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Dupilumab under FDA review for atopic dermatitis in children aged 6 months to 5 years
The and Sanofi.
If approved, dupilumab would be the first biologic approved for children in this age group in the United States, according to the statement. The proposed indication is as add-on therapy for children with moderate to severe AD not adequately controlled with topical prescription therapies or for whom topical therapies are not advised. The FDA granted breakthrough therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years in 2016.
Approximately 85%-95% of atopic dermatitis patients develop symptoms before 5 years of age, and these symptoms often continue into adulthood, with an increased risk of skin infections and a significant impact on quality of life, according to the statement.
The sBLA is based on data from a phase 3 pivotal study of 162 children aged 6 months to 5 years in which dupilumab was added to standard-of-care topical corticosteroids, presented in December 2021. In the study, dupilumab plus standard of care significantly improved skin clearance and reduced overall disease severity and itch at 16 weeks compared with standard of care alone. Overall, 28% of the children randomized to dupilumab achieved the primary endpoint of clear or almost-clear skin, compared with 4% with those on standard of care alone (P < .0001), according to the manufacturers. Patients in the dupilumab group received either 200 mg (for children weighing ≥ 5 to < 15 kg) or 300 mg (for children weighing ≥ 15 to < 30 kg) every 4 weeks. Safety results were similar to those seen with dupilumab for children aged 6 years and older.
Conjunctivitis and herpes infections were among the most common adverse events associated with dupilumab in the study, according to the statement.
The target action date for the FDA decision on this application is June 9, 2022.
The and Sanofi.
If approved, dupilumab would be the first biologic approved for children in this age group in the United States, according to the statement. The proposed indication is as add-on therapy for children with moderate to severe AD not adequately controlled with topical prescription therapies or for whom topical therapies are not advised. The FDA granted breakthrough therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years in 2016.
Approximately 85%-95% of atopic dermatitis patients develop symptoms before 5 years of age, and these symptoms often continue into adulthood, with an increased risk of skin infections and a significant impact on quality of life, according to the statement.
The sBLA is based on data from a phase 3 pivotal study of 162 children aged 6 months to 5 years in which dupilumab was added to standard-of-care topical corticosteroids, presented in December 2021. In the study, dupilumab plus standard of care significantly improved skin clearance and reduced overall disease severity and itch at 16 weeks compared with standard of care alone. Overall, 28% of the children randomized to dupilumab achieved the primary endpoint of clear or almost-clear skin, compared with 4% with those on standard of care alone (P < .0001), according to the manufacturers. Patients in the dupilumab group received either 200 mg (for children weighing ≥ 5 to < 15 kg) or 300 mg (for children weighing ≥ 15 to < 30 kg) every 4 weeks. Safety results were similar to those seen with dupilumab for children aged 6 years and older.
Conjunctivitis and herpes infections were among the most common adverse events associated with dupilumab in the study, according to the statement.
The target action date for the FDA decision on this application is June 9, 2022.
The and Sanofi.
If approved, dupilumab would be the first biologic approved for children in this age group in the United States, according to the statement. The proposed indication is as add-on therapy for children with moderate to severe AD not adequately controlled with topical prescription therapies or for whom topical therapies are not advised. The FDA granted breakthrough therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years in 2016.
Approximately 85%-95% of atopic dermatitis patients develop symptoms before 5 years of age, and these symptoms often continue into adulthood, with an increased risk of skin infections and a significant impact on quality of life, according to the statement.
The sBLA is based on data from a phase 3 pivotal study of 162 children aged 6 months to 5 years in which dupilumab was added to standard-of-care topical corticosteroids, presented in December 2021. In the study, dupilumab plus standard of care significantly improved skin clearance and reduced overall disease severity and itch at 16 weeks compared with standard of care alone. Overall, 28% of the children randomized to dupilumab achieved the primary endpoint of clear or almost-clear skin, compared with 4% with those on standard of care alone (P < .0001), according to the manufacturers. Patients in the dupilumab group received either 200 mg (for children weighing ≥ 5 to < 15 kg) or 300 mg (for children weighing ≥ 15 to < 30 kg) every 4 weeks. Safety results were similar to those seen with dupilumab for children aged 6 years and older.
Conjunctivitis and herpes infections were among the most common adverse events associated with dupilumab in the study, according to the statement.
The target action date for the FDA decision on this application is June 9, 2022.
FROM THE FDA
E-cigarettes don’t help smokers quit, suggests new research
From 2013 to 2017, e-cigarette sales in the United States nearly doubled, driven by a rapid uptake of use by adolescents, wrote Riufeng Chen, MD, of the University of California, San Diego, and colleagues, in their paper published in Tobacco Control. However, the subsequent effect of increased e-cigarette use on smoking cessation have not been examined, they said.
In their study, Dr. Chen and colleagues analyzed data from 3,578 previous-year smokers with a recent quit attempt and 1,323 recent former smokers who were part of the PATH cohort in 2017. The participants reported using e-cigarettes or other products to quit cigarette smoking. The primary outcomes were at least 12 months of cigarette abstinence, and tobacco abstinence in 2019. In 2017, 32.8% of established smokers reported trying to quit. Of these, 12.6% used e-cigarettes to help them quit. Cigarette abstinence for at least 12 months for these individuals was 9.9%, which was lower than for those who used either nicotine replacement therapy or a pharmaceutical aid only (15.2%), and about half of the 18.6% abstinence in those who used no products to help them quit.
“In our study, e-cigarettes resulted in seven fewer successful quitters than those who used pharmaceutical aids,” emphasized corresponding author, John P. Pierce, PhD, of the University of California, San Diego.
Among smokers attempting to quit, the adjusted risk difference for cigarette abstinence for a least 12 months with e-cigarettes vs. pharmaceutical aids was –7.3%, and –7.7% for e-cigarettes vs. other smoking cessation methods.
*“Among recent former smokers who had switched to daily use of e-cigarettes in 2017, 43.2% had successfully quit cigarette smoking by 2019, which was similar to those who used e-cigarettes on a nondaily basis (34.6%) or to those who switched to another tobacco product, whether daily (43.6%) or nondaily (44.7%),” the researchers wrote.
The rapid growth in e-cigarette use between 2014 and 2017 has been attributed in part to aggressive marketing of high-nicotine e-cigarettes, they said. “The high-nicotine JUUL e-cigarette has been noted as the closest match to cigarettes in both nicotine delivery and user satisfaction, which should make it one of the best candidates as a product to which smokers could switch in order to maintain their nicotine habit,” they said in their discussion of the findings.
More research needed
The researchers acknowledged the need to review more recent data.
“When we looked ahead to 2019, recent former smokers had started using high-nicotine e-cigarettes. The effectiveness of high-nicotine e-cigarettes at preventing relapse will require another follow-up PATH survey,” they said.
Among recent former smokers, 2.2% reported switching to a high-nicotine e-cigarette. Although individuals who switched to e-cigarettes showed a higher rate of relapse to cigarettes than those who did not switch to other tobacco or e-cigarette products, this difference was not significant.
The study findings were limited by several factors including the observational design and inability to control for all potential confounding factors, the researchers noted. However, the results were strengthened by the use of a large and representative study population, and the inclusion of biological samples to validate self-reported smoking, they said.
Several findings surprised study author
Dr. Pierce said he was surprised by several aspects of the study findings.
“First of all, contrary to what we expected, there was a 25% decline in using e-cigarettes to quit, compared to the previous year (not the 40% increase that was expected from the increase in e-cigarette sales) and almost no smokers were using high-nicotine JUUL products to help them quit,” he said. “In this study, e-cigarettes were much less helpful (7 less successful quitters per 100) than pharmaceutical cessation aids in helping people quit,” he added.
“The fact that the proportion of smokers using e-cigarettes for cessation dropped from 17% to 12% was unexpected, and it suggests that the belief that they are a cessation aid is declining,” he said.
The implication for clinical practice is that e-cigarettes are not a useful tool for smoking cessation, Dr. Pierce said. “We are not finding any evidence in this very large nationally representative study that smokers who switch to getting their nicotine from e-cigarettes are less likely to relapse back to cigarette smoking,” he said.
“We don’t know about the high-nicotine versions,” he added.
New review advises against e-cigarettes for cessation
A recent review article published in JAMA supported the use of pharmacotherapy and behavioral support for smokers wanting to quit. In the review, Nancy A. Rigotti, MD, of Massachusetts General Hospital, Boston, and colleagues summarized the evidence for managing tobacco smoking in clinical practice.
“The health risk from cigarette smoking is primarily due to chemicals produced by the burning of tobacco and not to nicotine,” they noted. However, the physical dependence on nicotine makes quitting a challenge, but it is one worth pursuing, the authors said.
The authors of this review identified 30 reviews, 12 randomized clinical trials, and 7 recent guidelines and evidence reviews. Their key message: Pharmacotherapy and behavioral support are effective when used alone, but even more effective when combined. Pharmacotherapy helps reduce the symptoms of nicotine withdrawal, while behavioral intervention tackles the challenge of changing learned behaviors associated with smoking, the researchers said.
Although combining medications, such as varenicline and nicotine replacement therapy or bupropion might improve successful quit rates, these combinations have not been well studied, they noted.
With regard to e-cigarettes, the researchers cited a 2021 Cochrane review of 16,759 individuals who used e-cigarettes for smoking cessation, which found no evidence of harm, but insufficient evidence to asses the balance of risks vs. benefits.
In addition to the lack of randomized trials, “the FDA regulates e-cigarettes as tobacco products, not as medical products and has not evaluated any e-cigarette for medical use as a cessation aid,” the authors of the new review noted.
The review was limited by several factors, including the lack of quality assessment for the selected studies and the exclusion of pharmacotherapy not licensed in the United States.
Commenting on the JAMA paper, Dr. Pierce said, “This review looks like a number of Cochrane Reports that have been published recently. Of course, it only considers randomized trials and not population evidence.”
“If public health had limited itself to this form of evidence, then we still would not know that smoking caused cancer,” he noted. “Randomized trials are very important for testing new drugs; they use selected populations and provide considerable support that is not available in the real world. Sometimes they do not generalize to the population.”
Findings may guide patient conversations
The Tobacco Control study was important, because few studies on e-cigarettes have been conducted, said Linda Girgis, MD, a family physician in private practice in South River, N.J., in an interview.
“As clinicians, we do not have a lot of data available in order to make clinical decisions that are evidence based. Also, getting patients to quit smoking is often very difficult, and having more tools available is a great benefit; however, we need to have the evidence that these tools are effective,” she said.
Dr. Girgis also said she was not surprised by the findings.
“Patients still have the same concerns from e-cigarettes regarding nicotine exposure, but just to a lesser degree; and we still don’t know the long-term effects of e-cigarette use, she said. Based on these studies, recommending e-cigarettes for smokers looking to quit may not be the best method, she noted.
“While it may seem reasonable that exposing lungs to lower doses of nicotine will reduce harm, we need to see actual evidence of this. Also, we also need to study the additives that are frequently used in e-cigs, such as artificial flavorings, to see what harms they may pose, she emphasized.
With regard to the JAMA review, Dr. Girgis said she agreed with the recommendations for pharmacotherapy and behavior therapy as first-line treatments for smoking cessation. “There is evidence regarding the efficacy and safety of these methods, and they have been used for decades,” she said.
Dr. Girgis added that there is a role for e-cigarettes in smoking cessation strategies as a method of harm reduction, but pointed out the problem of many people thinking these products are safe and not understanding the hazards they pose.
“They think they can replace smoking with e-cigarettes and be safe from the health risks associated with smoking. I think if the plan were to switch to e-cigarettes for a short period and then quit, there would be a role,” Dr. Girgis said. “However, replacing one risk for another may reduce harm, but doesn’t eliminate it.”
“To continue to use e-cigarettes indefinitely should not be the goal,” she added.
The Tobacco Control study was funded by the National Institutes of Health and the Tobacco-Related Disease Research Program of the University of California. The researchers had no financial conflicts to disclose.
The JAMA study was funded in part by a grant from the National Institute for Health Research, via Cochrane Infrastructure funds to the Cochrane Tobacco Addiction Group. Lead author Dr. Rigotti disclosed funding from the National Heart, Lung, and Blood Institute and Achieve Life Sciences and personal fees from UpToDate and Achieve Life Sciences. Dr. Girgis had no financial conflicts to disclose.
*This article was updated on 2/28/2022.
From 2013 to 2017, e-cigarette sales in the United States nearly doubled, driven by a rapid uptake of use by adolescents, wrote Riufeng Chen, MD, of the University of California, San Diego, and colleagues, in their paper published in Tobacco Control. However, the subsequent effect of increased e-cigarette use on smoking cessation have not been examined, they said.
In their study, Dr. Chen and colleagues analyzed data from 3,578 previous-year smokers with a recent quit attempt and 1,323 recent former smokers who were part of the PATH cohort in 2017. The participants reported using e-cigarettes or other products to quit cigarette smoking. The primary outcomes were at least 12 months of cigarette abstinence, and tobacco abstinence in 2019. In 2017, 32.8% of established smokers reported trying to quit. Of these, 12.6% used e-cigarettes to help them quit. Cigarette abstinence for at least 12 months for these individuals was 9.9%, which was lower than for those who used either nicotine replacement therapy or a pharmaceutical aid only (15.2%), and about half of the 18.6% abstinence in those who used no products to help them quit.
“In our study, e-cigarettes resulted in seven fewer successful quitters than those who used pharmaceutical aids,” emphasized corresponding author, John P. Pierce, PhD, of the University of California, San Diego.
Among smokers attempting to quit, the adjusted risk difference for cigarette abstinence for a least 12 months with e-cigarettes vs. pharmaceutical aids was –7.3%, and –7.7% for e-cigarettes vs. other smoking cessation methods.
*“Among recent former smokers who had switched to daily use of e-cigarettes in 2017, 43.2% had successfully quit cigarette smoking by 2019, which was similar to those who used e-cigarettes on a nondaily basis (34.6%) or to those who switched to another tobacco product, whether daily (43.6%) or nondaily (44.7%),” the researchers wrote.
The rapid growth in e-cigarette use between 2014 and 2017 has been attributed in part to aggressive marketing of high-nicotine e-cigarettes, they said. “The high-nicotine JUUL e-cigarette has been noted as the closest match to cigarettes in both nicotine delivery and user satisfaction, which should make it one of the best candidates as a product to which smokers could switch in order to maintain their nicotine habit,” they said in their discussion of the findings.
More research needed
The researchers acknowledged the need to review more recent data.
“When we looked ahead to 2019, recent former smokers had started using high-nicotine e-cigarettes. The effectiveness of high-nicotine e-cigarettes at preventing relapse will require another follow-up PATH survey,” they said.
Among recent former smokers, 2.2% reported switching to a high-nicotine e-cigarette. Although individuals who switched to e-cigarettes showed a higher rate of relapse to cigarettes than those who did not switch to other tobacco or e-cigarette products, this difference was not significant.
The study findings were limited by several factors including the observational design and inability to control for all potential confounding factors, the researchers noted. However, the results were strengthened by the use of a large and representative study population, and the inclusion of biological samples to validate self-reported smoking, they said.
Several findings surprised study author
Dr. Pierce said he was surprised by several aspects of the study findings.
“First of all, contrary to what we expected, there was a 25% decline in using e-cigarettes to quit, compared to the previous year (not the 40% increase that was expected from the increase in e-cigarette sales) and almost no smokers were using high-nicotine JUUL products to help them quit,” he said. “In this study, e-cigarettes were much less helpful (7 less successful quitters per 100) than pharmaceutical cessation aids in helping people quit,” he added.
“The fact that the proportion of smokers using e-cigarettes for cessation dropped from 17% to 12% was unexpected, and it suggests that the belief that they are a cessation aid is declining,” he said.
