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For people with severe symptomatic hip osteoarthritis, total hip replacement (THR) alleviates hip pain and improves function much more effectively than a resistance training program supervised by a physiotherapist, according to the results of a randomized controlled clinical trial. 

In the PROHIP study, the mean increases in Oxford Hip Scores from baseline to 6 months were 15.9 points for THR and 4.5 points for resistance training. The 11.4-point difference in scores was both statistically and clinically significant, the study’s investigators reported in The New England Journal of Medicine. 

“Our results are clear: Surgery is superior to exercise in patients who have hip osteoarthritis and indication for surgery, and now we have finally proven that with the highest level of evidence,” corresponding author Thomas Frydendal, PT, PhD, MSc, told this news organization.

Frydendal, who was involved in the study while working on his PhD at University Hospital of Southern Denmark – Lillebaelt Hospital, Vejle, Denmark, the primary center for the trial, is now a postdoctoral researcher at the Department of Clinical Medicine, Aarhus University, and Department of Orthopedic Surgery, Aarhus University Hospital.

“We believe that our findings are pretty robust,” Frydendal added. “I think if someone in the world conducts a trial similar to ours, they will find fairly close or consistent findings, no matter what type of exercise they choose.”

Charlotte Dahl, Lillebaelt Hospital–University Hospital of Southern Denmark, Vejle Hospital

The PROHIP Study

THR is routinely recommended for the management of severe hip osteoarthritis, but since there are no clinical trial data on the effectiveness of this procedure as compared with first-line treatment such as resistance training, the PROHIP study was conceived. 

The trial was conducted at four Danish orthopedic centers and designed as a superiority study, the hypothesis being that THR would be better at alleviating self-reported hip pain and improving hip function than resistance training. 

Of a possible 1474 individuals with a clinical suspicion of hip osteoarthritis, 791 were deemed eligible for inclusion in the trial. Inclusion criteria were being aged 50 years or older and having an indication for THR based on the presence of hip pain and clinical and radiographic findings.

However, the majority (86%) declined to enter the study, with almost half (43%) deciding to have a THR and enroll in a parallel observational cohort. This meant that only 110 (14%) individuals agreed to participate and underwent randomization, which does limit the study’s generalizability, the PROHIP investigators acknowledged. 
 

Design and Study Population

The change in Oxford Hip Score from baseline to 6 months was selected as the primary outcome measure based on the findings of a prior qualitative study. This 12-item, patient-reported outcome measure gives a score ranging from 0 to 48, with higher scores indicating less hip pain and better hip function. The estimated minimal clinically important difference is a change of 5 points. 

After a baseline assessment, 53 of 109 individuals were randomly assigned to undergo THR and 56 to participate in the resistance training program. Overall, the mean age of participants was 67.6 years, and half were women. The average duration of hip pain was a median of 1.7 years. 

The median time to receipt of the allocated treatment was 2.8 months in the THR group and 0.5 months in the resistance training group. 

Those allocated to the THR group also underwent a “fast track” program that involved patient education, pain management, and early mobilization. 

The resistance training group received 12 weeks of exercise supervised by a physiotherapist and then offered 12 weeks of additional exercise conducted on their own. The physiotherapist-supervised exercise sessions were held twice weekly and lasted for 1 hour. These started with a 10-minute warm-up on a stationary bike, followed by a standard set of resistance-based exercises that included a leg press, hip extension, hip flexion, and hip abduction. 
 

‘Reassuring’ Results

In a comment, consultant orthopedic surgeon Antony Palmer, MA, BMBCh, DPhil, said: “It’s reassuring that patients with advanced symptomatic osteoarthritis do well with hip replacements.”

THR does of course come with the potential risk for complications, but “the rate of these is what you’d expect for that procedure,” Palmer said, who works for the Nuffield Orthopaedic Centre, Oxford University Hospital NHS Foundation Trust, and is a senior clinical research fellow at Oxford University in England.

Dr. Palmer

Resistance Training Role 

A notable finding was that, at 6 months, five (9%) people assigned to the THR arm had not undergone surgery, and 12 (21%) people in the resistance training group had undergone a THR.

This could suggest two things, Palmer suggested in the interview. The first is that there could be a small proportion of people assigned to THR who may not need the operation and do well with exercise therapy. And, conversely, there may be those who would do well having the surgery without first going through the intermediate stage of physical therapy. 

It’s a suggestion that “maybe we’ve got to refine that a bit better and identify the patients that really do benefit from physiotherapy and who might not need hip replacement as a result,” Palmer said.

Or in other words, “should all patients undergo a program of physiotherapy before considering surgery?” he added.
 

Authors’ View

The PROHIP investigators conclude: “These results support current recommendations for the management of hip osteoarthritis and may be used to inform and guide shared decision making in clinical practice.”

Moreover, the results “do not oppose the use of resistance training as initial treatment,” says the authors. 

Frydendal highlighted in his interview that nearly three out of four of the patients reported not to have undertaken any type of supervised exercise before entry into the study, which is a first-line, guideline-recommended option.

“If a patient tells me, ‘I haven’t done any exercise previously,’ I’d recommend starting with completing a 6- to 12-week exercise program that is tailored to your individual needs and evaluate your symptoms afterward,” he said. 

“But we should refer the patient if our first-line treatment does not offer any improvements in the patient’s symptoms, as surgery with total hip replacement is clearly a really good treatment option,” Frydendal said.

The study was funded by the Danish Rheumatism Association, among other independent bodies. Frydendal and Palmer reported no relevant financial relationships. 
 

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

For people with severe symptomatic hip osteoarthritis, total hip replacement (THR) alleviates hip pain and improves function much more effectively than a resistance training program supervised by a physiotherapist, according to the results of a randomized controlled clinical trial. 

In the PROHIP study, the mean increases in Oxford Hip Scores from baseline to 6 months were 15.9 points for THR and 4.5 points for resistance training. The 11.4-point difference in scores was both statistically and clinically significant, the study’s investigators reported in The New England Journal of Medicine. 

“Our results are clear: Surgery is superior to exercise in patients who have hip osteoarthritis and indication for surgery, and now we have finally proven that with the highest level of evidence,” corresponding author Thomas Frydendal, PT, PhD, MSc, told this news organization.

Frydendal, who was involved in the study while working on his PhD at University Hospital of Southern Denmark – Lillebaelt Hospital, Vejle, Denmark, the primary center for the trial, is now a postdoctoral researcher at the Department of Clinical Medicine, Aarhus University, and Department of Orthopedic Surgery, Aarhus University Hospital.

“We believe that our findings are pretty robust,” Frydendal added. “I think if someone in the world conducts a trial similar to ours, they will find fairly close or consistent findings, no matter what type of exercise they choose.”

Charlotte Dahl, Lillebaelt Hospital–University Hospital of Southern Denmark, Vejle Hospital

The PROHIP Study

THR is routinely recommended for the management of severe hip osteoarthritis, but since there are no clinical trial data on the effectiveness of this procedure as compared with first-line treatment such as resistance training, the PROHIP study was conceived. 

The trial was conducted at four Danish orthopedic centers and designed as a superiority study, the hypothesis being that THR would be better at alleviating self-reported hip pain and improving hip function than resistance training. 

Of a possible 1474 individuals with a clinical suspicion of hip osteoarthritis, 791 were deemed eligible for inclusion in the trial. Inclusion criteria were being aged 50 years or older and having an indication for THR based on the presence of hip pain and clinical and radiographic findings.

However, the majority (86%) declined to enter the study, with almost half (43%) deciding to have a THR and enroll in a parallel observational cohort. This meant that only 110 (14%) individuals agreed to participate and underwent randomization, which does limit the study’s generalizability, the PROHIP investigators acknowledged. 
 

Design and Study Population

The change in Oxford Hip Score from baseline to 6 months was selected as the primary outcome measure based on the findings of a prior qualitative study. This 12-item, patient-reported outcome measure gives a score ranging from 0 to 48, with higher scores indicating less hip pain and better hip function. The estimated minimal clinically important difference is a change of 5 points. 

After a baseline assessment, 53 of 109 individuals were randomly assigned to undergo THR and 56 to participate in the resistance training program. Overall, the mean age of participants was 67.6 years, and half were women. The average duration of hip pain was a median of 1.7 years. 

The median time to receipt of the allocated treatment was 2.8 months in the THR group and 0.5 months in the resistance training group. 

Those allocated to the THR group also underwent a “fast track” program that involved patient education, pain management, and early mobilization. 

The resistance training group received 12 weeks of exercise supervised by a physiotherapist and then offered 12 weeks of additional exercise conducted on their own. The physiotherapist-supervised exercise sessions were held twice weekly and lasted for 1 hour. These started with a 10-minute warm-up on a stationary bike, followed by a standard set of resistance-based exercises that included a leg press, hip extension, hip flexion, and hip abduction. 
 

‘Reassuring’ Results

In a comment, consultant orthopedic surgeon Antony Palmer, MA, BMBCh, DPhil, said: “It’s reassuring that patients with advanced symptomatic osteoarthritis do well with hip replacements.”

THR does of course come with the potential risk for complications, but “the rate of these is what you’d expect for that procedure,” Palmer said, who works for the Nuffield Orthopaedic Centre, Oxford University Hospital NHS Foundation Trust, and is a senior clinical research fellow at Oxford University in England.

Dr. Palmer

Resistance Training Role 

A notable finding was that, at 6 months, five (9%) people assigned to the THR arm had not undergone surgery, and 12 (21%) people in the resistance training group had undergone a THR.

This could suggest two things, Palmer suggested in the interview. The first is that there could be a small proportion of people assigned to THR who may not need the operation and do well with exercise therapy. And, conversely, there may be those who would do well having the surgery without first going through the intermediate stage of physical therapy. 

It’s a suggestion that “maybe we’ve got to refine that a bit better and identify the patients that really do benefit from physiotherapy and who might not need hip replacement as a result,” Palmer said.

Or in other words, “should all patients undergo a program of physiotherapy before considering surgery?” he added.
 

Authors’ View

The PROHIP investigators conclude: “These results support current recommendations for the management of hip osteoarthritis and may be used to inform and guide shared decision making in clinical practice.”

Moreover, the results “do not oppose the use of resistance training as initial treatment,” says the authors. 

Frydendal highlighted in his interview that nearly three out of four of the patients reported not to have undertaken any type of supervised exercise before entry into the study, which is a first-line, guideline-recommended option.

“If a patient tells me, ‘I haven’t done any exercise previously,’ I’d recommend starting with completing a 6- to 12-week exercise program that is tailored to your individual needs and evaluate your symptoms afterward,” he said. 

“But we should refer the patient if our first-line treatment does not offer any improvements in the patient’s symptoms, as surgery with total hip replacement is clearly a really good treatment option,” Frydendal said.

