Digestive Health

Infants who are given nutrient- or supplement-enriched formula milk do not later have higher academic scores as adolescents than those fed with standard formula, a study published online in the BMJ suggests.

One goal of modifying infant formula has been to make long-term cognitive outcomes similar to those for breast-fed infants, the authors noted. Rates for breastfeeding beyond 6 weeks are low in many parts of the world and more than 60% of babies worldwide under the age of 6 months are given formula to replace or supplement breast milk, the paper states.

So far, research has been inconclusive on benefits, though enhancements continue to be added and claims have been made as to their benefits on cognition in advertising. Long-term trials are difficult as researchers move on and participants are lost to follow-up.

In a new study, however, researchers led by Maximiliane L. Verfürden, MsC, with the University College of London’s Great Ormond Street Institute of Child Health, linked data from seven dormant, randomized, controlled infant formula trials to participants’ performance later as adolescents in the United Kingdom on mandatory national school math and English exams at ages 11 and 16 and found no difference in scores.

They followed 1,763 adolescents who had been participants in the formula trials, which were conducted between 1993 and 2001, and were able to link 91.2% (1,607) to academic records.

They found “no benefit of the infant formula modifications on cognitive outcomes.”
 

Three types of formula studied

In this study, the researchers discuss three widely available types of modified infant formulas that have been promoted as benefiting cognitive development: formula enriched with nutrients; formula supplemented with long-chain polyunsaturated fatty acids (LCPUFAs); and follow-on formula fortified with iron.

In one supplement group the academic results were worse than for those given standard formula. At age 11, children who had been given the LCPUFA-enhanced formula scored lower in both English and math.

“Given the potential associations between the source of LCPUFAs and adverse cognitive outcomes, long-term follow-up of trials testing infant formulas from other sources of LCPUFAs is recommended,” the authors wrote.
 

Nutrients can harm, editorialist says

Charlotte Wright, BM BCH, MSc, a pediatrician and epidemiologist with the Glasgow Royal Hospital for Children in Glasgow, who was not part of the study, coauthored an editorial that accompanied the article in the BMJ.

Dr. Wright and nutritionist Ada L. Gargia, PhD, at the University of Glasgow, wrote that nutrients in some formula enhancements can harm and that infant milk trials often have been poorly conducted.

The editorialists point to a large systematic review of formula milk trials published this year in the BMJ by Helfer et al. that found that most were funded by industry.

“Helfer and colleagues’ review found that 80% of studies were at high risk of bias, mainly because of selective reporting, with 92% of abstracts mentioning positive findings, despite only 42% of trials finding statistically significant differences in a stated primary outcome,” they wrote.

Dr. Wright, who runs a specialist feeding clinic for children, said in an interview that the study is valuable in that it has follow-up “to an age when adult cognition can be robustly assessed.”

She noted that the authors say additives that have been shown to be harmful are still routinely added.

“There is now evidence that adding LCPUFAs results in lower cognition and that giving extra iron to healthy children increases their risk of infection and may even slow their growth,” she said.

But advertisements to the contrary are quickly found in an Internet search, she said, even if no specific claims are made for them.

She gave an example of an advertisement for a commonly used enhanced formula, which reads: “Our formulation contains our highest levels of DHA (Omega 3 LCPs) and is enriched with iron to support normal cognitive development.”

The formula studies were done more than 20 years ago, but Dr. Wright said that does not downplay their relevance.

The basic formulation of the formulas hasn’t changed much, she said, and the additives are still present.

This work was supported by the Economic and Social Research Council UCL, Bloomsbury and East London Doctoral Training Partnership and a Great Ormond Street Hospital Charity Research grant. Full disclosures for all authors are available with the full text of the paper. Dr. Wright and Dr. Garcia declared no relevant financial relationships.

Infants who are given nutrient- or supplement-enriched formula milk do not later have higher academic scores as adolescents than those fed with standard formula, a study published online in the BMJ suggests.

One goal of modifying infant formula has been to make long-term cognitive outcomes similar to those for breast-fed infants, the authors noted. Rates for breastfeeding beyond 6 weeks are low in many parts of the world and more than 60% of babies worldwide under the age of 6 months are given formula to replace or supplement breast milk, the paper states.

So far, research has been inconclusive on benefits, though enhancements continue to be added and claims have been made as to their benefits on cognition in advertising. Long-term trials are difficult as researchers move on and participants are lost to follow-up.

In a new study, however, researchers led by Maximiliane L. Verfürden, MsC, with the University College of London’s Great Ormond Street Institute of Child Health, linked data from seven dormant, randomized, controlled infant formula trials to participants’ performance later as adolescents in the United Kingdom on mandatory national school math and English exams at ages 11 and 16 and found no difference in scores.

They followed 1,763 adolescents who had been participants in the formula trials, which were conducted between 1993 and 2001, and were able to link 91.2% (1,607) to academic records.

They found “no benefit of the infant formula modifications on cognitive outcomes.”
 

Three types of formula studied

In this study, the researchers discuss three widely available types of modified infant formulas that have been promoted as benefiting cognitive development: formula enriched with nutrients; formula supplemented with long-chain polyunsaturated fatty acids (LCPUFAs); and follow-on formula fortified with iron.

In one supplement group the academic results were worse than for those given standard formula. At age 11, children who had been given the LCPUFA-enhanced formula scored lower in both English and math.

“Given the potential associations between the source of LCPUFAs and adverse cognitive outcomes, long-term follow-up of trials testing infant formulas from other sources of LCPUFAs is recommended,” the authors wrote.
 

Nutrients can harm, editorialist says

Charlotte Wright, BM BCH, MSc, a pediatrician and epidemiologist with the Glasgow Royal Hospital for Children in Glasgow, who was not part of the study, coauthored an editorial that accompanied the article in the BMJ.

Dr. Wright and nutritionist Ada L. Gargia, PhD, at the University of Glasgow, wrote that nutrients in some formula enhancements can harm and that infant milk trials often have been poorly conducted.

The editorialists point to a large systematic review of formula milk trials published this year in the BMJ by Helfer et al. that found that most were funded by industry.

“Helfer and colleagues’ review found that 80% of studies were at high risk of bias, mainly because of selective reporting, with 92% of abstracts mentioning positive findings, despite only 42% of trials finding statistically significant differences in a stated primary outcome,” they wrote.

Dr. Wright, who runs a specialist feeding clinic for children, said in an interview that the study is valuable in that it has follow-up “to an age when adult cognition can be robustly assessed.”

She noted that the authors say additives that have been shown to be harmful are still routinely added.

“There is now evidence that adding LCPUFAs results in lower cognition and that giving extra iron to healthy children increases their risk of infection and may even slow their growth,” she said.

But advertisements to the contrary are quickly found in an Internet search, she said, even if no specific claims are made for them.

She gave an example of an advertisement for a commonly used enhanced formula, which reads: “Our formulation contains our highest levels of DHA (Omega 3 LCPs) and is enriched with iron to support normal cognitive development.”

The formula studies were done more than 20 years ago, but Dr. Wright said that does not downplay their relevance.

The basic formulation of the formulas hasn’t changed much, she said, and the additives are still present.

This work was supported by the Economic and Social Research Council UCL, Bloomsbury and East London Doctoral Training Partnership and a Great Ormond Street Hospital Charity Research grant. Full disclosures for all authors are available with the full text of the paper. Dr. Wright and Dr. Garcia declared no relevant financial relationships.

Infants who are given nutrient- or supplement-enriched formula milk do not later have higher academic scores as adolescents than those fed with standard formula, a study published online in the BMJ suggests.

One goal of modifying infant formula has been to make long-term cognitive outcomes similar to those for breast-fed infants, the authors noted. Rates for breastfeeding beyond 6 weeks are low in many parts of the world and more than 60% of babies worldwide under the age of 6 months are given formula to replace or supplement breast milk, the paper states.

So far, research has been inconclusive on benefits, though enhancements continue to be added and claims have been made as to their benefits on cognition in advertising. Long-term trials are difficult as researchers move on and participants are lost to follow-up.

In a new study, however, researchers led by Maximiliane L. Verfürden, MsC, with the University College of London’s Great Ormond Street Institute of Child Health, linked data from seven dormant, randomized, controlled infant formula trials to participants’ performance later as adolescents in the United Kingdom on mandatory national school math and English exams at ages 11 and 16 and found no difference in scores.

They followed 1,763 adolescents who had been participants in the formula trials, which were conducted between 1993 and 2001, and were able to link 91.2% (1,607) to academic records.

They found “no benefit of the infant formula modifications on cognitive outcomes.”
 

Three types of formula studied

In this study, the researchers discuss three widely available types of modified infant formulas that have been promoted as benefiting cognitive development: formula enriched with nutrients; formula supplemented with long-chain polyunsaturated fatty acids (LCPUFAs); and follow-on formula fortified with iron.

In one supplement group the academic results were worse than for those given standard formula. At age 11, children who had been given the LCPUFA-enhanced formula scored lower in both English and math.

“Given the potential associations between the source of LCPUFAs and adverse cognitive outcomes, long-term follow-up of trials testing infant formulas from other sources of LCPUFAs is recommended,” the authors wrote.
 

Nutrients can harm, editorialist says

Charlotte Wright, BM BCH, MSc, a pediatrician and epidemiologist with the Glasgow Royal Hospital for Children in Glasgow, who was not part of the study, coauthored an editorial that accompanied the article in the BMJ.

Dr. Wright and nutritionist Ada L. Gargia, PhD, at the University of Glasgow, wrote that nutrients in some formula enhancements can harm and that infant milk trials often have been poorly conducted.

The editorialists point to a large systematic review of formula milk trials published this year in the BMJ by Helfer et al. that found that most were funded by industry.

“Helfer and colleagues’ review found that 80% of studies were at high risk of bias, mainly because of selective reporting, with 92% of abstracts mentioning positive findings, despite only 42% of trials finding statistically significant differences in a stated primary outcome,” they wrote.

Dr. Wright, who runs a specialist feeding clinic for children, said in an interview that the study is valuable in that it has follow-up “to an age when adult cognition can be robustly assessed.”

She noted that the authors say additives that have been shown to be harmful are still routinely added.

“There is now evidence that adding LCPUFAs results in lower cognition and that giving extra iron to healthy children increases their risk of infection and may even slow their growth,” she said.

But advertisements to the contrary are quickly found in an Internet search, she said, even if no specific claims are made for them.

She gave an example of an advertisement for a commonly used enhanced formula, which reads: “Our formulation contains our highest levels of DHA (Omega 3 LCPs) and is enriched with iron to support normal cognitive development.”

The formula studies were done more than 20 years ago, but Dr. Wright said that does not downplay their relevance.

The basic formulation of the formulas hasn’t changed much, she said, and the additives are still present.

This work was supported by the Economic and Social Research Council UCL, Bloomsbury and East London Doctoral Training Partnership and a Great Ormond Street Hospital Charity Research grant. Full disclosures for all authors are available with the full text of the paper. Dr. Wright and Dr. Garcia declared no relevant financial relationships.

When gastroenterologists resect polyps during colonoscopy, they may inadvertently leave some neoplastic tissue behind. Biopsies from resection margins sometimes contain polyp remnants, even after a lesion has been visibly removed, research has shown. But the significance of incomplete resection has been unclear.

A new study indicates that incomplete resection, compared with complete resection, substantially increases the likelihood that a polyp will be found during follow-up colonoscopy.

The evidence “strongly supports the hypothesis” that residual polyp tissue likely contributes to neoplastic polyp recurrence and, by extension, interval colorectal cancer, said study author Heiko Pohl, MD, and colleagues. Dr. Pohl is affiliated with the White River Junction Veterans Affairs Medical Center in Vermont and Dartmouth-Hitchcock Medical Center and Dartmouth Geisel School of Medicine in Hanover, N.H.

Among 166 participants in the Complete Adenoma Resection (CARE) study who went on to have a surveillance colonoscopy in the following years, metachronous neoplasia was detected more often in colon segments where polyps had been incompletely resected, compared with colon segments with complete resections (52% vs. 23%), according to a study in Annals of Internal Medicine.

In addition, colon segments that had had incomplete resections in the CARE study were more likely to have polyps that were 10 mm or greater (18% vs. 3%). The 32 participants who had at least one incomplete resection during the original CARE study were three times more likely to have a polyp at follow-up, Dr. Pohl and coauthors found.

There were no instances of cancer or high-grade dysplasia during follow-up, however.

Key questions remain, including “Why do people get cancer after colonoscopy?” said Shai Friedland, MD, MS, who was not involved in the study. “Maybe it is because of these polyps that were not removed completely.”

On the other hand, lesions that are more difficult to see in the first place and more dangerous might be responsible when colorectal cancer does occur after colonoscopy, said Dr. Friedland, professor of gastroenterology and hepatology at Stanford (Calif.) University and a gastroenterologist at Veterans Affairs Palo Alto (Calif.) Health Care System.

Although it is not surprising that polyp remnants may appear as polyps during follow-up examinations, the difference in polyp recurrence between groups “must be quite striking” for it to clearly be seen in this small study, Dr. Friedland said. The results suggest that there is a need to “redouble our efforts to make sure that we remove polyps completely and not just hope that they disappear after an incomplete job,” he added.

In the CARE study, which was conducted between 2009 and 2012 at two academic medical centers, researchers found that about 10% of neoplastic polyps with visibly complete removal may nonetheless be incompletely resected, based on the presence of neoplastic tissue in biopsies taken from resection margins.

The investigators focused on 5- to 20-mm nonpedunculated colorectal polyps that were removed during routine polypectomy using electrocautery snare resection.

Participants with incomplete polyp resections were encouraged to have a surveillance examination within 1 year, and those with complete resections received guideline-based surveillance recommendations. In the follow-up analysis, those with an incomplete resection had a median time to first examination of 17 months, and those with complete resections had a median time to first examination of 45 months.

“These results highlight the importance of achieving complete resection because the risk for subsequent advanced neoplasia detection statistically significantly increases without it,” Dr. Pohl said. “The large polyp size after incomplete resection within a generally short follow-up time may imply fast growth, even if none of the presumed recurrent polyps contained advanced histologic characteristics.”

Between-group differences in the participants and polyps could confound the observations, the authors noted. It is possible that endoscopists who did the follow-up colonoscopies looked harder for polyps in colon segments that had prior incomplete resections, on account of the initial study findings, they said. “It is also plausible that endoscopists with a greater incomplete resection rate would be more likely to miss polyps, which could then be detected at follow-up,” though detection and resection skills do not necessarily correlate, the investigators said.

With resection, the goal is to remove the polyp in one piece with clear margins, and researchers have known that the polyp removal techniques used in the study “are far from perfect,” Dr. Friedland said. One question is whether the field should focus on improving standard techniques, or incorporating newer, more advanced techniques such as endoscopic submucosal dissection, which is effective but may entail significant perforation risk when performed by someone who is not proficient, he said.

“One of the major focuses we had over the years is finding the polyps to prevent future cancer,” Dr. Pohl said in an interview. But the CARE study showed that “we do not do a good job of taking polyps off completely,” he added. The present analysis underscores that clinicians should do their best to remove polyps completely, even if they lack a way to confirm complete resection in routine practice, as is currently the case, Dr. Pohl said. To that end, clinicians should aim to refine their skills and techniques. Video evaluations with guidance from experts may prove helpful, he suggested. “We need to think hard about quality assessment,” Dr. Pohl said.

Dr. Pohl disclosed grants from Boston Scientific, Cosmo Pharmaceuticals, and Steris outside of the study. Dr. Friedland had no disclosures.
 

jremaly@mdedge.com

When gastroenterologists resect polyps during colonoscopy, they may inadvertently leave some neoplastic tissue behind. Biopsies from resection margins sometimes contain polyp remnants, even after a lesion has been visibly removed, research has shown. But the significance of incomplete resection has been unclear.

A new study indicates that incomplete resection, compared with complete resection, substantially increases the likelihood that a polyp will be found during follow-up colonoscopy.

The evidence “strongly supports the hypothesis” that residual polyp tissue likely contributes to neoplastic polyp recurrence and, by extension, interval colorectal cancer, said study author Heiko Pohl, MD, and colleagues. Dr. Pohl is affiliated with the White River Junction Veterans Affairs Medical Center in Vermont and Dartmouth-Hitchcock Medical Center and Dartmouth Geisel School of Medicine in Hanover, N.H.

