TOPLINE:

Women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive lobular carcinoma who are treated with endocrine therapy do not derive any additional survival benefit from neoadjuvant or adjuvant chemotherapy.

METHODOLOGY:

• Studies evaluating the long-term effects of chemotherapy in patients with invasive lobular carcinoma are limited and often “show inconclusive results,” the authors explained.
• Female patients diagnosed with ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy were identified from the breast cancer database at Erasmus Medical Center, Rotterdam, the Netherlands.
• Linked information on patient and tumor characteristics, vital status, and treatment were then obtained from the Netherlands Cancer Registry.
• Patients also had to have an indication for chemotherapy based on lymph node status, tumor size, histologic tumor grade, and hormone receptor status, in line with national guidelines.
• Among 716 patients with ER-positive, HER2-negative invasive lobular carcinoma, 520 who had an indication for chemotherapy were included. Of those, 379 received chemotherapy and 141 did not.

TAKEAWAY:

• Patients who received chemotherapy were younger at diagnosis than those who did not (51 vs 61 years), had an earlier average year of diagnosis (2010 vs 2015), and had longer follow-up (7.8 years vs 5.2 years).
• Chemotherapy recipients were more likely to have T3+ disease (33% vs 14%) and positive lymph node involvement (80% vs 49%), and less likely to undergo breast-conserving surgery (31% vs 43%).
• Researchers, however, found no difference between the chemotherapy and no-chemotherapy groups in terms of recurrence-free survival (hazard ratio [HR], 1.20; 95% CI, 0.63-2.31), breast cancer–specific survival (HR, 1.24; 95% CI, 0.60-2.58), and overall survival (HR, 0.97; 95% CI, 0.56-1.66) after adjustment for confounders.

IN PRACTICE:

The authors “observed no evidence for added value of chemotherapy” for ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy. “In view of the adverse effects of chemotherapy, our study takes an important step in answering a valuable question from the patient’s perspective,” the researchers wrote.

SOURCE:

The study, conducted by Bernadette A.M. Heemskerk-Gerritsen, PhD, from Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, was published in Cancer on November 20, 2023.

LIMITATIONS:

The retrospective design means that there is a risk for residual confounding from factors not recorded in the database. The researchers believe that some patients did not receive chemotherapy owing to having comorbidities or patient preference, which could have influenced the results. Moreover, the duration of endocrine therapy was not recorded.

DISCLOSURES:

No funding was declared. One author declares relationships with GlaxoSmithKline, Pfizer, Menarini Silicon Biosystems, and Novartis. No other relevant financial relationships were declared.

TOPLINE:

Women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive lobular carcinoma who are treated with endocrine therapy do not derive any additional survival benefit from neoadjuvant or adjuvant chemotherapy.

METHODOLOGY:

• Studies evaluating the long-term effects of chemotherapy in patients with invasive lobular carcinoma are limited and often “show inconclusive results,” the authors explained.
• Female patients diagnosed with ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy were identified from the breast cancer database at Erasmus Medical Center, Rotterdam, the Netherlands.
• Linked information on patient and tumor characteristics, vital status, and treatment were then obtained from the Netherlands Cancer Registry.
• Patients also had to have an indication for chemotherapy based on lymph node status, tumor size, histologic tumor grade, and hormone receptor status, in line with national guidelines.
• Among 716 patients with ER-positive, HER2-negative invasive lobular carcinoma, 520 who had an indication for chemotherapy were included. Of those, 379 received chemotherapy and 141 did not.

TAKEAWAY:

• Patients who received chemotherapy were younger at diagnosis than those who did not (51 vs 61 years), had an earlier average year of diagnosis (2010 vs 2015), and had longer follow-up (7.8 years vs 5.2 years).
• Chemotherapy recipients were more likely to have T3+ disease (33% vs 14%) and positive lymph node involvement (80% vs 49%), and less likely to undergo breast-conserving surgery (31% vs 43%).
• Researchers, however, found no difference between the chemotherapy and no-chemotherapy groups in terms of recurrence-free survival (hazard ratio [HR], 1.20; 95% CI, 0.63-2.31), breast cancer–specific survival (HR, 1.24; 95% CI, 0.60-2.58), and overall survival (HR, 0.97; 95% CI, 0.56-1.66) after adjustment for confounders.

IN PRACTICE:

The authors “observed no evidence for added value of chemotherapy” for ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy. “In view of the adverse effects of chemotherapy, our study takes an important step in answering a valuable question from the patient’s perspective,” the researchers wrote.

SOURCE:

The study, conducted by Bernadette A.M. Heemskerk-Gerritsen, PhD, from Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, was published in Cancer on November 20, 2023.

LIMITATIONS:

The retrospective design means that there is a risk for residual confounding from factors not recorded in the database. The researchers believe that some patients did not receive chemotherapy owing to having comorbidities or patient preference, which could have influenced the results. Moreover, the duration of endocrine therapy was not recorded.

DISCLOSURES:

No funding was declared. One author declares relationships with GlaxoSmithKline, Pfizer, Menarini Silicon Biosystems, and Novartis. No other relevant financial relationships were declared.

TOPLINE:

Women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive lobular carcinoma who are treated with endocrine therapy do not derive any additional survival benefit from neoadjuvant or adjuvant chemotherapy.

METHODOLOGY:

• Studies evaluating the long-term effects of chemotherapy in patients with invasive lobular carcinoma are limited and often “show inconclusive results,” the authors explained.
• Female patients diagnosed with ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy were identified from the breast cancer database at Erasmus Medical Center, Rotterdam, the Netherlands.
• Linked information on patient and tumor characteristics, vital status, and treatment were then obtained from the Netherlands Cancer Registry.
• Patients also had to have an indication for chemotherapy based on lymph node status, tumor size, histologic tumor grade, and hormone receptor status, in line with national guidelines.
• Among 716 patients with ER-positive, HER2-negative invasive lobular carcinoma, 520 who had an indication for chemotherapy were included. Of those, 379 received chemotherapy and 141 did not.

TAKEAWAY:

• Patients who received chemotherapy were younger at diagnosis than those who did not (51 vs 61 years), had an earlier average year of diagnosis (2010 vs 2015), and had longer follow-up (7.8 years vs 5.2 years).
• Chemotherapy recipients were more likely to have T3+ disease (33% vs 14%) and positive lymph node involvement (80% vs 49%), and less likely to undergo breast-conserving surgery (31% vs 43%).
• Researchers, however, found no difference between the chemotherapy and no-chemotherapy groups in terms of recurrence-free survival (hazard ratio [HR], 1.20; 95% CI, 0.63-2.31), breast cancer–specific survival (HR, 1.24; 95% CI, 0.60-2.58), and overall survival (HR, 0.97; 95% CI, 0.56-1.66) after adjustment for confounders.

IN PRACTICE:

The authors “observed no evidence for added value of chemotherapy” for ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy. “In view of the adverse effects of chemotherapy, our study takes an important step in answering a valuable question from the patient’s perspective,” the researchers wrote.

SOURCE:

The study, conducted by Bernadette A.M. Heemskerk-Gerritsen, PhD, from Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, was published in Cancer on November 20, 2023.

LIMITATIONS:

The retrospective design means that there is a risk for residual confounding from factors not recorded in the database. The researchers believe that some patients did not receive chemotherapy owing to having comorbidities or patient preference, which could have influenced the results. Moreover, the duration of endocrine therapy was not recorded.

DISCLOSURES:

No funding was declared. One author declares relationships with GlaxoSmithKline, Pfizer, Menarini Silicon Biosystems, and Novartis. No other relevant financial relationships were declared.

TOPLINE:

Attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders are associated with a twofold increased risk for schizophrenia, new research shows.

METHODOLOGY:

• Investigators analyzed the data of 211,705 people aged 5-19 years (74% male; 54% aged 5-9 years) diagnosed with ADHD during 2010-2018 from the Health Insurance Review and Assessment Service database of South Korea.
• Participants with a diagnosis of schizophrenia or psychosis anytime in the 3 years prior to ADHD diagnosis were excluded.
• Investigators split participants into two groups — a group of those diagnosed with at least one psychiatric comorbidity within a year of ADHD diagnosis and another group comprising those with ADHD and no psychiatric comorbidities.

TAKEAWAY:

• 37% (77,890) of those with ADHD had at least one comorbid psychiatric disorder.
• Participants with one psychiatric comorbidity had a 2.1-fold increased risk for a schizophrenia diagnosis than participants with no comorbidity (adjusted hazard ratio [aHR], 2.14; 95% CI, 2.05-2.23).
• Schizophrenia risk increased with each additional comorbidity. There was a fourfold increased risk for schizophrenia in study participants with three or more psychiatric comorbidities (aHR, 4.26; 95% CI, 3.90-4.65) than those with no comorbidity.
• Psychiatric comorbidities included autism spectrum disorder, which had the strongest link to increased schizophrenia risk (aHR, 2.43; 95% CI, 2.26-2.62). Other comorbidities that showed strong associations were intellectual disability (aHR, 1.83; 95% CI, 1.72-1.95), tic disorder (aHR, 1.77; 95% CI, 1.66-1.88), depression (aHR,1.68; 95% CI, 1.60-1.77), and bipolar disorder (aHR, 1.67; 95% CI, 1.53-1.83).

IN PRACTICE:

“To our knowledge, this is the first study to investigate schizophrenia risk among children and adolescents with ADHD, with a particular focus on psychiatric comorbidities,” the researchers wrote. They also noted that although patients had no psychiatric comorbidities at the time of ADHD diagnosis, the occurrence of psychiatric comorbidities was frequently observed prior to schizophrenia diagnosis. 

“These findings highlighted the significance of carefully monitoring psychiatric comorbidities in patients with ADHD to effectively mitigate the burden of schizophrenia,” they noted.

SOURCE:

Soo Min Jeon, PharmD, PhD, of Jeju National University in Jeju, South Korea, led the study, which was published online on November 30, 2023 in JAMA Network Open. 

LIMITATIONS:

Since the diagnosis of ADHD, schizophrenia, and other psychiatric comorbidities were based on diagnostic codes, the possibility of underdiagnosis or overdiagnosis cannot be ruled out. Also, some patients with ADHD chose the general health consultation (International Classification of Diseases - Z code) due to the social stigma surrounding mental health problems.

DISCLOSURES:

The study was funded by the Basic Science Research Program through the Ministry of Education and the Health Insurance Review and Assessment Service. Author disclosures can be found in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders are associated with a twofold increased risk for schizophrenia, new research shows.

METHODOLOGY:

• Investigators analyzed the data of 211,705 people aged 5-19 years (74% male; 54% aged 5-9 years) diagnosed with ADHD during 2010-2018 from the Health Insurance Review and Assessment Service database of South Korea.
• Participants with a diagnosis of schizophrenia or psychosis anytime in the 3 years prior to ADHD diagnosis were excluded.
• Investigators split participants into two groups — a group of those diagnosed with at least one psychiatric comorbidity within a year of ADHD diagnosis and another group comprising those with ADHD and no psychiatric comorbidities.

TAKEAWAY:

• 37% (77,890) of those with ADHD had at least one comorbid psychiatric disorder.
• Participants with one psychiatric comorbidity had a 2.1-fold increased risk for a schizophrenia diagnosis than participants with no comorbidity (adjusted hazard ratio [aHR], 2.14; 95% CI, 2.05-2.23).
• Schizophrenia risk increased with each additional comorbidity. There was a fourfold increased risk for schizophrenia in study participants with three or more psychiatric comorbidities (aHR, 4.26; 95% CI, 3.90-4.65) than those with no comorbidity.
• Psychiatric comorbidities included autism spectrum disorder, which had the strongest link to increased schizophrenia risk (aHR, 2.43; 95% CI, 2.26-2.62). Other comorbidities that showed strong associations were intellectual disability (aHR, 1.83; 95% CI, 1.72-1.95), tic disorder (aHR, 1.77; 95% CI, 1.66-1.88), depression (aHR,1.68; 95% CI, 1.60-1.77), and bipolar disorder (aHR, 1.67; 95% CI, 1.53-1.83).

IN PRACTICE:

“To our knowledge, this is the first study to investigate schizophrenia risk among children and adolescents with ADHD, with a particular focus on psychiatric comorbidities,” the researchers wrote. They also noted that although patients had no psychiatric comorbidities at the time of ADHD diagnosis, the occurrence of psychiatric comorbidities was frequently observed prior to schizophrenia diagnosis. 

“These findings highlighted the significance of carefully monitoring psychiatric comorbidities in patients with ADHD to effectively mitigate the burden of schizophrenia,” they noted.

SOURCE:

Soo Min Jeon, PharmD, PhD, of Jeju National University in Jeju, South Korea, led the study, which was published online on November 30, 2023 in JAMA Network Open. 

LIMITATIONS:

Since the diagnosis of ADHD, schizophrenia, and other psychiatric comorbidities were based on diagnostic codes, the possibility of underdiagnosis or overdiagnosis cannot be ruled out. Also, some patients with ADHD chose the general health consultation (International Classification of Diseases - Z code) due to the social stigma surrounding mental health problems.

DISCLOSURES:

The study was funded by the Basic Science Research Program through the Ministry of Education and the Health Insurance Review and Assessment Service. Author disclosures can be found in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders are associated with a twofold increased risk for schizophrenia, new research shows.

METHODOLOGY:

• Investigators analyzed the data of 211,705 people aged 5-19 years (74% male; 54% aged 5-9 years) diagnosed with ADHD during 2010-2018 from the Health Insurance Review and Assessment Service database of South Korea.
• Participants with a diagnosis of schizophrenia or psychosis anytime in the 3 years prior to ADHD diagnosis were excluded.
• Investigators split participants into two groups — a group of those diagnosed with at least one psychiatric comorbidity within a year of ADHD diagnosis and another group comprising those with ADHD and no psychiatric comorbidities.

TAKEAWAY:

• 37% (77,890) of those with ADHD had at least one comorbid psychiatric disorder.
• Participants with one psychiatric comorbidity had a 2.1-fold increased risk for a schizophrenia diagnosis than participants with no comorbidity (adjusted hazard ratio [aHR], 2.14; 95% CI, 2.05-2.23).
• Schizophrenia risk increased with each additional comorbidity. There was a fourfold increased risk for schizophrenia in study participants with three or more psychiatric comorbidities (aHR, 4.26; 95% CI, 3.90-4.65) than those with no comorbidity.
• Psychiatric comorbidities included autism spectrum disorder, which had the strongest link to increased schizophrenia risk (aHR, 2.43; 95% CI, 2.26-2.62). Other comorbidities that showed strong associations were intellectual disability (aHR, 1.83; 95% CI, 1.72-1.95), tic disorder (aHR, 1.77; 95% CI, 1.66-1.88), depression (aHR,1.68; 95% CI, 1.60-1.77), and bipolar disorder (aHR, 1.67; 95% CI, 1.53-1.83).

IN PRACTICE:

“To our knowledge, this is the first study to investigate schizophrenia risk among children and adolescents with ADHD, with a particular focus on psychiatric comorbidities,” the researchers wrote. They also noted that although patients had no psychiatric comorbidities at the time of ADHD diagnosis, the occurrence of psychiatric comorbidities was frequently observed prior to schizophrenia diagnosis. 

“These findings highlighted the significance of carefully monitoring psychiatric comorbidities in patients with ADHD to effectively mitigate the burden of schizophrenia,” they noted.

SOURCE:

Soo Min Jeon, PharmD, PhD, of Jeju National University in Jeju, South Korea, led the study, which was published online on November 30, 2023 in JAMA Network Open. 

LIMITATIONS:

Since the diagnosis of ADHD, schizophrenia, and other psychiatric comorbidities were based on diagnostic codes, the possibility of underdiagnosis or overdiagnosis cannot be ruled out. Also, some patients with ADHD chose the general health consultation (International Classification of Diseases - Z code) due to the social stigma surrounding mental health problems.

DISCLOSURES:

The study was funded by the Basic Science Research Program through the Ministry of Education and the Health Insurance Review and Assessment Service. Author disclosures can be found in the original paper.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) holds the promise of identifying premalignant and advanced malignant lesions during colonoscopy that might otherwise be missed. 

Is it living up to that promise? 

It seems that depends on where, how, and by whom it’s being implemented.
 

Clinical Trials vs the Real World

The majority of randomized clinical trials of AI use conducted worldwide “clearly show an increase in the adenoma detection rate (ADR) during colonoscopy,” Prateek Sharma, MD, a gastroenterologist at The University of Kansas Cancer Center, Kansas City, told this news. “But the real-world results have been quite varied; some show improvement, and others don’t.”

Dr. Sharma is coauthor of a recent pooled analysis of nine randomized controlled trials on the impact of AI on colonoscopy surveillance after polyp removal. It found that AI use increased the proportion of patients requiring intensive surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively). 

“While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs,” the authors concluded.

A recent retrospective analysis of staggered implementation of a computer-aided detection (CADe) system at a single academic center in Chicago found that for screening and surveillance colonoscopy combined, endoscopists using CADe identified more adenomas and serrated polyps — but only endoscopists who used CADe regularly (“majority” users). 

A systematic review and meta-analysis of 21 randomized controlled trials comparing CADe with standard colonoscopy found increased detection of adenomas, but not of advanced adenomas, as well as higher rates of unnecessary removal of non-neoplastic polyps. 

Adding to the mix, a multicenter randomized controlled trial of patients with a positive fecal immunochemical test found that AI use was not associated with better detection of advanced neoplasias. Lead author Carolina Mangas Sanjuán, MD, PhD, Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization the results were “surprising,” given previous studies showing benefit.

Similarly, a pragmatic implementation trial conducted by Stanford, California, researchers showed no significant effect of CADe on ADR, adenomas per colonoscopy, or any other detection metric. Furthermore, CADe had no effect on procedure times or non-neoplastic detection rates. 

The authors cautioned against viewing their study as an “outlier,” however, and pointed to an Israeli study comparing adenoma and polyp detection rates 6 months before and after the introduction of AI-aided colonoscopy. Those authors reported no performance improvement with the AI device and concluded that it was not useful in routine practice. 
 

A ‘Mishmash’ of Methods

“It’s not clear why some studies are positive, and some are negative,” Dr. Sharma acknowledged. 

Study design is a factor, particularly in real-world studies, he said. Some researchers use the before/after approach, as in the Israeli study; others compare use in different rooms — that is, one with a CADe device and one without. Like the Chicago analysis, findings from such studies probably depend on whether the colonoscopists with the CADe device in the room actually use it.

Other real-world studies look at detection by time, Dr. Sharma said. 

For example, a study of 1780 colonoscopies in China found that AI systems showed higher assistance ability among colonoscopies performed later in the day, when adenoma detection rates typically declined, perhaps owing to fatigue. 

These authors suggest that AI may have the potential to maintain high quality and homogeneity of colonoscopies and improve endoscopist performance in large screening programs and centers with high workloads.

“There’s a mishmash of different kinds of real-world studies coming in, and it’s very difficult to figure it all out,” Dr. Sharma said. “We just have to look at these devices as innovations and embrace them and work with them to see how it fits it in our practice.”
 

Perceptions and Expectations

Emerging evidence suggests that endoscopists’ perceptions and expectations may affect assessments of AI’s potential benefits in practice, Dr. Sharma noted.

“Someone might say, ‘I’m a trained physician. Why do I need a machine to help me?’ That can create a situation in which the endoscopist is constantly challenging the device, trying to overrule it or not give it credit.”

Others might perceive that the AI device will definitely help and therefore not look as carefully themselves for adenomas.

A study at The University of Texas MD Anderson Cancer Center in Houston in which activation of the AI system was at the discretion of the endoscopist found that real-time CADe did not improve adenoma detection among endoscopists with high baseline detection rates. 

However, despite its availability, AI-assisted colonoscopy was activated in only half of the cases, and multiple concerns were raised by staff and endoscopists in a postprocedural survey. In particular, endoscopists were concerned that the system would result in too many false-positive signals (82.4%), was too distracting (58.8%), and prolonged procedure time (47.1%). 

The authors of the Stanford study that found no benefit with CADe in routine practice noted, “Most concerning would be if, inadvertently, CADe use was accompanied by a simultaneous unconscious degradation in the quality of mucosal exposure, possibly due to a false sense of comfort that CADe would ensure a high-quality examination.”

“We’re trying to evaluate some of these interactions between endoscopists and AI devices both pragmatically in practice as well as in clinical trials,” Dr. Sharma said. “Much depends on the context of how you approach and present the devices. We tell physicians that this is an assist device, not something you’re competing against and not something that’s here to replace you. This is something which may make your lives easier, so try it out.”
 

Are Less Experienced Endoscopists Helped More?

It seems intuitive that less experienced endoscopists would be helped by AI, and indeed, some recent studies confirm this. 

A small randomized controlled trial in Japan, presented during the Presidential Plenary at the American Society for Gastrointestinal Endoscopy (ASGE) annual meeting in May 2023, showed that a CADe system was “particularly useful” for beginning endoscopists, who had lower adenoma miss rates with the device vs a white light control device.

Another randomized controlled trial in Japan found that CADe use was associated with an increased overall ADR among endoscopists in training.

But experienced endoscopists probably can benefit as well, noted Jennifer Christie, MD, Division Director, Gastroenterology and Hepatology at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora.

“We know that these AI devices can be useful in training our fellows to detect certain lesions in the colon,” she said. “However, they’re also helpful for many very seasoned practitioners, as an adjunctive tool to help in terms of diagnosis.” 

Some studies reflect that dual benefit. 

The AID-2 study, designed specifically to look at whether experience had an effect on AI findings during colonoscopy, was conducted among nonexpert endoscopists (lifetime volume of less than 2000 colonoscopies). The researchers, including Dr. Sharma, found that CADe increased the ADR by 22% compared with the control group.

An earlier study, AID-1 , used a similar design but was conducted among experienced endoscopists. In AID-1, the ADR was also significantly higher in the CADe group (54.8%) compared with the control group (40.4%), and adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07) than in the control group (mean, 0.71).

A multivariate post hoc analysis that pooled results from both AID-1 and AID-2 showed that use of CADe and colonoscopy indication, but not the level of examiner experience, were associated with ADR differences. This led the researchers to conclude, “Experience appears to play a minor role as a determining factor for ADR.”

Similarly, a 2023 study from China looked at the mean number of adenomas detected per colonoscopy according to the endoscopist’s experience. All rates were significantly higher in AI-assisted colonoscopies compared with conventional non-AI colonoscopy: overall ADR, 39.9% vs 32.4%; advanced ADR, 6.6% vs 4.9%; ADR of expert endoscopists, 42.3% vs 32.8%; ADR of nonexpert endoscopists, 37.5% vs 32.1%; and adenomas per colonoscopy, 0.59 vs 0.45, respectively. 

The authors concluded that “AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists.”
 

Improving the Algorithms 

Experts agree that current and future research will improve the accuracy and quality of AI colonoscopy for all users, leading to new standards and more consistent outcomes in both clinical trials and real-world applications. 

Work underway now to improve the algorithms will be an important step in that direction, according to Dr. Christie.

“We need to have enough information to create AI algorithms that allow us to detect early lesions, at least from an imaging standpoint, and we need to improve and increase the sensitivity and the specificity, as well as the predictive value,” she said.

AI can also play a role in health equity, she noted. 

“But it’s a double-edged sword, because it depends again on algorithms and machine learning. Perhaps AI can eliminate some of the bias in our clinical decision-making. However, if we don’t train the machine properly with a good, diverse sample of patients and figure out how to integrate some of the social determinants of health that a computer may not otherwise consider, it can create larger disparities and larger biases. AI devices can only be as good and as inclusive as we make them,” Dr. Christie said. 
 

Looking Ahead

Dr. Sharma predicts that “the next slew of studies are going to be on characterization — not just saying there’s an abnormality but distinguishing it further and saying whether the lesion is noncancerous, precancerous, or cancer.” 

Other studies will focus on quality improvement of factors, such as withdrawal time and bowel preparation. 

In its clinical practice update on AI, the American Gastroenterological Association states, “Eventually, we predict an AI suite of tools for colonoscopy will seem indispensable, as a powerful adjunct to support safe and efficient clinical practice. AI tools that improve colonoscopy quality may become more accepted, and perhaps demanded, by payors, administrators, and possibly even by well-informed patients who want to ensure the highest-quality examination of their colon.” 

Dr. Sharma and Dr. Christie disclose no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) holds the promise of identifying premalignant and advanced malignant lesions during colonoscopy that might otherwise be missed. 

Is it living up to that promise? 

It seems that depends on where, how, and by whom it’s being implemented.
 

Clinical Trials vs the Real World

The majority of randomized clinical trials of AI use conducted worldwide “clearly show an increase in the adenoma detection rate (ADR) during colonoscopy,” Prateek Sharma, MD, a gastroenterologist at The University of Kansas Cancer Center, Kansas City, told this news. “But the real-world results have been quite varied; some show improvement, and others don’t.”

Dr. Sharma is coauthor of a recent pooled analysis of nine randomized controlled trials on the impact of AI on colonoscopy surveillance after polyp removal. It found that AI use increased the proportion of patients requiring intensive surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively). 

“While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs,” the authors concluded.

A recent retrospective analysis of staggered implementation of a computer-aided detection (CADe) system at a single academic center in Chicago found that for screening and surveillance colonoscopy combined, endoscopists using CADe identified more adenomas and serrated polyps — but only endoscopists who used CADe regularly (“majority” users). 

A systematic review and meta-analysis of 21 randomized controlled trials comparing CADe with standard colonoscopy found increased detection of adenomas, but not of advanced adenomas, as well as higher rates of unnecessary removal of non-neoplastic polyps. 

Adding to the mix, a multicenter randomized controlled trial of patients with a positive fecal immunochemical test found that AI use was not associated with better detection of advanced neoplasias. Lead author Carolina Mangas Sanjuán, MD, PhD, Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization the results were “surprising,” given previous studies showing benefit.

Similarly, a pragmatic implementation trial conducted by Stanford, California, researchers showed no significant effect of CADe on ADR, adenomas per colonoscopy, or any other detection metric. Furthermore, CADe had no effect on procedure times or non-neoplastic detection rates. 

The authors cautioned against viewing their study as an “outlier,” however, and pointed to an Israeli study comparing adenoma and polyp detection rates 6 months before and after the introduction of AI-aided colonoscopy. Those authors reported no performance improvement with the AI device and concluded that it was not useful in routine practice. 
 

A ‘Mishmash’ of Methods

“It’s not clear why some studies are positive, and some are negative,” Dr. Sharma acknowledged. 

Study design is a factor, particularly in real-world studies, he said. Some researchers use the before/after approach, as in the Israeli study; others compare use in different rooms — that is, one with a CADe device and one without. Like the Chicago analysis, findings from such studies probably depend on whether the colonoscopists with the CADe device in the room actually use it.

Other real-world studies look at detection by time, Dr. Sharma said. 

For example, a study of 1780 colonoscopies in China found that AI systems showed higher assistance ability among colonoscopies performed later in the day, when adenoma detection rates typically declined, perhaps owing to fatigue. 

These authors suggest that AI may have the potential to maintain high quality and homogeneity of colonoscopies and improve endoscopist performance in large screening programs and centers with high workloads.

“There’s a mishmash of different kinds of real-world studies coming in, and it’s very difficult to figure it all out,” Dr. Sharma said. “We just have to look at these devices as innovations and embrace them and work with them to see how it fits it in our practice.”
 

Perceptions and Expectations

Emerging evidence suggests that endoscopists’ perceptions and expectations may affect assessments of AI’s potential benefits in practice, Dr. Sharma noted.

“Someone might say, ‘I’m a trained physician. Why do I need a machine to help me?’ That can create a situation in which the endoscopist is constantly challenging the device, trying to overrule it or not give it credit.”

Others might perceive that the AI device will definitely help and therefore not look as carefully themselves for adenomas.

A study at The University of Texas MD Anderson Cancer Center in Houston in which activation of the AI system was at the discretion of the endoscopist found that real-time CADe did not improve adenoma detection among endoscopists with high baseline detection rates. 

However, despite its availability, AI-assisted colonoscopy was activated in only half of the cases, and multiple concerns were raised by staff and endoscopists in a postprocedural survey. In particular, endoscopists were concerned that the system would result in too many false-positive signals (82.4%), was too distracting (58.8%), and prolonged procedure time (47.1%). 

The authors of the Stanford study that found no benefit with CADe in routine practice noted, “Most concerning would be if, inadvertently, CADe use was accompanied by a simultaneous unconscious degradation in the quality of mucosal exposure, possibly due to a false sense of comfort that CADe would ensure a high-quality examination.”

“We’re trying to evaluate some of these interactions between endoscopists and AI devices both pragmatically in practice as well as in clinical trials,” Dr. Sharma said. “Much depends on the context of how you approach and present the devices. We tell physicians that this is an assist device, not something you’re competing against and not something that’s here to replace you. This is something which may make your lives easier, so try it out.”
 

Are Less Experienced Endoscopists Helped More?

It seems intuitive that less experienced endoscopists would be helped by AI, and indeed, some recent studies confirm this. 

A small randomized controlled trial in Japan, presented during the Presidential Plenary at the American Society for Gastrointestinal Endoscopy (ASGE) annual meeting in May 2023, showed that a CADe system was “particularly useful” for beginning endoscopists, who had lower adenoma miss rates with the device vs a white light control device.

Another randomized controlled trial in Japan found that CADe use was associated with an increased overall ADR among endoscopists in training.

But experienced endoscopists probably can benefit as well, noted Jennifer Christie, MD, Division Director, Gastroenterology and Hepatology at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora.

“We know that these AI devices can be useful in training our fellows to detect certain lesions in the colon,” she said. “However, they’re also helpful for many very seasoned practitioners, as an adjunctive tool to help in terms of diagnosis.” 

Some studies reflect that dual benefit. 

The AID-2 study, designed specifically to look at whether experience had an effect on AI findings during colonoscopy, was conducted among nonexpert endoscopists (lifetime volume of less than 2000 colonoscopies). The researchers, including Dr. Sharma, found that CADe increased the ADR by 22% compared with the control group.

An earlier study, AID-1 , used a similar design but was conducted among experienced endoscopists. In AID-1, the ADR was also significantly higher in the CADe group (54.8%) compared with the control group (40.4%), and adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07) than in the control group (mean, 0.71).

A multivariate post hoc analysis that pooled results from both AID-1 and AID-2 showed that use of CADe and colonoscopy indication, but not the level of examiner experience, were associated with ADR differences. This led the researchers to conclude, “Experience appears to play a minor role as a determining factor for ADR.”

Similarly, a 2023 study from China looked at the mean number of adenomas detected per colonoscopy according to the endoscopist’s experience. All rates were significantly higher in AI-assisted colonoscopies compared with conventional non-AI colonoscopy: overall ADR, 39.9% vs 32.4%; advanced ADR, 6.6% vs 4.9%; ADR of expert endoscopists, 42.3% vs 32.8%; ADR of nonexpert endoscopists, 37.5% vs 32.1%; and adenomas per colonoscopy, 0.59 vs 0.45, respectively. 

The authors concluded that “AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists.”
 

Improving the Algorithms 

Experts agree that current and future research will improve the accuracy and quality of AI colonoscopy for all users, leading to new standards and more consistent outcomes in both clinical trials and real-world applications. 

Work underway now to improve the algorithms will be an important step in that direction, according to Dr. Christie.

“We need to have enough information to create AI algorithms that allow us to detect early lesions, at least from an imaging standpoint, and we need to improve and increase the sensitivity and the specificity, as well as the predictive value,” she said.

AI can also play a role in health equity, she noted. 

“But it’s a double-edged sword, because it depends again on algorithms and machine learning. Perhaps AI can eliminate some of the bias in our clinical decision-making. However, if we don’t train the machine properly with a good, diverse sample of patients and figure out how to integrate some of the social determinants of health that a computer may not otherwise consider, it can create larger disparities and larger biases. AI devices can only be as good and as inclusive as we make them,” Dr. Christie said. 
 

Looking Ahead

Dr. Sharma predicts that “the next slew of studies are going to be on characterization — not just saying there’s an abnormality but distinguishing it further and saying whether the lesion is noncancerous, precancerous, or cancer.” 

Other studies will focus on quality improvement of factors, such as withdrawal time and bowel preparation. 

In its clinical practice update on AI, the American Gastroenterological Association states, “Eventually, we predict an AI suite of tools for colonoscopy will seem indispensable, as a powerful adjunct to support safe and efficient clinical practice. AI tools that improve colonoscopy quality may become more accepted, and perhaps demanded, by payors, administrators, and possibly even by well-informed patients who want to ensure the highest-quality examination of their colon.” 

Dr. Sharma and Dr. Christie disclose no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) holds the promise of identifying premalignant and advanced malignant lesions during colonoscopy that might otherwise be missed. 

Is it living up to that promise? 

It seems that depends on where, how, and by whom it’s being implemented.
 

Clinical Trials vs the Real World

The majority of randomized clinical trials of AI use conducted worldwide “clearly show an increase in the adenoma detection rate (ADR) during colonoscopy,” Prateek Sharma, MD, a gastroenterologist at The University of Kansas Cancer Center, Kansas City, told this news. “But the real-world results have been quite varied; some show improvement, and others don’t.”

Dr. Sharma is coauthor of a recent pooled analysis of nine randomized controlled trials on the impact of AI on colonoscopy surveillance after polyp removal. It found that AI use increased the proportion of patients requiring intensive surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively). 

“While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs,” the authors concluded.

A recent retrospective analysis of staggered implementation of a computer-aided detection (CADe) system at a single academic center in Chicago found that for screening and surveillance colonoscopy combined, endoscopists using CADe identified more adenomas and serrated polyps — but only endoscopists who used CADe regularly (“majority” users). 

A systematic review and meta-analysis of 21 randomized controlled trials comparing CADe with standard colonoscopy found increased detection of adenomas, but not of advanced adenomas, as well as higher rates of unnecessary removal of non-neoplastic polyps. 

Adding to the mix, a multicenter randomized controlled trial of patients with a positive fecal immunochemical test found that AI use was not associated with better detection of advanced neoplasias. Lead author Carolina Mangas Sanjuán, MD, PhD, Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization the results were “surprising,” given previous studies showing benefit.

Similarly, a pragmatic implementation trial conducted by Stanford, California, researchers showed no significant effect of CADe on ADR, adenomas per colonoscopy, or any other detection metric. Furthermore, CADe had no effect on procedure times or non-neoplastic detection rates. 

The authors cautioned against viewing their study as an “outlier,” however, and pointed to an Israeli study comparing adenoma and polyp detection rates 6 months before and after the introduction of AI-aided colonoscopy. Those authors reported no performance improvement with the AI device and concluded that it was not useful in routine practice. 
 

A ‘Mishmash’ of Methods

“It’s not clear why some studies are positive, and some are negative,” Dr. Sharma acknowledged. 

Study design is a factor, particularly in real-world studies, he said. Some researchers use the before/after approach, as in the Israeli study; others compare use in different rooms — that is, one with a CADe device and one without. Like the Chicago analysis, findings from such studies probably depend on whether the colonoscopists with the CADe device in the room actually use it.

Other real-world studies look at detection by time, Dr. Sharma said. 

For example, a study of 1780 colonoscopies in China found that AI systems showed higher assistance ability among colonoscopies performed later in the day, when adenoma detection rates typically declined, perhaps owing to fatigue. 

These authors suggest that AI may have the potential to maintain high quality and homogeneity of colonoscopies and improve endoscopist performance in large screening programs and centers with high workloads.

“There’s a mishmash of different kinds of real-world studies coming in, and it’s very difficult to figure it all out,” Dr. Sharma said. “We just have to look at these devices as innovations and embrace them and work with them to see how it fits it in our practice.”
 

Perceptions and Expectations

Emerging evidence suggests that endoscopists’ perceptions and expectations may affect assessments of AI’s potential benefits in practice, Dr. Sharma noted.

“Someone might say, ‘I’m a trained physician. Why do I need a machine to help me?’ That can create a situation in which the endoscopist is constantly challenging the device, trying to overrule it or not give it credit.”

Others might perceive that the AI device will definitely help and therefore not look as carefully themselves for adenomas.

A study at The University of Texas MD Anderson Cancer Center in Houston in which activation of the AI system was at the discretion of the endoscopist found that real-time CADe did not improve adenoma detection among endoscopists with high baseline detection rates. 

However, despite its availability, AI-assisted colonoscopy was activated in only half of the cases, and multiple concerns were raised by staff and endoscopists in a postprocedural survey. In particular, endoscopists were concerned that the system would result in too many false-positive signals (82.4%), was too distracting (58.8%), and prolonged procedure time (47.1%). 

The authors of the Stanford study that found no benefit with CADe in routine practice noted, “Most concerning would be if, inadvertently, CADe use was accompanied by a simultaneous unconscious degradation in the quality of mucosal exposure, possibly due to a false sense of comfort that CADe would ensure a high-quality examination.”

“We’re trying to evaluate some of these interactions between endoscopists and AI devices both pragmatically in practice as well as in clinical trials,” Dr. Sharma said. “Much depends on the context of how you approach and present the devices. We tell physicians that this is an assist device, not something you’re competing against and not something that’s here to replace you. This is something which may make your lives easier, so try it out.”
 

Are Less Experienced Endoscopists Helped More?

It seems intuitive that less experienced endoscopists would be helped by AI, and indeed, some recent studies confirm this. 

A small randomized controlled trial in Japan, presented during the Presidential Plenary at the American Society for Gastrointestinal Endoscopy (ASGE) annual meeting in May 2023, showed that a CADe system was “particularly useful” for beginning endoscopists, who had lower adenoma miss rates with the device vs a white light control device.

Another randomized controlled trial in Japan found that CADe use was associated with an increased overall ADR among endoscopists in training.

But experienced endoscopists probably can benefit as well, noted Jennifer Christie, MD, Division Director, Gastroenterology and Hepatology at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora.

“We know that these AI devices can be useful in training our fellows to detect certain lesions in the colon,” she said. “However, they’re also helpful for many very seasoned practitioners, as an adjunctive tool to help in terms of diagnosis.” 

Some studies reflect that dual benefit. 

The AID-2 study, designed specifically to look at whether experience had an effect on AI findings during colonoscopy, was conducted among nonexpert endoscopists (lifetime volume of less than 2000 colonoscopies). The researchers, including Dr. Sharma, found that CADe increased the ADR by 22% compared with the control group.

An earlier study, AID-1 , used a similar design but was conducted among experienced endoscopists. In AID-1, the ADR was also significantly higher in the CADe group (54.8%) compared with the control group (40.4%), and adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07) than in the control group (mean, 0.71).

A multivariate post hoc analysis that pooled results from both AID-1 and AID-2 showed that use of CADe and colonoscopy indication, but not the level of examiner experience, were associated with ADR differences. This led the researchers to conclude, “Experience appears to play a minor role as a determining factor for ADR.”

Similarly, a 2023 study from China looked at the mean number of adenomas detected per colonoscopy according to the endoscopist’s experience. All rates were significantly higher in AI-assisted colonoscopies compared with conventional non-AI colonoscopy: overall ADR, 39.9% vs 32.4%; advanced ADR, 6.6% vs 4.9%; ADR of expert endoscopists, 42.3% vs 32.8%; ADR of nonexpert endoscopists, 37.5% vs 32.1%; and adenomas per colonoscopy, 0.59 vs 0.45, respectively. 

The authors concluded that “AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists.”
 

Improving the Algorithms 

Experts agree that current and future research will improve the accuracy and quality of AI colonoscopy for all users, leading to new standards and more consistent outcomes in both clinical trials and real-world applications. 

Work underway now to improve the algorithms will be an important step in that direction, according to Dr. Christie.

“We need to have enough information to create AI algorithms that allow us to detect early lesions, at least from an imaging standpoint, and we need to improve and increase the sensitivity and the specificity, as well as the predictive value,” she said.

AI can also play a role in health equity, she noted. 

“But it’s a double-edged sword, because it depends again on algorithms and machine learning. Perhaps AI can eliminate some of the bias in our clinical decision-making. However, if we don’t train the machine properly with a good, diverse sample of patients and figure out how to integrate some of the social determinants of health that a computer may not otherwise consider, it can create larger disparities and larger biases. AI devices can only be as good and as inclusive as we make them,” Dr. Christie said. 
 

Looking Ahead

Dr. Sharma predicts that “the next slew of studies are going to be on characterization — not just saying there’s an abnormality but distinguishing it further and saying whether the lesion is noncancerous, precancerous, or cancer.” 

Other studies will focus on quality improvement of factors, such as withdrawal time and bowel preparation. 

In its clinical practice update on AI, the American Gastroenterological Association states, “Eventually, we predict an AI suite of tools for colonoscopy will seem indispensable, as a powerful adjunct to support safe and efficient clinical practice. AI tools that improve colonoscopy quality may become more accepted, and perhaps demanded, by payors, administrators, and possibly even by well-informed patients who want to ensure the highest-quality examination of their colon.” 

Dr. Sharma and Dr. Christie disclose no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

Ten years ago, Clare Gerada, FRCGP, an advocate for physician well-being and today president of the UK’s Royal College of General Practitioners, made a prediction to the audience at the International Conference on Physician Health.

“We have seen a massive increase in eating disorders [among doctors],” she said. “I’m not sure anybody is quite aware of the tsunami of eating disorders,” she believed would soon strike predominantly female physicians.

That was 2014. Did the tsunami hit?

Quite possibly. Data are limited on the prevalence of eating disorders (EDs) among healthcare workers, but studies do exist. A 2019 global review and meta-analysis determined “the summary prevalence of eating disorder (ED) risk among medical students was 10.4%.”

A 2022 update of that review boosted the estimate to 17.35%.

Tsunami or not, that’s nearly double the 9% rate within the US general public (from a 2020 report from STRIPED and the Academy of Eating Disorders). And while the following stat isn’t an indicator of EDs per se, 19% of doctors admit to unhealthy eating habits, according to a recent Medscape Medical News physician survey.

To her credit, Dr. Gerada, awarded a damehood in 2020, was in a position to know what was coming. Her statement was informed by research showing an increasing number of young doctors seeking treatment for mental health issues, including EDs, through the NHS Practitioner Health program, a mental health service she established in 2008.

So ... what puts doctors at such a high risk for EDs?

Be Careful of ‘Overlap Traits’

As with many mental health issues, EDs have no single cause. Researchers believe they stem from a complex interaction of genetic, biological, behavioral, psychological, and social factors. But the medical field should take note: Some personality traits commonly associated with EDs are often shared by successful physicians.

“I think some of the overlap traits would be being highly driven, goal-oriented and self-critical,” said Lesley Williams, MD, a family medicine physician at the Mayo Clinic in Phoenix, Arizona. “A lot of those traits can make you a very successful physician and physician-in-training but could also potentially spill over into body image and rigidity around food.”

Of course, we want physicians to strive for excellence, and the majority of diligent, driven doctors will not develop an ED.

But when pushed too far, those admirable qualities can easily become perfectionism — which has long been recognized as a risk factor for EDs, an association supported by decades of research.

Medical School: Where EDs Begin and Little Education About Them Happens

“I think medicine in general attracts people that often share similar characteristics to those who struggle with EDs — high-achieving, hardworking perfectionists who put a lot of pressure on themselves,” said Elizabeth McNaught, MD, a general practitioner and medical director at Family Mental Wealth.

Diagnosed with an ED at 14, Dr. McNaught has experienced this firsthand and shared her story in a 2020 memoir, Life Hurts: A Doctor’s Personal Journey Through Anorexia.

Competitive, high-stress environments can also be a trigger, Dr. McNaught explained. “The pressure of medical school,” for example, “can perpetuate an eating disorder if that’s something that you’re struggling with,” she said.

Pressure to perform may not be the only problem. Medical students are taught to view weight as a key indicator of health. Multiple studies suggested that not only does weight stigma exist in healthcare but also it has increased over time and negatively affects patients’ psychological well-being and physical health.

There is far less public discourse about how weight stigma can be harmful to medical students and physicians themselves. Dr. Williams believed the weight-centric paradigm was key.

“For so long, we believed that health presents itself within these confines on a BMI chart and anything outside of that is unhealthy and must be fixed,” she said. “I can say from having gone through medical education, having that continual messaging does make someone feel that if I myself am not within those confines, then I need to do something to fix that immediately if I’m going to continue to care for patients.”

In general, Dr. Williams, and Dr. McNaught agreed that medical training around EDs is lacking, producing doctors who are ill-equipped to diagnose, treat, or even discuss them with patients. Dr. Williams recalled only one lecture on the topic in med school.

“And yet, anorexia carries the second highest death rate of all mental illnesses after opioid-use disorders,” she said, “so it’s astonishing that that just wasn’t included.”

MDs Hiding Mental Health Issues

Claire Anderson, MD (a pseudonym), emphatically stated she would never tell anyone at the hospital where she works in the emergency department that she has an ED.

“There is still a lot of misunderstanding about mental health, and I never want people to doubt my ability to care for people,” Dr. Anderson said. “There’s so much stigma around eating disorders, and I also feel like once it’s out there, I can’t take it back, and I don’t want to feel like people are watching me.”

Melissa Klein, PhD, a clinical psychologist specializing in EDs, has more than 25 years of experience working the inpatient ED unit at New York Presbyterian. Having treated medical professionals, Dr. Klein said they have legitimate concerns about revealing their struggles.

“Sometimes, they do get reported to higher ups — the boards,” Dr. Klein said, “and they’re told that they have to get help in order for them to continue to work in their profession. I think people might be scared to ask for help because of that reason.”

Doctors Often Ignore EDs or Teach ‘Bad Habits’

Dr. Anderson firmly believed that if her early treatment from doctors had been better, she might not be struggling so much today.

The first time Dr. Anderson’s mother brought up her daughter’s sudden weight loss at 14, their family doctor conferred with a chart and said there was no reason to worry; Dr. Anderson’s weight was “normal.” “I was eating like 500 calories a day and swimming for 3 hours, and [by saying that], they assured me I was fine,” she recalls.

At 15, when Dr. Anderson went in for an initial assessment for an ED, she thought she’d be connected with a nutritionist and sent home. “I didn’t have a lot of classic thoughts of wanting to be thin or wanting to lose weight,” she said.

Instead, Dr. Anderson was sent to inpatient care, which she credits with escalating her ED. “I picked up on a lot of really bad habits when I went there — I sort of learned how to have an eating disorder,” she said. “When I left, it was very different than when I went in, which is kind of sad.”

Throughout high school, Dr. Anderson went in and out of so many hospitals and treatment programs that she’s lost track of them. Then, in 2008, she left formal treatment altogether. “I had been really angry with the treatment programs for trying to fit me into their box with a rigid schedule of inpatient and outpatient care,” she recalled. “I didn’t want to live in that world anymore.”

After working with a new psychiatrist, Dr. Anderson’s situation improved until a particularly stressful second year of residency. “That’s when I just tanked,” she said. “Residency, and especially being on my own and with COVID, things have not been great for me.”

Dr. Anderson now sees an eating disorder specialist, but she pays for this out-of-pocket. “I have terrible insurance,” she said with a laugh, aware of that irony.

If You Are Struggling, Don’t Be Ashamed

Some physicians who’ve experienced EDs firsthand are working to improve training on diagnosing and treating the conditions. Dr. McNaught has developed and launched a new eLearning program for healthcare workers on how to recognize the early signs and symptoms of an ED and provide support.

“It’s not only so they can recognize it in their patients but also if colleagues and family and friends are struggling,” she said.

In 2021, the American Psychiatric Association (APA) approved the APA Practice Guideline for the Treatment of Patients With Eating Disorders, which aims to improve patient care and treatment outcomes.

But Dr. Klein is concerned that increased stress since the COVID-19 pandemic may be putting healthcare workers at even greater risk.

“When people are under stress or when they feel like there are things in their life that maybe they can’t control, sometimes turning to an eating disorder is a way to cope,” she said, “In that sense, the stress on medical professionals is something that could lead to eating disorder behaviors.”

Dr. Klein’s message to healthcare workers: Don’t be ashamed. She described an ED as “a monster that takes over your brain. Once it starts, it’s very hard to turn it around on your own. So, I hope anyone who is suffering, in whatever field they’re in, that they are able to ask for help.”

A version of this article appeared on Medscape.com.

Ten years ago, Clare Gerada, FRCGP, an advocate for physician well-being and today president of the UK’s Royal College of General Practitioners, made a prediction to the audience at the International Conference on Physician Health.

“We have seen a massive increase in eating disorders [among doctors],” she said. “I’m not sure anybody is quite aware of the tsunami of eating disorders,” she believed would soon strike predominantly female physicians.

That was 2014. Did the tsunami hit?

Quite possibly. Data are limited on the prevalence of eating disorders (EDs) among healthcare workers, but studies do exist. A 2019 global review and meta-analysis determined “the summary prevalence of eating disorder (ED) risk among medical students was 10.4%.”

A 2022 update of that review boosted the estimate to 17.35%.

Tsunami or not, that’s nearly double the 9% rate within the US general public (from a 2020 report from STRIPED and the Academy of Eating Disorders). And while the following stat isn’t an indicator of EDs per se, 19% of doctors admit to unhealthy eating habits, according to a recent Medscape Medical News physician survey.

To her credit, Dr. Gerada, awarded a damehood in 2020, was in a position to know what was coming. Her statement was informed by research showing an increasing number of young doctors seeking treatment for mental health issues, including EDs, through the NHS Practitioner Health program, a mental health service she established in 2008.

So ... what puts doctors at such a high risk for EDs?

Be Careful of ‘Overlap Traits’

As with many mental health issues, EDs have no single cause. Researchers believe they stem from a complex interaction of genetic, biological, behavioral, psychological, and social factors. But the medical field should take note: Some personality traits commonly associated with EDs are often shared by successful physicians.

“I think some of the overlap traits would be being highly driven, goal-oriented and self-critical,” said Lesley Williams, MD, a family medicine physician at the Mayo Clinic in Phoenix, Arizona. “A lot of those traits can make you a very successful physician and physician-in-training but could also potentially spill over into body image and rigidity around food.”

Of course, we want physicians to strive for excellence, and the majority of diligent, driven doctors will not develop an ED.

But when pushed too far, those admirable qualities can easily become perfectionism — which has long been recognized as a risk factor for EDs, an association supported by decades of research.

Medical School: Where EDs Begin and Little Education About Them Happens

“I think medicine in general attracts people that often share similar characteristics to those who struggle with EDs — high-achieving, hardworking perfectionists who put a lot of pressure on themselves,” said Elizabeth McNaught, MD, a general practitioner and medical director at Family Mental Wealth.

Diagnosed with an ED at 14, Dr. McNaught has experienced this firsthand and shared her story in a 2020 memoir, Life Hurts: A Doctor’s Personal Journey Through Anorexia.

Competitive, high-stress environments can also be a trigger, Dr. McNaught explained. “The pressure of medical school,” for example, “can perpetuate an eating disorder if that’s something that you’re struggling with,” she said.

Pressure to perform may not be the only problem. Medical students are taught to view weight as a key indicator of health. Multiple studies suggested that not only does weight stigma exist in healthcare but also it has increased over time and negatively affects patients’ psychological well-being and physical health.

There is far less public discourse about how weight stigma can be harmful to medical students and physicians themselves. Dr. Williams believed the weight-centric paradigm was key.

“For so long, we believed that health presents itself within these confines on a BMI chart and anything outside of that is unhealthy and must be fixed,” she said. “I can say from having gone through medical education, having that continual messaging does make someone feel that if I myself am not within those confines, then I need to do something to fix that immediately if I’m going to continue to care for patients.”

In general, Dr. Williams, and Dr. McNaught agreed that medical training around EDs is lacking, producing doctors who are ill-equipped to diagnose, treat, or even discuss them with patients. Dr. Williams recalled only one lecture on the topic in med school.

“And yet, anorexia carries the second highest death rate of all mental illnesses after opioid-use disorders,” she said, “so it’s astonishing that that just wasn’t included.”

MDs Hiding Mental Health Issues

Claire Anderson, MD (a pseudonym), emphatically stated she would never tell anyone at the hospital where she works in the emergency department that she has an ED.

“There is still a lot of misunderstanding about mental health, and I never want people to doubt my ability to care for people,” Dr. Anderson said. “There’s so much stigma around eating disorders, and I also feel like once it’s out there, I can’t take it back, and I don’t want to feel like people are watching me.”

Melissa Klein, PhD, a clinical psychologist specializing in EDs, has more than 25 years of experience working the inpatient ED unit at New York Presbyterian. Having treated medical professionals, Dr. Klein said they have legitimate concerns about revealing their struggles.

“Sometimes, they do get reported to higher ups — the boards,” Dr. Klein said, “and they’re told that they have to get help in order for them to continue to work in their profession. I think people might be scared to ask for help because of that reason.”

Doctors Often Ignore EDs or Teach ‘Bad Habits’

Dr. Anderson firmly believed that if her early treatment from doctors had been better, she might not be struggling so much today.

The first time Dr. Anderson’s mother brought up her daughter’s sudden weight loss at 14, their family doctor conferred with a chart and said there was no reason to worry; Dr. Anderson’s weight was “normal.” “I was eating like 500 calories a day and swimming for 3 hours, and [by saying that], they assured me I was fine,” she recalls.

At 15, when Dr. Anderson went in for an initial assessment for an ED, she thought she’d be connected with a nutritionist and sent home. “I didn’t have a lot of classic thoughts of wanting to be thin or wanting to lose weight,” she said.

Instead, Dr. Anderson was sent to inpatient care, which she credits with escalating her ED. “I picked up on a lot of really bad habits when I went there — I sort of learned how to have an eating disorder,” she said. “When I left, it was very different than when I went in, which is kind of sad.”

Throughout high school, Dr. Anderson went in and out of so many hospitals and treatment programs that she’s lost track of them. Then, in 2008, she left formal treatment altogether. “I had been really angry with the treatment programs for trying to fit me into their box with a rigid schedule of inpatient and outpatient care,” she recalled. “I didn’t want to live in that world anymore.”

After working with a new psychiatrist, Dr. Anderson’s situation improved until a particularly stressful second year of residency. “That’s when I just tanked,” she said. “Residency, and especially being on my own and with COVID, things have not been great for me.”

Dr. Anderson now sees an eating disorder specialist, but she pays for this out-of-pocket. “I have terrible insurance,” she said with a laugh, aware of that irony.

If You Are Struggling, Don’t Be Ashamed

Some physicians who’ve experienced EDs firsthand are working to improve training on diagnosing and treating the conditions. Dr. McNaught has developed and launched a new eLearning program for healthcare workers on how to recognize the early signs and symptoms of an ED and provide support.

“It’s not only so they can recognize it in their patients but also if colleagues and family and friends are struggling,” she said.

In 2021, the American Psychiatric Association (APA) approved the APA Practice Guideline for the Treatment of Patients With Eating Disorders, which aims to improve patient care and treatment outcomes.

But Dr. Klein is concerned that increased stress since the COVID-19 pandemic may be putting healthcare workers at even greater risk.

“When people are under stress or when they feel like there are things in their life that maybe they can’t control, sometimes turning to an eating disorder is a way to cope,” she said, “In that sense, the stress on medical professionals is something that could lead to eating disorder behaviors.”

Dr. Klein’s message to healthcare workers: Don’t be ashamed. She described an ED as “a monster that takes over your brain. Once it starts, it’s very hard to turn it around on your own. So, I hope anyone who is suffering, in whatever field they’re in, that they are able to ask for help.”

A version of this article appeared on Medscape.com.

Ten years ago, Clare Gerada, FRCGP, an advocate for physician well-being and today president of the UK’s Royal College of General Practitioners, made a prediction to the audience at the International Conference on Physician Health.

“We have seen a massive increase in eating disorders [among doctors],” she said. “I’m not sure anybody is quite aware of the tsunami of eating disorders,” she believed would soon strike predominantly female physicians.

That was 2014. Did the tsunami hit?

Quite possibly. Data are limited on the prevalence of eating disorders (EDs) among healthcare workers, but studies do exist. A 2019 global review and meta-analysis determined “the summary prevalence of eating disorder (ED) risk among medical students was 10.4%.”

A 2022 update of that review boosted the estimate to 17.35%.

Tsunami or not, that’s nearly double the 9% rate within the US general public (from a 2020 report from STRIPED and the Academy of Eating Disorders). And while the following stat isn’t an indicator of EDs per se, 19% of doctors admit to unhealthy eating habits, according to a recent Medscape Medical News physician survey.

To her credit, Dr. Gerada, awarded a damehood in 2020, was in a position to know what was coming. Her statement was informed by research showing an increasing number of young doctors seeking treatment for mental health issues, including EDs, through the NHS Practitioner Health program, a mental health service she established in 2008.

So ... what puts doctors at such a high risk for EDs?

Be Careful of ‘Overlap Traits’

As with many mental health issues, EDs have no single cause. Researchers believe they stem from a complex interaction of genetic, biological, behavioral, psychological, and social factors. But the medical field should take note: Some personality traits commonly associated with EDs are often shared by successful physicians.

“I think some of the overlap traits would be being highly driven, goal-oriented and self-critical,” said Lesley Williams, MD, a family medicine physician at the Mayo Clinic in Phoenix, Arizona. “A lot of those traits can make you a very successful physician and physician-in-training but could also potentially spill over into body image and rigidity around food.”

Of course, we want physicians to strive for excellence, and the majority of diligent, driven doctors will not develop an ED.

But when pushed too far, those admirable qualities can easily become perfectionism — which has long been recognized as a risk factor for EDs, an association supported by decades of research.

Medical School: Where EDs Begin and Little Education About Them Happens

“I think medicine in general attracts people that often share similar characteristics to those who struggle with EDs — high-achieving, hardworking perfectionists who put a lot of pressure on themselves,” said Elizabeth McNaught, MD, a general practitioner and medical director at Family Mental Wealth.

Diagnosed with an ED at 14, Dr. McNaught has experienced this firsthand and shared her story in a 2020 memoir, Life Hurts: A Doctor’s Personal Journey Through Anorexia.

Competitive, high-stress environments can also be a trigger, Dr. McNaught explained. “The pressure of medical school,” for example, “can perpetuate an eating disorder if that’s something that you’re struggling with,” she said.

Pressure to perform may not be the only problem. Medical students are taught to view weight as a key indicator of health. Multiple studies suggested that not only does weight stigma exist in healthcare but also it has increased over time and negatively affects patients’ psychological well-being and physical health.

There is far less public discourse about how weight stigma can be harmful to medical students and physicians themselves. Dr. Williams believed the weight-centric paradigm was key.

“For so long, we believed that health presents itself within these confines on a BMI chart and anything outside of that is unhealthy and must be fixed,” she said. “I can say from having gone through medical education, having that continual messaging does make someone feel that if I myself am not within those confines, then I need to do something to fix that immediately if I’m going to continue to care for patients.”

In general, Dr. Williams, and Dr. McNaught agreed that medical training around EDs is lacking, producing doctors who are ill-equipped to diagnose, treat, or even discuss them with patients. Dr. Williams recalled only one lecture on the topic in med school.

“And yet, anorexia carries the second highest death rate of all mental illnesses after opioid-use disorders,” she said, “so it’s astonishing that that just wasn’t included.”

MDs Hiding Mental Health Issues

Claire Anderson, MD (a pseudonym), emphatically stated she would never tell anyone at the hospital where she works in the emergency department that she has an ED.

“There is still a lot of misunderstanding about mental health, and I never want people to doubt my ability to care for people,” Dr. Anderson said. “There’s so much stigma around eating disorders, and I also feel like once it’s out there, I can’t take it back, and I don’t want to feel like people are watching me.”

Melissa Klein, PhD, a clinical psychologist specializing in EDs, has more than 25 years of experience working the inpatient ED unit at New York Presbyterian. Having treated medical professionals, Dr. Klein said they have legitimate concerns about revealing their struggles.

“Sometimes, they do get reported to higher ups — the boards,” Dr. Klein said, “and they’re told that they have to get help in order for them to continue to work in their profession. I think people might be scared to ask for help because of that reason.”

Doctors Often Ignore EDs or Teach ‘Bad Habits’

Dr. Anderson firmly believed that if her early treatment from doctors had been better, she might not be struggling so much today.

The first time Dr. Anderson’s mother brought up her daughter’s sudden weight loss at 14, their family doctor conferred with a chart and said there was no reason to worry; Dr. Anderson’s weight was “normal.” “I was eating like 500 calories a day and swimming for 3 hours, and [by saying that], they assured me I was fine,” she recalls.

At 15, when Dr. Anderson went in for an initial assessment for an ED, she thought she’d be connected with a nutritionist and sent home. “I didn’t have a lot of classic thoughts of wanting to be thin or wanting to lose weight,” she said.

Instead, Dr. Anderson was sent to inpatient care, which she credits with escalating her ED. “I picked up on a lot of really bad habits when I went there — I sort of learned how to have an eating disorder,” she said. “When I left, it was very different than when I went in, which is kind of sad.”

Throughout high school, Dr. Anderson went in and out of so many hospitals and treatment programs that she’s lost track of them. Then, in 2008, she left formal treatment altogether. “I had been really angry with the treatment programs for trying to fit me into their box with a rigid schedule of inpatient and outpatient care,” she recalled. “I didn’t want to live in that world anymore.”

After working with a new psychiatrist, Dr. Anderson’s situation improved until a particularly stressful second year of residency. “That’s when I just tanked,” she said. “Residency, and especially being on my own and with COVID, things have not been great for me.”

Dr. Anderson now sees an eating disorder specialist, but she pays for this out-of-pocket. “I have terrible insurance,” she said with a laugh, aware of that irony.

If You Are Struggling, Don’t Be Ashamed

Some physicians who’ve experienced EDs firsthand are working to improve training on diagnosing and treating the conditions. Dr. McNaught has developed and launched a new eLearning program for healthcare workers on how to recognize the early signs and symptoms of an ED and provide support.

“It’s not only so they can recognize it in their patients but also if colleagues and family and friends are struggling,” she said.

In 2021, the American Psychiatric Association (APA) approved the APA Practice Guideline for the Treatment of Patients With Eating Disorders, which aims to improve patient care and treatment outcomes.

But Dr. Klein is concerned that increased stress since the COVID-19 pandemic may be putting healthcare workers at even greater risk.

“When people are under stress or when they feel like there are things in their life that maybe they can’t control, sometimes turning to an eating disorder is a way to cope,” she said, “In that sense, the stress on medical professionals is something that could lead to eating disorder behaviors.”

Dr. Klein’s message to healthcare workers: Don’t be ashamed. She described an ED as “a monster that takes over your brain. Once it starts, it’s very hard to turn it around on your own. So, I hope anyone who is suffering, in whatever field they’re in, that they are able to ask for help.”

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

Use of oral amoxicillin-clavulanic acid for 5 days was noninferior to a 10-day course of treatment among children with noncomplicated febrile urinary tract infections (UTIs), according to new research.

Well-appearing children with febrile UTIs are generally treated with a 10-day course of oral antibiotics, but the effectiveness of a 5-day course has not been evaluated, wrote Giovanni Montini, MD, of the University of Milan, Milan, Italy, and colleagues.

Robert W. Frenck Jr, MD, a director of the Center for Vaccine Research at Cincinnati Children’s Hospital Medical Center, Ohio, said he was not surprised that the shorter course was sufficient to treat these cases. The antibiotic concentration in the urine often significantly exceeds the levels in the blood, he said.

Dr. Frenck, who was not involved in the study, said that he saw no real barriers to the use of a shorter course of therapy in clinical practice.

“I think both parents and the medical team would be happy to be able to use a shorter course of therapy,” he said.

In the study published in Pediatrics , researchers randomized 142 children aged 3 months to 5 years with uncomplicated febrile UTIs to 50 mg/kg/d of amoxicillin-clavulanate for either the short or standard period. The study took place at eight pediatric emergency departments in Italy between May 2020 and September 2022. All patients received prescriptions for 5 days of antibiotics, and those randomized to the standard course received a second prescription after randomization.

The primary endpoint was recurrence of the UTI within 30 days of completion of therapy. Secondary endpoints included clinical recovery at the end of treatment, adverse events related to the therapy, and signs of antibiotic resistance.

The UTI recurrence rate within 30 days of treatment completion was 2.8% in the short-course group and 14.3% in the standard group. A post hoc analysis excluding patients with vesicoureteral reflux and non–Escherichia coli UTIs further confirmed the noninferiority of short-course treatment.

“It is a bit surprising that the short-course group had fewer relapses within 30 days of discontinuing antibiotics,” Dr. Frenck said. “However, the differences may be due to small sample sizes and do not appear to be statistically significant differences in recurrence rates.”

Resolution of symptoms was similar between the short-course and standard groups (97.2% and 92.9%, respectively), and indications of antibiotic resistance were similar between the groups. No adverse events were reported in the standard group, and one case of diarrhea occurred in the short-course group.

The findings were limited by the study’s unblinded randomization, so parents were aware of the trial and were potentially sensitized to look for signs of infection. Researchers also relied on parent reports of adverse drug effects rather than through a standardized questionnaire, the researchers noted.

Dr. Frenck said a potential benefit to shortening treatment is that adherence usually increases.

“But you only want to decrease the length of a course of medicine if you can do so without compromising the effectiveness of the treatment,” Dr. Frenck said.

Dr. Frenck also noted a recent study, which demonstrated that 5 days of antibiotics had equivalent efficacy as 10 days for uncomplicated pneumonia.

“The current paper further demonstrates that shorter courses of antibiotics may be possible for other mild forms of infections.”

Looking ahead, researchers could evaluate the use of short-course antibiotics for other common infections such as otitis media, he noted.

The study was supported by the Ministry of Health, Rome, Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. The researchers report no financial conflicts. Dr. Frenck disclosed conducting clinical trials for Pfizer, Moderna, AstraZeneca, Merck, and GSK; none of those trials were for antibiotics or urinary tract infections.

A version of this article appeared on Medscape.com.

Use of oral amoxicillin-clavulanic acid for 5 days was noninferior to a 10-day course of treatment among children with noncomplicated febrile urinary tract infections (UTIs), according to new research.

Well-appearing children with febrile UTIs are generally treated with a 10-day course of oral antibiotics, but the effectiveness of a 5-day course has not been evaluated, wrote Giovanni Montini, MD, of the University of Milan, Milan, Italy, and colleagues.

Robert W. Frenck Jr, MD, a director of the Center for Vaccine Research at Cincinnati Children’s Hospital Medical Center, Ohio, said he was not surprised that the shorter course was sufficient to treat these cases. The antibiotic concentration in the urine often significantly exceeds the levels in the blood, he said.

Dr. Frenck, who was not involved in the study, said that he saw no real barriers to the use of a shorter course of therapy in clinical practice.

“I think both parents and the medical team would be happy to be able to use a shorter course of therapy,” he said.

In the study published in Pediatrics , researchers randomized 142 children aged 3 months to 5 years with uncomplicated febrile UTIs to 50 mg/kg/d of amoxicillin-clavulanate for either the short or standard period. The study took place at eight pediatric emergency departments in Italy between May 2020 and September 2022. All patients received prescriptions for 5 days of antibiotics, and those randomized to the standard course received a second prescription after randomization.

The primary endpoint was recurrence of the UTI within 30 days of completion of therapy. Secondary endpoints included clinical recovery at the end of treatment, adverse events related to the therapy, and signs of antibiotic resistance.

The UTI recurrence rate within 30 days of treatment completion was 2.8% in the short-course group and 14.3% in the standard group. A post hoc analysis excluding patients with vesicoureteral reflux and non–Escherichia coli UTIs further confirmed the noninferiority of short-course treatment.

“It is a bit surprising that the short-course group had fewer relapses within 30 days of discontinuing antibiotics,” Dr. Frenck said. “However, the differences may be due to small sample sizes and do not appear to be statistically significant differences in recurrence rates.”

Resolution of symptoms was similar between the short-course and standard groups (97.2% and 92.9%, respectively), and indications of antibiotic resistance were similar between the groups. No adverse events were reported in the standard group, and one case of diarrhea occurred in the short-course group.

The findings were limited by the study’s unblinded randomization, so parents were aware of the trial and were potentially sensitized to look for signs of infection. Researchers also relied on parent reports of adverse drug effects rather than through a standardized questionnaire, the researchers noted.

Dr. Frenck said a potential benefit to shortening treatment is that adherence usually increases.

“But you only want to decrease the length of a course of medicine if you can do so without compromising the effectiveness of the treatment,” Dr. Frenck said.

Dr. Frenck also noted a recent study, which demonstrated that 5 days of antibiotics had equivalent efficacy as 10 days for uncomplicated pneumonia.

“The current paper further demonstrates that shorter courses of antibiotics may be possible for other mild forms of infections.”

Looking ahead, researchers could evaluate the use of short-course antibiotics for other common infections such as otitis media, he noted.

The study was supported by the Ministry of Health, Rome, Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. The researchers report no financial conflicts. Dr. Frenck disclosed conducting clinical trials for Pfizer, Moderna, AstraZeneca, Merck, and GSK; none of those trials were for antibiotics or urinary tract infections.

A version of this article appeared on Medscape.com.

Use of oral amoxicillin-clavulanic acid for 5 days was noninferior to a 10-day course of treatment among children with noncomplicated febrile urinary tract infections (UTIs), according to new research.

Well-appearing children with febrile UTIs are generally treated with a 10-day course of oral antibiotics, but the effectiveness of a 5-day course has not been evaluated, wrote Giovanni Montini, MD, of the University of Milan, Milan, Italy, and colleagues.

Robert W. Frenck Jr, MD, a director of the Center for Vaccine Research at Cincinnati Children’s Hospital Medical Center, Ohio, said he was not surprised that the shorter course was sufficient to treat these cases. The antibiotic concentration in the urine often significantly exceeds the levels in the blood, he said.

Dr. Frenck, who was not involved in the study, said that he saw no real barriers to the use of a shorter course of therapy in clinical practice.

“I think both parents and the medical team would be happy to be able to use a shorter course of therapy,” he said.

In the study published in Pediatrics , researchers randomized 142 children aged 3 months to 5 years with uncomplicated febrile UTIs to 50 mg/kg/d of amoxicillin-clavulanate for either the short or standard period. The study took place at eight pediatric emergency departments in Italy between May 2020 and September 2022. All patients received prescriptions for 5 days of antibiotics, and those randomized to the standard course received a second prescription after randomization.

The primary endpoint was recurrence of the UTI within 30 days of completion of therapy. Secondary endpoints included clinical recovery at the end of treatment, adverse events related to the therapy, and signs of antibiotic resistance.

The UTI recurrence rate within 30 days of treatment completion was 2.8% in the short-course group and 14.3% in the standard group. A post hoc analysis excluding patients with vesicoureteral reflux and non–Escherichia coli UTIs further confirmed the noninferiority of short-course treatment.

“It is a bit surprising that the short-course group had fewer relapses within 30 days of discontinuing antibiotics,” Dr. Frenck said. “However, the differences may be due to small sample sizes and do not appear to be statistically significant differences in recurrence rates.”

Resolution of symptoms was similar between the short-course and standard groups (97.2% and 92.9%, respectively), and indications of antibiotic resistance were similar between the groups. No adverse events were reported in the standard group, and one case of diarrhea occurred in the short-course group.

The findings were limited by the study’s unblinded randomization, so parents were aware of the trial and were potentially sensitized to look for signs of infection. Researchers also relied on parent reports of adverse drug effects rather than through a standardized questionnaire, the researchers noted.

Dr. Frenck said a potential benefit to shortening treatment is that adherence usually increases.

“But you only want to decrease the length of a course of medicine if you can do so without compromising the effectiveness of the treatment,” Dr. Frenck said.

Dr. Frenck also noted a recent study, which demonstrated that 5 days of antibiotics had equivalent efficacy as 10 days for uncomplicated pneumonia.

“The current paper further demonstrates that shorter courses of antibiotics may be possible for other mild forms of infections.”

Looking ahead, researchers could evaluate the use of short-course antibiotics for other common infections such as otitis media, he noted.

The study was supported by the Ministry of Health, Rome, Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. The researchers report no financial conflicts. Dr. Frenck disclosed conducting clinical trials for Pfizer, Moderna, AstraZeneca, Merck, and GSK; none of those trials were for antibiotics or urinary tract infections.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

To the Editor:

Treatment of cancer, including cutaneous malignancy, has been transformed by the use of immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte-associated antigen 4, programmed cell-death protein 1 (PD-1), or programmed cell-death ligand 1 (PD-L1). However, these drugs are associated with a distinct set of immune-related adverse events (IRAEs). We present a case of generalized eruptive keratoacanthoma of Grzybowski associated with the ICI cemiplimab.

A 94-year-old White woman presented to the dermatology clinic with acute onset of extensive, locally advanced cutaneous squamous cell carcinoma (cSCC) of the upper right posterolateral calf as well as multiple noninvasive cSCCs of the arms and legs. Her medical history was remarkable for widespread actinic keratoses and numerous cSCCs. The patient had no personal or family history of melanoma. Various cSCCs had required treatment with electrodesiccation and curettage, topical or intralesional 5-fluorouracil, and Mohs micrographic surgery. Approximately 1 year prior to presentation, oral acitretin was initiated to help control the cSCC. Given the extent of locally advanced disease, which was considered unresectable, she was referred to oncology but continued to follow up with dermatology. Positron emission tomography was remarkable for hypermetabolic cutaneous thickening in the upper right posterolateral calf with no evidence of visceral disease.

The patient was started on cemiplimab, an anti-PD-1 monoclonal antibody ICI indicated for the treatment of both metastatic and advanced cSCC. After 4 cycles of intravenous cemiplimab, the patient developed widespread nodules covering the arms and legs (Figure 1) as well as associated tenderness and pruritus. Biopsies of nodules revealed superficially invasive, well-differentiated cSCC consistent with keratoacanthoma. Although a lymphocytic infiltrate was present, no other specific reaction pattern, such as a lichenoid infiltrate, was present (Figure 2).

Positron emission tomography was repeated, demonstrating resolution of the right calf lesion; however, new diffuse cutaneous lesions and inguinal lymph node involvement were present, again without evidence of visceral disease. Given the clinical and histologic findings, a diagnosis of generalized eruptive keratoacanthoma of Grzybowski was made. Cemiplimab was discontinued after the fifth cycle. The patient declined further systemic treatment, instead choosing a regimen of topical steroids and an emollient. 

Immunotherapeutics have transformed cancer therapy, which includes ICIs that target cytotoxic T lymphocyte-associated antigen 4, PD-1, or PD-L1. Increased activity of these checkpoints allows tumor cells to downregulate T-cell activation, thereby evading immune destruction. When PD-1 on T cells binds PD-L1 on tumor cells, T lymphocytes are inhibited from cytotoxic-mediated killing. Therefore, anti-PD-1 ICIs such as cemiplimab permit T-lymphocyte activation and destruction of malignant cells. However, this unique mechanism of immunotherapy is associated with an array of IRAEs, which often manifest in a delayed and prolonged fashion.¹ Immune-related adverse events most commonly affect the gastrointestinal tract as well as the endocrine and dermatologic systems.² Notably, patients with certain tumors who experience these adverse effects might be more likely to have superior overall survival; therefore, IRAEs are sometimes used as an indicator of favorable treatment response.^2,3

Dermatologic IRAEs associated with the use of a PD-1 inhibitor include lichenoid reactions, pruritus, morbilliform eruptions, vitiligo, and bullous pemphigoid.^4,5 Eruptions of keratoacanthoma rarely have been reported following treatment with the PD-1 inhibitors nivolumab and pembrolizumab.^3,6,7 In our patient, we believe the profound and generalized eruptive keratoacanthoma—a well-differentiated cSCC variant—was related to treatment of locally advanced cSCC with cemiplimab. The mechanism underlying the formation of anti-PD-1 eruptive keratoacanthoma is not well understood. In susceptible patients, it is plausible that the inflammatory environment permitted by ICIs paradoxically induces regression of tumors such as locally invasive cSCC and simultaneously promotes formation of keratoacanthoma.

The role of inflammation in the pathogenesis and progression of cSCC is complex and possibly involves contrasting roles of leukocyte subpopulations.⁸ The increased incidence of cSCC in the immunocompromised population,⁸ PD-L1 overexpression in cSCC,^9,10 and successful treatment of cSCC with PD-1 inhibition¹⁰ all suggest that inhibition of specific inflammatory pathways is pivotal in tumor pathogenesis. However, increased inflammation, particularly inflammation driven by T lymphocytes and Langerhans cells, also is believed to play a key role in the formation of cSCCs, including the degeneration of actinic keratosis into cSCC. Moreover, because keratoacanthomas are believed to be a cSCC variant and also are associated with PD-L1 overexpression,⁹ it is perplexing that PD-1 blockade may result in eruptive keratoacanthoma in some patients while also treating locally advanced cSCC, as seen in our patient. Successful treatment of keratoacanthoma with anti-inflammatory intralesional or topical corticosteroids adds to this complicated picture.³

We hypothesize that the pathogenesis of invasive cSCC and keratoacanthoma shares certain immune-mediated mechanisms but also differs in distinct manners. To understand the relationship between systemic treatment of cSCC and eruptive keratoacanthoma, further research is required.

In addition, the RAS/BRAF/MEK oncogenic pathway may be involved in the development of cSCCs associated with anti-PD-1. It is hypothesized that BRAF and MEK inhibition increases T-cell infiltration and increases PD-L1 expression on tumor cells,¹¹ thus increasing the susceptibility of those cells to PD-1 blockade. Further supporting a relationship between the RAS/BRAF/MEK and PD-1 pathways, BRAF inhibitors are associated with development of SCCs and verrucal keratosis by upregulation of the RAS pathway.^12,13 Perhaps a common mechanism underlying these pathways results in their shared association for an increased risk for cSCC upon blockade. More research is needed to fully elucidate the underlying biochemical mechanism of immunotherapy and formation of SCCs, such as keratoacanthoma. 

Treatment of solitary keratoacanthoma often involves surgical excision; however, the sheer number of lesions in eruptive keratoacanthoma presents a larger dilemma. Because oral systemic retinoids have been shown to be most effective for treating eruptive keratoacanthoma, they are considered first-line therapy as monotherapy or in combination with surgical excision.³ Other treatment options include intralesional or topical corticosteroids, cyclosporine, 5-fluorouracil, imiquimod, and cryotherapy.^3,6

The development of ICIs has revolutionized the treatment of cutaneous malignancy, yet we have a great deal more to comprehend on the systemic effects of these medications. Although IRAEs may signal a better response to therapy, some of these effects regrettably can be dose limiting. In our patient, cemiplimab was successful in treating locally advanced cSCC, but treatment also resulted in devastating widespread eruptive keratoacanthoma. The mechanism of this kind of eruption has yet to be understood; we hypothesize that it likely involves T lymphocyte–driven inflammation and the interplay of molecular and immune-mediated pathways.

To the Editor:

Treatment of cancer, including cutaneous malignancy, has been transformed by the use of immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte-associated antigen 4, programmed cell-death protein 1 (PD-1), or programmed cell-death ligand 1 (PD-L1). However, these drugs are associated with a distinct set of immune-related adverse events (IRAEs). We present a case of generalized eruptive keratoacanthoma of Grzybowski associated with the ICI cemiplimab.

A 94-year-old White woman presented to the dermatology clinic with acute onset of extensive, locally advanced cutaneous squamous cell carcinoma (cSCC) of the upper right posterolateral calf as well as multiple noninvasive cSCCs of the arms and legs. Her medical history was remarkable for widespread actinic keratoses and numerous cSCCs. The patient had no personal or family history of melanoma. Various cSCCs had required treatment with electrodesiccation and curettage, topical or intralesional 5-fluorouracil, and Mohs micrographic surgery. Approximately 1 year prior to presentation, oral acitretin was initiated to help control the cSCC. Given the extent of locally advanced disease, which was considered unresectable, she was referred to oncology but continued to follow up with dermatology. Positron emission tomography was remarkable for hypermetabolic cutaneous thickening in the upper right posterolateral calf with no evidence of visceral disease.

The patient was started on cemiplimab, an anti-PD-1 monoclonal antibody ICI indicated for the treatment of both metastatic and advanced cSCC. After 4 cycles of intravenous cemiplimab, the patient developed widespread nodules covering the arms and legs (Figure 1) as well as associated tenderness and pruritus. Biopsies of nodules revealed superficially invasive, well-differentiated cSCC consistent with keratoacanthoma. Although a lymphocytic infiltrate was present, no other specific reaction pattern, such as a lichenoid infiltrate, was present (Figure 2).

Positron emission tomography was repeated, demonstrating resolution of the right calf lesion; however, new diffuse cutaneous lesions and inguinal lymph node involvement were present, again without evidence of visceral disease. Given the clinical and histologic findings, a diagnosis of generalized eruptive keratoacanthoma of Grzybowski was made. Cemiplimab was discontinued after the fifth cycle. The patient declined further systemic treatment, instead choosing a regimen of topical steroids and an emollient. 

Immunotherapeutics have transformed cancer therapy, which includes ICIs that target cytotoxic T lymphocyte-associated antigen 4, PD-1, or PD-L1. Increased activity of these checkpoints allows tumor cells to downregulate T-cell activation, thereby evading immune destruction. When PD-1 on T cells binds PD-L1 on tumor cells, T lymphocytes are inhibited from cytotoxic-mediated killing. Therefore, anti-PD-1 ICIs such as cemiplimab permit T-lymphocyte activation and destruction of malignant cells. However, this unique mechanism of immunotherapy is associated with an array of IRAEs, which often manifest in a delayed and prolonged fashion.¹ Immune-related adverse events most commonly affect the gastrointestinal tract as well as the endocrine and dermatologic systems.² Notably, patients with certain tumors who experience these adverse effects might be more likely to have superior overall survival; therefore, IRAEs are sometimes used as an indicator of favorable treatment response.^2,3

Dermatologic IRAEs associated with the use of a PD-1 inhibitor include lichenoid reactions, pruritus, morbilliform eruptions, vitiligo, and bullous pemphigoid.^4,5 Eruptions of keratoacanthoma rarely have been reported following treatment with the PD-1 inhibitors nivolumab and pembrolizumab.^3,6,7 In our patient, we believe the profound and generalized eruptive keratoacanthoma—a well-differentiated cSCC variant—was related to treatment of locally advanced cSCC with cemiplimab. The mechanism underlying the formation of anti-PD-1 eruptive keratoacanthoma is not well understood. In susceptible patients, it is plausible that the inflammatory environment permitted by ICIs paradoxically induces regression of tumors such as locally invasive cSCC and simultaneously promotes formation of keratoacanthoma.

The role of inflammation in the pathogenesis and progression of cSCC is complex and possibly involves contrasting roles of leukocyte subpopulations.⁸ The increased incidence of cSCC in the immunocompromised population,⁸ PD-L1 overexpression in cSCC,^9,10 and successful treatment of cSCC with PD-1 inhibition¹⁰ all suggest that inhibition of specific inflammatory pathways is pivotal in tumor pathogenesis. However, increased inflammation, particularly inflammation driven by T lymphocytes and Langerhans cells, also is believed to play a key role in the formation of cSCCs, including the degeneration of actinic keratosis into cSCC. Moreover, because keratoacanthomas are believed to be a cSCC variant and also are associated with PD-L1 overexpression,⁹ it is perplexing that PD-1 blockade may result in eruptive keratoacanthoma in some patients while also treating locally advanced cSCC, as seen in our patient. Successful treatment of keratoacanthoma with anti-inflammatory intralesional or topical corticosteroids adds to this complicated picture.³

We hypothesize that the pathogenesis of invasive cSCC and keratoacanthoma shares certain immune-mediated mechanisms but also differs in distinct manners. To understand the relationship between systemic treatment of cSCC and eruptive keratoacanthoma, further research is required.

In addition, the RAS/BRAF/MEK oncogenic pathway may be involved in the development of cSCCs associated with anti-PD-1. It is hypothesized that BRAF and MEK inhibition increases T-cell infiltration and increases PD-L1 expression on tumor cells,¹¹ thus increasing the susceptibility of those cells to PD-1 blockade. Further supporting a relationship between the RAS/BRAF/MEK and PD-1 pathways, BRAF inhibitors are associated with development of SCCs and verrucal keratosis by upregulation of the RAS pathway.^12,13 Perhaps a common mechanism underlying these pathways results in their shared association for an increased risk for cSCC upon blockade. More research is needed to fully elucidate the underlying biochemical mechanism of immunotherapy and formation of SCCs, such as keratoacanthoma. 

Treatment of solitary keratoacanthoma often involves surgical excision; however, the sheer number of lesions in eruptive keratoacanthoma presents a larger dilemma. Because oral systemic retinoids have been shown to be most effective for treating eruptive keratoacanthoma, they are considered first-line therapy as monotherapy or in combination with surgical excision.³ Other treatment options include intralesional or topical corticosteroids, cyclosporine, 5-fluorouracil, imiquimod, and cryotherapy.^3,6

The development of ICIs has revolutionized the treatment of cutaneous malignancy, yet we have a great deal more to comprehend on the systemic effects of these medications. Although IRAEs may signal a better response to therapy, some of these effects regrettably can be dose limiting. In our patient, cemiplimab was successful in treating locally advanced cSCC, but treatment also resulted in devastating widespread eruptive keratoacanthoma. The mechanism of this kind of eruption has yet to be understood; we hypothesize that it likely involves T lymphocyte–driven inflammation and the interplay of molecular and immune-mediated pathways.

To the Editor:

Treatment of cancer, including cutaneous malignancy, has been transformed by the use of immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte-associated antigen 4, programmed cell-death protein 1 (PD-1), or programmed cell-death ligand 1 (PD-L1). However, these drugs are associated with a distinct set of immune-related adverse events (IRAEs). We present a case of generalized eruptive keratoacanthoma of Grzybowski associated with the ICI cemiplimab.

A 94-year-old White woman presented to the dermatology clinic with acute onset of extensive, locally advanced cutaneous squamous cell carcinoma (cSCC) of the upper right posterolateral calf as well as multiple noninvasive cSCCs of the arms and legs. Her medical history was remarkable for widespread actinic keratoses and numerous cSCCs. The patient had no personal or family history of melanoma. Various cSCCs had required treatment with electrodesiccation and curettage, topical or intralesional 5-fluorouracil, and Mohs micrographic surgery. Approximately 1 year prior to presentation, oral acitretin was initiated to help control the cSCC. Given the extent of locally advanced disease, which was considered unresectable, she was referred to oncology but continued to follow up with dermatology. Positron emission tomography was remarkable for hypermetabolic cutaneous thickening in the upper right posterolateral calf with no evidence of visceral disease.

The patient was started on cemiplimab, an anti-PD-1 monoclonal antibody ICI indicated for the treatment of both metastatic and advanced cSCC. After 4 cycles of intravenous cemiplimab, the patient developed widespread nodules covering the arms and legs (Figure 1) as well as associated tenderness and pruritus. Biopsies of nodules revealed superficially invasive, well-differentiated cSCC consistent with keratoacanthoma. Although a lymphocytic infiltrate was present, no other specific reaction pattern, such as a lichenoid infiltrate, was present (Figure 2).

Positron emission tomography was repeated, demonstrating resolution of the right calf lesion; however, new diffuse cutaneous lesions and inguinal lymph node involvement were present, again without evidence of visceral disease. Given the clinical and histologic findings, a diagnosis of generalized eruptive keratoacanthoma of Grzybowski was made. Cemiplimab was discontinued after the fifth cycle. The patient declined further systemic treatment, instead choosing a regimen of topical steroids and an emollient. 

Immunotherapeutics have transformed cancer therapy, which includes ICIs that target cytotoxic T lymphocyte-associated antigen 4, PD-1, or PD-L1. Increased activity of these checkpoints allows tumor cells to downregulate T-cell activation, thereby evading immune destruction. When PD-1 on T cells binds PD-L1 on tumor cells, T lymphocytes are inhibited from cytotoxic-mediated killing. Therefore, anti-PD-1 ICIs such as cemiplimab permit T-lymphocyte activation and destruction of malignant cells. However, this unique mechanism of immunotherapy is associated with an array of IRAEs, which often manifest in a delayed and prolonged fashion.¹ Immune-related adverse events most commonly affect the gastrointestinal tract as well as the endocrine and dermatologic systems.² Notably, patients with certain tumors who experience these adverse effects might be more likely to have superior overall survival; therefore, IRAEs are sometimes used as an indicator of favorable treatment response.^2,3

Dermatologic IRAEs associated with the use of a PD-1 inhibitor include lichenoid reactions, pruritus, morbilliform eruptions, vitiligo, and bullous pemphigoid.^4,5 Eruptions of keratoacanthoma rarely have been reported following treatment with the PD-1 inhibitors nivolumab and pembrolizumab.^3,6,7 In our patient, we believe the profound and generalized eruptive keratoacanthoma—a well-differentiated cSCC variant—was related to treatment of locally advanced cSCC with cemiplimab. The mechanism underlying the formation of anti-PD-1 eruptive keratoacanthoma is not well understood. In susceptible patients, it is plausible that the inflammatory environment permitted by ICIs paradoxically induces regression of tumors such as locally invasive cSCC and simultaneously promotes formation of keratoacanthoma.

The role of inflammation in the pathogenesis and progression of cSCC is complex and possibly involves contrasting roles of leukocyte subpopulations.⁸ The increased incidence of cSCC in the immunocompromised population,⁸ PD-L1 overexpression in cSCC,^9,10 and successful treatment of cSCC with PD-1 inhibition¹⁰ all suggest that inhibition of specific inflammatory pathways is pivotal in tumor pathogenesis. However, increased inflammation, particularly inflammation driven by T lymphocytes and Langerhans cells, also is believed to play a key role in the formation of cSCCs, including the degeneration of actinic keratosis into cSCC. Moreover, because keratoacanthomas are believed to be a cSCC variant and also are associated with PD-L1 overexpression,⁹ it is perplexing that PD-1 blockade may result in eruptive keratoacanthoma in some patients while also treating locally advanced cSCC, as seen in our patient. Successful treatment of keratoacanthoma with anti-inflammatory intralesional or topical corticosteroids adds to this complicated picture.³

We hypothesize that the pathogenesis of invasive cSCC and keratoacanthoma shares certain immune-mediated mechanisms but also differs in distinct manners. To understand the relationship between systemic treatment of cSCC and eruptive keratoacanthoma, further research is required.

In addition, the RAS/BRAF/MEK oncogenic pathway may be involved in the development of cSCCs associated with anti-PD-1. It is hypothesized that BRAF and MEK inhibition increases T-cell infiltration and increases PD-L1 expression on tumor cells,¹¹ thus increasing the susceptibility of those cells to PD-1 blockade. Further supporting a relationship between the RAS/BRAF/MEK and PD-1 pathways, BRAF inhibitors are associated with development of SCCs and verrucal keratosis by upregulation of the RAS pathway.^12,13 Perhaps a common mechanism underlying these pathways results in their shared association for an increased risk for cSCC upon blockade. More research is needed to fully elucidate the underlying biochemical mechanism of immunotherapy and formation of SCCs, such as keratoacanthoma. 

Treatment of solitary keratoacanthoma often involves surgical excision; however, the sheer number of lesions in eruptive keratoacanthoma presents a larger dilemma. Because oral systemic retinoids have been shown to be most effective for treating eruptive keratoacanthoma, they are considered first-line therapy as monotherapy or in combination with surgical excision.³ Other treatment options include intralesional or topical corticosteroids, cyclosporine, 5-fluorouracil, imiquimod, and cryotherapy.^3,6

The development of ICIs has revolutionized the treatment of cutaneous malignancy, yet we have a great deal more to comprehend on the systemic effects of these medications. Although IRAEs may signal a better response to therapy, some of these effects regrettably can be dose limiting. In our patient, cemiplimab was successful in treating locally advanced cSCC, but treatment also resulted in devastating widespread eruptive keratoacanthoma. The mechanism of this kind of eruption has yet to be understood; we hypothesize that it likely involves T lymphocyte–driven inflammation and the interplay of molecular and immune-mediated pathways.

While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.

The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.

“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.

Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.

Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»

But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.

Insurance Denials Also Growing

In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.

The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.

Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.

Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.

Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.

Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.

All the pediatricians said they expect greater restrictions in 2024.

Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.

“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
 

Some Parents Asking for GLP-1 Agonists

Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.

Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.

“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.

In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
 

Lifelong Medication?

Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.

With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.

She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”

Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”

“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”

“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.

Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.

She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”

Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.

A version of this article appeared on Medscape.com.

While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.

The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.

“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.

Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.

Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»

But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.

Insurance Denials Also Growing

In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.

The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.

Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.

Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.

Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.

Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.

All the pediatricians said they expect greater restrictions in 2024.

Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.

“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
 

Some Parents Asking for GLP-1 Agonists

Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.

Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.

“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.

In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
 

Lifelong Medication?

Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.

With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.

She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”

Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”

“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”

“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.

Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.

She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”

Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.

A version of this article appeared on Medscape.com.

While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.

The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.

“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.

Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.

Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»

But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.

Insurance Denials Also Growing

In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.

The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.

Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.

Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.

Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.

Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.

All the pediatricians said they expect greater restrictions in 2024.

Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.

“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
 

Some Parents Asking for GLP-1 Agonists

Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.

Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.

“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.

In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
 

Lifelong Medication?

Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.

With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.

She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”

Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”

“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”

“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.

Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.

She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”

Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.

A version of this article appeared on Medscape.com.