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Don’t Forget Adult Hepatitis Vaccinations
Hepatitis B (Hep B) is a liver infection against which vaccination was previously recommended for certain eligible risk groups. However, in 2022, the Centers for Disease Control and Prevention (CDC) switched from recommending vaccination for at-risk persons to recommending universal vaccination for children and adults.
That includes infants, children 18 years of age and younger, adults aged 19-59, and people aged 60 and up with risk factors for this viral infection. Even those aged 60 and older without known risk factors for hepatitis B may receive Hep B vaccines.
Risk factors under prior recommendations included potential criminal or stigmatizing behaviors such as injection-drug use, incarceration, or multiple sex partners, which limited risk assessment by providers. The CDC points out that universal adult Hep B vaccination through age 59 obviates the need for the previous approach of risk-factor screening and sensitive disclosures to determine eligibility and could increase vaccination coverage and reduce cases.
“A universal recommendation for Hep B vaccination could increase the number of persons who receive vaccination before the onset of chronic liver disease and other comorbidities (e.g., obesity or diabetes) that might make vaccination less effective,” the CDC stated, noting that patients with chronic liver disease have a reduced immune response to Hep B vaccination. Hep B vaccination also protects against hepatitis D.
“Most people born in the US are vaccinated during infancy, beginning on the first day of life,” Lauren D. Block, MD, an internist at Northwell Health and an assistant professor in the Institute of Health System Science at the Feinstein Institutes for Medical Research at sites in metropolitan New York City, said in an interview.
Typically, Dr. Block added, at-risk persons will have titers drawn to make sure they are immune to Hep B. “Titers can wane over the decades in healthy people, in which case a booster shot may be needed, or a restart of the three-part vaccination series if a person is not sure if they were vaccinated previously.” Those at greater risk include people with weakened immune systems, people with diabetes or on immunosuppressives, healthcare workers, travelers to higher-risk countries, people with multiple sexual partners, and IV drug users.
Although Hep B vaccines have demonstrated safety, immunogenicity, and efficacy during the past four decades, coverage among US adults has been suboptimal, limiting further reduction in infections, the CDC noted.
Hepatitis A
Though not widely endemic to North America, Hep A can be acquired during travel abroad, particularly to developing countries, or through exposure to unsanitary conditions and contaminated food or water.
The CDC recommends routine Hep A vaccination for all children aged 12-23 months, all unvaccinated children and adolescents 2-18 years, and all persons, including those who are pregnant, with increased risk factors for this orally and fecally transmitted infection or at risk for severe disease from it. At-risk groups include international travelers to affected regions, men who have sex with men, incarcerated individuals or group-home residents, injection and non-injection drug users, and homeless persons.
Hepatitis C and E
There is no vaccine for Hep C, and no FDA-approved vaccine in the United States for hepatitis E, although a vaccine for the latter was approved in China in 2012.
As with Hep A, observing strict water, food, and sanitation standards is essential for preventing infection with hepatitis E.
Dr. Block disclosed no competing interests relevant to her comments.
Hepatitis B (Hep B) is a liver infection against which vaccination was previously recommended for certain eligible risk groups. However, in 2022, the Centers for Disease Control and Prevention (CDC) switched from recommending vaccination for at-risk persons to recommending universal vaccination for children and adults.
That includes infants, children 18 years of age and younger, adults aged 19-59, and people aged 60 and up with risk factors for this viral infection. Even those aged 60 and older without known risk factors for hepatitis B may receive Hep B vaccines.
Risk factors under prior recommendations included potential criminal or stigmatizing behaviors such as injection-drug use, incarceration, or multiple sex partners, which limited risk assessment by providers. The CDC points out that universal adult Hep B vaccination through age 59 obviates the need for the previous approach of risk-factor screening and sensitive disclosures to determine eligibility and could increase vaccination coverage and reduce cases.
“A universal recommendation for Hep B vaccination could increase the number of persons who receive vaccination before the onset of chronic liver disease and other comorbidities (e.g., obesity or diabetes) that might make vaccination less effective,” the CDC stated, noting that patients with chronic liver disease have a reduced immune response to Hep B vaccination. Hep B vaccination also protects against hepatitis D.
“Most people born in the US are vaccinated during infancy, beginning on the first day of life,” Lauren D. Block, MD, an internist at Northwell Health and an assistant professor in the Institute of Health System Science at the Feinstein Institutes for Medical Research at sites in metropolitan New York City, said in an interview.
Typically, Dr. Block added, at-risk persons will have titers drawn to make sure they are immune to Hep B. “Titers can wane over the decades in healthy people, in which case a booster shot may be needed, or a restart of the three-part vaccination series if a person is not sure if they were vaccinated previously.” Those at greater risk include people with weakened immune systems, people with diabetes or on immunosuppressives, healthcare workers, travelers to higher-risk countries, people with multiple sexual partners, and IV drug users.
Although Hep B vaccines have demonstrated safety, immunogenicity, and efficacy during the past four decades, coverage among US adults has been suboptimal, limiting further reduction in infections, the CDC noted.
Hepatitis A
Though not widely endemic to North America, Hep A can be acquired during travel abroad, particularly to developing countries, or through exposure to unsanitary conditions and contaminated food or water.
The CDC recommends routine Hep A vaccination for all children aged 12-23 months, all unvaccinated children and adolescents 2-18 years, and all persons, including those who are pregnant, with increased risk factors for this orally and fecally transmitted infection or at risk for severe disease from it. At-risk groups include international travelers to affected regions, men who have sex with men, incarcerated individuals or group-home residents, injection and non-injection drug users, and homeless persons.
Hepatitis C and E
There is no vaccine for Hep C, and no FDA-approved vaccine in the United States for hepatitis E, although a vaccine for the latter was approved in China in 2012.
As with Hep A, observing strict water, food, and sanitation standards is essential for preventing infection with hepatitis E.
Dr. Block disclosed no competing interests relevant to her comments.
Hepatitis B (Hep B) is a liver infection against which vaccination was previously recommended for certain eligible risk groups. However, in 2022, the Centers for Disease Control and Prevention (CDC) switched from recommending vaccination for at-risk persons to recommending universal vaccination for children and adults.
That includes infants, children 18 years of age and younger, adults aged 19-59, and people aged 60 and up with risk factors for this viral infection. Even those aged 60 and older without known risk factors for hepatitis B may receive Hep B vaccines.
Risk factors under prior recommendations included potential criminal or stigmatizing behaviors such as injection-drug use, incarceration, or multiple sex partners, which limited risk assessment by providers. The CDC points out that universal adult Hep B vaccination through age 59 obviates the need for the previous approach of risk-factor screening and sensitive disclosures to determine eligibility and could increase vaccination coverage and reduce cases.
“A universal recommendation for Hep B vaccination could increase the number of persons who receive vaccination before the onset of chronic liver disease and other comorbidities (e.g., obesity or diabetes) that might make vaccination less effective,” the CDC stated, noting that patients with chronic liver disease have a reduced immune response to Hep B vaccination. Hep B vaccination also protects against hepatitis D.
“Most people born in the US are vaccinated during infancy, beginning on the first day of life,” Lauren D. Block, MD, an internist at Northwell Health and an assistant professor in the Institute of Health System Science at the Feinstein Institutes for Medical Research at sites in metropolitan New York City, said in an interview.
Typically, Dr. Block added, at-risk persons will have titers drawn to make sure they are immune to Hep B. “Titers can wane over the decades in healthy people, in which case a booster shot may be needed, or a restart of the three-part vaccination series if a person is not sure if they were vaccinated previously.” Those at greater risk include people with weakened immune systems, people with diabetes or on immunosuppressives, healthcare workers, travelers to higher-risk countries, people with multiple sexual partners, and IV drug users.
Although Hep B vaccines have demonstrated safety, immunogenicity, and efficacy during the past four decades, coverage among US adults has been suboptimal, limiting further reduction in infections, the CDC noted.
Hepatitis A
Though not widely endemic to North America, Hep A can be acquired during travel abroad, particularly to developing countries, or through exposure to unsanitary conditions and contaminated food or water.
The CDC recommends routine Hep A vaccination for all children aged 12-23 months, all unvaccinated children and adolescents 2-18 years, and all persons, including those who are pregnant, with increased risk factors for this orally and fecally transmitted infection or at risk for severe disease from it. At-risk groups include international travelers to affected regions, men who have sex with men, incarcerated individuals or group-home residents, injection and non-injection drug users, and homeless persons.
Hepatitis C and E
There is no vaccine for Hep C, and no FDA-approved vaccine in the United States for hepatitis E, although a vaccine for the latter was approved in China in 2012.
As with Hep A, observing strict water, food, and sanitation standards is essential for preventing infection with hepatitis E.
Dr. Block disclosed no competing interests relevant to her comments.
Dupilumab Effective in PPI-Refractory Pediatric EoE
Good news for younger children suffering from the uncommon but debilitating gastrointestinal condition eosinophilic esophagitis (EoE): Data from this trial led to a January US Food and Drug Administration (FDA) approval of the anti-inflammatory biologic for patients aged 1-11 years weighing at least 15 kg.
In addition, the trial, published in The New England Journal of Medicine, found that a higher-exposure dupilumab regimen (approximating the trough concentration of a 300-mg dose administered once weekly versus every 2 weeks) improved key secondary end points, according to gastroenterologist Mirna Chehade, MD, MPH, AGAF, a professor of pediatrics at Icahn School of Medicine at Mount Sinai and Mount Sinai Kravis Children’s Hospital in New York City, and colleagues.
In 2022, the FDA approved the drug for those aged 12 or older weighing at least 40 kg.
“Left untreated or inadequately treated, EoE can progress to esophageal narrowing and strictures, leading to increased risk of food impactions and the need for esophageal dilations,” Dr. Chehade said in an interview. “Therefore, it’s important that children with EoE have the FDA-approved treatment option based on our study that can address their underlying disease starting at a young age.”
She added that dupilumab has the exciting potential to transform the standard of care for many young children living with EoE. “There are, however, factors to consider before switching a child to dupilumab — all related to the child’s specific medical history and therefore the perceived potential benefits from the drug.”
Commenting on the study but not involved in it, Toni Webster, DO, a pediatric gastroenterologist at Cohen Children’s Medical Center in Queens, New York, and an assistant professor at the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, said, “Like many allergic diseases, EoE is on the rise and, unfortunately, is affecting our children at alarming rates and at earlier ages. Given its efficacy and side-effect profile, dupilumab will vastly change our ability to treat EoE, especially for families who find diet and daily medication to be a challenge.”
Dr. Webster noted that an elimination diet is a rigorous choice that is often difficult to navigate. And the oral administration of off-label choices, proton pump inhibitors, and swallowed topical steroids, as well as the newly FDA-approved oral budesonide therapy (Eohilia), may also be challenging because many children have precluding aversions to oral therapy. “Regardless of age, treatment choice for EoE should be a good fit that is a plausible addition to a family’s lifestyle,” she said.
Blocking interleukin 4 and interleukin 13 inflammatory pathways, dupilumab has shown efficacy in other atopic diseases such as eczema. It broadly inhibits most aspects of type 2 inflammation and that action is reflected in its histologic and transcriptomic effects in affected tissues, Dr. Chehade and associates explained.
The Trial
Conducted at one Canadian and 26 US sites, the two-part phase 3 study randomly assigned 102 EoE patients aged 1-11 years who were refractory to proton pump inhibition in a 2:2:1:1 ratio.
Part A enrolled 102 patients and evaluated dupilumab at a weight-tiered higher-dose or lower-dose regimen vs placebo (two groups) for 16 weeks.
Part B was a 36-week extended active treatment period in which eligible dupilumab recipients from part A maintained their weight-tiered higher- or lower-dose regimen, whereas those in the placebo groups switched to weight-tiered higher- or lower-dose dupilumab.
The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤ 6 per high-power field) at week 16. Continued dupilumab treatment appeared to maintain its effect through week 52.
During part A, histologic remission occurred in 25 of the 37 higher-exposure patients (68%), 18 of the 31 lower-exposure patients (58%), and one of the 34 placebo patients (3%).
The difference between the higher-exposure regimen and placebo was 65 percentage points (95% confidence interval [CI], 48-81; P < .001), whereas that between the lower-exposure regimen and placebo was 55 percentage points (95% CI, 37-73; P < .001).
Higher exposure led to significant improvements in histologic, endoscopic, and transcriptomic measures over placebo. Improvements between baseline and week 52 in all patients were generally similar to those between baseline and week 16 in patients who received dupilumab in part A.
As for adverse events, in part A, the incidence of coronavirus disease, nausea, injection-site pain, and headache was at least 10 percentage points higher among dupilumab recipients at either dose than among placebo recipients. Serious adverse events were reported in three dupilumab patients during part A and in six patients overall during part B.
A Balanced Approach
On a cautionary note, Eric H. Chiou, MD, an assistant professor of pediatrics at Baylor College of Medicine and a pediatric gastroenterologist at Texas Children’s Hospital in Houston, said that while dupilumab shows great promise, further research is needed on its cost-effectiveness in EoE.
“The cost of treatment will need to be compared relative to potential long-term savings from reduced hospitalizations, fewer complications, and improved quality of life,” said Dr. Chiou, who was not involved in the study. “A balanced approach that considers clinical efficacy, patient well-being, cost-effectiveness, and equity is essential.”
He added that despite the study’s encouraging results, long-term safety and efficacy data are needed to fully understand the impact of dupilumab on pediatric patients with EoE. “Dupilumab will need to be compared with existing treatments for EoE such as dietary management and swallowed topical corticosteroids in terms of efficacy, safety, and quality of life improvements.”
Additionally, further research is required to identify which patients are most likely to benefit from this therapy and to explore any potential complications associated with its long-term use. “Understanding the optimal dosing and duration of treatment will also be crucial for maximizing benefits while minimizing risks,” Dr. Chiou said.
Dr. Chehade agreed. “While it’s that great that young children finally have an FDA-approved drug to treat their EoE, more research is needed to learn which patient subsets would derive maximum benefit from dupilumab and at which specific steps in their medical management journey should dupilumab be used.”
This study was supported by Sanofi and Regeneron Pharmaceuticals. Dr. Chehade disclosed research funding from and consulting for numerous private sector companies, among others, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Shire-Takeda, and Bristol-Myers Squibb. Multiple study coauthors disclosed various relationships with private-sector companies, including Sanofi and Regeneron Pharmaceuticals, for research funding, consulting, travel, employment, and stock or intellectual ownership. Dr. Webster and Dr. Chiou disclosed no competing interests relevant to their comments.
A version of this article first appeared on Medscape.com.
Good news for younger children suffering from the uncommon but debilitating gastrointestinal condition eosinophilic esophagitis (EoE): Data from this trial led to a January US Food and Drug Administration (FDA) approval of the anti-inflammatory biologic for patients aged 1-11 years weighing at least 15 kg.
In addition, the trial, published in The New England Journal of Medicine, found that a higher-exposure dupilumab regimen (approximating the trough concentration of a 300-mg dose administered once weekly versus every 2 weeks) improved key secondary end points, according to gastroenterologist Mirna Chehade, MD, MPH, AGAF, a professor of pediatrics at Icahn School of Medicine at Mount Sinai and Mount Sinai Kravis Children’s Hospital in New York City, and colleagues.
In 2022, the FDA approved the drug for those aged 12 or older weighing at least 40 kg.
“Left untreated or inadequately treated, EoE can progress to esophageal narrowing and strictures, leading to increased risk of food impactions and the need for esophageal dilations,” Dr. Chehade said in an interview. “Therefore, it’s important that children with EoE have the FDA-approved treatment option based on our study that can address their underlying disease starting at a young age.”
She added that dupilumab has the exciting potential to transform the standard of care for many young children living with EoE. “There are, however, factors to consider before switching a child to dupilumab — all related to the child’s specific medical history and therefore the perceived potential benefits from the drug.”
Commenting on the study but not involved in it, Toni Webster, DO, a pediatric gastroenterologist at Cohen Children’s Medical Center in Queens, New York, and an assistant professor at the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, said, “Like many allergic diseases, EoE is on the rise and, unfortunately, is affecting our children at alarming rates and at earlier ages. Given its efficacy and side-effect profile, dupilumab will vastly change our ability to treat EoE, especially for families who find diet and daily medication to be a challenge.”
