Lorraine L. Janeczko, MPH

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) are more likely to develop infections than are those who take a tumor necrosis factor inhibitor (TNFi), results of an industry-sponsored randomized controlled trial suggest.

The Janus kinase (JAK) inhibitor tofacitinib and TNFi biologics are common RA treatments that, along with factors including age, disease activity, and comorbidities, can put patients with RA at increased risk for infections.

“In this secondary analysis of the ORAL Surveillance trial, infections were increased with tofacitinib, compared with TNFi,” study coauthor Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, both in Boston, explained in an interview.

As reported in Annals of the Rheumatic Diseases, Dr. Bhatt and colleagues performed a subanalysis of the final dataset from the phase 3b/4 open-label safety trial of tofacitinib in RA conducted between March 2014 and July 2020, in 345 study locations worldwide.

Study participants were 50 years of age or older with moderate to severe RA who were taking methotrexate but having inadequate symptom control. They had at least one cardiovascular risk factor such as being a current smoker or having hypertension, past heart attack, family history of coronary heart disease, high cholesterol, diabetes mellitus, or extra-articular RA. Patients with current or recent infection, clinically significant laboratory abnormalities, or pregnancy, were excluded from the study.

In the study, 1,455 participants received oral tofacitinib 5 mg twice per day; 1,456 received oral tofacitinib 10 mg twice per day; and 1,451 were treated with subcutaneous TNFi (40 mg subcutaneous adalimumab [Humira] injection every 2 weeks in the United States, Puerto Rico, and Canada; and 50 mg subcutaneous etanercept [Enbrel] injection every week in all other countries. Participants continued their prestudy stable dose of methotrexate if clinically indicated.

The researchers calculated incidence rates and hazard ratios for infections, overall and by age (50-64 years, compared with 65 years and older). They calculated probabilities of infection using Kaplan-Meier estimates and identified infection risk factors through Cox modeling.

They found higher infection rates, serious infection events (SIEs), and nonserious infections (NSIs) with tofacitinib than with TNFi, including:

• Patients taking tofacitinib 5 mg (HR, 1.17; 95% confidence interval, 0.92-1.50) and 10 mg (HR, 1.48; 95% CI, 1.17-1.87) were at greater risk for SIEs.
• Patients older than 65 who were taking tofacitinib 10 mg had increased IRs and HRs for all infections and for SIEs, compared with those aged 50-64.
• The probability of a SIE rose from month 18 onward in participants taking tofacitinib 5 mg, as well as before month 6 in those taking tofacitinib 10 mg.
• In both tofacitinib groups, the probability of NSI increased before month 6.

The most common risk factors for SIEs were higher age, baseline opioid use, history of chronic lung disease, and time-dependent oral corticosteroid use. Risk factors for NSIs were female sex, history of chronic lung disease or infection, history of smoking, as well as time-dependent higher Disease Activity Score in 28 joints and C-reactive protein score.
 

‘Best information to date’

Michael George, MD, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, welcomed the study’s results.

“This study provides the best information to date on the risk of infection with the JAK inhibitor tofacitinib, compared to a TNF inhibitor,” Dr. George, who was not involved in the study, said in an interview. “It is rare to have such a large randomized trial with an active comparator focused on safety. This is a major strength.

“Being able to quantify the amount of increased risk will help with shared decision-making when counseling patients,” he added.

Dr. George said that, while the small overall risk may not be clinically meaningful for younger, healthier patients, trying biologics such as TNFi before tofacitinib may be optimal for high-risk patients who are older or have comorbidities.

Dr. Bhatt agreed.

“In deciding on appropriate therapies for RA (or other conditions where tofacitinib is used), it is important for the prescribing physician to explain the risks to the patient and weigh them against the potential benefits,” he advised.

Dr. Bhatt noted that increased infection is not the first risk that’s been linked with tofacitinib.

“ORAL Surveillance was designed primarily to assess cardiovascular safety and showed higher rates of cardiovascular events such as myocardial infarction and pulmonary embolism, as well as cancer, with tofacitinib,” he explained.

He recommended further related research.

“Randomized trials are needed to determine the best ways to treat conditions such as RA while trying to minimize cardiovascular, cancer, and infectious risks,” he said.

The study was sponsored by Pfizer. All authors reported financial involvements with Pfizer; most have financial involvements with other pharmaceutical companies as well; four authors are employees of Pfizer and three are also stockholders in the company. Dr. George reported involvements with the pharmaceutical industry.

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) are more likely to develop infections than are those who take a tumor necrosis factor inhibitor (TNFi), results of an industry-sponsored randomized controlled trial suggest.

The Janus kinase (JAK) inhibitor tofacitinib and TNFi biologics are common RA treatments that, along with factors including age, disease activity, and comorbidities, can put patients with RA at increased risk for infections.

“In this secondary analysis of the ORAL Surveillance trial, infections were increased with tofacitinib, compared with TNFi,” study coauthor Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, both in Boston, explained in an interview.

As reported in Annals of the Rheumatic Diseases, Dr. Bhatt and colleagues performed a subanalysis of the final dataset from the phase 3b/4 open-label safety trial of tofacitinib in RA conducted between March 2014 and July 2020, in 345 study locations worldwide.

Study participants were 50 years of age or older with moderate to severe RA who were taking methotrexate but having inadequate symptom control. They had at least one cardiovascular risk factor such as being a current smoker or having hypertension, past heart attack, family history of coronary heart disease, high cholesterol, diabetes mellitus, or extra-articular RA. Patients with current or recent infection, clinically significant laboratory abnormalities, or pregnancy, were excluded from the study.

In the study, 1,455 participants received oral tofacitinib 5 mg twice per day; 1,456 received oral tofacitinib 10 mg twice per day; and 1,451 were treated with subcutaneous TNFi (40 mg subcutaneous adalimumab [Humira] injection every 2 weeks in the United States, Puerto Rico, and Canada; and 50 mg subcutaneous etanercept [Enbrel] injection every week in all other countries. Participants continued their prestudy stable dose of methotrexate if clinically indicated.

The researchers calculated incidence rates and hazard ratios for infections, overall and by age (50-64 years, compared with 65 years and older). They calculated probabilities of infection using Kaplan-Meier estimates and identified infection risk factors through Cox modeling.

They found higher infection rates, serious infection events (SIEs), and nonserious infections (NSIs) with tofacitinib than with TNFi, including:

• Patients taking tofacitinib 5 mg (HR, 1.17; 95% confidence interval, 0.92-1.50) and 10 mg (HR, 1.48; 95% CI, 1.17-1.87) were at greater risk for SIEs.
• Patients older than 65 who were taking tofacitinib 10 mg had increased IRs and HRs for all infections and for SIEs, compared with those aged 50-64.
• The probability of a SIE rose from month 18 onward in participants taking tofacitinib 5 mg, as well as before month 6 in those taking tofacitinib 10 mg.
• In both tofacitinib groups, the probability of NSI increased before month 6.

The most common risk factors for SIEs were higher age, baseline opioid use, history of chronic lung disease, and time-dependent oral corticosteroid use. Risk factors for NSIs were female sex, history of chronic lung disease or infection, history of smoking, as well as time-dependent higher Disease Activity Score in 28 joints and C-reactive protein score.
 

‘Best information to date’

Michael George, MD, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, welcomed the study’s results.

“This study provides the best information to date on the risk of infection with the JAK inhibitor tofacitinib, compared to a TNF inhibitor,” Dr. George, who was not involved in the study, said in an interview. “It is rare to have such a large randomized trial with an active comparator focused on safety. This is a major strength.

“Being able to quantify the amount of increased risk will help with shared decision-making when counseling patients,” he added.

Dr. George said that, while the small overall risk may not be clinically meaningful for younger, healthier patients, trying biologics such as TNFi before tofacitinib may be optimal for high-risk patients who are older or have comorbidities.

Dr. Bhatt agreed.

“In deciding on appropriate therapies for RA (or other conditions where tofacitinib is used), it is important for the prescribing physician to explain the risks to the patient and weigh them against the potential benefits,” he advised.

Dr. Bhatt noted that increased infection is not the first risk that’s been linked with tofacitinib.

“ORAL Surveillance was designed primarily to assess cardiovascular safety and showed higher rates of cardiovascular events such as myocardial infarction and pulmonary embolism, as well as cancer, with tofacitinib,” he explained.

He recommended further related research.

“Randomized trials are needed to determine the best ways to treat conditions such as RA while trying to minimize cardiovascular, cancer, and infectious risks,” he said.

The study was sponsored by Pfizer. All authors reported financial involvements with Pfizer; most have financial involvements with other pharmaceutical companies as well; four authors are employees of Pfizer and three are also stockholders in the company. Dr. George reported involvements with the pharmaceutical industry.

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) are more likely to develop infections than are those who take a tumor necrosis factor inhibitor (TNFi), results of an industry-sponsored randomized controlled trial suggest.

The Janus kinase (JAK) inhibitor tofacitinib and TNFi biologics are common RA treatments that, along with factors including age, disease activity, and comorbidities, can put patients with RA at increased risk for infections.

“In this secondary analysis of the ORAL Surveillance trial, infections were increased with tofacitinib, compared with TNFi,” study coauthor Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, both in Boston, explained in an interview.

As reported in Annals of the Rheumatic Diseases, Dr. Bhatt and colleagues performed a subanalysis of the final dataset from the phase 3b/4 open-label safety trial of tofacitinib in RA conducted between March 2014 and July 2020, in 345 study locations worldwide.

Study participants were 50 years of age or older with moderate to severe RA who were taking methotrexate but having inadequate symptom control. They had at least one cardiovascular risk factor such as being a current smoker or having hypertension, past heart attack, family history of coronary heart disease, high cholesterol, diabetes mellitus, or extra-articular RA. Patients with current or recent infection, clinically significant laboratory abnormalities, or pregnancy, were excluded from the study.

In the study, 1,455 participants received oral tofacitinib 5 mg twice per day; 1,456 received oral tofacitinib 10 mg twice per day; and 1,451 were treated with subcutaneous TNFi (40 mg subcutaneous adalimumab [Humira] injection every 2 weeks in the United States, Puerto Rico, and Canada; and 50 mg subcutaneous etanercept [Enbrel] injection every week in all other countries. Participants continued their prestudy stable dose of methotrexate if clinically indicated.

The researchers calculated incidence rates and hazard ratios for infections, overall and by age (50-64 years, compared with 65 years and older). They calculated probabilities of infection using Kaplan-Meier estimates and identified infection risk factors through Cox modeling.

They found higher infection rates, serious infection events (SIEs), and nonserious infections (NSIs) with tofacitinib than with TNFi, including:

• Patients taking tofacitinib 5 mg (HR, 1.17; 95% confidence interval, 0.92-1.50) and 10 mg (HR, 1.48; 95% CI, 1.17-1.87) were at greater risk for SIEs.
• Patients older than 65 who were taking tofacitinib 10 mg had increased IRs and HRs for all infections and for SIEs, compared with those aged 50-64.
• The probability of a SIE rose from month 18 onward in participants taking tofacitinib 5 mg, as well as before month 6 in those taking tofacitinib 10 mg.
• In both tofacitinib groups, the probability of NSI increased before month 6.

The most common risk factors for SIEs were higher age, baseline opioid use, history of chronic lung disease, and time-dependent oral corticosteroid use. Risk factors for NSIs were female sex, history of chronic lung disease or infection, history of smoking, as well as time-dependent higher Disease Activity Score in 28 joints and C-reactive protein score.
 

‘Best information to date’

Michael George, MD, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, welcomed the study’s results.

“This study provides the best information to date on the risk of infection with the JAK inhibitor tofacitinib, compared to a TNF inhibitor,” Dr. George, who was not involved in the study, said in an interview. “It is rare to have such a large randomized trial with an active comparator focused on safety. This is a major strength.

“Being able to quantify the amount of increased risk will help with shared decision-making when counseling patients,” he added.

Dr. George said that, while the small overall risk may not be clinically meaningful for younger, healthier patients, trying biologics such as TNFi before tofacitinib may be optimal for high-risk patients who are older or have comorbidities.

Dr. Bhatt agreed.

“In deciding on appropriate therapies for RA (or other conditions where tofacitinib is used), it is important for the prescribing physician to explain the risks to the patient and weigh them against the potential benefits,” he advised.

Dr. Bhatt noted that increased infection is not the first risk that’s been linked with tofacitinib.

“ORAL Surveillance was designed primarily to assess cardiovascular safety and showed higher rates of cardiovascular events such as myocardial infarction and pulmonary embolism, as well as cancer, with tofacitinib,” he explained.

He recommended further related research.

“Randomized trials are needed to determine the best ways to treat conditions such as RA while trying to minimize cardiovascular, cancer, and infectious risks,” he said.

The study was sponsored by Pfizer. All authors reported financial involvements with Pfizer; most have financial involvements with other pharmaceutical companies as well; four authors are employees of Pfizer and three are also stockholders in the company. Dr. George reported involvements with the pharmaceutical industry.

Young children with allergies may be more likely to develop attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) by the time they’re 18, according to a large retrospective study.

“Our study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD,” Shay Nemet, MD, of the Kaplan Medical Center, Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. “The risk of those children to develop ASD was less significant.”

The researchers analyzed data from 117,022 consecutive children diagnosed with at least one allergic disorder – asthma, conjunctivitis, rhinitis, and drug, food, or skin allergy – and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.

The children who were diagnosed with one or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio, 2.45; 95% confidence interval, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.

Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.
 

Allergy correlation with ADHD and ASD

Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children’s Mercy Kansas City, Missouri, told this news organization that children and adults with neurodevelopmental differences are also more likely to have other health problems.

“Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood,” he added.

“Studies like this can’t be accomplished without large health care databases, but this approach has drawbacks, too,” Dr. Nadler said in an email. “Without more information about these patients’ co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations.”

Dr. Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, gender, and number of annual visits, the link between allergy and ASD diagnosis was not significant.

“It is important to remember not to interpret these study results as causal,” he added.

Desha M. Jordan, MD, FAAP, an assistant professor of pediatrics at UPMC Children’s Hospital of Pittsburgh, called the study “an interesting new area that has been speculated about for some time” and “one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions.”
 

More questions for future studies

Health care providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.

Although symptoms and diagnoses were confirmed for all patients, the study’s retrospective design and the possibility of recall bias were limitations, said Dr. Jordan in an email. She also was not involved in the study.

“For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child’s past, while the family of a child without these conditions may not have recalled allergic symptoms as important,” she explained.

Another question that arises is whether some patients were treated and managed well while others were not and whether this disparity in care affected the development or severity of ADHD or ASD, she added.

“Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?”

“While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research,” Dr. Jordan said. “More studies in this area are necessary to confirm the findings of this paper.”

The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr. Nadler, and Dr. Jordan report no relevant financial relationships.

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

Young children with allergies may be more likely to develop attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) by the time they’re 18, according to a large retrospective study.

“Our study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD,” Shay Nemet, MD, of the Kaplan Medical Center, Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. “The risk of those children to develop ASD was less significant.”

The researchers analyzed data from 117,022 consecutive children diagnosed with at least one allergic disorder – asthma, conjunctivitis, rhinitis, and drug, food, or skin allergy – and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.

The children who were diagnosed with one or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio, 2.45; 95% confidence interval, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.

Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.
 

Allergy correlation with ADHD and ASD

Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children’s Mercy Kansas City, Missouri, told this news organization that children and adults with neurodevelopmental differences are also more likely to have other health problems.

“Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood,” he added.

“Studies like this can’t be accomplished without large health care databases, but this approach has drawbacks, too,” Dr. Nadler said in an email. “Without more information about these patients’ co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations.”

Dr. Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, gender, and number of annual visits, the link between allergy and ASD diagnosis was not significant.

“It is important to remember not to interpret these study results as causal,” he added.

Desha M. Jordan, MD, FAAP, an assistant professor of pediatrics at UPMC Children’s Hospital of Pittsburgh, called the study “an interesting new area that has been speculated about for some time” and “one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions.”
 

More questions for future studies

Health care providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.

Although symptoms and diagnoses were confirmed for all patients, the study’s retrospective design and the possibility of recall bias were limitations, said Dr. Jordan in an email. She also was not involved in the study.

“For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child’s past, while the family of a child without these conditions may not have recalled allergic symptoms as important,” she explained.

Another question that arises is whether some patients were treated and managed well while others were not and whether this disparity in care affected the development or severity of ADHD or ASD, she added.

“Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?”

“While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research,” Dr. Jordan said. “More studies in this area are necessary to confirm the findings of this paper.”

The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr. Nadler, and Dr. Jordan report no relevant financial relationships.

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

Young children with allergies may be more likely to develop attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) by the time they’re 18, according to a large retrospective study.

“Our study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD,” Shay Nemet, MD, of the Kaplan Medical Center, Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. “The risk of those children to develop ASD was less significant.”

The researchers analyzed data from 117,022 consecutive children diagnosed with at least one allergic disorder – asthma, conjunctivitis, rhinitis, and drug, food, or skin allergy – and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.

The children who were diagnosed with one or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio, 2.45; 95% confidence interval, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.

Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.
 

Allergy correlation with ADHD and ASD

Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children’s Mercy Kansas City, Missouri, told this news organization that children and adults with neurodevelopmental differences are also more likely to have other health problems.

“Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood,” he added.

“Studies like this can’t be accomplished without large health care databases, but this approach has drawbacks, too,” Dr. Nadler said in an email. “Without more information about these patients’ co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations.”

Dr. Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, gender, and number of annual visits, the link between allergy and ASD diagnosis was not significant.

“It is important to remember not to interpret these study results as causal,” he added.

Desha M. Jordan, MD, FAAP, an assistant professor of pediatrics at UPMC Children’s Hospital of Pittsburgh, called the study “an interesting new area that has been speculated about for some time” and “one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions.”
 

More questions for future studies

Health care providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.

Although symptoms and diagnoses were confirmed for all patients, the study’s retrospective design and the possibility of recall bias were limitations, said Dr. Jordan in an email. She also was not involved in the study.

“For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child’s past, while the family of a child without these conditions may not have recalled allergic symptoms as important,” she explained.

Another question that arises is whether some patients were treated and managed well while others were not and whether this disparity in care affected the development or severity of ADHD or ASD, she added.

“Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?”

“While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research,” Dr. Jordan said. “More studies in this area are necessary to confirm the findings of this paper.”

The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr. Nadler, and Dr. Jordan report no relevant financial relationships.

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

Children born to mothers who take antibiotics during pregnancy may be at an increased risk of developing pediatric asthma and other diseases involved in the atopic march, a systematic review and meta-analysis reports.

“Antibiotic use during pregnancy is significantly associated with the development of asthma in children. Additionally prenatal antibiotic exposure is also associated with disorders present in the atopic march including atopic sensitization, dermatitis/eczema, food allergy, allergic rhinitis, and wheeze,” lead study author Alissa Cait, PhD, of Malaghan Institute of Medical Research in Wellington, New Zealand, and colleagues write in Allergy.

“Antibiotics account for 80% of prescribed medications during pregnancy, and it is estimated that 20%-25% of pregnant women receive at least one course of an antibiotic during this time period,” they add.

The researchers evaluated prenatal antibiotic exposure and the risk for childhood wheeze or asthma, as well as for diseases associated with the atopic march, by searching standard medical databases for controlled trials in English, German, French, Dutch, or Arabic involving the use of any antibiotic at any time during pregnancy and for atopic disease incidence in children with asthma or wheeze as primary outcome. They excluded reviews, preclinical data, and descriptive studies.

From the 6,060 citations the search returned, 11 prospective and 16 retrospective studies met the authors’ selection criteria. For each study, they evaluated risk of bias using the Newcastle-Ottawa Quality Assessment Scale, and they rated certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) protocol.

The studies, published between 2002 and 2020, were conducted in Europe, North America, Asia, and South America. Exposure to antibiotics during the prenatal period was assessed through unsupervised questionnaires, interviews by medical professionals, or extraction from official medical databases.

The results showed that:

• Antibiotic use during pregnancy was linked with increased relative risk of developing wheeze (relative risk, 1.51; 95% confidence interval, 1.17-1.94) or asthma (RR, 1.28; 95% CI, 1.22-1.34) during childhood.
• Antibiotic use during pregnancy also increased a child’s risk for eczema or dermatitis (RR, 1.28; 95% CI, 1.06-1.53) and allergic rhinitis (RR, 1.13; 95% CI, 1.02-1.25).
• Food allergy increased in one study (RR, 1.81; 95% CI, 1.11-2.95).

Quality of studies

“These results have importance for antibiotic stewardship throughout the prenatal period,” the authors write. However, due to issues including high heterogeneity, publication bias, and lack of population numbers in some studies, the overall quality of the evidence presented in the studies was low. Other limitations include mainly White and European study populations, underpowered studies, and study protocol inconsistencies.

“Though there is evidence that antibiotic treatment during pregnancy is a driver of the atopic march, due to a large heterogeneity between studies more research is needed to draw firm conclusions on this matter,” the authors add. “Future studies should employ and report more direct and objective measurement methods rather than self-reported questionnaires.”

Dustin D. Flannery, DO, MSCE, a neonatologist and clinical researcher in perinatal infectious diseases and neonatal antimicrobial resistance and stewardship at Children’s Hospital of Philadelphia, said in an email that the study was well done.

He noted, though, that “although the study reports an association, it cannot prove causation. The relationship between prenatal antibiotics and childhood allergic disorders is likely multifactorial and quite complex.”

He joins the authors in recommending further related research. “Due to the variation in how exposures and outcomes were defined across the studies, more rigorous research will be needed in this area.”

Despite the study’s limitations, “given that some studies have found associations between prenatal antibiotic exposure and childhood atopic and allergic disorders, including asthma, while other studies have not, this systematic review and meta-analysis asks an important question,” Dr. Flannery, who was not involved in the study, said in an interview.

“Investigators found a strong association between prenatal antibiotic exposure and risk of childhood asthma and other disorders,” he said. “This finding supports efforts to safely reduce antibiotic use during pregnancy.”

The study was supported by the Deutsche Forschungsgemeinschaft and by the Konrad Adenauer Foundation. The authors and Dr. Flannery have disclosed no relevant financial relationships.

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

Children born to mothers who take antibiotics during pregnancy may be at an increased risk of developing pediatric asthma and other diseases involved in the atopic march, a systematic review and meta-analysis reports.

“Antibiotic use during pregnancy is significantly associated with the development of asthma in children. Additionally prenatal antibiotic exposure is also associated with disorders present in the atopic march including atopic sensitization, dermatitis/eczema, food allergy, allergic rhinitis, and wheeze,” lead study author Alissa Cait, PhD, of Malaghan Institute of Medical Research in Wellington, New Zealand, and colleagues write in Allergy.

“Antibiotics account for 80% of prescribed medications during pregnancy, and it is estimated that 20%-25% of pregnant women receive at least one course of an antibiotic during this time period,” they add.

The researchers evaluated prenatal antibiotic exposure and the risk for childhood wheeze or asthma, as well as for diseases associated with the atopic march, by searching standard medical databases for controlled trials in English, German, French, Dutch, or Arabic involving the use of any antibiotic at any time during pregnancy and for atopic disease incidence in children with asthma or wheeze as primary outcome. They excluded reviews, preclinical data, and descriptive studies.

From the 6,060 citations the search returned, 11 prospective and 16 retrospective studies met the authors’ selection criteria. For each study, they evaluated risk of bias using the Newcastle-Ottawa Quality Assessment Scale, and they rated certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) protocol.

The studies, published between 2002 and 2020, were conducted in Europe, North America, Asia, and South America. Exposure to antibiotics during the prenatal period was assessed through unsupervised questionnaires, interviews by medical professionals, or extraction from official medical databases.

The results showed that:

• Antibiotic use during pregnancy was linked with increased relative risk of developing wheeze (relative risk, 1.51; 95% confidence interval, 1.17-1.94) or asthma (RR, 1.28; 95% CI, 1.22-1.34) during childhood.
• Antibiotic use during pregnancy also increased a child’s risk for eczema or dermatitis (RR, 1.28; 95% CI, 1.06-1.53) and allergic rhinitis (RR, 1.13; 95% CI, 1.02-1.25).
• Food allergy increased in one study (RR, 1.81; 95% CI, 1.11-2.95).

Quality of studies

“These results have importance for antibiotic stewardship throughout the prenatal period,” the authors write. However, due to issues including high heterogeneity, publication bias, and lack of population numbers in some studies, the overall quality of the evidence presented in the studies was low. Other limitations include mainly White and European study populations, underpowered studies, and study protocol inconsistencies.

“Though there is evidence that antibiotic treatment during pregnancy is a driver of the atopic march, due to a large heterogeneity between studies more research is needed to draw firm conclusions on this matter,” the authors add. “Future studies should employ and report more direct and objective measurement methods rather than self-reported questionnaires.”

Dustin D. Flannery, DO, MSCE, a neonatologist and clinical researcher in perinatal infectious diseases and neonatal antimicrobial resistance and stewardship at Children’s Hospital of Philadelphia, said in an email that the study was well done.

He noted, though, that “although the study reports an association, it cannot prove causation. The relationship between prenatal antibiotics and childhood allergic disorders is likely multifactorial and quite complex.”

He joins the authors in recommending further related research. “Due to the variation in how exposures and outcomes were defined across the studies, more rigorous research will be needed in this area.”

Despite the study’s limitations, “given that some studies have found associations between prenatal antibiotic exposure and childhood atopic and allergic disorders, including asthma, while other studies have not, this systematic review and meta-analysis asks an important question,” Dr. Flannery, who was not involved in the study, said in an interview.

“Investigators found a strong association between prenatal antibiotic exposure and risk of childhood asthma and other disorders,” he said. “This finding supports efforts to safely reduce antibiotic use during pregnancy.”

The study was supported by the Deutsche Forschungsgemeinschaft and by the Konrad Adenauer Foundation. The authors and Dr. Flannery have disclosed no relevant financial relationships.

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

Children born to mothers who take antibiotics during pregnancy may be at an increased risk of developing pediatric asthma and other diseases involved in the atopic march, a systematic review and meta-analysis reports.

“Antibiotic use during pregnancy is significantly associated with the development of asthma in children. Additionally prenatal antibiotic exposure is also associated with disorders present in the atopic march including atopic sensitization, dermatitis/eczema, food allergy, allergic rhinitis, and wheeze,” lead study author Alissa Cait, PhD, of Malaghan Institute of Medical Research in Wellington, New Zealand, and colleagues write in Allergy.

“Antibiotics account for 80% of prescribed medications during pregnancy, and it is estimated that 20%-25% of pregnant women receive at least one course of an antibiotic during this time period,” they add.

The researchers evaluated prenatal antibiotic exposure and the risk for childhood wheeze or asthma, as well as for diseases associated with the atopic march, by searching standard medical databases for controlled trials in English, German, French, Dutch, or Arabic involving the use of any antibiotic at any time during pregnancy and for atopic disease incidence in children with asthma or wheeze as primary outcome. They excluded reviews, preclinical data, and descriptive studies.

From the 6,060 citations the search returned, 11 prospective and 16 retrospective studies met the authors’ selection criteria. For each study, they evaluated risk of bias using the Newcastle-Ottawa Quality Assessment Scale, and they rated certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) protocol.

The studies, published between 2002 and 2020, were conducted in Europe, North America, Asia, and South America. Exposure to antibiotics during the prenatal period was assessed through unsupervised questionnaires, interviews by medical professionals, or extraction from official medical databases.

The results showed that:

• Antibiotic use during pregnancy was linked with increased relative risk of developing wheeze (relative risk, 1.51; 95% confidence interval, 1.17-1.94) or asthma (RR, 1.28; 95% CI, 1.22-1.34) during childhood.
• Antibiotic use during pregnancy also increased a child’s risk for eczema or dermatitis (RR, 1.28; 95% CI, 1.06-1.53) and allergic rhinitis (RR, 1.13; 95% CI, 1.02-1.25).
• Food allergy increased in one study (RR, 1.81; 95% CI, 1.11-2.95).

Quality of studies

“These results have importance for antibiotic stewardship throughout the prenatal period,” the authors write. However, due to issues including high heterogeneity, publication bias, and lack of population numbers in some studies, the overall quality of the evidence presented in the studies was low. Other limitations include mainly White and European study populations, underpowered studies, and study protocol inconsistencies.

“Though there is evidence that antibiotic treatment during pregnancy is a driver of the atopic march, due to a large heterogeneity between studies more research is needed to draw firm conclusions on this matter,” the authors add. “Future studies should employ and report more direct and objective measurement methods rather than self-reported questionnaires.”

Dustin D. Flannery, DO, MSCE, a neonatologist and clinical researcher in perinatal infectious diseases and neonatal antimicrobial resistance and stewardship at Children’s Hospital of Philadelphia, said in an email that the study was well done.

He noted, though, that “although the study reports an association, it cannot prove causation. The relationship between prenatal antibiotics and childhood allergic disorders is likely multifactorial and quite complex.”

He joins the authors in recommending further related research. “Due to the variation in how exposures and outcomes were defined across the studies, more rigorous research will be needed in this area.”

Despite the study’s limitations, “given that some studies have found associations between prenatal antibiotic exposure and childhood atopic and allergic disorders, including asthma, while other studies have not, this systematic review and meta-analysis asks an important question,” Dr. Flannery, who was not involved in the study, said in an interview.

“Investigators found a strong association between prenatal antibiotic exposure and risk of childhood asthma and other disorders,” he said. “This finding supports efforts to safely reduce antibiotic use during pregnancy.”

The study was supported by the Deutsche Forschungsgemeinschaft and by the Konrad Adenauer Foundation. The authors and Dr. Flannery have disclosed no relevant financial relationships.

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

It’s rare for a child to die after a tonsillectomy, but children who die are more likely to have a complex chronic condition such as cerebral palsy or Down syndrome, according to a retrospective cohort study published in JAMA.

“Among children undergoing tonsillectomy, the rate of postoperative death was 7 per 100,000 operations overall, [but] among children with complex chronic conditions, the rate of postoperative death was 117 per 100,000 operations, representing 44% of overall deaths,” write researchers at the University of Wisconsin–Madison. “These findings may inform decisionmaking for pediatric tonsillectomy.”

The rate of death in children after tonsillectomy has been uncertain, the authors write. Specific mortality rates for children at increased risk for complications, including those under 3 years old and those with sleep-disordered breathing or complex chronic conditions, have not been available.

To learn how likely children undergoing tonsillectomy are to die after their surgery, as well as which children are most at risk, lead study author M. Bruce Edmonson, MD, MPH, department of pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, and his colleagues drew data from five states, including ambulatory surgery, inpatient, and emergency department discharge data sets provided by the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for California, Florida, Maryland, New York, and Wisconsin.

Participants included 504,262 patients under 21 years of age whose discharge records linked their inpatient or outpatient tonsillectomy, with or without adenoidectomy, with at least 90 days of follow-up.

In a longitudinal analysis, the research team investigated postoperative death within 30 days or during a surgical stay lasting over 30 days. They calculated postoperative mortality per 100,000 operations, both overall and classified by age group, sleep-disordered breathing, and complex chronic conditions.

The 504,262 children ranged in age from 0 to 20 years and underwent a total of 505,182 tonsillectomies. Of these, 10.1% were performed in children aged under 3 years, 28.9% in children with sleep-disordered breathing, and 2.8% in those with complex chronic conditions.

The 36 linked postoperative deaths occurred between 2 and 20.5 days after surgical admission, and 19 (53%) of the deaths occurred after surgical discharge.

The unadjusted mortality rate was 7.04 (95% confidence interval, 4.97-9.98) deaths per 100,000 procedures. In multivariable models, children younger than 3 years and children with sleep-disordered breathing were not significantly more likely to die.

But children with complex chronic conditions were significantly more likely to die than were children without those conditions (117.22 vs. 3.87 deaths per 100,000 procedures, respectively).

Children with complex chronic conditions underwent only 2.8% of all tonsillectomies, but they accounted for 44% of postoperative deaths. Most deaths linked with complex chronic conditions occurred among children with neurologic, neuromuscular, congenital, or genetic disorders.
 

Findings can help providers advise patients and their families about tonsillectomy risks

Kavita Dedhia, MD, MSHP, attending otolaryngologist, Division of Otolaryngology, Children’s Hospital of Philadelphia, Pennsylvania, told this news organization that she was not surprised by the findings.

“This study suggests that mortality is an extremely rare complication of tonsillectomy, and that children with complex medical conditions are at highest risk,” Dr. Dedhia, who was not involved in the study, said in an email.

“Due to their underlying comorbidities, medically fragile children are considered to be at higher risk while undergoing anesthesia and surgical procedures,” she added.

Dr. Dedhia noted that nonpatient factors the study did not explore may have affected the mortality rates, including each hospital’s experience with managing children with complex medical conditions, as well as whether the hospitals were tertiary care facilities, and pediatric or adult hospitals.

She would like to know what hospital or practice characteristics may have contributed to the mortality risk and whether increased mortality in these patients is limited to tonsillectomy or is also found with other surgical procedures.

“The strength of this study is that it is large and multi-regional and that it informs providers about patient factors impacting mortality in pediatric tonsillectomy,” Dr. Dedhia said. “This study arms surgeons with data to discuss mortality risk with the families of medically complex children undergoing tonsillectomy.”

The study authors and Dr. Dedhia report no relevant financial relationships. Funding information was not provided.

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

It’s rare for a child to die after a tonsillectomy, but children who die are more likely to have a complex chronic condition such as cerebral palsy or Down syndrome, according to a retrospective cohort study published in JAMA.

“Among children undergoing tonsillectomy, the rate of postoperative death was 7 per 100,000 operations overall, [but] among children with complex chronic conditions, the rate of postoperative death was 117 per 100,000 operations, representing 44% of overall deaths,” write researchers at the University of Wisconsin–Madison. “These findings may inform decisionmaking for pediatric tonsillectomy.”

The rate of death in children after tonsillectomy has been uncertain, the authors write. Specific mortality rates for children at increased risk for complications, including those under 3 years old and those with sleep-disordered breathing or complex chronic conditions, have not been available.

To learn how likely children undergoing tonsillectomy are to die after their surgery, as well as which children are most at risk, lead study author M. Bruce Edmonson, MD, MPH, department of pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, and his colleagues drew data from five states, including ambulatory surgery, inpatient, and emergency department discharge data sets provided by the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for California, Florida, Maryland, New York, and Wisconsin.

Participants included 504,262 patients under 21 years of age whose discharge records linked their inpatient or outpatient tonsillectomy, with or without adenoidectomy, with at least 90 days of follow-up.

In a longitudinal analysis, the research team investigated postoperative death within 30 days or during a surgical stay lasting over 30 days. They calculated postoperative mortality per 100,000 operations, both overall and classified by age group, sleep-disordered breathing, and complex chronic conditions.

The 504,262 children ranged in age from 0 to 20 years and underwent a total of 505,182 tonsillectomies. Of these, 10.1% were performed in children aged under 3 years, 28.9% in children with sleep-disordered breathing, and 2.8% in those with complex chronic conditions.

The 36 linked postoperative deaths occurred between 2 and 20.5 days after surgical admission, and 19 (53%) of the deaths occurred after surgical discharge.

The unadjusted mortality rate was 7.04 (95% confidence interval, 4.97-9.98) deaths per 100,000 procedures. In multivariable models, children younger than 3 years and children with sleep-disordered breathing were not significantly more likely to die.

But children with complex chronic conditions were significantly more likely to die than were children without those conditions (117.22 vs. 3.87 deaths per 100,000 procedures, respectively).

Children with complex chronic conditions underwent only 2.8% of all tonsillectomies, but they accounted for 44% of postoperative deaths. Most deaths linked with complex chronic conditions occurred among children with neurologic, neuromuscular, congenital, or genetic disorders.
 

Findings can help providers advise patients and their families about tonsillectomy risks

Kavita Dedhia, MD, MSHP, attending otolaryngologist, Division of Otolaryngology, Children’s Hospital of Philadelphia, Pennsylvania, told this news organization that she was not surprised by the findings.

“This study suggests that mortality is an extremely rare complication of tonsillectomy, and that children with complex medical conditions are at highest risk,” Dr. Dedhia, who was not involved in the study, said in an email.

“Due to their underlying comorbidities, medically fragile children are considered to be at higher risk while undergoing anesthesia and surgical procedures,” she added.

Dr. Dedhia noted that nonpatient factors the study did not explore may have affected the mortality rates, including each hospital’s experience with managing children with complex medical conditions, as well as whether the hospitals were tertiary care facilities, and pediatric or adult hospitals.

She would like to know what hospital or practice characteristics may have contributed to the mortality risk and whether increased mortality in these patients is limited to tonsillectomy or is also found with other surgical procedures.

“The strength of this study is that it is large and multi-regional and that it informs providers about patient factors impacting mortality in pediatric tonsillectomy,” Dr. Dedhia said. “This study arms surgeons with data to discuss mortality risk with the families of medically complex children undergoing tonsillectomy.”

The study authors and Dr. Dedhia report no relevant financial relationships. Funding information was not provided.

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

It’s rare for a child to die after a tonsillectomy, but children who die are more likely to have a complex chronic condition such as cerebral palsy or Down syndrome, according to a retrospective cohort study published in JAMA.

“Among children undergoing tonsillectomy, the rate of postoperative death was 7 per 100,000 operations overall, [but] among children with complex chronic conditions, the rate of postoperative death was 117 per 100,000 operations, representing 44% of overall deaths,” write researchers at the University of Wisconsin–Madison. “These findings may inform decisionmaking for pediatric tonsillectomy.”

The rate of death in children after tonsillectomy has been uncertain, the authors write. Specific mortality rates for children at increased risk for complications, including those under 3 years old and those with sleep-disordered breathing or complex chronic conditions, have not been available.

To learn how likely children undergoing tonsillectomy are to die after their surgery, as well as which children are most at risk, lead study author M. Bruce Edmonson, MD, MPH, department of pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, and his colleagues drew data from five states, including ambulatory surgery, inpatient, and emergency department discharge data sets provided by the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for California, Florida, Maryland, New York, and Wisconsin.

Participants included 504,262 patients under 21 years of age whose discharge records linked their inpatient or outpatient tonsillectomy, with or without adenoidectomy, with at least 90 days of follow-up.

In a longitudinal analysis, the research team investigated postoperative death within 30 days or during a surgical stay lasting over 30 days. They calculated postoperative mortality per 100,000 operations, both overall and classified by age group, sleep-disordered breathing, and complex chronic conditions.

The 504,262 children ranged in age from 0 to 20 years and underwent a total of 505,182 tonsillectomies. Of these, 10.1% were performed in children aged under 3 years, 28.9% in children with sleep-disordered breathing, and 2.8% in those with complex chronic conditions.

The 36 linked postoperative deaths occurred between 2 and 20.5 days after surgical admission, and 19 (53%) of the deaths occurred after surgical discharge.

The unadjusted mortality rate was 7.04 (95% confidence interval, 4.97-9.98) deaths per 100,000 procedures. In multivariable models, children younger than 3 years and children with sleep-disordered breathing were not significantly more likely to die.

But children with complex chronic conditions were significantly more likely to die than were children without those conditions (117.22 vs. 3.87 deaths per 100,000 procedures, respectively).

Children with complex chronic conditions underwent only 2.8% of all tonsillectomies, but they accounted for 44% of postoperative deaths. Most deaths linked with complex chronic conditions occurred among children with neurologic, neuromuscular, congenital, or genetic disorders.
 

Findings can help providers advise patients and their families about tonsillectomy risks

Kavita Dedhia, MD, MSHP, attending otolaryngologist, Division of Otolaryngology, Children’s Hospital of Philadelphia, Pennsylvania, told this news organization that she was not surprised by the findings.

“This study suggests that mortality is an extremely rare complication of tonsillectomy, and that children with complex medical conditions are at highest risk,” Dr. Dedhia, who was not involved in the study, said in an email.

“Due to their underlying comorbidities, medically fragile children are considered to be at higher risk while undergoing anesthesia and surgical procedures,” she added.

Dr. Dedhia noted that nonpatient factors the study did not explore may have affected the mortality rates, including each hospital’s experience with managing children with complex medical conditions, as well as whether the hospitals were tertiary care facilities, and pediatric or adult hospitals.

She would like to know what hospital or practice characteristics may have contributed to the mortality risk and whether increased mortality in these patients is limited to tonsillectomy or is also found with other surgical procedures.

“The strength of this study is that it is large and multi-regional and that it informs providers about patient factors impacting mortality in pediatric tonsillectomy,” Dr. Dedhia said. “This study arms surgeons with data to discuss mortality risk with the families of medically complex children undergoing tonsillectomy.”

The study authors and Dr. Dedhia report no relevant financial relationships. Funding information was not provided.

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

According to a consensus study, many infants in some countries are misdiagnosed with allergy to cow, sheep, or goat milk, and they’re prescribed specialized formulas they don’t need.

“Milk allergy overdiagnosis is common in some regions and can potentially harm mothers and infants,” the authors write in Clinical & Experimental Allergy. “These new consensus recommendations on the safe detection and management of milk allergy in children under 2 years aim to reduce harms associated with milk allergy overdiagnosis.”

“This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and [to] support ... breastfeeding and less use of specialized formula, compared with current guidelines,” they add.

Up to 1% of European infants 2 years of age and younger are considered allergic to cow’s milk. Prescriptions for specialized formula for bottle-fed infants allergic to cow’s milk in Australia, England, and Norway have grown to over 10 times the expected volumes.

Lead study author Hilary I. Allen, National Heart and Lung Institute, Imperial College London, and her colleagues on several continents developed practical guidance for providers on safely detecting and managing milk allergy in infants.

Due to lack of high-certainty research evidence in this area, they used the Delphi consensus method.

The study involved two rounds of anonymous consensus-building surveys and one formal meeting in 2021.

The team identified experts from diverse geographic and cultural settings by searching medical databases for the term “milk hypersensitivity.” They asked those experts to recommend colleagues. The researchers also contacted experts with ties to international professional organizations, such as the International Board of Lactation Consultant Examiners, as well as societies associated with the World Allergy Organization.

The 17 study participants included clinicians and researchers in general practice, health visiting, lactation support, midwifery, nutrition, and relevant areas of pediatrics from Africa, Asia, Australia, Europe, the Middle East, and North America. Experts with recent conflicts of interest with the breastmilk substitute (formula) industry were excluded from the study. Five authors of earlier milk allergy guidelines and seven parents contributed feedback.

In each survey round, participants used a nine-point scale to rank the importance of each proposed statement that addressed prevention of overdiagnosis or underdiagnosis, support of breastfeeding women, and the role of specialized formula products.

Based on the number of total points participants assigned, each statement was classified as “essential,” “recommended,” “no consensus,” or “excluded” due to lack of relevance.

The experts agreed on 38 essential statements in several categories, including:

• Maternal dietary restriction is often not necessary to manage milk allergy
• In infants with chronic symptoms who are exclusively breastfed, milk allergy diagnosis should be considered only in specific, rare circumstances
• Milk allergy diagnosis does not usually need to be considered for stool changes, aversive feeding, or occasional spots of blood in stool, if not related in time with milk protein ingestion

The consensus recommendations provide more restrictive criteria than earlier guidelines for detecting milk allergy, fewer maternal dietary exclusions, and less use of specialized formula.
 

During an infant formula shortage in the U.S., a timely study

Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program, Children’s Mercy Kansas City, Missouri, welcomed the study’s engagement of specialists in various fields and avoidance of bias from formula companies.

“Food allergies have received a lot of attention, especially through websites and social media,” Ms. Shroba, who was not involved in the study, told this news organization in an email. “Unfortunately, a lot of that information is incorrect and can lead to misunderstanding and misdiagnosis.”

“This article helps guide practitioners through identifying the concerning symptoms of milk allergy versus normal infant symptoms,” she said. “It can help providers discern when testing, elimination diets, and changes in formula are warranted.

“This guidance emphasizes the reproducibility and specificity of symptoms, which are key elements of a food allergy diagnosis,” she explained. “By eliminating unnecessary milk allergy labeling, we can keep infants on appropriate diets for their age, such as breastfeeding or milk-based formulas. Proper diagnosis can also reduce unnecessary financial strain of specialty formulas, stress to the family regarding feedings, and a restrictive diet for the breastfeeding mother.”

The study will be useful to a wide range of health care providers, Jennifer Anne Dantzer, MD, assistant professor of pediatrics, Johns Hopkins Medicine, Baltimore, said in an email.

“With the current formula shortage, there has perhaps never been a more important time to do this study and provide additional guidance on who does or does not need special formula,” noted Dr. Dantzer, who also was not involved in the study. “A milk allergy diagnosis impacts the child and the family, so it is very important to avoid overdiagnosis and to support the breastfeeding mother.”

“These findings should provide reassurance that dietary exclusions for the breastfeeding mother are not needed for most children with milk allergy,” she said. “If a milk allergy is suspected, the child should be referred to an allergist.”

The authors recommend further related research into the safety and effectiveness of using the guidance in practice.

One coauthor reports financial relationships with a biotech company. Ms. Allen and her remaining coauthors, as well as Ms. Shroba and Dr. Dantzer, report no relevant financial relationships. The study was funded through fellowships.

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

According to a consensus study, many infants in some countries are misdiagnosed with allergy to cow, sheep, or goat milk, and they’re prescribed specialized formulas they don’t need.

“Milk allergy overdiagnosis is common in some regions and can potentially harm mothers and infants,” the authors write in Clinical & Experimental Allergy. “These new consensus recommendations on the safe detection and management of milk allergy in children under 2 years aim to reduce harms associated with milk allergy overdiagnosis.”

“This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and [to] support ... breastfeeding and less use of specialized formula, compared with current guidelines,” they add.

Up to 1% of European infants 2 years of age and younger are considered allergic to cow’s milk. Prescriptions for specialized formula for bottle-fed infants allergic to cow’s milk in Australia, England, and Norway have grown to over 10 times the expected volumes.

Lead study author Hilary I. Allen, National Heart and Lung Institute, Imperial College London, and her colleagues on several continents developed practical guidance for providers on safely detecting and managing milk allergy in infants.

Due to lack of high-certainty research evidence in this area, they used the Delphi consensus method.

The study involved two rounds of anonymous consensus-building surveys and one formal meeting in 2021.

The team identified experts from diverse geographic and cultural settings by searching medical databases for the term “milk hypersensitivity.” They asked those experts to recommend colleagues. The researchers also contacted experts with ties to international professional organizations, such as the International Board of Lactation Consultant Examiners, as well as societies associated with the World Allergy Organization.

The 17 study participants included clinicians and researchers in general practice, health visiting, lactation support, midwifery, nutrition, and relevant areas of pediatrics from Africa, Asia, Australia, Europe, the Middle East, and North America. Experts with recent conflicts of interest with the breastmilk substitute (formula) industry were excluded from the study. Five authors of earlier milk allergy guidelines and seven parents contributed feedback.

In each survey round, participants used a nine-point scale to rank the importance of each proposed statement that addressed prevention of overdiagnosis or underdiagnosis, support of breastfeeding women, and the role of specialized formula products.

Based on the number of total points participants assigned, each statement was classified as “essential,” “recommended,” “no consensus,” or “excluded” due to lack of relevance.

The experts agreed on 38 essential statements in several categories, including:

• Maternal dietary restriction is often not necessary to manage milk allergy
• In infants with chronic symptoms who are exclusively breastfed, milk allergy diagnosis should be considered only in specific, rare circumstances
• Milk allergy diagnosis does not usually need to be considered for stool changes, aversive feeding, or occasional spots of blood in stool, if not related in time with milk protein ingestion

The consensus recommendations provide more restrictive criteria than earlier guidelines for detecting milk allergy, fewer maternal dietary exclusions, and less use of specialized formula.
 

During an infant formula shortage in the U.S., a timely study

Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program, Children’s Mercy Kansas City, Missouri, welcomed the study’s engagement of specialists in various fields and avoidance of bias from formula companies.

“Food allergies have received a lot of attention, especially through websites and social media,” Ms. Shroba, who was not involved in the study, told this news organization in an email. “Unfortunately, a lot of that information is incorrect and can lead to misunderstanding and misdiagnosis.”

“This article helps guide practitioners through identifying the concerning symptoms of milk allergy versus normal infant symptoms,” she said. “It can help providers discern when testing, elimination diets, and changes in formula are warranted.

“This guidance emphasizes the reproducibility and specificity of symptoms, which are key elements of a food allergy diagnosis,” she explained. “By eliminating unnecessary milk allergy labeling, we can keep infants on appropriate diets for their age, such as breastfeeding or milk-based formulas. Proper diagnosis can also reduce unnecessary financial strain of specialty formulas, stress to the family regarding feedings, and a restrictive diet for the breastfeeding mother.”

The study will be useful to a wide range of health care providers, Jennifer Anne Dantzer, MD, assistant professor of pediatrics, Johns Hopkins Medicine, Baltimore, said in an email.

“With the current formula shortage, there has perhaps never been a more important time to do this study and provide additional guidance on who does or does not need special formula,” noted Dr. Dantzer, who also was not involved in the study. “A milk allergy diagnosis impacts the child and the family, so it is very important to avoid overdiagnosis and to support the breastfeeding mother.”

“These findings should provide reassurance that dietary exclusions for the breastfeeding mother are not needed for most children with milk allergy,” she said. “If a milk allergy is suspected, the child should be referred to an allergist.”

The authors recommend further related research into the safety and effectiveness of using the guidance in practice.

One coauthor reports financial relationships with a biotech company. Ms. Allen and her remaining coauthors, as well as Ms. Shroba and Dr. Dantzer, report no relevant financial relationships. The study was funded through fellowships.

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

According to a consensus study, many infants in some countries are misdiagnosed with allergy to cow, sheep, or goat milk, and they’re prescribed specialized formulas they don’t need.

“Milk allergy overdiagnosis is common in some regions and can potentially harm mothers and infants,” the authors write in Clinical & Experimental Allergy. “These new consensus recommendations on the safe detection and management of milk allergy in children under 2 years aim to reduce harms associated with milk allergy overdiagnosis.”

“This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and [to] support ... breastfeeding and less use of specialized formula, compared with current guidelines,” they add.

Up to 1% of European infants 2 years of age and younger are considered allergic to cow’s milk. Prescriptions for specialized formula for bottle-fed infants allergic to cow’s milk in Australia, England, and Norway have grown to over 10 times the expected volumes.

Lead study author Hilary I. Allen, National Heart and Lung Institute, Imperial College London, and her colleagues on several continents developed practical guidance for providers on safely detecting and managing milk allergy in infants.

Due to lack of high-certainty research evidence in this area, they used the Delphi consensus method.

The study involved two rounds of anonymous consensus-building surveys and one formal meeting in 2021.

The team identified experts from diverse geographic and cultural settings by searching medical databases for the term “milk hypersensitivity.” They asked those experts to recommend colleagues. The researchers also contacted experts with ties to international professional organizations, such as the International Board of Lactation Consultant Examiners, as well as societies associated with the World Allergy Organization.

The 17 study participants included clinicians and researchers in general practice, health visiting, lactation support, midwifery, nutrition, and relevant areas of pediatrics from Africa, Asia, Australia, Europe, the Middle East, and North America. Experts with recent conflicts of interest with the breastmilk substitute (formula) industry were excluded from the study. Five authors of earlier milk allergy guidelines and seven parents contributed feedback.

In each survey round, participants used a nine-point scale to rank the importance of each proposed statement that addressed prevention of overdiagnosis or underdiagnosis, support of breastfeeding women, and the role of specialized formula products.

Based on the number of total points participants assigned, each statement was classified as “essential,” “recommended,” “no consensus,” or “excluded” due to lack of relevance.

The experts agreed on 38 essential statements in several categories, including:

• Maternal dietary restriction is often not necessary to manage milk allergy
• In infants with chronic symptoms who are exclusively breastfed, milk allergy diagnosis should be considered only in specific, rare circumstances
• Milk allergy diagnosis does not usually need to be considered for stool changes, aversive feeding, or occasional spots of blood in stool, if not related in time with milk protein ingestion

The consensus recommendations provide more restrictive criteria than earlier guidelines for detecting milk allergy, fewer maternal dietary exclusions, and less use of specialized formula.
 

During an infant formula shortage in the U.S., a timely study

Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program, Children’s Mercy Kansas City, Missouri, welcomed the study’s engagement of specialists in various fields and avoidance of bias from formula companies.

“Food allergies have received a lot of attention, especially through websites and social media,” Ms. Shroba, who was not involved in the study, told this news organization in an email. “Unfortunately, a lot of that information is incorrect and can lead to misunderstanding and misdiagnosis.”

“This article helps guide practitioners through identifying the concerning symptoms of milk allergy versus normal infant symptoms,” she said. “It can help providers discern when testing, elimination diets, and changes in formula are warranted.

“This guidance emphasizes the reproducibility and specificity of symptoms, which are key elements of a food allergy diagnosis,” she explained. “By eliminating unnecessary milk allergy labeling, we can keep infants on appropriate diets for their age, such as breastfeeding or milk-based formulas. Proper diagnosis can also reduce unnecessary financial strain of specialty formulas, stress to the family regarding feedings, and a restrictive diet for the breastfeeding mother.”

The study will be useful to a wide range of health care providers, Jennifer Anne Dantzer, MD, assistant professor of pediatrics, Johns Hopkins Medicine, Baltimore, said in an email.

“With the current formula shortage, there has perhaps never been a more important time to do this study and provide additional guidance on who does or does not need special formula,” noted Dr. Dantzer, who also was not involved in the study. “A milk allergy diagnosis impacts the child and the family, so it is very important to avoid overdiagnosis and to support the breastfeeding mother.”

“These findings should provide reassurance that dietary exclusions for the breastfeeding mother are not needed for most children with milk allergy,” she said. “If a milk allergy is suspected, the child should be referred to an allergist.”

The authors recommend further related research into the safety and effectiveness of using the guidance in practice.

One coauthor reports financial relationships with a biotech company. Ms. Allen and her remaining coauthors, as well as Ms. Shroba and Dr. Dantzer, report no relevant financial relationships. The study was funded through fellowships.

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

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Teamwork by a wide range of professional staff, coupled with support from leadership, enabled one academic community hospital to cut its rate of hospital-onset Clostridioides difficile infections (HO-CDIs) by almost two-thirds in 1 year and by over three-quarters in 3 years, a study published in the American Journal of Infection Control reports.

C. diff. is a major health threat. According to the U.S. Centers for Disease Control and Prevention, CDIs, mainly linked with hospitals, caused an estimated 223,900 cases in hospitalized patients and 12,800 deaths in the United States in 2017.

“The interventions and outcomes of the project improved patient care by ensuring early testing, diagnosis, treatment if warranted, and proper isolation, which helped reduce C. diff. transmission to staff and other patients,” lead study author Cherith Walter, MSN, RN, a clinical nurse specialist at Emory Saint Joseph’s Hospital, Atlanta, told this news organization. “Had we not worked together as a team, we would not have had the ability to carry out such a robust project,” she added in an email.

Each HO-CDI case costs a health care system an estimated $12,313, and high rates of HO-CDIs incur fines from the Hospital-Acquired Condition Reduction Program of the Centers for Medicare & Medicaid Services (CMS), the authors write.
 

A diverse staff team collaborated

Emory Saint Joseph’s, a 410-bed hospital in Atlanta, had a history of being above the national CMS benchmark for HO-CDIs. To reduce these infections, comply with CMS requirements, and avoid fines, Ms. Walter and colleagues launched a quality improvement project between 2015 and 2020.

With the approval of the chief nursing officer, chief quality officer, and hospital board, researchers mobilized a diverse team of professionals: a clinical nurse specialist, a physician champion, unit nurse champions, a hospital epidemiologist, an infection preventionist, a clinical microbiologist, an antimicrobial stewardship pharmacist, and an environmental services representative.

The team investigated what caused their hospital’s HO-CDIs from 2014 through 2016 and developed appropriate, evidence-based infection prevention interventions. The integrated approach involved:

• Diagnostic stewardship, including a diarrhea decision-tree algorithm that enabled nurses to order tests of any loose or unformed stool for C. diff. during the first 3 days of admission.
• Enhanced environmental cleaning, which involved switching from sporicidal disinfectant only in isolation rooms to using a more effective Environmental Protection Agency–approved sporicidal disinfectant containing hydrogen peroxide and peracetic acid in all patient rooms for daily cleaning and after discharge. Every day, high-touch surfaces in C. diff. isolation rooms were cleaned and shared equipment was disinfected with bleach wipes. After patient discharge, staff cleaned mattresses on all sides, wiped walls with disinfectant, and used ultraviolet light.
• Antimicrobial stewardship. Formulary fluoroquinolones were removed as standalone orders and made available only through order sets with built-in clinical decision support.
• Education of staff on best practices, through emails, flyers, meetings, and training sessions. Two nurses needed to approve the appropriateness of testing specific specimens for CDI. All HO-CDIs were reviewed and findings presented at CDI team meetings.
• Accountability. Staff on the team and units received emailed notices about compliance issues and held meetings to discuss how to improve compliance.

After 1 year, HO-CDI incidence dropped 63% from baseline, from above 12 cases per 10,000 patient-days to 4.72 per 10,000 patient-days. And after 3 years, infections dropped 77% to 2.80 per 10,000 patient-days.

The hospital’s HO-CDI standardized infection ratio – the total number of infections divided by the National Healthcare Safety Network’s risk-adjusted predicted number of infections – dropped below the national benchmark, from 1.11 in 2015 to 0.43 in 2020.

The hospital also increased testing of appropriate patients for CDI within the first 3 days of admission, from 54% in 2014 to 81% in late 2019.

“By testing patients within 3 days of admission, we discovered that many had acquired C. diff. before admission,” Ms. Walter said. “I don’t think we realized how prevalent C. diff. was in the community.”

Benjamin D. Galvan, MLS(ASCP), CIC, an infection preventionist at Tampa General Hospital and a member of the Association for Professionals in Infection Control and Epidemiology, welcomed the study’s results.  

“Effective collaboration within the health care setting is a highly effective way to implement and sustain evidence-based practices related to infection reduction. When buy-in is obtained from the top, and pertinent stakeholders are engaged for their expertise, we can see sustainable change and improved patient outcomes,” Mr. Galvan, who was not involved in the study, said in an email.

“The researchers did a fantastic job,” he added. “I am grateful to see this important work addressed in the literature, as it will only improve buy-in for improvement efforts aimed at reducing infections moving forward across the health care continuum.”

Douglas S. Paauw, MD, a professor of medicine and chair for patient-centered clinical education at the University of Washington School of Medicine, Seattle, said that the team’s most important interventions were changing the environmental cleaning protocol and using agents that kill C. diff. spores.

“We know that as many as 10%-20% of hospitalized patients carry C. diff. Cleaning only the rooms where you know you have C. diff. (isolation rooms) will miss most of it,” said Dr. Paauw, who was also not involved in the study. “Cleaning every room with cleaners that actually work is very important but costs money.”
 

Handwashing with soap and water works, alcohol hand gels do not

“We know that handwashing with soap and water is the most important way to prevent hospital C. diff. transmission,” Dr. Paauw noted. “Handwashing protocols implemented prior to the study were probably a big part of the team’s success.”

Handwashing with soap and water works but alcohol hand gels do not, he cautioned.

“C. diff. rates in hospitals went up years ago when we started putting alcohol gels outside patients’ rooms,” Dr. Paauw explained. “Now, instead of washing their hands, staff quickly pump gel before they see patients. Applying gel is easy, but gel does not eliminate C. diff. spores. Handwashing is such a simple way to fix the C. diff. problem, but doctors don’t take the time.”

“We need to take the C. diff. problem seriously. We have enough information, and we know the right things to do. We need to wash our hands. We need to clean the rooms. We need to stop cutting corners if we want to give good care,” he said.

The authors plan to conduct further related research.

The study was not funded. All study authors, as well as Mr. Galvan and Dr. Paauw, have reported no relevant financial interests.

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

Teamwork by a wide range of professional staff, coupled with support from leadership, enabled one academic community hospital to cut its rate of hospital-onset Clostridioides difficile infections (HO-CDIs) by almost two-thirds in 1 year and by over three-quarters in 3 years, a study published in the American Journal of Infection Control reports.

C. diff. is a major health threat. According to the U.S. Centers for Disease Control and Prevention, CDIs, mainly linked with hospitals, caused an estimated 223,900 cases in hospitalized patients and 12,800 deaths in the United States in 2017.

“The interventions and outcomes of the project improved patient care by ensuring early testing, diagnosis, treatment if warranted, and proper isolation, which helped reduce C. diff. transmission to staff and other patients,” lead study author Cherith Walter, MSN, RN, a clinical nurse specialist at Emory Saint Joseph’s Hospital, Atlanta, told this news organization. “Had we not worked together as a team, we would not have had the ability to carry out such a robust project,” she added in an email.

Each HO-CDI case costs a health care system an estimated $12,313, and high rates of HO-CDIs incur fines from the Hospital-Acquired Condition Reduction Program of the Centers for Medicare & Medicaid Services (CMS), the authors write.
 

A diverse staff team collaborated

Emory Saint Joseph’s, a 410-bed hospital in Atlanta, had a history of being above the national CMS benchmark for HO-CDIs. To reduce these infections, comply with CMS requirements, and avoid fines, Ms. Walter and colleagues launched a quality improvement project between 2015 and 2020.

With the approval of the chief nursing officer, chief quality officer, and hospital board, researchers mobilized a diverse team of professionals: a clinical nurse specialist, a physician champion, unit nurse champions, a hospital epidemiologist, an infection preventionist, a clinical microbiologist, an antimicrobial stewardship pharmacist, and an environmental services representative.

The team investigated what caused their hospital’s HO-CDIs from 2014 through 2016 and developed appropriate, evidence-based infection prevention interventions. The integrated approach involved:

• Diagnostic stewardship, including a diarrhea decision-tree algorithm that enabled nurses to order tests of any loose or unformed stool for C. diff. during the first 3 days of admission.
• Enhanced environmental cleaning, which involved switching from sporicidal disinfectant only in isolation rooms to using a more effective Environmental Protection Agency–approved sporicidal disinfectant containing hydrogen peroxide and peracetic acid in all patient rooms for daily cleaning and after discharge. Every day, high-touch surfaces in C. diff. isolation rooms were cleaned and shared equipment was disinfected with bleach wipes. After patient discharge, staff cleaned mattresses on all sides, wiped walls with disinfectant, and used ultraviolet light.
• Antimicrobial stewardship. Formulary fluoroquinolones were removed as standalone orders and made available only through order sets with built-in clinical decision support.
• Education of staff on best practices, through emails, flyers, meetings, and training sessions. Two nurses needed to approve the appropriateness of testing specific specimens for CDI. All HO-CDIs were reviewed and findings presented at CDI team meetings.
• Accountability. Staff on the team and units received emailed notices about compliance issues and held meetings to discuss how to improve compliance.

After 1 year, HO-CDI incidence dropped 63% from baseline, from above 12 cases per 10,000 patient-days to 4.72 per 10,000 patient-days. And after 3 years, infections dropped 77% to 2.80 per 10,000 patient-days.

The hospital’s HO-CDI standardized infection ratio – the total number of infections divided by the National Healthcare Safety Network’s risk-adjusted predicted number of infections – dropped below the national benchmark, from 1.11 in 2015 to 0.43 in 2020.

The hospital also increased testing of appropriate patients for CDI within the first 3 days of admission, from 54% in 2014 to 81% in late 2019.

“By testing patients within 3 days of admission, we discovered that many had acquired C. diff. before admission,” Ms. Walter said. “I don’t think we realized how prevalent C. diff. was in the community.”

Benjamin D. Galvan, MLS(ASCP), CIC, an infection preventionist at Tampa General Hospital and a member of the Association for Professionals in Infection Control and Epidemiology, welcomed the study’s results.  

“Effective collaboration within the health care setting is a highly effective way to implement and sustain evidence-based practices related to infection reduction. When buy-in is obtained from the top, and pertinent stakeholders are engaged for their expertise, we can see sustainable change and improved patient outcomes,” Mr. Galvan, who was not involved in the study, said in an email.

“The researchers did a fantastic job,” he added. “I am grateful to see this important work addressed in the literature, as it will only improve buy-in for improvement efforts aimed at reducing infections moving forward across the health care continuum.”

Douglas S. Paauw, MD, a professor of medicine and chair for patient-centered clinical education at the University of Washington School of Medicine, Seattle, said that the team’s most important interventions were changing the environmental cleaning protocol and using agents that kill C. diff. spores.

“We know that as many as 10%-20% of hospitalized patients carry C. diff. Cleaning only the rooms where you know you have C. diff. (isolation rooms) will miss most of it,” said Dr. Paauw, who was also not involved in the study. “Cleaning every room with cleaners that actually work is very important but costs money.”
 

Handwashing with soap and water works, alcohol hand gels do not

“We know that handwashing with soap and water is the most important way to prevent hospital C. diff. transmission,” Dr. Paauw noted. “Handwashing protocols implemented prior to the study were probably a big part of the team’s success.”

Handwashing with soap and water works but alcohol hand gels do not, he cautioned.

“C. diff. rates in hospitals went up years ago when we started putting alcohol gels outside patients’ rooms,” Dr. Paauw explained. “Now, instead of washing their hands, staff quickly pump gel before they see patients. Applying gel is easy, but gel does not eliminate C. diff. spores. Handwashing is such a simple way to fix the C. diff. problem, but doctors don’t take the time.”

“We need to take the C. diff. problem seriously. We have enough information, and we know the right things to do. We need to wash our hands. We need to clean the rooms. We need to stop cutting corners if we want to give good care,” he said.

The authors plan to conduct further related research.

The study was not funded. All study authors, as well as Mr. Galvan and Dr. Paauw, have reported no relevant financial interests.

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

Teamwork by a wide range of professional staff, coupled with support from leadership, enabled one academic community hospital to cut its rate of hospital-onset Clostridioides difficile infections (HO-CDIs) by almost two-thirds in 1 year and by over three-quarters in 3 years, a study published in the American Journal of Infection Control reports.

C. diff. is a major health threat. According to the U.S. Centers for Disease Control and Prevention, CDIs, mainly linked with hospitals, caused an estimated 223,900 cases in hospitalized patients and 12,800 deaths in the United States in 2017.

“The interventions and outcomes of the project improved patient care by ensuring early testing, diagnosis, treatment if warranted, and proper isolation, which helped reduce C. diff. transmission to staff and other patients,” lead study author Cherith Walter, MSN, RN, a clinical nurse specialist at Emory Saint Joseph’s Hospital, Atlanta, told this news organization. “Had we not worked together as a team, we would not have had the ability to carry out such a robust project,” she added in an email.

Each HO-CDI case costs a health care system an estimated $12,313, and high rates of HO-CDIs incur fines from the Hospital-Acquired Condition Reduction Program of the Centers for Medicare & Medicaid Services (CMS), the authors write.
 

A diverse staff team collaborated

Emory Saint Joseph’s, a 410-bed hospital in Atlanta, had a history of being above the national CMS benchmark for HO-CDIs. To reduce these infections, comply with CMS requirements, and avoid fines, Ms. Walter and colleagues launched a quality improvement project between 2015 and 2020.

With the approval of the chief nursing officer, chief quality officer, and hospital board, researchers mobilized a diverse team of professionals: a clinical nurse specialist, a physician champion, unit nurse champions, a hospital epidemiologist, an infection preventionist, a clinical microbiologist, an antimicrobial stewardship pharmacist, and an environmental services representative.

The team investigated what caused their hospital’s HO-CDIs from 2014 through 2016 and developed appropriate, evidence-based infection prevention interventions. The integrated approach involved:

• Diagnostic stewardship, including a diarrhea decision-tree algorithm that enabled nurses to order tests of any loose or unformed stool for C. diff. during the first 3 days of admission.
• Enhanced environmental cleaning, which involved switching from sporicidal disinfectant only in isolation rooms to using a more effective Environmental Protection Agency–approved sporicidal disinfectant containing hydrogen peroxide and peracetic acid in all patient rooms for daily cleaning and after discharge. Every day, high-touch surfaces in C. diff. isolation rooms were cleaned and shared equipment was disinfected with bleach wipes. After patient discharge, staff cleaned mattresses on all sides, wiped walls with disinfectant, and used ultraviolet light.
• Antimicrobial stewardship. Formulary fluoroquinolones were removed as standalone orders and made available only through order sets with built-in clinical decision support.
• Education of staff on best practices, through emails, flyers, meetings, and training sessions. Two nurses needed to approve the appropriateness of testing specific specimens for CDI. All HO-CDIs were reviewed and findings presented at CDI team meetings.
• Accountability. Staff on the team and units received emailed notices about compliance issues and held meetings to discuss how to improve compliance.

After 1 year, HO-CDI incidence dropped 63% from baseline, from above 12 cases per 10,000 patient-days to 4.72 per 10,000 patient-days. And after 3 years, infections dropped 77% to 2.80 per 10,000 patient-days.

The hospital’s HO-CDI standardized infection ratio – the total number of infections divided by the National Healthcare Safety Network’s risk-adjusted predicted number of infections – dropped below the national benchmark, from 1.11 in 2015 to 0.43 in 2020.

The hospital also increased testing of appropriate patients for CDI within the first 3 days of admission, from 54% in 2014 to 81% in late 2019.

“By testing patients within 3 days of admission, we discovered that many had acquired C. diff. before admission,” Ms. Walter said. “I don’t think we realized how prevalent C. diff. was in the community.”

Benjamin D. Galvan, MLS(ASCP), CIC, an infection preventionist at Tampa General Hospital and a member of the Association for Professionals in Infection Control and Epidemiology, welcomed the study’s results.  

“Effective collaboration within the health care setting is a highly effective way to implement and sustain evidence-based practices related to infection reduction. When buy-in is obtained from the top, and pertinent stakeholders are engaged for their expertise, we can see sustainable change and improved patient outcomes,” Mr. Galvan, who was not involved in the study, said in an email.

“The researchers did a fantastic job,” he added. “I am grateful to see this important work addressed in the literature, as it will only improve buy-in for improvement efforts aimed at reducing infections moving forward across the health care continuum.”

Douglas S. Paauw, MD, a professor of medicine and chair for patient-centered clinical education at the University of Washington School of Medicine, Seattle, said that the team’s most important interventions were changing the environmental cleaning protocol and using agents that kill C. diff. spores.

“We know that as many as 10%-20% of hospitalized patients carry C. diff. Cleaning only the rooms where you know you have C. diff. (isolation rooms) will miss most of it,” said Dr. Paauw, who was also not involved in the study. “Cleaning every room with cleaners that actually work is very important but costs money.”
 

Handwashing with soap and water works, alcohol hand gels do not

“We know that handwashing with soap and water is the most important way to prevent hospital C. diff. transmission,” Dr. Paauw noted. “Handwashing protocols implemented prior to the study were probably a big part of the team’s success.”

Handwashing with soap and water works but alcohol hand gels do not, he cautioned.

“C. diff. rates in hospitals went up years ago when we started putting alcohol gels outside patients’ rooms,” Dr. Paauw explained. “Now, instead of washing their hands, staff quickly pump gel before they see patients. Applying gel is easy, but gel does not eliminate C. diff. spores. Handwashing is such a simple way to fix the C. diff. problem, but doctors don’t take the time.”

“We need to take the C. diff. problem seriously. We have enough information, and we know the right things to do. We need to wash our hands. We need to clean the rooms. We need to stop cutting corners if we want to give good care,” he said.

The authors plan to conduct further related research.

The study was not funded. All study authors, as well as Mr. Galvan and Dr. Paauw, have reported no relevant financial interests.

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

Over-the-counter medications, food supplements, and other drugs may interact with antiretroviral therapy (ART) in people living with HIV and be harmful, an industry-sponsored clinical survey from Denmark reports.

“Our study confirms that polypharmacy and being on a protease inhibitor–based regimen increase the risk of potential drug-drug interactions [PDDIs] considerably and highlights the importance of questioning people living with HIV [PLWH] about dietary supplement intake,” the authors, led by Michaela Tinggaard, MD, Copenhagen University Hospital, wrote in HIV Medicine.

“Potential drug-drug interactions were common among our study population. Although the clinical significance of the majority of the identified PDDIs may be low, most of them were avoidable through a change or discontinuation of the comedication, a change in ART or by spacing drugs,” they added.

Senior author Thomas Benfield, MD, DTMH, DMSc, a professor of infectious diseases at the University of Copenhagen, and colleagues collected information on prescription medication, over-the-counter medication, and dietary supplements from adults living with HIV who received ART from two outpatient clinics.

The researchers estimated the prevalence of non-HIV comedications, and they used the University of Liverpool HIV Drug Interactions database to identify potential drug-drug interactions. They evaluated PDDIs and used logistic regression models to investigate links between PDDIs and relevant variables.

The study included 337 people living with HIV receiving ART. The median age was 53 years, 77% of them were male, and 96% were virally suppressed, with HIV-RNA viral load less than 50 copies/mL.

Overall, 26% of participants received five or more comedications, and 56% took dietary supplements.

In the medication lists of 52% of patients, the authors identified coadministration of drugs that required dose adjustment or monitoring; 4.5% of patients were taking drugs that should not be coadministered.

The researchers detected several factors that independently predicted PDDIs:

• Male sex (odds ratio, 1.9; 95% confidence interval, 1.0-3.4)
• Being on a protease inhibitor (OR, 4.3; 95% CI, 1.9-9.7)
• Receiving five or more comedications (OR, 3.3; 95% CI, 1.5-7.2)
• Taking over-the-counter medications (OR, 1.9; 95% CI, 1.1-3.3)
• Taking dietary supplements (OR, 2.0; 95% CI, 1.2-3.3)

Comorbidities and OTC medications increase in aging people with HIV

Indira Brar, MD, an infectious diseases senior staff physician and the medical director of HIV services at Henry Ford Health in Detroit, called the study and important resource for educating providers and patients about over-the-counter drugs.

“The main strength of the study is that it includes a decent number of aging patients living with HIV, the age group in which we worry about drug interactions,” she said in an interview.

“As patients get older, they have increased comorbidities. As comorbidities increase, the number of medications increases. As the number of medications increases, the drug interactions increase,” said Dr. Brar, who was not involved in the study. “Also, as patients get older, they tend to take more over-the-counter drugs.”

Dr. Brar explained how drug-drug interactions can harm patients.

“Drugs added to a patient who is already on ART could decrease the level of the ART and cause the patient to develop a drug-resistant HIV infection,” she said. “Or the ART the patient is on can increase the levels of the new drugs that have been added, and that could have potential toxicity and side effects.

“Food supplements, including multivitamins, calcium, and magnesium, are often overlooked because we think they’re benign. But these drugs can bind our new antiretrovirals, the integrase inhibitors. They can decrease their levels in the patient and cause drug-resistant HIV infection.

“In our clinic, we always tell our patients to please call us before they take any medication, so we can make sure there is no drug interaction,” Dr. Brar said.

Nan Wang, PharmD, a clinical pharmacy specialist at University Hospitals Cleveland Medical Center, noted in an email that drug-drug interactions with ARTs are common.

“Understanding the prevalence of antiretroviral drug interactions in a patient population can help identify certain medications that require enhanced vigilance and can guide our clinical interventions,” said Dr. Wang, who was not associated with the research.

Joseph Alvarnas, MD, a hematologist and oncologist at City of Hope Comprehensive Cancer Center in Duarte, Calif., said that this is “a methodologically sound and well-designed study that’s a timely, important reminder that providers need to think carefully and comprehensively when caring for their patients living with HIV.”

Dr. Alvarnas, who was not involved in the study, said that, with the widespread availability of ART, HIV has become a chronic, manageable condition in an aging population.

“ART agents, particularly the ritonavir-boosted protease inhibitors, increase the likelihood of patients having a potentially significant drug-drug interaction with one of their chronic care medications,” he added. “Even seemingly low-risk supplements such as multivitamins may result in a negative impact upon effective ART treatment of PLWH.”

“The essential next step is that these findings are integrated carefully into decision-support systems, electronic health record prescribing systems, and pharmacy safety-check systems to ensure that we reduce the risk of patient harm,” Dr. Alvarnas advised.

Dr. Benfield and several study coauthors reported financial relationships with GlaxoSmithKline and other pharmaceutical companies. Other coauthors, as well as Dr. Alvarnas, Dr. Brar, and Dr. Wang, reported no relevant financial relationships. The study was supported by GlaxoSmithKline.

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

Over-the-counter medications, food supplements, and other drugs may interact with antiretroviral therapy (ART) in people living with HIV and be harmful, an industry-sponsored clinical survey from Denmark reports.

“Our study confirms that polypharmacy and being on a protease inhibitor–based regimen increase the risk of potential drug-drug interactions [PDDIs] considerably and highlights the importance of questioning people living with HIV [PLWH] about dietary supplement intake,” the authors, led by Michaela Tinggaard, MD, Copenhagen University Hospital, wrote in HIV Medicine.

“Potential drug-drug interactions were common among our study population. Although the clinical significance of the majority of the identified PDDIs may be low, most of them were avoidable through a change or discontinuation of the comedication, a change in ART or by spacing drugs,” they added.

Senior author Thomas Benfield, MD, DTMH, DMSc, a professor of infectious diseases at the University of Copenhagen, and colleagues collected information on prescription medication, over-the-counter medication, and dietary supplements from adults living with HIV who received ART from two outpatient clinics.

The researchers estimated the prevalence of non-HIV comedications, and they used the University of Liverpool HIV Drug Interactions database to identify potential drug-drug interactions. They evaluated PDDIs and used logistic regression models to investigate links between PDDIs and relevant variables.

The study included 337 people living with HIV receiving ART. The median age was 53 years, 77% of them were male, and 96% were virally suppressed, with HIV-RNA viral load less than 50 copies/mL.

Overall, 26% of participants received five or more comedications, and 56% took dietary supplements.

In the medication lists of 52% of patients, the authors identified coadministration of drugs that required dose adjustment or monitoring; 4.5% of patients were taking drugs that should not be coadministered.

The researchers detected several factors that independently predicted PDDIs:

• Male sex (odds ratio, 1.9; 95% confidence interval, 1.0-3.4)
• Being on a protease inhibitor (OR, 4.3; 95% CI, 1.9-9.7)
• Receiving five or more comedications (OR, 3.3; 95% CI, 1.5-7.2)
• Taking over-the-counter medications (OR, 1.9; 95% CI, 1.1-3.3)
• Taking dietary supplements (OR, 2.0; 95% CI, 1.2-3.3)

Comorbidities and OTC medications increase in aging people with HIV

Indira Brar, MD, an infectious diseases senior staff physician and the medical director of HIV services at Henry Ford Health in Detroit, called the study and important resource for educating providers and patients about over-the-counter drugs.

“The main strength of the study is that it includes a decent number of aging patients living with HIV, the age group in which we worry about drug interactions,” she said in an interview.

“As patients get older, they have increased comorbidities. As comorbidities increase, the number of medications increases. As the number of medications increases, the drug interactions increase,” said Dr. Brar, who was not involved in the study. “Also, as patients get older, they tend to take more over-the-counter drugs.”

Dr. Brar explained how drug-drug interactions can harm patients.

“Drugs added to a patient who is already on ART could decrease the level of the ART and cause the patient to develop a drug-resistant HIV infection,” she said. “Or the ART the patient is on can increase the levels of the new drugs that have been added, and that could have potential toxicity and side effects.

“Food supplements, including multivitamins, calcium, and magnesium, are often overlooked because we think they’re benign. But these drugs can bind our new antiretrovirals, the integrase inhibitors. They can decrease their levels in the patient and cause drug-resistant HIV infection.

“In our clinic, we always tell our patients to please call us before they take any medication, so we can make sure there is no drug interaction,” Dr. Brar said.

Nan Wang, PharmD, a clinical pharmacy specialist at University Hospitals Cleveland Medical Center, noted in an email that drug-drug interactions with ARTs are common.

“Understanding the prevalence of antiretroviral drug interactions in a patient population can help identify certain medications that require enhanced vigilance and can guide our clinical interventions,” said Dr. Wang, who was not associated with the research.

Joseph Alvarnas, MD, a hematologist and oncologist at City of Hope Comprehensive Cancer Center in Duarte, Calif., said that this is “a methodologically sound and well-designed study that’s a timely, important reminder that providers need to think carefully and comprehensively when caring for their patients living with HIV.”

Dr. Alvarnas, who was not involved in the study, said that, with the widespread availability of ART, HIV has become a chronic, manageable condition in an aging population.

“ART agents, particularly the ritonavir-boosted protease inhibitors, increase the likelihood of patients having a potentially significant drug-drug interaction with one of their chronic care medications,” he added. “Even seemingly low-risk supplements such as multivitamins may result in a negative impact upon effective ART treatment of PLWH.”

“The essential next step is that these findings are integrated carefully into decision-support systems, electronic health record prescribing systems, and pharmacy safety-check systems to ensure that we reduce the risk of patient harm,” Dr. Alvarnas advised.

Dr. Benfield and several study coauthors reported financial relationships with GlaxoSmithKline and other pharmaceutical companies. Other coauthors, as well as Dr. Alvarnas, Dr. Brar, and Dr. Wang, reported no relevant financial relationships. The study was supported by GlaxoSmithKline.

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

Over-the-counter medications, food supplements, and other drugs may interact with antiretroviral therapy (ART) in people living with HIV and be harmful, an industry-sponsored clinical survey from Denmark reports.

“Our study confirms that polypharmacy and being on a protease inhibitor–based regimen increase the risk of potential drug-drug interactions [PDDIs] considerably and highlights the importance of questioning people living with HIV [PLWH] about dietary supplement intake,” the authors, led by Michaela Tinggaard, MD, Copenhagen University Hospital, wrote in HIV Medicine.

“Potential drug-drug interactions were common among our study population. Although the clinical significance of the majority of the identified PDDIs may be low, most of them were avoidable through a change or discontinuation of the comedication, a change in ART or by spacing drugs,” they added.

Senior author Thomas Benfield, MD, DTMH, DMSc, a professor of infectious diseases at the University of Copenhagen, and colleagues collected information on prescription medication, over-the-counter medication, and dietary supplements from adults living with HIV who received ART from two outpatient clinics.

The researchers estimated the prevalence of non-HIV comedications, and they used the University of Liverpool HIV Drug Interactions database to identify potential drug-drug interactions. They evaluated PDDIs and used logistic regression models to investigate links between PDDIs and relevant variables.

The study included 337 people living with HIV receiving ART. The median age was 53 years, 77% of them were male, and 96% were virally suppressed, with HIV-RNA viral load less than 50 copies/mL.

Overall, 26% of participants received five or more comedications, and 56% took dietary supplements.

In the medication lists of 52% of patients, the authors identified coadministration of drugs that required dose adjustment or monitoring; 4.5% of patients were taking drugs that should not be coadministered.

The researchers detected several factors that independently predicted PDDIs:

• Male sex (odds ratio, 1.9; 95% confidence interval, 1.0-3.4)
• Being on a protease inhibitor (OR, 4.3; 95% CI, 1.9-9.7)
• Receiving five or more comedications (OR, 3.3; 95% CI, 1.5-7.2)
• Taking over-the-counter medications (OR, 1.9; 95% CI, 1.1-3.3)
• Taking dietary supplements (OR, 2.0; 95% CI, 1.2-3.3)

Comorbidities and OTC medications increase in aging people with HIV

Indira Brar, MD, an infectious diseases senior staff physician and the medical director of HIV services at Henry Ford Health in Detroit, called the study and important resource for educating providers and patients about over-the-counter drugs.

“The main strength of the study is that it includes a decent number of aging patients living with HIV, the age group in which we worry about drug interactions,” she said in an interview.

“As patients get older, they have increased comorbidities. As comorbidities increase, the number of medications increases. As the number of medications increases, the drug interactions increase,” said Dr. Brar, who was not involved in the study. “Also, as patients get older, they tend to take more over-the-counter drugs.”

Dr. Brar explained how drug-drug interactions can harm patients.

“Drugs added to a patient who is already on ART could decrease the level of the ART and cause the patient to develop a drug-resistant HIV infection,” she said. “Or the ART the patient is on can increase the levels of the new drugs that have been added, and that could have potential toxicity and side effects.

“Food supplements, including multivitamins, calcium, and magnesium, are often overlooked because we think they’re benign. But these drugs can bind our new antiretrovirals, the integrase inhibitors. They can decrease their levels in the patient and cause drug-resistant HIV infection.

“In our clinic, we always tell our patients to please call us before they take any medication, so we can make sure there is no drug interaction,” Dr. Brar said.

Nan Wang, PharmD, a clinical pharmacy specialist at University Hospitals Cleveland Medical Center, noted in an email that drug-drug interactions with ARTs are common.

“Understanding the prevalence of antiretroviral drug interactions in a patient population can help identify certain medications that require enhanced vigilance and can guide our clinical interventions,” said Dr. Wang, who was not associated with the research.

Joseph Alvarnas, MD, a hematologist and oncologist at City of Hope Comprehensive Cancer Center in Duarte, Calif., said that this is “a methodologically sound and well-designed study that’s a timely, important reminder that providers need to think carefully and comprehensively when caring for their patients living with HIV.”

Dr. Alvarnas, who was not involved in the study, said that, with the widespread availability of ART, HIV has become a chronic, manageable condition in an aging population.

“ART agents, particularly the ritonavir-boosted protease inhibitors, increase the likelihood of patients having a potentially significant drug-drug interaction with one of their chronic care medications,” he added. “Even seemingly low-risk supplements such as multivitamins may result in a negative impact upon effective ART treatment of PLWH.”

“The essential next step is that these findings are integrated carefully into decision-support systems, electronic health record prescribing systems, and pharmacy safety-check systems to ensure that we reduce the risk of patient harm,” Dr. Alvarnas advised.

Dr. Benfield and several study coauthors reported financial relationships with GlaxoSmithKline and other pharmaceutical companies. Other coauthors, as well as Dr. Alvarnas, Dr. Brar, and Dr. Wang, reported no relevant financial relationships. The study was supported by GlaxoSmithKline.

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

Good hand hygiene and other cost-effective infection prevention and control (IPC) practices can eliminate between 35% and 70% of health care–setting infections in all countries regardless of economic status, the World Health Organization reports.

IPC uses a practical, evidence-based approach to help patients, health care workers, and visitors to health care facilities avoid harmful infections, which can range from infections caused by localized antibiotic-resistant bacteria to pandemic viruses. The WHO calls the report the first global analysis of IPC implementation.

“Hospitals across the world saw increased rates of health care–associated infections (HAIs) during the COVID-19 pandemic. This included SARS-CoV-2 infections and other HAIs that increased as our health care systems were stretched to the breaking point and fewer resources were available for HAI prevention,” Daniel Diekema, MD, who was not involved in the report, said in an email.

“As we enter the third year of the pandemic, this WHO report should serve as an urgent call to action,” Dr. Diekema, a clinical professor of internal medicine at University of Iowa Health Care and an associate hospital epidemiologist with University of Iowa Hospitals and Clinics, both in Iowa City, noted. “Investing more resources in IPC programs will not only improve pandemic response, it will reduce morbidity, mortality, and global costs from all HAIs.”
 

No country or health system is free of HAIs

“Disparities in IPC investments between high- and low-income countries is the greatest challenge outlined in this report,” Dr. Diekema said in an email. “If the pandemic has taught us anything, it is that an infection spread anywhere in the world can soon become a problem everywhere. Thus, it is in everyone’s interest to ensure that IPC resources are more equitably distributed across the world.”

The report notes that HAIs are among the most common adverse events experienced in health care, and many HAIs are caused by multidrug-resistant organisms. The report includes these details:

It is predicted that of every 100 patients in acute-care hospitals, an average of 7 patients in high-income countries and 15 in low- and middle-income countries will acquire at least one HAI while hospitalized; as many as 30% of patients in intensive care encounter HAIs.

Of all cases of hospital-treated sepsis, 23.6% were linked to health care; 48.7% of all sepsis cases involving organ dysfunction treated in adult intensive care were acquired in the hospital; 24.4% of patients and 52.3% of those in intensive care who were affected by health care–associated sepsis died.

The European Centre for Disease Prevention and Control calculated that 4.5 million episodes of HAIs occurred each year among patients in acute-care hospitals in countries of the European Union and the European Economic Area.

The Centers for Disease Control and Prevention estimated that on any day, 1 in 31 hospital patients and 1 in 43 nursing home residents has an HAI.

Up to 41% of hospitalized patients with confirmed COVID-19 were infected with SARS-CoV-2 in health care settings.

Over roughly the first 18 months of the pandemic, COVID-19 killed between 80,000 and 180,000 health care workers worldwide.
 

The COVID-19 pandemic highlights the need for IPC

Despite the pandemic, high-income countries were eight times more likely to implement more advanced IPC than low-income countries, and IPC national programs in low- and middle-income countries improved only slightly.

Only 4 (3.8%) of the 106 evaluated countries met all the minimum requirements for IPC in place at the national level, and only 15.2% of health care facilities met all IPC minimum requirements.

Libby A. Richards, RN, MSN, PhD, CHES, an associate professor of nursing and the director of the PhD program in the Purdue University School of Nursing in West Lafayette, Ind., welcomed the report.

“While the principles of infection prevention and control have been fundamental for well over a hundred years, the COVID-19 pandemic brought these critical issues to everyone’s attention,” Dr. Richards, who was not involved in the report, said by email. “During the pandemic, the impact on our overburdened and understaffed health care system left little or no room for other acutely ill patients.

“This report brings timely attention to the importance of IPC across health care services,” she added.

Suzanne Wagester, RN, MSN, director of infection prevention at the University of Pittsburgh Medical Center, said in an email, “The pandemic has united us as a society as we recognize that infections impact us all. We struggle with the same universal challenges that directly impact the work of infection prevention.

“IPC programs are vital to facilities, patients, and countries,” Ms. Wagester, who also was not involved in the report, added. “The WHO report highlights the call to action that will hopefully ignite the movement to advance IPC programs across the globe to combat preventable infections.”

The WHO Global IPC Portal helps health care professionals in all countries analyze, track progress, and improve IPC at facility and national levels.

The report was funded by core WHO funds. The authors and Dr. Diekema, Dr. Richards, and Ms. Wagester have disclosed no relevant financial relationships.

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

Good hand hygiene and other cost-effective infection prevention and control (IPC) practices can eliminate between 35% and 70% of health care–setting infections in all countries regardless of economic status, the World Health Organization reports.

IPC uses a practical, evidence-based approach to help patients, health care workers, and visitors to health care facilities avoid harmful infections, which can range from infections caused by localized antibiotic-resistant bacteria to pandemic viruses. The WHO calls the report the first global analysis of IPC implementation.

“Hospitals across the world saw increased rates of health care–associated infections (HAIs) during the COVID-19 pandemic. This included SARS-CoV-2 infections and other HAIs that increased as our health care systems were stretched to the breaking point and fewer resources were available for HAI prevention,” Daniel Diekema, MD, who was not involved in the report, said in an email.

“As we enter the third year of the pandemic, this WHO report should serve as an urgent call to action,” Dr. Diekema, a clinical professor of internal medicine at University of Iowa Health Care and an associate hospital epidemiologist with University of Iowa Hospitals and Clinics, both in Iowa City, noted. “Investing more resources in IPC programs will not only improve pandemic response, it will reduce morbidity, mortality, and global costs from all HAIs.”
 

No country or health system is free of HAIs

“Disparities in IPC investments between high- and low-income countries is the greatest challenge outlined in this report,” Dr. Diekema said in an email. “If the pandemic has taught us anything, it is that an infection spread anywhere in the world can soon become a problem everywhere. Thus, it is in everyone’s interest to ensure that IPC resources are more equitably distributed across the world.”

The report notes that HAIs are among the most common adverse events experienced in health care, and many HAIs are caused by multidrug-resistant organisms. The report includes these details:

It is predicted that of every 100 patients in acute-care hospitals, an average of 7 patients in high-income countries and 15 in low- and middle-income countries will acquire at least one HAI while hospitalized; as many as 30% of patients in intensive care encounter HAIs.

Of all cases of hospital-treated sepsis, 23.6% were linked to health care; 48.7% of all sepsis cases involving organ dysfunction treated in adult intensive care were acquired in the hospital; 24.4% of patients and 52.3% of those in intensive care who were affected by health care–associated sepsis died.

The European Centre for Disease Prevention and Control calculated that 4.5 million episodes of HAIs occurred each year among patients in acute-care hospitals in countries of the European Union and the European Economic Area.

The Centers for Disease Control and Prevention estimated that on any day, 1 in 31 hospital patients and 1 in 43 nursing home residents has an HAI.

Up to 41% of hospitalized patients with confirmed COVID-19 were infected with SARS-CoV-2 in health care settings.

Over roughly the first 18 months of the pandemic, COVID-19 killed between 80,000 and 180,000 health care workers worldwide.
 

The COVID-19 pandemic highlights the need for IPC

Despite the pandemic, high-income countries were eight times more likely to implement more advanced IPC than low-income countries, and IPC national programs in low- and middle-income countries improved only slightly.

Only 4 (3.8%) of the 106 evaluated countries met all the minimum requirements for IPC in place at the national level, and only 15.2% of health care facilities met all IPC minimum requirements.

Libby A. Richards, RN, MSN, PhD, CHES, an associate professor of nursing and the director of the PhD program in the Purdue University School of Nursing in West Lafayette, Ind., welcomed the report.

“While the principles of infection prevention and control have been fundamental for well over a hundred years, the COVID-19 pandemic brought these critical issues to everyone’s attention,” Dr. Richards, who was not involved in the report, said by email. “During the pandemic, the impact on our overburdened and understaffed health care system left little or no room for other acutely ill patients.

“This report brings timely attention to the importance of IPC across health care services,” she added.

Suzanne Wagester, RN, MSN, director of infection prevention at the University of Pittsburgh Medical Center, said in an email, “The pandemic has united us as a society as we recognize that infections impact us all. We struggle with the same universal challenges that directly impact the work of infection prevention.

“IPC programs are vital to facilities, patients, and countries,” Ms. Wagester, who also was not involved in the report, added. “The WHO report highlights the call to action that will hopefully ignite the movement to advance IPC programs across the globe to combat preventable infections.”

The WHO Global IPC Portal helps health care professionals in all countries analyze, track progress, and improve IPC at facility and national levels.

The report was funded by core WHO funds. The authors and Dr. Diekema, Dr. Richards, and Ms. Wagester have disclosed no relevant financial relationships.

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

Good hand hygiene and other cost-effective infection prevention and control (IPC) practices can eliminate between 35% and 70% of health care–setting infections in all countries regardless of economic status, the World Health Organization reports.

IPC uses a practical, evidence-based approach to help patients, health care workers, and visitors to health care facilities avoid harmful infections, which can range from infections caused by localized antibiotic-resistant bacteria to pandemic viruses. The WHO calls the report the first global analysis of IPC implementation.

“Hospitals across the world saw increased rates of health care–associated infections (HAIs) during the COVID-19 pandemic. This included SARS-CoV-2 infections and other HAIs that increased as our health care systems were stretched to the breaking point and fewer resources were available for HAI prevention,” Daniel Diekema, MD, who was not involved in the report, said in an email.

“As we enter the third year of the pandemic, this WHO report should serve as an urgent call to action,” Dr. Diekema, a clinical professor of internal medicine at University of Iowa Health Care and an associate hospital epidemiologist with University of Iowa Hospitals and Clinics, both in Iowa City, noted. “Investing more resources in IPC programs will not only improve pandemic response, it will reduce morbidity, mortality, and global costs from all HAIs.”
 

No country or health system is free of HAIs

“Disparities in IPC investments between high- and low-income countries is the greatest challenge outlined in this report,” Dr. Diekema said in an email. “If the pandemic has taught us anything, it is that an infection spread anywhere in the world can soon become a problem everywhere. Thus, it is in everyone’s interest to ensure that IPC resources are more equitably distributed across the world.”

The report notes that HAIs are among the most common adverse events experienced in health care, and many HAIs are caused by multidrug-resistant organisms. The report includes these details:

It is predicted that of every 100 patients in acute-care hospitals, an average of 7 patients in high-income countries and 15 in low- and middle-income countries will acquire at least one HAI while hospitalized; as many as 30% of patients in intensive care encounter HAIs.

Of all cases of hospital-treated sepsis, 23.6% were linked to health care; 48.7% of all sepsis cases involving organ dysfunction treated in adult intensive care were acquired in the hospital; 24.4% of patients and 52.3% of those in intensive care who were affected by health care–associated sepsis died.

The European Centre for Disease Prevention and Control calculated that 4.5 million episodes of HAIs occurred each year among patients in acute-care hospitals in countries of the European Union and the European Economic Area.

The Centers for Disease Control and Prevention estimated that on any day, 1 in 31 hospital patients and 1 in 43 nursing home residents has an HAI.

Up to 41% of hospitalized patients with confirmed COVID-19 were infected with SARS-CoV-2 in health care settings.

Over roughly the first 18 months of the pandemic, COVID-19 killed between 80,000 and 180,000 health care workers worldwide.
 

The COVID-19 pandemic highlights the need for IPC

Despite the pandemic, high-income countries were eight times more likely to implement more advanced IPC than low-income countries, and IPC national programs in low- and middle-income countries improved only slightly.

Only 4 (3.8%) of the 106 evaluated countries met all the minimum requirements for IPC in place at the national level, and only 15.2% of health care facilities met all IPC minimum requirements.

Libby A. Richards, RN, MSN, PhD, CHES, an associate professor of nursing and the director of the PhD program in the Purdue University School of Nursing in West Lafayette, Ind., welcomed the report.

“While the principles of infection prevention and control have been fundamental for well over a hundred years, the COVID-19 pandemic brought these critical issues to everyone’s attention,” Dr. Richards, who was not involved in the report, said by email. “During the pandemic, the impact on our overburdened and understaffed health care system left little or no room for other acutely ill patients.

“This report brings timely attention to the importance of IPC across health care services,” she added.

Suzanne Wagester, RN, MSN, director of infection prevention at the University of Pittsburgh Medical Center, said in an email, “The pandemic has united us as a society as we recognize that infections impact us all. We struggle with the same universal challenges that directly impact the work of infection prevention.

“IPC programs are vital to facilities, patients, and countries,” Ms. Wagester, who also was not involved in the report, added. “The WHO report highlights the call to action that will hopefully ignite the movement to advance IPC programs across the globe to combat preventable infections.”

The WHO Global IPC Portal helps health care professionals in all countries analyze, track progress, and improve IPC at facility and national levels.

The report was funded by core WHO funds. The authors and Dr. Diekema, Dr. Richards, and Ms. Wagester have disclosed no relevant financial relationships.

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

Children who have greater acute appendicitis pain may be less likely to improve if they’re treated with antibiotics alone, according to a secondary analysis of a nonrandomized clinical trial.

“While approximately 35% of families chose nonoperative management, a high pain score between 7-10 on a 10-point scale nearly doubled in-hospital treatment failure,” Rebecca M. Rentea, MD, a pediatric surgeon and the director of the Comprehensive Colorectal Center at Children’s Mercy Kansas City, Mo., told this news organization in an email.

“Even if nonoperative management of pediatric appendicitis did not work – resulting in the need to remove the appendix in 34% of cases – families were happy with their decisions 1 year later,” added Dr. Rentea, who coauthored an invited commentary about the study.

Lead study author Peter C. Minneci, MD, MHSc, a pediatric surgeon at Nationwide Children’s Hospital, Columbus, Ohio, and colleagues analyzed a subgroup of patients from a larger study in 10 tertiary children’s hospitals in the Midwest Pediatric Surgery Consortium.

As they reported in JAMA Network Open, the larger prospective, nonrandomized clinical trial enrolled 1,068 children between 2015 and 2018. The children ranged in age from 7 to 17 years, and they had imaging-confirmed appendicitis with an appendix diameter of 1.1 cm or less, no abscess, no appendicolith, and no phlegmon. White blood cell count was between 5,000 and 18,000 cells/μL, and abdominal pain began less than 48 hours before they received antibiotic therapy.

Caregivers chose either surgery or nonoperative antibiotic management. Patients who were treated first with antibiotics alone and who did not undergo appendectomy within 1 year were considered to have successfully completed nonoperative treatment.

The secondary analysis included the 370 children enrolled in the nonoperative group. Of these, 229 were boys, and the median age was 12.3 years. In this subgroup, the researchers compared outcomes after nonoperative, antibiotic management vs. surgery.

At 1 year, treatment failure had occurred in 125 patients, with 53 having undergone appendectomy during their first hospitalization, and 72 having experienced delayed treatment failure after being discharged.

• Higher patient-reported pain at presentation was linked to higher risk for in-hospital treatment failure (relative risk, 2.1; 95% confidence interval, 1.0-4.4) but not for delayed treatment failure (RR, 1.3; 95% CI, 0.7-2.3) or overall treatment failure at 1 year (RR, 1.5; 95% CI, 1.0-2.2).
• Pain lasting longer than 24 hours was linked to lower risk for delayed treatment failure (RR, 0.3; 95% CI, 0.1-1.0) but not for in-hospital treatment failure (RR, 1.2; 95% CI, 0.5-2.7) or treatment failure at 1 year (RR, 0.7; 95% CI, 0.4-1.2).
• Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs. 27.0; difference, 1.0; 95% CI, 0.01-2.0) and at 1 year (28.1 vs 27.0; difference, 1.1; 95% CI, 0.2-2.0).

The researchers found no increased risk for treatment failure based on age, sex, race, ethnicity, white blood cell count, primary language, insurance status, transfer status, presentation symptoms, or imaging results.

Antibiotics-only is a safe option for children

“This study suggests that pediatric patients with uncomplicated acute appendicitis should be offered treatment options, including nonoperative management,” the authors write. “Treatment with antibiotics alone is a safe and equitable option for children, with no increased risk of treatment failure based on sociodemographic or objective clinical characteristics at presentation.”

But, the authors advise: “Families need to be made aware that treatment failure is not uncommon, and they should be provided with anticipatory guidance on how to proceed should symptoms recur.”

The investigators acknowledged limitations to the study, including the nonrandomized design that may have introduced bias, the loss to follow-up, and the study population being U.S. Midwest children, who may differ from children elsewhere in the country.

Shawn D. St Peter, MD, a pediatric surgeon, medical chair, and a senior vice president at Children’s Mercy Kansas City told this news organization in an email that having a nonoperative alternative to surgical appendectomy is important.

“Antibiotics are the initial treatment for appendicitis and can be the definitive treatment,” he said.

“Surprisingly, no sociodemographic or clinical characteristics were associated with an increased risk of nonoperative appendicitis treatment failure,” added Dr. St Peter, who coauthored the commentary with Dr. Rentea.

Howard C. Jen, MD, a pediatric surgeon at University of California, Los Angeles, Mattel Children’s Hospital, was not surprised by the findings.

“Nonoperative management for acute noncomplicated appendicitis in children continues to be safe and effective in highly selected patients,” he said in an email. “This alternative to surgery should be offered routinely to patients with early acute appendicitis.” 

Dr. Jen, who was not involved with the current study, noted that it did not address the impact and costs to families of nonoperative management vs. surgery.

“For the most vulnerable children who had difficulties accessing medical care, what is the best treatment option? What factors are important to the families when making this decision?” he asked.

All study and editorial authors report no relevant financial relationships. The study was funded by the Patient-Centered Outcomes Research Institute and the National Center for Advancing Translational Sciences.

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

Children who have greater acute appendicitis pain may be less likely to improve if they’re treated with antibiotics alone, according to a secondary analysis of a nonrandomized clinical trial.

“While approximately 35% of families chose nonoperative management, a high pain score between 7-10 on a 10-point scale nearly doubled in-hospital treatment failure,” Rebecca M. Rentea, MD, a pediatric surgeon and the director of the Comprehensive Colorectal Center at Children’s Mercy Kansas City, Mo., told this news organization in an email.

“Even if nonoperative management of pediatric appendicitis did not work – resulting in the need to remove the appendix in 34% of cases – families were happy with their decisions 1 year later,” added Dr. Rentea, who coauthored an invited commentary about the study.

Lead study author Peter C. Minneci, MD, MHSc, a pediatric surgeon at Nationwide Children’s Hospital, Columbus, Ohio, and colleagues analyzed a subgroup of patients from a larger study in 10 tertiary children’s hospitals in the Midwest Pediatric Surgery Consortium.

As they reported in JAMA Network Open, the larger prospective, nonrandomized clinical trial enrolled 1,068 children between 2015 and 2018. The children ranged in age from 7 to 17 years, and they had imaging-confirmed appendicitis with an appendix diameter of 1.1 cm or less, no abscess, no appendicolith, and no phlegmon. White blood cell count was between 5,000 and 18,000 cells/μL, and abdominal pain began less than 48 hours before they received antibiotic therapy.

Caregivers chose either surgery or nonoperative antibiotic management. Patients who were treated first with antibiotics alone and who did not undergo appendectomy within 1 year were considered to have successfully completed nonoperative treatment.

The secondary analysis included the 370 children enrolled in the nonoperative group. Of these, 229 were boys, and the median age was 12.3 years. In this subgroup, the researchers compared outcomes after nonoperative, antibiotic management vs. surgery.

At 1 year, treatment failure had occurred in 125 patients, with 53 having undergone appendectomy during their first hospitalization, and 72 having experienced delayed treatment failure after being discharged.

• Higher patient-reported pain at presentation was linked to higher risk for in-hospital treatment failure (relative risk, 2.1; 95% confidence interval, 1.0-4.4) but not for delayed treatment failure (RR, 1.3; 95% CI, 0.7-2.3) or overall treatment failure at 1 year (RR, 1.5; 95% CI, 1.0-2.2).
• Pain lasting longer than 24 hours was linked to lower risk for delayed treatment failure (RR, 0.3; 95% CI, 0.1-1.0) but not for in-hospital treatment failure (RR, 1.2; 95% CI, 0.5-2.7) or treatment failure at 1 year (RR, 0.7; 95% CI, 0.4-1.2).
• Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs. 27.0; difference, 1.0; 95% CI, 0.01-2.0) and at 1 year (28.1 vs 27.0; difference, 1.1; 95% CI, 0.2-2.0).

The researchers found no increased risk for treatment failure based on age, sex, race, ethnicity, white blood cell count, primary language, insurance status, transfer status, presentation symptoms, or imaging results.

Antibiotics-only is a safe option for children

“This study suggests that pediatric patients with uncomplicated acute appendicitis should be offered treatment options, including nonoperative management,” the authors write. “Treatment with antibiotics alone is a safe and equitable option for children, with no increased risk of treatment failure based on sociodemographic or objective clinical characteristics at presentation.”

But, the authors advise: “Families need to be made aware that treatment failure is not uncommon, and they should be provided with anticipatory guidance on how to proceed should symptoms recur.”

The investigators acknowledged limitations to the study, including the nonrandomized design that may have introduced bias, the loss to follow-up, and the study population being U.S. Midwest children, who may differ from children elsewhere in the country.

Shawn D. St Peter, MD, a pediatric surgeon, medical chair, and a senior vice president at Children’s Mercy Kansas City told this news organization in an email that having a nonoperative alternative to surgical appendectomy is important.

“Antibiotics are the initial treatment for appendicitis and can be the definitive treatment,” he said.

“Surprisingly, no sociodemographic or clinical characteristics were associated with an increased risk of nonoperative appendicitis treatment failure,” added Dr. St Peter, who coauthored the commentary with Dr. Rentea.

Howard C. Jen, MD, a pediatric surgeon at University of California, Los Angeles, Mattel Children’s Hospital, was not surprised by the findings.

“Nonoperative management for acute noncomplicated appendicitis in children continues to be safe and effective in highly selected patients,” he said in an email. “This alternative to surgery should be offered routinely to patients with early acute appendicitis.” 

Dr. Jen, who was not involved with the current study, noted that it did not address the impact and costs to families of nonoperative management vs. surgery.

“For the most vulnerable children who had difficulties accessing medical care, what is the best treatment option? What factors are important to the families when making this decision?” he asked.

All study and editorial authors report no relevant financial relationships. The study was funded by the Patient-Centered Outcomes Research Institute and the National Center for Advancing Translational Sciences.

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

Children who have greater acute appendicitis pain may be less likely to improve if they’re treated with antibiotics alone, according to a secondary analysis of a nonrandomized clinical trial.

“While approximately 35% of families chose nonoperative management, a high pain score between 7-10 on a 10-point scale nearly doubled in-hospital treatment failure,” Rebecca M. Rentea, MD, a pediatric surgeon and the director of the Comprehensive Colorectal Center at Children’s Mercy Kansas City, Mo., told this news organization in an email.

“Even if nonoperative management of pediatric appendicitis did not work – resulting in the need to remove the appendix in 34% of cases – families were happy with their decisions 1 year later,” added Dr. Rentea, who coauthored an invited commentary about the study.

Lead study author Peter C. Minneci, MD, MHSc, a pediatric surgeon at Nationwide Children’s Hospital, Columbus, Ohio, and colleagues analyzed a subgroup of patients from a larger study in 10 tertiary children’s hospitals in the Midwest Pediatric Surgery Consortium.

As they reported in JAMA Network Open, the larger prospective, nonrandomized clinical trial enrolled 1,068 children between 2015 and 2018. The children ranged in age from 7 to 17 years, and they had imaging-confirmed appendicitis with an appendix diameter of 1.1 cm or less, no abscess, no appendicolith, and no phlegmon. White blood cell count was between 5,000 and 18,000 cells/μL, and abdominal pain began less than 48 hours before they received antibiotic therapy.

Caregivers chose either surgery or nonoperative antibiotic management. Patients who were treated first with antibiotics alone and who did not undergo appendectomy within 1 year were considered to have successfully completed nonoperative treatment.

The secondary analysis included the 370 children enrolled in the nonoperative group. Of these, 229 were boys, and the median age was 12.3 years. In this subgroup, the researchers compared outcomes after nonoperative, antibiotic management vs. surgery.

At 1 year, treatment failure had occurred in 125 patients, with 53 having undergone appendectomy during their first hospitalization, and 72 having experienced delayed treatment failure after being discharged.

• Higher patient-reported pain at presentation was linked to higher risk for in-hospital treatment failure (relative risk, 2.1; 95% confidence interval, 1.0-4.4) but not for delayed treatment failure (RR, 1.3; 95% CI, 0.7-2.3) or overall treatment failure at 1 year (RR, 1.5; 95% CI, 1.0-2.2).
• Pain lasting longer than 24 hours was linked to lower risk for delayed treatment failure (RR, 0.3; 95% CI, 0.1-1.0) but not for in-hospital treatment failure (RR, 1.2; 95% CI, 0.5-2.7) or treatment failure at 1 year (RR, 0.7; 95% CI, 0.4-1.2).
• Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs. 27.0; difference, 1.0; 95% CI, 0.01-2.0) and at 1 year (28.1 vs 27.0; difference, 1.1; 95% CI, 0.2-2.0).

The researchers found no increased risk for treatment failure based on age, sex, race, ethnicity, white blood cell count, primary language, insurance status, transfer status, presentation symptoms, or imaging results.

Antibiotics-only is a safe option for children

“This study suggests that pediatric patients with uncomplicated acute appendicitis should be offered treatment options, including nonoperative management,” the authors write. “Treatment with antibiotics alone is a safe and equitable option for children, with no increased risk of treatment failure based on sociodemographic or objective clinical characteristics at presentation.”

But, the authors advise: “Families need to be made aware that treatment failure is not uncommon, and they should be provided with anticipatory guidance on how to proceed should symptoms recur.”

The investigators acknowledged limitations to the study, including the nonrandomized design that may have introduced bias, the loss to follow-up, and the study population being U.S. Midwest children, who may differ from children elsewhere in the country.

Shawn D. St Peter, MD, a pediatric surgeon, medical chair, and a senior vice president at Children’s Mercy Kansas City told this news organization in an email that having a nonoperative alternative to surgical appendectomy is important.

“Antibiotics are the initial treatment for appendicitis and can be the definitive treatment,” he said.

“Surprisingly, no sociodemographic or clinical characteristics were associated with an increased risk of nonoperative appendicitis treatment failure,” added Dr. St Peter, who coauthored the commentary with Dr. Rentea.

Howard C. Jen, MD, a pediatric surgeon at University of California, Los Angeles, Mattel Children’s Hospital, was not surprised by the findings.

“Nonoperative management for acute noncomplicated appendicitis in children continues to be safe and effective in highly selected patients,” he said in an email. “This alternative to surgery should be offered routinely to patients with early acute appendicitis.” 

Dr. Jen, who was not involved with the current study, noted that it did not address the impact and costs to families of nonoperative management vs. surgery.

“For the most vulnerable children who had difficulties accessing medical care, what is the best treatment option? What factors are important to the families when making this decision?” he asked.

All study and editorial authors report no relevant financial relationships. The study was funded by the Patient-Centered Outcomes Research Institute and the National Center for Advancing Translational Sciences.

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