Among 166 participants in the Complete Adenoma Resection (CARE) study who went on to have a surveillance colonoscopy in the following years, metachronous neoplasia was detected more often in colon segments where polyps had been incompletely resected, compared with colon segments with complete resections (52% vs. 23%), according to a study in Annals of Internal Medicine.

In addition, colon segments that had had incomplete resections in the CARE study were more likely to have polyps that were 10 mm or greater (18% vs. 3%). The 32 participants who had at least one incomplete resection during the original CARE study were three times more likely to have a polyp at follow-up, Dr. Pohl and coauthors found.

There were no instances of cancer or high-grade dysplasia during follow-up, however.

Key questions remain, including “Why do people get cancer after colonoscopy?” said Shai Friedland, MD, MS, who was not involved in the study. “Maybe it is because of these polyps that were not removed completely.”

On the other hand, lesions that are more difficult to see in the first place and more dangerous might be responsible when colorectal cancer does occur after colonoscopy, said Dr. Friedland, professor of gastroenterology and hepatology at Stanford (Calif.) University and a gastroenterologist at Veterans Affairs Palo Alto (Calif.) Health Care System.

Although it is not surprising that polyp remnants may appear as polyps during follow-up examinations, the difference in polyp recurrence between groups “must be quite striking” for it to clearly be seen in this small study, Dr. Friedland said. The results suggest that there is a need to “redouble our efforts to make sure that we remove polyps completely and not just hope that they disappear after an incomplete job,” he added.

In the CARE study, which was conducted between 2009 and 2012 at two academic medical centers, researchers found that about 10% of neoplastic polyps with visibly complete removal may nonetheless be incompletely resected, based on the presence of neoplastic tissue in biopsies taken from resection margins.

The investigators focused on 5- to 20-mm nonpedunculated colorectal polyps that were removed during routine polypectomy using electrocautery snare resection.

Participants with incomplete polyp resections were encouraged to have a surveillance examination within 1 year, and those with complete resections received guideline-based surveillance recommendations. In the follow-up analysis, those with an incomplete resection had a median time to first examination of 17 months, and those with complete resections had a median time to first examination of 45 months.

“These results highlight the importance of achieving complete resection because the risk for subsequent advanced neoplasia detection statistically significantly increases without it,” Dr. Pohl said. “The large polyp size after incomplete resection within a generally short follow-up time may imply fast growth, even if none of the presumed recurrent polyps contained advanced histologic characteristics.”

Between-group differences in the participants and polyps could confound the observations, the authors noted. It is possible that endoscopists who did the follow-up colonoscopies looked harder for polyps in colon segments that had prior incomplete resections, on account of the initial study findings, they said. “It is also plausible that endoscopists with a greater incomplete resection rate would be more likely to miss polyps, which could then be detected at follow-up,” though detection and resection skills do not necessarily correlate, the investigators said.

With resection, the goal is to remove the polyp in one piece with clear margins, and researchers have known that the polyp removal techniques used in the study “are far from perfect,” Dr. Friedland said. One question is whether the field should focus on improving standard techniques, or incorporating newer, more advanced techniques such as endoscopic submucosal dissection, which is effective but may entail significant perforation risk when performed by someone who is not proficient, he said.

“One of the major focuses we had over the years is finding the polyps to prevent future cancer,” Dr. Pohl said in an interview. But the CARE study showed that “we do not do a good job of taking polyps off completely,” he added. The present analysis underscores that clinicians should do their best to remove polyps completely, even if they lack a way to confirm complete resection in routine practice, as is currently the case, Dr. Pohl said. To that end, clinicians should aim to refine their skills and techniques. Video evaluations with guidance from experts may prove helpful, he suggested. “We need to think hard about quality assessment,” Dr. Pohl said.

Dr. Pohl disclosed grants from Boston Scientific, Cosmo Pharmaceuticals, and Steris outside of the study. Dr. Friedland had no disclosures.
 

jremaly@mdedge.com

When gastroenterologists resect polyps during colonoscopy, they may inadvertently leave some neoplastic tissue behind. Biopsies from resection margins sometimes contain polyp remnants, even after a lesion has been visibly removed, research has shown. But the significance of incomplete resection has been unclear.

A new study indicates that incomplete resection, compared with complete resection, substantially increases the likelihood that a polyp will be found during follow-up colonoscopy.

The evidence “strongly supports the hypothesis” that residual polyp tissue likely contributes to neoplastic polyp recurrence and, by extension, interval colorectal cancer, said study author Heiko Pohl, MD, and colleagues. Dr. Pohl is affiliated with the White River Junction Veterans Affairs Medical Center in Vermont and Dartmouth-Hitchcock Medical Center and Dartmouth Geisel School of Medicine in Hanover, N.H.

Among 166 participants in the Complete Adenoma Resection (CARE) study who went on to have a surveillance colonoscopy in the following years, metachronous neoplasia was detected more often in colon segments where polyps had been incompletely resected, compared with colon segments with complete resections (52% vs. 23%), according to a study in Annals of Internal Medicine.

In addition, colon segments that had had incomplete resections in the CARE study were more likely to have polyps that were 10 mm or greater (18% vs. 3%). The 32 participants who had at least one incomplete resection during the original CARE study were three times more likely to have a polyp at follow-up, Dr. Pohl and coauthors found.

There were no instances of cancer or high-grade dysplasia during follow-up, however.

Key questions remain, including “Why do people get cancer after colonoscopy?” said Shai Friedland, MD, MS, who was not involved in the study. “Maybe it is because of these polyps that were not removed completely.”

On the other hand, lesions that are more difficult to see in the first place and more dangerous might be responsible when colorectal cancer does occur after colonoscopy, said Dr. Friedland, professor of gastroenterology and hepatology at Stanford (Calif.) University and a gastroenterologist at Veterans Affairs Palo Alto (Calif.) Health Care System.

Although it is not surprising that polyp remnants may appear as polyps during follow-up examinations, the difference in polyp recurrence between groups “must be quite striking” for it to clearly be seen in this small study, Dr. Friedland said. The results suggest that there is a need to “redouble our efforts to make sure that we remove polyps completely and not just hope that they disappear after an incomplete job,” he added.

In the CARE study, which was conducted between 2009 and 2012 at two academic medical centers, researchers found that about 10% of neoplastic polyps with visibly complete removal may nonetheless be incompletely resected, based on the presence of neoplastic tissue in biopsies taken from resection margins.

The investigators focused on 5- to 20-mm nonpedunculated colorectal polyps that were removed during routine polypectomy using electrocautery snare resection.

Participants with incomplete polyp resections were encouraged to have a surveillance examination within 1 year, and those with complete resections received guideline-based surveillance recommendations. In the follow-up analysis, those with an incomplete resection had a median time to first examination of 17 months, and those with complete resections had a median time to first examination of 45 months.

“These results highlight the importance of achieving complete resection because the risk for subsequent advanced neoplasia detection statistically significantly increases without it,” Dr. Pohl said. “The large polyp size after incomplete resection within a generally short follow-up time may imply fast growth, even if none of the presumed recurrent polyps contained advanced histologic characteristics.”

Between-group differences in the participants and polyps could confound the observations, the authors noted. It is possible that endoscopists who did the follow-up colonoscopies looked harder for polyps in colon segments that had prior incomplete resections, on account of the initial study findings, they said. “It is also plausible that endoscopists with a greater incomplete resection rate would be more likely to miss polyps, which could then be detected at follow-up,” though detection and resection skills do not necessarily correlate, the investigators said.

With resection, the goal is to remove the polyp in one piece with clear margins, and researchers have known that the polyp removal techniques used in the study “are far from perfect,” Dr. Friedland said. One question is whether the field should focus on improving standard techniques, or incorporating newer, more advanced techniques such as endoscopic submucosal dissection, which is effective but may entail significant perforation risk when performed by someone who is not proficient, he said.

“One of the major focuses we had over the years is finding the polyps to prevent future cancer,” Dr. Pohl said in an interview. But the CARE study showed that “we do not do a good job of taking polyps off completely,” he added. The present analysis underscores that clinicians should do their best to remove polyps completely, even if they lack a way to confirm complete resection in routine practice, as is currently the case, Dr. Pohl said. To that end, clinicians should aim to refine their skills and techniques. Video evaluations with guidance from experts may prove helpful, he suggested. “We need to think hard about quality assessment,” Dr. Pohl said.

Dr. Pohl disclosed grants from Boston Scientific, Cosmo Pharmaceuticals, and Steris outside of the study. Dr. Friedland had no disclosures.
 

jremaly@mdedge.com

Medical admissions for adolescents with restrictive eating disorders more than doubled at one hospital during the first 12 months of the COVID-19 pandemic, relative to the average number of admissions in prior years, a new study shows.

Doctors are seeing similar increases across the United States and in other countries.

Providers and health care systems “may need to rapidly adapt in response to increasing demands for care during the COVID-19 pandemic,” the researchers said in their study, which was published online in Pediatrics.

To assess whether admission patterns among adolescents with restrictive eating disorders changed during the pandemic, Alana K. Otto, MD, MPH, with the division of adolescent medicine at the University of Michigan, Ann Arbor, and colleagues reviewed the charts of patients admitted to C.S. Mott Children’s Hospital, also in Ann Arbor.

Their analysis included 297 admissions among 248 patients aged 10-23 years between March 1, 2017, and March 31, 2021. Patients had an average age of about 15 years. Approximately 90% were female, and most had a diagnosis of anorexia nervosa or atypical anorexia nervosa.

Indications for medical admission included physiological instability (for example, heart rate less than 50 beats per minute while awake or blood pressure less than 90/40 mm Hg), electrolyte derangements, and acute medical complications of malnutrition such as syncope. Other possible indications included uncontrolled purging, body mass index less than 75% of the median for age and sex, acute food refusal, and failure of outpatient treatment.

Eating disorder–related admissions per month were stable prior to the pandemic. Admissions then decreased in April 2020, but subsequently increased significantly throughout the study period. In all, there were 125 admissions between April 1, 2020, and March 31, 2021. During the previous 3 years, the average number of admissions per year was 56.

Patients’ insurance status was one factor that differed before and during the pandemic. Prepandemic, about 20% of admissions were for adolescents with public insurance. During the pandemic, however, the proportion with public insurance was approximately 9%, the researchers noted. Other characteristics were generally similar.

The study was retrospective and relatively small and only looked at patients with restrictive eating disorders who were severely ill and admitted for medical stabilization. It does not reflect adolescents with eating disorders in different settings, the authors noted.

Primary care pediatricians should be familiar with indications for medical admission, such as severe bradycardia, as outlined by the Society for Adolescent Health and Medicine, they said.
 

Consistent trends

Unfortunately, the trend seems consistent across the nation, said Michaela M. Voss, MD, director of the the Eating Disorders Center at Children’s Mercy in Kansas City, Mo. “Our outpatient setting went from availability to get in immediately to a 6-month wait list.”

As in Michigan, Dr. Voss noted a drop in admissions as lockdowns started, followed by a spike in treatment demand that has not let up.

Dr. Voss described two of the more common presentations. In one, parents might note that their child had been getting into healthy eating and exercise before the pandemic and seemed fine. “But then COVID came, the lockdown happened, and they became overly obsessed with those things,” Dr. Voss said.

In the other presentation, kids with anxiety, depression, or OCD who lost access to their usual coping strategies and outlets developed eating disorders during the pandemic. “They focused on one of the few things they could during the lockdown, which was their own body, and then their anxiety, depression, [obsessive-compulsive disorder], and other mental health comorbidities presented as an eating disorder,” Dr. Voss said.

The increasing need for treatment over the course of the pandemic may reflect the time that it has taken for the disorders to develop, as well as the time that it takes parents to recognize the problem.

Not only are doctors seeing more cases, but patients are arriving sicker than usual, Dr. Voss said.

Major medical concerns for patients in starvation mode center on the heart, brain, and bones. In addition, refeeding syndrome poses an extreme risk, Dr. Voss noted.

The Academy for Eating Disorders has created a guide to help doctors recognize and manage risks for patients with eating disorders, which may be useful for primary care providers while they are trying to get a patient into more intensive treatment, Dr. Voss suggested. The American Academy of Pediatrics recently published a clinical report on the identification and management of eating disorders in children and adolescents.

At Johns Hopkins Hospital Children’s Center in Baltimore, “we have seen a pretty remarkable increase in the number of eating disorders in the child and adolescent space since COVID,” said Jennifer Leah Goetz, MD, a psychiatrist and medical director of the child and adolescent inpatient unit. “We have seen increasing numbers of kids presenting for acute medical stabilization and refeeding and for specific treatment for the eating disorder.”

It could be that, for people with a genetic predisposition to eating disorders, a confluence of factors related to the pandemic unmasked it. For example, children may have spent more time looking at themselves on virtual meeting platforms, which could stir lingering body image and appearance-related concerns in those who are vulnerable. And some teens who were not able to participate in athletics as usual started to watch what they eat more closely, Dr. Goetz said.
 

A treatment bottleneck

Patients with eating disorders “can be quite ill from a psychiatric and general medical perspective,” Dr. Goetz said. “Most psychiatrists are not particularly comfortable with the medical complications, and most internists or pediatricians are not particularly comfortable with the psychiatric complications. You end up with a patient population that can only see a really highly specialized group of individuals for care. And it is a problem. It was a problem before the pandemic, and it has been really exacerbated by what we have been going through with COVID.”

Natalie Muth, MD, MPH, RDN, a pediatrician at Children’s Primary Care Medical Group La Costa in Carlsbad, Calif., has also noticed the increase in eating disorders since COVID.

In-patient colleagues “have longer wait lists and more severe cases than they have ever seen previously,” said Dr. Muth, who chairs the American Academy of Pediatrics Section on Obesity and is an adjunct assistant professor at the University of California, Los Angeles. “In primary care, we are all having to better educate and prepare ourselves for identifying and managing patients with eating disorders.”

That could mean connecting with mental health professionals, registered dietitians, and higher levels of care. But that may be a challenge. “Accessing these resources has been more difficult due to the increasing incidence of eating disorders recently,” Dr. Muth said.

Dr. Voss acknowledged that childhood obesity is another concern for pediatricians. “However, there are appropriate and healthy and safe ways to address that,” she said. A patient with overweight or obesity who loses weight may not be doing so in a healthy way.

Clinicians should wonder if a patient’s weight is decreasing too fast. And they should ask patients questions that could help identify a problem, such as: What are they doing to cause the weight loss? Why do they want to lose the weight?

Dr. Voss added that eating disorders “do not discriminate.” While there may be a perception that all patients with eating disorders are White, upper middle–class females who are thin, “that is not the case,” Dr. Voss said. They “come in all genders, all races, all weight classes, and all ages,” she said, “and we see that variety.”

In general, there may be a need to shift how weight is discussed in clinics and society more broadly, Dr. Goetz said. Weight is an incredibly personal thing, and everyone’s genetics, metabolism, and life circumstances vary. At the same time, body mass index is not necessarily the best measure of a person’s health.

Asking a child, teen, or even an adult to go on a diet is not a benign intervention, Dr. Goetz noted. In addition, dieting is unlikely to help in the long term.

Emerging from lockdown, pressure to lose “COVID pounds” is a dangerous message for people with eating disorders, Dr. Goetz said. It also could be a dangerous message for people without eating disorders. “There are so many more interesting things about each one of us than our weight,” she added.

The study authors, Dr. Voss, Dr. Goetz, and Dr. Muth had no relevant disclosures.

jremaly@mdedge.com

Medical admissions for adolescents with restrictive eating disorders more than doubled at one hospital during the first 12 months of the COVID-19 pandemic, relative to the average number of admissions in prior years, a new study shows.

Doctors are seeing similar increases across the United States and in other countries.

Providers and health care systems “may need to rapidly adapt in response to increasing demands for care during the COVID-19 pandemic,” the researchers said in their study, which was published online in Pediatrics.

To assess whether admission patterns among adolescents with restrictive eating disorders changed during the pandemic, Alana K. Otto, MD, MPH, with the division of adolescent medicine at the University of Michigan, Ann Arbor, and colleagues reviewed the charts of patients admitted to C.S. Mott Children’s Hospital, also in Ann Arbor.

Their analysis included 297 admissions among 248 patients aged 10-23 years between March 1, 2017, and March 31, 2021. Patients had an average age of about 15 years. Approximately 90% were female, and most had a diagnosis of anorexia nervosa or atypical anorexia nervosa.

Indications for medical admission included physiological instability (for example, heart rate less than 50 beats per minute while awake or blood pressure less than 90/40 mm Hg), electrolyte derangements, and acute medical complications of malnutrition such as syncope. Other possible indications included uncontrolled purging, body mass index less than 75% of the median for age and sex, acute food refusal, and failure of outpatient treatment.

Eating disorder–related admissions per month were stable prior to the pandemic. Admissions then decreased in April 2020, but subsequently increased significantly throughout the study period. In all, there were 125 admissions between April 1, 2020, and March 31, 2021. During the previous 3 years, the average number of admissions per year was 56.

Patients’ insurance status was one factor that differed before and during the pandemic. Prepandemic, about 20% of admissions were for adolescents with public insurance. During the pandemic, however, the proportion with public insurance was approximately 9%, the researchers noted. Other characteristics were generally similar.

The study was retrospective and relatively small and only looked at patients with restrictive eating disorders who were severely ill and admitted for medical stabilization. It does not reflect adolescents with eating disorders in different settings, the authors noted.

Primary care pediatricians should be familiar with indications for medical admission, such as severe bradycardia, as outlined by the Society for Adolescent Health and Medicine, they said.
 

Consistent trends

Unfortunately, the trend seems consistent across the nation, said Michaela M. Voss, MD, director of the the Eating Disorders Center at Children’s Mercy in Kansas City, Mo. “Our outpatient setting went from availability to get in immediately to a 6-month wait list.”

As in Michigan, Dr. Voss noted a drop in admissions as lockdowns started, followed by a spike in treatment demand that has not let up.

Dr. Voss described two of the more common presentations. In one, parents might note that their child had been getting into healthy eating and exercise before the pandemic and seemed fine. “But then COVID came, the lockdown happened, and they became overly obsessed with those things,” Dr. Voss said.

In the other presentation, kids with anxiety, depression, or OCD who lost access to their usual coping strategies and outlets developed eating disorders during the pandemic. “They focused on one of the few things they could during the lockdown, which was their own body, and then their anxiety, depression, [obsessive-compulsive disorder], and other mental health comorbidities presented as an eating disorder,” Dr. Voss said.

The increasing need for treatment over the course of the pandemic may reflect the time that it has taken for the disorders to develop, as well as the time that it takes parents to recognize the problem.

Not only are doctors seeing more cases, but patients are arriving sicker than usual, Dr. Voss said.

Major medical concerns for patients in starvation mode center on the heart, brain, and bones. In addition, refeeding syndrome poses an extreme risk, Dr. Voss noted.

The Academy for Eating Disorders has created a guide to help doctors recognize and manage risks for patients with eating disorders, which may be useful for primary care providers while they are trying to get a patient into more intensive treatment, Dr. Voss suggested. The American Academy of Pediatrics recently published a clinical report on the identification and management of eating disorders in children and adolescents.

At Johns Hopkins Hospital Children’s Center in Baltimore, “we have seen a pretty remarkable increase in the number of eating disorders in the child and adolescent space since COVID,” said Jennifer Leah Goetz, MD, a psychiatrist and medical director of the child and adolescent inpatient unit. “We have seen increasing numbers of kids presenting for acute medical stabilization and refeeding and for specific treatment for the eating disorder.”

It could be that, for people with a genetic predisposition to eating disorders, a confluence of factors related to the pandemic unmasked it. For example, children may have spent more time looking at themselves on virtual meeting platforms, which could stir lingering body image and appearance-related concerns in those who are vulnerable. And some teens who were not able to participate in athletics as usual started to watch what they eat more closely, Dr. Goetz said.
 

A treatment bottleneck

Patients with eating disorders “can be quite ill from a psychiatric and general medical perspective,” Dr. Goetz said. “Most psychiatrists are not particularly comfortable with the medical complications, and most internists or pediatricians are not particularly comfortable with the psychiatric complications. You end up with a patient population that can only see a really highly specialized group of individuals for care. And it is a problem. It was a problem before the pandemic, and it has been really exacerbated by what we have been going through with COVID.”

Natalie Muth, MD, MPH, RDN, a pediatrician at Children’s Primary Care Medical Group La Costa in Carlsbad, Calif., has also noticed the increase in eating disorders since COVID.

In-patient colleagues “have longer wait lists and more severe cases than they have ever seen previously,” said Dr. Muth, who chairs the American Academy of Pediatrics Section on Obesity and is an adjunct assistant professor at the University of California, Los Angeles. “In primary care, we are all having to better educate and prepare ourselves for identifying and managing patients with eating disorders.”

That could mean connecting with mental health professionals, registered dietitians, and higher levels of care. But that may be a challenge. “Accessing these resources has been more difficult due to the increasing incidence of eating disorders recently,” Dr. Muth said.

Dr. Voss acknowledged that childhood obesity is another concern for pediatricians. “However, there are appropriate and healthy and safe ways to address that,” she said. A patient with overweight or obesity who loses weight may not be doing so in a healthy way.

Clinicians should wonder if a patient’s weight is decreasing too fast. And they should ask patients questions that could help identify a problem, such as: What are they doing to cause the weight loss? Why do they want to lose the weight?

Dr. Voss added that eating disorders “do not discriminate.” While there may be a perception that all patients with eating disorders are White, upper middle–class females who are thin, “that is not the case,” Dr. Voss said. They “come in all genders, all races, all weight classes, and all ages,” she said, “and we see that variety.”

In general, there may be a need to shift how weight is discussed in clinics and society more broadly, Dr. Goetz said. Weight is an incredibly personal thing, and everyone’s genetics, metabolism, and life circumstances vary. At the same time, body mass index is not necessarily the best measure of a person’s health.

Asking a child, teen, or even an adult to go on a diet is not a benign intervention, Dr. Goetz noted. In addition, dieting is unlikely to help in the long term.

Emerging from lockdown, pressure to lose “COVID pounds” is a dangerous message for people with eating disorders, Dr. Goetz said. It also could be a dangerous message for people without eating disorders. “There are so many more interesting things about each one of us than our weight,” she added.

The study authors, Dr. Voss, Dr. Goetz, and Dr. Muth had no relevant disclosures.

jremaly@mdedge.com

Medical admissions for adolescents with restrictive eating disorders more than doubled at one hospital during the first 12 months of the COVID-19 pandemic, relative to the average number of admissions in prior years, a new study shows.

Doctors are seeing similar increases across the United States and in other countries.

Providers and health care systems “may need to rapidly adapt in response to increasing demands for care during the COVID-19 pandemic,” the researchers said in their study, which was published online in Pediatrics.

To assess whether admission patterns among adolescents with restrictive eating disorders changed during the pandemic, Alana K. Otto, MD, MPH, with the division of adolescent medicine at the University of Michigan, Ann Arbor, and colleagues reviewed the charts of patients admitted to C.S. Mott Children’s Hospital, also in Ann Arbor.

Their analysis included 297 admissions among 248 patients aged 10-23 years between March 1, 2017, and March 31, 2021. Patients had an average age of about 15 years. Approximately 90% were female, and most had a diagnosis of anorexia nervosa or atypical anorexia nervosa.

Indications for medical admission included physiological instability (for example, heart rate less than 50 beats per minute while awake or blood pressure less than 90/40 mm Hg), electrolyte derangements, and acute medical complications of malnutrition such as syncope. Other possible indications included uncontrolled purging, body mass index less than 75% of the median for age and sex, acute food refusal, and failure of outpatient treatment.

Eating disorder–related admissions per month were stable prior to the pandemic. Admissions then decreased in April 2020, but subsequently increased significantly throughout the study period. In all, there were 125 admissions between April 1, 2020, and March 31, 2021. During the previous 3 years, the average number of admissions per year was 56.

Patients’ insurance status was one factor that differed before and during the pandemic. Prepandemic, about 20% of admissions were for adolescents with public insurance. During the pandemic, however, the proportion with public insurance was approximately 9%, the researchers noted. Other characteristics were generally similar.

The study was retrospective and relatively small and only looked at patients with restrictive eating disorders who were severely ill and admitted for medical stabilization. It does not reflect adolescents with eating disorders in different settings, the authors noted.

Primary care pediatricians should be familiar with indications for medical admission, such as severe bradycardia, as outlined by the Society for Adolescent Health and Medicine, they said.
 

Consistent trends

Unfortunately, the trend seems consistent across the nation, said Michaela M. Voss, MD, director of the the Eating Disorders Center at Children’s Mercy in Kansas City, Mo. “Our outpatient setting went from availability to get in immediately to a 6-month wait list.”

As in Michigan, Dr. Voss noted a drop in admissions as lockdowns started, followed by a spike in treatment demand that has not let up.

Dr. Voss described two of the more common presentations. In one, parents might note that their child had been getting into healthy eating and exercise before the pandemic and seemed fine. “But then COVID came, the lockdown happened, and they became overly obsessed with those things,” Dr. Voss said.

In the other presentation, kids with anxiety, depression, or OCD who lost access to their usual coping strategies and outlets developed eating disorders during the pandemic. “They focused on one of the few things they could during the lockdown, which was their own body, and then their anxiety, depression, [obsessive-compulsive disorder], and other mental health comorbidities presented as an eating disorder,” Dr. Voss said.

The increasing need for treatment over the course of the pandemic may reflect the time that it has taken for the disorders to develop, as well as the time that it takes parents to recognize the problem.

Not only are doctors seeing more cases, but patients are arriving sicker than usual, Dr. Voss said.

Major medical concerns for patients in starvation mode center on the heart, brain, and bones. In addition, refeeding syndrome poses an extreme risk, Dr. Voss noted.

The Academy for Eating Disorders has created a guide to help doctors recognize and manage risks for patients with eating disorders, which may be useful for primary care providers while they are trying to get a patient into more intensive treatment, Dr. Voss suggested. The American Academy of Pediatrics recently published a clinical report on the identification and management of eating disorders in children and adolescents.

At Johns Hopkins Hospital Children’s Center in Baltimore, “we have seen a pretty remarkable increase in the number of eating disorders in the child and adolescent space since COVID,” said Jennifer Leah Goetz, MD, a psychiatrist and medical director of the child and adolescent inpatient unit. “We have seen increasing numbers of kids presenting for acute medical stabilization and refeeding and for specific treatment for the eating disorder.”

It could be that, for people with a genetic predisposition to eating disorders, a confluence of factors related to the pandemic unmasked it. For example, children may have spent more time looking at themselves on virtual meeting platforms, which could stir lingering body image and appearance-related concerns in those who are vulnerable. And some teens who were not able to participate in athletics as usual started to watch what they eat more closely, Dr. Goetz said.
 

A treatment bottleneck

Patients with eating disorders “can be quite ill from a psychiatric and general medical perspective,” Dr. Goetz said. “Most psychiatrists are not particularly comfortable with the medical complications, and most internists or pediatricians are not particularly comfortable with the psychiatric complications. You end up with a patient population that can only see a really highly specialized group of individuals for care. And it is a problem. It was a problem before the pandemic, and it has been really exacerbated by what we have been going through with COVID.”

Natalie Muth, MD, MPH, RDN, a pediatrician at Children’s Primary Care Medical Group La Costa in Carlsbad, Calif., has also noticed the increase in eating disorders since COVID.

In-patient colleagues “have longer wait lists and more severe cases than they have ever seen previously,” said Dr. Muth, who chairs the American Academy of Pediatrics Section on Obesity and is an adjunct assistant professor at the University of California, Los Angeles. “In primary care, we are all having to better educate and prepare ourselves for identifying and managing patients with eating disorders.”

That could mean connecting with mental health professionals, registered dietitians, and higher levels of care. But that may be a challenge. “Accessing these resources has been more difficult due to the increasing incidence of eating disorders recently,” Dr. Muth said.

Dr. Voss acknowledged that childhood obesity is another concern for pediatricians. “However, there are appropriate and healthy and safe ways to address that,” she said. A patient with overweight or obesity who loses weight may not be doing so in a healthy way.

Clinicians should wonder if a patient’s weight is decreasing too fast. And they should ask patients questions that could help identify a problem, such as: What are they doing to cause the weight loss? Why do they want to lose the weight?

Dr. Voss added that eating disorders “do not discriminate.” While there may be a perception that all patients with eating disorders are White, upper middle–class females who are thin, “that is not the case,” Dr. Voss said. They “come in all genders, all races, all weight classes, and all ages,” she said, “and we see that variety.”

In general, there may be a need to shift how weight is discussed in clinics and society more broadly, Dr. Goetz said. Weight is an incredibly personal thing, and everyone’s genetics, metabolism, and life circumstances vary. At the same time, body mass index is not necessarily the best measure of a person’s health.

Asking a child, teen, or even an adult to go on a diet is not a benign intervention, Dr. Goetz noted. In addition, dieting is unlikely to help in the long term.

Emerging from lockdown, pressure to lose “COVID pounds” is a dangerous message for people with eating disorders, Dr. Goetz said. It also could be a dangerous message for people without eating disorders. “There are so many more interesting things about each one of us than our weight,” she added.

The study authors, Dr. Voss, Dr. Goetz, and Dr. Muth had no relevant disclosures.

jremaly@mdedge.com

Supplementing breastfed infants with bifidobacteria promotes development of a well-regulated immune system, theoretically reducing risk of immune-mediated conditions like allergies and asthma, according to investigators.

These findings support the importance of early gut colonization with beneficial microbes, an event that may affect the immune system throughout life, reported lead author Bethany M. Henrick, PhD, director of immunology and diagnostics at Evolve Biosystems, Davis, Calif., and adjunct assistant professor at the University of Nebraska, Lincoln, and colleagues.

“Dysbiosis of the infant gut microbiome is common in modern societies and a likely contributing factor to the increased incidences of immune-mediated disorders,” the investigators wrote in Cell. “Therefore, there is great interest in identifying microbial factors that can support healthier immune system imprinting and hopefully prevent cases of allergy, autoimmunity, and possibly other conditions involving the immune system.”

Prevailing theory suggests that the rising incidence of neonatal intestinal dysbiosis – which is typical in developed countries – may be caused by a variety of factors, including cesarean sections; modern hygiene practices; antibiotics, antiseptics, and other medications; diets high in fat and sugar; and infant formula.

According to Dr. Henrick and colleagues, a healthy gut microbiome plays the greatest role in immunological development during the first 3 months post partum; specifically, a lack of bifidobacteria during this time has been linked with increased risks of autoimmunity and enteric inflammation, although underlying immune mechanisms remain unclear.

Bifidobacteria also exemplify the symbiotic relationship between mothers, babies, and beneficial microbes. The investigators pointed out that breast milk contains human milk oligosaccharides (HMOs), which humans cannot digest, but are an excellent source of energy for bifidobacteria and other beneficial microbes, giving them a “selective nutritional advantage.”

Bifidobacteria should therefore be common residents within the infant gut, but this is often not now the case, leading Dr. Henrick and colleagues to zero in on the microbe, in hopes of determining the exactly how beneficial bacteria shape immune development.

It is only recently that the necessary knowledge and techniques to perform studies like this one have become available, the investigators wrote, noting a better understanding of cell-regulatory relationships, advances in immune profiling at the systems level, and new technology that allows for profiling small-volume samples from infants.

The present study involved a series of observational experiments and a small interventional trial.

First, the investigators conducted a wide array of blood- and fecal-based longitudinal analyses from 208 infants in Sweden to characterize immune cell expansion and microbiome colonization of the gut, with a focus on bifidobacteria.

Their results showed that infants lacking bifidobacteria, and HMO-utilization genes (which are expressed by bifidobacteria and other beneficial microbes), had higher levels of systemic inflammation, including increased T helper 2 (Th2) and Th17 responses.

“Infants not colonized by Bifidobacteriaceae or in cases where these microbes fail to expand during the first months of life there is evidence of systemic and intestinal inflammation, increased frequencies of activated immune cells, and reduced levels of regulatory cells indicative of systemic immune dysregulation,” the investigators wrote.

The interventional part of the study involved 60 breastfed infants in California. Twenty-nine of the newborns were given 1.8 x 10¹⁰ colony-forming units (CFUs) of B. longum subsp. infantis EVC001 daily from postnatal day 7 to day 28, while the remaining 31 infants were given no supplementation.

Fecal samples were collected on day 6 and day 60. At day 60, supplemented infants had high levels of HMO-utilization genes, plus significantly greater alpha diversity (P = .0001; Wilcoxon), compared with controls. Infants receiving EVC001 also had less inflammatory fecal cytokines, suggesting that microbes expressing HMO-utilization genes cause a shift away from proinflammatory Th2 and Th17 responses, and toward Th1.

“It is not the simple presence of bifidobacteria that is responsible for the immune effects but the metabolic partnership between the bacteria and HMOs,” the investigators noted.

According to principal investigator Petter Brodin, MD, PhD, professor of pediatric immunology at Karolinska Institutet, Solna, Sweden, the findings deserve further investigation.

“Our data indicate that substitution with beneficial microbes efficiently metabolizing HMOs could open a way to prevent cases of immune-mediated diseases, but larger, randomized trials aimed at this will be required to determine this potential,” Dr. Brodin said in an interview.

Carolynn Dude, MD, PhD, assistant professor in the division of maternal-fetal medicine at Emory University, Atlanta, agreed that more work is needed.

“While this study provides some insight into the mechanisms that may set up a newborn for poor health outcomes later in life, the data is still very limited, and more long-term follow-up on these infants is needed before recommending any sort of bacterial supplementation to a newborn,” Dr. Dude said in an interview.

Dr. Brodin and colleagues are planning an array of related studies, including larger clinical trials; further investigations into mechanisms of action; comparisons between the present cohort and infants in Kenya, where immune-mediated diseases are rare; and evaluations of vaccine responses and infectious disease susceptibility.

The study was supported by the European Research Council, the Swedish Research Council, the Marianne & Marcus Wallenberg Foundation, and others. The investigators disclosed relationships with Cytodelics, Scailyte, Kancera, and others. Dr. Dude reported no relevant conflicts of interest.

Supplementing breastfed infants with bifidobacteria promotes development of a well-regulated immune system, theoretically reducing risk of immune-mediated conditions like allergies and asthma, according to investigators.

These findings support the importance of early gut colonization with beneficial microbes, an event that may affect the immune system throughout life, reported lead author Bethany M. Henrick, PhD, director of immunology and diagnostics at Evolve Biosystems, Davis, Calif., and adjunct assistant professor at the University of Nebraska, Lincoln, and colleagues.

“Dysbiosis of the infant gut microbiome is common in modern societies and a likely contributing factor to the increased incidences of immune-mediated disorders,” the investigators wrote in Cell. “Therefore, there is great interest in identifying microbial factors that can support healthier immune system imprinting and hopefully prevent cases of allergy, autoimmunity, and possibly other conditions involving the immune system.”

Prevailing theory suggests that the rising incidence of neonatal intestinal dysbiosis – which is typical in developed countries – may be caused by a variety of factors, including cesarean sections; modern hygiene practices; antibiotics, antiseptics, and other medications; diets high in fat and sugar; and infant formula.

According to Dr. Henrick and colleagues, a healthy gut microbiome plays the greatest role in immunological development during the first 3 months post partum; specifically, a lack of bifidobacteria during this time has been linked with increased risks of autoimmunity and enteric inflammation, although underlying immune mechanisms remain unclear.

Bifidobacteria also exemplify the symbiotic relationship between mothers, babies, and beneficial microbes. The investigators pointed out that breast milk contains human milk oligosaccharides (HMOs), which humans cannot digest, but are an excellent source of energy for bifidobacteria and other beneficial microbes, giving them a “selective nutritional advantage.”

Bifidobacteria should therefore be common residents within the infant gut, but this is often not now the case, leading Dr. Henrick and colleagues to zero in on the microbe, in hopes of determining the exactly how beneficial bacteria shape immune development.

It is only recently that the necessary knowledge and techniques to perform studies like this one have become available, the investigators wrote, noting a better understanding of cell-regulatory relationships, advances in immune profiling at the systems level, and new technology that allows for profiling small-volume samples from infants.

The present study involved a series of observational experiments and a small interventional trial.

First, the investigators conducted a wide array of blood- and fecal-based longitudinal analyses from 208 infants in Sweden to characterize immune cell expansion and microbiome colonization of the gut, with a focus on bifidobacteria.

Their results showed that infants lacking bifidobacteria, and HMO-utilization genes (which are expressed by bifidobacteria and other beneficial microbes), had higher levels of systemic inflammation, including increased T helper 2 (Th2) and Th17 responses.

“Infants not colonized by Bifidobacteriaceae or in cases where these microbes fail to expand during the first months of life there is evidence of systemic and intestinal inflammation, increased frequencies of activated immune cells, and reduced levels of regulatory cells indicative of systemic immune dysregulation,” the investigators wrote.

The interventional part of the study involved 60 breastfed infants in California. Twenty-nine of the newborns were given 1.8 x 10¹⁰ colony-forming units (CFUs) of B. longum subsp. infantis EVC001 daily from postnatal day 7 to day 28, while the remaining 31 infants were given no supplementation.

Fecal samples were collected on day 6 and day 60. At day 60, supplemented infants had high levels of HMO-utilization genes, plus significantly greater alpha diversity (P = .0001; Wilcoxon), compared with controls. Infants receiving EVC001 also had less inflammatory fecal cytokines, suggesting that microbes expressing HMO-utilization genes cause a shift away from proinflammatory Th2 and Th17 responses, and toward Th1.

“It is not the simple presence of bifidobacteria that is responsible for the immune effects but the metabolic partnership between the bacteria and HMOs,” the investigators noted.

According to principal investigator Petter Brodin, MD, PhD, professor of pediatric immunology at Karolinska Institutet, Solna, Sweden, the findings deserve further investigation.

“Our data indicate that substitution with beneficial microbes efficiently metabolizing HMOs could open a way to prevent cases of immune-mediated diseases, but larger, randomized trials aimed at this will be required to determine this potential,” Dr. Brodin said in an interview.

Carolynn Dude, MD, PhD, assistant professor in the division of maternal-fetal medicine at Emory University, Atlanta, agreed that more work is needed.

“While this study provides some insight into the mechanisms that may set up a newborn for poor health outcomes later in life, the data is still very limited, and more long-term follow-up on these infants is needed before recommending any sort of bacterial supplementation to a newborn,” Dr. Dude said in an interview.

Dr. Brodin and colleagues are planning an array of related studies, including larger clinical trials; further investigations into mechanisms of action; comparisons between the present cohort and infants in Kenya, where immune-mediated diseases are rare; and evaluations of vaccine responses and infectious disease susceptibility.

The study was supported by the European Research Council, the Swedish Research Council, the Marianne & Marcus Wallenberg Foundation, and others. The investigators disclosed relationships with Cytodelics, Scailyte, Kancera, and others. Dr. Dude reported no relevant conflicts of interest.

Supplementing breastfed infants with bifidobacteria promotes development of a well-regulated immune system, theoretically reducing risk of immune-mediated conditions like allergies and asthma, according to investigators.

These findings support the importance of early gut colonization with beneficial microbes, an event that may affect the immune system throughout life, reported lead author Bethany M. Henrick, PhD, director of immunology and diagnostics at Evolve Biosystems, Davis, Calif., and adjunct assistant professor at the University of Nebraska, Lincoln, and colleagues.

“Dysbiosis of the infant gut microbiome is common in modern societies and a likely contributing factor to the increased incidences of immune-mediated disorders,” the investigators wrote in Cell. “Therefore, there is great interest in identifying microbial factors that can support healthier immune system imprinting and hopefully prevent cases of allergy, autoimmunity, and possibly other conditions involving the immune system.”

Prevailing theory suggests that the rising incidence of neonatal intestinal dysbiosis – which is typical in developed countries – may be caused by a variety of factors, including cesarean sections; modern hygiene practices; antibiotics, antiseptics, and other medications; diets high in fat and sugar; and infant formula.

According to Dr. Henrick and colleagues, a healthy gut microbiome plays the greatest role in immunological development during the first 3 months post partum; specifically, a lack of bifidobacteria during this time has been linked with increased risks of autoimmunity and enteric inflammation, although underlying immune mechanisms remain unclear.

Bifidobacteria also exemplify the symbiotic relationship between mothers, babies, and beneficial microbes. The investigators pointed out that breast milk contains human milk oligosaccharides (HMOs), which humans cannot digest, but are an excellent source of energy for bifidobacteria and other beneficial microbes, giving them a “selective nutritional advantage.”

Bifidobacteria should therefore be common residents within the infant gut, but this is often not now the case, leading Dr. Henrick and colleagues to zero in on the microbe, in hopes of determining the exactly how beneficial bacteria shape immune development.

It is only recently that the necessary knowledge and techniques to perform studies like this one have become available, the investigators wrote, noting a better understanding of cell-regulatory relationships, advances in immune profiling at the systems level, and new technology that allows for profiling small-volume samples from infants.

The present study involved a series of observational experiments and a small interventional trial.

First, the investigators conducted a wide array of blood- and fecal-based longitudinal analyses from 208 infants in Sweden to characterize immune cell expansion and microbiome colonization of the gut, with a focus on bifidobacteria.

Their results showed that infants lacking bifidobacteria, and HMO-utilization genes (which are expressed by bifidobacteria and other beneficial microbes), had higher levels of systemic inflammation, including increased T helper 2 (Th2) and Th17 responses.

“Infants not colonized by Bifidobacteriaceae or in cases where these microbes fail to expand during the first months of life there is evidence of systemic and intestinal inflammation, increased frequencies of activated immune cells, and reduced levels of regulatory cells indicative of systemic immune dysregulation,” the investigators wrote.

The interventional part of the study involved 60 breastfed infants in California. Twenty-nine of the newborns were given 1.8 x 10¹⁰ colony-forming units (CFUs) of B. longum subsp. infantis EVC001 daily from postnatal day 7 to day 28, while the remaining 31 infants were given no supplementation.

Fecal samples were collected on day 6 and day 60. At day 60, supplemented infants had high levels of HMO-utilization genes, plus significantly greater alpha diversity (P = .0001; Wilcoxon), compared with controls. Infants receiving EVC001 also had less inflammatory fecal cytokines, suggesting that microbes expressing HMO-utilization genes cause a shift away from proinflammatory Th2 and Th17 responses, and toward Th1.

“It is not the simple presence of bifidobacteria that is responsible for the immune effects but the metabolic partnership between the bacteria and HMOs,” the investigators noted.

According to principal investigator Petter Brodin, MD, PhD, professor of pediatric immunology at Karolinska Institutet, Solna, Sweden, the findings deserve further investigation.

“Our data indicate that substitution with beneficial microbes efficiently metabolizing HMOs could open a way to prevent cases of immune-mediated diseases, but larger, randomized trials aimed at this will be required to determine this potential,” Dr. Brodin said in an interview.

Carolynn Dude, MD, PhD, assistant professor in the division of maternal-fetal medicine at Emory University, Atlanta, agreed that more work is needed.

“While this study provides some insight into the mechanisms that may set up a newborn for poor health outcomes later in life, the data is still very limited, and more long-term follow-up on these infants is needed before recommending any sort of bacterial supplementation to a newborn,” Dr. Dude said in an interview.

Dr. Brodin and colleagues are planning an array of related studies, including larger clinical trials; further investigations into mechanisms of action; comparisons between the present cohort and infants in Kenya, where immune-mediated diseases are rare; and evaluations of vaccine responses and infectious disease susceptibility.

The study was supported by the European Research Council, the Swedish Research Council, the Marianne & Marcus Wallenberg Foundation, and others. The investigators disclosed relationships with Cytodelics, Scailyte, Kancera, and others. Dr. Dude reported no relevant conflicts of interest.

Bovine meat and milk factors (BMMF), the recently discovered pathogenic agents found in milk products and beef, could play a role in the development of colorectal cancer, say German scientists.

The team was headed by Harald zur Hausen, MD, PhD, division of episomal-persistent DNA in cancer and chronic diseases, German Cancer Research Center, Heidelberg, who received the Nobel Prize in Physiology or Medicine in 2008 for his discovery of the role of human papillomaviruses in the development of cervical cancer.

The team has been researching the link between BMMF and colorectal cancer for some years, and the latest study was published in the Proceedings of the National Academy of Sciences.

“The results support our hypothesis that the consumption of milk and beef is causally linked to the development of colon cancer,” Dr. Hausen said in a related press statement.
 

Pathogenic agents, found in vicinity of tumors

BMMF are infectious agents that occur as circular single strands of DNA and have a notable similarity to the sequences of some bacterial plasmids.

A few years ago, Dr. Hausen and colleagues found these pathogenic agents in colon cancer patients, in the immediate vicinity of tumors.

They therefore put forward the hypothesis that BMMF could trigger chronic local inflammation, which in turn could cause genetic mutations via oxidative stress and lead to the development of cancer over the long term.

The German researchers were also able to show in in vitro models that BMMF multiply in human cells where the H1MSB.1 Rep protein, which is required for their replication, is synthesized.

In their latest study, the scientists analyzed tissue samples from colorectal cancer patients and from individuals without the disease.

The team found that BMMF could trigger chronic inflammation in the intestinal tissue of cancer patients, as demonstrated via the presence of proinflammatory macrophages.

The researchers also used anti-Rep antibodies to show that the Rep protein was present around and inside the macrophages. In cancer patients, 7.3% of all the intestinal cells in the tumor environment were positive for Rep versus just 1.7% of those in the control group.

In addition, the researchers reported increased levels of reactive oxygen species close to Rep-positive cells.

“These oxygen radicals promote the development of genetic changes,” Dr. Hausen said.

The inflammation was particularly localized to the immediate vicinity of the intestinal crypts, where the intestinal stem cells, which are responsible for the constant regeneration of the intestinal mucosa, are found.

“We therefore think of the BMMF as indirect carcinogens, some of which will probably have an impact on dividing cells in the intestinal mucosa for decades,” Dr. Hausen explained.

He assumes that infection with BMMF typically occurs early in life. This “opens up the possibility of early intervention,” he suggested.

The early detection of BMMF could allow the identification of individuals particularly at risk, and for these patients to be offered timely colon cancer screening.

The researchers stressed, however, that further study will be required to confirm the results.

They nevertheless believed that BMMF could help explain the link between the consumption of red meat and dairy products and other cancers and diseases, in particular breast, prostate, and lung cancers.

Finally, the pathogenic agents could partially explain the preventive effect of anti-inflammatory dugs such as aspirin and ibuprofen on the incidence of colon cancer and other cancers via the reduction of chronic inflammation.

This work was supported by an unrestricted grant from ORYX Alpha. One coauthor was supported by the EOS Foundation, the SFBTR-179 and 209, and a European Research Council consolidator grant. The other coauthors disclosed no relevant financial relationships.

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

Bovine meat and milk factors (BMMF), the recently discovered pathogenic agents found in milk products and beef, could play a role in the development of colorectal cancer, say German scientists.

The team was headed by Harald zur Hausen, MD, PhD, division of episomal-persistent DNA in cancer and chronic diseases, German Cancer Research Center, Heidelberg, who received the Nobel Prize in Physiology or Medicine in 2008 for his discovery of the role of human papillomaviruses in the development of cervical cancer.

The team has been researching the link between BMMF and colorectal cancer for some years, and the latest study was published in the Proceedings of the National Academy of Sciences.

“The results support our hypothesis that the consumption of milk and beef is causally linked to the development of colon cancer,” Dr. Hausen said in a related press statement.
 

Pathogenic agents, found in vicinity of tumors

BMMF are infectious agents that occur as circular single strands of DNA and have a notable similarity to the sequences of some bacterial plasmids.

A few years ago, Dr. Hausen and colleagues found these pathogenic agents in colon cancer patients, in the immediate vicinity of tumors.

They therefore put forward the hypothesis that BMMF could trigger chronic local inflammation, which in turn could cause genetic mutations via oxidative stress and lead to the development of cancer over the long term.

The German researchers were also able to show in in vitro models that BMMF multiply in human cells where the H1MSB.1 Rep protein, which is required for their replication, is synthesized.