The implication for clinical practice is that e-cigarettes are not a useful tool for smoking cessation, Dr. Pierce said. “We are not finding any evidence in this very large nationally representative study that smokers who switch to getting their nicotine from e-cigarettes are less likely to relapse back to cigarette smoking,” he said.
“We don’t know about the high-nicotine versions,” he added.
New review advises against e-cigarettes for cessation
A recent review article published in JAMA supported the use of pharmacotherapy and behavioral support for smokers wanting to quit. In the review, Nancy A. Rigotti, MD, of Massachusetts General Hospital, Boston, and colleagues summarized the evidence for managing tobacco smoking in clinical practice.
“The health risk from cigarette smoking is primarily due to chemicals produced by the burning of tobacco and not to nicotine,” they noted. However, the physical dependence on nicotine makes quitting a challenge, but it is one worth pursuing, the authors said.
The authors of this review identified 30 reviews, 12 randomized clinical trials, and 7 recent guidelines and evidence reviews. Their key message: Pharmacotherapy and behavioral support are effective when used alone, but even more effective when combined. Pharmacotherapy helps reduce the symptoms of nicotine withdrawal, while behavioral intervention tackles the challenge of changing learned behaviors associated with smoking, the researchers said.
Although combining medications, such as varenicline and nicotine replacement therapy or bupropion might improve successful quit rates, these combinations have not been well studied, they noted.
With regard to e-cigarettes, the researchers cited a 2021 Cochrane review of 16,759 individuals who used e-cigarettes for smoking cessation, which found no evidence of harm, but insufficient evidence to asses the balance of risks vs. benefits.
In addition to the lack of randomized trials, “the FDA regulates e-cigarettes as tobacco products, not as medical products and has not evaluated any e-cigarette for medical use as a cessation aid,” the authors of the new review noted.
The review was limited by several factors, including the lack of quality assessment for the selected studies and the exclusion of pharmacotherapy not licensed in the United States.
Commenting on the JAMA paper, Dr. Pierce said, “This review looks like a number of Cochrane Reports that have been published recently. Of course, it only considers randomized trials and not population evidence.”
“If public health had limited itself to this form of evidence, then we still would not know that smoking caused cancer,” he noted. “Randomized trials are very important for testing new drugs; they use selected populations and provide considerable support that is not available in the real world. Sometimes they do not generalize to the population.”
Findings may guide patient conversations
The Tobacco Control study was important, because few studies on e-cigarettes have been conducted, said Linda Girgis, MD, a family physician in private practice in South River, N.J., in an interview.
“As clinicians, we do not have a lot of data available in order to make clinical decisions that are evidence based. Also, getting patients to quit smoking is often very difficult, and having more tools available is a great benefit; however, we need to have the evidence that these tools are effective,” she said.
Dr. Girgis also said she was not surprised by the findings.
“Patients still have the same concerns from e-cigarettes regarding nicotine exposure, but just to a lesser degree; and we still don’t know the long-term effects of e-cigarette use, she said. Based on these studies, recommending e-cigarettes for smokers looking to quit may not be the best method, she noted.
“While it may seem reasonable that exposing lungs to lower doses of nicotine will reduce harm, we need to see actual evidence of this. Also, we also need to study the additives that are frequently used in e-cigs, such as artificial flavorings, to see what harms they may pose, she emphasized.
With regard to the JAMA review, Dr. Girgis said she agreed with the recommendations for pharmacotherapy and behavior therapy as first-line treatments for smoking cessation. “There is evidence regarding the efficacy and safety of these methods, and they have been used for decades,” she said.
Dr. Girgis added that there is a role for e-cigarettes in smoking cessation strategies as a method of harm reduction, but pointed out the problem of many people thinking these products are safe and not understanding the hazards they pose.
“They think they can replace smoking with e-cigarettes and be safe from the health risks associated with smoking. I think if the plan were to switch to e-cigarettes for a short period and then quit, there would be a role,” Dr. Girgis said. “However, replacing one risk for another may reduce harm, but doesn’t eliminate it.”
“To continue to use e-cigarettes indefinitely should not be the goal,” she added.
The Tobacco Control study was funded by the National Institutes of Health and the Tobacco-Related Disease Research Program of the University of California. The researchers had no financial conflicts to disclose.
The JAMA study was funded in part by a grant from the National Institute for Health Research, via Cochrane Infrastructure funds to the Cochrane Tobacco Addiction Group. Lead author Dr. Rigotti disclosed funding from the National Heart, Lung, and Blood Institute and Achieve Life Sciences and personal fees from UpToDate and Achieve Life Sciences. Dr. Girgis had no financial conflicts to disclose.
*This article was updated on 2/28/2022.
From 2013 to 2017, e-cigarette sales in the United States nearly doubled, driven by a rapid uptake of use by adolescents, wrote Riufeng Chen, MD, of the University of California, San Diego, and colleagues, in their paper published in Tobacco Control. However, the subsequent effect of increased e-cigarette use on smoking cessation have not been examined, they said.
In their study, Dr. Chen and colleagues analyzed data from 3,578 previous-year smokers with a recent quit attempt and 1,323 recent former smokers who were part of the PATH cohort in 2017. The participants reported using e-cigarettes or other products to quit cigarette smoking. The primary outcomes were at least 12 months of cigarette abstinence, and tobacco abstinence in 2019. In 2017, 32.8% of established smokers reported trying to quit. Of these, 12.6% used e-cigarettes to help them quit. Cigarette abstinence for at least 12 months for these individuals was 9.9%, which was lower than for those who used either nicotine replacement therapy or a pharmaceutical aid only (15.2%), and about half of the 18.6% abstinence in those who used no products to help them quit.
“In our study, e-cigarettes resulted in seven fewer successful quitters than those who used pharmaceutical aids,” emphasized corresponding author, John P. Pierce, PhD, of the University of California, San Diego.
Among smokers attempting to quit, the adjusted risk difference for cigarette abstinence for a least 12 months with e-cigarettes vs. pharmaceutical aids was –7.3%, and –7.7% for e-cigarettes vs. other smoking cessation methods.
*“Among recent former smokers who had switched to daily use of e-cigarettes in 2017, 43.2% had successfully quit cigarette smoking by 2019, which was similar to those who used e-cigarettes on a nondaily basis (34.6%) or to those who switched to another tobacco product, whether daily (43.6%) or nondaily (44.7%),” the researchers wrote.
The rapid growth in e-cigarette use between 2014 and 2017 has been attributed in part to aggressive marketing of high-nicotine e-cigarettes, they said. “The high-nicotine JUUL e-cigarette has been noted as the closest match to cigarettes in both nicotine delivery and user satisfaction, which should make it one of the best candidates as a product to which smokers could switch in order to maintain their nicotine habit,” they said in their discussion of the findings.
More research needed
The researchers acknowledged the need to review more recent data.
“When we looked ahead to 2019, recent former smokers had started using high-nicotine e-cigarettes. The effectiveness of high-nicotine e-cigarettes at preventing relapse will require another follow-up PATH survey,” they said.
Among recent former smokers, 2.2% reported switching to a high-nicotine e-cigarette. Although individuals who switched to e-cigarettes showed a higher rate of relapse to cigarettes than those who did not switch to other tobacco or e-cigarette products, this difference was not significant.
The study findings were limited by several factors including the observational design and inability to control for all potential confounding factors, the researchers noted. However, the results were strengthened by the use of a large and representative study population, and the inclusion of biological samples to validate self-reported smoking, they said.
Several findings surprised study author
Dr. Pierce said he was surprised by several aspects of the study findings.
“First of all, contrary to what we expected, there was a 25% decline in using e-cigarettes to quit, compared to the previous year (not the 40% increase that was expected from the increase in e-cigarette sales) and almost no smokers were using high-nicotine JUUL products to help them quit,” he said. “In this study, e-cigarettes were much less helpful (7 less successful quitters per 100) than pharmaceutical cessation aids in helping people quit,” he added.
“The fact that the proportion of smokers using e-cigarettes for cessation dropped from 17% to 12% was unexpected, and it suggests that the belief that they are a cessation aid is declining,” he said.
The implication for clinical practice is that e-cigarettes are not a useful tool for smoking cessation, Dr. Pierce said. “We are not finding any evidence in this very large nationally representative study that smokers who switch to getting their nicotine from e-cigarettes are less likely to relapse back to cigarette smoking,” he said.
“We don’t know about the high-nicotine versions,” he added.
New review advises against e-cigarettes for cessation
A recent review article published in JAMA supported the use of pharmacotherapy and behavioral support for smokers wanting to quit. In the review, Nancy A. Rigotti, MD, of Massachusetts General Hospital, Boston, and colleagues summarized the evidence for managing tobacco smoking in clinical practice.
“The health risk from cigarette smoking is primarily due to chemicals produced by the burning of tobacco and not to nicotine,” they noted. However, the physical dependence on nicotine makes quitting a challenge, but it is one worth pursuing, the authors said.
The authors of this review identified 30 reviews, 12 randomized clinical trials, and 7 recent guidelines and evidence reviews. Their key message: Pharmacotherapy and behavioral support are effective when used alone, but even more effective when combined. Pharmacotherapy helps reduce the symptoms of nicotine withdrawal, while behavioral intervention tackles the challenge of changing learned behaviors associated with smoking, the researchers said.
Although combining medications, such as varenicline and nicotine replacement therapy or bupropion might improve successful quit rates, these combinations have not been well studied, they noted.
With regard to e-cigarettes, the researchers cited a 2021 Cochrane review of 16,759 individuals who used e-cigarettes for smoking cessation, which found no evidence of harm, but insufficient evidence to asses the balance of risks vs. benefits.
In addition to the lack of randomized trials, “the FDA regulates e-cigarettes as tobacco products, not as medical products and has not evaluated any e-cigarette for medical use as a cessation aid,” the authors of the new review noted.
The review was limited by several factors, including the lack of quality assessment for the selected studies and the exclusion of pharmacotherapy not licensed in the United States.
Commenting on the JAMA paper, Dr. Pierce said, “This review looks like a number of Cochrane Reports that have been published recently. Of course, it only considers randomized trials and not population evidence.”
“If public health had limited itself to this form of evidence, then we still would not know that smoking caused cancer,” he noted. “Randomized trials are very important for testing new drugs; they use selected populations and provide considerable support that is not available in the real world. Sometimes they do not generalize to the population.”
Findings may guide patient conversations
The Tobacco Control study was important, because few studies on e-cigarettes have been conducted, said Linda Girgis, MD, a family physician in private practice in South River, N.J., in an interview.
“As clinicians, we do not have a lot of data available in order to make clinical decisions that are evidence based. Also, getting patients to quit smoking is often very difficult, and having more tools available is a great benefit; however, we need to have the evidence that these tools are effective,” she said.
Dr. Girgis also said she was not surprised by the findings.
“Patients still have the same concerns from e-cigarettes regarding nicotine exposure, but just to a lesser degree; and we still don’t know the long-term effects of e-cigarette use, she said. Based on these studies, recommending e-cigarettes for smokers looking to quit may not be the best method, she noted.
“While it may seem reasonable that exposing lungs to lower doses of nicotine will reduce harm, we need to see actual evidence of this. Also, we also need to study the additives that are frequently used in e-cigs, such as artificial flavorings, to see what harms they may pose, she emphasized.
With regard to the JAMA review, Dr. Girgis said she agreed with the recommendations for pharmacotherapy and behavior therapy as first-line treatments for smoking cessation. “There is evidence regarding the efficacy and safety of these methods, and they have been used for decades,” she said.
Dr. Girgis added that there is a role for e-cigarettes in smoking cessation strategies as a method of harm reduction, but pointed out the problem of many people thinking these products are safe and not understanding the hazards they pose.
“They think they can replace smoking with e-cigarettes and be safe from the health risks associated with smoking. I think if the plan were to switch to e-cigarettes for a short period and then quit, there would be a role,” Dr. Girgis said. “However, replacing one risk for another may reduce harm, but doesn’t eliminate it.”
“To continue to use e-cigarettes indefinitely should not be the goal,” she added.
The Tobacco Control study was funded by the National Institutes of Health and the Tobacco-Related Disease Research Program of the University of California. The researchers had no financial conflicts to disclose.
The JAMA study was funded in part by a grant from the National Institute for Health Research, via Cochrane Infrastructure funds to the Cochrane Tobacco Addiction Group. Lead author Dr. Rigotti disclosed funding from the National Heart, Lung, and Blood Institute and Achieve Life Sciences and personal fees from UpToDate and Achieve Life Sciences. Dr. Girgis had no financial conflicts to disclose.
*This article was updated on 2/28/2022.
FROM TOBACCO CONTROL
Growth in early life may predict early puberty
Faster gains in weight, length or height, or body mass index in the first 5 years of life were associated with an earlier onset of puberty in boys and girls, based on data from a cohort study of more than 7,000 children.
In recent decades, clinicians and parents have raised concerns about an earlier onset of puberty in children in the United States and other countries, Izzudin M. Aris, PhD, of Harvard Medical School, Boston, and colleagues wrote.
“Children with earlier pubertal onset not only may be at increased risk for long-term chronic diseases, but also may experience adverse consequences during adolescence, including psychosocial difficulties and dysmetabolism,” they said. However, the effect of growth in the first 5 years of life on pubertal onset has not been well studied.
In a study published in JAMA Network Open, the researchers identified 7,495 children from 36 cohorts participating in the Environmental Influences on Child Health Outcomes program from Jan. 1, 1986, to Dec. 31, 2015.
The study population included 3,772 girls and 3,723 boys; 60% reported as White, 23% as Black, 15% as Hispanic, 12% as one of the following: American Indian or Alaska Native, Native Hawaiian or Pacific Islander, multiple races, or other race. Most (84.1%) were born during or after the year 2000.
The primary outcome was the pubertal growth spurt, also known as age at peak height velocity (APHV). The researchers measured growth at 3 age periods in the first 5 years (early infancy, late infancy, and early childhood) and estimated rates of weight, length or height, and body mass index (BMI) gain. Secondary outcomes included self-reported pubic hair staging and scores on the Pubertal Development Scale.
Overall, weight and length or height gain velocities declined in the first 5 years of life, and boys had faster gains in early infancy, compared with girls.
APHV was negatively correlated with puberty scores and Tanner staging for pubic hair development in both boys and girls, while puberty score was positively correlated with Tanner staging for pubic hair in both sexes.
After controlling for maternal and child confounders including maternal age at delivery, maternal education level, and year of birth, faster gains in weight, length or height, or BMI at each of the three measurement periods in early life was associated with earlier APHV in boys. No effect was noted for race, maternal education level, or birth year.
In girls, faster gains in weight, length, or height, only at the latest measurement period (early childhood) were associated with younger APHV. No associations with APHV occurred for velocities of BMI gain at any age period in girls, the researchers noted. However, age at menarche was positively correlated with early APHV and negatively correlated with puberty score and Tanner staging for pubic hair.
The findings support previous studies of associations between child growth and pubertal onset, the researchers wrote. The mechanisms of action are many, and have not been explained, the researchers wrote in their discussion of the findings.
“We speculate that insulinlike growth factor 1 may be a factor in the associations observed in the present study, either directly or indirectly through sex steroid synthesis and secretion. Alternatively, in girls, androgens and adipokines may be factors in the observed associations for pubic hair staging and menarche, respectively,” they said. Genetics and other factors including social factors, environmental exposures, diet, and physical activity also affect growth in early life.
The study findings were limited by several factors including the use of child-reported measures of pubic hair staging and parent reports of pubertal scores, with the potential for error and misclassification, the researchers noted. Other limitations include a lack of data on maternal age at menarche and the use of weight-for-length rather than BMI for children younger than 2 years.
However, the results were strengthened by the large sample size, long-term follow-up, and especially the use of a nationally representative contemporary cohort that addresses gaps in the current literature from later time periods. The results support the associations of sex-specific early pubertal onset in children with faster growth early in life. “In the long term, results of the present study may inform future research that aims to develop and/or test preventive interventions to optimize nutrition, environmental exposures, physical activity, and other behaviors related to growth during these age periods,” they concluded.