Dr. Webster noted that an elimination diet is a rigorous choice that is often difficult to navigate. And the oral administration of off-label choices, proton pump inhibitors, and swallowed topical steroids, as well as the newly FDA-approved oral budesonide therapy (Eohilia), may also be challenging because many children have precluding aversions to oral therapy. “Regardless of age, treatment choice for EoE should be a good fit that is a plausible addition to a family’s lifestyle,” she said.
Blocking interleukin 4 and interleukin 13 inflammatory pathways, dupilumab has shown efficacy in other atopic diseases such as eczema. It broadly inhibits most aspects of type 2 inflammation and that action is reflected in its histologic and transcriptomic effects in affected tissues, Dr. Chehade and associates explained.
The Trial
Conducted at one Canadian and 26 US sites, the two-part phase 3 study randomly assigned 102 EoE patients aged 1-11 years who were refractory to proton pump inhibition in a 2:2:1:1 ratio.
Part A enrolled 102 patients and evaluated dupilumab at a weight-tiered higher-dose or lower-dose regimen vs placebo (two groups) for 16 weeks.
Part B was a 36-week extended active treatment period in which eligible dupilumab recipients from part A maintained their weight-tiered higher- or lower-dose regimen, whereas those in the placebo groups switched to weight-tiered higher- or lower-dose dupilumab.
The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤ 6 per high-power field) at week 16. Continued dupilumab treatment appeared to maintain its effect through week 52.
During part A, histologic remission occurred in 25 of the 37 higher-exposure patients (68%), 18 of the 31 lower-exposure patients (58%), and one of the 34 placebo patients (3%).
The difference between the higher-exposure regimen and placebo was 65 percentage points (95% confidence interval [CI], 48-81; P < .001), whereas that between the lower-exposure regimen and placebo was 55 percentage points (95% CI, 37-73; P < .001).
Higher exposure led to significant improvements in histologic, endoscopic, and transcriptomic measures over placebo. Improvements between baseline and week 52 in all patients were generally similar to those between baseline and week 16 in patients who received dupilumab in part A.
As for adverse events, in part A, the incidence of coronavirus disease, nausea, injection-site pain, and headache was at least 10 percentage points higher among dupilumab recipients at either dose than among placebo recipients. Serious adverse events were reported in three dupilumab patients during part A and in six patients overall during part B.
A Balanced Approach
On a cautionary note, Eric H. Chiou, MD, an assistant professor of pediatrics at Baylor College of Medicine and a pediatric gastroenterologist at Texas Children’s Hospital in Houston, said that while dupilumab shows great promise, further research is needed on its cost-effectiveness in EoE.
“The cost of treatment will need to be compared relative to potential long-term savings from reduced hospitalizations, fewer complications, and improved quality of life,” said Dr. Chiou, who was not involved in the study. “A balanced approach that considers clinical efficacy, patient well-being, cost-effectiveness, and equity is essential.”
He added that despite the study’s encouraging results, long-term safety and efficacy data are needed to fully understand the impact of dupilumab on pediatric patients with EoE. “Dupilumab will need to be compared with existing treatments for EoE such as dietary management and swallowed topical corticosteroids in terms of efficacy, safety, and quality of life improvements.”
Additionally, further research is required to identify which patients are most likely to benefit from this therapy and to explore any potential complications associated with its long-term use. “Understanding the optimal dosing and duration of treatment will also be crucial for maximizing benefits while minimizing risks,” Dr. Chiou said.
Dr. Chehade agreed. “While it’s that great that young children finally have an FDA-approved drug to treat their EoE, more research is needed to learn which patient subsets would derive maximum benefit from dupilumab and at which specific steps in their medical management journey should dupilumab be used.”
This study was supported by Sanofi and Regeneron Pharmaceuticals. Dr. Chehade disclosed research funding from and consulting for numerous private sector companies, among others, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Shire-Takeda, and Bristol-Myers Squibb. Multiple study coauthors disclosed various relationships with private-sector companies, including Sanofi and Regeneron Pharmaceuticals, for research funding, consulting, travel, employment, and stock or intellectual ownership. Dr. Webster and Dr. Chiou disclosed no competing interests relevant to their comments.
A version of this article first appeared on Medscape.com.
Good news for younger children suffering from the uncommon but debilitating gastrointestinal condition eosinophilic esophagitis (EoE): Data from this trial led to a January US Food and Drug Administration (FDA) approval of the anti-inflammatory biologic for patients aged 1-11 years weighing at least 15 kg.
In addition, the trial, published in The New England Journal of Medicine, found that a higher-exposure dupilumab regimen (approximating the trough concentration of a 300-mg dose administered once weekly versus every 2 weeks) improved key secondary end points, according to gastroenterologist Mirna Chehade, MD, MPH, AGAF, a professor of pediatrics at Icahn School of Medicine at Mount Sinai and Mount Sinai Kravis Children’s Hospital in New York City, and colleagues.
In 2022, the FDA approved the drug for those aged 12 or older weighing at least 40 kg.
“Left untreated or inadequately treated, EoE can progress to esophageal narrowing and strictures, leading to increased risk of food impactions and the need for esophageal dilations,” Dr. Chehade said in an interview. “Therefore, it’s important that children with EoE have the FDA-approved treatment option based on our study that can address their underlying disease starting at a young age.”
She added that dupilumab has the exciting potential to transform the standard of care for many young children living with EoE. “There are, however, factors to consider before switching a child to dupilumab — all related to the child’s specific medical history and therefore the perceived potential benefits from the drug.”
Commenting on the study but not involved in it, Toni Webster, DO, a pediatric gastroenterologist at Cohen Children’s Medical Center in Queens, New York, and an assistant professor at the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, said, “Like many allergic diseases, EoE is on the rise and, unfortunately, is affecting our children at alarming rates and at earlier ages. Given its efficacy and side-effect profile, dupilumab will vastly change our ability to treat EoE, especially for families who find diet and daily medication to be a challenge.”
Dr. Webster noted that an elimination diet is a rigorous choice that is often difficult to navigate. And the oral administration of off-label choices, proton pump inhibitors, and swallowed topical steroids, as well as the newly FDA-approved oral budesonide therapy (Eohilia), may also be challenging because many children have precluding aversions to oral therapy. “Regardless of age, treatment choice for EoE should be a good fit that is a plausible addition to a family’s lifestyle,” she said.
Blocking interleukin 4 and interleukin 13 inflammatory pathways, dupilumab has shown efficacy in other atopic diseases such as eczema. It broadly inhibits most aspects of type 2 inflammation and that action is reflected in its histologic and transcriptomic effects in affected tissues, Dr. Chehade and associates explained.
The Trial
Conducted at one Canadian and 26 US sites, the two-part phase 3 study randomly assigned 102 EoE patients aged 1-11 years who were refractory to proton pump inhibition in a 2:2:1:1 ratio.
Part A enrolled 102 patients and evaluated dupilumab at a weight-tiered higher-dose or lower-dose regimen vs placebo (two groups) for 16 weeks.
Part B was a 36-week extended active treatment period in which eligible dupilumab recipients from part A maintained their weight-tiered higher- or lower-dose regimen, whereas those in the placebo groups switched to weight-tiered higher- or lower-dose dupilumab.
The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤ 6 per high-power field) at week 16. Continued dupilumab treatment appeared to maintain its effect through week 52.
During part A, histologic remission occurred in 25 of the 37 higher-exposure patients (68%), 18 of the 31 lower-exposure patients (58%), and one of the 34 placebo patients (3%).
The difference between the higher-exposure regimen and placebo was 65 percentage points (95% confidence interval [CI], 48-81; P < .001), whereas that between the lower-exposure regimen and placebo was 55 percentage points (95% CI, 37-73; P < .001).
Higher exposure led to significant improvements in histologic, endoscopic, and transcriptomic measures over placebo. Improvements between baseline and week 52 in all patients were generally similar to those between baseline and week 16 in patients who received dupilumab in part A.
As for adverse events, in part A, the incidence of coronavirus disease, nausea, injection-site pain, and headache was at least 10 percentage points higher among dupilumab recipients at either dose than among placebo recipients. Serious adverse events were reported in three dupilumab patients during part A and in six patients overall during part B.
A Balanced Approach
On a cautionary note, Eric H. Chiou, MD, an assistant professor of pediatrics at Baylor College of Medicine and a pediatric gastroenterologist at Texas Children’s Hospital in Houston, said that while dupilumab shows great promise, further research is needed on its cost-effectiveness in EoE.
“The cost of treatment will need to be compared relative to potential long-term savings from reduced hospitalizations, fewer complications, and improved quality of life,” said Dr. Chiou, who was not involved in the study. “A balanced approach that considers clinical efficacy, patient well-being, cost-effectiveness, and equity is essential.”
He added that despite the study’s encouraging results, long-term safety and efficacy data are needed to fully understand the impact of dupilumab on pediatric patients with EoE. “Dupilumab will need to be compared with existing treatments for EoE such as dietary management and swallowed topical corticosteroids in terms of efficacy, safety, and quality of life improvements.”
Additionally, further research is required to identify which patients are most likely to benefit from this therapy and to explore any potential complications associated with its long-term use. “Understanding the optimal dosing and duration of treatment will also be crucial for maximizing benefits while minimizing risks,” Dr. Chiou said.
Dr. Chehade agreed. “While it’s that great that young children finally have an FDA-approved drug to treat their EoE, more research is needed to learn which patient subsets would derive maximum benefit from dupilumab and at which specific steps in their medical management journey should dupilumab be used.”
This study was supported by Sanofi and Regeneron Pharmaceuticals. Dr. Chehade disclosed research funding from and consulting for numerous private sector companies, among others, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Shire-Takeda, and Bristol-Myers Squibb. Multiple study coauthors disclosed various relationships with private-sector companies, including Sanofi and Regeneron Pharmaceuticals, for research funding, consulting, travel, employment, and stock or intellectual ownership. Dr. Webster and Dr. Chiou disclosed no competing interests relevant to their comments.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Medicare Advantage Plans Not Always Advantageous
While Medicare Advantage (MA) plans are marketed as providing more generous benefits than traditional Medicare (TM), differences in the financial burden between beneficiaries switching to MA and staying with TM, are minimal, a longitudinal cohort analysis found.
In fact, according to a study by Sungchul Park, PhD, a health economist at Korea University in Seoul, and colleagues, the estimated annual out-of-pocket spending when switching to MA was $168 higher than staying in TM. That amounted to a 10.5% relative increase based on baseline out-of-pocket spending of $1597 annually among switchers, ranging widely, however, from a $133 decrease to a $469 increase. And for some, MA enrollment was associated with a higher likelihood of catastrophic financial burden.
“Our findings contrast with the notion that MA’s apparently more generous health insurance benefits lead to financial savings for enrollees,” Dr. Park and associates wrote in Annals of Internal Medicine.
The study
The analysis looked at costs for 7054 TM stayers and 1544 TM-to-MA switchers from the 2014-2020 Medical Expenditure Panel Survey, focusing on a cohort in which 18% of TM-covered individuals in year 1 switched to MA in year 2.
Comparative financial outcome measures included individual healthcare costs (out-of-pocket spending/cost sharing), financial burden (high/catastrophic), and subjective financial hardship (difficulty paying medical bills).
Although the overall out-of-pocket differences for MA were minimal and amounted to less than 1% of total healthcare expenses, MA was associated with a greater financial burden in vulnerable, especially in low-income populations. For every 100 beneficiaries with family incomes below 200% of the federal poverty level, one to six more switchers faced a catastrophic financial burden, with their out-of-pocket costs consuming more than 40% of household income in the year after switching.
The gap between the perception of lower costs and reality may be caused by a substantially heavier cost-sharing burden for certain services in MA plans, Dr. Park and associates pointed out. While MA enrollees generally paid less in some studies than the Part A hospital deductible for TM for inpatient stays of 3 days, they were more likely to face higher cost sharing for stays exceeding 7 days
Furthermore, whereas TM covers home health services without cost sharing, some MA plans have copayments. In addition, out-of-network health services can cost more. MA enrollees paid an average of $9 more for mental health services than for other in-network services and often encountered limited access to in-network providers. According to a 2021 study, only 18.2% of mental health professionals, 34.4% of cardiologists, 50.0% of psychiatrists, and 57.9% of primary care providers were included in MA networks,
An accompanying editorial noted that private MA plans will reap $83 billion in overpayments from U.S. taxpayers this year, according to Congress’s Medicare Payment Advisory Commission.
And as the data from Dr. Park and colleagues reveal, switchers don’t get much financial protection, according to primary care physician and healthcare researcher Steffi J. Woolhandler, MD, MPH, and internist David U. Himmelstein, MD, both of City University of New York at Hunter College in New York City.
“Medicare Advantage looks good when you’re healthy and don’t need much care. But when you need coverage, it often fails, leaving you with big bills and narrow choices for care,” Dr. Woolhandler said in an interview.
So how do these findings square with insurers’ hard-sell claims and enrollees’ perceptions that MA cuts out-of-pocket costs? “The likeliest explanation is that MA insurers have structured their benefits to advantage low-cost (that is, profitable) enrollees and disadvantage those requiring expensive care,” the editorial commentators wrote. For beneficiaries on inexpensive medications, MA plans would be a financial win. “But for patients requiring expensive chemotherapies, the 20% coinsurance that most MA plans charge could be financially ruinous.”
Commenting on the study but not involved in it, David A. Lipschutz, JD, LLB, associate director of the Center for Medicare Advocacy in Washington, DC, called the study an important one that provides more evidence that significant overpayments to MA plans don’t translate to better financial protections for plan enrollees, particularly lower-income individuals. “While there has been some recent movement to hold plans more accountable for providing necessary care, much more impactful action by policymakers is required to mitigate the harms of the growing privatization of the Medicare program,” he said. “MA overpayments could be redistributed to traditional Medicare in order to enrich all Medicare beneficiaries instead of just insurance companies.”
This study was supported by the National Research Foundation of Korea. Dr. Park disclosed no competing interests. One study coauthor reported support from government and not-for-profit research-funding bodies. Editorialists Dr. Woolhandler and Dr. Himmelstein had no competing interests to declare. Dr. Lipschutz disclosed Medicare advocacy work.
While Medicare Advantage (MA) plans are marketed as providing more generous benefits than traditional Medicare (TM), differences in the financial burden between beneficiaries switching to MA and staying with TM, are minimal, a longitudinal cohort analysis found.
In fact, according to a study by Sungchul Park, PhD, a health economist at Korea University in Seoul, and colleagues, the estimated annual out-of-pocket spending when switching to MA was $168 higher than staying in TM. That amounted to a 10.5% relative increase based on baseline out-of-pocket spending of $1597 annually among switchers, ranging widely, however, from a $133 decrease to a $469 increase. And for some, MA enrollment was associated with a higher likelihood of catastrophic financial burden.
“Our findings contrast with the notion that MA’s apparently more generous health insurance benefits lead to financial savings for enrollees,” Dr. Park and associates wrote in Annals of Internal Medicine.
The study
The analysis looked at costs for 7054 TM stayers and 1544 TM-to-MA switchers from the 2014-2020 Medical Expenditure Panel Survey, focusing on a cohort in which 18% of TM-covered individuals in year 1 switched to MA in year 2.
Comparative financial outcome measures included individual healthcare costs (out-of-pocket spending/cost sharing), financial burden (high/catastrophic), and subjective financial hardship (difficulty paying medical bills).
Although the overall out-of-pocket differences for MA were minimal and amounted to less than 1% of total healthcare expenses, MA was associated with a greater financial burden in vulnerable, especially in low-income populations. For every 100 beneficiaries with family incomes below 200% of the federal poverty level, one to six more switchers faced a catastrophic financial burden, with their out-of-pocket costs consuming more than 40% of household income in the year after switching.