In their latest study, the scientists analyzed tissue samples from colorectal cancer patients and from individuals without the disease.

The team found that BMMF could trigger chronic inflammation in the intestinal tissue of cancer patients, as demonstrated via the presence of proinflammatory macrophages.

The researchers also used anti-Rep antibodies to show that the Rep protein was present around and inside the macrophages. In cancer patients, 7.3% of all the intestinal cells in the tumor environment were positive for Rep versus just 1.7% of those in the control group.

In addition, the researchers reported increased levels of reactive oxygen species close to Rep-positive cells.

“These oxygen radicals promote the development of genetic changes,” Dr. Hausen said.

The inflammation was particularly localized to the immediate vicinity of the intestinal crypts, where the intestinal stem cells, which are responsible for the constant regeneration of the intestinal mucosa, are found.

“We therefore think of the BMMF as indirect carcinogens, some of which will probably have an impact on dividing cells in the intestinal mucosa for decades,” Dr. Hausen explained.

He assumes that infection with BMMF typically occurs early in life. This “opens up the possibility of early intervention,” he suggested.

The early detection of BMMF could allow the identification of individuals particularly at risk, and for these patients to be offered timely colon cancer screening.

The researchers stressed, however, that further study will be required to confirm the results.

They nevertheless believed that BMMF could help explain the link between the consumption of red meat and dairy products and other cancers and diseases, in particular breast, prostate, and lung cancers.

Finally, the pathogenic agents could partially explain the preventive effect of anti-inflammatory dugs such as aspirin and ibuprofen on the incidence of colon cancer and other cancers via the reduction of chronic inflammation.

This work was supported by an unrestricted grant from ORYX Alpha. One coauthor was supported by the EOS Foundation, the SFBTR-179 and 209, and a European Research Council consolidator grant. The other coauthors disclosed no relevant financial relationships.

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

Bovine meat and milk factors (BMMF), the recently discovered pathogenic agents found in milk products and beef, could play a role in the development of colorectal cancer, say German scientists.

The team was headed by Harald zur Hausen, MD, PhD, division of episomal-persistent DNA in cancer and chronic diseases, German Cancer Research Center, Heidelberg, who received the Nobel Prize in Physiology or Medicine in 2008 for his discovery of the role of human papillomaviruses in the development of cervical cancer.

The team has been researching the link between BMMF and colorectal cancer for some years, and the latest study was published in the Proceedings of the National Academy of Sciences.

“The results support our hypothesis that the consumption of milk and beef is causally linked to the development of colon cancer,” Dr. Hausen said in a related press statement.
 

Pathogenic agents, found in vicinity of tumors

BMMF are infectious agents that occur as circular single strands of DNA and have a notable similarity to the sequences of some bacterial plasmids.

A few years ago, Dr. Hausen and colleagues found these pathogenic agents in colon cancer patients, in the immediate vicinity of tumors.

They therefore put forward the hypothesis that BMMF could trigger chronic local inflammation, which in turn could cause genetic mutations via oxidative stress and lead to the development of cancer over the long term.

The German researchers were also able to show in in vitro models that BMMF multiply in human cells where the H1MSB.1 Rep protein, which is required for their replication, is synthesized.

In their latest study, the scientists analyzed tissue samples from colorectal cancer patients and from individuals without the disease.

The team found that BMMF could trigger chronic inflammation in the intestinal tissue of cancer patients, as demonstrated via the presence of proinflammatory macrophages.

The researchers also used anti-Rep antibodies to show that the Rep protein was present around and inside the macrophages. In cancer patients, 7.3% of all the intestinal cells in the tumor environment were positive for Rep versus just 1.7% of those in the control group.

In addition, the researchers reported increased levels of reactive oxygen species close to Rep-positive cells.

“These oxygen radicals promote the development of genetic changes,” Dr. Hausen said.

The inflammation was particularly localized to the immediate vicinity of the intestinal crypts, where the intestinal stem cells, which are responsible for the constant regeneration of the intestinal mucosa, are found.

“We therefore think of the BMMF as indirect carcinogens, some of which will probably have an impact on dividing cells in the intestinal mucosa for decades,” Dr. Hausen explained.

He assumes that infection with BMMF typically occurs early in life. This “opens up the possibility of early intervention,” he suggested.

The early detection of BMMF could allow the identification of individuals particularly at risk, and for these patients to be offered timely colon cancer screening.

The researchers stressed, however, that further study will be required to confirm the results.

They nevertheless believed that BMMF could help explain the link between the consumption of red meat and dairy products and other cancers and diseases, in particular breast, prostate, and lung cancers.

Finally, the pathogenic agents could partially explain the preventive effect of anti-inflammatory dugs such as aspirin and ibuprofen on the incidence of colon cancer and other cancers via the reduction of chronic inflammation.

This work was supported by an unrestricted grant from ORYX Alpha. One coauthor was supported by the EOS Foundation, the SFBTR-179 and 209, and a European Research Council consolidator grant. The other coauthors disclosed no relevant financial relationships.

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

When Lesley Solomon’s son was 10 years old, he was standing in an unlucky spot on the playground when a schoolmate kicked over a cup of hot chocolate, sending droplets flying into the air. For the young boy with a severe milk allergy, the hot liquid splattering was less of a hazard for him than the dairy stirred into the drink.

copyright/Jupiterimages/Getty Images

Ms. Solomon’s son quickly washed the fluids off his clothes and skin, took some Benadryl, and called his parents. But on the car ride home, his throat began to close and his pulse raced. It was one of about a dozen times he has needed an epinephrine injection, which increases blood flow, reduces swelling, and reverses anaphylaxis.

“Until you see a child going through that anaphylaxis and not being able to breathe, or throwing up so much that they can’t breathe, you don’t understand” how serious food allergies can be, said Ms. Solomon, who is senior vice president and chief innovation officer of the Dana-Farber Cancer Institute in Boston and cofounder of the Food Allergy Science Initiative, an independent nonprofit that funds food allergy research.

The rate of children hospitalized for food-induced anaphylaxis rose by 25% from 2006 to 2012 – from 1.2 to 1.5 per 100,000 – according to a 2019 analysis of data from pediatric hospitals in the United States. And severe symptoms were more often linked to milk than to peanuts or tree nuts, the study showed.

Cow’s milk is the most common food allergy in children aged younger than 5 years, and accounts for about half of all food allergies in children younger than 1. Most children grow out of it, but when milk allergy persists into the teenage years and adulthood, it is more likely to cause severe reactions.
 

A dangerous allergy

“Cow’s milk allergy is the most distressing of the food allergies. Many people are unaware that it can cause anaphylaxis that is so severe,” said Carla Davis, MD, director of the food allergy program at the Texas Children’s Hospital in Houston. “People do not think about how much of this is in our food.”

And cow’s milk was shown to be the food allergy most likely to lead to death in school-aged children in the United Kingdom, according to an analysis of national data reported by this news organization.

Lack of awareness is what makes milk allergy so dangerous, said Paul Turner, BMBCh, PhD, a pediatric allergist and immunologist from Imperial College London, who was involved in the British analysis. “We need to get that information out to the public and businesses so they take the same level of care that they have with nuts, and when someone says they have milk allergy, they take it seriously.

In food allergy, the body treats certain proteins, such as the casein and whey in milk, as invaders, mounting an immune response. Antibodies known as IgE – which normally protect against bacteria, viruses, and parasites – trigger inflammation, the release of histamine, and can lead to symptoms, typically within minutes, ranging from rash and swelling to vomiting, difficulty swallowing, and difficulty breathing.

So, the very thing that makes milk a healthy choice for kids – its high protein content – can cause serious reactions in a small portion of children and adults. “You don’t need much milk to get a decent dose” of the allergen, Dr. Turner pointed out.

The mechanisms of milk allergy are complex, even compared with other food allergies. The IgE antibody can be detected with a skin-prick test or IgE blood test, but some people have positive results even though they are not allergic. To complicate things further, people can also have non–IgE-mediated milk allergy, which cannot be detected with testing and can lead to symptoms that emerge hours or even days after exposure.
 

More serious than lactose intolerance

Unfortunately, milk allergy is often confused with a milk-related digestive problem. Globally, about 70% of people lack the enzyme to break down the sugar in milk; the condition, known as lactose intolerance, can cause bloating, abdominal cramps, and diarrhea but is not life-threatening.

“Because lactose intolerance is so common, people don’t think of milk allergy as something that can be significant or severe,” said Ruchi Gupta, MD, MPH, director of the Center for Food Allergy and Asthma Research at the Northwestern University, Chicago.

In babies, colic, the regurgitation of milk-based formula, and rash are sometimes misinterpreted as a milk allergy, leading parents to buy expensive, specialized formula unnecessarily.

Frustrated by a lack of data about food allergies, Dr. Gupta and colleagues launched a nationally representative survey of 38,408 American parents in 2009, which was updated in 2015 and 2016.

On average, children with milk allergy had their first reaction before the age of 2, most commonly vomiting, diarrhea, hives, and eczema; this is a younger age of onset than for other food allergies. And children with milk allergy were twice as likely as children with other allergies to grow out of it.

Yet about one-third of milk-allergic children in the updated study were 11 years and older. And in a similar survey of adults who self-reported symptoms, milk allergy was as common as peanut allergy (1.9% vs 1.8%). “We don’t know why milk allergy is becoming more persistent,” Dr. Gupta said. And, she warned, only one in four children with a milk allergy had a current prescription for an epinephrine autoinjector, compared with about 70% of children with peanut allergy.

Food allergy can’t be caused by genetics alone, said Christine Olsen, MD, cofounder and CEO of the Food Allergy Science Initiative at the Broad Institute in Cambridge, Mass. “There may be a genetic predisposition, but there must be something environmental” that has influenced the development of food allergies.

One theory is that the body’s natural defense against noxious substances has been disrupted in the modern world by processed foods, chemical additives, and hygienic surroundings.

Dr. Olson’s own son vomited when he had his first small taste of hummus as a baby; he is severely allergic to sesame. The immediacy of his bodily reaction made Dr. Olsen think that the response involved neurons, not just a misguided immune system.

Researchers are currently looking for drug targets that could shut off the immune response as quickly as it starts. If you think of the fact that some kids outgrow their allergies and some adults get allergies, that suggests there’s some lever that you can turn on and off,” said Dr. Olsen, who is also a radiation oncologist.
 

Preventing allergy

The approach to food allergy prevention has already been transformed by the Learning Early About Peanut Allergy (LEAP) study conducted in the United Kingdom. LEAP investigators randomly assigned 640 infants to ingest regular amounts of peanut snacks or peanut butter or to avoid peanut products until they reached 5 years of age. The babies who had regular exposure to peanut from an early age were much less likely to develop a peanut allergy than those who avoided peanuts.

The National Institute of Allergy and Infectious Diseases revised its guidelines and now recommends that all babies be exposed to peanut-containing food at around 6 months of age; for high-risk babies, that can start as early as 4 months.

Allergy experts are planning to study that concept again with other foods, including cow’s milk. The 5-year iREACH study, launched by the Center for Food Allergy & Asthma Research at Northwestern and Lurie Children’s Hospital in Chicago, is currently enrolling 10,500 infants to test early exposure to peanuts, milk, egg, and cashew. A portion of the infants will have severe eczema, putting them at high risk for food allergies, and others will be low risk, said Dr. Gupta, who is the principal iREACH investigator.

“Hopefully in the next 5 years we will have data showing whether this prevention technique will work for other common food allergens, in addition to peanuts,” she said.

Introducing foods early “promotes tolerance rather than early sensitization,” explained Stephanie Leeds, MD, an allergist and immunologist at Yale University, New Haven, Conn. In the future, rather than just diagnosing and treating food allergies, allergists might work with pediatricians to help prevent them from ever happening.

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

When Lesley Solomon’s son was 10 years old, he was standing in an unlucky spot on the playground when a schoolmate kicked over a cup of hot chocolate, sending droplets flying into the air. For the young boy with a severe milk allergy, the hot liquid splattering was less of a hazard for him than the dairy stirred into the drink.

copyright/Jupiterimages/Getty Images

Ms. Solomon’s son quickly washed the fluids off his clothes and skin, took some Benadryl, and called his parents. But on the car ride home, his throat began to close and his pulse raced. It was one of about a dozen times he has needed an epinephrine injection, which increases blood flow, reduces swelling, and reverses anaphylaxis.

“Until you see a child going through that anaphylaxis and not being able to breathe, or throwing up so much that they can’t breathe, you don’t understand” how serious food allergies can be, said Ms. Solomon, who is senior vice president and chief innovation officer of the Dana-Farber Cancer Institute in Boston and cofounder of the Food Allergy Science Initiative, an independent nonprofit that funds food allergy research.

The rate of children hospitalized for food-induced anaphylaxis rose by 25% from 2006 to 2012 – from 1.2 to 1.5 per 100,000 – according to a 2019 analysis of data from pediatric hospitals in the United States. And severe symptoms were more often linked to milk than to peanuts or tree nuts, the study showed.

Cow’s milk is the most common food allergy in children aged younger than 5 years, and accounts for about half of all food allergies in children younger than 1. Most children grow out of it, but when milk allergy persists into the teenage years and adulthood, it is more likely to cause severe reactions.
 

A dangerous allergy

“Cow’s milk allergy is the most distressing of the food allergies. Many people are unaware that it can cause anaphylaxis that is so severe,” said Carla Davis, MD, director of the food allergy program at the Texas Children’s Hospital in Houston. “People do not think about how much of this is in our food.”

And cow’s milk was shown to be the food allergy most likely to lead to death in school-aged children in the United Kingdom, according to an analysis of national data reported by this news organization.

Lack of awareness is what makes milk allergy so dangerous, said Paul Turner, BMBCh, PhD, a pediatric allergist and immunologist from Imperial College London, who was involved in the British analysis. “We need to get that information out to the public and businesses so they take the same level of care that they have with nuts, and when someone says they have milk allergy, they take it seriously.

In food allergy, the body treats certain proteins, such as the casein and whey in milk, as invaders, mounting an immune response. Antibodies known as IgE – which normally protect against bacteria, viruses, and parasites – trigger inflammation, the release of histamine, and can lead to symptoms, typically within minutes, ranging from rash and swelling to vomiting, difficulty swallowing, and difficulty breathing.

So, the very thing that makes milk a healthy choice for kids – its high protein content – can cause serious reactions in a small portion of children and adults. “You don’t need much milk to get a decent dose” of the allergen, Dr. Turner pointed out.

The mechanisms of milk allergy are complex, even compared with other food allergies. The IgE antibody can be detected with a skin-prick test or IgE blood test, but some people have positive results even though they are not allergic. To complicate things further, people can also have non–IgE-mediated milk allergy, which cannot be detected with testing and can lead to symptoms that emerge hours or even days after exposure.
 

More serious than lactose intolerance

Unfortunately, milk allergy is often confused with a milk-related digestive problem. Globally, about 70% of people lack the enzyme to break down the sugar in milk; the condition, known as lactose intolerance, can cause bloating, abdominal cramps, and diarrhea but is not life-threatening.

“Because lactose intolerance is so common, people don’t think of milk allergy as something that can be significant or severe,” said Ruchi Gupta, MD, MPH, director of the Center for Food Allergy and Asthma Research at the Northwestern University, Chicago.

In babies, colic, the regurgitation of milk-based formula, and rash are sometimes misinterpreted as a milk allergy, leading parents to buy expensive, specialized formula unnecessarily.

Frustrated by a lack of data about food allergies, Dr. Gupta and colleagues launched a nationally representative survey of 38,408 American parents in 2009, which was updated in 2015 and 2016.

On average, children with milk allergy had their first reaction before the age of 2, most commonly vomiting, diarrhea, hives, and eczema; this is a younger age of onset than for other food allergies. And children with milk allergy were twice as likely as children with other allergies to grow out of it.

Yet about one-third of milk-allergic children in the updated study were 11 years and older. And in a similar survey of adults who self-reported symptoms, milk allergy was as common as peanut allergy (1.9% vs 1.8%). “We don’t know why milk allergy is becoming more persistent,” Dr. Gupta said. And, she warned, only one in four children with a milk allergy had a current prescription for an epinephrine autoinjector, compared with about 70% of children with peanut allergy.