Time and timing limit practical application of results
The current study addresses two issues that are ongoing concerns for clinicians, specifically, the rise in obesity in childhood and its potential link to an earlier age of entry into puberty, M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview.
“Authors in prior studies have suggested that earlier puberty, and indeed earlier menarche, in females may be associated with the potential of long-term health issues,” Dr. Jay noted. “It has also been suggested that both early maturing females and males may be impacted psychosocially. Others have suggested that the pathways through puberty are key and environmental factors as well as nutrition can have an impact on adolescence as well as health consequences later in life.”
The current study is important because it focused on children born in the present era of the obesity epidemic, while earlier studies were conducted on a group in the 1960s-1980s. “This study suggests that there are sex-specific associations of faster growth and earlier entry into puberty,” Dr. Jay said.
“While it is exciting to consider closer monitoring of pubertal progression in pediatric settings, often patients and families do not present in a timely manner for assessment,” she said. “Also, the authors suggest that preventive support may be offered to children who are traversing puberty at earlier ages. However, given the current stress on practices with COVID as well as stress on providers offering clinical services, identifying supportive interventions may be a stretch at best for practitioners already burdened by clinical and administrative demands.
“Ongoing studies are needed to address the knowledge gaps that exist in the arena of pubertal onset and growth during childhood across life periods,” said Dr. Jay. “In the long term, the present study may help direct research that could focus on preventive interventions to optimize nutrition, physical activity, environmental exposures, and other factors that intersect growth during infancy through early childhood, which may hasten early pubertal development’s later sequelae in adulthood.”
The study was supported by various grants to the researchers from the Environmental Influences on Child Health Outcomes program, Office of the Director, National Institutes of Health, as well as the Colorado Clinical and Translational Sciences Institute, University of Colorado at Denver. Lead author Dr. Aris had no financial conflicts to disclose. Dr. Jay had no conflicts to disclose and serves on the editorial advisory board of Pediatric News.
Faster gains in weight, length or height, or body mass index in the first 5 years of life were associated with an earlier onset of puberty in boys and girls, based on data from a cohort study of more than 7,000 children.
In recent decades, clinicians and parents have raised concerns about an earlier onset of puberty in children in the United States and other countries, Izzudin M. Aris, PhD, of Harvard Medical School, Boston, and colleagues wrote.
“Children with earlier pubertal onset not only may be at increased risk for long-term chronic diseases, but also may experience adverse consequences during adolescence, including psychosocial difficulties and dysmetabolism,” they said. However, the effect of growth in the first 5 years of life on pubertal onset has not been well studied.
In a study published in JAMA Network Open, the researchers identified 7,495 children from 36 cohorts participating in the Environmental Influences on Child Health Outcomes program from Jan. 1, 1986, to Dec. 31, 2015.
The study population included 3,772 girls and 3,723 boys; 60% reported as White, 23% as Black, 15% as Hispanic, 12% as one of the following: American Indian or Alaska Native, Native Hawaiian or Pacific Islander, multiple races, or other race. Most (84.1%) were born during or after the year 2000.
The primary outcome was the pubertal growth spurt, also known as age at peak height velocity (APHV). The researchers measured growth at 3 age periods in the first 5 years (early infancy, late infancy, and early childhood) and estimated rates of weight, length or height, and body mass index (BMI) gain. Secondary outcomes included self-reported pubic hair staging and scores on the Pubertal Development Scale.
Overall, weight and length or height gain velocities declined in the first 5 years of life, and boys had faster gains in early infancy, compared with girls.
APHV was negatively correlated with puberty scores and Tanner staging for pubic hair development in both boys and girls, while puberty score was positively correlated with Tanner staging for pubic hair in both sexes.
After controlling for maternal and child confounders including maternal age at delivery, maternal education level, and year of birth, faster gains in weight, length or height, or BMI at each of the three measurement periods in early life was associated with earlier APHV in boys. No effect was noted for race, maternal education level, or birth year.
In girls, faster gains in weight, length, or height, only at the latest measurement period (early childhood) were associated with younger APHV. No associations with APHV occurred for velocities of BMI gain at any age period in girls, the researchers noted. However, age at menarche was positively correlated with early APHV and negatively correlated with puberty score and Tanner staging for pubic hair.
The findings support previous studies of associations between child growth and pubertal onset, the researchers wrote. The mechanisms of action are many, and have not been explained, the researchers wrote in their discussion of the findings.
“We speculate that insulinlike growth factor 1 may be a factor in the associations observed in the present study, either directly or indirectly through sex steroid synthesis and secretion. Alternatively, in girls, androgens and adipokines may be factors in the observed associations for pubic hair staging and menarche, respectively,” they said. Genetics and other factors including social factors, environmental exposures, diet, and physical activity also affect growth in early life.
The study findings were limited by several factors including the use of child-reported measures of pubic hair staging and parent reports of pubertal scores, with the potential for error and misclassification, the researchers noted. Other limitations include a lack of data on maternal age at menarche and the use of weight-for-length rather than BMI for children younger than 2 years.
However, the results were strengthened by the large sample size, long-term follow-up, and especially the use of a nationally representative contemporary cohort that addresses gaps in the current literature from later time periods. The results support the associations of sex-specific early pubertal onset in children with faster growth early in life. “In the long term, results of the present study may inform future research that aims to develop and/or test preventive interventions to optimize nutrition, environmental exposures, physical activity, and other behaviors related to growth during these age periods,” they concluded.
Time and timing limit practical application of results
The current study addresses two issues that are ongoing concerns for clinicians, specifically, the rise in obesity in childhood and its potential link to an earlier age of entry into puberty, M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview.
“Authors in prior studies have suggested that earlier puberty, and indeed earlier menarche, in females may be associated with the potential of long-term health issues,” Dr. Jay noted. “It has also been suggested that both early maturing females and males may be impacted psychosocially. Others have suggested that the pathways through puberty are key and environmental factors as well as nutrition can have an impact on adolescence as well as health consequences later in life.”
The current study is important because it focused on children born in the present era of the obesity epidemic, while earlier studies were conducted on a group in the 1960s-1980s. “This study suggests that there are sex-specific associations of faster growth and earlier entry into puberty,” Dr. Jay said.
“While it is exciting to consider closer monitoring of pubertal progression in pediatric settings, often patients and families do not present in a timely manner for assessment,” she said. “Also, the authors suggest that preventive support may be offered to children who are traversing puberty at earlier ages. However, given the current stress on practices with COVID as well as stress on providers offering clinical services, identifying supportive interventions may be a stretch at best for practitioners already burdened by clinical and administrative demands.
“Ongoing studies are needed to address the knowledge gaps that exist in the arena of pubertal onset and growth during childhood across life periods,” said Dr. Jay. “In the long term, the present study may help direct research that could focus on preventive interventions to optimize nutrition, physical activity, environmental exposures, and other factors that intersect growth during infancy through early childhood, which may hasten early pubertal development’s later sequelae in adulthood.”
The study was supported by various grants to the researchers from the Environmental Influences on Child Health Outcomes program, Office of the Director, National Institutes of Health, as well as the Colorado Clinical and Translational Sciences Institute, University of Colorado at Denver. Lead author Dr. Aris had no financial conflicts to disclose. Dr. Jay had no conflicts to disclose and serves on the editorial advisory board of Pediatric News.
Faster gains in weight, length or height, or body mass index in the first 5 years of life were associated with an earlier onset of puberty in boys and girls, based on data from a cohort study of more than 7,000 children.
In recent decades, clinicians and parents have raised concerns about an earlier onset of puberty in children in the United States and other countries, Izzudin M. Aris, PhD, of Harvard Medical School, Boston, and colleagues wrote.
“Children with earlier pubertal onset not only may be at increased risk for long-term chronic diseases, but also may experience adverse consequences during adolescence, including psychosocial difficulties and dysmetabolism,” they said. However, the effect of growth in the first 5 years of life on pubertal onset has not been well studied.
In a study published in JAMA Network Open, the researchers identified 7,495 children from 36 cohorts participating in the Environmental Influences on Child Health Outcomes program from Jan. 1, 1986, to Dec. 31, 2015.
The study population included 3,772 girls and 3,723 boys; 60% reported as White, 23% as Black, 15% as Hispanic, 12% as one of the following: American Indian or Alaska Native, Native Hawaiian or Pacific Islander, multiple races, or other race. Most (84.1%) were born during or after the year 2000.
The primary outcome was the pubertal growth spurt, also known as age at peak height velocity (APHV). The researchers measured growth at 3 age periods in the first 5 years (early infancy, late infancy, and early childhood) and estimated rates of weight, length or height, and body mass index (BMI) gain. Secondary outcomes included self-reported pubic hair staging and scores on the Pubertal Development Scale.
Overall, weight and length or height gain velocities declined in the first 5 years of life, and boys had faster gains in early infancy, compared with girls.
APHV was negatively correlated with puberty scores and Tanner staging for pubic hair development in both boys and girls, while puberty score was positively correlated with Tanner staging for pubic hair in both sexes.
After controlling for maternal and child confounders including maternal age at delivery, maternal education level, and year of birth, faster gains in weight, length or height, or BMI at each of the three measurement periods in early life was associated with earlier APHV in boys. No effect was noted for race, maternal education level, or birth year.
In girls, faster gains in weight, length, or height, only at the latest measurement period (early childhood) were associated with younger APHV. No associations with APHV occurred for velocities of BMI gain at any age period in girls, the researchers noted. However, age at menarche was positively correlated with early APHV and negatively correlated with puberty score and Tanner staging for pubic hair.
The findings support previous studies of associations between child growth and pubertal onset, the researchers wrote. The mechanisms of action are many, and have not been explained, the researchers wrote in their discussion of the findings.
“We speculate that insulinlike growth factor 1 may be a factor in the associations observed in the present study, either directly or indirectly through sex steroid synthesis and secretion. Alternatively, in girls, androgens and adipokines may be factors in the observed associations for pubic hair staging and menarche, respectively,” they said. Genetics and other factors including social factors, environmental exposures, diet, and physical activity also affect growth in early life.
The study findings were limited by several factors including the use of child-reported measures of pubic hair staging and parent reports of pubertal scores, with the potential for error and misclassification, the researchers noted. Other limitations include a lack of data on maternal age at menarche and the use of weight-for-length rather than BMI for children younger than 2 years.
However, the results were strengthened by the large sample size, long-term follow-up, and especially the use of a nationally representative contemporary cohort that addresses gaps in the current literature from later time periods. The results support the associations of sex-specific early pubertal onset in children with faster growth early in life. “In the long term, results of the present study may inform future research that aims to develop and/or test preventive interventions to optimize nutrition, environmental exposures, physical activity, and other behaviors related to growth during these age periods,” they concluded.
Time and timing limit practical application of results
The current study addresses two issues that are ongoing concerns for clinicians, specifically, the rise in obesity in childhood and its potential link to an earlier age of entry into puberty, M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview.
“Authors in prior studies have suggested that earlier puberty, and indeed earlier menarche, in females may be associated with the potential of long-term health issues,” Dr. Jay noted. “It has also been suggested that both early maturing females and males may be impacted psychosocially. Others have suggested that the pathways through puberty are key and environmental factors as well as nutrition can have an impact on adolescence as well as health consequences later in life.”
The current study is important because it focused on children born in the present era of the obesity epidemic, while earlier studies were conducted on a group in the 1960s-1980s. “This study suggests that there are sex-specific associations of faster growth and earlier entry into puberty,” Dr. Jay said.
“While it is exciting to consider closer monitoring of pubertal progression in pediatric settings, often patients and families do not present in a timely manner for assessment,” she said. “Also, the authors suggest that preventive support may be offered to children who are traversing puberty at earlier ages. However, given the current stress on practices with COVID as well as stress on providers offering clinical services, identifying supportive interventions may be a stretch at best for practitioners already burdened by clinical and administrative demands.
“Ongoing studies are needed to address the knowledge gaps that exist in the arena of pubertal onset and growth during childhood across life periods,” said Dr. Jay. “In the long term, the present study may help direct research that could focus on preventive interventions to optimize nutrition, physical activity, environmental exposures, and other factors that intersect growth during infancy through early childhood, which may hasten early pubertal development’s later sequelae in adulthood.”
The study was supported by various grants to the researchers from the Environmental Influences on Child Health Outcomes program, Office of the Director, National Institutes of Health, as well as the Colorado Clinical and Translational Sciences Institute, University of Colorado at Denver. Lead author Dr. Aris had no financial conflicts to disclose. Dr. Jay had no conflicts to disclose and serves on the editorial advisory board of Pediatric News.
FROM JAMA NETWORK OPEN
Updated endometriosis guidelines emphasize less laparoscopy, more hormone therapy
Updated guidelines for the management and treatment of endometriosis reflect changes in clinical practice to guide clinician and patient decision-making, according to a statement from the European Society of Human Reproduction and Embryology, which issued the guidelines in February 2022.
Although the exact prevalence of endometriosis remains unclear, estimates suggest that approximately 190 million women and adolescent girls are affected by endometriosis during their reproductive years, and women continue to suffer beyond menopause, according to the authors. Endometriosis has a significant impact on society through both direct and indirect health care costs comparable to those of type 2 diabetes, rheumatoid arthritis, and Crohn’s disease, they noted.
The guidelines are the first update on the topic of endometriosis since 2014, and include more than 100 recommendations, according to the European Society of Human Reproduction and Embryology (ESHRE). The target audience, according to the authors, is secondary and tertiary health care providers who treat women with endometriosis. The recommendations were based on research papers published up to Dec. 1, 2020.
Although most of the recent studies confirm previous ESHRE recommendations, several topics reflect significant changes in clinical practice.
Notably, laparoscopy is no longer recommended as the diagnostic gold standard, and should be used only in patients with negative imaging for whom empirical treatment was unsuccessful.
For pain management, studies support the use of GnRH antagonists as a second-line treatment, while laparoscopic uterosacral nerve ablation and presacral neurectomy are no longer included in the recommendations.
The guidelines include new information on pregnancy and fertility preservation for women with endometriosis. The Endometriosis Fertility Index (EFI) was added to support joint decision-making for women seeking pregnancy after surgery. However, the extended use of GnRH antagonist prior to assisted reproductive technology treatments to improve live birth rate is not recommended.
Endometriosis in adolescent patients is included in the guidelines for the first time, and strong recommendations include taking a careful history and using ultrasound if appropriate, but the use of serum biomarkers is not recommended for diagnosis. Strong recommendations for treatment strategies for adolescents include hormonal contraceptives or progestins as a first-line therapy.
Recommendations for managing endometriosis in menopause are more extensive than in previous guidelines and the strongest update is against the use of estrogen-only treatment in these patients. However, the guidelines continue to recommend treating women with a history of endometriosis after surgical menopause with combined estrogen-progestogen therapy “at least up to the age of natural menopause.”
Expanded recommendations related to endometriosis and cancer begin with a strong recommendation for clinicians to advise women that endometriosis is not associated with a significantly higher risk of cancer overall. “Although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low,” the authors wrote. Other strong recommendations include reassuring women with endometriosis of the low risk of malignancy associated with hormonal contraceptive use, and performing cancer screening according to the existing population-based guidelines without additional screening. Epidemiologic data show that complete excision of visible endometriosis may reduce the risk of ovarian cancer, but the potential benefits must be weighed against the risks of surgery, including morbidity, pain, and ovarian reserve, the authors said.
The guidelines include recommendations related to asymptomatic endometriosis, extrapelvic endometriosis, and primary prevention of endometriosis, but without major changes to the 2014 guidelines.
Guidelines expand strategies, but research gaps remain
In 2021, an international working group of the American Association of Gynecologic Laparoscopists, the European Society for Gynecologic Endoscopy, ESHRE, and the World Endometriosis Society defined endometriosis as “a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process,” Mark P. Trolice, MD, director of The IVF Center, Orlando, Fla., and professor of obstetrics and gynecology at the University of Central Florida, said in an interview.