The gap between the perception of lower costs and reality may be caused by a substantially heavier cost-sharing burden for certain services in MA plans, Dr. Park and associates pointed out. While MA enrollees generally paid less in some studies than the Part A hospital deductible for TM for inpatient stays of 3 days, they were more likely to face higher cost sharing for stays exceeding 7 days
Furthermore, whereas TM covers home health services without cost sharing, some MA plans have copayments. In addition, out-of-network health services can cost more. MA enrollees paid an average of $9 more for mental health services than for other in-network services and often encountered limited access to in-network providers. According to a 2021 study, only 18.2% of mental health professionals, 34.4% of cardiologists, 50.0% of psychiatrists, and 57.9% of primary care providers were included in MA networks,
An accompanying editorial noted that private MA plans will reap $83 billion in overpayments from U.S. taxpayers this year, according to Congress’s Medicare Payment Advisory Commission.
And as the data from Dr. Park and colleagues reveal, switchers don’t get much financial protection, according to primary care physician and healthcare researcher Steffi J. Woolhandler, MD, MPH, and internist David U. Himmelstein, MD, both of City University of New York at Hunter College in New York City.
“Medicare Advantage looks good when you’re healthy and don’t need much care. But when you need coverage, it often fails, leaving you with big bills and narrow choices for care,” Dr. Woolhandler said in an interview.
So how do these findings square with insurers’ hard-sell claims and enrollees’ perceptions that MA cuts out-of-pocket costs? “The likeliest explanation is that MA insurers have structured their benefits to advantage low-cost (that is, profitable) enrollees and disadvantage those requiring expensive care,” the editorial commentators wrote. For beneficiaries on inexpensive medications, MA plans would be a financial win. “But for patients requiring expensive chemotherapies, the 20% coinsurance that most MA plans charge could be financially ruinous.”
Commenting on the study but not involved in it, David A. Lipschutz, JD, LLB, associate director of the Center for Medicare Advocacy in Washington, DC, called the study an important one that provides more evidence that significant overpayments to MA plans don’t translate to better financial protections for plan enrollees, particularly lower-income individuals. “While there has been some recent movement to hold plans more accountable for providing necessary care, much more impactful action by policymakers is required to mitigate the harms of the growing privatization of the Medicare program,” he said. “MA overpayments could be redistributed to traditional Medicare in order to enrich all Medicare beneficiaries instead of just insurance companies.”
This study was supported by the National Research Foundation of Korea. Dr. Park disclosed no competing interests. One study coauthor reported support from government and not-for-profit research-funding bodies. Editorialists Dr. Woolhandler and Dr. Himmelstein had no competing interests to declare. Dr. Lipschutz disclosed Medicare advocacy work.
While Medicare Advantage (MA) plans are marketed as providing more generous benefits than traditional Medicare (TM), differences in the financial burden between beneficiaries switching to MA and staying with TM, are minimal, a longitudinal cohort analysis found.
In fact, according to a study by Sungchul Park, PhD, a health economist at Korea University in Seoul, and colleagues, the estimated annual out-of-pocket spending when switching to MA was $168 higher than staying in TM. That amounted to a 10.5% relative increase based on baseline out-of-pocket spending of $1597 annually among switchers, ranging widely, however, from a $133 decrease to a $469 increase. And for some, MA enrollment was associated with a higher likelihood of catastrophic financial burden.
“Our findings contrast with the notion that MA’s apparently more generous health insurance benefits lead to financial savings for enrollees,” Dr. Park and associates wrote in Annals of Internal Medicine.
The study
The analysis looked at costs for 7054 TM stayers and 1544 TM-to-MA switchers from the 2014-2020 Medical Expenditure Panel Survey, focusing on a cohort in which 18% of TM-covered individuals in year 1 switched to MA in year 2.
Comparative financial outcome measures included individual healthcare costs (out-of-pocket spending/cost sharing), financial burden (high/catastrophic), and subjective financial hardship (difficulty paying medical bills).
Although the overall out-of-pocket differences for MA were minimal and amounted to less than 1% of total healthcare expenses, MA was associated with a greater financial burden in vulnerable, especially in low-income populations. For every 100 beneficiaries with family incomes below 200% of the federal poverty level, one to six more switchers faced a catastrophic financial burden, with their out-of-pocket costs consuming more than 40% of household income in the year after switching.
The gap between the perception of lower costs and reality may be caused by a substantially heavier cost-sharing burden for certain services in MA plans, Dr. Park and associates pointed out. While MA enrollees generally paid less in some studies than the Part A hospital deductible for TM for inpatient stays of 3 days, they were more likely to face higher cost sharing for stays exceeding 7 days
Furthermore, whereas TM covers home health services without cost sharing, some MA plans have copayments. In addition, out-of-network health services can cost more. MA enrollees paid an average of $9 more for mental health services than for other in-network services and often encountered limited access to in-network providers. According to a 2021 study, only 18.2% of mental health professionals, 34.4% of cardiologists, 50.0% of psychiatrists, and 57.9% of primary care providers were included in MA networks,
An accompanying editorial noted that private MA plans will reap $83 billion in overpayments from U.S. taxpayers this year, according to Congress’s Medicare Payment Advisory Commission.
And as the data from Dr. Park and colleagues reveal, switchers don’t get much financial protection, according to primary care physician and healthcare researcher Steffi J. Woolhandler, MD, MPH, and internist David U. Himmelstein, MD, both of City University of New York at Hunter College in New York City.
“Medicare Advantage looks good when you’re healthy and don’t need much care. But when you need coverage, it often fails, leaving you with big bills and narrow choices for care,” Dr. Woolhandler said in an interview.
So how do these findings square with insurers’ hard-sell claims and enrollees’ perceptions that MA cuts out-of-pocket costs? “The likeliest explanation is that MA insurers have structured their benefits to advantage low-cost (that is, profitable) enrollees and disadvantage those requiring expensive care,” the editorial commentators wrote. For beneficiaries on inexpensive medications, MA plans would be a financial win. “But for patients requiring expensive chemotherapies, the 20% coinsurance that most MA plans charge could be financially ruinous.”
Commenting on the study but not involved in it, David A. Lipschutz, JD, LLB, associate director of the Center for Medicare Advocacy in Washington, DC, called the study an important one that provides more evidence that significant overpayments to MA plans don’t translate to better financial protections for plan enrollees, particularly lower-income individuals. “While there has been some recent movement to hold plans more accountable for providing necessary care, much more impactful action by policymakers is required to mitigate the harms of the growing privatization of the Medicare program,” he said. “MA overpayments could be redistributed to traditional Medicare in order to enrich all Medicare beneficiaries instead of just insurance companies.”
This study was supported by the National Research Foundation of Korea. Dr. Park disclosed no competing interests. One study coauthor reported support from government and not-for-profit research-funding bodies. Editorialists Dr. Woolhandler and Dr. Himmelstein had no competing interests to declare. Dr. Lipschutz disclosed Medicare advocacy work.
FROM ANNALS OF INTERNAL MEDICINE
Metformin Gets a Reproductive Reprieve — For Diabetic Moms and Dads Alike
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
Nonanemic Iron Deficiency Underdiagnosed in Women
Three different definitions of nonanemic iron deficiency (ID), a common disorder causing substantial morbidity in women, were significantly associated with different population prevalence estimates, a data analysis of the cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS) study found.
These differences held, regardless of self-reported age, pregnancy, or race and ethnicity, according to HEIRS researchers led by James C. Barton, MD, professor of hematology at the University of Alabama at Birmingham.
“Using higher serum ferritin thresholds to define ID could lead to diagnosis and treatment of more women with ID and greater reduction of related morbidity,” the investigators wrote. The study was published in JAMA Network Open.
The authors noted that ID affects about 2 billion people worldwide, mainly women and children, increasing risks of fatigue, impaired muscular performance, cold intolerance, mucosal and epithelial abnormalities, pica, disturbances of menstruation, and adverse pregnancy outcomes.
Manifestations of ID, including anemia, are less prevalent or less severe in adults with higher serum ferritin (SF), and the three definitions correspond, in sequence, to ID of increasing prevalence and decreasing severity, they explained.
The Study
HEIRS conducted multiethnic, primary care–based screening for iron disorders during 2001-2003 at four field centers in the United States and one in Canada at primary care venues.
In data for the current study analyzed from June to December, 2023, the three ID definitions were: combined transferrin saturation less than 10% and SF less than 15 ng/mL (HEIRS); SF less than 15 ng/mL (World Health Organization [WHO]); and SF less than 25 ng/mL, the threshold for ID-deficient erythropoiesis [IDE).
Among the cohort’s 62,685 women (mean age, 49.58 years, 27,072 White, 17,272 Black), the estimated prevalence of ID emerged as follows across the different definitions:
- 1957 (3.12%) according to HEIRS
- 4659 (7.43%) according to WHO
- 9611 (15.33%) according to IDE
Those figures translated to an increased relative ID prevalence of 2.4-fold (95% CI, 2.3-2.5; P < .001) according to the WHO standard and 4.9-fold (95% CI, 4.7-5.2; P < .001) according IDEs.
In addition, prevalence was higher in younger women, and within each racial and ethnic subgroup of participants aged 25-54 years, prevalence rose significantly from the HEIRS definition to the WHO and IDE definitions.
Notably, ID was significantly higher among Black and Hispanic participants than Asian and White participants.
An accompanying editorial pointed to gender-based health equity issues raised by the HEIRS analysis and argued that a similar passive acceptance of laboratory definitions of a debilitating but correctable condition in White males would be “frankly unimaginable.”
“Iron deficiency is the leading cause of years lived with disability among women of reproductive age,” wrote hematologist Michelle Sholzberg, MDCM, MSc, and Grace H. Tang, MSc, of St. Michael’s Hospital in Toronto, Canada. “It is a factor clearly associated with maternal death and morbidity (including diminished IQ), and it is correctable, and, thus, unnecessary, in high-income, middle-income, and low-income geographic settings.”
The authors listed no specific funding for this analysis of HEIRS data. Dr. Barton reported contracts from the National Institutes of Health, National Human Genome Research Institute, outside of the submitted work. A coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute outside of the submitted work. Dr. Sholzberg reported unrestricted research funding to her institution from Octapharma and Pfizer and speakers’ honoraria from Takeda, Sobi, and Medison outside of the submitted work.
Three different definitions of nonanemic iron deficiency (ID), a common disorder causing substantial morbidity in women, were significantly associated with different population prevalence estimates, a data analysis of the cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS) study found.
These differences held, regardless of self-reported age, pregnancy, or race and ethnicity, according to HEIRS researchers led by James C. Barton, MD, professor of hematology at the University of Alabama at Birmingham.
“Using higher serum ferritin thresholds to define ID could lead to diagnosis and treatment of more women with ID and greater reduction of related morbidity,” the investigators wrote. The study was published in JAMA Network Open.
The authors noted that ID affects about 2 billion people worldwide, mainly women and children, increasing risks of fatigue, impaired muscular performance, cold intolerance, mucosal and epithelial abnormalities, pica, disturbances of menstruation, and adverse pregnancy outcomes.
Manifestations of ID, including anemia, are less prevalent or less severe in adults with higher serum ferritin (SF), and the three definitions correspond, in sequence, to ID of increasing prevalence and decreasing severity, they explained.
The Study
HEIRS conducted multiethnic, primary care–based screening for iron disorders during 2001-2003 at four field centers in the United States and one in Canada at primary care venues.
In data for the current study analyzed from June to December, 2023, the three ID definitions were: combined transferrin saturation less than 10% and SF less than 15 ng/mL (HEIRS); SF less than 15 ng/mL (World Health Organization [WHO]); and SF less than 25 ng/mL, the threshold for ID-deficient erythropoiesis [IDE).
Among the cohort’s 62,685 women (mean age, 49.58 years, 27,072 White, 17,272 Black), the estimated prevalence of ID emerged as follows across the different definitions:
- 1957 (3.12%) according to HEIRS
- 4659 (7.43%) according to WHO
- 9611 (15.33%) according to IDE
Those figures translated to an increased relative ID prevalence of 2.4-fold (95% CI, 2.3-2.5; P < .001) according to the WHO standard and 4.9-fold (95% CI, 4.7-5.2; P < .001) according IDEs.
In addition, prevalence was higher in younger women, and within each racial and ethnic subgroup of participants aged 25-54 years, prevalence rose significantly from the HEIRS definition to the WHO and IDE definitions.
Notably, ID was significantly higher among Black and Hispanic participants than Asian and White participants.
An accompanying editorial pointed to gender-based health equity issues raised by the HEIRS analysis and argued that a similar passive acceptance of laboratory definitions of a debilitating but correctable condition in White males would be “frankly unimaginable.”
“Iron deficiency is the leading cause of years lived with disability among women of reproductive age,” wrote hematologist Michelle Sholzberg, MDCM, MSc, and Grace H. Tang, MSc, of St. Michael’s Hospital in Toronto, Canada. “It is a factor clearly associated with maternal death and morbidity (including diminished IQ), and it is correctable, and, thus, unnecessary, in high-income, middle-income, and low-income geographic settings.”
The authors listed no specific funding for this analysis of HEIRS data. Dr. Barton reported contracts from the National Institutes of Health, National Human Genome Research Institute, outside of the submitted work. A coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute outside of the submitted work. Dr. Sholzberg reported unrestricted research funding to her institution from Octapharma and Pfizer and speakers’ honoraria from Takeda, Sobi, and Medison outside of the submitted work.
Three different definitions of nonanemic iron deficiency (ID), a common disorder causing substantial morbidity in women, were significantly associated with different population prevalence estimates, a data analysis of the cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS) study found.
These differences held, regardless of self-reported age, pregnancy, or race and ethnicity, according to HEIRS researchers led by James C. Barton, MD, professor of hematology at the University of Alabama at Birmingham.
“Using higher serum ferritin thresholds to define ID could lead to diagnosis and treatment of more women with ID and greater reduction of related morbidity,” the investigators wrote. The study was published in JAMA Network Open.
The authors noted that ID affects about 2 billion people worldwide, mainly women and children, increasing risks of fatigue, impaired muscular performance, cold intolerance, mucosal and epithelial abnormalities, pica, disturbances of menstruation, and adverse pregnancy outcomes.
Manifestations of ID, including anemia, are less prevalent or less severe in adults with higher serum ferritin (SF), and the three definitions correspond, in sequence, to ID of increasing prevalence and decreasing severity, they explained.
The Study
HEIRS conducted multiethnic, primary care–based screening for iron disorders during 2001-2003 at four field centers in the United States and one in Canada at primary care venues.
In data for the current study analyzed from June to December, 2023, the three ID definitions were: combined transferrin saturation less than 10% and SF less than 15 ng/mL (HEIRS); SF less than 15 ng/mL (World Health Organization [WHO]); and SF less than 25 ng/mL, the threshold for ID-deficient erythropoiesis [IDE).
Among the cohort’s 62,685 women (mean age, 49.58 years, 27,072 White, 17,272 Black), the estimated prevalence of ID emerged as follows across the different definitions:
- 1957 (3.12%) according to HEIRS
- 4659 (7.43%) according to WHO
- 9611 (15.33%) according to IDE
Those figures translated to an increased relative ID prevalence of 2.4-fold (95% CI, 2.3-2.5; P < .001) according to the WHO standard and 4.9-fold (95% CI, 4.7-5.2; P < .001) according IDEs.
In addition, prevalence was higher in younger women, and within each racial and ethnic subgroup of participants aged 25-54 years, prevalence rose significantly from the HEIRS definition to the WHO and IDE definitions.
Notably, ID was significantly higher among Black and Hispanic participants than Asian and White participants.
An accompanying editorial pointed to gender-based health equity issues raised by the HEIRS analysis and argued that a similar passive acceptance of laboratory definitions of a debilitating but correctable condition in White males would be “frankly unimaginable.”
“Iron deficiency is the leading cause of years lived with disability among women of reproductive age,” wrote hematologist Michelle Sholzberg, MDCM, MSc, and Grace H. Tang, MSc, of St. Michael’s Hospital in Toronto, Canada. “It is a factor clearly associated with maternal death and morbidity (including diminished IQ), and it is correctable, and, thus, unnecessary, in high-income, middle-income, and low-income geographic settings.”
The authors listed no specific funding for this analysis of HEIRS data. Dr. Barton reported contracts from the National Institutes of Health, National Human Genome Research Institute, outside of the submitted work. A coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute outside of the submitted work. Dr. Sholzberg reported unrestricted research funding to her institution from Octapharma and Pfizer and speakers’ honoraria from Takeda, Sobi, and Medison outside of the submitted work.