Food allergy can’t be caused by genetics alone, said Christine Olsen, MD, cofounder and CEO of the Food Allergy Science Initiative at the Broad Institute in Cambridge, Mass. “There may be a genetic predisposition, but there must be something environmental” that has influenced the development of food allergies.

One theory is that the body’s natural defense against noxious substances has been disrupted in the modern world by processed foods, chemical additives, and hygienic surroundings.

Dr. Olson’s own son vomited when he had his first small taste of hummus as a baby; he is severely allergic to sesame. The immediacy of his bodily reaction made Dr. Olsen think that the response involved neurons, not just a misguided immune system.

Researchers are currently looking for drug targets that could shut off the immune response as quickly as it starts. If you think of the fact that some kids outgrow their allergies and some adults get allergies, that suggests there’s some lever that you can turn on and off,” said Dr. Olsen, who is also a radiation oncologist.
 

Preventing allergy

The approach to food allergy prevention has already been transformed by the Learning Early About Peanut Allergy (LEAP) study conducted in the United Kingdom. LEAP investigators randomly assigned 640 infants to ingest regular amounts of peanut snacks or peanut butter or to avoid peanut products until they reached 5 years of age. The babies who had regular exposure to peanut from an early age were much less likely to develop a peanut allergy than those who avoided peanuts.

The National Institute of Allergy and Infectious Diseases revised its guidelines and now recommends that all babies be exposed to peanut-containing food at around 6 months of age; for high-risk babies, that can start as early as 4 months.

Allergy experts are planning to study that concept again with other foods, including cow’s milk. The 5-year iREACH study, launched by the Center for Food Allergy & Asthma Research at Northwestern and Lurie Children’s Hospital in Chicago, is currently enrolling 10,500 infants to test early exposure to peanuts, milk, egg, and cashew. A portion of the infants will have severe eczema, putting them at high risk for food allergies, and others will be low risk, said Dr. Gupta, who is the principal iREACH investigator.

“Hopefully in the next 5 years we will have data showing whether this prevention technique will work for other common food allergens, in addition to peanuts,” she said.

Introducing foods early “promotes tolerance rather than early sensitization,” explained Stephanie Leeds, MD, an allergist and immunologist at Yale University, New Haven, Conn. In the future, rather than just diagnosing and treating food allergies, allergists might work with pediatricians to help prevent them from ever happening.

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

When Lesley Solomon’s son was 10 years old, he was standing in an unlucky spot on the playground when a schoolmate kicked over a cup of hot chocolate, sending droplets flying into the air. For the young boy with a severe milk allergy, the hot liquid splattering was less of a hazard for him than the dairy stirred into the drink.

copyright/Jupiterimages/Getty Images

Ms. Solomon’s son quickly washed the fluids off his clothes and skin, took some Benadryl, and called his parents. But on the car ride home, his throat began to close and his pulse raced. It was one of about a dozen times he has needed an epinephrine injection, which increases blood flow, reduces swelling, and reverses anaphylaxis.

“Until you see a child going through that anaphylaxis and not being able to breathe, or throwing up so much that they can’t breathe, you don’t understand” how serious food allergies can be, said Ms. Solomon, who is senior vice president and chief innovation officer of the Dana-Farber Cancer Institute in Boston and cofounder of the Food Allergy Science Initiative, an independent nonprofit that funds food allergy research.

The rate of children hospitalized for food-induced anaphylaxis rose by 25% from 2006 to 2012 – from 1.2 to 1.5 per 100,000 – according to a 2019 analysis of data from pediatric hospitals in the United States. And severe symptoms were more often linked to milk than to peanuts or tree nuts, the study showed.

Cow’s milk is the most common food allergy in children aged younger than 5 years, and accounts for about half of all food allergies in children younger than 1. Most children grow out of it, but when milk allergy persists into the teenage years and adulthood, it is more likely to cause severe reactions.
 

A dangerous allergy

“Cow’s milk allergy is the most distressing of the food allergies. Many people are unaware that it can cause anaphylaxis that is so severe,” said Carla Davis, MD, director of the food allergy program at the Texas Children’s Hospital in Houston. “People do not think about how much of this is in our food.”

And cow’s milk was shown to be the food allergy most likely to lead to death in school-aged children in the United Kingdom, according to an analysis of national data reported by this news organization.

Lack of awareness is what makes milk allergy so dangerous, said Paul Turner, BMBCh, PhD, a pediatric allergist and immunologist from Imperial College London, who was involved in the British analysis. “We need to get that information out to the public and businesses so they take the same level of care that they have with nuts, and when someone says they have milk allergy, they take it seriously.

In food allergy, the body treats certain proteins, such as the casein and whey in milk, as invaders, mounting an immune response. Antibodies known as IgE – which normally protect against bacteria, viruses, and parasites – trigger inflammation, the release of histamine, and can lead to symptoms, typically within minutes, ranging from rash and swelling to vomiting, difficulty swallowing, and difficulty breathing.

So, the very thing that makes milk a healthy choice for kids – its high protein content – can cause serious reactions in a small portion of children and adults. “You don’t need much milk to get a decent dose” of the allergen, Dr. Turner pointed out.

The mechanisms of milk allergy are complex, even compared with other food allergies. The IgE antibody can be detected with a skin-prick test or IgE blood test, but some people have positive results even though they are not allergic. To complicate things further, people can also have non–IgE-mediated milk allergy, which cannot be detected with testing and can lead to symptoms that emerge hours or even days after exposure.
 

More serious than lactose intolerance

Unfortunately, milk allergy is often confused with a milk-related digestive problem. Globally, about 70% of people lack the enzyme to break down the sugar in milk; the condition, known as lactose intolerance, can cause bloating, abdominal cramps, and diarrhea but is not life-threatening.

“Because lactose intolerance is so common, people don’t think of milk allergy as something that can be significant or severe,” said Ruchi Gupta, MD, MPH, director of the Center for Food Allergy and Asthma Research at the Northwestern University, Chicago.

In babies, colic, the regurgitation of milk-based formula, and rash are sometimes misinterpreted as a milk allergy, leading parents to buy expensive, specialized formula unnecessarily.

Frustrated by a lack of data about food allergies, Dr. Gupta and colleagues launched a nationally representative survey of 38,408 American parents in 2009, which was updated in 2015 and 2016.

On average, children with milk allergy had their first reaction before the age of 2, most commonly vomiting, diarrhea, hives, and eczema; this is a younger age of onset than for other food allergies. And children with milk allergy were twice as likely as children with other allergies to grow out of it.

Yet about one-third of milk-allergic children in the updated study were 11 years and older. And in a similar survey of adults who self-reported symptoms, milk allergy was as common as peanut allergy (1.9% vs 1.8%). “We don’t know why milk allergy is becoming more persistent,” Dr. Gupta said. And, she warned, only one in four children with a milk allergy had a current prescription for an epinephrine autoinjector, compared with about 70% of children with peanut allergy.

Food allergy can’t be caused by genetics alone, said Christine Olsen, MD, cofounder and CEO of the Food Allergy Science Initiative at the Broad Institute in Cambridge, Mass. “There may be a genetic predisposition, but there must be something environmental” that has influenced the development of food allergies.

One theory is that the body’s natural defense against noxious substances has been disrupted in the modern world by processed foods, chemical additives, and hygienic surroundings.

Dr. Olson’s own son vomited when he had his first small taste of hummus as a baby; he is severely allergic to sesame. The immediacy of his bodily reaction made Dr. Olsen think that the response involved neurons, not just a misguided immune system.

Researchers are currently looking for drug targets that could shut off the immune response as quickly as it starts. If you think of the fact that some kids outgrow their allergies and some adults get allergies, that suggests there’s some lever that you can turn on and off,” said Dr. Olsen, who is also a radiation oncologist.
 

Preventing allergy

The approach to food allergy prevention has already been transformed by the Learning Early About Peanut Allergy (LEAP) study conducted in the United Kingdom. LEAP investigators randomly assigned 640 infants to ingest regular amounts of peanut snacks or peanut butter or to avoid peanut products until they reached 5 years of age. The babies who had regular exposure to peanut from an early age were much less likely to develop a peanut allergy than those who avoided peanuts.

The National Institute of Allergy and Infectious Diseases revised its guidelines and now recommends that all babies be exposed to peanut-containing food at around 6 months of age; for high-risk babies, that can start as early as 4 months.

Allergy experts are planning to study that concept again with other foods, including cow’s milk. The 5-year iREACH study, launched by the Center for Food Allergy & Asthma Research at Northwestern and Lurie Children’s Hospital in Chicago, is currently enrolling 10,500 infants to test early exposure to peanuts, milk, egg, and cashew. A portion of the infants will have severe eczema, putting them at high risk for food allergies, and others will be low risk, said Dr. Gupta, who is the principal iREACH investigator.

“Hopefully in the next 5 years we will have data showing whether this prevention technique will work for other common food allergens, in addition to peanuts,” she said.

Introducing foods early “promotes tolerance rather than early sensitization,” explained Stephanie Leeds, MD, an allergist and immunologist at Yale University, New Haven, Conn. In the future, rather than just diagnosing and treating food allergies, allergists might work with pediatricians to help prevent them from ever happening.

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

Among women without celiac disease, dietary gluten intake was not associated with the risk of developing either Crohn’s disease or ulcerative colitis, investigators reported.

The findings spanned subgroups stratified by age, body mass index, smoking status, and whether individuals primarily consumed refined or whole grains, said Emily Walsh Lopes, MD, gastroenterology clinical and research fellow at Massachusetts General Hospital in Boston. She and associates reported the combined analysis of the prospective Nurses’ Health Study and Nurses’ Health Study II in an abstract released as part of the annual Digestive Disease Week.^®

“Avoidance of dietary gluten is common, and many patients attribute gastrointestinal symptoms to gluten intake,” Dr. Lopes said in an interview. “Though our findings warrant further study, the results suggest to patients and providers that eating gluten does not increase a person’s chance of getting diagnosed with inflammatory bowel disease.”

Prior studies have found that many individuals with inflammatory bowel disease avoid gluten and report subsequent improvements in gastrointestinal symptoms, even if they do not have celiac disease. However, it remains unclear whether dietary gluten is a risk factor for new-onset inflammatory bowel disease.

To address this question, Dr. Lopes and associates analyzed data collected from 165,327 women who took part in the Nurses’ Health Study (1986 to 2016) or the Nurses’ Health Study II (1991 through 2017). None of the women had a preexisting diagnosis of celiac disease or inflammatory bowel disease. Dietary gluten intake was estimated based on food frequency questionnaires completed by the women at baseline and every 4 years. The researchers also reviewed medical records to confirm self-reported cases of new-onset ulcerative colitis and Crohn’s disease.

Over 4.02 million person-years of follow-up, 277 women developed Crohn’s disease and 359 developed ulcerative colitis. Gluten intake was not associated with the risk of either type of inflammatory bowel disease, even after the researchers controlled for multiple demographic and clinical risk factors.

After submitting their abstract, Dr. Lopes and coinvestigators expanded the dataset to include a large cohort of men from the prospective Health Professionals Follow-up Study. The final pooled cohort included more than 208,000 women and men followed for more than 20 years. Through the end of follow-up, the researchers documented 337 cases of Crohn’s disease and 446 cases of ulcerative colitis. “Inclusion of the male cohort in the pooled analysis did not materially change our estimates,” Dr. Lopes told MDedge. “That is, no association was seen between gluten intake and risk of either Crohn’s disease or ulcerative colitis in the final cohort.”

She noted that the findings cannot be extrapolated to individuals who are already diagnosed with inflammatory bowel disease. “It is possible that different mechanisms exist to explain how gluten intake impacts those already diagnosed with IBD, and this topic warrants further study,” she said. Also, because the three cohort studies were observational, they are subject to bias. “While we tried to account for this in our analyses, residual bias may still exist.”

Dr. Lopes reported having no conflicts of interest.

SOURCE: Walsh Lopes E et al. DDW 2020, abstract 847.

Among women without celiac disease, dietary gluten intake was not associated with the risk of developing either Crohn’s disease or ulcerative colitis, investigators reported.

The findings spanned subgroups stratified by age, body mass index, smoking status, and whether individuals primarily consumed refined or whole grains, said Emily Walsh Lopes, MD, gastroenterology clinical and research fellow at Massachusetts General Hospital in Boston. She and associates reported the combined analysis of the prospective Nurses’ Health Study and Nurses’ Health Study II in an abstract released as part of the annual Digestive Disease Week.^®

“Avoidance of dietary gluten is common, and many patients attribute gastrointestinal symptoms to gluten intake,” Dr. Lopes said in an interview. “Though our findings warrant further study, the results suggest to patients and providers that eating gluten does not increase a person’s chance of getting diagnosed with inflammatory bowel disease.”

Prior studies have found that many individuals with inflammatory bowel disease avoid gluten and report subsequent improvements in gastrointestinal symptoms, even if they do not have celiac disease. However, it remains unclear whether dietary gluten is a risk factor for new-onset inflammatory bowel disease.

To address this question, Dr. Lopes and associates analyzed data collected from 165,327 women who took part in the Nurses’ Health Study (1986 to 2016) or the Nurses’ Health Study II (1991 through 2017). None of the women had a preexisting diagnosis of celiac disease or inflammatory bowel disease. Dietary gluten intake was estimated based on food frequency questionnaires completed by the women at baseline and every 4 years. The researchers also reviewed medical records to confirm self-reported cases of new-onset ulcerative colitis and Crohn’s disease.

Over 4.02 million person-years of follow-up, 277 women developed Crohn’s disease and 359 developed ulcerative colitis. Gluten intake was not associated with the risk of either type of inflammatory bowel disease, even after the researchers controlled for multiple demographic and clinical risk factors.

After submitting their abstract, Dr. Lopes and coinvestigators expanded the dataset to include a large cohort of men from the prospective Health Professionals Follow-up Study. The final pooled cohort included more than 208,000 women and men followed for more than 20 years. Through the end of follow-up, the researchers documented 337 cases of Crohn’s disease and 446 cases of ulcerative colitis. “Inclusion of the male cohort in the pooled analysis did not materially change our estimates,” Dr. Lopes told MDedge. “That is, no association was seen between gluten intake and risk of either Crohn’s disease or ulcerative colitis in the final cohort.”

She noted that the findings cannot be extrapolated to individuals who are already diagnosed with inflammatory bowel disease. “It is possible that different mechanisms exist to explain how gluten intake impacts those already diagnosed with IBD, and this topic warrants further study,” she said. Also, because the three cohort studies were observational, they are subject to bias. “While we tried to account for this in our analyses, residual bias may still exist.”

Dr. Lopes reported having no conflicts of interest.

SOURCE: Walsh Lopes E et al. DDW 2020, abstract 847.

Among women without celiac disease, dietary gluten intake was not associated with the risk of developing either Crohn’s disease or ulcerative colitis, investigators reported.

The findings spanned subgroups stratified by age, body mass index, smoking status, and whether individuals primarily consumed refined or whole grains, said Emily Walsh Lopes, MD, gastroenterology clinical and research fellow at Massachusetts General Hospital in Boston. She and associates reported the combined analysis of the prospective Nurses’ Health Study and Nurses’ Health Study II in an abstract released as part of the annual Digestive Disease Week.^®

“Avoidance of dietary gluten is common, and many patients attribute gastrointestinal symptoms to gluten intake,” Dr. Lopes said in an interview. “Though our findings warrant further study, the results suggest to patients and providers that eating gluten does not increase a person’s chance of getting diagnosed with inflammatory bowel disease.”

Prior studies have found that many individuals with inflammatory bowel disease avoid gluten and report subsequent improvements in gastrointestinal symptoms, even if they do not have celiac disease. However, it remains unclear whether dietary gluten is a risk factor for new-onset inflammatory bowel disease.

To address this question, Dr. Lopes and associates analyzed data collected from 165,327 women who took part in the Nurses’ Health Study (1986 to 2016) or the Nurses’ Health Study II (1991 through 2017). None of the women had a preexisting diagnosis of celiac disease or inflammatory bowel disease. Dietary gluten intake was estimated based on food frequency questionnaires completed by the women at baseline and every 4 years. The researchers also reviewed medical records to confirm self-reported cases of new-onset ulcerative colitis and Crohn’s disease.

Over 4.02 million person-years of follow-up, 277 women developed Crohn’s disease and 359 developed ulcerative colitis. Gluten intake was not associated with the risk of either type of inflammatory bowel disease, even after the researchers controlled for multiple demographic and clinical risk factors.

After submitting their abstract, Dr. Lopes and coinvestigators expanded the dataset to include a large cohort of men from the prospective Health Professionals Follow-up Study. The final pooled cohort included more than 208,000 women and men followed for more than 20 years. Through the end of follow-up, the researchers documented 337 cases of Crohn’s disease and 446 cases of ulcerative colitis. “Inclusion of the male cohort in the pooled analysis did not materially change our estimates,” Dr. Lopes told MDedge. “That is, no association was seen between gluten intake and risk of either Crohn’s disease or ulcerative colitis in the final cohort.”

She noted that the findings cannot be extrapolated to individuals who are already diagnosed with inflammatory bowel disease. “It is possible that different mechanisms exist to explain how gluten intake impacts those already diagnosed with IBD, and this topic warrants further study,” she said. Also, because the three cohort studies were observational, they are subject to bias. “While we tried to account for this in our analyses, residual bias may still exist.”

Dr. Lopes reported having no conflicts of interest.

SOURCE: Walsh Lopes E et al. DDW 2020, abstract 847.

Irritable bowel syndrome symptoms were improved in about one-third of patients who took an inactivated bacterial treatment, pointing the way to a therapeutic path that could avoid some risks of live probiotic use.

Of 443 patients taking part in a randomized, double-blind, placebo-controlled trial of a heat-inactivated nonviable Bifidobacterium probiotic, 221 received the probiotic while 222 received placebo capsules. The study’s primary endpoint was a composite of at least 30% improvement in abdominal pain and “adequate relief” of overall irritable bowel syndrome (IBS) symptoms in at least 4 of the 8 weeks of the study.

Within the B. bifidum group, 74 patients (34%) reached this endpoint, compared with 43 (19%) of those in the placebo group, for a risk ratio of 1.7 (P = .0007). Patients had no serious adverse events from the oral therapy, which they took in the form of two capsules daily for 8 weeks, and participants found both the inactivated Bifidobacterium treatment and placebo tolerable overall.

Bowel movements became more frequent in those who received B. bifidum capsules who had constipation-predominant IBS and less frequent in those with diarrhea-predominant IBS; the changes were statistically significant in both subgroups.

“Some probiotic strains can adhere well to epithelial cells and strengthen intestinal barrier function, providing an explanation for the efficacy of at least some probiotics in the treatment of IBS,” wrote Viola Andresen, MD, MSc, the study‘s lead author.

“Accordingly, enhancing the gut barrier is a useful treatment approach for patients with IBS,” added Dr. Andresen, of the department of internal medicine at the University of Hamburg (Germany) Teaching Hospital, and collaborators. The adherent properties of some strains of Bifidobacteria are mainly dependent on properties of the cell surface that are not changed by heat inactivation, which makes the bacteria nonviable – and removes the risk of infection.

Additional benefits of using nonviable bacteria for IBS therapy might include more stability and enhanced standardization, although previous studies have shown a reduction in efficacy when bacteria are made nonviable. Inactivated B. bifidum MIMBb75 was used in this study because it had previously been shown effective against IBS symptoms, noted Dr. Andresen and coauthors.

Adult patients were included if they met criteria for IBS according to Rome III and had abdominal pain rated at least 4 on an 11-point scale for at least 2 days of a 2-week run-in phase. Among the many criteria for exclusion from the study were history of inflammatory gastrointestinal disease, cancer, other serious stomach diseases, diabetes, many abdominal surgeries, and recent antipsychotic or steroid use.

During the study, participants recorded their abdominal pain over the last 24 hours daily; weekly averages were tallied for each patient. Patients were also asked to rate their relief of IBS symptoms, including abdominal pain, bowel habits, and other symptoms over the past week at weekly time points on a 7-point Likert scale, where scores of 3 or less indicated some measure of relief; IBS symptoms were considered to be adequately relieved with a score of 3 or less.

Secondary outcome measures for the study included changes in the Subjects’ Global Assessment of symptoms, and changes in individual symptoms. Number of bowel movements, stool form, sensation of incomplete evacuation, and medication use were also recorded daily.

Participants were aged a mean of 41 years, and about 70% were female. The mean body mass index was just under 25 kg/m². About half of each study arm had diarrhea-predominant IBS. About a quarter had constipation-predominant IBS, and most of the rest were not subtyped.

Looking at the primary endpoint, the number needed to treat for benefit was 7.1 in favor of the inactivated bacterium, using an intention-to-treat analysis. Results were similar when a per-protocol analysis was applied. The investigators saw response to treatment climb through the duration of the study for both the probiotic and the placebo arms, with the gap in improvement between the groups widening over the 8-week study period.

“It might be assumed that the use of nonviable bacteria for the treatment of IBS could be a safe alternative, even in patients who are potentially susceptible to infection,” concluded Dr. Andresen and colleagues. A further advantage, noted the researchers, is greater product stability in fluctuating temperatures compared with viable bacteria, ensuring better standardization even in regions with warm or changing climates.

Perspective was offered in an accompanying commentary whose lead author was Nicholas Talley, MD, PhD, a gastroenterologist, adjunct professor, and pro vice-chancellor for global research at the University of Newcastle (Australia).

“By heat inactivating the bacteria the researchers did not administer a probiotic but a bacterial therapy,” wrote Dr. Talley and coauthors. In any event, they added, the exact mechanism by which probiotics benefit individuals with IBS is unknown.

“The concept that a probiotic might be efficacious in IBS even if nonviable organisms are administered is an important observation,” they wrote. Fewer benefits have been seen with oral probiotic therapy than with fecal microbial transfer, and oral therapy does not produce durable results unless administered on a chronic basis, Dr. Talley and coauthors added.

“The absence of fundamental knowledge in terms of how bacterial therapy alters mechanisms in IBS continues to hamper improvements in treatment, limiting any success to short-term symptom control rather than the true goal, reversal of disease,” they concluded.

The study was funded by Synformulas. Dr. Andresen reported financial relationships with several pharmaceutical companies. Dr. Talley reported financial relationships with several pharmaceutical and nutritional companies.

koakes@mdedge.com

SOURCE: Andresen V et al. Lancet Gastroenterol Hepatol. 2020 Apr 8. doi: 10.1016/S2468-1253(20)30079-0

Irritable bowel syndrome symptoms were improved in about one-third of patients who took an inactivated bacterial treatment, pointing the way to a therapeutic path that could avoid some risks of live probiotic use.

Of 443 patients taking part in a randomized, double-blind, placebo-controlled trial of a heat-inactivated nonviable Bifidobacterium probiotic, 221 received the probiotic while 222 received placebo capsules. The study’s primary endpoint was a composite of at least 30% improvement in abdominal pain and “adequate relief” of overall irritable bowel syndrome (IBS) symptoms in at least 4 of the 8 weeks of the study.

Within the B. bifidum group, 74 patients (34%) reached this endpoint, compared with 43 (19%) of those in the placebo group, for a risk ratio of 1.7 (P = .0007). Patients had no serious adverse events from the oral therapy, which they took in the form of two capsules daily for 8 weeks, and participants found both the inactivated Bifidobacterium treatment and placebo tolerable overall.

Bowel movements became more frequent in those who received B. bifidum capsules who had constipation-predominant IBS and less frequent in those with diarrhea-predominant IBS; the changes were statistically significant in both subgroups.

“Some probiotic strains can adhere well to epithelial cells and strengthen intestinal barrier function, providing an explanation for the efficacy of at least some probiotics in the treatment of IBS,” wrote Viola Andresen, MD, MSc, the study‘s lead author.

“Accordingly, enhancing the gut barrier is a useful treatment approach for patients with IBS,” added Dr. Andresen, of the department of internal medicine at the University of Hamburg (Germany) Teaching Hospital, and collaborators. The adherent properties of some strains of Bifidobacteria are mainly dependent on properties of the cell surface that are not changed by heat inactivation, which makes the bacteria nonviable – and removes the risk of infection.

Additional benefits of using nonviable bacteria for IBS therapy might include more stability and enhanced standardization, although previous studies have shown a reduction in efficacy when bacteria are made nonviable. Inactivated B. bifidum MIMBb75 was used in this study because it had previously been shown effective against IBS symptoms, noted Dr. Andresen and coauthors.

Adult patients were included if they met criteria for IBS according to Rome III and had abdominal pain rated at least 4 on an 11-point scale for at least 2 days of a 2-week run-in phase. Among the many criteria for exclusion from the study were history of inflammatory gastrointestinal disease, cancer, other serious stomach diseases, diabetes, many abdominal surgeries, and recent antipsychotic or steroid use.

During the study, participants recorded their abdominal pain over the last 24 hours daily; weekly averages were tallied for each patient. Patients were also asked to rate their relief of IBS symptoms, including abdominal pain, bowel habits, and other symptoms over the past week at weekly time points on a 7-point Likert scale, where scores of 3 or less indicated some measure of relief; IBS symptoms were considered to be adequately relieved with a score of 3 or less.

Secondary outcome measures for the study included changes in the Subjects’ Global Assessment of symptoms, and changes in individual symptoms. Number of bowel movements, stool form, sensation of incomplete evacuation, and medication use were also recorded daily.

Participants were aged a mean of 41 years, and about 70% were female. The mean body mass index was just under 25 kg/m². About half of each study arm had diarrhea-predominant IBS. About a quarter had constipation-predominant IBS, and most of the rest were not subtyped.

Looking at the primary endpoint, the number needed to treat for benefit was 7.1 in favor of the inactivated bacterium, using an intention-to-treat analysis. Results were similar when a per-protocol analysis was applied. The investigators saw response to treatment climb through the duration of the study for both the probiotic and the placebo arms, with the gap in improvement between the groups widening over the 8-week study period.

“It might be assumed that the use of nonviable bacteria for the treatment of IBS could be a safe alternative, even in patients who are potentially susceptible to infection,” concluded Dr. Andresen and colleagues. A further advantage, noted the researchers, is greater product stability in fluctuating temperatures compared with viable bacteria, ensuring better standardization even in regions with warm or changing climates.

Perspective was offered in an accompanying commentary whose lead author was Nicholas Talley, MD, PhD, a gastroenterologist, adjunct professor, and pro vice-chancellor for global research at the University of Newcastle (Australia).

“By heat inactivating the bacteria the researchers did not administer a probiotic but a bacterial therapy,” wrote Dr. Talley and coauthors. In any event, they added, the exact mechanism by which probiotics benefit individuals with IBS is unknown.

“The concept that a probiotic might be efficacious in IBS even if nonviable organisms are administered is an important observation,” they wrote. Fewer benefits have been seen with oral probiotic therapy than with fecal microbial transfer, and oral therapy does not produce durable results unless administered on a chronic basis, Dr. Talley and coauthors added.

“The absence of fundamental knowledge in terms of how bacterial therapy alters mechanisms in IBS continues to hamper improvements in treatment, limiting any success to short-term symptom control rather than the true goal, reversal of disease,” they concluded.

The study was funded by Synformulas. Dr. Andresen reported financial relationships with several pharmaceutical companies. Dr. Talley reported financial relationships with several pharmaceutical and nutritional companies.

koakes@mdedge.com

SOURCE: Andresen V et al. Lancet Gastroenterol Hepatol. 2020 Apr 8. doi: 10.1016/S2468-1253(20)30079-0

Irritable bowel syndrome symptoms were improved in about one-third of patients who took an inactivated bacterial treatment, pointing the way to a therapeutic path that could avoid some risks of live probiotic use.

Of 443 patients taking part in a randomized, double-blind, placebo-controlled trial of a heat-inactivated nonviable Bifidobacterium probiotic, 221 received the probiotic while 222 received placebo capsules. The study’s primary endpoint was a composite of at least 30% improvement in abdominal pain and “adequate relief” of overall irritable bowel syndrome (IBS) symptoms in at least 4 of the 8 weeks of the study.

Within the B. bifidum group, 74 patients (34%) reached this endpoint, compared with 43 (19%) of those in the placebo group, for a risk ratio of 1.7 (P = .0007). Patients had no serious adverse events from the oral therapy, which they took in the form of two capsules daily for 8 weeks, and participants found both the inactivated Bifidobacterium treatment and placebo tolerable overall.

Bowel movements became more frequent in those who received B. bifidum capsules who had constipation-predominant IBS and less frequent in those with diarrhea-predominant IBS; the changes were statistically significant in both subgroups.

“Some probiotic strains can adhere well to epithelial cells and strengthen intestinal barrier function, providing an explanation for the efficacy of at least some probiotics in the treatment of IBS,” wrote Viola Andresen, MD, MSc, the study‘s lead author.

“Accordingly, enhancing the gut barrier is a useful treatment approach for patients with IBS,” added Dr. Andresen, of the department of internal medicine at the University of Hamburg (Germany) Teaching Hospital, and collaborators. The adherent properties of some strains of Bifidobacteria are mainly dependent on properties of the cell surface that are not changed by heat inactivation, which makes the bacteria nonviable – and removes the risk of infection.

Additional benefits of using nonviable bacteria for IBS therapy might include more stability and enhanced standardization, although previous studies have shown a reduction in efficacy when bacteria are made nonviable. Inactivated B. bifidum MIMBb75 was used in this study because it had previously been shown effective against IBS symptoms, noted Dr. Andresen and coauthors.

Adult patients were included if they met criteria for IBS according to Rome III and had abdominal pain rated at least 4 on an 11-point scale for at least 2 days of a 2-week run-in phase. Among the many criteria for exclusion from the study were history of inflammatory gastrointestinal disease, cancer, other serious stomach diseases, diabetes, many abdominal surgeries, and recent antipsychotic or steroid use.

During the study, participants recorded their abdominal pain over the last 24 hours daily; weekly averages were tallied for each patient. Patients were also asked to rate their relief of IBS symptoms, including abdominal pain, bowel habits, and other symptoms over the past week at weekly time points on a 7-point Likert scale, where scores of 3 or less indicated some measure of relief; IBS symptoms were considered to be adequately relieved with a score of 3 or less.

Secondary outcome measures for the study included changes in the Subjects’ Global Assessment of symptoms, and changes in individual symptoms. Number of bowel movements, stool form, sensation of incomplete evacuation, and medication use were also recorded daily.

Participants were aged a mean of 41 years, and about 70% were female. The mean body mass index was just under 25 kg/m². About half of each study arm had diarrhea-predominant IBS. About a quarter had constipation-predominant IBS, and most of the rest were not subtyped.

Looking at the primary endpoint, the number needed to treat for benefit was 7.1 in favor of the inactivated bacterium, using an intention-to-treat analysis. Results were similar when a per-protocol analysis was applied. The investigators saw response to treatment climb through the duration of the study for both the probiotic and the placebo arms, with the gap in improvement between the groups widening over the 8-week study period.

“It might be assumed that the use of nonviable bacteria for the treatment of IBS could be a safe alternative, even in patients who are potentially susceptible to infection,” concluded Dr. Andresen and colleagues. A further advantage, noted the researchers, is greater product stability in fluctuating temperatures compared with viable bacteria, ensuring better standardization even in regions with warm or changing climates.

Perspective was offered in an accompanying commentary whose lead author was Nicholas Talley, MD, PhD, a gastroenterologist, adjunct professor, and pro vice-chancellor for global research at the University of Newcastle (Australia).

“By heat inactivating the bacteria the researchers did not administer a probiotic but a bacterial therapy,” wrote Dr. Talley and coauthors. In any event, they added, the exact mechanism by which probiotics benefit individuals with IBS is unknown.

“The concept that a probiotic might be efficacious in IBS even if nonviable organisms are administered is an important observation,” they wrote. Fewer benefits have been seen with oral probiotic therapy than with fecal microbial transfer, and oral therapy does not produce durable results unless administered on a chronic basis, Dr. Talley and coauthors added.

“The absence of fundamental knowledge in terms of how bacterial therapy alters mechanisms in IBS continues to hamper improvements in treatment, limiting any success to short-term symptom control rather than the true goal, reversal of disease,” they concluded.

The study was funded by Synformulas. Dr. Andresen reported financial relationships with several pharmaceutical companies. Dr. Talley reported financial relationships with several pharmaceutical and nutritional companies.

koakes@mdedge.com

SOURCE: Andresen V et al. Lancet Gastroenterol Hepatol. 2020 Apr 8. doi: 10.1016/S2468-1253(20)30079-0

Infant rice cereal contains lower levels of arsenic than it did in 2014, according to test results released by the Food and Drug Administration.

In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.

Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.

The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.

“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.

“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.

klennon@mdedge.com

Infant rice cereal contains lower levels of arsenic than it did in 2014, according to test results released by the Food and Drug Administration.

In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.

Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.

The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.

“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.

“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.

klennon@mdedge.com

Infant rice cereal contains lower levels of arsenic than it did in 2014, according to test results released by the Food and Drug Administration.

In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.

Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.

The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.

“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.

“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.

klennon@mdedge.com

Importance

The prevention and treatment of traveler’s diarrhea (TD) is a common reason that patients consult their physician prior to foreign travel. TD can result in lost time and opportunity, as well as overseas medical encounters and hospitalization. This guideline by the International Society of Travel Medicine provides clinically relevant, useful, and practical guidance to providers regarding the use of antibiotic and nonantibiotic therapies for the prevention and treatment of TD.

Prophylaxis

The panel recommends that antimicrobial prophylaxis should not be used routinely in travelers, but it should be considered for travelers who are at high risk of health-related complications of TD (both strong recommendations, low/very low level of evidence [LOE]). High-risk individuals include those with a history of clinically significant long-term morbidity following an enteric infection or serious chronic illnesses that predisposes them for TD-related complications. Bismuth subsalicylate (BSS) may be considered for any traveler to prevent TD (3, strong recommendation, high LOE). Studies show that a lower dose of 1.05 g/day is preventive, although it is unclear whether it is as effective as higher doses of 2.1 g/day or 4.2 g/day. When prophylaxis is indicated, travelers should be prescribed rifaximin (strong recommendation, moderate LOE) based on susceptibility of most enteric pathogens and the drug’s extremely favorable safety profile. Fluoroquinolones (FQ) are no longer recommended for prophylaxis (strong recommendation, low/very low LOE) because of neurologic and musculoskeletal side effects that may outweigh benefits, as well as emerging resistance of enteric pathogens (70%-80% in Campylobacter spp. from Nepal and Thailand and 65% in Enterotoxigenic Escherichia coli [ETEC] and Enteroaggregative E. coli [EAEC] in India).

Treatment

The following treatment recommendations are based on the classification of TD using functional effects of severity; therefore, the panel made new definitions for TD severity. This is a change from previous definitions that utilized a traditional frequency-based algorithm in order to tailor therapy for the individual. Individuals can be prescribed antibiotics and antimotility agents to take with them during travel, along with advice regarding how to judge when to use each agent.

Mild: diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.

Encourage supportive measures such as rehydration and nonantibiotic, antimotility drugs, such as loperamide or BSS (both strong recommendations, moderate LOE).

Moderate: diarrhea that is distressing or interferes with planned activities.

Antibiotics may be used (weak recommendation, moderate LOE) as early and effective treatment may mitigate the well-described chronic health consequences including irritable bowel syndrome. Three options exist. FQs may be used outside of Southeast and South Asia (strong recommendation, moderate LOE), but their potential for adverse effects and musculoskeletal consequences must be considered. Azithromycin may be used (strong recommendation, high LOE) because studies show no significant differences in efficacy between it and FQs, limited resistance to common TD pathogens (although concerns exist in Nepal), and good side effect profile. Another choice is rifaximin (weak recommendation, moderate LOE), although one should exercise caution for empirical therapy in regions in which being at high risk of invasive pathogens is anticipated.

Loperamide may be used as adjunctive therapy for moderate to severe TD (strong recommendation, high LOE) to add symptomatic relief with curative treatment or as monotherapy in moderate TD (strong recommendation, high LOE). This is specifically true in children aged 2-11 years, in whom loperamide is beneficial without causing severe side effects.

Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools).

Antibiotics should be used (strong recommendation, high LOE). Azithromycin is the preferred choice and is first-line for dysentery or febrile diarrhea (strong recommendation, moderate LOE) because of the likelihood of FQ-resistant bacteria being the cause of dysentery. FQs and rifaximin are also choices that can be used to treat severe, nondysenteric TD (both weak recommendations, moderate LOE).

Furthermore, single-dose antibiotics may be used to treat moderate or severe TD (strong recommendation, high LOE) because studies have shown equivalent efficacy for treatment of watery noninvasive diarrhea among FQs (3 days, single dose), azithromycin (3 days, single dose), and rifaximin (3 days, three times daily).

Persistent: diarrhea lasting longer than 2 weeks.

Functional bowel disease (FBD) may occur after bouts of TD and may meet Rome III or IV criteria for irritable bowel syndrome. Thus, in a traveler without pretravel GI disease, in whom the evaluation for microbial etiologies and underlying GI disease is negative, postinfectious FBD must be considered.

Follow-up and diagnostic testing

The panel recommends microbiological testing in returning travelers with severe or persistent symptoms, bloody/mucousy diarrhea, or in those who fail empiric therapy (strong recommendation, low/very low LOE). Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis. Furthermore, molecular testing may, in some cases, detect colonization rather than infection.
 

The bottom line

The expert panel made 20 graded recommendations to help guide the provider with nonantibiotic and antibiotic prophylaxis and treatment of TD. The main take-home points include:

• Prophylaxis should be considered only in high-risk groups; rifaximin is the first choice, and BSS is a second option.
• All travelers should be provided with loperamide and an antibiotic for self-treatment if needed.
• Mild diarrhea should be treated with increased fluid intake and loperamide or BSS.
• Moderate to severe diarrhea should be treated with single-dose antimicrobial therapy of FQ or azithromycin or with rifaximin dosing three times a day.
• Instead of antibiotics, loperamide may be considered as monotherapy for moderate diarrhea; loperamide can be used with antibiotics for both moderate and severe TD.

Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

Reference:

J Travel Med. 2017 Apr 1;24(suppl_1):S57-74.

Importance

The prevention and treatment of traveler’s diarrhea (TD) is a common reason that patients consult their physician prior to foreign travel. TD can result in lost time and opportunity, as well as overseas medical encounters and hospitalization. This guideline by the International Society of Travel Medicine provides clinically relevant, useful, and practical guidance to providers regarding the use of antibiotic and nonantibiotic therapies for the prevention and treatment of TD.

Prophylaxis

The panel recommends that antimicrobial prophylaxis should not be used routinely in travelers, but it should be considered for travelers who are at high risk of health-related complications of TD (both strong recommendations, low/very low level of evidence [LOE]). High-risk individuals include those with a history of clinically significant long-term morbidity following an enteric infection or serious chronic illnesses that predisposes them for TD-related complications. Bismuth subsalicylate (BSS) may be considered for any traveler to prevent TD (3, strong recommendation, high LOE). Studies show that a lower dose of 1.05 g/day is preventive, although it is unclear whether it is as effective as higher doses of 2.1 g/day or 4.2 g/day. When prophylaxis is indicated, travelers should be prescribed rifaximin (strong recommendation, moderate LOE) based on susceptibility of most enteric pathogens and the drug’s extremely favorable safety profile. Fluoroquinolones (FQ) are no longer recommended for prophylaxis (strong recommendation, low/very low LOE) because of neurologic and musculoskeletal side effects that may outweigh benefits, as well as emerging resistance of enteric pathogens (70%-80% in Campylobacter spp. from Nepal and Thailand and 65% in Enterotoxigenic Escherichia coli [ETEC] and Enteroaggregative E. coli [EAEC] in India).

Treatment

The following treatment recommendations are based on the classification of TD using functional effects of severity; therefore, the panel made new definitions for TD severity. This is a change from previous definitions that utilized a traditional frequency-based algorithm in order to tailor therapy for the individual. Individuals can be prescribed antibiotics and antimotility agents to take with them during travel, along with advice regarding how to judge when to use each agent.

Mild: diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.

Encourage supportive measures such as rehydration and nonantibiotic, antimotility drugs, such as loperamide or BSS (both strong recommendations, moderate LOE).

Moderate: diarrhea that is distressing or interferes with planned activities.

Antibiotics may be used (weak recommendation, moderate LOE) as early and effective treatment may mitigate the well-described chronic health consequences including irritable bowel syndrome. Three options exist. FQs may be used outside of Southeast and South Asia (strong recommendation, moderate LOE), but their potential for adverse effects and musculoskeletal consequences must be considered. Azithromycin may be used (strong recommendation, high LOE) because studies show no significant differences in efficacy between it and FQs, limited resistance to common TD pathogens (although concerns exist in Nepal), and good side effect profile. Another choice is rifaximin (weak recommendation, moderate LOE), although one should exercise caution for empirical therapy in regions in which being at high risk of invasive pathogens is anticipated.

Loperamide may be used as adjunctive therapy for moderate to severe TD (strong recommendation, high LOE) to add symptomatic relief with curative treatment or as monotherapy in moderate TD (strong recommendation, high LOE). This is specifically true in children aged 2-11 years, in whom loperamide is beneficial without causing severe side effects.

Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools).

Antibiotics should be used (strong recommendation, high LOE). Azithromycin is the preferred choice and is first-line for dysentery or febrile diarrhea (strong recommendation, moderate LOE) because of the likelihood of FQ-resistant bacteria being the cause of dysentery. FQs and rifaximin are also choices that can be used to treat severe, nondysenteric TD (both weak recommendations, moderate LOE).

Furthermore, single-dose antibiotics may be used to treat moderate or severe TD (strong recommendation, high LOE) because studies have shown equivalent efficacy for treatment of watery noninvasive diarrhea among FQs (3 days, single dose), azithromycin (3 days, single dose), and rifaximin (3 days, three times daily).

Persistent: diarrhea lasting longer than 2 weeks.

Functional bowel disease (FBD) may occur after bouts of TD and may meet Rome III or IV criteria for irritable bowel syndrome. Thus, in a traveler without pretravel GI disease, in whom the evaluation for microbial etiologies and underlying GI disease is negative, postinfectious FBD must be considered.

Follow-up and diagnostic testing

The panel recommends microbiological testing in returning travelers with severe or persistent symptoms, bloody/mucousy diarrhea, or in those who fail empiric therapy (strong recommendation, low/very low LOE). Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis. Furthermore, molecular testing may, in some cases, detect colonization rather than infection.
 

The bottom line

The expert panel made 20 graded recommendations to help guide the provider with nonantibiotic and antibiotic prophylaxis and treatment of TD. The main take-home points include:

• Prophylaxis should be considered only in high-risk groups; rifaximin is the first choice, and BSS is a second option.
• All travelers should be provided with loperamide and an antibiotic for self-treatment if needed.
• Mild diarrhea should be treated with increased fluid intake and loperamide or BSS.
• Moderate to severe diarrhea should be treated with single-dose antimicrobial therapy of FQ or azithromycin or with rifaximin dosing three times a day.
• Instead of antibiotics, loperamide may be considered as monotherapy for moderate diarrhea; loperamide can be used with antibiotics for both moderate and severe TD.

Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

Reference:

J Travel Med. 2017 Apr 1;24(suppl_1):S57-74.

Importance

The prevention and treatment of traveler’s diarrhea (TD) is a common reason that patients consult their physician prior to foreign travel. TD can result in lost time and opportunity, as well as overseas medical encounters and hospitalization. This guideline by the International Society of Travel Medicine provides clinically relevant, useful, and practical guidance to providers regarding the use of antibiotic and nonantibiotic therapies for the prevention and treatment of TD.

Prophylaxis

The panel recommends that antimicrobial prophylaxis should not be used routinely in travelers, but it should be considered for travelers who are at high risk of health-related complications of TD (both strong recommendations, low/very low level of evidence [LOE]). High-risk individuals include those with a history of clinically significant long-term morbidity following an enteric infection or serious chronic illnesses that predisposes them for TD-related complications. Bismuth subsalicylate (BSS) may be considered for any traveler to prevent TD (3, strong recommendation, high LOE). Studies show that a lower dose of 1.05 g/day is preventive, although it is unclear whether it is as effective as higher doses of 2.1 g/day or 4.2 g/day. When prophylaxis is indicated, travelers should be prescribed rifaximin (strong recommendation, moderate LOE) based on susceptibility of most enteric pathogens and the drug’s extremely favorable safety profile. Fluoroquinolones (FQ) are no longer recommended for prophylaxis (strong recommendation, low/very low LOE) because of neurologic and musculoskeletal side effects that may outweigh benefits, as well as emerging resistance of enteric pathogens (70%-80% in Campylobacter spp. from Nepal and Thailand and 65% in Enterotoxigenic Escherichia coli [ETEC] and Enteroaggregative E. coli [EAEC] in India).

Treatment

The following treatment recommendations are based on the classification of TD using functional effects of severity; therefore, the panel made new definitions for TD severity. This is a change from previous definitions that utilized a traditional frequency-based algorithm in order to tailor therapy for the individual. Individuals can be prescribed antibiotics and antimotility agents to take with them during travel, along with advice regarding how to judge when to use each agent.

Mild: diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.

Encourage supportive measures such as rehydration and nonantibiotic, antimotility drugs, such as loperamide or BSS (both strong recommendations, moderate LOE).

Moderate: diarrhea that is distressing or interferes with planned activities.

Antibiotics may be used (weak recommendation, moderate LOE) as early and effective treatment may mitigate the well-described chronic health consequences including irritable bowel syndrome. Three options exist. FQs may be used outside of Southeast and South Asia (strong recommendation, moderate LOE), but their potential for adverse effects and musculoskeletal consequences must be considered. Azithromycin may be used (strong recommendation, high LOE) because studies show no significant differences in efficacy between it and FQs, limited resistance to common TD pathogens (although concerns exist in Nepal), and good side effect profile. Another choice is rifaximin (weak recommendation, moderate LOE), although one should exercise caution for empirical therapy in regions in which being at high risk of invasive pathogens is anticipated.

Loperamide may be used as adjunctive therapy for moderate to severe TD (strong recommendation, high LOE) to add symptomatic relief with curative treatment or as monotherapy in moderate TD (strong recommendation, high LOE). This is specifically true in children aged 2-11 years, in whom loperamide is beneficial without causing severe side effects.

Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools).

Antibiotics should be used (strong recommendation, high LOE). Azithromycin is the preferred choice and is first-line for dysentery or febrile diarrhea (strong recommendation, moderate LOE) because of the likelihood of FQ-resistant bacteria being the cause of dysentery. FQs and rifaximin are also choices that can be used to treat severe, nondysenteric TD (both weak recommendations, moderate LOE).

Furthermore, single-dose antibiotics may be used to treat moderate or severe TD (strong recommendation, high LOE) because studies have shown equivalent efficacy for treatment of watery noninvasive diarrhea among FQs (3 days, single dose), azithromycin (3 days, single dose), and rifaximin (3 days, three times daily).

Persistent: diarrhea lasting longer than 2 weeks.

Functional bowel disease (FBD) may occur after bouts of TD and may meet Rome III or IV criteria for irritable bowel syndrome. Thus, in a traveler without pretravel GI disease, in whom the evaluation for microbial etiologies and underlying GI disease is negative, postinfectious FBD must be considered.

Follow-up and diagnostic testing

The panel recommends microbiological testing in returning travelers with severe or persistent symptoms, bloody/mucousy diarrhea, or in those who fail empiric therapy (strong recommendation, low/very low LOE). Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis. Furthermore, molecular testing may, in some cases, detect colonization rather than infection.
 

The bottom line

The expert panel made 20 graded recommendations to help guide the provider with nonantibiotic and antibiotic prophylaxis and treatment of TD. The main take-home points include:

• Prophylaxis should be considered only in high-risk groups; rifaximin is the first choice, and BSS is a second option.
• All travelers should be provided with loperamide and an antibiotic for self-treatment if needed.
• Mild diarrhea should be treated with increased fluid intake and loperamide or BSS.
• Moderate to severe diarrhea should be treated with single-dose antimicrobial therapy of FQ or azithromycin or with rifaximin dosing three times a day.
• Instead of antibiotics, loperamide may be considered as monotherapy for moderate diarrhea; loperamide can be used with antibiotics for both moderate and severe TD.

Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

Reference:

J Travel Med. 2017 Apr 1;24(suppl_1):S57-74.