Although the current guidelines represent the second update since 2005, many unanswered questions remain, Dr. Trolice said. “There is a large diagnostic void between the onset of symptoms and the time to a reliable diagnosis averaging between 8 and 12 years,” he emphasized.
Dr. Trolice noted the change of the addition of an oral GnRH antagonist, “now FDA approved for the treatment of pain associated with endometriosis,” he said. However, “Extended GnRH agonist prior to ART is not recommended due to the lack of any clear benefit,” he noted.
Dr. Trolice noted the inclusion of the Endometriosis Fertility Index (EFI), published in 2010, “as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and IUI [intrauterine insemination]) based on patient characteristics, revised ASRM staging, and ‘least function score of the adnexa.’ ” He agreed with the need for expanded information on the topics of endometriosis and adolescence and endometriosis and cancer.
The most important changes for clinical practice include reducing unnecessary laparoscopy and procedures without benefit, such as laparoscopic uterosacral nerve ablation and presacral neurectomy, and GnRH suppression using an oral antagonist, said Dr. Trolice. Other especially practical guidance includes the recommendation to discontinue advising patients that pregnancy will reduce symptoms of endometriosis, and to avoid prescribing estrogen-only treatment in menopause given the risk of malignant transformation of endometriosis, he said.
Another clinically useful recommendation, though not a significant update, is the need to identify extrapelvic endometriosis symptoms, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules that enlarge during menses, Dr. Trolice added.
Barriers to implementing the updated guidelines include lack of education of clinicians, including primary care providers, and the lack of definitive evidence for many areas, he noted.
As for additional research, more data are needed to explore the genetic, mutational, and epigenetic profile of endometriosis, and to identify biomarkers to noninvasively detect and provide a prognosis for endometriosis, and optimal methods for prevention and management, said Dr. Trolice. Other research gaps include “definitive medical and surgical treatment of endometriosis for improvement of fertility, quality of life, and reduction of pain,” he noted. From a fertility standpoint, more studies are needed on “the use of ovarian tissue or oocytes cryopreservation in adolescents and adults who undergo ovarian surgery for endometriomas, and the role of the EFI as a presurgical triage tool and to predict IUI outcomes,” said Dr. Trolice.
Overall, society recommendations such as these from ESHRE “serve as guides for physicians by providing evidence-based medicine and dispelling prior unproven practices so patients may receive the most effective care of endometriosis, throughout a woman’s life,” Dr. Trolice emphasized.
The current guideline will be considered for revision in 2025, and the full version is available on the ESHRE website.
Members of the ESHRE guideline development group received no payment for participating in the development process, although they were reimbursed for travel expenses related to guideline meetings.
Dr. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.
Updated guidelines for the management and treatment of endometriosis reflect changes in clinical practice to guide clinician and patient decision-making, according to a statement from the European Society of Human Reproduction and Embryology, which issued the guidelines in February 2022.
Although the exact prevalence of endometriosis remains unclear, estimates suggest that approximately 190 million women and adolescent girls are affected by endometriosis during their reproductive years, and women continue to suffer beyond menopause, according to the authors. Endometriosis has a significant impact on society through both direct and indirect health care costs comparable to those of type 2 diabetes, rheumatoid arthritis, and Crohn’s disease, they noted.
The guidelines are the first update on the topic of endometriosis since 2014, and include more than 100 recommendations, according to the European Society of Human Reproduction and Embryology (ESHRE). The target audience, according to the authors, is secondary and tertiary health care providers who treat women with endometriosis. The recommendations were based on research papers published up to Dec. 1, 2020.
Although most of the recent studies confirm previous ESHRE recommendations, several topics reflect significant changes in clinical practice.
Notably, laparoscopy is no longer recommended as the diagnostic gold standard, and should be used only in patients with negative imaging for whom empirical treatment was unsuccessful.
For pain management, studies support the use of GnRH antagonists as a second-line treatment, while laparoscopic uterosacral nerve ablation and presacral neurectomy are no longer included in the recommendations.
The guidelines include new information on pregnancy and fertility preservation for women with endometriosis. The Endometriosis Fertility Index (EFI) was added to support joint decision-making for women seeking pregnancy after surgery. However, the extended use of GnRH antagonist prior to assisted reproductive technology treatments to improve live birth rate is not recommended.
Endometriosis in adolescent patients is included in the guidelines for the first time, and strong recommendations include taking a careful history and using ultrasound if appropriate, but the use of serum biomarkers is not recommended for diagnosis. Strong recommendations for treatment strategies for adolescents include hormonal contraceptives or progestins as a first-line therapy.
Recommendations for managing endometriosis in menopause are more extensive than in previous guidelines and the strongest update is against the use of estrogen-only treatment in these patients. However, the guidelines continue to recommend treating women with a history of endometriosis after surgical menopause with combined estrogen-progestogen therapy “at least up to the age of natural menopause.”
Expanded recommendations related to endometriosis and cancer begin with a strong recommendation for clinicians to advise women that endometriosis is not associated with a significantly higher risk of cancer overall. “Although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low,” the authors wrote. Other strong recommendations include reassuring women with endometriosis of the low risk of malignancy associated with hormonal contraceptive use, and performing cancer screening according to the existing population-based guidelines without additional screening. Epidemiologic data show that complete excision of visible endometriosis may reduce the risk of ovarian cancer, but the potential benefits must be weighed against the risks of surgery, including morbidity, pain, and ovarian reserve, the authors said.
The guidelines include recommendations related to asymptomatic endometriosis, extrapelvic endometriosis, and primary prevention of endometriosis, but without major changes to the 2014 guidelines.
Guidelines expand strategies, but research gaps remain
In 2021, an international working group of the American Association of Gynecologic Laparoscopists, the European Society for Gynecologic Endoscopy, ESHRE, and the World Endometriosis Society defined endometriosis as “a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process,” Mark P. Trolice, MD, director of The IVF Center, Orlando, Fla., and professor of obstetrics and gynecology at the University of Central Florida, said in an interview.
Although the current guidelines represent the second update since 2005, many unanswered questions remain, Dr. Trolice said. “There is a large diagnostic void between the onset of symptoms and the time to a reliable diagnosis averaging between 8 and 12 years,” he emphasized.
Dr. Trolice noted the change of the addition of an oral GnRH antagonist, “now FDA approved for the treatment of pain associated with endometriosis,” he said. However, “Extended GnRH agonist prior to ART is not recommended due to the lack of any clear benefit,” he noted.
Dr. Trolice noted the inclusion of the Endometriosis Fertility Index (EFI), published in 2010, “as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and IUI [intrauterine insemination]) based on patient characteristics, revised ASRM staging, and ‘least function score of the adnexa.’ ” He agreed with the need for expanded information on the topics of endometriosis and adolescence and endometriosis and cancer.
The most important changes for clinical practice include reducing unnecessary laparoscopy and procedures without benefit, such as laparoscopic uterosacral nerve ablation and presacral neurectomy, and GnRH suppression using an oral antagonist, said Dr. Trolice. Other especially practical guidance includes the recommendation to discontinue advising patients that pregnancy will reduce symptoms of endometriosis, and to avoid prescribing estrogen-only treatment in menopause given the risk of malignant transformation of endometriosis, he said.
Another clinically useful recommendation, though not a significant update, is the need to identify extrapelvic endometriosis symptoms, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules that enlarge during menses, Dr. Trolice added.
Barriers to implementing the updated guidelines include lack of education of clinicians, including primary care providers, and the lack of definitive evidence for many areas, he noted.
As for additional research, more data are needed to explore the genetic, mutational, and epigenetic profile of endometriosis, and to identify biomarkers to noninvasively detect and provide a prognosis for endometriosis, and optimal methods for prevention and management, said Dr. Trolice. Other research gaps include “definitive medical and surgical treatment of endometriosis for improvement of fertility, quality of life, and reduction of pain,” he noted. From a fertility standpoint, more studies are needed on “the use of ovarian tissue or oocytes cryopreservation in adolescents and adults who undergo ovarian surgery for endometriomas, and the role of the EFI as a presurgical triage tool and to predict IUI outcomes,” said Dr. Trolice.
Overall, society recommendations such as these from ESHRE “serve as guides for physicians by providing evidence-based medicine and dispelling prior unproven practices so patients may receive the most effective care of endometriosis, throughout a woman’s life,” Dr. Trolice emphasized.
The current guideline will be considered for revision in 2025, and the full version is available on the ESHRE website.
Members of the ESHRE guideline development group received no payment for participating in the development process, although they were reimbursed for travel expenses related to guideline meetings.
Dr. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.
Updated guidelines for the management and treatment of endometriosis reflect changes in clinical practice to guide clinician and patient decision-making, according to a statement from the European Society of Human Reproduction and Embryology, which issued the guidelines in February 2022.
Although the exact prevalence of endometriosis remains unclear, estimates suggest that approximately 190 million women and adolescent girls are affected by endometriosis during their reproductive years, and women continue to suffer beyond menopause, according to the authors. Endometriosis has a significant impact on society through both direct and indirect health care costs comparable to those of type 2 diabetes, rheumatoid arthritis, and Crohn’s disease, they noted.
The guidelines are the first update on the topic of endometriosis since 2014, and include more than 100 recommendations, according to the European Society of Human Reproduction and Embryology (ESHRE). The target audience, according to the authors, is secondary and tertiary health care providers who treat women with endometriosis. The recommendations were based on research papers published up to Dec. 1, 2020.
Although most of the recent studies confirm previous ESHRE recommendations, several topics reflect significant changes in clinical practice.
Notably, laparoscopy is no longer recommended as the diagnostic gold standard, and should be used only in patients with negative imaging for whom empirical treatment was unsuccessful.
For pain management, studies support the use of GnRH antagonists as a second-line treatment, while laparoscopic uterosacral nerve ablation and presacral neurectomy are no longer included in the recommendations.
The guidelines include new information on pregnancy and fertility preservation for women with endometriosis. The Endometriosis Fertility Index (EFI) was added to support joint decision-making for women seeking pregnancy after surgery. However, the extended use of GnRH antagonist prior to assisted reproductive technology treatments to improve live birth rate is not recommended.
Endometriosis in adolescent patients is included in the guidelines for the first time, and strong recommendations include taking a careful history and using ultrasound if appropriate, but the use of serum biomarkers is not recommended for diagnosis. Strong recommendations for treatment strategies for adolescents include hormonal contraceptives or progestins as a first-line therapy.
Recommendations for managing endometriosis in menopause are more extensive than in previous guidelines and the strongest update is against the use of estrogen-only treatment in these patients. However, the guidelines continue to recommend treating women with a history of endometriosis after surgical menopause with combined estrogen-progestogen therapy “at least up to the age of natural menopause.”
Expanded recommendations related to endometriosis and cancer begin with a strong recommendation for clinicians to advise women that endometriosis is not associated with a significantly higher risk of cancer overall. “Although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low,” the authors wrote. Other strong recommendations include reassuring women with endometriosis of the low risk of malignancy associated with hormonal contraceptive use, and performing cancer screening according to the existing population-based guidelines without additional screening. Epidemiologic data show that complete excision of visible endometriosis may reduce the risk of ovarian cancer, but the potential benefits must be weighed against the risks of surgery, including morbidity, pain, and ovarian reserve, the authors said.
The guidelines include recommendations related to asymptomatic endometriosis, extrapelvic endometriosis, and primary prevention of endometriosis, but without major changes to the 2014 guidelines.
Guidelines expand strategies, but research gaps remain
In 2021, an international working group of the American Association of Gynecologic Laparoscopists, the European Society for Gynecologic Endoscopy, ESHRE, and the World Endometriosis Society defined endometriosis as “a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process,” Mark P. Trolice, MD, director of The IVF Center, Orlando, Fla., and professor of obstetrics and gynecology at the University of Central Florida, said in an interview.
Although the current guidelines represent the second update since 2005, many unanswered questions remain, Dr. Trolice said. “There is a large diagnostic void between the onset of symptoms and the time to a reliable diagnosis averaging between 8 and 12 years,” he emphasized.
Dr. Trolice noted the change of the addition of an oral GnRH antagonist, “now FDA approved for the treatment of pain associated with endometriosis,” he said. However, “Extended GnRH agonist prior to ART is not recommended due to the lack of any clear benefit,” he noted.
Dr. Trolice noted the inclusion of the Endometriosis Fertility Index (EFI), published in 2010, “as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and IUI [intrauterine insemination]) based on patient characteristics, revised ASRM staging, and ‘least function score of the adnexa.’ ” He agreed with the need for expanded information on the topics of endometriosis and adolescence and endometriosis and cancer.
The most important changes for clinical practice include reducing unnecessary laparoscopy and procedures without benefit, such as laparoscopic uterosacral nerve ablation and presacral neurectomy, and GnRH suppression using an oral antagonist, said Dr. Trolice. Other especially practical guidance includes the recommendation to discontinue advising patients that pregnancy will reduce symptoms of endometriosis, and to avoid prescribing estrogen-only treatment in menopause given the risk of malignant transformation of endometriosis, he said.
Another clinically useful recommendation, though not a significant update, is the need to identify extrapelvic endometriosis symptoms, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules that enlarge during menses, Dr. Trolice added.
Barriers to implementing the updated guidelines include lack of education of clinicians, including primary care providers, and the lack of definitive evidence for many areas, he noted.
As for additional research, more data are needed to explore the genetic, mutational, and epigenetic profile of endometriosis, and to identify biomarkers to noninvasively detect and provide a prognosis for endometriosis, and optimal methods for prevention and management, said Dr. Trolice. Other research gaps include “definitive medical and surgical treatment of endometriosis for improvement of fertility, quality of life, and reduction of pain,” he noted. From a fertility standpoint, more studies are needed on “the use of ovarian tissue or oocytes cryopreservation in adolescents and adults who undergo ovarian surgery for endometriomas, and the role of the EFI as a presurgical triage tool and to predict IUI outcomes,” said Dr. Trolice.
Overall, society recommendations such as these from ESHRE “serve as guides for physicians by providing evidence-based medicine and dispelling prior unproven practices so patients may receive the most effective care of endometriosis, throughout a woman’s life,” Dr. Trolice emphasized.
The current guideline will be considered for revision in 2025, and the full version is available on the ESHRE website.
Members of the ESHRE guideline development group received no payment for participating in the development process, although they were reimbursed for travel expenses related to guideline meetings.
Dr. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.
Bowel prep: Electrolyte disturbances remain rare but serious
Patients undergoing bowel prep for colonoscopy had significantly greater decreases in potassium after prep with sodium phosphate, compared with those whose prep involved polyethylene glycol, based on data from a meta-analysis of more than 2,000 patients.
Electrolyte disturbances, though rare, represent a serious adverse event associated with bowel preparation, and the prevalence remains unclear, Atsushi Sakuraba, MD, of the University of Chicago said in an interview. Dr. Sakuraba, who was not involved in the study, said he was surprised by some of the study findings. “The incidence and degree of hypokalemia associated with sodium phosphate bowel preparation was greater than what I would have thought.”
Authors of the current analysis, led by Ankie Reumkens, MD, of Maastricht (the Netherlands) University Medical Center, noted in Digestive Endoscopy that the severity of adverse events is not directly related to the degree of electrolyte disturbance. “Electrolyte disturbances may vary from asymptomatic via mild and moderate symptoms (i.e., muscle weakness, constipation, nausea, and vomiting), to severe symptoms (i.e., paralysis, seizures, cardiac arrhythmias, coma, and death).” Although current guidelines do not include recommendations for electrolyte measurement, the European Society of Gastrointestinal Endoscopy recommends against routine use of sodium phosphate (NaP) despite a low level of evidence. Although polyethylene glycol (PEG) is the preferred choice for older patients and in patients with renal impairment, heart failure, and inflammatory bowel disease, the investigators noted that NaP and picosulfate with magnesium titrate (SPMC) have been associated with higher patient tolerance and compliance.