The study was funded by the Danish Rheumatism Association, among other independent bodies. Frydendal and Palmer reported no relevant financial relationships. 
 

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

For people with severe symptomatic hip osteoarthritis, total hip replacement (THR) alleviates hip pain and improves function much more effectively than a resistance training program supervised by a physiotherapist, according to the results of a randomized controlled clinical trial. 

In the PROHIP study, the mean increases in Oxford Hip Scores from baseline to 6 months were 15.9 points for THR and 4.5 points for resistance training. The 11.4-point difference in scores was both statistically and clinically significant, the study’s investigators reported in The New England Journal of Medicine. 

“Our results are clear: Surgery is superior to exercise in patients who have hip osteoarthritis and indication for surgery, and now we have finally proven that with the highest level of evidence,” corresponding author Thomas Frydendal, PT, PhD, MSc, told this news organization.

Frydendal, who was involved in the study while working on his PhD at University Hospital of Southern Denmark – Lillebaelt Hospital, Vejle, Denmark, the primary center for the trial, is now a postdoctoral researcher at the Department of Clinical Medicine, Aarhus University, and Department of Orthopedic Surgery, Aarhus University Hospital.

“We believe that our findings are pretty robust,” Frydendal added. “I think if someone in the world conducts a trial similar to ours, they will find fairly close or consistent findings, no matter what type of exercise they choose.”

Charlotte Dahl, Lillebaelt Hospital–University Hospital of Southern Denmark, Vejle Hospital

The PROHIP Study

THR is routinely recommended for the management of severe hip osteoarthritis, but since there are no clinical trial data on the effectiveness of this procedure as compared with first-line treatment such as resistance training, the PROHIP study was conceived. 

The trial was conducted at four Danish orthopedic centers and designed as a superiority study, the hypothesis being that THR would be better at alleviating self-reported hip pain and improving hip function than resistance training. 

Of a possible 1474 individuals with a clinical suspicion of hip osteoarthritis, 791 were deemed eligible for inclusion in the trial. Inclusion criteria were being aged 50 years or older and having an indication for THR based on the presence of hip pain and clinical and radiographic findings.

However, the majority (86%) declined to enter the study, with almost half (43%) deciding to have a THR and enroll in a parallel observational cohort. This meant that only 110 (14%) individuals agreed to participate and underwent randomization, which does limit the study’s generalizability, the PROHIP investigators acknowledged. 
 

Design and Study Population

The change in Oxford Hip Score from baseline to 6 months was selected as the primary outcome measure based on the findings of a prior qualitative study. This 12-item, patient-reported outcome measure gives a score ranging from 0 to 48, with higher scores indicating less hip pain and better hip function. The estimated minimal clinically important difference is a change of 5 points. 

After a baseline assessment, 53 of 109 individuals were randomly assigned to undergo THR and 56 to participate in the resistance training program. Overall, the mean age of participants was 67.6 years, and half were women. The average duration of hip pain was a median of 1.7 years. 

The median time to receipt of the allocated treatment was 2.8 months in the THR group and 0.5 months in the resistance training group. 

Those allocated to the THR group also underwent a “fast track” program that involved patient education, pain management, and early mobilization. 

The resistance training group received 12 weeks of exercise supervised by a physiotherapist and then offered 12 weeks of additional exercise conducted on their own. The physiotherapist-supervised exercise sessions were held twice weekly and lasted for 1 hour. These started with a 10-minute warm-up on a stationary bike, followed by a standard set of resistance-based exercises that included a leg press, hip extension, hip flexion, and hip abduction. 
 

‘Reassuring’ Results

In a comment, consultant orthopedic surgeon Antony Palmer, MA, BMBCh, DPhil, said: “It’s reassuring that patients with advanced symptomatic osteoarthritis do well with hip replacements.”

THR does of course come with the potential risk for complications, but “the rate of these is what you’d expect for that procedure,” Palmer said, who works for the Nuffield Orthopaedic Centre, Oxford University Hospital NHS Foundation Trust, and is a senior clinical research fellow at Oxford University in England.

Dr. Palmer

Resistance Training Role 

A notable finding was that, at 6 months, five (9%) people assigned to the THR arm had not undergone surgery, and 12 (21%) people in the resistance training group had undergone a THR.

This could suggest two things, Palmer suggested in the interview. The first is that there could be a small proportion of people assigned to THR who may not need the operation and do well with exercise therapy. And, conversely, there may be those who would do well having the surgery without first going through the intermediate stage of physical therapy. 

It’s a suggestion that “maybe we’ve got to refine that a bit better and identify the patients that really do benefit from physiotherapy and who might not need hip replacement as a result,” Palmer said.

Or in other words, “should all patients undergo a program of physiotherapy before considering surgery?” he added.
 

Authors’ View

The PROHIP investigators conclude: “These results support current recommendations for the management of hip osteoarthritis and may be used to inform and guide shared decision making in clinical practice.”

Moreover, the results “do not oppose the use of resistance training as initial treatment,” says the authors. 

Frydendal highlighted in his interview that nearly three out of four of the patients reported not to have undertaken any type of supervised exercise before entry into the study, which is a first-line, guideline-recommended option.

“If a patient tells me, ‘I haven’t done any exercise previously,’ I’d recommend starting with completing a 6- to 12-week exercise program that is tailored to your individual needs and evaluate your symptoms afterward,” he said. 

“But we should refer the patient if our first-line treatment does not offer any improvements in the patient’s symptoms, as surgery with total hip replacement is clearly a really good treatment option,” Frydendal said.

The study was funded by the Danish Rheumatism Association, among other independent bodies. Frydendal and Palmer reported no relevant financial relationships. 
 

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

PHILADELPHIA — Low-volume bowel preparation is noninferior in adequacy to standard-volume prep in hospitalized patients undergoing colonoscopy, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.

Yale School of Medicine

“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.

Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.

“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.

In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.

After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.

In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.

Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.

Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.

In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
 

Ease of Use Is a Plus

On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”

In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).

“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.

Mayo Clinic

“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”

Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.

“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”

The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Low-volume bowel preparation is noninferior in adequacy to standard-volume prep in hospitalized patients undergoing colonoscopy, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.

Yale School of Medicine

“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.

Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.

“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.

In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.

After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.

In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.

Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.

Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.

In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
 

Ease of Use Is a Plus

On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”

In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).

“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.

Mayo Clinic

“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”

Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.

“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”

The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Low-volume bowel preparation is noninferior in adequacy to standard-volume prep in hospitalized patients undergoing colonoscopy, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.

Yale School of Medicine

“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.

Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.

“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.

In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.

After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.

In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.

Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.

Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.

In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
 

Ease of Use Is a Plus

On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”

In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).

“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.

Mayo Clinic

“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”

Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.

“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”

The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Non-fasting breath gas patterns may help identify patients with irritable bowel syndrome (IBS) who are most likely to respond to a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet, according to a new study.

The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”

Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”

He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens. 

Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 
 

Breaths That Can Predict Response

To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale. 

Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.

Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.

Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet. 

The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day. 

Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.

The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
 

A Potential New Biomarker

Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit. 

Massachusetts General Hospital

There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.” 

Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness. 

“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role. 

Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Non-fasting breath gas patterns may help identify patients with irritable bowel syndrome (IBS) who are most likely to respond to a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet, according to a new study.

The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”

Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”

He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens. 

Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 
 

Breaths That Can Predict Response

To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale. 

Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.

Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.

Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet. 

The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day. 

Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.

The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
 

A Potential New Biomarker

Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit. 

Massachusetts General Hospital

There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.” 

Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness. 

“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role. 

Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Non-fasting breath gas patterns may help identify patients with irritable bowel syndrome (IBS) who are most likely to respond to a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet, according to a new study.

The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”

Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”

He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens. 

Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 
 

Breaths That Can Predict Response

To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale. 

Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.

Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.

Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet. 

The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day. 

Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.

The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
 

A Potential New Biomarker

Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit. 

Massachusetts General Hospital

There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.” 

Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness. 

“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role. 

Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.

A version of this article appeared on Medscape.com.

PHILADELPHIA — The use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is associated with a significant decrease in the risk for early-onset colorectal cancer (EO-CRC) in patients with type 2 diabetes (T2D), according to the results of a retrospective study.

“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.

The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.

Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.

The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
 

Retrospective Database Analysis

Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.

They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.

Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).

Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
 

A Proposed Protective Effect

Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.

“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”

This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”

These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.

“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”

Hypothesis-Generating Results

Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research. 

"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News. 

She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D. 

Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said. 

“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained. 

Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention." 

The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.

A version of this article appeared on Medscape.com.

PHILADELPHIA — The use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is associated with a significant decrease in the risk for early-onset colorectal cancer (EO-CRC) in patients with type 2 diabetes (T2D), according to the results of a retrospective study.

“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.

The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.

Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.

The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
 

Retrospective Database Analysis

Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.

They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.

Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).

Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
 

A Proposed Protective Effect

Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.

“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”

This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”

These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.

“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”

Hypothesis-Generating Results

Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research. 

"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News. 

She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D. 

Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said. 

“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained. 

Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention." 

The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.

A version of this article appeared on Medscape.com.

PHILADELPHIA — The use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is associated with a significant decrease in the risk for early-onset colorectal cancer (EO-CRC) in patients with type 2 diabetes (T2D), according to the results of a retrospective study.

“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.

The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.

Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.

The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
 

Retrospective Database Analysis

Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.

They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.

Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).

Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
 

A Proposed Protective Effect

Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.

“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”

This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”

These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.

“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”

Hypothesis-Generating Results

Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research. 

"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News. 

She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D. 

Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said. 

“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained. 

Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention." 

The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Researchers have developed an artificial intelligence (AI) tool capable of detecting and differentiating cystic and solid pancreatic lesions during endoscopic ultrasound (EUS) with high accuracy.

This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.

Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.

Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.

EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.

With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.

They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.

The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.

For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
 

Real-Time Validation Next

“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.

This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.

The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.

“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.

Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.

“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.

“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.

“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.

The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Researchers have developed an artificial intelligence (AI) tool capable of detecting and differentiating cystic and solid pancreatic lesions during endoscopic ultrasound (EUS) with high accuracy.

This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.

Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.

Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.

EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.

With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.

They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.

The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.

For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
 

Real-Time Validation Next

“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.

This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.

The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.

“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.

Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.

“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.

“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.

“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.

The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Researchers have developed an artificial intelligence (AI) tool capable of detecting and differentiating cystic and solid pancreatic lesions during endoscopic ultrasound (EUS) with high accuracy.

This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.

Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.

Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.

EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.

With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.

They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.

The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.

For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
 

Real-Time Validation Next

“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.

This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.

The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.

“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.

Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.

“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.

“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.

“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.

The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

I suspect you all have some experience with childhood migraine. It can mean a painful several hours for the patient, arriving often without warning, with recurrences spaced months or sometimes even years apart. It may be accompanied by vomiting, which in some cases overshadows the severity of the headache. It can result in lost days from school and ruin family activities. It can occur so infrequently that the family can’t recall accurately when the last episode happened. In some ways it is a different animal than the adult version.

Most of the pediatric patients with migraine I have seen have experienced attacks that were occurring so infrequently that the families and I seldom discussed medication as an option. Back then imipramine was the only choice. However, currently there are more than a half dozen medications and combinations that have been tried. Recently a review of 45 clinical trials of these medications was published in JAMA Network Open.

I will let you review for yourself the details of these Iranian investigators’ network meta-analysis, but the bottom line is that some medications were associated with a reduction in migraine frequency. Others were associated with headache intensity. “However, no treatments were associated with significant improvements in quality of life or reduction of the duration of migraine attacks.”

Obviously, this paper illustrates clearly that we have not yet discovered the medicinal magic bullet for pediatric migraine prophylaxis. This doesn’t surprise me. After listening to scores of families tell their migraine stories, it became apparent to me that there was often a pattern in which the child’s headache had arrived after a period of acute sleep deprivation. For example, a trip to an amusement park in which travel or excitement may have resulted in the child going to bed later and/or getting up earlier. By afternoon the child’s reserves of something (currently unknown) were depleted to a point that the headache and/or vomiting struck.

Because these episodes were often so infrequent, separated by months, that taking a history demonstrating a recurring pattern could take considerable patience on the part of the family and the provider, even for a physician like myself who believes that better sleep is the answer for everything. However, once I could convince a family of the connection between the sleep deprivation and the headaches, they could often recall other episodes in the past that substantiated my explanation.

In some cases there was no obvious history of acute sleep deprivation, or at least it was so subtle that even a history taker with a sleep obsession couldn’t detect it. However, in these cases I could usually elicit a history of chronic sleep deprivation. For example, falling asleep instantly on automobile rides, difficulty with waking in the morning, or unhealthy bedtime routines. With this underlying vulnerability of chronic sleep deprivation, a slightly more exciting or vigorous day was all that was necessary to trigger the headache.

For those of you who don’t share my contention that childhood migraine is usually the result of sleep deprivation, consider the similarity between an epileptic seizure, which can be triggered by fatigue. Both events are usually followed by a deep sleep from which the child wakes refreshed and symptom free.

I think it is interesting that this recent meta-analysis could find no benefit in the quality of life for any of the medications. The explanation may be that the child with migraine already had a somewhat diminished quality of life as a result of the sleep deprivation, either acute or chronic.

When speaking with parents of migraine sufferers, I would tell them that once the headache had started there was little I had to offer to forestall the inevitable pain and vomiting. Certainly not in the form of an oral medication. While many adults will have an aura that warns them of the headache onset, I have found that most children don’t describe an aura. It may be they simply lack the ability to express it. Occasionally an observant parent may detect pallor or a behavior change that indicates a migraine is beginning. On rare occasions a parent may be able to abort the attack by quickly getting the child to a quiet, dark, and calm environment.

Although this recent meta-analysis review of treatment options is discouraging, it may be providing a clue to effective prophylaxis. Some of the medications that decrease the frequency of the attacks may be doing so because they improve the patient’s sleep patterns. Those that decrease the intensity of the pain are probably working on pain pathway that is not specific to migraine.

Continuing a search for a prophylactic medication is a worthy goal, particularly for those patients in which their migraines are debilitating. However, based on my experience, enhanced by my bias, the safest and most effective prophylaxis results from increasing the family’s awareness of the role that sleep deprivation plays in the illness. Even when the family buys into the message and attempts to avoid situations that will tax their vulnerable children, parents will need to accept that sometimes stuff happens even though siblings and peers may be able to tolerate the situation. Spontaneous activities can converge on a day when for whatever reason the migraine-prone child is overtired and the headache and vomiting will erupt.

A lifestyle change is always preferable to a pharmacological intervention. However, that doesn’t mean it is always easy to achieve.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I suspect you all have some experience with childhood migraine. It can mean a painful several hours for the patient, arriving often without warning, with recurrences spaced months or sometimes even years apart. It may be accompanied by vomiting, which in some cases overshadows the severity of the headache. It can result in lost days from school and ruin family activities. It can occur so infrequently that the family can’t recall accurately when the last episode happened. In some ways it is a different animal than the adult version.

Most of the pediatric patients with migraine I have seen have experienced attacks that were occurring so infrequently that the families and I seldom discussed medication as an option. Back then imipramine was the only choice. However, currently there are more than a half dozen medications and combinations that have been tried. Recently a review of 45 clinical trials of these medications was published in JAMA Network Open.

I will let you review for yourself the details of these Iranian investigators’ network meta-analysis, but the bottom line is that some medications were associated with a reduction in migraine frequency. Others were associated with headache intensity. “However, no treatments were associated with significant improvements in quality of life or reduction of the duration of migraine attacks.”

Obviously, this paper illustrates clearly that we have not yet discovered the medicinal magic bullet for pediatric migraine prophylaxis. This doesn’t surprise me. After listening to scores of families tell their migraine stories, it became apparent to me that there was often a pattern in which the child’s headache had arrived after a period of acute sleep deprivation. For example, a trip to an amusement park in which travel or excitement may have resulted in the child going to bed later and/or getting up earlier. By afternoon the child’s reserves of something (currently unknown) were depleted to a point that the headache and/or vomiting struck.

Because these episodes were often so infrequent, separated by months, that taking a history demonstrating a recurring pattern could take considerable patience on the part of the family and the provider, even for a physician like myself who believes that better sleep is the answer for everything. However, once I could convince a family of the connection between the sleep deprivation and the headaches, they could often recall other episodes in the past that substantiated my explanation.

In some cases there was no obvious history of acute sleep deprivation, or at least it was so subtle that even a history taker with a sleep obsession couldn’t detect it. However, in these cases I could usually elicit a history of chronic sleep deprivation. For example, falling asleep instantly on automobile rides, difficulty with waking in the morning, or unhealthy bedtime routines. With this underlying vulnerability of chronic sleep deprivation, a slightly more exciting or vigorous day was all that was necessary to trigger the headache.

For those of you who don’t share my contention that childhood migraine is usually the result of sleep deprivation, consider the similarity between an epileptic seizure, which can be triggered by fatigue. Both events are usually followed by a deep sleep from which the child wakes refreshed and symptom free.

I think it is interesting that this recent meta-analysis could find no benefit in the quality of life for any of the medications. The explanation may be that the child with migraine already had a somewhat diminished quality of life as a result of the sleep deprivation, either acute or chronic.

When speaking with parents of migraine sufferers, I would tell them that once the headache had started there was little I had to offer to forestall the inevitable pain and vomiting. Certainly not in the form of an oral medication. While many adults will have an aura that warns them of the headache onset, I have found that most children don’t describe an aura. It may be they simply lack the ability to express it. Occasionally an observant parent may detect pallor or a behavior change that indicates a migraine is beginning. On rare occasions a parent may be able to abort the attack by quickly getting the child to a quiet, dark, and calm environment.

Although this recent meta-analysis review of treatment options is discouraging, it may be providing a clue to effective prophylaxis. Some of the medications that decrease the frequency of the attacks may be doing so because they improve the patient’s sleep patterns. Those that decrease the intensity of the pain are probably working on pain pathway that is not specific to migraine.

Continuing a search for a prophylactic medication is a worthy goal, particularly for those patients in which their migraines are debilitating. However, based on my experience, enhanced by my bias, the safest and most effective prophylaxis results from increasing the family’s awareness of the role that sleep deprivation plays in the illness. Even when the family buys into the message and attempts to avoid situations that will tax their vulnerable children, parents will need to accept that sometimes stuff happens even though siblings and peers may be able to tolerate the situation. Spontaneous activities can converge on a day when for whatever reason the migraine-prone child is overtired and the headache and vomiting will erupt.

A lifestyle change is always preferable to a pharmacological intervention. However, that doesn’t mean it is always easy to achieve.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I suspect you all have some experience with childhood migraine. It can mean a painful several hours for the patient, arriving often without warning, with recurrences spaced months or sometimes even years apart. It may be accompanied by vomiting, which in some cases overshadows the severity of the headache. It can result in lost days from school and ruin family activities. It can occur so infrequently that the family can’t recall accurately when the last episode happened. In some ways it is a different animal than the adult version.

Most of the pediatric patients with migraine I have seen have experienced attacks that were occurring so infrequently that the families and I seldom discussed medication as an option. Back then imipramine was the only choice. However, currently there are more than a half dozen medications and combinations that have been tried. Recently a review of 45 clinical trials of these medications was published in JAMA Network Open.

I will let you review for yourself the details of these Iranian investigators’ network meta-analysis, but the bottom line is that some medications were associated with a reduction in migraine frequency. Others were associated with headache intensity. “However, no treatments were associated with significant improvements in quality of life or reduction of the duration of migraine attacks.”

Obviously, this paper illustrates clearly that we have not yet discovered the medicinal magic bullet for pediatric migraine prophylaxis. This doesn’t surprise me. After listening to scores of families tell their migraine stories, it became apparent to me that there was often a pattern in which the child’s headache had arrived after a period of acute sleep deprivation. For example, a trip to an amusement park in which travel or excitement may have resulted in the child going to bed later and/or getting up earlier. By afternoon the child’s reserves of something (currently unknown) were depleted to a point that the headache and/or vomiting struck.

Because these episodes were often so infrequent, separated by months, that taking a history demonstrating a recurring pattern could take considerable patience on the part of the family and the provider, even for a physician like myself who believes that better sleep is the answer for everything. However, once I could convince a family of the connection between the sleep deprivation and the headaches, they could often recall other episodes in the past that substantiated my explanation.

In some cases there was no obvious history of acute sleep deprivation, or at least it was so subtle that even a history taker with a sleep obsession couldn’t detect it. However, in these cases I could usually elicit a history of chronic sleep deprivation. For example, falling asleep instantly on automobile rides, difficulty with waking in the morning, or unhealthy bedtime routines. With this underlying vulnerability of chronic sleep deprivation, a slightly more exciting or vigorous day was all that was necessary to trigger the headache.

For those of you who don’t share my contention that childhood migraine is usually the result of sleep deprivation, consider the similarity between an epileptic seizure, which can be triggered by fatigue. Both events are usually followed by a deep sleep from which the child wakes refreshed and symptom free.

I think it is interesting that this recent meta-analysis could find no benefit in the quality of life for any of the medications. The explanation may be that the child with migraine already had a somewhat diminished quality of life as a result of the sleep deprivation, either acute or chronic.

When speaking with parents of migraine sufferers, I would tell them that once the headache had started there was little I had to offer to forestall the inevitable pain and vomiting. Certainly not in the form of an oral medication. While many adults will have an aura that warns them of the headache onset, I have found that most children don’t describe an aura. It may be they simply lack the ability to express it. Occasionally an observant parent may detect pallor or a behavior change that indicates a migraine is beginning. On rare occasions a parent may be able to abort the attack by quickly getting the child to a quiet, dark, and calm environment.

Although this recent meta-analysis review of treatment options is discouraging, it may be providing a clue to effective prophylaxis. Some of the medications that decrease the frequency of the attacks may be doing so because they improve the patient’s sleep patterns. Those that decrease the intensity of the pain are probably working on pain pathway that is not specific to migraine.

Continuing a search for a prophylactic medication is a worthy goal, particularly for those patients in which their migraines are debilitating. However, based on my experience, enhanced by my bias, the safest and most effective prophylaxis results from increasing the family’s awareness of the role that sleep deprivation plays in the illness. Even when the family buys into the message and attempts to avoid situations that will tax their vulnerable children, parents will need to accept that sometimes stuff happens even though siblings and peers may be able to tolerate the situation. Spontaneous activities can converge on a day when for whatever reason the migraine-prone child is overtired and the headache and vomiting will erupt.

A lifestyle change is always preferable to a pharmacological intervention. However, that doesn’t mean it is always easy to achieve.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism. Recent research suggests that another metric, the body roundness index (BRI), might better gauge the health risks associated with obesity.

According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
 

Studies Support BRI

Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.

A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
 

Why Replace BMI?

Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”

Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
 

BMI Classifies Bodybuilders as Obese

The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:

BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass. 

BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example. 

In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.

The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:

BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)

In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
 

Could BRI Replace BMI?

Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.

Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.

However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.

Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
 

Anthropometric Measures Only for Clinical Use

Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.

“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”

Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.

He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”

Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
 

The BMI Might Be Responsible for the ‘Healthy Obese’

One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.

According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.

Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.

“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
 

This story was translated from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism. Recent research suggests that another metric, the body roundness index (BRI), might better gauge the health risks associated with obesity.

According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
 

Studies Support BRI

Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.

A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
 

Why Replace BMI?

Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”

Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
 

BMI Classifies Bodybuilders as Obese

The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:

BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass. 

BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example. 

In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.

The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:

BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)

In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
 

Could BRI Replace BMI?

Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.

Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.

However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.

Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
 

Anthropometric Measures Only for Clinical Use

Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.

“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”

Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.

He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”

Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
 

The BMI Might Be Responsible for the ‘Healthy Obese’

One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.

According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.

Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.

“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
 

This story was translated from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism. Recent research suggests that another metric, the body roundness index (BRI), might better gauge the health risks associated with obesity.

According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
 

Studies Support BRI

Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.

A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
 

Why Replace BMI?

Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”

Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
 

BMI Classifies Bodybuilders as Obese

The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:

BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass. 

BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example. 

In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.

The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:

BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)

In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
 

Could BRI Replace BMI?

Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.

Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.

However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.

Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
 

Anthropometric Measures Only for Clinical Use

Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.

“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”

Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.

He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”

Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
 

The BMI Might Be Responsible for the ‘Healthy Obese’

One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.

According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.

Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.

“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
 

This story was translated from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — The rationale for using obesity medications in pediatric patients is that it’s using “a biological intervention to treat a biologically based disease,” according to Claudia Fox, MD, MPH, an associate professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota, Minneapolis. At the annual meeting of the American Academy of Pediatrics (AAP), Fox provided an overview of what obesity medications are approved for in youth and how to determine which medications may be best for different patients.

“This field is changing so rapidly that even over the course of the last 3 or 4 months, the verbiage around what we should be calling these interventions has changed,” Fox noted. Instead of “anti-obesity” medications, “most of us are now using the term obesity medications to highlight or to reduce chances of stigma and bias that can come along with this topic.”

Jessica Ivers, MD, a pediatrician at Swedish Pediatrics in Seattle, Washington, said she found the session very informative, particularly because she doesn’t think many pediatricians currently feel very comfortable prescribing obesity medications.

“It answered questions that any general pediatrician would have, and it’s kind of a new field that people are learning about,” Ivers said. “I think we just need more education. It’s just too new, and people haven’t had the education and the support from colleagues to [use the medications].”

Fox first reminded attendees of precisely what obesity is: A chronic, relapsing, multifactorial, neurobehavioral disease that involves the accumulation and/or distribution of excess body fat that results in impaired health. AAP clinical practice guidelines currently advise that youth aged 12 years or older who have obesity be offered weight loss pharmacotherapy as an adjunct to lifestyle treatment, taking into consideration the indications, risks, and benefits of each medication.

That doesn’t necessarily mean every child aged 12 years or older with a body mass index (BMI) of at least the 95th percentile should be prescribed one of these medications, Fox said. But pediatricians should start becoming familiar with the options and recognize that part of reducing the stigma of this disease is emphasizing that these medications are prescribed not for “weight loss” but to treat the disease of obesity, Fox said. The guidelines advise “early, intensive care” and focusing on the whole child, “using a family-centered and nonstigmatizing approach that acknowledges obesity’s biologic, social, and structural drivers.”
 

Offer the Full Spectrum of Care Early On

Early intervention means starting obesity treatment at diagnosis, without watchful waiting or the previously recommended staged approach. Instead of trying lifestyle therapy for 3-6 months, then considering the addition of medication, and then considering bariatric surgery, “we should be offering the full spectrum of obesity care as appropriate for that individual patient,” Fox said.

Some children with severe obesity may need the combination of lifestyle therapy and pharmacotherapy right up front, whereas another might be able to try lifestyle therapy alone for a while first. “What we know is that, for most interventions, whether it is lifestyle therapy, a medication, or bariatric surgery, early response typically predicts longer-term response,” Fox said. A study conducted by her group, for example, found that a 3% BMI reduction after 1 month with lifestyle therapy was very predictive of clinically meaningful BMI reduction at 1 year.

As with any medical treatment, physicians need to weigh the risks of the medication — short-term side effects and unknown long-term risks (or benefits) — against the risks of not treating. Because obesity is a progressive disease, “if we don’t treat it, most will develop comorbid conditions, or worsening of their already present comorbid conditions, and this does indeed lead to shortened life expectancy,” Fox said. Those who should be treated with medication are obviously those in whom the benefits outweigh the risks, Fox said, which depends on their age, their comorbidities, the severity of obesity, and the safety and efficacy of medication options.

“If I have a patient who has maybe class 2 obesity but no other comorbid conditions, I may be less inclined to start an obesity medication than a kid who has class 1 obesity and obstructive sleep apnea, for instance,” Fox said. “Some of the medications are very, very potent and effective. If you have a kid who maybe has less severe forms of obesity, perhaps they don’t need something that’s so potent.”

BMI trajectory is also a factor to consider. She said she may not be too concerned about a 16-year-old who has always been at the 95th percentile and is otherwise healthy, but the situation is different for a 16-year-old who used to be in the 25th percentile and has rapidly progressed to the 50th and then 75th percentiles in a trajectory heading straight up.

Another factor that may come into play is the patient and family preferences, though Fox noted that weight bias and stigma often interfere here. If obesity medications are brought up, the family may bring up the need for more exercise and better meal prep at home.

“They have this sense that they just need to try harder, that if they did that, the obesity would somehow get better on its own,” Fox said. “That’s an internalized bias that it’s somehow their fault, rather than realizing that this is indeed a biological disorder.”

Finally, clinicians may want to consider the child’s response to lifestyle therapy and whether they have already had bariatric surgery because these medications can be prescribed in people who did not have an adequate response to surgery.
 

Overview of the Medications

There are currently six obesity medications approved by the Food and Drug Administration (FDA) for use in youth: Phentermine, orlistat, liraglutide, phentermine/topiramate, semaglutide, and setmelanotide.

Of these, orlistat is rarely used now because it results in the least amount of change in BMI (about a 3% loss change in BMI), has a lot of gastrointestinal side effects, often is not covered by insurance, and is expensive out of pocket. Setmelanotide is indicated only in those aged 6 years or older who have obesity because of Bardet-Biedl syndrome or one of three other rare genetic conditions: a POMC, LEPR, or PCSK1 deficiency. Fox therefore focused on the other medications besides these two.

While nearly all the currently available obesity medications are only approved in those aged 12 years or older, Fox noted that studies are ongoing at younger ages, so some of these medications may receive approval in younger populations in the future. The only one currently available for a younger age is liraglutide, which is approved down to 6 years old in children with type 2 diabetes.

“Very young kids who have very severe forms of obesity need intervention, and unfortunately, at this point, we really don’t have much to offer them,” Fox said.

Fox highlighted six key factors to consider in selecting a medication for those aged 12 years or older, though one of these, in the US healthcare system, can tend to trump all the others. Those factors are mechanism of action, side effect profile, effects on other diagnoses, patient/family preferences, provider comfort, and finally — the potentially overruling one — insurance coverage and access.

“These days, insurance coverage and access are really the No. 1 driver when I’m seeing a patient,” Fox said. “The first thing I do is look at their insurance and then also look at what kind of updates our pharmacist has given us about which medication is currently in stock.”

Each medication has different properties that should be considered with the child’s health profile. For example, topiramate is a carbonic anhydrase inhibitor so likely shouldn’t be prescribed in a child who is taking any other carbonic anhydrase inhibitor. Fox said she probably wouldn’t prescribe phentermine in a child with severe anxiety because it might enhance the anxiety effect. But if a child has migraines, she may be more inclined to try phentermine/topiramate first because the topiramate may help with the migraines. Similarly, if a child has type 2 diabetes or prediabetes, she may lean toward one of the glucagon-like peptide 1 (GLP-1) agonist drugs.
 

Liraglutide and Semaglutide

Liraglutide and semaglutide are both GLP-1 receptor agonists administered subcutaneously to reduce appetite, increase satiety, slow gastric emptying, and reduce the food reward response in the brain. Liraglutide can result in up to 4.5%-5% change in BMI, and semaglutide, the most potent of all the medications, can result in up to a 17% change in BMI.

Liraglutide and semaglutide are both approved for patients aged 12 years or older who weigh at least 60 kg and have a BMI of at least the 95th percentile. Liraglutide is also approved for those aged 10 years or older with type 2 diabetes. Both are contraindicated in those with a family history of medullary thyroid cancer or multiple endocrine neoplasia II. The risks to watch for include pancreatitis and gallbladder disease. Also keep in mind if you have a patient with type 1 diabetes and insulin resistance; prescribing a GLP-1 agonist is appropriate, but their insulin needs will decrease, necessitating close monitoring of their blood glucose, Fox noted.

These GLP-1 medications can be considered for those who have insurance coverage for them, who have diabetes or prediabetes, who are comfortable with daily (liraglutide) or weekly (semaglutide) injections, who have food cravings, and who have poor satiety or satiation. Without insurance, these medications are very expensive.

The most common side effects include injection site reactions and nausea, vomiting, and diarrhea, though all these usually fade and can be minimized with small portions and slower eating if needed. Less common possible side effects can include abdominal pain, constipation, headache, dizziness, fatigue, and hypoglycemia. If patients develop severe belly pain that radiates to their back, they should be assessed for pancreatitis.

It’s also important to demonstrate for patients how to do the injections, Fox said. Liraglutide dosing begins at 0.6 mg daily for a week, followed by a week at 1.2 mg, a week at 1.8 mg, a week at 2.4 mg, and then 3 mg daily. Semaglutide dosing starts at 0.25 mg weekly for 4 weeks, then going up each subsequent month as needed to 0.5 mg, then 1 mg, then 1.7 mg, and finally 2.4 mg. Though there’s no standard follow-up schedule for these medications, Fox suggested considering monthly visits for the first 3 months and then every 2-3 months to assess heart rate and blood pressure, the injection site, adherence, side effects, and the effect on BMI and eating.

“Are they getting appetite suppression, but not too much appetite suppression?” Fox said. “Just like in eating disorder treatment, we want our patients to eat regularly spaced meals. If their appetite is so suppressed that they are hardly eating anything, that’s a problem.”

Fox also offered the following additional pearls about these medications:

• Though manufacturers have struggled to keep up with demand, the shortages of these medications are improving. However, beware the compounding pharmacies filling the gap because compounded medications are not FDA approved, and quality control issues are a concern.
• Prior authorizations are usually needed, and common reasons for denial to anticipate include lack of documentation on not having contraindications, the patient not following a low-calorie diet or engaging in physical activity, and the patient not having seen a registered dietitian.
• Patients should expect gastrointestinal side effects, but ondansetron can be prescribed to lessen the intensity.

Phentermine/Topiramate

Phentermine/topiramate extended-release is a once-daily oral tablet, with the phentermine acting to reduce appetite (by simulating the release of norepinephrine) and the topiramate reducing caloric intake and food reward response (by increasing gamma-aminobutyric acid activity). It’s approved for those aged 12 years or older with a BMI of at least the 95th percentile and should be considered in those with strong hunger, low energy, binge eating disorder, or migraines, as well as those who have insurance coverage for it. It can result in up to a 10% change in BMI.

Contraindications include pregnancy, substance use, cardiovascular disease (though it’s okay in patients with controlled hypertension), hyperthyroidism, glaucoma, and monoamine oxidase inhibitor (MAOI) use. Fox emphasized the teratogenic effects, so patients capable of pregnancy need to be on reliable birth control. The most common side effects include paresthesia, dizziness, dysgeusia, insomnia, and constipation.

A risk of topiramate is kidney stones, so patients should drink a lot of water, especially in hot weather, Fox said. Other risks can include metabolic acidosis, suicidality, poor cognitive function, high blood pressure, and renal impairment.

“If your patient is struggling academically, I might use this medication a bit more cautiously, particularly when the dose gets above 100 mg a day,” Fox said. “That’s when the cognitive effects tend to emerge more strongly.”

Patients with congenital heart disease should meet with their cardiologist before starting this medication, and although patients taking selective serotonin reuptake inhibitors (SSRIs) can take this, there is a potential increased risk for serotonin syndrome because phentermine has a little bit of serotonergic activity, she said.

Before prescribing, do an exam to ensure the patient doesn’t have a heart murmur, isn’t hypertensive, isn’t pregnant, has normal kidney function, and has bicarbonate in a reasonable range. Dosing begins with a daily 3.75/23-mg capsule for 2 weeks, followed by 2 weeks at 7.5 mg/46 mg. As with the GLP-1 drugs, Fox advises considering monthly follow-ups for the first 3 months and then visits every 2-3 months. Each visit should include the assessment of cardiovascular health, heart rate, blood pressure, side effects, pregnancy risk, and the medication’s effect on BMI and eating. If the patient is tolerating a dose of 7.5 mg/46 mg, it can be increased to 11.25 mg/69 mg for 2 weeks and then to 15 mg/92 mg. Bicarbonate and creatinine should be checked every 6-12 months; if bicarbonate < 18 mEq/L, the dose should be reduced and then bicarbonate should be checked again a month later.

Fox noted that this drug is expected to go off patent in late 2024 or in 2025, which will substantially reduce the cost. It’s also possible to prescribe phentermine and topiramate separately, which may reduce costs or help with insurance coverage and can allow for evening dosing of topiramate.
 

Phentermine

Phentermine alone is only approved for those older than 16 years who have a BMI of at least 30, or at least 27 with weight-related comorbidities, and it’s not approved for use longer than 12 weeks. It results in a BMI change of up to 5%. It should be considered in those with strong hunger and low energy and in those who don’t have adequate insurance coverage because out-of-pocket costs can be as little as $5/mo.

Contraindications are the same as those for the combined pill above: Substance use, cardiovascular disease, hyperthyroidism, glaucoma, MAOI use, and agitation. Again, take caution with patients who have hypertension, have congenital heart disease, or take SSRIs or insulin.

Side effects can include palpitations, tachycardia, dry mouth, headache, insomnia, and anxiety. The dose starts at 15 mg daily, and Fox advises following a similar follow-up as with the other medications, at which clinicians should assess BMI, the medication’s effect on eating, cardiovascular health, and side effects and have a discussion about off-label use. Off-label use refers to prescriptions lasting longer than 12 weeks, but it’s arguably safer than attention-deficit/hyperactivity disorder stimulants because of the lower addiction potential, Fox said.
 

What Else to Know

Because obesity is a chronic disease, treatment will be ongoing, Fox noted. A lot of people will ask when or where the “off-ramp” for these medications is, but many people will need these medications long term just as someone with other chronic diseases requires lifetime pharmacotherapy. The treatment intensity will vary based on disease severity and individual characteristics, Fox said.

For those feeling overwhelmed by the options, Fox advises clinicians to start by picking one medication to learn and then spending the time to read the FDA package insert in full. Get samples and then closely follow patients to learn that medication well before moving on to learn another. She also noted the opportunity for pediatricians to see a pediatric obesity medicine fellowship.

No external funding was used for the presentation. Fox is a site principal investigator for clinical trials sponsored by Novo Nordisk and Eli Lilly. Ivers had no disclosures.

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

ORLANDO, FLORIDA — The rationale for using obesity medications in pediatric patients is that it’s using “a biological intervention to treat a biologically based disease,” according to Claudia Fox, MD, MPH, an associate professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota, Minneapolis. At the annual meeting of the American Academy of Pediatrics (AAP), Fox provided an overview of what obesity medications are approved for in youth and how to determine which medications may be best for different patients.

“This field is changing so rapidly that even over the course of the last 3 or 4 months, the verbiage around what we should be calling these interventions has changed,” Fox noted. Instead of “anti-obesity” medications, “most of us are now using the term obesity medications to highlight or to reduce chances of stigma and bias that can come along with this topic.”

Jessica Ivers, MD, a pediatrician at Swedish Pediatrics in Seattle, Washington, said she found the session very informative, particularly because she doesn’t think many pediatricians currently feel very comfortable prescribing obesity medications.

“It answered questions that any general pediatrician would have, and it’s kind of a new field that people are learning about,” Ivers said. “I think we just need more education. It’s just too new, and people haven’t had the education and the support from colleagues to [use the medications].”

Fox first reminded attendees of precisely what obesity is: A chronic, relapsing, multifactorial, neurobehavioral disease that involves the accumulation and/or distribution of excess body fat that results in impaired health. AAP clinical practice guidelines currently advise that youth aged 12 years or older who have obesity be offered weight loss pharmacotherapy as an adjunct to lifestyle treatment, taking into consideration the indications, risks, and benefits of each medication.

That doesn’t necessarily mean every child aged 12 years or older with a body mass index (BMI) of at least the 95th percentile should be prescribed one of these medications, Fox said. But pediatricians should start becoming familiar with the options and recognize that part of reducing the stigma of this disease is emphasizing that these medications are prescribed not for “weight loss” but to treat the disease of obesity, Fox said. The guidelines advise “early, intensive care” and focusing on the whole child, “using a family-centered and nonstigmatizing approach that acknowledges obesity’s biologic, social, and structural drivers.”
 

Offer the Full Spectrum of Care Early On

Early intervention means starting obesity treatment at diagnosis, without watchful waiting or the previously recommended staged approach. Instead of trying lifestyle therapy for 3-6 months, then considering the addition of medication, and then considering bariatric surgery, “we should be offering the full spectrum of obesity care as appropriate for that individual patient,” Fox said.

Some children with severe obesity may need the combination of lifestyle therapy and pharmacotherapy right up front, whereas another might be able to try lifestyle therapy alone for a while first. “What we know is that, for most interventions, whether it is lifestyle therapy, a medication, or bariatric surgery, early response typically predicts longer-term response,” Fox said. A study conducted by her group, for example, found that a 3% BMI reduction after 1 month with lifestyle therapy was very predictive of clinically meaningful BMI reduction at 1 year.

As with any medical treatment, physicians need to weigh the risks of the medication — short-term side effects and unknown long-term risks (or benefits) — against the risks of not treating. Because obesity is a progressive disease, “if we don’t treat it, most will develop comorbid conditions, or worsening of their already present comorbid conditions, and this does indeed lead to shortened life expectancy,” Fox said. Those who should be treated with medication are obviously those in whom the benefits outweigh the risks, Fox said, which depends on their age, their comorbidities, the severity of obesity, and the safety and efficacy of medication options.

“If I have a patient who has maybe class 2 obesity but no other comorbid conditions, I may be less inclined to start an obesity medication than a kid who has class 1 obesity and obstructive sleep apnea, for instance,” Fox said. “Some of the medications are very, very potent and effective. If you have a kid who maybe has less severe forms of obesity, perhaps they don’t need something that’s so potent.”

BMI trajectory is also a factor to consider. She said she may not be too concerned about a 16-year-old who has always been at the 95th percentile and is otherwise healthy, but the situation is different for a 16-year-old who used to be in the 25th percentile and has rapidly progressed to the 50th and then 75th percentiles in a trajectory heading straight up.

Another factor that may come into play is the patient and family preferences, though Fox noted that weight bias and stigma often interfere here. If obesity medications are brought up, the family may bring up the need for more exercise and better meal prep at home.

“They have this sense that they just need to try harder, that if they did that, the obesity would somehow get better on its own,” Fox said. “That’s an internalized bias that it’s somehow their fault, rather than realizing that this is indeed a biological disorder.”

Finally, clinicians may want to consider the child’s response to lifestyle therapy and whether they have already had bariatric surgery because these medications can be prescribed in people who did not have an adequate response to surgery.
 

Overview of the Medications

There are currently six obesity medications approved by the Food and Drug Administration (FDA) for use in youth: Phentermine, orlistat, liraglutide, phentermine/topiramate, semaglutide, and setmelanotide.

Of these, orlistat is rarely used now because it results in the least amount of change in BMI (about a 3% loss change in BMI), has a lot of gastrointestinal side effects, often is not covered by insurance, and is expensive out of pocket. Setmelanotide is indicated only in those aged 6 years or older who have obesity because of Bardet-Biedl syndrome or one of three other rare genetic conditions: a POMC, LEPR, or PCSK1 deficiency. Fox therefore focused on the other medications besides these two.

While nearly all the currently available obesity medications are only approved in those aged 12 years or older, Fox noted that studies are ongoing at younger ages, so some of these medications may receive approval in younger populations in the future. The only one currently available for a younger age is liraglutide, which is approved down to 6 years old in children with type 2 diabetes.

“Very young kids who have very severe forms of obesity need intervention, and unfortunately, at this point, we really don’t have much to offer them,” Fox said.

Fox highlighted six key factors to consider in selecting a medication for those aged 12 years or older, though one of these, in the US healthcare system, can tend to trump all the others. Those factors are mechanism of action, side effect profile, effects on other diagnoses, patient/family preferences, provider comfort, and finally — the potentially overruling one — insurance coverage and access.

“These days, insurance coverage and access are really the No. 1 driver when I’m seeing a patient,” Fox said. “The first thing I do is look at their insurance and then also look at what kind of updates our pharmacist has given us about which medication is currently in stock.”

Each medication has different properties that should be considered with the child’s health profile. For example, topiramate is a carbonic anhydrase inhibitor so likely shouldn’t be prescribed in a child who is taking any other carbonic anhydrase inhibitor. Fox said she probably wouldn’t prescribe phentermine in a child with severe anxiety because it might enhance the anxiety effect. But if a child has migraines, she may be more inclined to try phentermine/topiramate first because the topiramate may help with the migraines. Similarly, if a child has type 2 diabetes or prediabetes, she may lean toward one of the glucagon-like peptide 1 (GLP-1) agonist drugs.
 

Liraglutide and Semaglutide

Liraglutide and semaglutide are both GLP-1 receptor agonists administered subcutaneously to reduce appetite, increase satiety, slow gastric emptying, and reduce the food reward response in the brain. Liraglutide can result in up to 4.5%-5% change in BMI, and semaglutide, the most potent of all the medications, can result in up to a 17% change in BMI.

Liraglutide and semaglutide are both approved for patients aged 12 years or older who weigh at least 60 kg and have a BMI of at least the 95th percentile. Liraglutide is also approved for those aged 10 years or older with type 2 diabetes. Both are contraindicated in those with a family history of medullary thyroid cancer or multiple endocrine neoplasia II. The risks to watch for include pancreatitis and gallbladder disease. Also keep in mind if you have a patient with type 1 diabetes and insulin resistance; prescribing a GLP-1 agonist is appropriate, but their insulin needs will decrease, necessitating close monitoring of their blood glucose, Fox noted.

These GLP-1 medications can be considered for those who have insurance coverage for them, who have diabetes or prediabetes, who are comfortable with daily (liraglutide) or weekly (semaglutide) injections, who have food cravings, and who have poor satiety or satiation. Without insurance, these medications are very expensive.

The most common side effects include injection site reactions and nausea, vomiting, and diarrhea, though all these usually fade and can be minimized with small portions and slower eating if needed. Less common possible side effects can include abdominal pain, constipation, headache, dizziness, fatigue, and hypoglycemia. If patients develop severe belly pain that radiates to their back, they should be assessed for pancreatitis.

It’s also important to demonstrate for patients how to do the injections, Fox said. Liraglutide dosing begins at 0.6 mg daily for a week, followed by a week at 1.2 mg, a week at 1.8 mg, a week at 2.4 mg, and then 3 mg daily. Semaglutide dosing starts at 0.25 mg weekly for 4 weeks, then going up each subsequent month as needed to 0.5 mg, then 1 mg, then 1.7 mg, and finally 2.4 mg. Though there’s no standard follow-up schedule for these medications, Fox suggested considering monthly visits for the first 3 months and then every 2-3 months to assess heart rate and blood pressure, the injection site, adherence, side effects, and the effect on BMI and eating.

“Are they getting appetite suppression, but not too much appetite suppression?” Fox said. “Just like in eating disorder treatment, we want our patients to eat regularly spaced meals. If their appetite is so suppressed that they are hardly eating anything, that’s a problem.”

Fox also offered the following additional pearls about these medications:

• Though manufacturers have struggled to keep up with demand, the shortages of these medications are improving. However, beware the compounding pharmacies filling the gap because compounded medications are not FDA approved, and quality control issues are a concern.
• Prior authorizations are usually needed, and common reasons for denial to anticipate include lack of documentation on not having contraindications, the patient not following a low-calorie diet or engaging in physical activity, and the patient not having seen a registered dietitian.
• Patients should expect gastrointestinal side effects, but ondansetron can be prescribed to lessen the intensity.

Phentermine/Topiramate

Phentermine/topiramate extended-release is a once-daily oral tablet, with the phentermine acting to reduce appetite (by simulating the release of norepinephrine) and the topiramate reducing caloric intake and food reward response (by increasing gamma-aminobutyric acid activity). It’s approved for those aged 12 years or older with a BMI of at least the 95th percentile and should be considered in those with strong hunger, low energy, binge eating disorder, or migraines, as well as those who have insurance coverage for it. It can result in up to a 10% change in BMI.

Contraindications include pregnancy, substance use, cardiovascular disease (though it’s okay in patients with controlled hypertension), hyperthyroidism, glaucoma, and monoamine oxidase inhibitor (MAOI) use. Fox emphasized the teratogenic effects, so patients capable of pregnancy need to be on reliable birth control. The most common side effects include paresthesia, dizziness, dysgeusia, insomnia, and constipation.

A risk of topiramate is kidney stones, so patients should drink a lot of water, especially in hot weather, Fox said. Other risks can include metabolic acidosis, suicidality, poor cognitive function, high blood pressure, and renal impairment.

“If your patient is struggling academically, I might use this medication a bit more cautiously, particularly when the dose gets above 100 mg a day,” Fox said. “That’s when the cognitive effects tend to emerge more strongly.”

Patients with congenital heart disease should meet with their cardiologist before starting this medication, and although patients taking selective serotonin reuptake inhibitors (SSRIs) can take this, there is a potential increased risk for serotonin syndrome because phentermine has a little bit of serotonergic activity, she said.

Before prescribing, do an exam to ensure the patient doesn’t have a heart murmur, isn’t hypertensive, isn’t pregnant, has normal kidney function, and has bicarbonate in a reasonable range. Dosing begins with a daily 3.75/23-mg capsule for 2 weeks, followed by 2 weeks at 7.5 mg/46 mg. As with the GLP-1 drugs, Fox advises considering monthly follow-ups for the first 3 months and then visits every 2-3 months. Each visit should include the assessment of cardiovascular health, heart rate, blood pressure, side effects, pregnancy risk, and the medication’s effect on BMI and eating. If the patient is tolerating a dose of 7.5 mg/46 mg, it can be increased to 11.25 mg/69 mg for 2 weeks and then to 15 mg/92 mg. Bicarbonate and creatinine should be checked every 6-12 months; if bicarbonate < 18 mEq/L, the dose should be reduced and then bicarbonate should be checked again a month later.

Fox noted that this drug is expected to go off patent in late 2024 or in 2025, which will substantially reduce the cost. It’s also possible to prescribe phentermine and topiramate separately, which may reduce costs or help with insurance coverage and can allow for evening dosing of topiramate.
 

Phentermine

Phentermine alone is only approved for those older than 16 years who have a BMI of at least 30, or at least 27 with weight-related comorbidities, and it’s not approved for use longer than 12 weeks. It results in a BMI change of up to 5%. It should be considered in those with strong hunger and low energy and in those who don’t have adequate insurance coverage because out-of-pocket costs can be as little as $5/mo.

Contraindications are the same as those for the combined pill above: Substance use, cardiovascular disease, hyperthyroidism, glaucoma, MAOI use, and agitation. Again, take caution with patients who have hypertension, have congenital heart disease, or take SSRIs or insulin.

Side effects can include palpitations, tachycardia, dry mouth, headache, insomnia, and anxiety. The dose starts at 15 mg daily, and Fox advises following a similar follow-up as with the other medications, at which clinicians should assess BMI, the medication’s effect on eating, cardiovascular health, and side effects and have a discussion about off-label use. Off-label use refers to prescriptions lasting longer than 12 weeks, but it’s arguably safer than attention-deficit/hyperactivity disorder stimulants because of the lower addiction potential, Fox said.
 

What Else to Know

Because obesity is a chronic disease, treatment will be ongoing, Fox noted. A lot of people will ask when or where the “off-ramp” for these medications is, but many people will need these medications long term just as someone with other chronic diseases requires lifetime pharmacotherapy. The treatment intensity will vary based on disease severity and individual characteristics, Fox said.

For those feeling overwhelmed by the options, Fox advises clinicians to start by picking one medication to learn and then spending the time to read the FDA package insert in full. Get samples and then closely follow patients to learn that medication well before moving on to learn another. She also noted the opportunity for pediatricians to see a pediatric obesity medicine fellowship.

No external funding was used for the presentation. Fox is a site principal investigator for clinical trials sponsored by Novo Nordisk and Eli Lilly. Ivers had no disclosures.

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

ORLANDO, FLORIDA — The rationale for using obesity medications in pediatric patients is that it’s using “a biological intervention to treat a biologically based disease,” according to Claudia Fox, MD, MPH, an associate professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota, Minneapolis. At the annual meeting of the American Academy of Pediatrics (AAP), Fox provided an overview of what obesity medications are approved for in youth and how to determine which medications may be best for different patients.

“This field is changing so rapidly that even over the course of the last 3 or 4 months, the verbiage around what we should be calling these interventions has changed,” Fox noted. Instead of “anti-obesity” medications, “most of us are now using the term obesity medications to highlight or to reduce chances of stigma and bias that can come along with this topic.”

Jessica Ivers, MD, a pediatrician at Swedish Pediatrics in Seattle, Washington, said she found the session very informative, particularly because she doesn’t think many pediatricians currently feel very comfortable prescribing obesity medications.

“It answered questions that any general pediatrician would have, and it’s kind of a new field that people are learning about,” Ivers said. “I think we just need more education. It’s just too new, and people haven’t had the education and the support from colleagues to [use the medications].”

Fox first reminded attendees of precisely what obesity is: A chronic, relapsing, multifactorial, neurobehavioral disease that involves the accumulation and/or distribution of excess body fat that results in impaired health. AAP clinical practice guidelines currently advise that youth aged 12 years or older who have obesity be offered weight loss pharmacotherapy as an adjunct to lifestyle treatment, taking into consideration the indications, risks, and benefits of each medication.

That doesn’t necessarily mean every child aged 12 years or older with a body mass index (BMI) of at least the 95th percentile should be prescribed one of these medications, Fox said. But pediatricians should start becoming familiar with the options and recognize that part of reducing the stigma of this disease is emphasizing that these medications are prescribed not for “weight loss” but to treat the disease of obesity, Fox said. The guidelines advise “early, intensive care” and focusing on the whole child, “using a family-centered and nonstigmatizing approach that acknowledges obesity’s biologic, social, and structural drivers.”
 

Offer the Full Spectrum of Care Early On

Early intervention means starting obesity treatment at diagnosis, without watchful waiting or the previously recommended staged approach. Instead of trying lifestyle therapy for 3-6 months, then considering the addition of medication, and then considering bariatric surgery, “we should be offering the full spectrum of obesity care as appropriate for that individual patient,” Fox said.

Some children with severe obesity may need the combination of lifestyle therapy and pharmacotherapy right up front, whereas another might be able to try lifestyle therapy alone for a while first. “What we know is that, for most interventions, whether it is lifestyle therapy, a medication, or bariatric surgery, early response typically predicts longer-term response,” Fox said. A study conducted by her group, for example, found that a 3% BMI reduction after 1 month with lifestyle therapy was very predictive of clinically meaningful BMI reduction at 1 year.

As with any medical treatment, physicians need to weigh the risks of the medication — short-term side effects and unknown long-term risks (or benefits) — against the risks of not treating. Because obesity is a progressive disease, “if we don’t treat it, most will develop comorbid conditions, or worsening of their already present comorbid conditions, and this does indeed lead to shortened life expectancy,” Fox said. Those who should be treated with medication are obviously those in whom the benefits outweigh the risks, Fox said, which depends on their age, their comorbidities, the severity of obesity, and the safety and efficacy of medication options.

“If I have a patient who has maybe class 2 obesity but no other comorbid conditions, I may be less inclined to start an obesity medication than a kid who has class 1 obesity and obstructive sleep apnea, for instance,” Fox said. “Some of the medications are very, very potent and effective. If you have a kid who maybe has less severe forms of obesity, perhaps they don’t need something that’s so potent.”

BMI trajectory is also a factor to consider. She said she may not be too concerned about a 16-year-old who has always been at the 95th percentile and is otherwise healthy, but the situation is different for a 16-year-old who used to be in the 25th percentile and has rapidly progressed to the 50th and then 75th percentiles in a trajectory heading straight up.

Another factor that may come into play is the patient and family preferences, though Fox noted that weight bias and stigma often interfere here. If obesity medications are brought up, the family may bring up the need for more exercise and better meal prep at home.

“They have this sense that they just need to try harder, that if they did that, the obesity would somehow get better on its own,” Fox said. “That’s an internalized bias that it’s somehow their fault, rather than realizing that this is indeed a biological disorder.”

Finally, clinicians may want to consider the child’s response to lifestyle therapy and whether they have already had bariatric surgery because these medications can be prescribed in people who did not have an adequate response to surgery.
 

Overview of the Medications

There are currently six obesity medications approved by the Food and Drug Administration (FDA) for use in youth: Phentermine, orlistat, liraglutide, phentermine/topiramate, semaglutide, and setmelanotide.

Of these, orlistat is rarely used now because it results in the least amount of change in BMI (about a 3% loss change in BMI), has a lot of gastrointestinal side effects, often is not covered by insurance, and is expensive out of pocket. Setmelanotide is indicated only in those aged 6 years or older who have obesity because of Bardet-Biedl syndrome or one of three other rare genetic conditions: a POMC, LEPR, or PCSK1 deficiency. Fox therefore focused on the other medications besides these two.

While nearly all the currently available obesity medications are only approved in those aged 12 years or older, Fox noted that studies are ongoing at younger ages, so some of these medications may receive approval in younger populations in the future. The only one currently available for a younger age is liraglutide, which is approved down to 6 years old in children with type 2 diabetes.

“Very young kids who have very severe forms of obesity need intervention, and unfortunately, at this point, we really don’t have much to offer them,” Fox said.

Fox highlighted six key factors to consider in selecting a medication for those aged 12 years or older, though one of these, in the US healthcare system, can tend to trump all the others. Those factors are mechanism of action, side effect profile, effects on other diagnoses, patient/family preferences, provider comfort, and finally — the potentially overruling one — insurance coverage and access.

“These days, insurance coverage and access are really the No. 1 driver when I’m seeing a patient,” Fox said. “The first thing I do is look at their insurance and then also look at what kind of updates our pharmacist has given us about which medication is currently in stock.”

Each medication has different properties that should be considered with the child’s health profile. For example, topiramate is a carbonic anhydrase inhibitor so likely shouldn’t be prescribed in a child who is taking any other carbonic anhydrase inhibitor. Fox said she probably wouldn’t prescribe phentermine in a child with severe anxiety because it might enhance the anxiety effect. But if a child has migraines, she may be more inclined to try phentermine/topiramate first because the topiramate may help with the migraines. Similarly, if a child has type 2 diabetes or prediabetes, she may lean toward one of the glucagon-like peptide 1 (GLP-1) agonist drugs.
 

Liraglutide and Semaglutide

Liraglutide and semaglutide are both GLP-1 receptor agonists administered subcutaneously to reduce appetite, increase satiety, slow gastric emptying, and reduce the food reward response in the brain. Liraglutide can result in up to 4.5%-5% change in BMI, and semaglutide, the most potent of all the medications, can result in up to a 17% change in BMI.

Liraglutide and semaglutide are both approved for patients aged 12 years or older who weigh at least 60 kg and have a BMI of at least the 95th percentile. Liraglutide is also approved for those aged 10 years or older with type 2 diabetes. Both are contraindicated in those with a family history of medullary thyroid cancer or multiple endocrine neoplasia II. The risks to watch for include pancreatitis and gallbladder disease. Also keep in mind if you have a patient with type 1 diabetes and insulin resistance; prescribing a GLP-1 agonist is appropriate, but their insulin needs will decrease, necessitating close monitoring of their blood glucose, Fox noted.

These GLP-1 medications can be considered for those who have insurance coverage for them, who have diabetes or prediabetes, who are comfortable with daily (liraglutide) or weekly (semaglutide) injections, who have food cravings, and who have poor satiety or satiation. Without insurance, these medications are very expensive.

The most common side effects include injection site reactions and nausea, vomiting, and diarrhea, though all these usually fade and can be minimized with small portions and slower eating if needed. Less common possible side effects can include abdominal pain, constipation, headache, dizziness, fatigue, and hypoglycemia. If patients develop severe belly pain that radiates to their back, they should be assessed for pancreatitis.

It’s also important to demonstrate for patients how to do the injections, Fox said. Liraglutide dosing begins at 0.6 mg daily for a week, followed by a week at 1.2 mg, a week at 1.8 mg, a week at 2.4 mg, and then 3 mg daily. Semaglutide dosing starts at 0.25 mg weekly for 4 weeks, then going up each subsequent month as needed to 0.5 mg, then 1 mg, then 1.7 mg, and finally 2.4 mg. Though there’s no standard follow-up schedule for these medications, Fox suggested considering monthly visits for the first 3 months and then every 2-3 months to assess heart rate and blood pressure, the injection site, adherence, side effects, and the effect on BMI and eating.

“Are they getting appetite suppression, but not too much appetite suppression?” Fox said. “Just like in eating disorder treatment, we want our patients to eat regularly spaced meals. If their appetite is so suppressed that they are hardly eating anything, that’s a problem.”

Fox also offered the following additional pearls about these medications:

• Though manufacturers have struggled to keep up with demand, the shortages of these medications are improving. However, beware the compounding pharmacies filling the gap because compounded medications are not FDA approved, and quality control issues are a concern.
• Prior authorizations are usually needed, and common reasons for denial to anticipate include lack of documentation on not having contraindications, the patient not following a low-calorie diet or engaging in physical activity, and the patient not having seen a registered dietitian.
• Patients should expect gastrointestinal side effects, but ondansetron can be prescribed to lessen the intensity.

Phentermine/Topiramate

Phentermine/topiramate extended-release is a once-daily oral tablet, with the phentermine acting to reduce appetite (by simulating the release of norepinephrine) and the topiramate reducing caloric intake and food reward response (by increasing gamma-aminobutyric acid activity). It’s approved for those aged 12 years or older with a BMI of at least the 95th percentile and should be considered in those with strong hunger, low energy, binge eating disorder, or migraines, as well as those who have insurance coverage for it. It can result in up to a 10% change in BMI.

Contraindications include pregnancy, substance use, cardiovascular disease (though it’s okay in patients with controlled hypertension), hyperthyroidism, glaucoma, and monoamine oxidase inhibitor (MAOI) use. Fox emphasized the teratogenic effects, so patients capable of pregnancy need to be on reliable birth control. The most common side effects include paresthesia, dizziness, dysgeusia, insomnia, and constipation.

A risk of topiramate is kidney stones, so patients should drink a lot of water, especially in hot weather, Fox said. Other risks can include metabolic acidosis, suicidality, poor cognitive function, high blood pressure, and renal impairment.

“If your patient is struggling academically, I might use this medication a bit more cautiously, particularly when the dose gets above 100 mg a day,” Fox said. “That’s when the cognitive effects tend to emerge more strongly.”

Patients with congenital heart disease should meet with their cardiologist before starting this medication, and although patients taking selective serotonin reuptake inhibitors (SSRIs) can take this, there is a potential increased risk for serotonin syndrome because phentermine has a little bit of serotonergic activity, she said.

Before prescribing, do an exam to ensure the patient doesn’t have a heart murmur, isn’t hypertensive, isn’t pregnant, has normal kidney function, and has bicarbonate in a reasonable range. Dosing begins with a daily 3.75/23-mg capsule for 2 weeks, followed by 2 weeks at 7.5 mg/46 mg. As with the GLP-1 drugs, Fox advises considering monthly follow-ups for the first 3 months and then visits every 2-3 months. Each visit should include the assessment of cardiovascular health, heart rate, blood pressure, side effects, pregnancy risk, and the medication’s effect on BMI and eating. If the patient is tolerating a dose of 7.5 mg/46 mg, it can be increased to 11.25 mg/69 mg for 2 weeks and then to 15 mg/92 mg. Bicarbonate and creatinine should be checked every 6-12 months; if bicarbonate < 18 mEq/L, the dose should be reduced and then bicarbonate should be checked again a month later.

Fox noted that this drug is expected to go off patent in late 2024 or in 2025, which will substantially reduce the cost. It’s also possible to prescribe phentermine and topiramate separately, which may reduce costs or help with insurance coverage and can allow for evening dosing of topiramate.
 

Phentermine

Phentermine alone is only approved for those older than 16 years who have a BMI of at least 30, or at least 27 with weight-related comorbidities, and it’s not approved for use longer than 12 weeks. It results in a BMI change of up to 5%. It should be considered in those with strong hunger and low energy and in those who don’t have adequate insurance coverage because out-of-pocket costs can be as little as $5/mo.

Contraindications are the same as those for the combined pill above: Substance use, cardiovascular disease, hyperthyroidism, glaucoma, MAOI use, and agitation. Again, take caution with patients who have hypertension, have congenital heart disease, or take SSRIs or insulin.

Side effects can include palpitations, tachycardia, dry mouth, headache, insomnia, and anxiety. The dose starts at 15 mg daily, and Fox advises following a similar follow-up as with the other medications, at which clinicians should assess BMI, the medication’s effect on eating, cardiovascular health, and side effects and have a discussion about off-label use. Off-label use refers to prescriptions lasting longer than 12 weeks, but it’s arguably safer than attention-deficit/hyperactivity disorder stimulants because of the lower addiction potential, Fox said.
 

What Else to Know

Because obesity is a chronic disease, treatment will be ongoing, Fox noted. A lot of people will ask when or where the “off-ramp” for these medications is, but many people will need these medications long term just as someone with other chronic diseases requires lifetime pharmacotherapy. The treatment intensity will vary based on disease severity and individual characteristics, Fox said.

For those feeling overwhelmed by the options, Fox advises clinicians to start by picking one medication to learn and then spending the time to read the FDA package insert in full. Get samples and then closely follow patients to learn that medication well before moving on to learn another. She also noted the opportunity for pediatricians to see a pediatric obesity medicine fellowship.

No external funding was used for the presentation. Fox is a site principal investigator for clinical trials sponsored by Novo Nordisk and Eli Lilly. Ivers had no disclosures.

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

Efforts to curb overdiagnosis of thyroid cancer have made a difference in the United States and South Korea, but these countries still have high rates of excess treatment of indolent lesions, according to a recently published global study.

The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.

Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.

Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.

Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.

“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”

Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.

This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.

Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.

“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
 

Persisting Problem

Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.

The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”

“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.

In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.

If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.

In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.

“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.

“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.

The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.

“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.

In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.

Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
 

New Thinking on Thyroid Cancer

There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.

“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”

The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.

Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.

“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.

Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.

“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.

Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.

“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”

Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.

“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”

This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.

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

Efforts to curb overdiagnosis of thyroid cancer have made a difference in the United States and South Korea, but these countries still have high rates of excess treatment of indolent lesions, according to a recently published global study.

The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.

Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.

Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.

Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.

“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”

Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.

This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.

Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.

“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
 

Persisting Problem

Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.

The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”

“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.

In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.

If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.

In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.

“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.

“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.

The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.

“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.

In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.

Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
 

New Thinking on Thyroid Cancer

There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.

“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”

The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.

Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.

“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.

Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.

“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.

Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.

“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”

Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.

“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”

This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.

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

Efforts to curb overdiagnosis of thyroid cancer have made a difference in the United States and South Korea, but these countries still have high rates of excess treatment of indolent lesions, according to a recently published global study.

The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.

Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.

Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.

Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.

“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”

Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.

This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.

Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.

“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
 

Persisting Problem

Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.

The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”

“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.

In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.

If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.

In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.

“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.

“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.

The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.

“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.

In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.

Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
 

New Thinking on Thyroid Cancer

There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.

“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”

The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.

Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.

“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.

Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.

“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.

Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.

“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”

Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.

“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”

This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.

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

Adults aged 45-49 years are as likely as are those aged 50 years to complete a fecal immunochemical test (FIT) as an initial screen for colorectal cancer (CRC) and follow-up with a colonoscopy if needed, a new study has found.

The study also found a similar low 3% rate of CRC detected at colonoscopy in both the younger and older adults.

“Our study suggests that adults ages 45-49 have a colorectal cancer risk that is similar to what we see in adults age 50,” senior author Jeffrey K. Lee, MD, MPH, gastroenterologist and research scientist at Kaiser Permanente Northern California Division of Research (DOR) in Oakland, California, said in a news release.

“The low number of cancers we found also provides support for initially offering younger adults a non-invasive test, like FIT, to determine which patients would benefit from a colonoscopy,” Lee noted.

Kaiser Permanente Medical Center

Timely and Important Question

“This study addresses a timely and important clinical question, namely, is FIT an acceptable screening modality in patients aged 45-49,” Ziad F. Gellad, MD, MPH, AGAF, professor of medicine, Duke University Medical Center, Durham, North Carolina, who was not involved in the study, said in an interview.

“The finding that FIT completion and yield in younger patients is similar to those aged 50 and above is good news because it supports the use of this screening modality in the younger cohort,” said Gellad, section chief, gastroenterology, Durham VA Health Care System.

Duke University

FIT First Fits With Younger Adults’ Busy Lives

“Overall, people under 50 have lower incidence of cancer than people in their 50s, 60s, and 70s. However, if you do a test like FIT first, you can improve the yield of colonoscopy, which is a much more efficient strategy,” Levin said.

He noted that younger people are the least likely to be screened.

“They are busy with work and family responsibilities and may not realize that they are at risk for CRC. It is important to offer them a test that is easy to perform and does not require them to miss a day of work or arrange for a driver. They should be offered an option to screen with a stool-based test as an easy way to fit CRC screening into their busy lives,” Levin said.

Gellad said the study also highlights the limitations of FIT, “namely, that the low uptake and suboptimal colonoscopy follow-up of positive tests, also extend into the lower age group.”

Additionally, Gellad said he hopes other large systems will replicate this study to address the generalizability of these findings outside the Kaiser system.

The study was funded by the Kaiser Permanente Sydney R. Garfield Memorial Fund. Disclosures for study authors are available with the original article. Gellad consulted for Merck & Co. and Novo Nordisk and is a co-founder of Higgs Boson, Inc.

A version of this article appeared on Medscape.com.

Adults aged 45-49 years are as likely as are those aged 50 years to complete a fecal immunochemical test (FIT) as an initial screen for colorectal cancer (CRC) and follow-up with a colonoscopy if needed, a new study has found.

The study also found a similar low 3% rate of CRC detected at colonoscopy in both the younger and older adults.

“Our study suggests that adults ages 45-49 have a colorectal cancer risk that is similar to what we see in adults age 50,” senior author Jeffrey K. Lee, MD, MPH, gastroenterologist and research scientist at Kaiser Permanente Northern California Division of Research (DOR) in Oakland, California, said in a news release.

“The low number of cancers we found also provides support for initially offering younger adults a non-invasive test, like FIT, to determine which patients would benefit from a colonoscopy,” Lee noted.

Kaiser Permanente Medical Center

Timely and Important Question

“This study addresses a timely and important clinical question, namely, is FIT an acceptable screening modality in patients aged 45-49,” Ziad F. Gellad, MD, MPH, AGAF, professor of medicine, Duke University Medical Center, Durham, North Carolina, who was not involved in the study, said in an interview.

“The finding that FIT completion and yield in younger patients is similar to those aged 50 and above is good news because it supports the use of this screening modality in the younger cohort,” said Gellad, section chief, gastroenterology, Durham VA Health Care System.

Duke University

FIT First Fits With Younger Adults’ Busy Lives

“Overall, people under 50 have lower incidence of cancer than people in their 50s, 60s, and 70s. However, if you do a test like FIT first, you can improve the yield of colonoscopy, which is a much more efficient strategy,” Levin said.

He noted that younger people are the least likely to be screened.

“They are busy with work and family responsibilities and may not realize that they are at risk for CRC. It is important to offer them a test that is easy to perform and does not require them to miss a day of work or arrange for a driver. They should be offered an option to screen with a stool-based test as an easy way to fit CRC screening into their busy lives,” Levin said.

Gellad said the study also highlights the limitations of FIT, “namely, that the low uptake and suboptimal colonoscopy follow-up of positive tests, also extend into the lower age group.”

Additionally, Gellad said he hopes other large systems will replicate this study to address the generalizability of these findings outside the Kaiser system.

The study was funded by the Kaiser Permanente Sydney R. Garfield Memorial Fund. Disclosures for study authors are available with the original article. Gellad consulted for Merck & Co. and Novo Nordisk and is a co-founder of Higgs Boson, Inc.

A version of this article appeared on Medscape.com.

Adults aged 45-49 years are as likely as are those aged 50 years to complete a fecal immunochemical test (FIT) as an initial screen for colorectal cancer (CRC) and follow-up with a colonoscopy if needed, a new study has found.

The study also found a similar low 3% rate of CRC detected at colonoscopy in both the younger and older adults.

“Our study suggests that adults ages 45-49 have a colorectal cancer risk that is similar to what we see in adults age 50,” senior author Jeffrey K. Lee, MD, MPH, gastroenterologist and research scientist at Kaiser Permanente Northern California Division of Research (DOR) in Oakland, California, said in a news release.

“The low number of cancers we found also provides support for initially offering younger adults a non-invasive test, like FIT, to determine which patients would benefit from a colonoscopy,” Lee noted.

Kaiser Permanente Medical Center

Timely and Important Question

“This study addresses a timely and important clinical question, namely, is FIT an acceptable screening modality in patients aged 45-49,” Ziad F. Gellad, MD, MPH, AGAF, professor of medicine, Duke University Medical Center, Durham, North Carolina, who was not involved in the study, said in an interview.

“The finding that FIT completion and yield in younger patients is similar to those aged 50 and above is good news because it supports the use of this screening modality in the younger cohort,” said Gellad, section chief, gastroenterology, Durham VA Health Care System.

Duke University

FIT First Fits With Younger Adults’ Busy Lives

“Overall, people under 50 have lower incidence of cancer than people in their 50s, 60s, and 70s. However, if you do a test like FIT first, you can improve the yield of colonoscopy, which is a much more efficient strategy,” Levin said.

He noted that younger people are the least likely to be screened.

“They are busy with work and family responsibilities and may not realize that they are at risk for CRC. It is important to offer them a test that is easy to perform and does not require them to miss a day of work or arrange for a driver. They should be offered an option to screen with a stool-based test as an easy way to fit CRC screening into their busy lives,” Levin said.

Gellad said the study also highlights the limitations of FIT, “namely, that the low uptake and suboptimal colonoscopy follow-up of positive tests, also extend into the lower age group.”

Additionally, Gellad said he hopes other large systems will replicate this study to address the generalizability of these findings outside the Kaiser system.

The study was funded by the Kaiser Permanente Sydney R. Garfield Memorial Fund. Disclosures for study authors are available with the original article. Gellad consulted for Merck & Co. and Novo Nordisk and is a co-founder of Higgs Boson, Inc.

A version of this article appeared on Medscape.com.