FROM JAMA NETWORK OPEN
5 Vaccinations Adults Need Beyond COVID and Flu
Many adults are complacent about vaccinations, believing that annual COVID and flu shots aside, they had all the immunizations they need as children and teens. But adults need vaccines as well, especially if they have missed earlier doses. And older and health-compromised adults, in particular, can benefit from newer vaccines that were not part of the childhood schedule.
“The question is whether adults had the vaccinations they need in the first place,” Sandra Adamson Fryhofer, MD, an internist in Atlanta and the American Medical Association’s liaison to the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention, said in an interview. “Many do not even have reliable records of vaccination.”
Primary care physicians are ideally positioned to get adult patients to update their vaccination status on older vaccines and obtain newer ones as needed. “ACIP recommendations for adult vaccines are getting longer and more complicated and the way they’re administered is more complex, too, in that they’re not all given in the primary care office but sometimes in pharmacies,” Dr. Fryhofer said.
Not all adult patients want to update their vaccinations. “Vaccine hesitancy among many adults is accelerated by the several new vaccines that have been recommended in recent years,” Lauren Block, MD, MPH, an internist at Northwell Health and assistant professor in the Institute of Health System Science at the Feinstein Institutes for Medical Research in metropolitan New York City, said in an interview.
Physicians are rightly concerned about the lagging rates of adult vaccination, Dr. Block said. “Given the prevalence of conditions like pneumonia and shingles and the morbidity associated with them, healthcare providers should take every opportunity to discuss vaccination with patients, from well visits to hospital visits,” Dr. Block added.
She pointed to several obstacles to broader uptake, including product shortages, financial barriers, and, increasingly, the negative vocal messaging from media outlets and social media.
Current Recommendations
The main vaccines recommended for adults, besides flu and COVID shots, are for respiratory syncytial virus (RVS); shingles; pneumococcal disease; measles, mumps, and rubella (MMR); and tetanus, diphtheria, and pertussis (Tdap). Less commonly, booster vaccines for MM, and hepatitis are recommended when titers are proven to be low.
ACIP’s updated 2024 Adult Immunization Schedule can be downloaded from the website of the CDC.
The newest additions to the schedule include RSV vaccines, the mpox vaccine (Jynneos), a new MenACWY-MenB combo vaccine (Penbraya), and the new 2023-2024 formulation of updated COVID vaccines (both mRNA and protein-based adjuvanted versions).
1. Respiratory Syncytial Virus Vaccines
There are two licensed RSV vaccines, Arexvy and Abrysvo. The CDC schedule recommends a single-dose RSV vaccine for adults age 60 years and older, especially those at high risk of contracting the virus — but after shared decision-making based on a discussion of the risk-harm balance since this vaccine carries a small increased chance of developing the neurological symptoms of Guillain-Barré syndrome.
Chronic health conditions associated with a higher risk of severe RVS include cardiopulmonary disease, diabetes, and kidney, liver, and hematologic disorders, as well as compromised immunity, older age, and frailty.
2. Shingles Vaccines
This painful disease carries the potential complication of postherpetic neuralgia (PHN), which leads to long-term nerve pain in 10%-18% of patients, especially those over age 40. ACIP recommends two doses of the recombinant zoster vaccine (Shingrix) for individuals 50 years and older. Those 19 years and older with weakened immune systems due to disease or medical treatments should get two doses of the recombinant vaccine, as they have a higher risk of getting shingles and its complications, including neurological problems and skin and eye infections.
3 Pneumococcal Vaccines
There are three approved pneumococcal vaccines: PCV15 (Vaxneuvance), PCV20 (Prevnar20), and PPSV23 (Pneumovax23).
“The pneumococcal vaccine schedule is the most complicated one as higher-valent products continue to become available,” Dr. Fryhofer said.
The two types are pneumococcal conjugate vaccines (PCVs, specifically PCV15 and PCV20) and the pneumococcal polysaccharide vaccine (PPSV23). “While PPSV23 covers 23 strains, it doesn’t give the long-term immunity of the conjugate vaccine,” said Dr. Fryhofer. “A patient may have completed their vaccination with the polysaccharide vaccine but 5 years out may no longer be protected. So we offer the option of getting a dose of PCV20 to round out the protection and confer greater immune memory.”
The ACIP schedule recommends immunization against the Streptococcus pneumoniae pathogen for all older and all at-risk adults. Routine administration of PCV15 or PCV20 is advised for those 65 years or older who have never received any pneumococcal conjugate vaccine or whose previous vaccination history is unknown. If PCV15 is used, it should be followed by PPSV23. Those 65 years or older should get PPSV23 even if they already had one or more doses of pneumococcal vaccine before turning 65.
Further vaccination is recommended for younger at-risk adults aged 19-64 years who have received both PCV13 and PPSV23 but have incomplete vaccination status. These individuals are advised to complete their pneumococcal series by receiving either a single dose of PCV20 at an interval of at least 5 years after the last pneumococcal vaccine dose or more than one dose of PPSV23.
See Pneumococcal Vaccination: Summary of Who and When to Vaccinate for CDC guidance on vaccination options for adults who have previously received a pneumococcal conjugate vaccine. Or, to sort out quickly who gets what and when based on their age, concurrent conditions, and vaccination history, the CDC offers a type-in app called the PneumoRecs VaxAdvisor.
4. Measles, Mumps, and Rubella, and Varicella Vaccines
The two approved MMR vaccines are M-M-R II and PRIORIX. A third vaccine, ProQuad, adds varicella.
Adults lacking presumptive evidence of immunity should get at least one dose of the MMR combination vaccine.
Those born before 1957 are deemed to be immune, Dr. Fryhofer noted.
Two doses are recommended for adults entering high-risk settings for measles or mumps transmission such as healthcare personnel, students away at college, and international travelers. The two doses should be separated by at least 28 days. It’s no secret that measles, though preventable, is making a comeback, with 146 reported cases (48 in adults) across 21 states as of May 31 — most linked to international travel.
Women who plan to get pregnant should be vaccinated before but not during each pregnancy. (The vaccine is safe during lactation.) And those of childbearing age with no presumptive evidence of immunity are advised to get at least one dose of the MMR vaccine.
5. Tetanus, Diphtheria, and Pertussis Vaccine
Adults with no previous Tdap vaccination should receive a single dose of Adacel or Boostrix followed by a booster every 10 years. Boostrix is recommended for adults over 64 years.
During every pregnancy, women should have a single dose of Tdap, preferably in gestational weeks 27 through 36.
As to the immediate postpartum period, Tdap is recommended only for mothers who did not receive it during their current pregnancy and never received a prior dose. If a woman did not receive Tdap during her current pregnancy but did receive a prior dose of Tdap, she does not need Tdap postpartum.
The Challenges
According to Dr. Fryhofer, widespread disinformation about the risks of immunization against vaccine-preventable diseases has brought us to a flashpoint. “It’s now more important than ever to keep telling patients that vaccination is one of the most effective tools for preventing individual illness and protecting public health.”
She recommends that doctors follow the National Institutes of Health’s AIMS method to broach the subject of adult vaccination and increase participation in an inquiring, reassuring, and low-pressure way. Standing for Announce, Inquire, Mirror, and Secure, AIMS structures a nonjudgmental, patient-friendly conversation around immunization to elicit and acknowledge the reasons for hesitancy while explaining the safety and efficacy of vaccines.
Dr. Fryhofer frequently uses AIMS to bring inoculation-averse patients around. “Keep the conversation open with reluctant patients but leave them where they are. They need to see you as a reliable source and nonjudgmental source of information,” she said.
Dr. Block recommends outlining the diseases that have been eliminated through vaccines, from polio to measles, as well as the dangers of vaccine refusal, as indicated by recent outbreaks of vaccine-preventable diseases in areas with low immunization rates. “This approach highlights the opportunity we all have to get vaccinated to protect ourselves and our communities,” she said.
In Dr. Fryhofer’s view, the situation is urgent and doctors need to be proactive. “We’re now at a public-health tipping point where we may see a sliding back and a reversing of many years of progress.”
Dr. Fryhofer and Dr. Block disclosed no competing interests relevant to their comments.
Many adults are complacent about vaccinations, believing that annual COVID and flu shots aside, they had all the immunizations they need as children and teens. But adults need vaccines as well, especially if they have missed earlier doses. And older and health-compromised adults, in particular, can benefit from newer vaccines that were not part of the childhood schedule.
“The question is whether adults had the vaccinations they need in the first place,” Sandra Adamson Fryhofer, MD, an internist in Atlanta and the American Medical Association’s liaison to the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention, said in an interview. “Many do not even have reliable records of vaccination.”
Primary care physicians are ideally positioned to get adult patients to update their vaccination status on older vaccines and obtain newer ones as needed. “ACIP recommendations for adult vaccines are getting longer and more complicated and the way they’re administered is more complex, too, in that they’re not all given in the primary care office but sometimes in pharmacies,” Dr. Fryhofer said.
Not all adult patients want to update their vaccinations. “Vaccine hesitancy among many adults is accelerated by the several new vaccines that have been recommended in recent years,” Lauren Block, MD, MPH, an internist at Northwell Health and assistant professor in the Institute of Health System Science at the Feinstein Institutes for Medical Research in metropolitan New York City, said in an interview.
Physicians are rightly concerned about the lagging rates of adult vaccination, Dr. Block said. “Given the prevalence of conditions like pneumonia and shingles and the morbidity associated with them, healthcare providers should take every opportunity to discuss vaccination with patients, from well visits to hospital visits,” Dr. Block added.
She pointed to several obstacles to broader uptake, including product shortages, financial barriers, and, increasingly, the negative vocal messaging from media outlets and social media.
Current Recommendations
The main vaccines recommended for adults, besides flu and COVID shots, are for respiratory syncytial virus (RVS); shingles; pneumococcal disease; measles, mumps, and rubella (MMR); and tetanus, diphtheria, and pertussis (Tdap). Less commonly, booster vaccines for MM, and hepatitis are recommended when titers are proven to be low.
ACIP’s updated 2024 Adult Immunization Schedule can be downloaded from the website of the CDC.
The newest additions to the schedule include RSV vaccines, the mpox vaccine (Jynneos), a new MenACWY-MenB combo vaccine (Penbraya), and the new 2023-2024 formulation of updated COVID vaccines (both mRNA and protein-based adjuvanted versions).
1. Respiratory Syncytial Virus Vaccines
There are two licensed RSV vaccines, Arexvy and Abrysvo. The CDC schedule recommends a single-dose RSV vaccine for adults age 60 years and older, especially those at high risk of contracting the virus — but after shared decision-making based on a discussion of the risk-harm balance since this vaccine carries a small increased chance of developing the neurological symptoms of Guillain-Barré syndrome.
Chronic health conditions associated with a higher risk of severe RVS include cardiopulmonary disease, diabetes, and kidney, liver, and hematologic disorders, as well as compromised immunity, older age, and frailty.
2. Shingles Vaccines
This painful disease carries the potential complication of postherpetic neuralgia (PHN), which leads to long-term nerve pain in 10%-18% of patients, especially those over age 40. ACIP recommends two doses of the recombinant zoster vaccine (Shingrix) for individuals 50 years and older. Those 19 years and older with weakened immune systems due to disease or medical treatments should get two doses of the recombinant vaccine, as they have a higher risk of getting shingles and its complications, including neurological problems and skin and eye infections.
3 Pneumococcal Vaccines
There are three approved pneumococcal vaccines: PCV15 (Vaxneuvance), PCV20 (Prevnar20), and PPSV23 (Pneumovax23).
“The pneumococcal vaccine schedule is the most complicated one as higher-valent products continue to become available,” Dr. Fryhofer said.
The two types are pneumococcal conjugate vaccines (PCVs, specifically PCV15 and PCV20) and the pneumococcal polysaccharide vaccine (PPSV23). “While PPSV23 covers 23 strains, it doesn’t give the long-term immunity of the conjugate vaccine,” said Dr. Fryhofer. “A patient may have completed their vaccination with the polysaccharide vaccine but 5 years out may no longer be protected. So we offer the option of getting a dose of PCV20 to round out the protection and confer greater immune memory.”
The ACIP schedule recommends immunization against the Streptococcus pneumoniae pathogen for all older and all at-risk adults. Routine administration of PCV15 or PCV20 is advised for those 65 years or older who have never received any pneumococcal conjugate vaccine or whose previous vaccination history is unknown. If PCV15 is used, it should be followed by PPSV23. Those 65 years or older should get PPSV23 even if they already had one or more doses of pneumococcal vaccine before turning 65.
Further vaccination is recommended for younger at-risk adults aged 19-64 years who have received both PCV13 and PPSV23 but have incomplete vaccination status. These individuals are advised to complete their pneumococcal series by receiving either a single dose of PCV20 at an interval of at least 5 years after the last pneumococcal vaccine dose or more than one dose of PPSV23.
See Pneumococcal Vaccination: Summary of Who and When to Vaccinate for CDC guidance on vaccination options for adults who have previously received a pneumococcal conjugate vaccine. Or, to sort out quickly who gets what and when based on their age, concurrent conditions, and vaccination history, the CDC offers a type-in app called the PneumoRecs VaxAdvisor.
4. Measles, Mumps, and Rubella, and Varicella Vaccines
The two approved MMR vaccines are M-M-R II and PRIORIX. A third vaccine, ProQuad, adds varicella.
Adults lacking presumptive evidence of immunity should get at least one dose of the MMR combination vaccine.
Those born before 1957 are deemed to be immune, Dr. Fryhofer noted.
Two doses are recommended for adults entering high-risk settings for measles or mumps transmission such as healthcare personnel, students away at college, and international travelers. The two doses should be separated by at least 28 days. It’s no secret that measles, though preventable, is making a comeback, with 146 reported cases (48 in adults) across 21 states as of May 31 — most linked to international travel.
Women who plan to get pregnant should be vaccinated before but not during each pregnancy. (The vaccine is safe during lactation.) And those of childbearing age with no presumptive evidence of immunity are advised to get at least one dose of the MMR vaccine.
5. Tetanus, Diphtheria, and Pertussis Vaccine
Adults with no previous Tdap vaccination should receive a single dose of Adacel or Boostrix followed by a booster every 10 years. Boostrix is recommended for adults over 64 years.
During every pregnancy, women should have a single dose of Tdap, preferably in gestational weeks 27 through 36.
As to the immediate postpartum period, Tdap is recommended only for mothers who did not receive it during their current pregnancy and never received a prior dose. If a woman did not receive Tdap during her current pregnancy but did receive a prior dose of Tdap, she does not need Tdap postpartum.
The Challenges
According to Dr. Fryhofer, widespread disinformation about the risks of immunization against vaccine-preventable diseases has brought us to a flashpoint. “It’s now more important than ever to keep telling patients that vaccination is one of the most effective tools for preventing individual illness and protecting public health.”
She recommends that doctors follow the National Institutes of Health’s AIMS method to broach the subject of adult vaccination and increase participation in an inquiring, reassuring, and low-pressure way. Standing for Announce, Inquire, Mirror, and Secure, AIMS structures a nonjudgmental, patient-friendly conversation around immunization to elicit and acknowledge the reasons for hesitancy while explaining the safety and efficacy of vaccines.
Dr. Fryhofer frequently uses AIMS to bring inoculation-averse patients around. “Keep the conversation open with reluctant patients but leave them where they are. They need to see you as a reliable source and nonjudgmental source of information,” she said.
Dr. Block recommends outlining the diseases that have been eliminated through vaccines, from polio to measles, as well as the dangers of vaccine refusal, as indicated by recent outbreaks of vaccine-preventable diseases in areas with low immunization rates. “This approach highlights the opportunity we all have to get vaccinated to protect ourselves and our communities,” she said.
In Dr. Fryhofer’s view, the situation is urgent and doctors need to be proactive. “We’re now at a public-health tipping point where we may see a sliding back and a reversing of many years of progress.”
Dr. Fryhofer and Dr. Block disclosed no competing interests relevant to their comments.