Bowel preparation solutions are available in high-volume versions that include high-volume PEG, while low-volume options include low-volume PEG, NaP, and SPMC; despite the variety of choices, bowel preparations of any type may cause electrolyte disturbances, and their extent, magnitude, and risk factors have not been well studied.
In their systemic review and meta-analysis, the researchers examined the pooled prevalence of electrolyte disturbances; the primary endpoint was the pooled prevalence of hypokalemia, hyponatremia, hyperphosphatemia, and hypocalcemia after bowel preparation, and the changes in mean potassium values. The review was based on 13 studies published between Jan. 1, 1995, and July 1, 2021, with a total of 2,386 patients.
Overall, hypokalemia occurred in 17.2 % of patients who underwent NaP for bowel preparation versus 4.8% of those who underwent PEG. Hyponatremia occurred in 0.9% of NaP patients versus3.3% of PEG patients; hyperphosphatemia occurred in 37.3% and 0.65% of NaP and PEG patients, respectively; and hypocalcemia occurred in 15.6% and 8.1% of NaP and PEG patients, respectively.
Pharmacokinetics may explain the increased disturbances in electrolyte balance with NaP, the researchers noted.
“PEG is iso-osmotic with plasma, causing no net absorption or excretion of water or ions,” they said, but “NaP is highly osmotic and therefore results in fluid shifts from the systemic compartment to the gastrointestinal tract.”
The study findings were limited by several factors including the potential underreporting of the prevalence of electrolyte disturbances, the exclusion of patients with renal insufficiency, heart failure, and bowel problems, and the incomplete data on bowel cleansing scores and adverse events, the researchers noted. More data on the prevalences of electrolyte disturbances after low-volume bowel preparations are needed to inform evidence-based recommendations, especially in light of the increased numbers of colonoscopies and increasing numbers of older patients and patients with comorbidities.
From a clinical practice perspective, Dr. Sakuraba agreed with the authors’ conclusion that the results support the recommendations of some current guidelines against the routine use of sodium phosphate for bowel preparation, even if the number of included studies was small.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.
Patients undergoing bowel prep for colonoscopy had significantly greater decreases in potassium after prep with sodium phosphate, compared with those whose prep involved polyethylene glycol, based on data from a meta-analysis of more than 2,000 patients.
Electrolyte disturbances, though rare, represent a serious adverse event associated with bowel preparation, and the prevalence remains unclear, Atsushi Sakuraba, MD, of the University of Chicago said in an interview. Dr. Sakuraba, who was not involved in the study, said he was surprised by some of the study findings. “The incidence and degree of hypokalemia associated with sodium phosphate bowel preparation was greater than what I would have thought.”
Authors of the current analysis, led by Ankie Reumkens, MD, of Maastricht (the Netherlands) University Medical Center, noted in Digestive Endoscopy that the severity of adverse events is not directly related to the degree of electrolyte disturbance. “Electrolyte disturbances may vary from asymptomatic via mild and moderate symptoms (i.e., muscle weakness, constipation, nausea, and vomiting), to severe symptoms (i.e., paralysis, seizures, cardiac arrhythmias, coma, and death).” Although current guidelines do not include recommendations for electrolyte measurement, the European Society of Gastrointestinal Endoscopy recommends against routine use of sodium phosphate (NaP) despite a low level of evidence. Although polyethylene glycol (PEG) is the preferred choice for older patients and in patients with renal impairment, heart failure, and inflammatory bowel disease, the investigators noted that NaP and picosulfate with magnesium titrate (SPMC) have been associated with higher patient tolerance and compliance.
Bowel preparation solutions are available in high-volume versions that include high-volume PEG, while low-volume options include low-volume PEG, NaP, and SPMC; despite the variety of choices, bowel preparations of any type may cause electrolyte disturbances, and their extent, magnitude, and risk factors have not been well studied.
In their systemic review and meta-analysis, the researchers examined the pooled prevalence of electrolyte disturbances; the primary endpoint was the pooled prevalence of hypokalemia, hyponatremia, hyperphosphatemia, and hypocalcemia after bowel preparation, and the changes in mean potassium values. The review was based on 13 studies published between Jan. 1, 1995, and July 1, 2021, with a total of 2,386 patients.
Overall, hypokalemia occurred in 17.2 % of patients who underwent NaP for bowel preparation versus 4.8% of those who underwent PEG. Hyponatremia occurred in 0.9% of NaP patients versus3.3% of PEG patients; hyperphosphatemia occurred in 37.3% and 0.65% of NaP and PEG patients, respectively; and hypocalcemia occurred in 15.6% and 8.1% of NaP and PEG patients, respectively.
Pharmacokinetics may explain the increased disturbances in electrolyte balance with NaP, the researchers noted.
“PEG is iso-osmotic with plasma, causing no net absorption or excretion of water or ions,” they said, but “NaP is highly osmotic and therefore results in fluid shifts from the systemic compartment to the gastrointestinal tract.”
The study findings were limited by several factors including the potential underreporting of the prevalence of electrolyte disturbances, the exclusion of patients with renal insufficiency, heart failure, and bowel problems, and the incomplete data on bowel cleansing scores and adverse events, the researchers noted. More data on the prevalences of electrolyte disturbances after low-volume bowel preparations are needed to inform evidence-based recommendations, especially in light of the increased numbers of colonoscopies and increasing numbers of older patients and patients with comorbidities.
From a clinical practice perspective, Dr. Sakuraba agreed with the authors’ conclusion that the results support the recommendations of some current guidelines against the routine use of sodium phosphate for bowel preparation, even if the number of included studies was small.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.
Patients undergoing bowel prep for colonoscopy had significantly greater decreases in potassium after prep with sodium phosphate, compared with those whose prep involved polyethylene glycol, based on data from a meta-analysis of more than 2,000 patients.
Electrolyte disturbances, though rare, represent a serious adverse event associated with bowel preparation, and the prevalence remains unclear, Atsushi Sakuraba, MD, of the University of Chicago said in an interview. Dr. Sakuraba, who was not involved in the study, said he was surprised by some of the study findings. “The incidence and degree of hypokalemia associated with sodium phosphate bowel preparation was greater than what I would have thought.”
Authors of the current analysis, led by Ankie Reumkens, MD, of Maastricht (the Netherlands) University Medical Center, noted in Digestive Endoscopy that the severity of adverse events is not directly related to the degree of electrolyte disturbance. “Electrolyte disturbances may vary from asymptomatic via mild and moderate symptoms (i.e., muscle weakness, constipation, nausea, and vomiting), to severe symptoms (i.e., paralysis, seizures, cardiac arrhythmias, coma, and death).” Although current guidelines do not include recommendations for electrolyte measurement, the European Society of Gastrointestinal Endoscopy recommends against routine use of sodium phosphate (NaP) despite a low level of evidence. Although polyethylene glycol (PEG) is the preferred choice for older patients and in patients with renal impairment, heart failure, and inflammatory bowel disease, the investigators noted that NaP and picosulfate with magnesium titrate (SPMC) have been associated with higher patient tolerance and compliance.
Bowel preparation solutions are available in high-volume versions that include high-volume PEG, while low-volume options include low-volume PEG, NaP, and SPMC; despite the variety of choices, bowel preparations of any type may cause electrolyte disturbances, and their extent, magnitude, and risk factors have not been well studied.
In their systemic review and meta-analysis, the researchers examined the pooled prevalence of electrolyte disturbances; the primary endpoint was the pooled prevalence of hypokalemia, hyponatremia, hyperphosphatemia, and hypocalcemia after bowel preparation, and the changes in mean potassium values. The review was based on 13 studies published between Jan. 1, 1995, and July 1, 2021, with a total of 2,386 patients.
Overall, hypokalemia occurred in 17.2 % of patients who underwent NaP for bowel preparation versus 4.8% of those who underwent PEG. Hyponatremia occurred in 0.9% of NaP patients versus3.3% of PEG patients; hyperphosphatemia occurred in 37.3% and 0.65% of NaP and PEG patients, respectively; and hypocalcemia occurred in 15.6% and 8.1% of NaP and PEG patients, respectively.
Pharmacokinetics may explain the increased disturbances in electrolyte balance with NaP, the researchers noted.
“PEG is iso-osmotic with plasma, causing no net absorption or excretion of water or ions,” they said, but “NaP is highly osmotic and therefore results in fluid shifts from the systemic compartment to the gastrointestinal tract.”
The study findings were limited by several factors including the potential underreporting of the prevalence of electrolyte disturbances, the exclusion of patients with renal insufficiency, heart failure, and bowel problems, and the incomplete data on bowel cleansing scores and adverse events, the researchers noted. More data on the prevalences of electrolyte disturbances after low-volume bowel preparations are needed to inform evidence-based recommendations, especially in light of the increased numbers of colonoscopies and increasing numbers of older patients and patients with comorbidities.
From a clinical practice perspective, Dr. Sakuraba agreed with the authors’ conclusion that the results support the recommendations of some current guidelines against the routine use of sodium phosphate for bowel preparation, even if the number of included studies was small.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.
FROM DIGESTIVE ENDOSCOPY
IBD classification needs an upgrade
The current clinical classification tools for inflammatory bowel disease (IBD) are suboptimal, and revision beyond the broad categories of Crohn’s disease (CD) and ulcerative colitis (UC) could improve trial design, research, and ultimately patient outcomes, according to the authors of a recent review.
“Despite clear improvements in our understanding of disease biology and increasing treatment options, we still face an important therapeutic ceiling [in IBD],” wrote Bram Verstockt, MD, of University Hospitals Leuven, Belgium, and colleagues.
“In part, our limited therapeutic successes can be attributed to the disease heterogeneity of IBD: There is not one CD, nor a single UC phenotype,” therefore, a revision of the current systems based on better understanding of IBD is needed, the researchers said.
In a review article published in Gastroenterology, the researchers identified clinical features important to IBD heterogeneity, examined limitations of the current classifications, and proposed improvements.
Characterizing a complex condition
IBD diagnosis is challenging not only because of the overlapping phenotypes, but because other pathologies, including infections, can mimic IBD, the authors noted.
Age of onset should be considered in characterizing IBD, they wrote. Notably, patients with late-onset CD should be distinguished from elderly patients who have had CD for years. The authors cited research showing that “the development of IBD at extremes of age are specific sub-groups that require a different clinical recognition and clinical management,” and that large sample sizes and unbiased statistical methods are needed to define subgroups of IBD patients.
Current CD classification (the Montreal Classification) involves disease location, disease behavior, and age at diagnosis, and considers four phenotypes within disease location: involvement of the ileum, involvement of the colon, involvement of both the ileum and the colon, or isolated upper disease.* “Recently, there has been notable interest in the differential response rates among ileal predominant CD compared to colonic CD,” the authors wrote. Consequently, they proposed a revision of CD classification based on location. Genetic data appear to support this revision. In an IBD genotype-phenotype study including nearly 30,000 patients, three loci (NOD2, MHC, MST1 3p21) were strongly associated with disease location, they said. Other emerging evidence suggests that gut microbiota may vary according to disease location. The authors identified clinical aspects of CD classification based on disease location that distinguish small bowel predominant CD versus colonic predominant CD. Ileal disease patients have shown an increased risk for undergoing surgery, while those with colonic involvement have an increased risk for developing extraintestinal manifestations.
They also emphasized the value of considering rectal inflammation, which significantly impacts surgical procedures in CD.
Standard UC classification is based on macroscopic disease in the colon at the time of inflammation, the authors said. Although this approach allows for quick assessment of a patient’s risk of colectomy, the authors proposed improvements, including the use of serum biomarkers (C-reactive protein or erythrocyte sedimentation rate) to identify patients at highest risk for colectomy and colon cancer based on inflammation. The authors also suggested that patients with refractory proctitis be enrolled in UC clinical trials or in studies focusing on refractory proctitis in particular.
The pelvic pouch has become the most often performed surgical procedure for patients undergoing colectomy, but there is no agreement on classification of inflammatory pelvic pouch disorders, and studies of etiology and treatment are lacking, the authors noted. They advised a clinical assessment based on symptoms, including stool frequency, urgency, and incontinence. They also suggested that afferent limb ulcers of erosions should be classified separately from pouch inflammation.
The authors ended by noting that extraintestinal manifestations (EIMs) that occur in up to half of IBD patients may or may not be directly related to intestinal disease, and may represent a different phenotype, and the presence and type of EIM should be included in a revised IBD classification system, they said.
The authors emphasized that continuing to refer to IBD as only CD and UC “does a great disservice to our attempts to better understand IBD pathogenesis and to improve clinical patient management.”
They concluded: “Although revised clinical classification tools alone will not be sufficient and should be complemented by deeper and more detailed study into molecular subclassification of disease, the considerations here could be used as a springboard toward improved trial design, future translational research approaches and better treatment outcomes for patients.”
Review reflects complexity of IBD and challenges of change
The review is important at this time because of the growing recognition that IBD, while traditionally categorized as either UC or CD, is most likely composed of a range of heterogeneous conditions involving inflammation of the gastrointestinal tract, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview.
“Evidence that our current classification of IBD is suboptimal comes from both the wide range of clinical phenotypes as well as complexity in genetic markers that are associated with IBD,” he said. “It is well accepted in the gastroenterology community that IBD is a complex condition; so it is surprising to me that the dichotomy of UC vs. Crohn’s disease has rarely been challenged,” said Dr. Roper. “The authors of this review should be commended for raising the question of whether IBD deserves a more nuanced classification system that reflects the growing recognition of the wide heterogeneity of patient presentations and genetics,” he said.
“Challenging medical definitions is inherently difficult because patient diagnoses, treatment plans, as well as decades of clinical research have been based on well-accepted disease categories. Another major challenge in reclassification is that the course of IBD can vary greatly over time in the same patient in severity, range, and complexity, and potentially includes many disease subtypes noted by the authors of this review,” he added. “Therefore, I believe that the current system of dividing IBD in UC and CD is here to stay until subtypes based on mechanisms of disease pathogenesis are discovered.
“Additional research is needed to understand the molecular basis of IBD,” Dr. Roper emphasized. “Recent advances in RNA expression and proteomics at the single cell level may reveal distinct cell types or cell functions in tissues from IBD patients that may help us understand clinical phenotype or response to therapy.”
The study received no outside funding. The authors disclosed financial relationships with AbbVie, Biogen, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, and Truvion. Dr. Roper had no financial conflicts to disclose.
Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD.
*Correction, 4/11/22: An earlier version of this article misstated the Montreal Classification.
The current clinical classification tools for inflammatory bowel disease (IBD) are suboptimal, and revision beyond the broad categories of Crohn’s disease (CD) and ulcerative colitis (UC) could improve trial design, research, and ultimately patient outcomes, according to the authors of a recent review.
“Despite clear improvements in our understanding of disease biology and increasing treatment options, we still face an important therapeutic ceiling [in IBD],” wrote Bram Verstockt, MD, of University Hospitals Leuven, Belgium, and colleagues.
“In part, our limited therapeutic successes can be attributed to the disease heterogeneity of IBD: There is not one CD, nor a single UC phenotype,” therefore, a revision of the current systems based on better understanding of IBD is needed, the researchers said.
In a review article published in Gastroenterology, the researchers identified clinical features important to IBD heterogeneity, examined limitations of the current classifications, and proposed improvements.
Characterizing a complex condition
IBD diagnosis is challenging not only because of the overlapping phenotypes, but because other pathologies, including infections, can mimic IBD, the authors noted.
Age of onset should be considered in characterizing IBD, they wrote. Notably, patients with late-onset CD should be distinguished from elderly patients who have had CD for years. The authors cited research showing that “the development of IBD at extremes of age are specific sub-groups that require a different clinical recognition and clinical management,” and that large sample sizes and unbiased statistical methods are needed to define subgroups of IBD patients.
Current CD classification (the Montreal Classification) involves disease location, disease behavior, and age at diagnosis, and considers four phenotypes within disease location: involvement of the ileum, involvement of the colon, involvement of both the ileum and the colon, or isolated upper disease.* “Recently, there has been notable interest in the differential response rates among ileal predominant CD compared to colonic CD,” the authors wrote. Consequently, they proposed a revision of CD classification based on location. Genetic data appear to support this revision. In an IBD genotype-phenotype study including nearly 30,000 patients, three loci (NOD2, MHC, MST1 3p21) were strongly associated with disease location, they said. Other emerging evidence suggests that gut microbiota may vary according to disease location. The authors identified clinical aspects of CD classification based on disease location that distinguish small bowel predominant CD versus colonic predominant CD. Ileal disease patients have shown an increased risk for undergoing surgery, while those with colonic involvement have an increased risk for developing extraintestinal manifestations.
They also emphasized the value of considering rectal inflammation, which significantly impacts surgical procedures in CD.
Standard UC classification is based on macroscopic disease in the colon at the time of inflammation, the authors said. Although this approach allows for quick assessment of a patient’s risk of colectomy, the authors proposed improvements, including the use of serum biomarkers (C-reactive protein or erythrocyte sedimentation rate) to identify patients at highest risk for colectomy and colon cancer based on inflammation. The authors also suggested that patients with refractory proctitis be enrolled in UC clinical trials or in studies focusing on refractory proctitis in particular.
The pelvic pouch has become the most often performed surgical procedure for patients undergoing colectomy, but there is no agreement on classification of inflammatory pelvic pouch disorders, and studies of etiology and treatment are lacking, the authors noted. They advised a clinical assessment based on symptoms, including stool frequency, urgency, and incontinence. They also suggested that afferent limb ulcers of erosions should be classified separately from pouch inflammation.
The authors ended by noting that extraintestinal manifestations (EIMs) that occur in up to half of IBD patients may or may not be directly related to intestinal disease, and may represent a different phenotype, and the presence and type of EIM should be included in a revised IBD classification system, they said.
The authors emphasized that continuing to refer to IBD as only CD and UC “does a great disservice to our attempts to better understand IBD pathogenesis and to improve clinical patient management.”
They concluded: “Although revised clinical classification tools alone will not be sufficient and should be complemented by deeper and more detailed study into molecular subclassification of disease, the considerations here could be used as a springboard toward improved trial design, future translational research approaches and better treatment outcomes for patients.”
Review reflects complexity of IBD and challenges of change
The review is important at this time because of the growing recognition that IBD, while traditionally categorized as either UC or CD, is most likely composed of a range of heterogeneous conditions involving inflammation of the gastrointestinal tract, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview.
“Evidence that our current classification of IBD is suboptimal comes from both the wide range of clinical phenotypes as well as complexity in genetic markers that are associated with IBD,” he said. “It is well accepted in the gastroenterology community that IBD is a complex condition; so it is surprising to me that the dichotomy of UC vs. Crohn’s disease has rarely been challenged,” said Dr. Roper. “The authors of this review should be commended for raising the question of whether IBD deserves a more nuanced classification system that reflects the growing recognition of the wide heterogeneity of patient presentations and genetics,” he said.
“Challenging medical definitions is inherently difficult because patient diagnoses, treatment plans, as well as decades of clinical research have been based on well-accepted disease categories. Another major challenge in reclassification is that the course of IBD can vary greatly over time in the same patient in severity, range, and complexity, and potentially includes many disease subtypes noted by the authors of this review,” he added. “Therefore, I believe that the current system of dividing IBD in UC and CD is here to stay until subtypes based on mechanisms of disease pathogenesis are discovered.
“Additional research is needed to understand the molecular basis of IBD,” Dr. Roper emphasized. “Recent advances in RNA expression and proteomics at the single cell level may reveal distinct cell types or cell functions in tissues from IBD patients that may help us understand clinical phenotype or response to therapy.”
The study received no outside funding. The authors disclosed financial relationships with AbbVie, Biogen, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, and Truvion. Dr. Roper had no financial conflicts to disclose.
Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD.
*Correction, 4/11/22: An earlier version of this article misstated the Montreal Classification.
The current clinical classification tools for inflammatory bowel disease (IBD) are suboptimal, and revision beyond the broad categories of Crohn’s disease (CD) and ulcerative colitis (UC) could improve trial design, research, and ultimately patient outcomes, according to the authors of a recent review.
“Despite clear improvements in our understanding of disease biology and increasing treatment options, we still face an important therapeutic ceiling [in IBD],” wrote Bram Verstockt, MD, of University Hospitals Leuven, Belgium, and colleagues.
“In part, our limited therapeutic successes can be attributed to the disease heterogeneity of IBD: There is not one CD, nor a single UC phenotype,” therefore, a revision of the current systems based on better understanding of IBD is needed, the researchers said.
In a review article published in Gastroenterology, the researchers identified clinical features important to IBD heterogeneity, examined limitations of the current classifications, and proposed improvements.
Characterizing a complex condition
IBD diagnosis is challenging not only because of the overlapping phenotypes, but because other pathologies, including infections, can mimic IBD, the authors noted.
Age of onset should be considered in characterizing IBD, they wrote. Notably, patients with late-onset CD should be distinguished from elderly patients who have had CD for years. The authors cited research showing that “the development of IBD at extremes of age are specific sub-groups that require a different clinical recognition and clinical management,” and that large sample sizes and unbiased statistical methods are needed to define subgroups of IBD patients.
Current CD classification (the Montreal Classification) involves disease location, disease behavior, and age at diagnosis, and considers four phenotypes within disease location: involvement of the ileum, involvement of the colon, involvement of both the ileum and the colon, or isolated upper disease.* “Recently, there has been notable interest in the differential response rates among ileal predominant CD compared to colonic CD,” the authors wrote. Consequently, they proposed a revision of CD classification based on location. Genetic data appear to support this revision. In an IBD genotype-phenotype study including nearly 30,000 patients, three loci (NOD2, MHC, MST1 3p21) were strongly associated with disease location, they said. Other emerging evidence suggests that gut microbiota may vary according to disease location. The authors identified clinical aspects of CD classification based on disease location that distinguish small bowel predominant CD versus colonic predominant CD. Ileal disease patients have shown an increased risk for undergoing surgery, while those with colonic involvement have an increased risk for developing extraintestinal manifestations.
They also emphasized the value of considering rectal inflammation, which significantly impacts surgical procedures in CD.
Standard UC classification is based on macroscopic disease in the colon at the time of inflammation, the authors said. Although this approach allows for quick assessment of a patient’s risk of colectomy, the authors proposed improvements, including the use of serum biomarkers (C-reactive protein or erythrocyte sedimentation rate) to identify patients at highest risk for colectomy and colon cancer based on inflammation. The authors also suggested that patients with refractory proctitis be enrolled in UC clinical trials or in studies focusing on refractory proctitis in particular.
The pelvic pouch has become the most often performed surgical procedure for patients undergoing colectomy, but there is no agreement on classification of inflammatory pelvic pouch disorders, and studies of etiology and treatment are lacking, the authors noted. They advised a clinical assessment based on symptoms, including stool frequency, urgency, and incontinence. They also suggested that afferent limb ulcers of erosions should be classified separately from pouch inflammation.
The authors ended by noting that extraintestinal manifestations (EIMs) that occur in up to half of IBD patients may or may not be directly related to intestinal disease, and may represent a different phenotype, and the presence and type of EIM should be included in a revised IBD classification system, they said.
The authors emphasized that continuing to refer to IBD as only CD and UC “does a great disservice to our attempts to better understand IBD pathogenesis and to improve clinical patient management.”
They concluded: “Although revised clinical classification tools alone will not be sufficient and should be complemented by deeper and more detailed study into molecular subclassification of disease, the considerations here could be used as a springboard toward improved trial design, future translational research approaches and better treatment outcomes for patients.”
Review reflects complexity of IBD and challenges of change
The review is important at this time because of the growing recognition that IBD, while traditionally categorized as either UC or CD, is most likely composed of a range of heterogeneous conditions involving inflammation of the gastrointestinal tract, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview.
“Evidence that our current classification of IBD is suboptimal comes from both the wide range of clinical phenotypes as well as complexity in genetic markers that are associated with IBD,” he said. “It is well accepted in the gastroenterology community that IBD is a complex condition; so it is surprising to me that the dichotomy of UC vs. Crohn’s disease has rarely been challenged,” said Dr. Roper. “The authors of this review should be commended for raising the question of whether IBD deserves a more nuanced classification system that reflects the growing recognition of the wide heterogeneity of patient presentations and genetics,” he said.
“Challenging medical definitions is inherently difficult because patient diagnoses, treatment plans, as well as decades of clinical research have been based on well-accepted disease categories. Another major challenge in reclassification is that the course of IBD can vary greatly over time in the same patient in severity, range, and complexity, and potentially includes many disease subtypes noted by the authors of this review,” he added. “Therefore, I believe that the current system of dividing IBD in UC and CD is here to stay until subtypes based on mechanisms of disease pathogenesis are discovered.
“Additional research is needed to understand the molecular basis of IBD,” Dr. Roper emphasized. “Recent advances in RNA expression and proteomics at the single cell level may reveal distinct cell types or cell functions in tissues from IBD patients that may help us understand clinical phenotype or response to therapy.”
The study received no outside funding. The authors disclosed financial relationships with AbbVie, Biogen, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, and Truvion. Dr. Roper had no financial conflicts to disclose.
Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD.
*Correction, 4/11/22: An earlier version of this article misstated the Montreal Classification.
FROM GASTROENTEROLOGY
IBD classification needs an upgrade
The current clinical classification tools for inflammatory bowel disease (IBD) are suboptimal, and revision beyond the broad categories of Crohn’s disease (CD) and ulcerative colitis (UC) could improve trial design, research, and ultimately patient outcomes, according to the authors of a recent review.
“Despite clear improvements in our understanding of disease biology and increasing treatment options, we still face an important therapeutic ceiling [in IBD],” wrote Bram Verstockt, MD, of University Hospitals Leuven, Belgium, and colleagues.
“In part, our limited therapeutic successes can be attributed to the disease heterogeneity of IBD: There is not one CD, nor a single UC phenotype,” therefore, a revision of the current systems based on better understanding of IBD is needed, the researchers said.
In a review article published in Gastroenterology, the researchers identified clinical features important to IBD heterogeneity, examined limitations of the current classifications, and proposed improvements.
Characterizing a complex condition
IBD diagnosis is challenging not only because of the overlapping phenotypes, but because other pathologies, including infections, can mimic IBD, the authors noted.
Age of onset should be considered in characterizing IBD, they wrote. Notably, patients with late-onset CD should be distinguished from elderly patients who have had CD for years. The authors cited research showing that “the development of IBD at extremes of age are specific sub-groups that require a different clinical recognition and clinical management,” and that large sample sizes and unbiased statistical methods are needed to define subgroups of IBD patients.
Current CD classification (the Montreal Classification) involves disease location, disease behavior, and age at diagnosis, and considers four phenotypes within disease location: involvement of the ileum, involvement of the colon, involvement of both the ileum and the colon, or isolated upper disease.* “Recently, there has been notable interest in the differential response rates among ileal predominant CD compared to colonic CD,” the authors wrote. Consequently, they proposed a revision of CD classification based on location. Genetic data appear to support this revision. In an IBD genotype-phenotype study including nearly 30,000 patients, three loci (NOD2, MHC, MST1 3p21) were strongly associated with disease location, they said. Other emerging evidence suggests that gut microbiota may vary according to disease location. The authors identified clinical aspects of CD classification based on disease location that distinguish small bowel predominant CD versus colonic predominant CD. Ileal disease patients have shown an increased risk for undergoing surgery, while those with colonic involvement have an increased risk for developing extraintestinal manifestations.
They also emphasized the value of considering rectal inflammation, which significantly impacts surgical procedures in CD.
Standard UC classification is based on macroscopic disease in the colon at the time of inflammation, the authors said. Although this approach allows for quick assessment of a patient’s risk of colectomy, the authors proposed improvements, including the use of serum biomarkers (C-reactive protein or erythrocyte sedimentation rate) to identify patients at highest risk for colectomy and colon cancer based on inflammation. The authors also suggested that patients with refractory proctitis be enrolled in UC clinical trials or in studies focusing on refractory proctitis in particular.
The pelvic pouch has become the most often performed surgical procedure for patients undergoing colectomy, but there is no agreement on classification of inflammatory pelvic pouch disorders, and studies of etiology and treatment are lacking, the authors noted. They advised a clinical assessment based on symptoms, including stool frequency, urgency, and incontinence. They also suggested that afferent limb ulcers of erosions should be classified separately from pouch inflammation.
The authors ended by noting that extraintestinal manifestations (EIMs) that occur in up to half of IBD patients may or may not be directly related to intestinal disease, and may represent a different phenotype, and the presence and type of EIM should be included in a revised IBD classification system, they said.
The authors emphasized that continuing to refer to IBD as only CD and UC “does a great disservice to our attempts to better understand IBD pathogenesis and to improve clinical patient management.”
They concluded: “Although revised clinical classification tools alone will not be sufficient and should be complemented by deeper and more detailed study into molecular subclassification of disease, the considerations here could be used as a springboard toward improved trial design, future translational research approaches and better treatment outcomes for patients.”
Review reflects complexity of IBD and challenges of change
The review is important at this time because of the growing recognition that IBD, while traditionally categorized as either UC or CD, is most likely composed of a range of heterogeneous conditions involving inflammation of the gastrointestinal tract, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview.
“Evidence that our current classification of IBD is suboptimal comes from both the wide range of clinical phenotypes as well as complexity in genetic markers that are associated with IBD,” he said. “It is well accepted in the gastroenterology community that IBD is a complex condition; so it is surprising to me that the dichotomy of UC vs. Crohn’s disease has rarely been challenged,” said Dr. Roper. “The authors of this review should be commended for raising the question of whether IBD deserves a more nuanced classification system that reflects the growing recognition of the wide heterogeneity of patient presentations and genetics,” he said.
“Challenging medical definitions is inherently difficult because patient diagnoses, treatment plans, as well as decades of clinical research have been based on well-accepted disease categories. Another major challenge in reclassification is that the course of IBD can vary greatly over time in the same patient in severity, range, and complexity, and potentially includes many disease subtypes noted by the authors of this review,” he added. “Therefore, I believe that the current system of dividing IBD in UC and CD is here to stay until subtypes based on mechanisms of disease pathogenesis are discovered.
“Additional research is needed to understand the molecular basis of IBD,” Dr. Roper emphasized. “Recent advances in RNA expression and proteomics at the single cell level may reveal distinct cell types or cell functions in tissues from IBD patients that may help us understand clinical phenotype or response to therapy.”
The study received no outside funding. The authors disclosed financial relationships with AbbVie, Biogen, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, and Truvion. Dr. Roper had no financial conflicts to disclose.
Correction, 4/13/22: An earlier version of this article misstated the Montreal Classification.
The current clinical classification tools for inflammatory bowel disease (IBD) are suboptimal, and revision beyond the broad categories of Crohn’s disease (CD) and ulcerative colitis (UC) could improve trial design, research, and ultimately patient outcomes, according to the authors of a recent review.
“Despite clear improvements in our understanding of disease biology and increasing treatment options, we still face an important therapeutic ceiling [in IBD],” wrote Bram Verstockt, MD, of University Hospitals Leuven, Belgium, and colleagues.
“In part, our limited therapeutic successes can be attributed to the disease heterogeneity of IBD: There is not one CD, nor a single UC phenotype,” therefore, a revision of the current systems based on better understanding of IBD is needed, the researchers said.
In a review article published in Gastroenterology, the researchers identified clinical features important to IBD heterogeneity, examined limitations of the current classifications, and proposed improvements.
Characterizing a complex condition
IBD diagnosis is challenging not only because of the overlapping phenotypes, but because other pathologies, including infections, can mimic IBD, the authors noted.
Age of onset should be considered in characterizing IBD, they wrote. Notably, patients with late-onset CD should be distinguished from elderly patients who have had CD for years. The authors cited research showing that “the development of IBD at extremes of age are specific sub-groups that require a different clinical recognition and clinical management,” and that large sample sizes and unbiased statistical methods are needed to define subgroups of IBD patients.
Current CD classification (the Montreal Classification) involves disease location, disease behavior, and age at diagnosis, and considers four phenotypes within disease location: involvement of the ileum, involvement of the colon, involvement of both the ileum and the colon, or isolated upper disease.* “Recently, there has been notable interest in the differential response rates among ileal predominant CD compared to colonic CD,” the authors wrote. Consequently, they proposed a revision of CD classification based on location. Genetic data appear to support this revision. In an IBD genotype-phenotype study including nearly 30,000 patients, three loci (NOD2, MHC, MST1 3p21) were strongly associated with disease location, they said. Other emerging evidence suggests that gut microbiota may vary according to disease location. The authors identified clinical aspects of CD classification based on disease location that distinguish small bowel predominant CD versus colonic predominant CD. Ileal disease patients have shown an increased risk for undergoing surgery, while those with colonic involvement have an increased risk for developing extraintestinal manifestations.
They also emphasized the value of considering rectal inflammation, which significantly impacts surgical procedures in CD.
Standard UC classification is based on macroscopic disease in the colon at the time of inflammation, the authors said. Although this approach allows for quick assessment of a patient’s risk of colectomy, the authors proposed improvements, including the use of serum biomarkers (C-reactive protein or erythrocyte sedimentation rate) to identify patients at highest risk for colectomy and colon cancer based on inflammation. The authors also suggested that patients with refractory proctitis be enrolled in UC clinical trials or in studies focusing on refractory proctitis in particular.
The pelvic pouch has become the most often performed surgical procedure for patients undergoing colectomy, but there is no agreement on classification of inflammatory pelvic pouch disorders, and studies of etiology and treatment are lacking, the authors noted. They advised a clinical assessment based on symptoms, including stool frequency, urgency, and incontinence. They also suggested that afferent limb ulcers of erosions should be classified separately from pouch inflammation.
The authors ended by noting that extraintestinal manifestations (EIMs) that occur in up to half of IBD patients may or may not be directly related to intestinal disease, and may represent a different phenotype, and the presence and type of EIM should be included in a revised IBD classification system, they said.
The authors emphasized that continuing to refer to IBD as only CD and UC “does a great disservice to our attempts to better understand IBD pathogenesis and to improve clinical patient management.”
They concluded: “Although revised clinical classification tools alone will not be sufficient and should be complemented by deeper and more detailed study into molecular subclassification of disease, the considerations here could be used as a springboard toward improved trial design, future translational research approaches and better treatment outcomes for patients.”
Review reflects complexity of IBD and challenges of change
The review is important at this time because of the growing recognition that IBD, while traditionally categorized as either UC or CD, is most likely composed of a range of heterogeneous conditions involving inflammation of the gastrointestinal tract, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview.
“Evidence that our current classification of IBD is suboptimal comes from both the wide range of clinical phenotypes as well as complexity in genetic markers that are associated with IBD,” he said. “It is well accepted in the gastroenterology community that IBD is a complex condition; so it is surprising to me that the dichotomy of UC vs. Crohn’s disease has rarely been challenged,” said Dr. Roper. “The authors of this review should be commended for raising the question of whether IBD deserves a more nuanced classification system that reflects the growing recognition of the wide heterogeneity of patient presentations and genetics,” he said.
“Challenging medical definitions is inherently difficult because patient diagnoses, treatment plans, as well as decades of clinical research have been based on well-accepted disease categories. Another major challenge in reclassification is that the course of IBD can vary greatly over time in the same patient in severity, range, and complexity, and potentially includes many disease subtypes noted by the authors of this review,” he added. “Therefore, I believe that the current system of dividing IBD in UC and CD is here to stay until subtypes based on mechanisms of disease pathogenesis are discovered.
“Additional research is needed to understand the molecular basis of IBD,” Dr. Roper emphasized. “Recent advances in RNA expression and proteomics at the single cell level may reveal distinct cell types or cell functions in tissues from IBD patients that may help us understand clinical phenotype or response to therapy.”
The study received no outside funding. The authors disclosed financial relationships with AbbVie, Biogen, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, and Truvion. Dr. Roper had no financial conflicts to disclose.
Correction, 4/13/22: An earlier version of this article misstated the Montreal Classification.
The current clinical classification tools for inflammatory bowel disease (IBD) are suboptimal, and revision beyond the broad categories of Crohn’s disease (CD) and ulcerative colitis (UC) could improve trial design, research, and ultimately patient outcomes, according to the authors of a recent review.
“Despite clear improvements in our understanding of disease biology and increasing treatment options, we still face an important therapeutic ceiling [in IBD],” wrote Bram Verstockt, MD, of University Hospitals Leuven, Belgium, and colleagues.
“In part, our limited therapeutic successes can be attributed to the disease heterogeneity of IBD: There is not one CD, nor a single UC phenotype,” therefore, a revision of the current systems based on better understanding of IBD is needed, the researchers said.
In a review article published in Gastroenterology, the researchers identified clinical features important to IBD heterogeneity, examined limitations of the current classifications, and proposed improvements.
Characterizing a complex condition
IBD diagnosis is challenging not only because of the overlapping phenotypes, but because other pathologies, including infections, can mimic IBD, the authors noted.
Age of onset should be considered in characterizing IBD, they wrote. Notably, patients with late-onset CD should be distinguished from elderly patients who have had CD for years. The authors cited research showing that “the development of IBD at extremes of age are specific sub-groups that require a different clinical recognition and clinical management,” and that large sample sizes and unbiased statistical methods are needed to define subgroups of IBD patients.
Current CD classification (the Montreal Classification) involves disease location, disease behavior, and age at diagnosis, and considers four phenotypes within disease location: involvement of the ileum, involvement of the colon, involvement of both the ileum and the colon, or isolated upper disease.* “Recently, there has been notable interest in the differential response rates among ileal predominant CD compared to colonic CD,” the authors wrote. Consequently, they proposed a revision of CD classification based on location. Genetic data appear to support this revision. In an IBD genotype-phenotype study including nearly 30,000 patients, three loci (NOD2, MHC, MST1 3p21) were strongly associated with disease location, they said. Other emerging evidence suggests that gut microbiota may vary according to disease location. The authors identified clinical aspects of CD classification based on disease location that distinguish small bowel predominant CD versus colonic predominant CD. Ileal disease patients have shown an increased risk for undergoing surgery, while those with colonic involvement have an increased risk for developing extraintestinal manifestations.
They also emphasized the value of considering rectal inflammation, which significantly impacts surgical procedures in CD.
Standard UC classification is based on macroscopic disease in the colon at the time of inflammation, the authors said. Although this approach allows for quick assessment of a patient’s risk of colectomy, the authors proposed improvements, including the use of serum biomarkers (C-reactive protein or erythrocyte sedimentation rate) to identify patients at highest risk for colectomy and colon cancer based on inflammation. The authors also suggested that patients with refractory proctitis be enrolled in UC clinical trials or in studies focusing on refractory proctitis in particular.
The pelvic pouch has become the most often performed surgical procedure for patients undergoing colectomy, but there is no agreement on classification of inflammatory pelvic pouch disorders, and studies of etiology and treatment are lacking, the authors noted. They advised a clinical assessment based on symptoms, including stool frequency, urgency, and incontinence. They also suggested that afferent limb ulcers of erosions should be classified separately from pouch inflammation.
The authors ended by noting that extraintestinal manifestations (EIMs) that occur in up to half of IBD patients may or may not be directly related to intestinal disease, and may represent a different phenotype, and the presence and type of EIM should be included in a revised IBD classification system, they said.
The authors emphasized that continuing to refer to IBD as only CD and UC “does a great disservice to our attempts to better understand IBD pathogenesis and to improve clinical patient management.”
They concluded: “Although revised clinical classification tools alone will not be sufficient and should be complemented by deeper and more detailed study into molecular subclassification of disease, the considerations here could be used as a springboard toward improved trial design, future translational research approaches and better treatment outcomes for patients.”
Review reflects complexity of IBD and challenges of change
The review is important at this time because of the growing recognition that IBD, while traditionally categorized as either UC or CD, is most likely composed of a range of heterogeneous conditions involving inflammation of the gastrointestinal tract, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview.
“Evidence that our current classification of IBD is suboptimal comes from both the wide range of clinical phenotypes as well as complexity in genetic markers that are associated with IBD,” he said. “It is well accepted in the gastroenterology community that IBD is a complex condition; so it is surprising to me that the dichotomy of UC vs. Crohn’s disease has rarely been challenged,” said Dr. Roper. “The authors of this review should be commended for raising the question of whether IBD deserves a more nuanced classification system that reflects the growing recognition of the wide heterogeneity of patient presentations and genetics,” he said.
“Challenging medical definitions is inherently difficult because patient diagnoses, treatment plans, as well as decades of clinical research have been based on well-accepted disease categories. Another major challenge in reclassification is that the course of IBD can vary greatly over time in the same patient in severity, range, and complexity, and potentially includes many disease subtypes noted by the authors of this review,” he added. “Therefore, I believe that the current system of dividing IBD in UC and CD is here to stay until subtypes based on mechanisms of disease pathogenesis are discovered.
“Additional research is needed to understand the molecular basis of IBD,” Dr. Roper emphasized. “Recent advances in RNA expression and proteomics at the single cell level may reveal distinct cell types or cell functions in tissues from IBD patients that may help us understand clinical phenotype or response to therapy.”
The study received no outside funding. The authors disclosed financial relationships with AbbVie, Biogen, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, and Truvion. Dr. Roper had no financial conflicts to disclose.
Correction, 4/13/22: An earlier version of this article misstated the Montreal Classification.
FROM GASTROENTEROLOGY
Screen time in first year may raise autism risk at age 3
Boys exposed to at least 2 hours a day of screen time by 1 year of age were significantly more likely to have an autism spectrum disorder (ASD) diagnosis at 3 years, based on data from more than 80,000 children.
The World Health Organization and the American Academy of Pediatrics recommend against any screen time for infants up to 1 year of age and 18 months of age, respectively, wrote Megumi Kushima, MA, of the University of Yamanashi (Japan), and colleagues on behalf of the Japan Environment and Children’s Study Group.
The extent to which screen time duration in infancy is associated with subsequent ASD diagnosis remains unclear, the researchers said. The ongoing COVID-19 pandemic has increased screen time among children worldwide, which makes an examination of the impact of screen time on children’s health an important public health issue.
In a study published in JAMA Pediatrics, the researchers recruited pregnant women between 2011 and 2014; data were analyzed in December 2020. The final study population included 84,030 mother-child pairs. The primary exposure of screen time at 1 year of age was assessed by questionnaire, in which mothers were asked to report their number of hours they let their child watch TV or DVDs daily. Responses were none (no screen time), less than 1 hour, 1 hour or more but less than 2 hours, 2 hours or more but less than 4 hours, and 4 hours or more.
The primary outcome was ASD diagnosis at 3 years of age, and mothers were asked via questionnaire whether their 3-year-old had been diagnosed with ASD from age 2.
The study was conducted by the Japan Environment and Children’s Study Group at 15 regional centers across Japan.
Overall, 330 children had received an ASD diagnosis at age 3 years, a prevalence of 0.4%. Of these, 251 (76%) were boys, and 79 (24%) were girls. Independent of ASD, the most common response for screen time was less than 1 hour, which was reported by 27,707 mothers. The proportion of children with ASD at age 3 increased as screen time at age 1 increased, the percentages were 5.8%, 22.3%, 30.2%, and 31.7% for children with no screen time, less than 1 hour, 1 to less than 2 hours, and 2 to less than 4 hours, respectively. The percentage of children with ASD diagnoses who had 4 hours or more of daily screen time was 10%.
Logistic regression analysis showed that longer screen time at age 1 year was significantly associated with higher odds of ASD at 3 years in boys, but not in girls. The researchers controlled for variables including maternal maltreatment and children’s predisposition to ASD. Among boys, the adjusted odds ratios for screen times of less than 1 hour, 1 hour to less than 2 hours, 2 hours to less than 4 hours, and more than 4 hours were 1.38, 2.16, 3.48, and 3.02, respectively.
Screen time at age 3 years was not associated with ASD diagnosis at age 3 years, potentially “because the association with environmental factors on brain development varies with age,” the researchers noted.
The study findings were limited by several factors including the reliance on parental reports of screen time and potential for reporting bias, the researchers noted. Other limitations included the possible missed diagnoses of mild ASD cases at 3 years, and the inability to consider variables such as childcare environment, living conditions, diseases, genetics, and disabilities.
However, the results were strengthened by the large study population and examination of screen time in early childhood, they said. More research is needed to examine other factors that contribute to the association between ASD and screen time, but given the rapid increase in device use in children, “it is necessary to review its health effects on infants and control excessive screen time.”
Strong study, but some gaps appear
The study is strong in many respects, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.
However, “what I am not sure they addressed is that children on the spectrum are often not entertained by basic toys and may be hard to manage behaviorally,” Dr. Kinsella said. Consequently, parents may be more inclined to offer screen time as a way to pacify children with behavioral difficulties. “Parents also may see that their children are happier interacting with devices, so they may be more apt to let them continue with screen time.We know screen time is not good for the developing brain, however; I worry that the message from this study is that screen time causes autism in boys.
“What I would have liked to know from the parents who allowed more screen time was why they were offering it,” Dr. Kinsella said. “Was it because their child was difficult behaviorally or because that is the one place that they seemed to have satisfaction? To me, that would indicate the reverse hypothesis.” That said, the study findings “remind us to counsel families about screen time, especially in the age of COVID-19. Kids are home much longer than usual, which ultimately leads to more screen time.”
The study was funded by the Japanese Ministry of Environment. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.
Boys exposed to at least 2 hours a day of screen time by 1 year of age were significantly more likely to have an autism spectrum disorder (ASD) diagnosis at 3 years, based on data from more than 80,000 children.
The World Health Organization and the American Academy of Pediatrics recommend against any screen time for infants up to 1 year of age and 18 months of age, respectively, wrote Megumi Kushima, MA, of the University of Yamanashi (Japan), and colleagues on behalf of the Japan Environment and Children’s Study Group.
The extent to which screen time duration in infancy is associated with subsequent ASD diagnosis remains unclear, the researchers said. The ongoing COVID-19 pandemic has increased screen time among children worldwide, which makes an examination of the impact of screen time on children’s health an important public health issue.
In a study published in JAMA Pediatrics, the researchers recruited pregnant women between 2011 and 2014; data were analyzed in December 2020. The final study population included 84,030 mother-child pairs. The primary exposure of screen time at 1 year of age was assessed by questionnaire, in which mothers were asked to report their number of hours they let their child watch TV or DVDs daily. Responses were none (no screen time), less than 1 hour, 1 hour or more but less than 2 hours, 2 hours or more but less than 4 hours, and 4 hours or more.
The primary outcome was ASD diagnosis at 3 years of age, and mothers were asked via questionnaire whether their 3-year-old had been diagnosed with ASD from age 2.
The study was conducted by the Japan Environment and Children’s Study Group at 15 regional centers across Japan.
Overall, 330 children had received an ASD diagnosis at age 3 years, a prevalence of 0.4%. Of these, 251 (76%) were boys, and 79 (24%) were girls. Independent of ASD, the most common response for screen time was less than 1 hour, which was reported by 27,707 mothers. The proportion of children with ASD at age 3 increased as screen time at age 1 increased, the percentages were 5.8%, 22.3%, 30.2%, and 31.7% for children with no screen time, less than 1 hour, 1 to less than 2 hours, and 2 to less than 4 hours, respectively. The percentage of children with ASD diagnoses who had 4 hours or more of daily screen time was 10%.
Logistic regression analysis showed that longer screen time at age 1 year was significantly associated with higher odds of ASD at 3 years in boys, but not in girls. The researchers controlled for variables including maternal maltreatment and children’s predisposition to ASD. Among boys, the adjusted odds ratios for screen times of less than 1 hour, 1 hour to less than 2 hours, 2 hours to less than 4 hours, and more than 4 hours were 1.38, 2.16, 3.48, and 3.02, respectively.
Screen time at age 3 years was not associated with ASD diagnosis at age 3 years, potentially “because the association with environmental factors on brain development varies with age,” the researchers noted.
The study findings were limited by several factors including the reliance on parental reports of screen time and potential for reporting bias, the researchers noted. Other limitations included the possible missed diagnoses of mild ASD cases at 3 years, and the inability to consider variables such as childcare environment, living conditions, diseases, genetics, and disabilities.
However, the results were strengthened by the large study population and examination of screen time in early childhood, they said. More research is needed to examine other factors that contribute to the association between ASD and screen time, but given the rapid increase in device use in children, “it is necessary to review its health effects on infants and control excessive screen time.”
Strong study, but some gaps appear
The study is strong in many respects, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.
However, “what I am not sure they addressed is that children on the spectrum are often not entertained by basic toys and may be hard to manage behaviorally,” Dr. Kinsella said. Consequently, parents may be more inclined to offer screen time as a way to pacify children with behavioral difficulties. “Parents also may see that their children are happier interacting with devices, so they may be more apt to let them continue with screen time.We know screen time is not good for the developing brain, however; I worry that the message from this study is that screen time causes autism in boys.
“What I would have liked to know from the parents who allowed more screen time was why they were offering it,” Dr. Kinsella said. “Was it because their child was difficult behaviorally or because that is the one place that they seemed to have satisfaction? To me, that would indicate the reverse hypothesis.” That said, the study findings “remind us to counsel families about screen time, especially in the age of COVID-19. Kids are home much longer than usual, which ultimately leads to more screen time.”
The study was funded by the Japanese Ministry of Environment. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.
Boys exposed to at least 2 hours a day of screen time by 1 year of age were significantly more likely to have an autism spectrum disorder (ASD) diagnosis at 3 years, based on data from more than 80,000 children.
The World Health Organization and the American Academy of Pediatrics recommend against any screen time for infants up to 1 year of age and 18 months of age, respectively, wrote Megumi Kushima, MA, of the University of Yamanashi (Japan), and colleagues on behalf of the Japan Environment and Children’s Study Group.
The extent to which screen time duration in infancy is associated with subsequent ASD diagnosis remains unclear, the researchers said. The ongoing COVID-19 pandemic has increased screen time among children worldwide, which makes an examination of the impact of screen time on children’s health an important public health issue.
In a study published in JAMA Pediatrics, the researchers recruited pregnant women between 2011 and 2014; data were analyzed in December 2020. The final study population included 84,030 mother-child pairs. The primary exposure of screen time at 1 year of age was assessed by questionnaire, in which mothers were asked to report their number of hours they let their child watch TV or DVDs daily. Responses were none (no screen time), less than 1 hour, 1 hour or more but less than 2 hours, 2 hours or more but less than 4 hours, and 4 hours or more.
The primary outcome was ASD diagnosis at 3 years of age, and mothers were asked via questionnaire whether their 3-year-old had been diagnosed with ASD from age 2.
The study was conducted by the Japan Environment and Children’s Study Group at 15 regional centers across Japan.
Overall, 330 children had received an ASD diagnosis at age 3 years, a prevalence of 0.4%. Of these, 251 (76%) were boys, and 79 (24%) were girls. Independent of ASD, the most common response for screen time was less than 1 hour, which was reported by 27,707 mothers. The proportion of children with ASD at age 3 increased as screen time at age 1 increased, the percentages were 5.8%, 22.3%, 30.2%, and 31.7% for children with no screen time, less than 1 hour, 1 to less than 2 hours, and 2 to less than 4 hours, respectively. The percentage of children with ASD diagnoses who had 4 hours or more of daily screen time was 10%.
Logistic regression analysis showed that longer screen time at age 1 year was significantly associated with higher odds of ASD at 3 years in boys, but not in girls. The researchers controlled for variables including maternal maltreatment and children’s predisposition to ASD. Among boys, the adjusted odds ratios for screen times of less than 1 hour, 1 hour to less than 2 hours, 2 hours to less than 4 hours, and more than 4 hours were 1.38, 2.16, 3.48, and 3.02, respectively.
Screen time at age 3 years was not associated with ASD diagnosis at age 3 years, potentially “because the association with environmental factors on brain development varies with age,” the researchers noted.
The study findings were limited by several factors including the reliance on parental reports of screen time and potential for reporting bias, the researchers noted. Other limitations included the possible missed diagnoses of mild ASD cases at 3 years, and the inability to consider variables such as childcare environment, living conditions, diseases, genetics, and disabilities.
However, the results were strengthened by the large study population and examination of screen time in early childhood, they said. More research is needed to examine other factors that contribute to the association between ASD and screen time, but given the rapid increase in device use in children, “it is necessary to review its health effects on infants and control excessive screen time.”
Strong study, but some gaps appear
The study is strong in many respects, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.
However, “what I am not sure they addressed is that children on the spectrum are often not entertained by basic toys and may be hard to manage behaviorally,” Dr. Kinsella said. Consequently, parents may be more inclined to offer screen time as a way to pacify children with behavioral difficulties. “Parents also may see that their children are happier interacting with devices, so they may be more apt to let them continue with screen time.We know screen time is not good for the developing brain, however; I worry that the message from this study is that screen time causes autism in boys.
“What I would have liked to know from the parents who allowed more screen time was why they were offering it,” Dr. Kinsella said. “Was it because their child was difficult behaviorally or because that is the one place that they seemed to have satisfaction? To me, that would indicate the reverse hypothesis.” That said, the study findings “remind us to counsel families about screen time, especially in the age of COVID-19. Kids are home much longer than usual, which ultimately leads to more screen time.”
The study was funded by the Japanese Ministry of Environment. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.
FROM JAMA PEDIATRICS
Chronic respiratory conditions occur more often in RSV vs. flu
Hospitalized intensive care patients with respiratory syncytial virus were significantly more likely to be immunocompromised and to have chronic respiratory conditions than those with influenza infections, but in-hospital mortality rates were similar, based on data from 618 adults.
Respiratory syncytial virus is common in adults, but characteristics of RSV patients requiring ICU care have not been explored, despite routine testing for RSV in critically ill patients in many institutions, Julien Coussement, PhD, of Université Libre de Bruxelles, Brussels, and colleagues wrote.
“Influenza is another respiratory virus routinely tested for in ICU patients with respiratory symptoms because of its well-known morbidity and mortality, but there are no data specifically comparing RSV and influenza infections in adult ICU patients,” they noted.
In a retrospective, multicenter study published in the journal CHEST, the researchers analyzed data from 309 adult ICU patients with RSV infection and 309 with influenza infection between November 2011 and April 2018 from 17 sites in France and Belgium. Each RSV patient was matched to a flu patient according to institution and date of diagnosis.
The primary objective was a comparison of in-hospital mortality between the groups, defined as death from any cause during an index hospital stay in acute care. Secondary objectives were comparisons of the clinical and biological characteristics of patients with RSV versus flu.
Overall, in-hospital mortality was not significantly different between the RSV and influenza groups (23.9% vs. 25.6%, P = .63).
However, patients with RSV infection were significantly more likely than those with flu to have an underlying chronic respiratory condition (60.2% vs. 40.1%, P < .001) and to be immunocompromised (35% vs. 26.2%, P = .02). Very few of the patients overall (39 patients, 6.3%) were considered young and healthy prior to hospitalization; and significantly fewer of these were in the RSV group than in the influenza group (9 patients and 30 patients, respectively).
Airway obstruction at the time of diagnosis was significantly more common in the RSV patients than in influenza patients (49.5% vs. 39.5%, P = .01), but influenza patients were significantly more likely to have acute respiratory distress syndrome at the time of diagnosis (21.7% vs. 14.6%, P = .02). Rates of coinfections were similar between the groups, and approximately 60% of coinfected patients received at least 72 hours of therapeutic antibiotics. Overall length of hospital stay, ICU stay, and duration of mechanical ventilation were similar between the groups.
The results show that severe RSV occurs mainly in older patients with comorbidities, and these results reflect data from previous studies, the researchers wrote in their discussion. In addition, “patients with influenza infection were significantly more likely to have fever, myalgia, increased CPK level, thrombocytopenia and transaminitis at diagnosis than were those with RSV infection. Whether these differences may be used to guide patient management remains to be determined.”
The study findings were limited by several factors including the retrospective design, and testing for respiratory viruses on symptomatic patients only, rather than all ICU patients, the researchers noted. Other limitations include the inability to show a causal link between viral infections and patient outcomes and the heterogenous management of patients among different centers.
However, the results were strengthened by the large sample size and multivariate analysis, and support the need for interventions to prevent and treat severe RSV, they concluded.
The study received no outside funding. Lead author Dr. Coussement disclosed serving on advisory board for Sanofi.
Hospitalized intensive care patients with respiratory syncytial virus were significantly more likely to be immunocompromised and to have chronic respiratory conditions than those with influenza infections, but in-hospital mortality rates were similar, based on data from 618 adults.
Respiratory syncytial virus is common in adults, but characteristics of RSV patients requiring ICU care have not been explored, despite routine testing for RSV in critically ill patients in many institutions, Julien Coussement, PhD, of Université Libre de Bruxelles, Brussels, and colleagues wrote.
“Influenza is another respiratory virus routinely tested for in ICU patients with respiratory symptoms because of its well-known morbidity and mortality, but there are no data specifically comparing RSV and influenza infections in adult ICU patients,” they noted.
In a retrospective, multicenter study published in the journal CHEST, the researchers analyzed data from 309 adult ICU patients with RSV infection and 309 with influenza infection between November 2011 and April 2018 from 17 sites in France and Belgium. Each RSV patient was matched to a flu patient according to institution and date of diagnosis.
The primary objective was a comparison of in-hospital mortality between the groups, defined as death from any cause during an index hospital stay in acute care. Secondary objectives were comparisons of the clinical and biological characteristics of patients with RSV versus flu.
Overall, in-hospital mortality was not significantly different between the RSV and influenza groups (23.9% vs. 25.6%, P = .63).
However, patients with RSV infection were significantly more likely than those with flu to have an underlying chronic respiratory condition (60.2% vs. 40.1%, P < .001) and to be immunocompromised (35% vs. 26.2%, P = .02). Very few of the patients overall (39 patients, 6.3%) were considered young and healthy prior to hospitalization; and significantly fewer of these were in the RSV group than in the influenza group (9 patients and 30 patients, respectively).
Airway obstruction at the time of diagnosis was significantly more common in the RSV patients than in influenza patients (49.5% vs. 39.5%, P = .01), but influenza patients were significantly more likely to have acute respiratory distress syndrome at the time of diagnosis (21.7% vs. 14.6%, P = .02). Rates of coinfections were similar between the groups, and approximately 60% of coinfected patients received at least 72 hours of therapeutic antibiotics. Overall length of hospital stay, ICU stay, and duration of mechanical ventilation were similar between the groups.
The results show that severe RSV occurs mainly in older patients with comorbidities, and these results reflect data from previous studies, the researchers wrote in their discussion. In addition, “patients with influenza infection were significantly more likely to have fever, myalgia, increased CPK level, thrombocytopenia and transaminitis at diagnosis than were those with RSV infection. Whether these differences may be used to guide patient management remains to be determined.”
The study findings were limited by several factors including the retrospective design, and testing for respiratory viruses on symptomatic patients only, rather than all ICU patients, the researchers noted. Other limitations include the inability to show a causal link between viral infections and patient outcomes and the heterogenous management of patients among different centers.
However, the results were strengthened by the large sample size and multivariate analysis, and support the need for interventions to prevent and treat severe RSV, they concluded.
The study received no outside funding. Lead author Dr. Coussement disclosed serving on advisory board for Sanofi.
Hospitalized intensive care patients with respiratory syncytial virus were significantly more likely to be immunocompromised and to have chronic respiratory conditions than those with influenza infections, but in-hospital mortality rates were similar, based on data from 618 adults.
Respiratory syncytial virus is common in adults, but characteristics of RSV patients requiring ICU care have not been explored, despite routine testing for RSV in critically ill patients in many institutions, Julien Coussement, PhD, of Université Libre de Bruxelles, Brussels, and colleagues wrote.
“Influenza is another respiratory virus routinely tested for in ICU patients with respiratory symptoms because of its well-known morbidity and mortality, but there are no data specifically comparing RSV and influenza infections in adult ICU patients,” they noted.
In a retrospective, multicenter study published in the journal CHEST, the researchers analyzed data from 309 adult ICU patients with RSV infection and 309 with influenza infection between November 2011 and April 2018 from 17 sites in France and Belgium. Each RSV patient was matched to a flu patient according to institution and date of diagnosis.
The primary objective was a comparison of in-hospital mortality between the groups, defined as death from any cause during an index hospital stay in acute care. Secondary objectives were comparisons of the clinical and biological characteristics of patients with RSV versus flu.
Overall, in-hospital mortality was not significantly different between the RSV and influenza groups (23.9% vs. 25.6%, P = .63).
However, patients with RSV infection were significantly more likely than those with flu to have an underlying chronic respiratory condition (60.2% vs. 40.1%, P < .001) and to be immunocompromised (35% vs. 26.2%, P = .02). Very few of the patients overall (39 patients, 6.3%) were considered young and healthy prior to hospitalization; and significantly fewer of these were in the RSV group than in the influenza group (9 patients and 30 patients, respectively).
Airway obstruction at the time of diagnosis was significantly more common in the RSV patients than in influenza patients (49.5% vs. 39.5%, P = .01), but influenza patients were significantly more likely to have acute respiratory distress syndrome at the time of diagnosis (21.7% vs. 14.6%, P = .02). Rates of coinfections were similar between the groups, and approximately 60% of coinfected patients received at least 72 hours of therapeutic antibiotics. Overall length of hospital stay, ICU stay, and duration of mechanical ventilation were similar between the groups.
The results show that severe RSV occurs mainly in older patients with comorbidities, and these results reflect data from previous studies, the researchers wrote in their discussion. In addition, “patients with influenza infection were significantly more likely to have fever, myalgia, increased CPK level, thrombocytopenia and transaminitis at diagnosis than were those with RSV infection. Whether these differences may be used to guide patient management remains to be determined.”
The study findings were limited by several factors including the retrospective design, and testing for respiratory viruses on symptomatic patients only, rather than all ICU patients, the researchers noted. Other limitations include the inability to show a causal link between viral infections and patient outcomes and the heterogenous management of patients among different centers.
However, the results were strengthened by the large sample size and multivariate analysis, and support the need for interventions to prevent and treat severe RSV, they concluded.
The study received no outside funding. Lead author Dr. Coussement disclosed serving on advisory board for Sanofi.
FROM CHEST
Omalizumab curbs airway inflammation in severe asthma
Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.
Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.
“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.
In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).
Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).
Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.
Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.
These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.
A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.
However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.
The study was funded by Novartis. The researchers had no financial conflicts to disclose.
Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.
Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.
“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.
In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).
Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).
Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.
Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.
These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.
A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.
However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.
The study was funded by Novartis. The researchers had no financial conflicts to disclose.
Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.
Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.
“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.
In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).
Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).
Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.
Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.
These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.
A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.
However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.
The study was funded by Novartis. The researchers had no financial conflicts to disclose.
FROM ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY