. Amongst HCPs, only about two out of five (38%) responded that their ALwO patients had made a serious weight loss attempt in the past year.

Motivation is a key component of successful weight reduction and wanting to be more fit/in better shape (40%), not being happy with their weight (37%), and wanting to feel more confident (35%) were the most common motivators for ALwO, and also the most common motivators reported by caregivers for their ALwO. For HCPs, though, things were somewhat different, with the top three motivators they reported for ALwO to lose weight were wanting the have more confidence/self-esteem (69%), improved social life and popularity (69%), and wanting to look like peers their age (65%).

The top three barriers to losing weight reported by ALwO and by caregivers for their ALwO were not being able to control hunger (38%), lack of motivation (34%), and enjoying eating unhealthy food (32%). For HCPs, the top three barriers they reported for ALwO losing weight were unhealthy eating habits (93%), lack of exercise (92%), and enjoying eating unhealthy food (91%).

“Key motivations and barriers for weight loss were not aligned between ALwO and HCPs,” said the authors. They pointed out that these disconnects may “negatively impact the level of support and effectiveness” of obesity care ALwO receive from caregivers and HCPs.

Prof. Halford said: “There is urgent need for governments and society to recognize and treat obesity as a disease, so that more teens can get the right support to help them live happier and healthier lives.”

The conference posters have yet to be published in a journal but were peer reviewed by the ECO selection committee.

The studies were sponsored by Novo Nordisk A/S.

A version of this article first appeared on Univadis.

Editors’ note: For the April edition of Expert Perspectives, we asked 2 leading neurologists to present differing views on the use of calcitonin gene-related peptide  (CGRP) monoclonal antibodies (mAbs) for the treatment of migraine. Here, Lawrence Robbins, MD, of the Robbins Headache Clinic in Riverwoods, IL, discusses potential safety concerns associated with this drug class. To read a counterargument in which Jack D. Schim, MD, of the Neurology Center of Southern California, discusses the observed benefits of CGRP mAbs, click here. 

Lawrence Robbins, MD is an associate professor of neurology at Chicago Medical School and is in private practice in Riverwoods, IL. 
Dr. Robbins discloses speaker’s bureau remuneration from AbbVie, Amgen, Biohaven, Impel NeuroPharma, Lundbeck, and Teva.

 
The calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) were introduced in 2018 as efficacious with few adverse effects. Unfortunately, the phase 3 trials failed to indicate the considerable number of adverse effects that have since been identified. This is a common occurrence with new drugs and mAbs. 
 
There are few adverse events identified in the package insert (PI) for any of the 4 CGRP mAbs, but again that is not restricted to this class. Post-approval, it frequently takes time to piece together the true adverse effect profile. Reasons that phase 3 studies may miss adverse effects include 1) The studies are powered for efficacy but are not powered for adverse effects in terms of both the number of patients and the length of the study; 2) Studies do not use a checklist of likely adverse effects; and 3) Adverse effects become “disaggregated” (for example, 1 person states they have malaise, another tiredness, and another fatigue).                                                                
 
In the ensuing years since the launch of the CGRP mAbs, various lines of evidence pointed to the adverse effects attributed to these mAbs. These include the US Food and Drug Administration (FDA)/FDA Adverse Event Reporting System (FAERS) website, published studies, the collective experience of high prescribers, and filtered comments from patient chat boards. In addition, I have received hundreds of letters from providers and patients regarding serious adverse effects, which are detailed further in this article. 
 
As of March 2022, the FDA/FAERS website has listed approximately 50,000 adverse events in connection with the CGRP mAbs. The number of serious events (hospitalization or life-threatening issues) was about 7000. These large numbers, just 3.75 years after launch, are like those listed for onabotulinumtoxin A after 30 years! Most of the reports involve erenumab. This is because erenumab was approved first and is the most prescribed drug in this class. I do not believe it is more dangerous than the others. Considering that the vast majority of adverse events go unreported, these are staggering numbers. Regarding serious adverse events, only 1% to 10% are actually reported to the FDA. Nobody knows the true percentage of milder adverse events that are actually reported, but in my experience, it is extremely low.
 
Unfortunately, the FDA/FAERS website lists on only adverse events, not adverse effects, which are just as important to discuss. In my small practice I have observed 4 serious adverse effects in women I believe are attributable to CGRP mAbs. These include a cerebrovascular accident in a 21-year-old patient, a case of reversible cerebral vasoconstrictive syndrome in a 61-year-old patient, severe joint pain in a 66-year-old patient, and a constellation of symptoms that resembled multiple sclerosis in a 30-year-old patient. I have administered onabotulinumtoxinA to thousands of patients for 25 years, with no serious adverse effects.
 
There have been a number of post-approval articles, studies, and case reports published since the launch of the CGRP mAbs. Many “review” or “meta-analysis” articles tend to repeat the results of the pharma-sponsored studies. They typically characterize the CGRP mAbs as safe, with few adverse events. Long-term safety extension studies almost always conclude that the drug is safe. In my opinion, the results from these studies are not reliable because of their possible ties to phrama. 
 
Other studies tell a different tale. One observational study of erenumab concluded that adverse effects contributed to 33% of the discontinuations. Another study reported that 63.3% of patients taking mAbs described at least 1 adverse effect. A study of patients who had been prescribed erenumab indicated that 48% reported a non-serious adverse event after 3 months.  
 
Neurologists are generally unaware of the dangers posed by CGRP mAbs. In September 2021, I engaged in a debate on this topic during the International 15th World Congress on Controversies in Neurology (CONy). Prior to the debate, the audience members were polled. 94% believed the CGRP mAbs to be safe. After our debate, only 40% felt that these mAbs were safe. I think that the audience, primarily consisting of neurologists, was not informed as to the potential dangers of the CGRP mAbs.                                                        

                            
In our practice

For refractory patients, I do prescribe these CGRP mAbs. However, I feel they should only be prescribed after several other, safer options have failed. These include the natural approaches (butterbur, magnesium, riboflavin), several of the standard medications (amitriptyline, beta blockers, topiramate, valproate, angiotensin II receptor blockers), and onabotulinumtoxinA. Additionally, the newer gepants for prevention (rimegepant and atogepant) appear to be safer options than the CGRP mAbs, although we cannot say this definitively at this time.

In 2018, our clinic began a retrospective study that lasted until January 2020. We assessed 119 patients with chronic migraine who had been prescribed one of the CGRP mAbs. This study incorporated the use of a checklist of possible adverse effects. Each of these adverse effects had created a “signal.” We initially asked the patients, “Have you experienced any issues, problems, or side effects due to the CGRP monoclonal antibody?” The patients subsequently were interviewed and asked about each possible adverse effect included on the checklist. The patient and physician determined whether any adverse effect mentioned by the patient was due to the CGRP mAb. After discussing the checklist, 66% of the patients concluded they had experienced 1 additional adverse effect that they attributed to the CGRP mAb and had not originally disclosed in response to the initial question. Most of these patients identified more than 1 additional adverse effect through use of the checklist.  
 

Gathering data

To determine the true adverse event profile post-approval, we rely upon the input of high prescribers, who often can provide this necessary feedback. I have assessed input from headache provider chat boards, private correspondence with many providers, and discussions with colleagues at conferences. The opinions do vary, with some headache providers arguing that there are not that many adverse effects arising from the CGRP mAbs. Many others believe, as I do, that there are a large number of adverse events. In my observations, there is not a consensus among headache providers. 
 
The CGRP patient chat boards are another valuable line of evidence. I have screened 2800 comments from patients regarding adverse events. I filtered these down into 490 “highly believable” comments. Among those, the adverse events described align very well with our other lines of evidence. 
 
If we put all the post-approval lines of evidence together, we come up with the following list of “adverse effect signals” attribututed  to the CGRP mAbs. These include constipation (it may be severe; hence the warning in the erenumab PI), injection site reactions, joint pain, anxiety, muscle pain or cramps, hypertension or worsening hypertension (there is a warning in the erenumab PI), nausea (it may be severe; “area postrema syndrome” has occurred), rash, increased headache, fatigue, depression, insomnia, hair loss, tachycardia (and other cardiac arrhythmias), stroke, angina and myocardial infarction, weight gain or loss, irritability, and sexual dysfunction. There are also other adverse events. In his review of the CGRP mAbs, Thomas Moore, a leading expert in adverse events, cited the “sheer number of case reports, and it is likely that AEs of this migraine preventive were underestimated in the clinical trials.”   
 
This discussion has focused on short-term adverse events. We have no idea regarding long-term effects, but I suspect that we will encounter serious ones. Evolution has deemed CGRP to be vital for 450 million years. We ignore evolution at our peril. 
  
CGRP is a powerful vasodilator and protects our cardiovascular and cerebrovascular systems. CGRP resists the onset of hypertension. Wound and burn healing, as well as tissue repair, require CGRP. Bony metabolism and bone healing are partly dependent upon CGRP. CGRP protects from gastrointestinal (GI) ulcers and aids GI motility. CGRP mitigates the effects of sepsis. 
 
CGRP is also involved with flushing, thermoregulation, cold hypersensitivity, protecting the kidneys when under stress, helping regulate insulin release, and mediating the adrenal glucocorticoid response to acute stress (particularly in the mature fetus). Effects on the hypothalamic-pituitary-adrenal axis are worrisome but unknown. CGRP is important as a vasodilator during stress, and the CGRP mAbs have not yet been tested under stress.  

The CGRP mAbs have been terrific for many patients, and their efficacy is on par with onabotulinumtoxinA. However, in a short period of time we have witnessed a plethora of serious (and non-serious) adverse effects from short-term use. CGRP plays an important role in many physiologic processes. We have no idea as to the long-term consequences of blocking CGRP and we should proceed with caution.
 

Editors’ note: For the April edition of Expert Perspectives, we asked 2 leading neurologists to present differing views on the use of calcitonin gene-related peptide  (CGRP) monoclonal antibodies (mAbs) for the treatment of migraine. Here, Lawrence Robbins, MD, of the Robbins Headache Clinic in Riverwoods, IL, discusses potential safety concerns associated with this drug class. To read a counterargument in which Jack D. Schim, MD, of the Neurology Center of Southern California, discusses the observed benefits of CGRP mAbs, click here. 

Lawrence Robbins, MD is an associate professor of neurology at Chicago Medical School and is in private practice in Riverwoods, IL. 
Dr. Robbins discloses speaker’s bureau remuneration from AbbVie, Amgen, Biohaven, Impel NeuroPharma, Lundbeck, and Teva.

 
The calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) were introduced in 2018 as efficacious with few adverse effects. Unfortunately, the phase 3 trials failed to indicate the considerable number of adverse effects that have since been identified. This is a common occurrence with new drugs and mAbs. 
 
There are few adverse events identified in the package insert (PI) for any of the 4 CGRP mAbs, but again that is not restricted to this class. Post-approval, it frequently takes time to piece together the true adverse effect profile. Reasons that phase 3 studies may miss adverse effects include 1) The studies are powered for efficacy but are not powered for adverse effects in terms of both the number of patients and the length of the study; 2) Studies do not use a checklist of likely adverse effects; and 3) Adverse effects become “disaggregated” (for example, 1 person states they have malaise, another tiredness, and another fatigue).                                                                
 
In the ensuing years since the launch of the CGRP mAbs, various lines of evidence pointed to the adverse effects attributed to these mAbs. These include the US Food and Drug Administration (FDA)/FDA Adverse Event Reporting System (FAERS) website, published studies, the collective experience of high prescribers, and filtered comments from patient chat boards. In addition, I have received hundreds of letters from providers and patients regarding serious adverse effects, which are detailed further in this article. 
 
As of March 2022, the FDA/FAERS website has listed approximately 50,000 adverse events in connection with the CGRP mAbs. The number of serious events (hospitalization or life-threatening issues) was about 7000. These large numbers, just 3.75 years after launch, are like those listed for onabotulinumtoxin A after 30 years! Most of the reports involve erenumab. This is because erenumab was approved first and is the most prescribed drug in this class. I do not believe it is more dangerous than the others. Considering that the vast majority of adverse events go unreported, these are staggering numbers. Regarding serious adverse events, only 1% to 10% are actually reported to the FDA. Nobody knows the true percentage of milder adverse events that are actually reported, but in my experience, it is extremely low.
 
Unfortunately, the FDA/FAERS website lists on only adverse events, not adverse effects, which are just as important to discuss. In my small practice I have observed 4 serious adverse effects in women I believe are attributable to CGRP mAbs. These include a cerebrovascular accident in a 21-year-old patient, a case of reversible cerebral vasoconstrictive syndrome in a 61-year-old patient, severe joint pain in a 66-year-old patient, and a constellation of symptoms that resembled multiple sclerosis in a 30-year-old patient. I have administered onabotulinumtoxinA to thousands of patients for 25 years, with no serious adverse effects.
 
There have been a number of post-approval articles, studies, and case reports published since the launch of the CGRP mAbs. Many “review” or “meta-analysis” articles tend to repeat the results of the pharma-sponsored studies. They typically characterize the CGRP mAbs as safe, with few adverse events. Long-term safety extension studies almost always conclude that the drug is safe. In my opinion, the results from these studies are not reliable because of their possible ties to phrama. 
 
Other studies tell a different tale. One observational study of erenumab concluded that adverse effects contributed to 33% of the discontinuations. Another study reported that 63.3% of patients taking mAbs described at least 1 adverse effect. A study of patients who had been prescribed erenumab indicated that 48% reported a non-serious adverse event after 3 months.  
 
Neurologists are generally unaware of the dangers posed by CGRP mAbs. In September 2021, I engaged in a debate on this topic during the International 15th World Congress on Controversies in Neurology (CONy). Prior to the debate, the audience members were polled. 94% believed the CGRP mAbs to be safe. After our debate, only 40% felt that these mAbs were safe. I think that the audience, primarily consisting of neurologists, was not informed as to the potential dangers of the CGRP mAbs.                                                        

                            
In our practice

For refractory patients, I do prescribe these CGRP mAbs. However, I feel they should only be prescribed after several other, safer options have failed. These include the natural approaches (butterbur, magnesium, riboflavin), several of the standard medications (amitriptyline, beta blockers, topiramate, valproate, angiotensin II receptor blockers), and onabotulinumtoxinA. Additionally, the newer gepants for prevention (rimegepant and atogepant) appear to be safer options than the CGRP mAbs, although we cannot say this definitively at this time.

In 2018, our clinic began a retrospective study that lasted until January 2020. We assessed 119 patients with chronic migraine who had been prescribed one of the CGRP mAbs. This study incorporated the use of a checklist of possible adverse effects. Each of these adverse effects had created a “signal.” We initially asked the patients, “Have you experienced any issues, problems, or side effects due to the CGRP monoclonal antibody?” The patients subsequently were interviewed and asked about each possible adverse effect included on the checklist. The patient and physician determined whether any adverse effect mentioned by the patient was due to the CGRP mAb. After discussing the checklist, 66% of the patients concluded they had experienced 1 additional adverse effect that they attributed to the CGRP mAb and had not originally disclosed in response to the initial question. Most of these patients identified more than 1 additional adverse effect through use of the checklist.  
 

Gathering data

To determine the true adverse event profile post-approval, we rely upon the input of high prescribers, who often can provide this necessary feedback. I have assessed input from headache provider chat boards, private correspondence with many providers, and discussions with colleagues at conferences. The opinions do vary, with some headache providers arguing that there are not that many adverse effects arising from the CGRP mAbs. Many others believe, as I do, that there are a large number of adverse events. In my observations, there is not a consensus among headache providers. 
 
The CGRP patient chat boards are another valuable line of evidence. I have screened 2800 comments from patients regarding adverse events. I filtered these down into 490 “highly believable” comments. Among those, the adverse events described align very well with our other lines of evidence. 
 
If we put all the post-approval lines of evidence together, we come up with the following list of “adverse effect signals” attribututed  to the CGRP mAbs. These include constipation (it may be severe; hence the warning in the erenumab PI), injection site reactions, joint pain, anxiety, muscle pain or cramps, hypertension or worsening hypertension (there is a warning in the erenumab PI), nausea (it may be severe; “area postrema syndrome” has occurred), rash, increased headache, fatigue, depression, insomnia, hair loss, tachycardia (and other cardiac arrhythmias), stroke, angina and myocardial infarction, weight gain or loss, irritability, and sexual dysfunction. There are also other adverse events. In his review of the CGRP mAbs, Thomas Moore, a leading expert in adverse events, cited the “sheer number of case reports, and it is likely that AEs of this migraine preventive were underestimated in the clinical trials.”   
 
This discussion has focused on short-term adverse events. We have no idea regarding long-term effects, but I suspect that we will encounter serious ones. Evolution has deemed CGRP to be vital for 450 million years. We ignore evolution at our peril. 
  
CGRP is a powerful vasodilator and protects our cardiovascular and cerebrovascular systems. CGRP resists the onset of hypertension. Wound and burn healing, as well as tissue repair, require CGRP. Bony metabolism and bone healing are partly dependent upon CGRP. CGRP protects from gastrointestinal (GI) ulcers and aids GI motility. CGRP mitigates the effects of sepsis. 
 
CGRP is also involved with flushing, thermoregulation, cold hypersensitivity, protecting the kidneys when under stress, helping regulate insulin release, and mediating the adrenal glucocorticoid response to acute stress (particularly in the mature fetus). Effects on the hypothalamic-pituitary-adrenal axis are worrisome but unknown. CGRP is important as a vasodilator during stress, and the CGRP mAbs have not yet been tested under stress.  

The CGRP mAbs have been terrific for many patients, and their efficacy is on par with onabotulinumtoxinA. However, in a short period of time we have witnessed a plethora of serious (and non-serious) adverse effects from short-term use. CGRP plays an important role in many physiologic processes. We have no idea as to the long-term consequences of blocking CGRP and we should proceed with caution.
 

Editors’ note: For the April edition of Expert Perspectives, we asked 2 leading neurologists to present differing views on the use of calcitonin gene-related peptide  (CGRP) monoclonal antibodies (mAbs) for the treatment of migraine. Here, Lawrence Robbins, MD, of the Robbins Headache Clinic in Riverwoods, IL, discusses potential safety concerns associated with this drug class. To read a counterargument in which Jack D. Schim, MD, of the Neurology Center of Southern California, discusses the observed benefits of CGRP mAbs, click here. 

Lawrence Robbins, MD is an associate professor of neurology at Chicago Medical School and is in private practice in Riverwoods, IL. 
Dr. Robbins discloses speaker’s bureau remuneration from AbbVie, Amgen, Biohaven, Impel NeuroPharma, Lundbeck, and Teva.

 
The calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) were introduced in 2018 as efficacious with few adverse effects. Unfortunately, the phase 3 trials failed to indicate the considerable number of adverse effects that have since been identified. This is a common occurrence with new drugs and mAbs. 
 
There are few adverse events identified in the package insert (PI) for any of the 4 CGRP mAbs, but again that is not restricted to this class. Post-approval, it frequently takes time to piece together the true adverse effect profile. Reasons that phase 3 studies may miss adverse effects include 1) The studies are powered for efficacy but are not powered for adverse effects in terms of both the number of patients and the length of the study; 2) Studies do not use a checklist of likely adverse effects; and 3) Adverse effects become “disaggregated” (for example, 1 person states they have malaise, another tiredness, and another fatigue).                                                                
 
In the ensuing years since the launch of the CGRP mAbs, various lines of evidence pointed to the adverse effects attributed to these mAbs. These include the US Food and Drug Administration (FDA)/FDA Adverse Event Reporting System (FAERS) website, published studies, the collective experience of high prescribers, and filtered comments from patient chat boards. In addition, I have received hundreds of letters from providers and patients regarding serious adverse effects, which are detailed further in this article. 
 
As of March 2022, the FDA/FAERS website has listed approximately 50,000 adverse events in connection with the CGRP mAbs. The number of serious events (hospitalization or life-threatening issues) was about 7000. These large numbers, just 3.75 years after launch, are like those listed for onabotulinumtoxin A after 30 years! Most of the reports involve erenumab. This is because erenumab was approved first and is the most prescribed drug in this class. I do not believe it is more dangerous than the others. Considering that the vast majority of adverse events go unreported, these are staggering numbers. Regarding serious adverse events, only 1% to 10% are actually reported to the FDA. Nobody knows the true percentage of milder adverse events that are actually reported, but in my experience, it is extremely low.
 
Unfortunately, the FDA/FAERS website lists on only adverse events, not adverse effects, which are just as important to discuss. In my small practice I have observed 4 serious adverse effects in women I believe are attributable to CGRP mAbs. These include a cerebrovascular accident in a 21-year-old patient, a case of reversible cerebral vasoconstrictive syndrome in a 61-year-old patient, severe joint pain in a 66-year-old patient, and a constellation of symptoms that resembled multiple sclerosis in a 30-year-old patient. I have administered onabotulinumtoxinA to thousands of patients for 25 years, with no serious adverse effects.
 
There have been a number of post-approval articles, studies, and case reports published since the launch of the CGRP mAbs. Many “review” or “meta-analysis” articles tend to repeat the results of the pharma-sponsored studies. They typically characterize the CGRP mAbs as safe, with few adverse events. Long-term safety extension studies almost always conclude that the drug is safe. In my opinion, the results from these studies are not reliable because of their possible ties to phrama. 
 
Other studies tell a different tale. One observational study of erenumab concluded that adverse effects contributed to 33% of the discontinuations. Another study reported that 63.3% of patients taking mAbs described at least 1 adverse effect. A study of patients who had been prescribed erenumab indicated that 48% reported a non-serious adverse event after 3 months.  
 
Neurologists are generally unaware of the dangers posed by CGRP mAbs. In September 2021, I engaged in a debate on this topic during the International 15th World Congress on Controversies in Neurology (CONy). Prior to the debate, the audience members were polled. 94% believed the CGRP mAbs to be safe. After our debate, only 40% felt that these mAbs were safe. I think that the audience, primarily consisting of neurologists, was not informed as to the potential dangers of the CGRP mAbs.                                                        

                            
In our practice

For refractory patients, I do prescribe these CGRP mAbs. However, I feel they should only be prescribed after several other, safer options have failed. These include the natural approaches (butterbur, magnesium, riboflavin), several of the standard medications (amitriptyline, beta blockers, topiramate, valproate, angiotensin II receptor blockers), and onabotulinumtoxinA. Additionally, the newer gepants for prevention (rimegepant and atogepant) appear to be safer options than the CGRP mAbs, although we cannot say this definitively at this time.

In 2018, our clinic began a retrospective study that lasted until January 2020. We assessed 119 patients with chronic migraine who had been prescribed one of the CGRP mAbs. This study incorporated the use of a checklist of possible adverse effects. Each of these adverse effects had created a “signal.” We initially asked the patients, “Have you experienced any issues, problems, or side effects due to the CGRP monoclonal antibody?” The patients subsequently were interviewed and asked about each possible adverse effect included on the checklist. The patient and physician determined whether any adverse effect mentioned by the patient was due to the CGRP mAb. After discussing the checklist, 66% of the patients concluded they had experienced 1 additional adverse effect that they attributed to the CGRP mAb and had not originally disclosed in response to the initial question. Most of these patients identified more than 1 additional adverse effect through use of the checklist.  
 

Gathering data

To determine the true adverse event profile post-approval, we rely upon the input of high prescribers, who often can provide this necessary feedback. I have assessed input from headache provider chat boards, private correspondence with many providers, and discussions with colleagues at conferences. The opinions do vary, with some headache providers arguing that there are not that many adverse effects arising from the CGRP mAbs. Many others believe, as I do, that there are a large number of adverse events. In my observations, there is not a consensus among headache providers. 
 
The CGRP patient chat boards are another valuable line of evidence. I have screened 2800 comments from patients regarding adverse events. I filtered these down into 490 “highly believable” comments. Among those, the adverse events described align very well with our other lines of evidence. 
 
If we put all the post-approval lines of evidence together, we come up with the following list of “adverse effect signals” attribututed  to the CGRP mAbs. These include constipation (it may be severe; hence the warning in the erenumab PI), injection site reactions, joint pain, anxiety, muscle pain or cramps, hypertension or worsening hypertension (there is a warning in the erenumab PI), nausea (it may be severe; “area postrema syndrome” has occurred), rash, increased headache, fatigue, depression, insomnia, hair loss, tachycardia (and other cardiac arrhythmias), stroke, angina and myocardial infarction, weight gain or loss, irritability, and sexual dysfunction. There are also other adverse events. In his review of the CGRP mAbs, Thomas Moore, a leading expert in adverse events, cited the “sheer number of case reports, and it is likely that AEs of this migraine preventive were underestimated in the clinical trials.”   
 
This discussion has focused on short-term adverse events. We have no idea regarding long-term effects, but I suspect that we will encounter serious ones. Evolution has deemed CGRP to be vital for 450 million years. We ignore evolution at our peril. 
  
CGRP is a powerful vasodilator and protects our cardiovascular and cerebrovascular systems. CGRP resists the onset of hypertension. Wound and burn healing, as well as tissue repair, require CGRP. Bony metabolism and bone healing are partly dependent upon CGRP. CGRP protects from gastrointestinal (GI) ulcers and aids GI motility. CGRP mitigates the effects of sepsis. 
 
CGRP is also involved with flushing, thermoregulation, cold hypersensitivity, protecting the kidneys when under stress, helping regulate insulin release, and mediating the adrenal glucocorticoid response to acute stress (particularly in the mature fetus). Effects on the hypothalamic-pituitary-adrenal axis are worrisome but unknown. CGRP is important as a vasodilator during stress, and the CGRP mAbs have not yet been tested under stress.  

The CGRP mAbs have been terrific for many patients, and their efficacy is on par with onabotulinumtoxinA. However, in a short period of time we have witnessed a plethora of serious (and non-serious) adverse effects from short-term use. CGRP plays an important role in many physiologic processes. We have no idea as to the long-term consequences of blocking CGRP and we should proceed with caution.
 

Editors’ note: For the April edition of Expert Perspectives, we asked two leading neurologists to present differing views on the use of calcitonin gene-related peptide (CGRPs) monoclonal antibodies (mAbs) for the treatment of migraine. Here, Jack D. Schim, MD, of the Neurology Center of Southern California, discusses the observed benefits of the CGRP mAbs. To read a counter-argument in which Lawrence Robbins, MD, of the Robbins Headache Clinic in Riverwoods, IL, discusses potential safety concerns associated with this drug class, click here.

Dr. Schim is Co-Director of The Headache Center of Southern California, The Neurology Center.  He is Board Member and past President of the Headache Consortium of the Pacific, Board Member and past President, American Heart Association San Diego, a Past President of the California Neurologic Society, and an active member of the American Academy of Neurology, American Stroke Association, and American Headache Society.

The identification of CGRP as a crucial pain signaling molecule in the trigeminal pathway, thereby establishing its link to migraine pain, has transformed care for patients with episodic and chronic migraine. Since 2018, the FDA has approved 4 monoclonal antibodies (mAbs) that either block the CGRP receptor or bind its ligand to prevent attachment to the receptor. 

These medications are helping patients with medication overuse headache (MOH) and chronic migraine; one study involving 139 patients showed that half the patients saw their headache days per month cut by half, and migraine days per month cut by 62%. In another small study, 23 patients (47%) with medication overuse headache reported having no MOH issues after 3 months. Most of these patients had a history of medication overuse, but no specific diagnosis of MOH.

In a survey, 277 physicians said that nearly half of their patients had resistant migraine, and 29% had refractory migraine. For these patients, the mAbs have helped restore some normalcy in their lives.  

But are these medications safe? Some clinicians posed this question even before the 2018 approval.

It is a valid question. The CGRP neuropeptide is a powerful dilator, establishing vascular homeostasis, organ development in utero, wound healing, and more. It is expressed in the peripheral and central nervous system and found abundantly in neurons and the unmyelinated A-fibers of the peripheral trigeminovascular system and trigeminal ganglion.

So, would blocking CGRP function in one area affect its function in another? So far, I have to say the answer is no. Neither the literature nor my observations say otherwise. 

Trials vs the real world

Finding an answer to this question takes more than reading clinical trials data. Participants in these trials do not necessarily represent the real world – no complicated morbidities, no pregnant or lactating women. And trial lengths are generally short.

Thus, it is important to assess the safety of these medications in the real world.  

In the trials of the subcutaneous mAbs, local injection site reactions were the most common adverse event. More specifically, erenumab showed increased incidence of constipation, and  post-marketing surveillance has revealed some risk of hypertension; pooled analysis from 4 trial phases showed that across treatment groups, 20 people out of 2443 began treatment for hypertension. Some patients enrolled in trials for atogepant, an oral small molecule CGRP receptor agonist, also reported constipation and nausea, suggesting that receptor blockade may result in a higher incidence of GI disturbance. In addition, these medicines on occasion have caused alopecia, fatigue, or achiness. 

Eptinezumab is administered intravenously, every 3 months, and thus does not have injection site reactions as a safety concern. In clinical trials, the most common adverse event was nasopharyngitis and hypersensitivity; Datta et al have provided a summary of safety and efficacy.

Raynaud’s and cluster headaches

A retrospective chart review study from the Mayo Clinic looking at individuals with Raynaud’s disease who were treated with CGRP antagonists showed that 5.3% of 169 patients had microvascular complications such as gangrene or autoimmune necrosis. There was no significant difference in demographic characteristics or rheumatologic history among those with Raynaud's who did or did not experience complications. In addition, microvascular complications of migraine therapies have preceded the use of CGRP modulators, as this has been documented in the past with other vasoactive substances such as ergots, triptans, and beta blockers. 

In a tolerability and safety study of galcanezumab in patients with chronic cluster headache, with up to 15 months of treatment, the most common treatment emergent adverse events were nasopharyngitis and injection site pain. In this population with 11% to 12% of individuals having baseline hypertension and nearly 63% currently using tobacco, less than 2.5% had any abnormalities on ECG.  

Vascular complications including pulmonary embolism, TIA, myocardial infarction, and atrial fibrillation have been reported but with no apparent relation between galcanezumab dosing and onset, with onset following the second to up to the eleventh monthly dose. 

Antidrug antibodies can also occur as a complication of exposure to therapeutic antibodies of this class and have been detected in up to 12% of individuals treated. This might lead to therapeutic failure but would not likely be a safety issue.

Anaphylaxis or serious hypersensitivity reactions are uncommon, and in general are the only contraindication to the use of these agents. 

Pregnancy registry information is just starting to become available. The number of reports on adverse drug reactions remains limited, and thus it is wise to avoid pregnancy and breastfeeding exposures as best as possible.

FAERS

The FDA adverse event reporting system (FAERS) database does contain reports on adverse events of approved medications. However, even the FDA website warns that the information provided regarding individual cases is unverified and wouldn’t establish causation, considering the confounding variables involved, and this information can be duplicated as well as incomplete. In addition, rates of occurrence cannot be established with reports, as the denominator of exposure is uncertain.  

With those caveats established, the most common reports in FAERS concern injection site reactions, more frequent migraine or headache, or drug ineffectiveness. While constipation has been the second most common AE for erenumab, it did not make the top 10 for fremanezumab or galcanezumab, and cardiovascular events have not ranked in the top 10 for any product. Reasons for discontinuing treatment included withdrawal by the patient (147 of 1,890 [8%]) and lack of efficacy (77 of 1,890 [4%]). 

As the reader can ascertain, different studies point out different reasons for discontinuing CGRP therapies. Other studies note that the most frequent reasons for discontinuation are lack of efficacy, constipation, and lack of insurance .

Conclusions

These medications have been well received; I believe. Fremanezumab, manufactured by Teva Pharmaceuticals, was approved in September 2018. According to Teva’s 2021 annual report, Ajovy, fremanezumab’s brand name, reached 21% market share in the US and 21% in Europe.

Aimovig, or erenumab, has been prescribed 620,000 times since its approval, according to the Novartis 2021 annual report. Galcanezumab, or Emgality, was approved in 2019, and had 65,300 prescriptions written in the since then. . Adherence to treatment has generally been very high in clinical practice, with the most common reason for a patient to switch being lack of effectiveness, rather than adverse events.

Of note, adverse events of other migraine therapeutics are not insignificant, and considering the pain that people with migraine endure, side effects must be hard to contend with for individuals to stop taking them. Case in point: A year before erenumab was approved, a study was published that looked at medical records for medication persistence in 8,700 chronic migraine patients, who all had been prescribed beta blockers, anti-seizure medications, or antidepressants. By 6 months, only 1 out of 4 patients were still taking the prescribed medicines. By 12 months, that  was down to 14%. And about one-third of patients who stopped treatment stayed untreated for at least a year. 

The presumed reasons these patients stopped their medications: side effects and-or lack of efficacy. 

Migraine is a disabling disorder, for which the mAb class of medications has been highly beneficial for large numbers of patients, with far greater tolerability than prior oral preventives. While no treatments have absolute safety, the overall safety of this class of medications has been very high, leading to much improved clinical outcomes.

Editors’ note: For the April edition of Expert Perspectives, we asked two leading neurologists to present differing views on the use of calcitonin gene-related peptide (CGRPs) monoclonal antibodies (mAbs) for the treatment of migraine. Here, Jack D. Schim, MD, of the Neurology Center of Southern California, discusses the observed benefits of the CGRP mAbs. To read a counter-argument in which Lawrence Robbins, MD, of the Robbins Headache Clinic in Riverwoods, IL, discusses potential safety concerns associated with this drug class, click here.

Dr. Schim is Co-Director of The Headache Center of Southern California, The Neurology Center.  He is Board Member and past President of the Headache Consortium of the Pacific, Board Member and past President, American Heart Association San Diego, a Past President of the California Neurologic Society, and an active member of the American Academy of Neurology, American Stroke Association, and American Headache Society.

The identification of CGRP as a crucial pain signaling molecule in the trigeminal pathway, thereby establishing its link to migraine pain, has transformed care for patients with episodic and chronic migraine. Since 2018, the FDA has approved 4 monoclonal antibodies (mAbs) that either block the CGRP receptor or bind its ligand to prevent attachment to the receptor. 

These medications are helping patients with medication overuse headache (MOH) and chronic migraine; one study involving 139 patients showed that half the patients saw their headache days per month cut by half, and migraine days per month cut by 62%. In another small study, 23 patients (47%) with medication overuse headache reported having no MOH issues after 3 months. Most of these patients had a history of medication overuse, but no specific diagnosis of MOH.

In a survey, 277 physicians said that nearly half of their patients had resistant migraine, and 29% had refractory migraine. For these patients, the mAbs have helped restore some normalcy in their lives.  

But are these medications safe? Some clinicians posed this question even before the 2018 approval.

It is a valid question. The CGRP neuropeptide is a powerful dilator, establishing vascular homeostasis, organ development in utero, wound healing, and more. It is expressed in the peripheral and central nervous system and found abundantly in neurons and the unmyelinated A-fibers of the peripheral trigeminovascular system and trigeminal ganglion.

So, would blocking CGRP function in one area affect its function in another? So far, I have to say the answer is no. Neither the literature nor my observations say otherwise. 

Trials vs the real world

Finding an answer to this question takes more than reading clinical trials data. Participants in these trials do not necessarily represent the real world – no complicated morbidities, no pregnant or lactating women. And trial lengths are generally short.

Thus, it is important to assess the safety of these medications in the real world.  

In the trials of the subcutaneous mAbs, local injection site reactions were the most common adverse event. More specifically, erenumab showed increased incidence of constipation, and  post-marketing surveillance has revealed some risk of hypertension; pooled analysis from 4 trial phases showed that across treatment groups, 20 people out of 2443 began treatment for hypertension. Some patients enrolled in trials for atogepant, an oral small molecule CGRP receptor agonist, also reported constipation and nausea, suggesting that receptor blockade may result in a higher incidence of GI disturbance. In addition, these medicines on occasion have caused alopecia, fatigue, or achiness. 

Eptinezumab is administered intravenously, every 3 months, and thus does not have injection site reactions as a safety concern. In clinical trials, the most common adverse event was nasopharyngitis and hypersensitivity; Datta et al have provided a summary of safety and efficacy.

Raynaud’s and cluster headaches

A retrospective chart review study from the Mayo Clinic looking at individuals with Raynaud’s disease who were treated with CGRP antagonists showed that 5.3% of 169 patients had microvascular complications such as gangrene or autoimmune necrosis. There was no significant difference in demographic characteristics or rheumatologic history among those with Raynaud's who did or did not experience complications. In addition, microvascular complications of migraine therapies have preceded the use of CGRP modulators, as this has been documented in the past with other vasoactive substances such as ergots, triptans, and beta blockers. 

In a tolerability and safety study of galcanezumab in patients with chronic cluster headache, with up to 15 months of treatment, the most common treatment emergent adverse events were nasopharyngitis and injection site pain. In this population with 11% to 12% of individuals having baseline hypertension and nearly 63% currently using tobacco, less than 2.5% had any abnormalities on ECG.  

Vascular complications including pulmonary embolism, TIA, myocardial infarction, and atrial fibrillation have been reported but with no apparent relation between galcanezumab dosing and onset, with onset following the second to up to the eleventh monthly dose. 

Antidrug antibodies can also occur as a complication of exposure to therapeutic antibodies of this class and have been detected in up to 12% of individuals treated. This might lead to therapeutic failure but would not likely be a safety issue.

Anaphylaxis or serious hypersensitivity reactions are uncommon, and in general are the only contraindication to the use of these agents. 

Pregnancy registry information is just starting to become available. The number of reports on adverse drug reactions remains limited, and thus it is wise to avoid pregnancy and breastfeeding exposures as best as possible.

FAERS

The FDA adverse event reporting system (FAERS) database does contain reports on adverse events of approved medications. However, even the FDA website warns that the information provided regarding individual cases is unverified and wouldn’t establish causation, considering the confounding variables involved, and this information can be duplicated as well as incomplete. In addition, rates of occurrence cannot be established with reports, as the denominator of exposure is uncertain.  

With those caveats established, the most common reports in FAERS concern injection site reactions, more frequent migraine or headache, or drug ineffectiveness. While constipation has been the second most common AE for erenumab, it did not make the top 10 for fremanezumab or galcanezumab, and cardiovascular events have not ranked in the top 10 for any product. Reasons for discontinuing treatment included withdrawal by the patient (147 of 1,890 [8%]) and lack of efficacy (77 of 1,890 [4%]). 

As the reader can ascertain, different studies point out different reasons for discontinuing CGRP therapies. Other studies note that the most frequent reasons for discontinuation are lack of efficacy, constipation, and lack of insurance .

Conclusions

These medications have been well received; I believe. Fremanezumab, manufactured by Teva Pharmaceuticals, was approved in September 2018. According to Teva’s 2021 annual report, Ajovy, fremanezumab’s brand name, reached 21% market share in the US and 21% in Europe.

Aimovig, or erenumab, has been prescribed 620,000 times since its approval, according to the Novartis 2021 annual report. Galcanezumab, or Emgality, was approved in 2019, and had 65,300 prescriptions written in the since then. . Adherence to treatment has generally been very high in clinical practice, with the most common reason for a patient to switch being lack of effectiveness, rather than adverse events.

Of note, adverse events of other migraine therapeutics are not insignificant, and considering the pain that people with migraine endure, side effects must be hard to contend with for individuals to stop taking them. Case in point: A year before erenumab was approved, a study was published that looked at medical records for medication persistence in 8,700 chronic migraine patients, who all had been prescribed beta blockers, anti-seizure medications, or antidepressants. By 6 months, only 1 out of 4 patients were still taking the prescribed medicines. By 12 months, that  was down to 14%. And about one-third of patients who stopped treatment stayed untreated for at least a year. 

The presumed reasons these patients stopped their medications: side effects and-or lack of efficacy. 

Migraine is a disabling disorder, for which the mAb class of medications has been highly beneficial for large numbers of patients, with far greater tolerability than prior oral preventives. While no treatments have absolute safety, the overall safety of this class of medications has been very high, leading to much improved clinical outcomes.

Editors’ note: For the April edition of Expert Perspectives, we asked two leading neurologists to present differing views on the use of calcitonin gene-related peptide (CGRPs) monoclonal antibodies (mAbs) for the treatment of migraine. Here, Jack D. Schim, MD, of the Neurology Center of Southern California, discusses the observed benefits of the CGRP mAbs. To read a counter-argument in which Lawrence Robbins, MD, of the Robbins Headache Clinic in Riverwoods, IL, discusses potential safety concerns associated with this drug class, click here.

Dr. Schim is Co-Director of The Headache Center of Southern California, The Neurology Center.  He is Board Member and past President of the Headache Consortium of the Pacific, Board Member and past President, American Heart Association San Diego, a Past President of the California Neurologic Society, and an active member of the American Academy of Neurology, American Stroke Association, and American Headache Society.

The identification of CGRP as a crucial pain signaling molecule in the trigeminal pathway, thereby establishing its link to migraine pain, has transformed care for patients with episodic and chronic migraine. Since 2018, the FDA has approved 4 monoclonal antibodies (mAbs) that either block the CGRP receptor or bind its ligand to prevent attachment to the receptor. 

These medications are helping patients with medication overuse headache (MOH) and chronic migraine; one study involving 139 patients showed that half the patients saw their headache days per month cut by half, and migraine days per month cut by 62%. In another small study, 23 patients (47%) with medication overuse headache reported having no MOH issues after 3 months. Most of these patients had a history of medication overuse, but no specific diagnosis of MOH.

In a survey, 277 physicians said that nearly half of their patients had resistant migraine, and 29% had refractory migraine. For these patients, the mAbs have helped restore some normalcy in their lives.  

But are these medications safe? Some clinicians posed this question even before the 2018 approval.

It is a valid question. The CGRP neuropeptide is a powerful dilator, establishing vascular homeostasis, organ development in utero, wound healing, and more. It is expressed in the peripheral and central nervous system and found abundantly in neurons and the unmyelinated A-fibers of the peripheral trigeminovascular system and trigeminal ganglion.

So, would blocking CGRP function in one area affect its function in another? So far, I have to say the answer is no. Neither the literature nor my observations say otherwise. 

Trials vs the real world

Finding an answer to this question takes more than reading clinical trials data. Participants in these trials do not necessarily represent the real world – no complicated morbidities, no pregnant or lactating women. And trial lengths are generally short.

Thus, it is important to assess the safety of these medications in the real world.  

In the trials of the subcutaneous mAbs, local injection site reactions were the most common adverse event. More specifically, erenumab showed increased incidence of constipation, and  post-marketing surveillance has revealed some risk of hypertension; pooled analysis from 4 trial phases showed that across treatment groups, 20 people out of 2443 began treatment for hypertension. Some patients enrolled in trials for atogepant, an oral small molecule CGRP receptor agonist, also reported constipation and nausea, suggesting that receptor blockade may result in a higher incidence of GI disturbance. In addition, these medicines on occasion have caused alopecia, fatigue, or achiness. 

Eptinezumab is administered intravenously, every 3 months, and thus does not have injection site reactions as a safety concern. In clinical trials, the most common adverse event was nasopharyngitis and hypersensitivity; Datta et al have provided a summary of safety and efficacy.

Raynaud’s and cluster headaches

A retrospective chart review study from the Mayo Clinic looking at individuals with Raynaud’s disease who were treated with CGRP antagonists showed that 5.3% of 169 patients had microvascular complications such as gangrene or autoimmune necrosis. There was no significant difference in demographic characteristics or rheumatologic history among those with Raynaud's who did or did not experience complications. In addition, microvascular complications of migraine therapies have preceded the use of CGRP modulators, as this has been documented in the past with other vasoactive substances such as ergots, triptans, and beta blockers. 

In a tolerability and safety study of galcanezumab in patients with chronic cluster headache, with up to 15 months of treatment, the most common treatment emergent adverse events were nasopharyngitis and injection site pain. In this population with 11% to 12% of individuals having baseline hypertension and nearly 63% currently using tobacco, less than 2.5% had any abnormalities on ECG.  

Vascular complications including pulmonary embolism, TIA, myocardial infarction, and atrial fibrillation have been reported but with no apparent relation between galcanezumab dosing and onset, with onset following the second to up to the eleventh monthly dose. 

Antidrug antibodies can also occur as a complication of exposure to therapeutic antibodies of this class and have been detected in up to 12% of individuals treated. This might lead to therapeutic failure but would not likely be a safety issue.

Anaphylaxis or serious hypersensitivity reactions are uncommon, and in general are the only contraindication to the use of these agents. 

Pregnancy registry information is just starting to become available. The number of reports on adverse drug reactions remains limited, and thus it is wise to avoid pregnancy and breastfeeding exposures as best as possible.

FAERS

The FDA adverse event reporting system (FAERS) database does contain reports on adverse events of approved medications. However, even the FDA website warns that the information provided regarding individual cases is unverified and wouldn’t establish causation, considering the confounding variables involved, and this information can be duplicated as well as incomplete. In addition, rates of occurrence cannot be established with reports, as the denominator of exposure is uncertain.  

With those caveats established, the most common reports in FAERS concern injection site reactions, more frequent migraine or headache, or drug ineffectiveness. While constipation has been the second most common AE for erenumab, it did not make the top 10 for fremanezumab or galcanezumab, and cardiovascular events have not ranked in the top 10 for any product. Reasons for discontinuing treatment included withdrawal by the patient (147 of 1,890 [8%]) and lack of efficacy (77 of 1,890 [4%]). 

As the reader can ascertain, different studies point out different reasons for discontinuing CGRP therapies. Other studies note that the most frequent reasons for discontinuation are lack of efficacy, constipation, and lack of insurance .

Conclusions

These medications have been well received; I believe. Fremanezumab, manufactured by Teva Pharmaceuticals, was approved in September 2018. According to Teva’s 2021 annual report, Ajovy, fremanezumab’s brand name, reached 21% market share in the US and 21% in Europe.

Aimovig, or erenumab, has been prescribed 620,000 times since its approval, according to the Novartis 2021 annual report. Galcanezumab, or Emgality, was approved in 2019, and had 65,300 prescriptions written in the since then. . Adherence to treatment has generally been very high in clinical practice, with the most common reason for a patient to switch being lack of effectiveness, rather than adverse events.

Of note, adverse events of other migraine therapeutics are not insignificant, and considering the pain that people with migraine endure, side effects must be hard to contend with for individuals to stop taking them. Case in point: A year before erenumab was approved, a study was published that looked at medical records for medication persistence in 8,700 chronic migraine patients, who all had been prescribed beta blockers, anti-seizure medications, or antidepressants. By 6 months, only 1 out of 4 patients were still taking the prescribed medicines. By 12 months, that  was down to 14%. And about one-third of patients who stopped treatment stayed untreated for at least a year. 

The presumed reasons these patients stopped their medications: side effects and-or lack of efficacy. 

Migraine is a disabling disorder, for which the mAb class of medications has been highly beneficial for large numbers of patients, with far greater tolerability than prior oral preventives. While no treatments have absolute safety, the overall safety of this class of medications has been very high, leading to much improved clinical outcomes.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

Signs of cardiometabolic damage in children who are overweight appear as early as 6-8 years of age, but were not evident in preschoolers, providing a window of opportunity for intervention, show the latest results from a long-running Danish study of childhood weight.

The proportion of children who were overweight (nearly 14% in 2015) was similar between the two groups – those of preschool age (2-5 years) and school age (6-8 years) – but only the latter showed significant signs of cardiometabolic abnormalities.

The results, published in Obesity Research & Clinical Practice, are the latest in a series of many findings from the HOLBAEK study (formerly known as The Danish Childhood Obesity Biobank) that have emerged since it began in 2007. They were presented, along with a meta-analysis of much of their work, at the European Congress on Obesity (ECO) 2022.

“When comparing children with and without overweight, there were only barely significant differences among the preschool children,” said investigator Christine Frithioff-Bøjsøe, MD, but in contrast, “the school children with overweight exhibited significantly higher systolic blood pressure, glucose, insulin, and higher HDL cholesterol,” among other markers, she noted.

“Detection needs to start as early as age 2-5 years because if you wait just a few years longer these children will show early signs of disease starting to take hold. This could provide a critical window to detect and manage overweight,” said Frithioff-Bøjsøe, PhD, of the Children’s Obesity Clinic, Copenhagen University, Hospital Holbaek, Denmark.

Asked to comment, Aaron S. Kelly, PhD, professor of pediatrics, codirector, University of Minnesota Center for Pediatric Obesity Medicine in Minneapolis, said: “Recent results from HOLBAEK highlight the critical importance of identifying obesity early in life, before its complications spring up.

“Ideally, we should be in the business of managing and reducing excess adiposity as soon as it surfaces with the goal of preventing the onset of cardiometabolic risk factors, not watchful waiting and hoping for the best.”
 

Routine dental visits checked overweight

In the newest study, the researchers trained dental assistants to measure weight and height and carried out body mass index assessments during routine appointments.

A total of 335 preschool and 657 school-age children were recruited for the study. Of these, 40% attended additional hospital-based examinations including blood pressure measurement and a blood sample. Children were reexamined approximately 1 year later.

Systolic blood pressure, for example, was significantly higher in 6- to 8-year-olds with overweight compared to those of normal weight (P = .001). There was no significant difference between systolic blood pressure of 2.5- to 5-year-olds without and with overweight.

Likewise, with insulin resistance, there was no significant difference between preschoolers with and without overweight. However, in schoolchildren, homoeostasis model of assessment–insulin resistance (HOMA-IR) was significantly higher in those with overweight, at 2.2, compared to those without, at 0.9 (P < .001).

Also, during follow-up (around a year later), the prevalence of overweight did not change in preschool children but increased from 13.7% to 17.0% in schoolchildren.

The researchers noted that, in Europe, it is the primary health care sector that has continuous contact with the pediatric population, with the potential for early evaluation of children at risk. Their decision to use dental health care assistants to assess weight in this particular study is novel, but feasible, they observed.
 

Danish model for treating overweight and obesity is ‘game-changing’

As part of the HOLBAEK initiative, clinical data and biological samples have been collected from children and adolescents receiving treatment at The Children’s Obesity Clinic, Holbaek Hospital, using a population-based cohort as a reference group. Data have been collected on about 8,000 children and adolescents so far.

Jens-Christian Holm, PhD, along with colleague and research assistant Maria Frauland, both from Copenhagen University, Hospital Holbaek, presented a review of the HOLBAEK studies (2007-2021) at ECO 2022. They said the results highlight the importance of taking an integrated approach to managing children and adolescents with obesity.

The review, which included 82 papers, found a wide variety of obesity-related complications already present at a young age in some of the cross-sectional studies, including dyslipidemia in 28% of children with obesity, hepatic steatosis in 31%, obstructive sleep apnea in 45%, and prehypertension or hypertension in 52%.

The family-based interventional weight management programs adopted by HOLBAEK showed a 75% reduction in the “degree of obesity,” which comprised a measure of dyslipidemia, hypertension, hepatic steatosis, sleep apnea, and parental obesity.

“The HOLBAEK method is a holistic approach where we integrate everything,” Dr. Holm told this news organization.

Ms. Frauland said: “The HOLBAEK study has provided important insights into childhood overweight. It has highlighted that obesity is a serious multisystem disease that can be managed and treated effectively, reducing the degree of overweight and improving overweight-related complications.”

Dr. Kelly, the U.S. pediatrician, applauded the HOLBAEK philosophy, which emphasizes that obesity is not the fault of the child or parent, but rather the manifestation of dysregulated energy metabolism. “The recognition that obesity is a biologically driven, chronic, refractory, and relapsing disease is interwoven into the approach, which shifts the responsibility to the care provider for ensuring positive outcomes of treatment.

“Highlighting this fact to the parents and child can be game-changing since it removes the blame and shame associated with obesity and unburdens the family by framing the problem in a different light,” Dr. Kelly stressed.

Dr. Frithioff-Bøjsøe has reported no relevant financial relationships. Dr. Holm has an obesity management company called Holm. Dr. Kelly serves as an unpaid consultant for Novo Nordisk, Vivus, Eli Lilly, and Boehringer Ingelheim and receives donated drug/placebo from Vivus for a clinical trial funded by the National Institutes of Health.

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

Signs of cardiometabolic damage in children who are overweight appear as early as 6-8 years of age, but were not evident in preschoolers, providing a window of opportunity for intervention, show the latest results from a long-running Danish study of childhood weight.

The proportion of children who were overweight (nearly 14% in 2015) was similar between the two groups – those of preschool age (2-5 years) and school age (6-8 years) – but only the latter showed significant signs of cardiometabolic abnormalities.

The results, published in Obesity Research & Clinical Practice, are the latest in a series of many findings from the HOLBAEK study (formerly known as The Danish Childhood Obesity Biobank) that have emerged since it began in 2007. They were presented, along with a meta-analysis of much of their work, at the European Congress on Obesity (ECO) 2022.

“When comparing children with and without overweight, there were only barely significant differences among the preschool children,” said investigator Christine Frithioff-Bøjsøe, MD, but in contrast, “the school children with overweight exhibited significantly higher systolic blood pressure, glucose, insulin, and higher HDL cholesterol,” among other markers, she noted.

“Detection needs to start as early as age 2-5 years because if you wait just a few years longer these children will show early signs of disease starting to take hold. This could provide a critical window to detect and manage overweight,” said Frithioff-Bøjsøe, PhD, of the Children’s Obesity Clinic, Copenhagen University, Hospital Holbaek, Denmark.

Asked to comment, Aaron S. Kelly, PhD, professor of pediatrics, codirector, University of Minnesota Center for Pediatric Obesity Medicine in Minneapolis, said: “Recent results from HOLBAEK highlight the critical importance of identifying obesity early in life, before its complications spring up.

“Ideally, we should be in the business of managing and reducing excess adiposity as soon as it surfaces with the goal of preventing the onset of cardiometabolic risk factors, not watchful waiting and hoping for the best.”
 

Routine dental visits checked overweight

In the newest study, the researchers trained dental assistants to measure weight and height and carried out body mass index assessments during routine appointments.

A total of 335 preschool and 657 school-age children were recruited for the study. Of these, 40% attended additional hospital-based examinations including blood pressure measurement and a blood sample. Children were reexamined approximately 1 year later.

Systolic blood pressure, for example, was significantly higher in 6- to 8-year-olds with overweight compared to those of normal weight (P = .001). There was no significant difference between systolic blood pressure of 2.5- to 5-year-olds without and with overweight.

Likewise, with insulin resistance, there was no significant difference between preschoolers with and without overweight. However, in schoolchildren, homoeostasis model of assessment–insulin resistance (HOMA-IR) was significantly higher in those with overweight, at 2.2, compared to those without, at 0.9 (P < .001).

Also, during follow-up (around a year later), the prevalence of overweight did not change in preschool children but increased from 13.7% to 17.0% in schoolchildren.

The researchers noted that, in Europe, it is the primary health care sector that has continuous contact with the pediatric population, with the potential for early evaluation of children at risk. Their decision to use dental health care assistants to assess weight in this particular study is novel, but feasible, they observed.
 

Danish model for treating overweight and obesity is ‘game-changing’

As part of the HOLBAEK initiative, clinical data and biological samples have been collected from children and adolescents receiving treatment at The Children’s Obesity Clinic, Holbaek Hospital, using a population-based cohort as a reference group. Data have been collected on about 8,000 children and adolescents so far.

Jens-Christian Holm, PhD, along with colleague and research assistant Maria Frauland, both from Copenhagen University, Hospital Holbaek, presented a review of the HOLBAEK studies (2007-2021) at ECO 2022. They said the results highlight the importance of taking an integrated approach to managing children and adolescents with obesity.

The review, which included 82 papers, found a wide variety of obesity-related complications already present at a young age in some of the cross-sectional studies, including dyslipidemia in 28% of children with obesity, hepatic steatosis in 31%, obstructive sleep apnea in 45%, and prehypertension or hypertension in 52%.

The family-based interventional weight management programs adopted by HOLBAEK showed a 75% reduction in the “degree of obesity,” which comprised a measure of dyslipidemia, hypertension, hepatic steatosis, sleep apnea, and parental obesity.

“The HOLBAEK method is a holistic approach where we integrate everything,” Dr. Holm told this news organization.

Ms. Frauland said: “The HOLBAEK study has provided important insights into childhood overweight. It has highlighted that obesity is a serious multisystem disease that can be managed and treated effectively, reducing the degree of overweight and improving overweight-related complications.”

Dr. Kelly, the U.S. pediatrician, applauded the HOLBAEK philosophy, which emphasizes that obesity is not the fault of the child or parent, but rather the manifestation of dysregulated energy metabolism. “The recognition that obesity is a biologically driven, chronic, refractory, and relapsing disease is interwoven into the approach, which shifts the responsibility to the care provider for ensuring positive outcomes of treatment.

“Highlighting this fact to the parents and child can be game-changing since it removes the blame and shame associated with obesity and unburdens the family by framing the problem in a different light,” Dr. Kelly stressed.

Dr. Frithioff-Bøjsøe has reported no relevant financial relationships. Dr. Holm has an obesity management company called Holm. Dr. Kelly serves as an unpaid consultant for Novo Nordisk, Vivus, Eli Lilly, and Boehringer Ingelheim and receives donated drug/placebo from Vivus for a clinical trial funded by the National Institutes of Health.

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

Signs of cardiometabolic damage in children who are overweight appear as early as 6-8 years of age, but were not evident in preschoolers, providing a window of opportunity for intervention, show the latest results from a long-running Danish study of childhood weight.

The proportion of children who were overweight (nearly 14% in 2015) was similar between the two groups – those of preschool age (2-5 years) and school age (6-8 years) – but only the latter showed significant signs of cardiometabolic abnormalities.

The results, published in Obesity Research & Clinical Practice, are the latest in a series of many findings from the HOLBAEK study (formerly known as The Danish Childhood Obesity Biobank) that have emerged since it began in 2007. They were presented, along with a meta-analysis of much of their work, at the European Congress on Obesity (ECO) 2022.

“When comparing children with and without overweight, there were only barely significant differences among the preschool children,” said investigator Christine Frithioff-Bøjsøe, MD, but in contrast, “the school children with overweight exhibited significantly higher systolic blood pressure, glucose, insulin, and higher HDL cholesterol,” among other markers, she noted.

“Detection needs to start as early as age 2-5 years because if you wait just a few years longer these children will show early signs of disease starting to take hold. This could provide a critical window to detect and manage overweight,” said Frithioff-Bøjsøe, PhD, of the Children’s Obesity Clinic, Copenhagen University, Hospital Holbaek, Denmark.

Asked to comment, Aaron S. Kelly, PhD, professor of pediatrics, codirector, University of Minnesota Center for Pediatric Obesity Medicine in Minneapolis, said: “Recent results from HOLBAEK highlight the critical importance of identifying obesity early in life, before its complications spring up.

“Ideally, we should be in the business of managing and reducing excess adiposity as soon as it surfaces with the goal of preventing the onset of cardiometabolic risk factors, not watchful waiting and hoping for the best.”
 

Routine dental visits checked overweight

In the newest study, the researchers trained dental assistants to measure weight and height and carried out body mass index assessments during routine appointments.

A total of 335 preschool and 657 school-age children were recruited for the study. Of these, 40% attended additional hospital-based examinations including blood pressure measurement and a blood sample. Children were reexamined approximately 1 year later.

Systolic blood pressure, for example, was significantly higher in 6- to 8-year-olds with overweight compared to those of normal weight (P = .001). There was no significant difference between systolic blood pressure of 2.5- to 5-year-olds without and with overweight.

Likewise, with insulin resistance, there was no significant difference between preschoolers with and without overweight. However, in schoolchildren, homoeostasis model of assessment–insulin resistance (HOMA-IR) was significantly higher in those with overweight, at 2.2, compared to those without, at 0.9 (P < .001).

Also, during follow-up (around a year later), the prevalence of overweight did not change in preschool children but increased from 13.7% to 17.0% in schoolchildren.

The researchers noted that, in Europe, it is the primary health care sector that has continuous contact with the pediatric population, with the potential for early evaluation of children at risk. Their decision to use dental health care assistants to assess weight in this particular study is novel, but feasible, they observed.
 

Danish model for treating overweight and obesity is ‘game-changing’

As part of the HOLBAEK initiative, clinical data and biological samples have been collected from children and adolescents receiving treatment at The Children’s Obesity Clinic, Holbaek Hospital, using a population-based cohort as a reference group. Data have been collected on about 8,000 children and adolescents so far.

Jens-Christian Holm, PhD, along with colleague and research assistant Maria Frauland, both from Copenhagen University, Hospital Holbaek, presented a review of the HOLBAEK studies (2007-2021) at ECO 2022. They said the results highlight the importance of taking an integrated approach to managing children and adolescents with obesity.

The review, which included 82 papers, found a wide variety of obesity-related complications already present at a young age in some of the cross-sectional studies, including dyslipidemia in 28% of children with obesity, hepatic steatosis in 31%, obstructive sleep apnea in 45%, and prehypertension or hypertension in 52%.

The family-based interventional weight management programs adopted by HOLBAEK showed a 75% reduction in the “degree of obesity,” which comprised a measure of dyslipidemia, hypertension, hepatic steatosis, sleep apnea, and parental obesity.

“The HOLBAEK method is a holistic approach where we integrate everything,” Dr. Holm told this news organization.

Ms. Frauland said: “The HOLBAEK study has provided important insights into childhood overweight. It has highlighted that obesity is a serious multisystem disease that can be managed and treated effectively, reducing the degree of overweight and improving overweight-related complications.”

Dr. Kelly, the U.S. pediatrician, applauded the HOLBAEK philosophy, which emphasizes that obesity is not the fault of the child or parent, but rather the manifestation of dysregulated energy metabolism. “The recognition that obesity is a biologically driven, chronic, refractory, and relapsing disease is interwoven into the approach, which shifts the responsibility to the care provider for ensuring positive outcomes of treatment.

“Highlighting this fact to the parents and child can be game-changing since it removes the blame and shame associated with obesity and unburdens the family by framing the problem in a different light,” Dr. Kelly stressed.

Dr. Frithioff-Bøjsøe has reported no relevant financial relationships. Dr. Holm has an obesity management company called Holm. Dr. Kelly serves as an unpaid consultant for Novo Nordisk, Vivus, Eli Lilly, and Boehringer Ingelheim and receives donated drug/placebo from Vivus for a clinical trial funded by the National Institutes of Health.

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