Many adults are complacent about vaccinations, believing that annual COVID and flu shots aside, they had all the immunizations they need as children and teens. But adults need vaccines as well, especially if they have missed earlier doses. And older and health-compromised adults, in particular, can benefit from newer vaccines that were not part of the childhood schedule.
“The question is whether adults had the vaccinations they need in the first place,” Sandra Adamson Fryhofer, MD, an internist in Atlanta and the American Medical Association’s liaison to the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention, said in an interview. “Many do not even have reliable records of vaccination.”
Primary care physicians are ideally positioned to get adult patients to update their vaccination status on older vaccines and obtain newer ones as needed. “ACIP recommendations for adult vaccines are getting longer and more complicated and the way they’re administered is more complex, too, in that they’re not all given in the primary care office but sometimes in pharmacies,” Dr. Fryhofer said.
Not all adult patients want to update their vaccinations. “Vaccine hesitancy among many adults is accelerated by the several new vaccines that have been recommended in recent years,” Lauren Block, MD, MPH, an internist at Northwell Health and assistant professor in the Institute of Health System Science at the Feinstein Institutes for Medical Research in metropolitan New York City, said in an interview.
Physicians are rightly concerned about the lagging rates of adult vaccination, Dr. Block said. “Given the prevalence of conditions like pneumonia and shingles and the morbidity associated with them, healthcare providers should take every opportunity to discuss vaccination with patients, from well visits to hospital visits,” Dr. Block added.
She pointed to several obstacles to broader uptake, including product shortages, financial barriers, and, increasingly, the negative vocal messaging from media outlets and social media.
Current Recommendations
The main vaccines recommended for adults, besides flu and COVID shots, are for respiratory syncytial virus (RVS); shingles; pneumococcal disease; measles, mumps, and rubella (MMR); and tetanus, diphtheria, and pertussis (Tdap). Less commonly, booster vaccines for MM, and hepatitis are recommended when titers are proven to be low.
ACIP’s updated 2024 Adult Immunization Schedule can be downloaded from the website of the CDC.
The newest additions to the schedule include RSV vaccines, the mpox vaccine (Jynneos), a new MenACWY-MenB combo vaccine (Penbraya), and the new 2023-2024 formulation of updated COVID vaccines (both mRNA and protein-based adjuvanted versions).
1. Respiratory Syncytial Virus Vaccines
There are two licensed RSV vaccines, Arexvy and Abrysvo. The CDC schedule recommends a single-dose RSV vaccine for adults age 60 years and older, especially those at high risk of contracting the virus — but after shared decision-making based on a discussion of the risk-harm balance since this vaccine carries a small increased chance of developing the neurological symptoms of Guillain-Barré syndrome.
Chronic health conditions associated with a higher risk of severe RVS include cardiopulmonary disease, diabetes, and kidney, liver, and hematologic disorders, as well as compromised immunity, older age, and frailty.
2. Shingles Vaccines
This painful disease carries the potential complication of postherpetic neuralgia (PHN), which leads to long-term nerve pain in 10%-18% of patients, especially those over age 40. ACIP recommends two doses of the recombinant zoster vaccine (Shingrix) for individuals 50 years and older. Those 19 years and older with weakened immune systems due to disease or medical treatments should get two doses of the recombinant vaccine, as they have a higher risk of getting shingles and its complications, including neurological problems and skin and eye infections.
3 Pneumococcal Vaccines
There are three approved pneumococcal vaccines: PCV15 (Vaxneuvance), PCV20 (Prevnar20), and PPSV23 (Pneumovax23).
“The pneumococcal vaccine schedule is the most complicated one as higher-valent products continue to become available,” Dr. Fryhofer said.
The two types are pneumococcal conjugate vaccines (PCVs, specifically PCV15 and PCV20) and the pneumococcal polysaccharide vaccine (PPSV23). “While PPSV23 covers 23 strains, it doesn’t give the long-term immunity of the conjugate vaccine,” said Dr. Fryhofer. “A patient may have completed their vaccination with the polysaccharide vaccine but 5 years out may no longer be protected. So we offer the option of getting a dose of PCV20 to round out the protection and confer greater immune memory.”
The ACIP schedule recommends immunization against the Streptococcus pneumoniae pathogen for all older and all at-risk adults. Routine administration of PCV15 or PCV20 is advised for those 65 years or older who have never received any pneumococcal conjugate vaccine or whose previous vaccination history is unknown. If PCV15 is used, it should be followed by PPSV23. Those 65 years or older should get PPSV23 even if they already had one or more doses of pneumococcal vaccine before turning 65.
Further vaccination is recommended for younger at-risk adults aged 19-64 years who have received both PCV13 and PPSV23 but have incomplete vaccination status. These individuals are advised to complete their pneumococcal series by receiving either a single dose of PCV20 at an interval of at least 5 years after the last pneumococcal vaccine dose or more than one dose of PPSV23.
See Pneumococcal Vaccination: Summary of Who and When to Vaccinate for CDC guidance on vaccination options for adults who have previously received a pneumococcal conjugate vaccine. Or, to sort out quickly who gets what and when based on their age, concurrent conditions, and vaccination history, the CDC offers a type-in app called the PneumoRecs VaxAdvisor.
4. Measles, Mumps, and Rubella, and Varicella Vaccines
The two approved MMR vaccines are M-M-R II and PRIORIX. A third vaccine, ProQuad, adds varicella.
Adults lacking presumptive evidence of immunity should get at least one dose of the MMR combination vaccine.
Those born before 1957 are deemed to be immune, Dr. Fryhofer noted.
Two doses are recommended for adults entering high-risk settings for measles or mumps transmission such as healthcare personnel, students away at college, and international travelers. The two doses should be separated by at least 28 days. It’s no secret that measles, though preventable, is making a comeback, with 146 reported cases (48 in adults) across 21 states as of May 31 — most linked to international travel.
Women who plan to get pregnant should be vaccinated before but not during each pregnancy. (The vaccine is safe during lactation.) And those of childbearing age with no presumptive evidence of immunity are advised to get at least one dose of the MMR vaccine.
5. Tetanus, Diphtheria, and Pertussis Vaccine
Adults with no previous Tdap vaccination should receive a single dose of Adacel or Boostrix followed by a booster every 10 years. Boostrix is recommended for adults over 64 years.
During every pregnancy, women should have a single dose of Tdap, preferably in gestational weeks 27 through 36.
As to the immediate postpartum period, Tdap is recommended only for mothers who did not receive it during their current pregnancy and never received a prior dose. If a woman did not receive Tdap during her current pregnancy but did receive a prior dose of Tdap, she does not need Tdap postpartum.
The Challenges
According to Dr. Fryhofer, widespread disinformation about the risks of immunization against vaccine-preventable diseases has brought us to a flashpoint. “It’s now more important than ever to keep telling patients that vaccination is one of the most effective tools for preventing individual illness and protecting public health.”
She recommends that doctors follow the National Institutes of Health’s AIMS method to broach the subject of adult vaccination and increase participation in an inquiring, reassuring, and low-pressure way. Standing for Announce, Inquire, Mirror, and Secure, AIMS structures a nonjudgmental, patient-friendly conversation around immunization to elicit and acknowledge the reasons for hesitancy while explaining the safety and efficacy of vaccines.
Dr. Fryhofer frequently uses AIMS to bring inoculation-averse patients around. “Keep the conversation open with reluctant patients but leave them where they are. They need to see you as a reliable source and nonjudgmental source of information,” she said.
Dr. Block recommends outlining the diseases that have been eliminated through vaccines, from polio to measles, as well as the dangers of vaccine refusal, as indicated by recent outbreaks of vaccine-preventable diseases in areas with low immunization rates. “This approach highlights the opportunity we all have to get vaccinated to protect ourselves and our communities,” she said.
In Dr. Fryhofer’s view, the situation is urgent and doctors need to be proactive. “We’re now at a public-health tipping point where we may see a sliding back and a reversing of many years of progress.”
Dr. Fryhofer and Dr. Block disclosed no competing interests relevant to their comments.
Culture of Sexual Harassment, Bullying Plagues Ob.Gyn.
Sexual harassment, bullying, and gender bias are still very real occupational hazards for ob.gyn. trainees and practitioners alike — even in this female-dominated field, a systematic evidence review found.
Published in JAMA Network Open, by Ankita Gupta, MD, MPH, a urogynecology and reconstructive pelvic surgery specialist at the University of Louisville in Kentucky, and colleagues, the analysis found rates as high as 71% for sexual harassment, coercion, or unwanted advances. It also noted high rates of bullying, gender bias, and microaggressions. “We were struck by the continued high rates of harassment,” Dr. Gupta said in an interview. “Much of the literature within academic medicine has suggested the unequal distribution of women among medical specialties is the cause of sexual and gender harassment, but despite ob.gyns. being overwhelmingly female, we found that gender bias continues to occur at alarmingly high rates.”
Furthermore, among studies where this was reported, almost 25% of respondents had experienced sexual coercion. Not unexpectedly, this mistreatment often went unreported to institutional leadership out of fear of retaliation.
“We were also surprised to find a high rate of 51% for sexual harassment among male respondents as well, suggesting that both gender and power dynamics play a role in harassment,” Dr. Gupta said.
The primary perpetrators of unwanted behaviors were other doctors, overwhelmingly attending physicians, although residents and fellows were also identified as perpetrators, especially when harassment was reported by medical students, she added. “This once again points to the underreported abuse of professional power.” Women were rarely the perpetrators — just 10% — although they were the perpetrators in 57.7% of cases when the victim was male.
“Another interesting aspect of this is gender bias and microaggressions in the operating room,” she continued. While female surgeons often experience bias coming from OR staff, the review found that 94.4% of female ob.gyns. had been mistaken for non-physicians, 88.9% had pre-apologized for asking for something from a surgical technician or nurse, and 83.3% needed to make such requests multiple times. “These instances demonstrate gender bias in both male and female operating room staff toward female ob.gyns.”
Undermining and bullying behaviors are common in surgical specialties, Dr. Gupta explained, and the tantrums, swearing, and humiliation of trainees may be considered as much a rite of passage as the long hours. “As a trainee, you are taught to ignore such behavior as reporting it comes with fear of repercussions.”
This review bore this out, with only 8%-12% of respondents across studies reporting harassment and then predominantly to another trainee. “Sexual harassment and microaggressions can further lead to loss of career opportunities and burnout and I have come across many ob.gyns. who have chosen alternate paths owing to negative experiences,” Dr. Gupta said.
The Analysis
A joint effort by the Society of Gynecologic Surgeons and the and Society of Gynecologic Oncology, the analysis looked at existing literature from inception through June 2023.
A total of 10 eligible studies with 5852 participants addressed prevalence and 12 eligible studies in 2906 participants addressed interventions. Among the findings across different studies:
- Sexual harassment was noted by 250 of 907 physicians (27.6%) and 181 of 255 female gynecologic oncologists (70.9%).
- Workplace discrimination ranged from 142 of 249 female gynecologic oncologists (57.0%) to 354 of 527 female gynecologic oncologists (67.2%); among male gynecologic oncologists 138 of 358 (38.5%) reported discrimination.
- Bullying was reported by 131 of 248 female gynecologic oncologists (52.8%).
- Ob.gyn. trainees commonly experienced sexual harassment: 253 of 366 respondents (69.1%); this included gender harassment, unwanted sexual attention, and sexual coercion.
- Mistreatment of medical students during ob.gyn. rotation was indicated by 168 of 668 (25.1%).
- Perpetrators of harassment included physicians (30.1%), other trainees (13.1%), and OR staff (7.7%).
These findings are consistent with those of other recent investigations. A systematic review from 2022 found that 25% of ob.gyn., 32% of general surgery, and 21% of medical interns and students reported bullying .
In another 2022 review, in which ob.gyn. program directors were mainly women and department chairs mainly men, the prevalence of sexual harassment did not differ based on the gender of program directors and chairs.
A study from 2021 reported that 27% of academic surgical trainees, including ob.gyns., reported sexual harassment.
Going back to 2004, a study across multiple medical specialties found that ob.gyn. was second only to general surgery as the specialty associated with the highest rates of sexual harassment.
Despite institutional anti-discrimination policies, real-life interventions seem ineffective. “Disappointingly, we found that most interventions to address harassment had not been appropriately evaluated and did not show a decrease in sexual harassment,” Dr. Gupta said. “Interventions that were successful in reducing mistreatment of trainees required institutional buy-in at multiple levels, including leadership, management, and administration,” she said.
Multi-pronged strategies might include providing tools to educate healthcare staff about harassment and empowering bystanders to intervene when encountering such situations. “Further, independent offices where all complaints are evaluated by an intermediary third party and requiring professionalism to be a criterion for promotion criterion can be useful strategies,” she said.
She noted that residents may model harassing behavior perpetrated by senior attending physicians, thereby creating a cycle of mistreatment. “Equipping clinicians to be better surgical educators, providing clinical support, and modeling positive behavior may help disrupt the culture of harassment.” While the best solutions may be unclear, it is clear that much work remains to be done before the ob.gyn. working environment catches up to official institutional anti-discrimination policies.
This study was supported by the Society of Gynecologic Surgeons. Dr. Gupta disclosed no competing interests. Several coauthors disclosed relationships with multiple pharmaceutical or biomedical companies.
Sexual harassment, bullying, and gender bias are still very real occupational hazards for ob.gyn. trainees and practitioners alike — even in this female-dominated field, a systematic evidence review found.
Published in JAMA Network Open, by Ankita Gupta, MD, MPH, a urogynecology and reconstructive pelvic surgery specialist at the University of Louisville in Kentucky, and colleagues, the analysis found rates as high as 71% for sexual harassment, coercion, or unwanted advances. It also noted high rates of bullying, gender bias, and microaggressions. “We were struck by the continued high rates of harassment,” Dr. Gupta said in an interview. “Much of the literature within academic medicine has suggested the unequal distribution of women among medical specialties is the cause of sexual and gender harassment, but despite ob.gyns. being overwhelmingly female, we found that gender bias continues to occur at alarmingly high rates.”
Furthermore, among studies where this was reported, almost 25% of respondents had experienced sexual coercion. Not unexpectedly, this mistreatment often went unreported to institutional leadership out of fear of retaliation.
“We were also surprised to find a high rate of 51% for sexual harassment among male respondents as well, suggesting that both gender and power dynamics play a role in harassment,” Dr. Gupta said.
The primary perpetrators of unwanted behaviors were other doctors, overwhelmingly attending physicians, although residents and fellows were also identified as perpetrators, especially when harassment was reported by medical students, she added. “This once again points to the underreported abuse of professional power.” Women were rarely the perpetrators — just 10% — although they were the perpetrators in 57.7% of cases when the victim was male.
“Another interesting aspect of this is gender bias and microaggressions in the operating room,” she continued. While female surgeons often experience bias coming from OR staff, the review found that 94.4% of female ob.gyns. had been mistaken for non-physicians, 88.9% had pre-apologized for asking for something from a surgical technician or nurse, and 83.3% needed to make such requests multiple times. “These instances demonstrate gender bias in both male and female operating room staff toward female ob.gyns.”
Undermining and bullying behaviors are common in surgical specialties, Dr. Gupta explained, and the tantrums, swearing, and humiliation of trainees may be considered as much a rite of passage as the long hours. “As a trainee, you are taught to ignore such behavior as reporting it comes with fear of repercussions.”
This review bore this out, with only 8%-12% of respondents across studies reporting harassment and then predominantly to another trainee. “Sexual harassment and microaggressions can further lead to loss of career opportunities and burnout and I have come across many ob.gyns. who have chosen alternate paths owing to negative experiences,” Dr. Gupta said.
The Analysis
A joint effort by the Society of Gynecologic Surgeons and the and Society of Gynecologic Oncology, the analysis looked at existing literature from inception through June 2023.
A total of 10 eligible studies with 5852 participants addressed prevalence and 12 eligible studies in 2906 participants addressed interventions. Among the findings across different studies:
- Sexual harassment was noted by 250 of 907 physicians (27.6%) and 181 of 255 female gynecologic oncologists (70.9%).
- Workplace discrimination ranged from 142 of 249 female gynecologic oncologists (57.0%) to 354 of 527 female gynecologic oncologists (67.2%); among male gynecologic oncologists 138 of 358 (38.5%) reported discrimination.
- Bullying was reported by 131 of 248 female gynecologic oncologists (52.8%).
- Ob.gyn. trainees commonly experienced sexual harassment: 253 of 366 respondents (69.1%); this included gender harassment, unwanted sexual attention, and sexual coercion.
- Mistreatment of medical students during ob.gyn. rotation was indicated by 168 of 668 (25.1%).
- Perpetrators of harassment included physicians (30.1%), other trainees (13.1%), and OR staff (7.7%).
These findings are consistent with those of other recent investigations. A systematic review from 2022 found that 25% of ob.gyn., 32% of general surgery, and 21% of medical interns and students reported bullying .
In another 2022 review, in which ob.gyn. program directors were mainly women and department chairs mainly men, the prevalence of sexual harassment did not differ based on the gender of program directors and chairs.
A study from 2021 reported that 27% of academic surgical trainees, including ob.gyns., reported sexual harassment.
Going back to 2004, a study across multiple medical specialties found that ob.gyn. was second only to general surgery as the specialty associated with the highest rates of sexual harassment.
Despite institutional anti-discrimination policies, real-life interventions seem ineffective. “Disappointingly, we found that most interventions to address harassment had not been appropriately evaluated and did not show a decrease in sexual harassment,” Dr. Gupta said. “Interventions that were successful in reducing mistreatment of trainees required institutional buy-in at multiple levels, including leadership, management, and administration,” she said.
Multi-pronged strategies might include providing tools to educate healthcare staff about harassment and empowering bystanders to intervene when encountering such situations. “Further, independent offices where all complaints are evaluated by an intermediary third party and requiring professionalism to be a criterion for promotion criterion can be useful strategies,” she said.
She noted that residents may model harassing behavior perpetrated by senior attending physicians, thereby creating a cycle of mistreatment. “Equipping clinicians to be better surgical educators, providing clinical support, and modeling positive behavior may help disrupt the culture of harassment.” While the best solutions may be unclear, it is clear that much work remains to be done before the ob.gyn. working environment catches up to official institutional anti-discrimination policies.
This study was supported by the Society of Gynecologic Surgeons. Dr. Gupta disclosed no competing interests. Several coauthors disclosed relationships with multiple pharmaceutical or biomedical companies.
Sexual harassment, bullying, and gender bias are still very real occupational hazards for ob.gyn. trainees and practitioners alike — even in this female-dominated field, a systematic evidence review found.
Published in JAMA Network Open, by Ankita Gupta, MD, MPH, a urogynecology and reconstructive pelvic surgery specialist at the University of Louisville in Kentucky, and colleagues, the analysis found rates as high as 71% for sexual harassment, coercion, or unwanted advances. It also noted high rates of bullying, gender bias, and microaggressions. “We were struck by the continued high rates of harassment,” Dr. Gupta said in an interview. “Much of the literature within academic medicine has suggested the unequal distribution of women among medical specialties is the cause of sexual and gender harassment, but despite ob.gyns. being overwhelmingly female, we found that gender bias continues to occur at alarmingly high rates.”
Furthermore, among studies where this was reported, almost 25% of respondents had experienced sexual coercion. Not unexpectedly, this mistreatment often went unreported to institutional leadership out of fear of retaliation.
“We were also surprised to find a high rate of 51% for sexual harassment among male respondents as well, suggesting that both gender and power dynamics play a role in harassment,” Dr. Gupta said.
The primary perpetrators of unwanted behaviors were other doctors, overwhelmingly attending physicians, although residents and fellows were also identified as perpetrators, especially when harassment was reported by medical students, she added. “This once again points to the underreported abuse of professional power.” Women were rarely the perpetrators — just 10% — although they were the perpetrators in 57.7% of cases when the victim was male.
“Another interesting aspect of this is gender bias and microaggressions in the operating room,” she continued. While female surgeons often experience bias coming from OR staff, the review found that 94.4% of female ob.gyns. had been mistaken for non-physicians, 88.9% had pre-apologized for asking for something from a surgical technician or nurse, and 83.3% needed to make such requests multiple times. “These instances demonstrate gender bias in both male and female operating room staff toward female ob.gyns.”
Undermining and bullying behaviors are common in surgical specialties, Dr. Gupta explained, and the tantrums, swearing, and humiliation of trainees may be considered as much a rite of passage as the long hours. “As a trainee, you are taught to ignore such behavior as reporting it comes with fear of repercussions.”
This review bore this out, with only 8%-12% of respondents across studies reporting harassment and then predominantly to another trainee. “Sexual harassment and microaggressions can further lead to loss of career opportunities and burnout and I have come across many ob.gyns. who have chosen alternate paths owing to negative experiences,” Dr. Gupta said.
The Analysis
A joint effort by the Society of Gynecologic Surgeons and the and Society of Gynecologic Oncology, the analysis looked at existing literature from inception through June 2023.
A total of 10 eligible studies with 5852 participants addressed prevalence and 12 eligible studies in 2906 participants addressed interventions. Among the findings across different studies:
- Sexual harassment was noted by 250 of 907 physicians (27.6%) and 181 of 255 female gynecologic oncologists (70.9%).
- Workplace discrimination ranged from 142 of 249 female gynecologic oncologists (57.0%) to 354 of 527 female gynecologic oncologists (67.2%); among male gynecologic oncologists 138 of 358 (38.5%) reported discrimination.
- Bullying was reported by 131 of 248 female gynecologic oncologists (52.8%).
- Ob.gyn. trainees commonly experienced sexual harassment: 253 of 366 respondents (69.1%); this included gender harassment, unwanted sexual attention, and sexual coercion.
- Mistreatment of medical students during ob.gyn. rotation was indicated by 168 of 668 (25.1%).
- Perpetrators of harassment included physicians (30.1%), other trainees (13.1%), and OR staff (7.7%).
These findings are consistent with those of other recent investigations. A systematic review from 2022 found that 25% of ob.gyn., 32% of general surgery, and 21% of medical interns and students reported bullying .
In another 2022 review, in which ob.gyn. program directors were mainly women and department chairs mainly men, the prevalence of sexual harassment did not differ based on the gender of program directors and chairs.
A study from 2021 reported that 27% of academic surgical trainees, including ob.gyns., reported sexual harassment.
Going back to 2004, a study across multiple medical specialties found that ob.gyn. was second only to general surgery as the specialty associated with the highest rates of sexual harassment.
Despite institutional anti-discrimination policies, real-life interventions seem ineffective. “Disappointingly, we found that most interventions to address harassment had not been appropriately evaluated and did not show a decrease in sexual harassment,” Dr. Gupta said. “Interventions that were successful in reducing mistreatment of trainees required institutional buy-in at multiple levels, including leadership, management, and administration,” she said.
Multi-pronged strategies might include providing tools to educate healthcare staff about harassment and empowering bystanders to intervene when encountering such situations. “Further, independent offices where all complaints are evaluated by an intermediary third party and requiring professionalism to be a criterion for promotion criterion can be useful strategies,” she said.
She noted that residents may model harassing behavior perpetrated by senior attending physicians, thereby creating a cycle of mistreatment. “Equipping clinicians to be better surgical educators, providing clinical support, and modeling positive behavior may help disrupt the culture of harassment.” While the best solutions may be unclear, it is clear that much work remains to be done before the ob.gyn. working environment catches up to official institutional anti-discrimination policies.
This study was supported by the Society of Gynecologic Surgeons. Dr. Gupta disclosed no competing interests. Several coauthors disclosed relationships with multiple pharmaceutical or biomedical companies.
FROM JAMA NETWORK OPEN
AGA Clinical Guideline Stresses Patient Preferences in Barrett’s Treatment
Published in Gastroenterology , the clinical practice guideline makes five main recommendations — one strong and four conditional — based on very low to moderate evidence. It also stresses that providers should practice shared decision making according to patient preferences and risk perception.
For the most part, the new guideline is not a significant departure from the way expert endoscopists are currently practicing EET for BE and related neoplasia, gastroenterologist Joel H. Rubenstein, MD, MSc, AGAF, of the Barrett’s Esophagus Program in the Division of Gastroenterology at University of Michigan Medical School at Ann Arbor, said in an interview. One of three first authors of the guideline, Dr. Rubenstein added, “There is, however, considerable variability in how endoscopists practice, and we hope this guidance will serve as a useful resource to refer to for best practices.”
Added gastroenterologist Tarek Sawas, MD, MPH, assistant professor of internal medicine at UT Southwestern Medical Center in Dallas, “We hope the update will provide some clarity for practice and for implementation, while allowing gastroenterologists the freedom to decide what is best for patients based on lesion characteristics.”
Dr. Sawas added that one of the differences in the new guideline relates to the approach to low-grade dysplasia. While earlier guidance favored treatment over surveillance, patient preferences should now be factored into management. “Some patients are risk-averse and prefer to wait and watch, while others place more value on treatment and just want to get on with it,” he said.
When this guideline was circulated for public comment, “the areas prompting the most feedback was on our current suggestions against the routine use of EET in non-dysplastic BE and for the use of either endoscopic mucosal resection [EMR] or endoscopic submucosal dissection [ESD] for resection — with the expectation that the vast majority may be managed with EMR,” Dr. Rubenstein said.
“We felt that ESD would work best for larger lesions,” explained Dr. Sawas. “There aren’t a lot data in this area, just some observational studies, but we should have more data for comparison in the next few years.”
The incidence of esophageal adenocarcinoma continues to rise and an update was deemed in order since the AGA’s last formal guidance on this subject using the systematic GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology was issued in 2011. “In the following time span, there’s been a lot of research, particularly with regard to management of low-grade dysplasia and endoscopic resection techniques,” Dr. Rubenstein said.
Key Recommendations
The 14 guideline panelists made the following suggestions for treatment and implementation based on different levels of certainty of evidence (CoE):
1. If high-grade dysplasia (HGD) is present, EET is recommended over surveillance, with subsequent surveillance performed at 3, 6, and 12 months, and annually thereafter. (Strong recommendation, moderate CoE).
Surveillance endoscopies should obtain targeted tissue samples of visible lesions and random biopsies of the cardia and distal 2 cm of the tubular esophagus.
2. In patients with low-grade dysplasia, EET is also preferred to surveillance. But for those placing a higher value on the certain harms and a lower value on the uncertain benefits of EET for reducing mortality, surveillance endoscopy is a reasonable option. (Conditional recommendation, low CoE).
Following EET, clinicians should perform surveillance at years 1 and 3 after complete eradication of intestinal metaplasia, then revert to the surveillance intervals used in non-dysplastic BE.
3. For non-dysplastic BE, the AGA advises against the routine use of EET. (Conditional recommendation, low CoE).
4. Patients undergoing EET should have resection of visible lesions followed by ablation of the remaining BE segment rather than resection of the entire segment.
In patients with only a small area of BE beyond the visible lesion, endoscopic resection is acceptable and may be preferred over repeated ablation. Radiofrequency ablation is the preferred ablative modality. (Conditional recommendation, very low CoE).
5. For treating visible neoplastic lesions the AGA suggests either EMR or ESD based on lesion characteristics. (Conditional recommendation, very low CoE).
Patients with suspected T1 esophageal adenocarcinoma (EAC) should be considered for EET. Endoscopic resection is recommended over endoscopic ultrasound for distinguishing EAC from HGD and for staging depth of invasion.
The vast majority of neoplastic lesions may be managed with EMR rather than ESD. Patients who have bulky lesions, or lesions highly suspicious of at least T1b invasion and are deemed candidates for endoscopic resection might benefit from ESD over EMR. Those with previously failed EMR might benefit from ESD.
As to the generally low quality of the supporting evidence, Dr. Rubenstein said, “Unfortunately, very few decisions we make in medicine are supported by high certainty of evidence, but we still have to make a decision.” He pointed out that the guideline highlights areas for future research that could help strengthen or change the guideline’s recommendations.
Considering benefits and harms, the panelists concluded that overall CoE across critical desirable outcomes of disease progression to EAC was moderate. Patient-important outcomes informing the harms were strictures, major bleeding perforation, and serious adverse events.
Lifestyle
The guidance also urges providers to counsel BE patients on tobacco cessation and weight loss if needed, and notes the specter of cancer may incentivize patients to make lifestyle changes.
The most common causes of death in EET patients are cardiovascular disease and other cancers, for which tobacco use and obesity are also major risk factors, and tobacco is associated with strictures, the panelists wrote. “The prospect of progression to cancer in patients with dysplastic BE often holds greater valence than prior counseling attempts, and patients may re-commit to such efforts following consultation for EET.”
Going Forward
Areas for future attention include:
- Identifying populations with non-dysplastic BE whose risk warrants EET
- Balancing risk and benefit of EET in low-grade dysplasia
- Randomized controlled trials comparing EMR and ESD in higher-risk lesions
- Optimal management of post-EET pain
- Stricture prevention and control
- Managing resistant/recurrent disease beyond reflux control
- Optimal surveillance and biopsy strategies following EETThis guideline was supported by the National Institutes of Health, the Department of Defense, the Veterans Administration Health Services and Research Division, and the Katy O. and Paul M. Rady Endowed Chair in Esophageal Cancer Research at the University of Colorado.
Dr. Sawas had no competing interests to disclose. Dr. Rubenstein reported research funding from Lucid Diagnostics.
Several other panelists reported research funding or consultation fees from various pharmaceutical and biotechnology companies.
Published in Gastroenterology , the clinical practice guideline makes five main recommendations — one strong and four conditional — based on very low to moderate evidence. It also stresses that providers should practice shared decision making according to patient preferences and risk perception.
For the most part, the new guideline is not a significant departure from the way expert endoscopists are currently practicing EET for BE and related neoplasia, gastroenterologist Joel H. Rubenstein, MD, MSc, AGAF, of the Barrett’s Esophagus Program in the Division of Gastroenterology at University of Michigan Medical School at Ann Arbor, said in an interview. One of three first authors of the guideline, Dr. Rubenstein added, “There is, however, considerable variability in how endoscopists practice, and we hope this guidance will serve as a useful resource to refer to for best practices.”
Added gastroenterologist Tarek Sawas, MD, MPH, assistant professor of internal medicine at UT Southwestern Medical Center in Dallas, “We hope the update will provide some clarity for practice and for implementation, while allowing gastroenterologists the freedom to decide what is best for patients based on lesion characteristics.”
Dr. Sawas added that one of the differences in the new guideline relates to the approach to low-grade dysplasia. While earlier guidance favored treatment over surveillance, patient preferences should now be factored into management. “Some patients are risk-averse and prefer to wait and watch, while others place more value on treatment and just want to get on with it,” he said.
When this guideline was circulated for public comment, “the areas prompting the most feedback was on our current suggestions against the routine use of EET in non-dysplastic BE and for the use of either endoscopic mucosal resection [EMR] or endoscopic submucosal dissection [ESD] for resection — with the expectation that the vast majority may be managed with EMR,” Dr. Rubenstein said.
“We felt that ESD would work best for larger lesions,” explained Dr. Sawas. “There aren’t a lot data in this area, just some observational studies, but we should have more data for comparison in the next few years.”
The incidence of esophageal adenocarcinoma continues to rise and an update was deemed in order since the AGA’s last formal guidance on this subject using the systematic GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology was issued in 2011. “In the following time span, there’s been a lot of research, particularly with regard to management of low-grade dysplasia and endoscopic resection techniques,” Dr. Rubenstein said.
Key Recommendations
The 14 guideline panelists made the following suggestions for treatment and implementation based on different levels of certainty of evidence (CoE):
1. If high-grade dysplasia (HGD) is present, EET is recommended over surveillance, with subsequent surveillance performed at 3, 6, and 12 months, and annually thereafter. (Strong recommendation, moderate CoE).
Surveillance endoscopies should obtain targeted tissue samples of visible lesions and random biopsies of the cardia and distal 2 cm of the tubular esophagus.
2. In patients with low-grade dysplasia, EET is also preferred to surveillance. But for those placing a higher value on the certain harms and a lower value on the uncertain benefits of EET for reducing mortality, surveillance endoscopy is a reasonable option. (Conditional recommendation, low CoE).
Following EET, clinicians should perform surveillance at years 1 and 3 after complete eradication of intestinal metaplasia, then revert to the surveillance intervals used in non-dysplastic BE.
3. For non-dysplastic BE, the AGA advises against the routine use of EET. (Conditional recommendation, low CoE).
4. Patients undergoing EET should have resection of visible lesions followed by ablation of the remaining BE segment rather than resection of the entire segment.
In patients with only a small area of BE beyond the visible lesion, endoscopic resection is acceptable and may be preferred over repeated ablation. Radiofrequency ablation is the preferred ablative modality. (Conditional recommendation, very low CoE).
5. For treating visible neoplastic lesions the AGA suggests either EMR or ESD based on lesion characteristics. (Conditional recommendation, very low CoE).
Patients with suspected T1 esophageal adenocarcinoma (EAC) should be considered for EET. Endoscopic resection is recommended over endoscopic ultrasound for distinguishing EAC from HGD and for staging depth of invasion.
The vast majority of neoplastic lesions may be managed with EMR rather than ESD. Patients who have bulky lesions, or lesions highly suspicious of at least T1b invasion and are deemed candidates for endoscopic resection might benefit from ESD over EMR. Those with previously failed EMR might benefit from ESD.
As to the generally low quality of the supporting evidence, Dr. Rubenstein said, “Unfortunately, very few decisions we make in medicine are supported by high certainty of evidence, but we still have to make a decision.” He pointed out that the guideline highlights areas for future research that could help strengthen or change the guideline’s recommendations.
Considering benefits and harms, the panelists concluded that overall CoE across critical desirable outcomes of disease progression to EAC was moderate. Patient-important outcomes informing the harms were strictures, major bleeding perforation, and serious adverse events.
Lifestyle
The guidance also urges providers to counsel BE patients on tobacco cessation and weight loss if needed, and notes the specter of cancer may incentivize patients to make lifestyle changes.
The most common causes of death in EET patients are cardiovascular disease and other cancers, for which tobacco use and obesity are also major risk factors, and tobacco is associated with strictures, the panelists wrote. “The prospect of progression to cancer in patients with dysplastic BE often holds greater valence than prior counseling attempts, and patients may re-commit to such efforts following consultation for EET.”
Going Forward
Areas for future attention include:
- Identifying populations with non-dysplastic BE whose risk warrants EET
- Balancing risk and benefit of EET in low-grade dysplasia
- Randomized controlled trials comparing EMR and ESD in higher-risk lesions
- Optimal management of post-EET pain
- Stricture prevention and control
- Managing resistant/recurrent disease beyond reflux control
- Optimal surveillance and biopsy strategies following EETThis guideline was supported by the National Institutes of Health, the Department of Defense, the Veterans Administration Health Services and Research Division, and the Katy O. and Paul M. Rady Endowed Chair in Esophageal Cancer Research at the University of Colorado.
Dr. Sawas had no competing interests to disclose. Dr. Rubenstein reported research funding from Lucid Diagnostics.
Several other panelists reported research funding or consultation fees from various pharmaceutical and biotechnology companies.
Published in Gastroenterology , the clinical practice guideline makes five main recommendations — one strong and four conditional — based on very low to moderate evidence. It also stresses that providers should practice shared decision making according to patient preferences and risk perception.
For the most part, the new guideline is not a significant departure from the way expert endoscopists are currently practicing EET for BE and related neoplasia, gastroenterologist Joel H. Rubenstein, MD, MSc, AGAF, of the Barrett’s Esophagus Program in the Division of Gastroenterology at University of Michigan Medical School at Ann Arbor, said in an interview. One of three first authors of the guideline, Dr. Rubenstein added, “There is, however, considerable variability in how endoscopists practice, and we hope this guidance will serve as a useful resource to refer to for best practices.”
Added gastroenterologist Tarek Sawas, MD, MPH, assistant professor of internal medicine at UT Southwestern Medical Center in Dallas, “We hope the update will provide some clarity for practice and for implementation, while allowing gastroenterologists the freedom to decide what is best for patients based on lesion characteristics.”
Dr. Sawas added that one of the differences in the new guideline relates to the approach to low-grade dysplasia. While earlier guidance favored treatment over surveillance, patient preferences should now be factored into management. “Some patients are risk-averse and prefer to wait and watch, while others place more value on treatment and just want to get on with it,” he said.
When this guideline was circulated for public comment, “the areas prompting the most feedback was on our current suggestions against the routine use of EET in non-dysplastic BE and for the use of either endoscopic mucosal resection [EMR] or endoscopic submucosal dissection [ESD] for resection — with the expectation that the vast majority may be managed with EMR,” Dr. Rubenstein said.
“We felt that ESD would work best for larger lesions,” explained Dr. Sawas. “There aren’t a lot data in this area, just some observational studies, but we should have more data for comparison in the next few years.”
The incidence of esophageal adenocarcinoma continues to rise and an update was deemed in order since the AGA’s last formal guidance on this subject using the systematic GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology was issued in 2011. “In the following time span, there’s been a lot of research, particularly with regard to management of low-grade dysplasia and endoscopic resection techniques,” Dr. Rubenstein said.
Key Recommendations
The 14 guideline panelists made the following suggestions for treatment and implementation based on different levels of certainty of evidence (CoE):
1. If high-grade dysplasia (HGD) is present, EET is recommended over surveillance, with subsequent surveillance performed at 3, 6, and 12 months, and annually thereafter. (Strong recommendation, moderate CoE).
Surveillance endoscopies should obtain targeted tissue samples of visible lesions and random biopsies of the cardia and distal 2 cm of the tubular esophagus.
2. In patients with low-grade dysplasia, EET is also preferred to surveillance. But for those placing a higher value on the certain harms and a lower value on the uncertain benefits of EET for reducing mortality, surveillance endoscopy is a reasonable option. (Conditional recommendation, low CoE).
Following EET, clinicians should perform surveillance at years 1 and 3 after complete eradication of intestinal metaplasia, then revert to the surveillance intervals used in non-dysplastic BE.
3. For non-dysplastic BE, the AGA advises against the routine use of EET. (Conditional recommendation, low CoE).
4. Patients undergoing EET should have resection of visible lesions followed by ablation of the remaining BE segment rather than resection of the entire segment.
In patients with only a small area of BE beyond the visible lesion, endoscopic resection is acceptable and may be preferred over repeated ablation. Radiofrequency ablation is the preferred ablative modality. (Conditional recommendation, very low CoE).
5. For treating visible neoplastic lesions the AGA suggests either EMR or ESD based on lesion characteristics. (Conditional recommendation, very low CoE).
Patients with suspected T1 esophageal adenocarcinoma (EAC) should be considered for EET. Endoscopic resection is recommended over endoscopic ultrasound for distinguishing EAC from HGD and for staging depth of invasion.
The vast majority of neoplastic lesions may be managed with EMR rather than ESD. Patients who have bulky lesions, or lesions highly suspicious of at least T1b invasion and are deemed candidates for endoscopic resection might benefit from ESD over EMR. Those with previously failed EMR might benefit from ESD.
As to the generally low quality of the supporting evidence, Dr. Rubenstein said, “Unfortunately, very few decisions we make in medicine are supported by high certainty of evidence, but we still have to make a decision.” He pointed out that the guideline highlights areas for future research that could help strengthen or change the guideline’s recommendations.
Considering benefits and harms, the panelists concluded that overall CoE across critical desirable outcomes of disease progression to EAC was moderate. Patient-important outcomes informing the harms were strictures, major bleeding perforation, and serious adverse events.
Lifestyle
The guidance also urges providers to counsel BE patients on tobacco cessation and weight loss if needed, and notes the specter of cancer may incentivize patients to make lifestyle changes.
The most common causes of death in EET patients are cardiovascular disease and other cancers, for which tobacco use and obesity are also major risk factors, and tobacco is associated with strictures, the panelists wrote. “The prospect of progression to cancer in patients with dysplastic BE often holds greater valence than prior counseling attempts, and patients may re-commit to such efforts following consultation for EET.”
Going Forward
Areas for future attention include:
- Identifying populations with non-dysplastic BE whose risk warrants EET
- Balancing risk and benefit of EET in low-grade dysplasia
- Randomized controlled trials comparing EMR and ESD in higher-risk lesions
- Optimal management of post-EET pain
- Stricture prevention and control
- Managing resistant/recurrent disease beyond reflux control
- Optimal surveillance and biopsy strategies following EETThis guideline was supported by the National Institutes of Health, the Department of Defense, the Veterans Administration Health Services and Research Division, and the Katy O. and Paul M. Rady Endowed Chair in Esophageal Cancer Research at the University of Colorado.
Dr. Sawas had no competing interests to disclose. Dr. Rubenstein reported research funding from Lucid Diagnostics.
Several other panelists reported research funding or consultation fees from various pharmaceutical and biotechnology companies.
FROM GASTROENTEROLOGY
High-Alcohol Intake in MASLD Increases Risk of Cirrhosis
Moreover, the combination of steatotic liver disease and high-risk alcohol intake carried a more than 43% higher long-term risk of liver cirrhosis compared with no alcohol use, according to researchers led by Robert J. Wong, MD, MS, of the Division of Gastroenterology and Hepatology, Veterans Affairs Healthcare System Palo Alto, at Stanford University School of Medicine in Palo Alto, California.
However, the study found that “reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease,” Dr. Wong and associates wrote in Gastroenterology.
Although concurrent moderate to heavy alcohol intake would be expected to lead more rapidly to liver disease progression, the existing literature has been conflicting, the authors noted. Several studies have even found moderate alcohol associated with a lower risk of advanced liver disease among MASLD patients, including that by Dunn et al. .
The Study
MASLD patients were identified through the US Veterans Affairs Corporate Data Warehouse from January 1, 2010, through December 31, 2017, with follow-up through December 31, 2022.
Alcohol use was assessed by Alcohol Use Disorders Identification Test–Concise (AUDIT-C) scores and was categorized as follows: no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1-2 for women and 1–3 for men), and high-risk alcohol (AUDIT-C ≥ 3 for women and ≥ 4 for men).
Among the 1,156,189 veterans with MASLD, 54.2% reported no alcohol, 34.6% low-risk alcohol, and 11.2% high-risk alcohol use. In median follow-up of nine to 10 years, incidence rates of cirrhosis were .53 per 100 person-years for no use, .42 for low-risk use, and .76 for high-risk use.
In contrast to patients with baseline high-risk alcohol intake who reported no change in use, those who decreased their alcohol intake during follow-up experienced a 39% reduction in the long-term risk of cirrhosis, for a hazard ratio of .61 (95% CI, .45-.83, P < .01).
About 70% of patients were non-Hispanic Whites and more than 90% were male in all consumption categories. The no-alcohol group was older than the high-risk alcohol group: 64 years vs 59.9 years (P < .0001). Compared with the high-risk alcohol group, the no-alcohol group had a significantly greater proportion of comorbid diabetes (62.3% vs 42.5%), hypertension (77.9% vs 69.1%), or cardiovascular disease (40.2% vs 25.9%, P < .0001 for all comparisons).
In a significant study observation, fewer than 5% of patients with high-risk use received behavioral or pharmacologic therapy and of those who did, most were referred for or received treatment at or near the time of cirrhosis diagnosis. “This highlights a major gap in linking patients with high-risk alcohol use to appropriate behavioral or pharmacologic therapy in a timely manner and may reflect missed opportunities to prevent further alcohol-related morbidity and mortality,” Dr. Wong and colleagues wrote.
They called for studies of novel interventions for timely assessment of alcohol use with linkage to addiction services. They cited the need to understand the interaction between levels of alcohol use and underlying MASLD, adding, “More research is also needed to understand whether this interaction varies across different populations.”
This study received no specific funding. Dr. Wong reported funding through his institution from Gilead Sciences, Exact Sciences, and Thera Technologies.
Recent consensus in defining metabolic dysfunction-associated steatotic liver disease (MASLD) has raised awareness for the combined impact of cardiometabolic risk factors and alcohol consumption on liver disease progression. This study by Wong et al. highlights the undeniable influence of high-risk alcohol use on the development of advanced liver disease.
In a national cohort of over 1 million US veterans with steatotic liver disease (SLD), patients with high-risk alcohol use based on AUDIT-C assessment exhibited > 43% greater risk of cirrhosis compared to those with no alcohol use. The relationship between alcohol and liver severity in SLD was observed even after excluding patients meeting classification for predominant alcohol-associated liver disease. While increased alcohol use was associated with increased incidence of cirrhosis, decreased alcohol use led to a notable 39% reduction in cirrhosis risk over time.
Reducing alcohol consumption remains best practice guidelines for mitigating risk of progression in steatotic liver disease. However, results of this study emphasize the critical need for early identification and treatment of high-risk alcohol use in all patients with SLD. While universal recommendations for alcohol abstinence provides pragmatic implementation, there is a significant need to better understand the interaction of specific metabolic risk factors and patterns of alcohol use across the spectrum of MetALD to guide personalized recommendations for patient education and management.
Further research using prospective clinical trial design is needed to evaluate the interplay of alcohol consumption and metabolic risk factors across variable age, sex, genetics, and environmental exposures that are increasingly being recognized as vital drivers of health and disease.
Tiffany Wu, MD, MS, is a fellow in Transplant Hepatology at Mayo Clinic in Rochester, Minnesota. She has no conflicts.
Recent consensus in defining metabolic dysfunction-associated steatotic liver disease (MASLD) has raised awareness for the combined impact of cardiometabolic risk factors and alcohol consumption on liver disease progression. This study by Wong et al. highlights the undeniable influence of high-risk alcohol use on the development of advanced liver disease.
In a national cohort of over 1 million US veterans with steatotic liver disease (SLD), patients with high-risk alcohol use based on AUDIT-C assessment exhibited > 43% greater risk of cirrhosis compared to those with no alcohol use. The relationship between alcohol and liver severity in SLD was observed even after excluding patients meeting classification for predominant alcohol-associated liver disease. While increased alcohol use was associated with increased incidence of cirrhosis, decreased alcohol use led to a notable 39% reduction in cirrhosis risk over time.
Reducing alcohol consumption remains best practice guidelines for mitigating risk of progression in steatotic liver disease. However, results of this study emphasize the critical need for early identification and treatment of high-risk alcohol use in all patients with SLD. While universal recommendations for alcohol abstinence provides pragmatic implementation, there is a significant need to better understand the interaction of specific metabolic risk factors and patterns of alcohol use across the spectrum of MetALD to guide personalized recommendations for patient education and management.
Further research using prospective clinical trial design is needed to evaluate the interplay of alcohol consumption and metabolic risk factors across variable age, sex, genetics, and environmental exposures that are increasingly being recognized as vital drivers of health and disease.
Tiffany Wu, MD, MS, is a fellow in Transplant Hepatology at Mayo Clinic in Rochester, Minnesota. She has no conflicts.
Recent consensus in defining metabolic dysfunction-associated steatotic liver disease (MASLD) has raised awareness for the combined impact of cardiometabolic risk factors and alcohol consumption on liver disease progression. This study by Wong et al. highlights the undeniable influence of high-risk alcohol use on the development of advanced liver disease.
In a national cohort of over 1 million US veterans with steatotic liver disease (SLD), patients with high-risk alcohol use based on AUDIT-C assessment exhibited > 43% greater risk of cirrhosis compared to those with no alcohol use. The relationship between alcohol and liver severity in SLD was observed even after excluding patients meeting classification for predominant alcohol-associated liver disease. While increased alcohol use was associated with increased incidence of cirrhosis, decreased alcohol use led to a notable 39% reduction in cirrhosis risk over time.
Reducing alcohol consumption remains best practice guidelines for mitigating risk of progression in steatotic liver disease. However, results of this study emphasize the critical need for early identification and treatment of high-risk alcohol use in all patients with SLD. While universal recommendations for alcohol abstinence provides pragmatic implementation, there is a significant need to better understand the interaction of specific metabolic risk factors and patterns of alcohol use across the spectrum of MetALD to guide personalized recommendations for patient education and management.
Further research using prospective clinical trial design is needed to evaluate the interplay of alcohol consumption and metabolic risk factors across variable age, sex, genetics, and environmental exposures that are increasingly being recognized as vital drivers of health and disease.
Tiffany Wu, MD, MS, is a fellow in Transplant Hepatology at Mayo Clinic in Rochester, Minnesota. She has no conflicts.
Moreover, the combination of steatotic liver disease and high-risk alcohol intake carried a more than 43% higher long-term risk of liver cirrhosis compared with no alcohol use, according to researchers led by Robert J. Wong, MD, MS, of the Division of Gastroenterology and Hepatology, Veterans Affairs Healthcare System Palo Alto, at Stanford University School of Medicine in Palo Alto, California.
However, the study found that “reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease,” Dr. Wong and associates wrote in Gastroenterology.
Although concurrent moderate to heavy alcohol intake would be expected to lead more rapidly to liver disease progression, the existing literature has been conflicting, the authors noted. Several studies have even found moderate alcohol associated with a lower risk of advanced liver disease among MASLD patients, including that by Dunn et al. .
The Study
MASLD patients were identified through the US Veterans Affairs Corporate Data Warehouse from January 1, 2010, through December 31, 2017, with follow-up through December 31, 2022.
Alcohol use was assessed by Alcohol Use Disorders Identification Test–Concise (AUDIT-C) scores and was categorized as follows: no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1-2 for women and 1–3 for men), and high-risk alcohol (AUDIT-C ≥ 3 for women and ≥ 4 for men).
Among the 1,156,189 veterans with MASLD, 54.2% reported no alcohol, 34.6% low-risk alcohol, and 11.2% high-risk alcohol use. In median follow-up of nine to 10 years, incidence rates of cirrhosis were .53 per 100 person-years for no use, .42 for low-risk use, and .76 for high-risk use.
In contrast to patients with baseline high-risk alcohol intake who reported no change in use, those who decreased their alcohol intake during follow-up experienced a 39% reduction in the long-term risk of cirrhosis, for a hazard ratio of .61 (95% CI, .45-.83, P < .01).
About 70% of patients were non-Hispanic Whites and more than 90% were male in all consumption categories. The no-alcohol group was older than the high-risk alcohol group: 64 years vs 59.9 years (P < .0001). Compared with the high-risk alcohol group, the no-alcohol group had a significantly greater proportion of comorbid diabetes (62.3% vs 42.5%), hypertension (77.9% vs 69.1%), or cardiovascular disease (40.2% vs 25.9%, P < .0001 for all comparisons).
In a significant study observation, fewer than 5% of patients with high-risk use received behavioral or pharmacologic therapy and of those who did, most were referred for or received treatment at or near the time of cirrhosis diagnosis. “This highlights a major gap in linking patients with high-risk alcohol use to appropriate behavioral or pharmacologic therapy in a timely manner and may reflect missed opportunities to prevent further alcohol-related morbidity and mortality,” Dr. Wong and colleagues wrote.
They called for studies of novel interventions for timely assessment of alcohol use with linkage to addiction services. They cited the need to understand the interaction between levels of alcohol use and underlying MASLD, adding, “More research is also needed to understand whether this interaction varies across different populations.”
This study received no specific funding. Dr. Wong reported funding through his institution from Gilead Sciences, Exact Sciences, and Thera Technologies.
Moreover, the combination of steatotic liver disease and high-risk alcohol intake carried a more than 43% higher long-term risk of liver cirrhosis compared with no alcohol use, according to researchers led by Robert J. Wong, MD, MS, of the Division of Gastroenterology and Hepatology, Veterans Affairs Healthcare System Palo Alto, at Stanford University School of Medicine in Palo Alto, California.
However, the study found that “reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease,” Dr. Wong and associates wrote in Gastroenterology.
Although concurrent moderate to heavy alcohol intake would be expected to lead more rapidly to liver disease progression, the existing literature has been conflicting, the authors noted. Several studies have even found moderate alcohol associated with a lower risk of advanced liver disease among MASLD patients, including that by Dunn et al. .
The Study
MASLD patients were identified through the US Veterans Affairs Corporate Data Warehouse from January 1, 2010, through December 31, 2017, with follow-up through December 31, 2022.
Alcohol use was assessed by Alcohol Use Disorders Identification Test–Concise (AUDIT-C) scores and was categorized as follows: no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1-2 for women and 1–3 for men), and high-risk alcohol (AUDIT-C ≥ 3 for women and ≥ 4 for men).
Among the 1,156,189 veterans with MASLD, 54.2% reported no alcohol, 34.6% low-risk alcohol, and 11.2% high-risk alcohol use. In median follow-up of nine to 10 years, incidence rates of cirrhosis were .53 per 100 person-years for no use, .42 for low-risk use, and .76 for high-risk use.
In contrast to patients with baseline high-risk alcohol intake who reported no change in use, those who decreased their alcohol intake during follow-up experienced a 39% reduction in the long-term risk of cirrhosis, for a hazard ratio of .61 (95% CI, .45-.83, P < .01).
About 70% of patients were non-Hispanic Whites and more than 90% were male in all consumption categories. The no-alcohol group was older than the high-risk alcohol group: 64 years vs 59.9 years (P < .0001). Compared with the high-risk alcohol group, the no-alcohol group had a significantly greater proportion of comorbid diabetes (62.3% vs 42.5%), hypertension (77.9% vs 69.1%), or cardiovascular disease (40.2% vs 25.9%, P < .0001 for all comparisons).
In a significant study observation, fewer than 5% of patients with high-risk use received behavioral or pharmacologic therapy and of those who did, most were referred for or received treatment at or near the time of cirrhosis diagnosis. “This highlights a major gap in linking patients with high-risk alcohol use to appropriate behavioral or pharmacologic therapy in a timely manner and may reflect missed opportunities to prevent further alcohol-related morbidity and mortality,” Dr. Wong and colleagues wrote.
They called for studies of novel interventions for timely assessment of alcohol use with linkage to addiction services. They cited the need to understand the interaction between levels of alcohol use and underlying MASLD, adding, “More research is also needed to understand whether this interaction varies across different populations.”
This study received no specific funding. Dr. Wong reported funding through his institution from Gilead Sciences, Exact Sciences, and Thera Technologies.
FROM GASTROENTEROLOGY
Genes May Govern Intestinal Sites of Pediatric Crohn’s
, a small analysis in Cellular and Molecular Gastroenterology and Hepatology suggests.
Richard Kellermayer, MD, PhD, professor of pediatrics in the Section of Pediatric Gastroenterology, Hepatology and Nutrition at Baylor College of Medicine in Houston, Texas, and colleagues compared the genetic makeup of patients based on their Crohn’s disease location — predominantly in the small bowel (L4) or predominantly in the colon (L2 and/or L3). They then generated bipartite networks of susceptibility genes to study the polygenic background of the disease subtypes. They hypothesize that such networks may govern where a patient develops Crohn’s disease.
According to current understanding, as Dr. Kellermayer told GI & Hepatology News, most autoimmune disorders, CD included, develop in people with a genetic predisposition after serial environmental insults between conception and young adulthood. “As opposed to single-gene-associated genetic disorders, autoimmune diseases are linked to several hundred genes in which subtle anomalies can work in concert to predispose someone to a certain disorder,” he said. “We hope our findings will guide the development of personalized treatments based on the disease location at diagnosis to advance precision medicine.”
CD cases
Eight cases of SB-CD and 11 of C-CD met the inclusion criteria. Mean age at CD diagnosis was about 11 years for both subtypes, while 36.3% of patients with C-CD were female vs 25% of those with SB-CD. Ethnicity was 72.2% White in the C-CD group and 87.5% in the SB-CD group.
As to the main ileocolonic locations according to the Paris Classification of pediatric inflammatory bowel disease, 54.5% in the C-CD group had involvement at L2 and 45.5% at L3. In SB-CD cases, 100% had disease at L4b, 37.5% at L4, and 50% at L1.
The researchers identified 115 single-nucleotide polymorphisms (SNPs) with a combined annotation-dependent depletion (CADD) score on Phil’s Read Editor (PHRED) of >10 that was associated with 97 genes. PHRED is a computer program measuring the quality of the identification of nucleobases generated by automated DNA sequencing and scores the deleteriousness of single-nucleotide variants. The identified genes in this study had a significantly (P < .01) different allele variation between C-CD and SB-CD.
Among the top 28 candidates was an SNP in the EFNA3 gene with a CADD score > 20 for differentiating between the two phenotypically distinct CD groups. Furthermore, the EFNA3 rs17723260 (predicted to be deleterious) was found to have a significantly lower allele frequency (4.5%) in C-CD compared with its allele frequency of 37.5% in SB-CD (chi square P = .0097).
“This finding indicates that EFNA3 might play a role in modulating colonic inflammation, in which a deleterious genetic defect might provide protection against colitis (and direct autoimmunity against the proximal small bowel) in the polygenic background of CD,” the investigators wrote.
EFNA3 has been linked to both CD and ulcerative colitis. Another four genes associated with the top five SNP candidates had already been connected with IBD or mammalian intestinal inflammation.
According to the authors, the biomedical literature and mouse model findings “implicate the translational relevance of our candidate gene compendium for directing colon- vs small-bowel–predominant CD development.” They hope the findings will be replicated in larger CD cohorts differentiated by disease location. “Our work may set the nidus for CD subtype–based precision medicine by guiding individualized treatment strategies,” they wrote.
This study was supported by the ProKIIDS Network of the Crohn’s and Colitis Foundation and the Public Health Service. It was also supported by the Wagner, Frugoni, and Klaasmeyer families’ Gutsy Kids Fund and by the DR and GL Laws Fund. The authors disclosed no conflicts of interest.
, a small analysis in Cellular and Molecular Gastroenterology and Hepatology suggests.
Richard Kellermayer, MD, PhD, professor of pediatrics in the Section of Pediatric Gastroenterology, Hepatology and Nutrition at Baylor College of Medicine in Houston, Texas, and colleagues compared the genetic makeup of patients based on their Crohn’s disease location — predominantly in the small bowel (L4) or predominantly in the colon (L2 and/or L3). They then generated bipartite networks of susceptibility genes to study the polygenic background of the disease subtypes. They hypothesize that such networks may govern where a patient develops Crohn’s disease.
According to current understanding, as Dr. Kellermayer told GI & Hepatology News, most autoimmune disorders, CD included, develop in people with a genetic predisposition after serial environmental insults between conception and young adulthood. “As opposed to single-gene-associated genetic disorders, autoimmune diseases are linked to several hundred genes in which subtle anomalies can work in concert to predispose someone to a certain disorder,” he said. “We hope our findings will guide the development of personalized treatments based on the disease location at diagnosis to advance precision medicine.”
CD cases
Eight cases of SB-CD and 11 of C-CD met the inclusion criteria. Mean age at CD diagnosis was about 11 years for both subtypes, while 36.3% of patients with C-CD were female vs 25% of those with SB-CD. Ethnicity was 72.2% White in the C-CD group and 87.5% in the SB-CD group.
As to the main ileocolonic locations according to the Paris Classification of pediatric inflammatory bowel disease, 54.5% in the C-CD group had involvement at L2 and 45.5% at L3. In SB-CD cases, 100% had disease at L4b, 37.5% at L4, and 50% at L1.
The researchers identified 115 single-nucleotide polymorphisms (SNPs) with a combined annotation-dependent depletion (CADD) score on Phil’s Read Editor (PHRED) of >10 that was associated with 97 genes. PHRED is a computer program measuring the quality of the identification of nucleobases generated by automated DNA sequencing and scores the deleteriousness of single-nucleotide variants. The identified genes in this study had a significantly (P < .01) different allele variation between C-CD and SB-CD.
Among the top 28 candidates was an SNP in the EFNA3 gene with a CADD score > 20 for differentiating between the two phenotypically distinct CD groups. Furthermore, the EFNA3 rs17723260 (predicted to be deleterious) was found to have a significantly lower allele frequency (4.5%) in C-CD compared with its allele frequency of 37.5% in SB-CD (chi square P = .0097).
“This finding indicates that EFNA3 might play a role in modulating colonic inflammation, in which a deleterious genetic defect might provide protection against colitis (and direct autoimmunity against the proximal small bowel) in the polygenic background of CD,” the investigators wrote.
EFNA3 has been linked to both CD and ulcerative colitis. Another four genes associated with the top five SNP candidates had already been connected with IBD or mammalian intestinal inflammation.
According to the authors, the biomedical literature and mouse model findings “implicate the translational relevance of our candidate gene compendium for directing colon- vs small-bowel–predominant CD development.” They hope the findings will be replicated in larger CD cohorts differentiated by disease location. “Our work may set the nidus for CD subtype–based precision medicine by guiding individualized treatment strategies,” they wrote.
This study was supported by the ProKIIDS Network of the Crohn’s and Colitis Foundation and the Public Health Service. It was also supported by the Wagner, Frugoni, and Klaasmeyer families’ Gutsy Kids Fund and by the DR and GL Laws Fund. The authors disclosed no conflicts of interest.
, a small analysis in Cellular and Molecular Gastroenterology and Hepatology suggests.
Richard Kellermayer, MD, PhD, professor of pediatrics in the Section of Pediatric Gastroenterology, Hepatology and Nutrition at Baylor College of Medicine in Houston, Texas, and colleagues compared the genetic makeup of patients based on their Crohn’s disease location — predominantly in the small bowel (L4) or predominantly in the colon (L2 and/or L3). They then generated bipartite networks of susceptibility genes to study the polygenic background of the disease subtypes. They hypothesize that such networks may govern where a patient develops Crohn’s disease.
According to current understanding, as Dr. Kellermayer told GI & Hepatology News, most autoimmune disorders, CD included, develop in people with a genetic predisposition after serial environmental insults between conception and young adulthood. “As opposed to single-gene-associated genetic disorders, autoimmune diseases are linked to several hundred genes in which subtle anomalies can work in concert to predispose someone to a certain disorder,” he said. “We hope our findings will guide the development of personalized treatments based on the disease location at diagnosis to advance precision medicine.”
CD cases
Eight cases of SB-CD and 11 of C-CD met the inclusion criteria. Mean age at CD diagnosis was about 11 years for both subtypes, while 36.3% of patients with C-CD were female vs 25% of those with SB-CD. Ethnicity was 72.2% White in the C-CD group and 87.5% in the SB-CD group.
As to the main ileocolonic locations according to the Paris Classification of pediatric inflammatory bowel disease, 54.5% in the C-CD group had involvement at L2 and 45.5% at L3. In SB-CD cases, 100% had disease at L4b, 37.5% at L4, and 50% at L1.
The researchers identified 115 single-nucleotide polymorphisms (SNPs) with a combined annotation-dependent depletion (CADD) score on Phil’s Read Editor (PHRED) of >10 that was associated with 97 genes. PHRED is a computer program measuring the quality of the identification of nucleobases generated by automated DNA sequencing and scores the deleteriousness of single-nucleotide variants. The identified genes in this study had a significantly (P < .01) different allele variation between C-CD and SB-CD.
Among the top 28 candidates was an SNP in the EFNA3 gene with a CADD score > 20 for differentiating between the two phenotypically distinct CD groups. Furthermore, the EFNA3 rs17723260 (predicted to be deleterious) was found to have a significantly lower allele frequency (4.5%) in C-CD compared with its allele frequency of 37.5% in SB-CD (chi square P = .0097).
“This finding indicates that EFNA3 might play a role in modulating colonic inflammation, in which a deleterious genetic defect might provide protection against colitis (and direct autoimmunity against the proximal small bowel) in the polygenic background of CD,” the investigators wrote.
EFNA3 has been linked to both CD and ulcerative colitis. Another four genes associated with the top five SNP candidates had already been connected with IBD or mammalian intestinal inflammation.
According to the authors, the biomedical literature and mouse model findings “implicate the translational relevance of our candidate gene compendium for directing colon- vs small-bowel–predominant CD development.” They hope the findings will be replicated in larger CD cohorts differentiated by disease location. “Our work may set the nidus for CD subtype–based precision medicine by guiding individualized treatment strategies,” they wrote.
This study was supported by the ProKIIDS Network of the Crohn’s and Colitis Foundation and the Public Health Service. It was also supported by the Wagner, Frugoni, and Klaasmeyer families’ Gutsy Kids Fund and by the DR and GL Laws Fund. The authors disclosed no conflicts of interest.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY