Pediatric News

SAVANNAH, GEORGIA — At a pathophysiological level, juvenile myasthenia gravis (MG) seems to be identical to the adult form, neuromuscular specialists learned. But there are still important differences between children and their elders that affect pediatric care.

For example, “we have to think a little bit differently about the side effect profiles of the medications and their toxicity because children may react to medications differently,” said Matthew Ginsberg, MD, a pediatric neurologist based in Akron, Ohio, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

And then there’s the matter of adherence. “It’s hard to get adults to take medication, but a teenager is sometimes an exceptional challenge,” Ginsberg said.
 

Case In Point: A 13-Year-Old With MG

Pediatric MG is rare. Cases in children are estimated to account for 10% of MG cases diagnosed each year. According to a 2020 report, “the majority will present with ptosis and a variable degree of ophthalmoplegia [paralysis of eye muscles].”

Ginsberg highlighted a case of a 13-year-old girl who’d been healthy but developed fatigable ptosis and mild restriction of extraocular movements. The patient’s acetylcholine receptor antibodies were very elevated, but she didn’t have MuSK antibodies.

“This isn’t a diagnostic conundrum. She has autoimmune myasthenia gravis with ocular manifestations,” Ginsberg said. “For someone like this, whether it’s an adult or a child, many people would start symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine.”

The use of the drug in children is similar to that in adults, he said, although weight-based dosing is used. “Usually it’s around 3-7 mg/kg/d, but it’s still very individualized based on patient response.” The timing of symptoms can affect the distribution of doses throughout the day, he said.

“There are extended-release formulations of the medication, and I think some people use them more than I do,” he said. “The side effects are basically similar to adults. Most of the patients I have on it tolerate it really well and don’t have a lot of the muscarinic side effects that you would expect.”
 

Consider Prescription Eye Drops for Ptosis

Alpha-1A agonists oxymetazoline and apraclonidine in the form of topical eye drops can help with ptosis. “They potentially avoid some of the systemic toxicity of the other medications,” Ginsberg said. “So they might be an option if you’re really just trying to target ptosis as a symptom.”

However, it can be difficult to get insurers to cover these medications, he said.

The 13-year-old patient initially improved but developed difficulty walking. “Her hands began to feel heavy, and she had difficulty chewing and nasal regurgitation. On her exam, she still had fatigable ptosis plus hypernasal speech and generalized weakness. At this point, we’re starting to see that she has generalized myasthenia gravis that may be an impending crisis.”
 

The Young Patient Worsens. Now What?

The patient was admitted and given intravenous immunoglobulin at 2 g/kg over a couple days. But her symptoms worsened following initial improvement.

Glucocorticoids can play a larger role in treatment at this stage, and the patient was initially on prednisone. But there are reasons for caution, including effects on bone growth and interference with live vaccines.

However, live vaccines aren’t common in children, with the exception of the MMRV vaccine, he said. “It’s worth noting that you can give that second dose as early as 3 months after the initial one, so most patients really should be able to complete a course before they start on immunosuppression,” he said.

Another option is immunotherapy. “There’s a really large menu of options for immunotherapy in myasthenia gravis right now,” Ginsberg said. “It’s great that we have all these options, but it adds to the complexity.”

Rituximab may be considered based on early data, he said. And thymectomy — removal of the thymus gland — should be considered early.
 

Don’t Neglect Supportive Care

Ginsberg urged colleagues to consider supportive care measures. Advocacy groups such as the Myasthenia Gravis Foundation of America can help with weight management and diet/exercise counseling, especially in patients taking glucocorticoids.

He added that “school accommodations are very important in this age group. They might need a plan, for example, to have modified gym class or an excuse not to carry a book bag between classes.”

How did the 13-year-old do? She underwent thymectomy, and her disease remained stable after 6 months. “Her rituximab was discontinued,” Ginsberg said. “She considered participating in a clinical trial but then started seeing improvements. About a year after the thymectomy, she just stopped her steroids on her own, and she was fine.”

Ginsberg had no disclosures.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — At a pathophysiological level, juvenile myasthenia gravis (MG) seems to be identical to the adult form, neuromuscular specialists learned. But there are still important differences between children and their elders that affect pediatric care.

For example, “we have to think a little bit differently about the side effect profiles of the medications and their toxicity because children may react to medications differently,” said Matthew Ginsberg, MD, a pediatric neurologist based in Akron, Ohio, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

And then there’s the matter of adherence. “It’s hard to get adults to take medication, but a teenager is sometimes an exceptional challenge,” Ginsberg said.
 

Case In Point: A 13-Year-Old With MG

Pediatric MG is rare. Cases in children are estimated to account for 10% of MG cases diagnosed each year. According to a 2020 report, “the majority will present with ptosis and a variable degree of ophthalmoplegia [paralysis of eye muscles].”

Ginsberg highlighted a case of a 13-year-old girl who’d been healthy but developed fatigable ptosis and mild restriction of extraocular movements. The patient’s acetylcholine receptor antibodies were very elevated, but she didn’t have MuSK antibodies.

“This isn’t a diagnostic conundrum. She has autoimmune myasthenia gravis with ocular manifestations,” Ginsberg said. “For someone like this, whether it’s an adult or a child, many people would start symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine.”

The use of the drug in children is similar to that in adults, he said, although weight-based dosing is used. “Usually it’s around 3-7 mg/kg/d, but it’s still very individualized based on patient response.” The timing of symptoms can affect the distribution of doses throughout the day, he said.

“There are extended-release formulations of the medication, and I think some people use them more than I do,” he said. “The side effects are basically similar to adults. Most of the patients I have on it tolerate it really well and don’t have a lot of the muscarinic side effects that you would expect.”
 

Consider Prescription Eye Drops for Ptosis

Alpha-1A agonists oxymetazoline and apraclonidine in the form of topical eye drops can help with ptosis. “They potentially avoid some of the systemic toxicity of the other medications,” Ginsberg said. “So they might be an option if you’re really just trying to target ptosis as a symptom.”

However, it can be difficult to get insurers to cover these medications, he said.

The 13-year-old patient initially improved but developed difficulty walking. “Her hands began to feel heavy, and she had difficulty chewing and nasal regurgitation. On her exam, she still had fatigable ptosis plus hypernasal speech and generalized weakness. At this point, we’re starting to see that she has generalized myasthenia gravis that may be an impending crisis.”
 

The Young Patient Worsens. Now What?

The patient was admitted and given intravenous immunoglobulin at 2 g/kg over a couple days. But her symptoms worsened following initial improvement.

Glucocorticoids can play a larger role in treatment at this stage, and the patient was initially on prednisone. But there are reasons for caution, including effects on bone growth and interference with live vaccines.

However, live vaccines aren’t common in children, with the exception of the MMRV vaccine, he said. “It’s worth noting that you can give that second dose as early as 3 months after the initial one, so most patients really should be able to complete a course before they start on immunosuppression,” he said.

Another option is immunotherapy. “There’s a really large menu of options for immunotherapy in myasthenia gravis right now,” Ginsberg said. “It’s great that we have all these options, but it adds to the complexity.”

Rituximab may be considered based on early data, he said. And thymectomy — removal of the thymus gland — should be considered early.
 

Don’t Neglect Supportive Care

Ginsberg urged colleagues to consider supportive care measures. Advocacy groups such as the Myasthenia Gravis Foundation of America can help with weight management and diet/exercise counseling, especially in patients taking glucocorticoids.

He added that “school accommodations are very important in this age group. They might need a plan, for example, to have modified gym class or an excuse not to carry a book bag between classes.”

How did the 13-year-old do? She underwent thymectomy, and her disease remained stable after 6 months. “Her rituximab was discontinued,” Ginsberg said. “She considered participating in a clinical trial but then started seeing improvements. About a year after the thymectomy, she just stopped her steroids on her own, and she was fine.”

Ginsberg had no disclosures.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — At a pathophysiological level, juvenile myasthenia gravis (MG) seems to be identical to the adult form, neuromuscular specialists learned. But there are still important differences between children and their elders that affect pediatric care.

For example, “we have to think a little bit differently about the side effect profiles of the medications and their toxicity because children may react to medications differently,” said Matthew Ginsberg, MD, a pediatric neurologist based in Akron, Ohio, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

And then there’s the matter of adherence. “It’s hard to get adults to take medication, but a teenager is sometimes an exceptional challenge,” Ginsberg said.
 

Case In Point: A 13-Year-Old With MG

Pediatric MG is rare. Cases in children are estimated to account for 10% of MG cases diagnosed each year. According to a 2020 report, “the majority will present with ptosis and a variable degree of ophthalmoplegia [paralysis of eye muscles].”

Ginsberg highlighted a case of a 13-year-old girl who’d been healthy but developed fatigable ptosis and mild restriction of extraocular movements. The patient’s acetylcholine receptor antibodies were very elevated, but she didn’t have MuSK antibodies.

“This isn’t a diagnostic conundrum. She has autoimmune myasthenia gravis with ocular manifestations,” Ginsberg said. “For someone like this, whether it’s an adult or a child, many people would start symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine.”

The use of the drug in children is similar to that in adults, he said, although weight-based dosing is used. “Usually it’s around 3-7 mg/kg/d, but it’s still very individualized based on patient response.” The timing of symptoms can affect the distribution of doses throughout the day, he said.

“There are extended-release formulations of the medication, and I think some people use them more than I do,” he said. “The side effects are basically similar to adults. Most of the patients I have on it tolerate it really well and don’t have a lot of the muscarinic side effects that you would expect.”
 

Consider Prescription Eye Drops for Ptosis

Alpha-1A agonists oxymetazoline and apraclonidine in the form of topical eye drops can help with ptosis. “They potentially avoid some of the systemic toxicity of the other medications,” Ginsberg said. “So they might be an option if you’re really just trying to target ptosis as a symptom.”

However, it can be difficult to get insurers to cover these medications, he said.

The 13-year-old patient initially improved but developed difficulty walking. “Her hands began to feel heavy, and she had difficulty chewing and nasal regurgitation. On her exam, she still had fatigable ptosis plus hypernasal speech and generalized weakness. At this point, we’re starting to see that she has generalized myasthenia gravis that may be an impending crisis.”
 

The Young Patient Worsens. Now What?

The patient was admitted and given intravenous immunoglobulin at 2 g/kg over a couple days. But her symptoms worsened following initial improvement.

Glucocorticoids can play a larger role in treatment at this stage, and the patient was initially on prednisone. But there are reasons for caution, including effects on bone growth and interference with live vaccines.

However, live vaccines aren’t common in children, with the exception of the MMRV vaccine, he said. “It’s worth noting that you can give that second dose as early as 3 months after the initial one, so most patients really should be able to complete a course before they start on immunosuppression,” he said.

Another option is immunotherapy. “There’s a really large menu of options for immunotherapy in myasthenia gravis right now,” Ginsberg said. “It’s great that we have all these options, but it adds to the complexity.”

Rituximab may be considered based on early data, he said. And thymectomy — removal of the thymus gland — should be considered early.
 

Don’t Neglect Supportive Care

Ginsberg urged colleagues to consider supportive care measures. Advocacy groups such as the Myasthenia Gravis Foundation of America can help with weight management and diet/exercise counseling, especially in patients taking glucocorticoids.

He added that “school accommodations are very important in this age group. They might need a plan, for example, to have modified gym class or an excuse not to carry a book bag between classes.”

How did the 13-year-old do? She underwent thymectomy, and her disease remained stable after 6 months. “Her rituximab was discontinued,” Ginsberg said. “She considered participating in a clinical trial but then started seeing improvements. About a year after the thymectomy, she just stopped her steroids on her own, and she was fine.”

Ginsberg had no disclosures.
 

A version of this article appeared on Medscape.com.

Diagnostic errors are common in hospitals and are largely preventable, according to a new observational study led by Anuj K. Dalal, MD, from the Division of General Internal Medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston, published in BMJ Quality & Safety.

Dalal and his colleagues found that 1 in 14 general medicine patients (7%) suffer harm due to diagnostic errors, and up to 85% of these cases could be prevented.
 

Few Studies on Diagnostic Errors

The study found that adverse event surveillance in hospital underestimated the prevalence of harmful diagnostic errors.

“It is difficult to quantify and characterize diagnostic errors, which have been studied less than medication errors,” Micaela La Regina, MD, an internist and head of the Clinical Governance and Risk Management Unit at ASL 5 in La Spezia, Italy, told Univadis Italy. “Generally, it is estimated that around 50% of diagnostic errors are preventable, but the authors of this study went beyond simply observing the hospital admission period and followed their sample for 90 days after discharge. Their findings will need to be verified in other studies, but they seem convincing.”

The researchers in Boston selected a random sample of 675 hospital patients from a total of 9147 eligible cases who received general medical care between July 2019 and September 2021, excluding the peak of the COVID-19 pandemic (April-December 2020). They retrospectively reviewed the patients’ electronic health records using a structured method to evaluate the diagnostic process for potential errors and then estimated the impact and severity of any harm.

Cases sampled were those featuring transfer to intensive care more than 24 hours after admission (100% of 130 cases), death within 90 days of hospital admission or after discharge (38.5% of 141 cases), complex clinical problems without transfer to intensive care or death within 90 days of admission (7% of 298 cases), and 2.4% of 106 cases without high-risk criteria.

Each case was reviewed by two experts trained in the use of diagnostic error evaluation and research taxonomy, modified for acute care. Harm was classified as mild, moderate, severe, or fatal. The review assessed whether diagnostic error contributed to the harm and whether it was preventable. Cases with discrepancies or uncertainties regarding the diagnostic error or its impact were further examined by an expert panel.
 

Most Frequent Situations

Among all the cases examined, diagnostic errors were identified in 160 instances in 154 patients. The most frequent situations with diagnostic errors involved transfer to intensive care (54 cases), death within 90 days (34 cases), and complex clinical problems (52 cases). Diagnostic errors causing harm were found in 84 cases (82 patients), of which 37 (28.5%) occurred in those transferred to intensive care; 18 (13%) among patients who died within 90 days; 23 (8%) among patients with complex clinical issues; and 6 (6%) in low-risk cases.

The severity of harm was categorized as minor in 5 cases (6%), moderate in 36 (43%), major in 25 (30%), and fatal in 18 cases (21.5%). Overall, the researchers estimated that the proportion of harmful, preventable diagnostic errors with serious harm in general medicine patients was slightly more than 7%, 6%, and 1%, respectively.
 

Most Frequent Diagnoses

The most common diagnoses associated with diagnostic errors in the study included heart failure, acute kidney injury, sepsis, pneumonia, respiratory failure, altered mental state, abdominal pain, and hypoxemia. Dalal and colleagues emphasize the need for more attention to diagnostic error analysis, including the adoption of artificial intelligence–based tools for medical record screening.

“The technological approach, with alert-based systems, can certainly be helpful, but more attention must also be paid to continuous training and the well-being of healthcare workers. It is also crucial to encourage greater listening to caregivers and patients,” said La Regina. She noted that in the past, a focus on error prevention has often led to an increased workload and administrative burden on healthcare workers. However, the well-being of healthcare workers is key to ensuring patient safety.

“Countermeasures to reduce diagnostic errors require a multimodal approach, targeting professionals, the healthcare system, and organizational aspects, because even waiting lists are a critical factor,” she said. As a clinical risk expert, she recently proposed an adaptation of the value-based medicine formula in the International Journal for Quality in Health Care to include healthcare professionals’ care experience as one of the elements that contribute to determining high-value healthcare interventions. “Experiments are already underway to reimburse healthcare costs based on this formula, which also allows the assessment of the value of skills and expertise acquired by healthcare workers,” concluded La Regina.
 

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Diagnostic errors are common in hospitals and are largely preventable, according to a new observational study led by Anuj K. Dalal, MD, from the Division of General Internal Medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston, published in BMJ Quality & Safety.

Dalal and his colleagues found that 1 in 14 general medicine patients (7%) suffer harm due to diagnostic errors, and up to 85% of these cases could be prevented.
 

Few Studies on Diagnostic Errors

The study found that adverse event surveillance in hospital underestimated the prevalence of harmful diagnostic errors.

“It is difficult to quantify and characterize diagnostic errors, which have been studied less than medication errors,” Micaela La Regina, MD, an internist and head of the Clinical Governance and Risk Management Unit at ASL 5 in La Spezia, Italy, told Univadis Italy. “Generally, it is estimated that around 50% of diagnostic errors are preventable, but the authors of this study went beyond simply observing the hospital admission period and followed their sample for 90 days after discharge. Their findings will need to be verified in other studies, but they seem convincing.”

The researchers in Boston selected a random sample of 675 hospital patients from a total of 9147 eligible cases who received general medical care between July 2019 and September 2021, excluding the peak of the COVID-19 pandemic (April-December 2020). They retrospectively reviewed the patients’ electronic health records using a structured method to evaluate the diagnostic process for potential errors and then estimated the impact and severity of any harm.

Cases sampled were those featuring transfer to intensive care more than 24 hours after admission (100% of 130 cases), death within 90 days of hospital admission or after discharge (38.5% of 141 cases), complex clinical problems without transfer to intensive care or death within 90 days of admission (7% of 298 cases), and 2.4% of 106 cases without high-risk criteria.

Each case was reviewed by two experts trained in the use of diagnostic error evaluation and research taxonomy, modified for acute care. Harm was classified as mild, moderate, severe, or fatal. The review assessed whether diagnostic error contributed to the harm and whether it was preventable. Cases with discrepancies or uncertainties regarding the diagnostic error or its impact were further examined by an expert panel.
 

Most Frequent Situations

Among all the cases examined, diagnostic errors were identified in 160 instances in 154 patients. The most frequent situations with diagnostic errors involved transfer to intensive care (54 cases), death within 90 days (34 cases), and complex clinical problems (52 cases). Diagnostic errors causing harm were found in 84 cases (82 patients), of which 37 (28.5%) occurred in those transferred to intensive care; 18 (13%) among patients who died within 90 days; 23 (8%) among patients with complex clinical issues; and 6 (6%) in low-risk cases.

The severity of harm was categorized as minor in 5 cases (6%), moderate in 36 (43%), major in 25 (30%), and fatal in 18 cases (21.5%). Overall, the researchers estimated that the proportion of harmful, preventable diagnostic errors with serious harm in general medicine patients was slightly more than 7%, 6%, and 1%, respectively.
 

Most Frequent Diagnoses

The most common diagnoses associated with diagnostic errors in the study included heart failure, acute kidney injury, sepsis, pneumonia, respiratory failure, altered mental state, abdominal pain, and hypoxemia. Dalal and colleagues emphasize the need for more attention to diagnostic error analysis, including the adoption of artificial intelligence–based tools for medical record screening.

“The technological approach, with alert-based systems, can certainly be helpful, but more attention must also be paid to continuous training and the well-being of healthcare workers. It is also crucial to encourage greater listening to caregivers and patients,” said La Regina. She noted that in the past, a focus on error prevention has often led to an increased workload and administrative burden on healthcare workers. However, the well-being of healthcare workers is key to ensuring patient safety.

“Countermeasures to reduce diagnostic errors require a multimodal approach, targeting professionals, the healthcare system, and organizational aspects, because even waiting lists are a critical factor,” she said. As a clinical risk expert, she recently proposed an adaptation of the value-based medicine formula in the International Journal for Quality in Health Care to include healthcare professionals’ care experience as one of the elements that contribute to determining high-value healthcare interventions. “Experiments are already underway to reimburse healthcare costs based on this formula, which also allows the assessment of the value of skills and expertise acquired by healthcare workers,” concluded La Regina.
 

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Diagnostic errors are common in hospitals and are largely preventable, according to a new observational study led by Anuj K. Dalal, MD, from the Division of General Internal Medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston, published in BMJ Quality & Safety.

Dalal and his colleagues found that 1 in 14 general medicine patients (7%) suffer harm due to diagnostic errors, and up to 85% of these cases could be prevented.
 

Few Studies on Diagnostic Errors

The study found that adverse event surveillance in hospital underestimated the prevalence of harmful diagnostic errors.

“It is difficult to quantify and characterize diagnostic errors, which have been studied less than medication errors,” Micaela La Regina, MD, an internist and head of the Clinical Governance and Risk Management Unit at ASL 5 in La Spezia, Italy, told Univadis Italy. “Generally, it is estimated that around 50% of diagnostic errors are preventable, but the authors of this study went beyond simply observing the hospital admission period and followed their sample for 90 days after discharge. Their findings will need to be verified in other studies, but they seem convincing.”

The researchers in Boston selected a random sample of 675 hospital patients from a total of 9147 eligible cases who received general medical care between July 2019 and September 2021, excluding the peak of the COVID-19 pandemic (April-December 2020). They retrospectively reviewed the patients’ electronic health records using a structured method to evaluate the diagnostic process for potential errors and then estimated the impact and severity of any harm.

Cases sampled were those featuring transfer to intensive care more than 24 hours after admission (100% of 130 cases), death within 90 days of hospital admission or after discharge (38.5% of 141 cases), complex clinical problems without transfer to intensive care or death within 90 days of admission (7% of 298 cases), and 2.4% of 106 cases without high-risk criteria.

Each case was reviewed by two experts trained in the use of diagnostic error evaluation and research taxonomy, modified for acute care. Harm was classified as mild, moderate, severe, or fatal. The review assessed whether diagnostic error contributed to the harm and whether it was preventable. Cases with discrepancies or uncertainties regarding the diagnostic error or its impact were further examined by an expert panel.
 

Most Frequent Situations

Among all the cases examined, diagnostic errors were identified in 160 instances in 154 patients. The most frequent situations with diagnostic errors involved transfer to intensive care (54 cases), death within 90 days (34 cases), and complex clinical problems (52 cases). Diagnostic errors causing harm were found in 84 cases (82 patients), of which 37 (28.5%) occurred in those transferred to intensive care; 18 (13%) among patients who died within 90 days; 23 (8%) among patients with complex clinical issues; and 6 (6%) in low-risk cases.

The severity of harm was categorized as minor in 5 cases (6%), moderate in 36 (43%), major in 25 (30%), and fatal in 18 cases (21.5%). Overall, the researchers estimated that the proportion of harmful, preventable diagnostic errors with serious harm in general medicine patients was slightly more than 7%, 6%, and 1%, respectively.
 

Most Frequent Diagnoses

The most common diagnoses associated with diagnostic errors in the study included heart failure, acute kidney injury, sepsis, pneumonia, respiratory failure, altered mental state, abdominal pain, and hypoxemia. Dalal and colleagues emphasize the need for more attention to diagnostic error analysis, including the adoption of artificial intelligence–based tools for medical record screening.

“The technological approach, with alert-based systems, can certainly be helpful, but more attention must also be paid to continuous training and the well-being of healthcare workers. It is also crucial to encourage greater listening to caregivers and patients,” said La Regina. She noted that in the past, a focus on error prevention has often led to an increased workload and administrative burden on healthcare workers. However, the well-being of healthcare workers is key to ensuring patient safety.

“Countermeasures to reduce diagnostic errors require a multimodal approach, targeting professionals, the healthcare system, and organizational aspects, because even waiting lists are a critical factor,” she said. As a clinical risk expert, she recently proposed an adaptation of the value-based medicine formula in the International Journal for Quality in Health Care to include healthcare professionals’ care experience as one of the elements that contribute to determining high-value healthcare interventions. “Experiments are already underway to reimburse healthcare costs based on this formula, which also allows the assessment of the value of skills and expertise acquired by healthcare workers,” concluded La Regina.
 

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Treatment with ritlecitinib sustained hair regrowth through week 48 in patients with alopecia areata (AA), and up to one third of nonresponders at week 24 also achieved responses by week 48.

METHODOLOGY:

• Researchers conducted a post hoc analysis of an international, randomized, double-blind, placebo-controlled, phase 2b/3 trial (ALLEGRO) and included 718 adults and adolescents aged 12 or older with severe AA (Severity of Alopecia Tool [SALT] score ≥ 50).
• Patients received various doses of the oral Janus kinase inhibitor ritlecitinib, with or without a 4-week loading dose, including 200/50 mg, 200/30 mg, 50 mg, or 30 mg, with or without a 4-week loading dose for up to 24 weeks and continued to receive their assigned maintenance dose.
• Researchers assessed sustained clinical responses at week 48 for those who had achieved SALT scores ≤ 20 and ≤ 10 at 24 weeks, and nonresponders at week 24 were assessed for responses through week 48.
• Adverse events were also evaluated.

TAKEAWAY:

• Among patients on ritlecitinib who had responded at week 24, SALT responses ≤ 20 were sustained in 85.2%-100% of patients through week 48. Similar results were seen among patients who achieved a SALT score ≤ 10 (68.8%-91.7%) and improvements in eyebrow (70.4%-96.9%) or eyelash (52.4%-94.1%) assessment scores.
• Among those who were nonresponders at week 24, 22.2%-33.7% achieved a SALT score ≤ 20 and 19.8%-25.5% achieved a SALT score ≤ 10 by week 48. Similarly, among those with no eyebrow or eyelash responses at week 24, 19.7%-32.8% and 16.7%-30.2% had improved eyebrow or eyelash assessment scores, respectively, at week 48.
• Between weeks 24 and 48, adverse events were reported in 74%-93% of patients who achieved a SALT score ≤ 20, most were mild or moderate; two serious events were reported but deemed unrelated to treatment. The safety profile was similar across all subgroups.
• No deaths, malignancies, major cardiovascular events, opportunistic infections, or herpes zoster infections were observed.

IN PRACTICE:

“The majority of ritlecitinib-treated patients with AA who met target clinical response based on scalp, eyebrow, or eyelash regrowth at week 24 sustained their response through week 48 with continued treatment,” the authors wrote. “Some patients, including those with more extensive hair loss, may require ritlecitinib treatment beyond 6 months to achieve target clinical response,” they added.

SOURCE:

The study was led by Melissa Piliang, MD, of the Department of Dermatology, Cleveland Clinic, and was published online on October 17 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis was limited by its post hoc nature, small sample size in each treatment group, and a follow-up period of only 48 weeks.

DISCLOSURES:

This study was funded by Pfizer. Piliang disclosed being a consultant or investigator for Pfizer, Eli Lilly, and Procter & Gamble. Six authors were employees or shareholders of or received salary from Pfizer. Other authors also reported financial relationships with pharmaceutical companies outside this work, including Pfizer.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Treatment with ritlecitinib sustained hair regrowth through week 48 in patients with alopecia areata (AA), and up to one third of nonresponders at week 24 also achieved responses by week 48.

METHODOLOGY:

• Researchers conducted a post hoc analysis of an international, randomized, double-blind, placebo-controlled, phase 2b/3 trial (ALLEGRO) and included 718 adults and adolescents aged 12 or older with severe AA (Severity of Alopecia Tool [SALT] score ≥ 50).
• Patients received various doses of the oral Janus kinase inhibitor ritlecitinib, with or without a 4-week loading dose, including 200/50 mg, 200/30 mg, 50 mg, or 30 mg, with or without a 4-week loading dose for up to 24 weeks and continued to receive their assigned maintenance dose.
• Researchers assessed sustained clinical responses at week 48 for those who had achieved SALT scores ≤ 20 and ≤ 10 at 24 weeks, and nonresponders at week 24 were assessed for responses through week 48.
• Adverse events were also evaluated.

TAKEAWAY:

• Among patients on ritlecitinib who had responded at week 24, SALT responses ≤ 20 were sustained in 85.2%-100% of patients through week 48. Similar results were seen among patients who achieved a SALT score ≤ 10 (68.8%-91.7%) and improvements in eyebrow (70.4%-96.9%) or eyelash (52.4%-94.1%) assessment scores.
• Among those who were nonresponders at week 24, 22.2%-33.7% achieved a SALT score ≤ 20 and 19.8%-25.5% achieved a SALT score ≤ 10 by week 48. Similarly, among those with no eyebrow or eyelash responses at week 24, 19.7%-32.8% and 16.7%-30.2% had improved eyebrow or eyelash assessment scores, respectively, at week 48.
• Between weeks 24 and 48, adverse events were reported in 74%-93% of patients who achieved a SALT score ≤ 20, most were mild or moderate; two serious events were reported but deemed unrelated to treatment. The safety profile was similar across all subgroups.
• No deaths, malignancies, major cardiovascular events, opportunistic infections, or herpes zoster infections were observed.

IN PRACTICE:

“The majority of ritlecitinib-treated patients with AA who met target clinical response based on scalp, eyebrow, or eyelash regrowth at week 24 sustained their response through week 48 with continued treatment,” the authors wrote. “Some patients, including those with more extensive hair loss, may require ritlecitinib treatment beyond 6 months to achieve target clinical response,” they added.

SOURCE:

The study was led by Melissa Piliang, MD, of the Department of Dermatology, Cleveland Clinic, and was published online on October 17 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis was limited by its post hoc nature, small sample size in each treatment group, and a follow-up period of only 48 weeks.

DISCLOSURES:

This study was funded by Pfizer. Piliang disclosed being a consultant or investigator for Pfizer, Eli Lilly, and Procter & Gamble. Six authors were employees or shareholders of or received salary from Pfizer. Other authors also reported financial relationships with pharmaceutical companies outside this work, including Pfizer.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Treatment with ritlecitinib sustained hair regrowth through week 48 in patients with alopecia areata (AA), and up to one third of nonresponders at week 24 also achieved responses by week 48.

METHODOLOGY:

• Researchers conducted a post hoc analysis of an international, randomized, double-blind, placebo-controlled, phase 2b/3 trial (ALLEGRO) and included 718 adults and adolescents aged 12 or older with severe AA (Severity of Alopecia Tool [SALT] score ≥ 50).
• Patients received various doses of the oral Janus kinase inhibitor ritlecitinib, with or without a 4-week loading dose, including 200/50 mg, 200/30 mg, 50 mg, or 30 mg, with or without a 4-week loading dose for up to 24 weeks and continued to receive their assigned maintenance dose.
• Researchers assessed sustained clinical responses at week 48 for those who had achieved SALT scores ≤ 20 and ≤ 10 at 24 weeks, and nonresponders at week 24 were assessed for responses through week 48.
• Adverse events were also evaluated.

TAKEAWAY:

• Among patients on ritlecitinib who had responded at week 24, SALT responses ≤ 20 were sustained in 85.2%-100% of patients through week 48. Similar results were seen among patients who achieved a SALT score ≤ 10 (68.8%-91.7%) and improvements in eyebrow (70.4%-96.9%) or eyelash (52.4%-94.1%) assessment scores.
• Among those who were nonresponders at week 24, 22.2%-33.7% achieved a SALT score ≤ 20 and 19.8%-25.5% achieved a SALT score ≤ 10 by week 48. Similarly, among those with no eyebrow or eyelash responses at week 24, 19.7%-32.8% and 16.7%-30.2% had improved eyebrow or eyelash assessment scores, respectively, at week 48.
• Between weeks 24 and 48, adverse events were reported in 74%-93% of patients who achieved a SALT score ≤ 20, most were mild or moderate; two serious events were reported but deemed unrelated to treatment. The safety profile was similar across all subgroups.
• No deaths, malignancies, major cardiovascular events, opportunistic infections, or herpes zoster infections were observed.

IN PRACTICE:

“The majority of ritlecitinib-treated patients with AA who met target clinical response based on scalp, eyebrow, or eyelash regrowth at week 24 sustained their response through week 48 with continued treatment,” the authors wrote. “Some patients, including those with more extensive hair loss, may require ritlecitinib treatment beyond 6 months to achieve target clinical response,” they added.

SOURCE:

The study was led by Melissa Piliang, MD, of the Department of Dermatology, Cleveland Clinic, and was published online on October 17 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis was limited by its post hoc nature, small sample size in each treatment group, and a follow-up period of only 48 weeks.

DISCLOSURES:

This study was funded by Pfizer. Piliang disclosed being a consultant or investigator for Pfizer, Eli Lilly, and Procter & Gamble. Six authors were employees or shareholders of or received salary from Pfizer. Other authors also reported financial relationships with pharmaceutical companies outside this work, including Pfizer.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

LOS ANGELES — Embedding a new discharge order set into electronic health records (EHRs) with a preselected 5-day antibiotic course for children aged 2 years or older diagnosed with acute otitis media (AOM) cut antibiotic duration sharply, according to new data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

“We were effectively able to cut antibiotic use in half by shortening the duration of treatment,” said lead author Joana Dimo, DO, a Pediatric Infectious Diseases fellow at the University of Colorado Denver/Children’s Hospital Colorado.

In the United States, 80% of children will experience otitis media during their lifetime. Untreated ear infections can lead to symptoms ranging from mild ear discharge to life-threatening conditions such as mastoiditis and intracranial abscesses.
 

Most Cases Resolve Without Antibiotics

Ear infections “are the leading reason for antibiotic prescriptions in kids,” Dimo noted, adding that 24% of all pediatric antibiotic prescriptions are for AOM. Amoxicillin is the preferred first-line treatment. “Research supports that 75% of children get better on their own without antibiotics, and when needed, short courses of just 5 days are safe and effective.”

Antibiotics can cause side effects such as diarrhea and rashes. “Each additional day of antibiotics that are not needed leads to more side effects,” Dimo said, as well as contributing to antibiotic resistance.

Dimo’s team implemented new EHR order sets across the University of Colorado/Children’s Hospital Colorado health network’s four emergency departments and four urgent care centers and included 31,929 patients in the study.

Then they conducted a retrospective review of patients 61 days to 18 years old who entered those settings and had confirmed AOM between January 2019 through December 2023, before and after the April 2021 intervention. The researchers also developed a guideline on managing ear infections to support clinicians as part of the intervention in December 2022.
 

Compliance Grew From 3% to 83%

Dimo said they found very few clinicians in their study had been prescribing according to current guidelines. Their results showed a jump from 3% to 83% in providers prescribing 5-day durations of antibiotics for children aged 2 years or older after their intervention.

The intervention did not lead to increased treatment failures or complications, she added. The team looked for diagnostic codes for mastoiditis, subperiosteal abscess, petrositis, labyrinthitis, meningitis, and intracranial abscess, and “none of our patients” developed any of those complications, Dimo said.

Dimo said the overall rate of prescribing, however, increased. Finding out why prescribing rates remained high throughout the study, before and after their intervention, is a question they are investigating in future work, she said.
 

Cost-Effective and Scalable

“The benefit of this strategy to other institutions is that it’s not labor-intensive. It’s cost-effective, and it can result in dramatic changes in antibiotic use,” Dimo said.

“In the outpatient setting, there’s still a lot of antibiotics being given unnecessarily to children with acute otitis media,” said William Schaffner, MD, infectious disease specialist at Vanderbilt University School of Medicine in Nashville, Tennessee, who was not part of the research. “The American Academy of Pediatrics has been working on that for about a decade — to get pediatricians attuned to when you use them. Most of these episodes of acute otitis media — it’s now well-established — are due to viral infections.”

He said that some physicians may still be defaulting to the longer doses — up to 10 days — that they may have learned in medical school or residency.

“The data would indicate that 5 days of treatment — when treatment is appropriate — is, in the vast majority of instances, sufficient,” Schaffner said.

The researchers “were remarkably successful,” he said, adding that another question is ripe for research. “They still have to get to this issue of whether all of these antibiotic starts were necessary.”

Not knowing whether antibiotic prescriptions in this study were warranted is a limitation of the study, Dimo said, as was not being able to track whether patients presented to institutions outside their own for a return visit or for complications.

She said she thinks one of the reasons for such a sharp increase in compliance was that clinicians in their system routinely use order sets, so using the new order sets easily became part of their workflow.

Dimo and Schaffner reported no relevant financial relationships.

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

LOS ANGELES — Embedding a new discharge order set into electronic health records (EHRs) with a preselected 5-day antibiotic course for children aged 2 years or older diagnosed with acute otitis media (AOM) cut antibiotic duration sharply, according to new data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

“We were effectively able to cut antibiotic use in half by shortening the duration of treatment,” said lead author Joana Dimo, DO, a Pediatric Infectious Diseases fellow at the University of Colorado Denver/Children’s Hospital Colorado.

In the United States, 80% of children will experience otitis media during their lifetime. Untreated ear infections can lead to symptoms ranging from mild ear discharge to life-threatening conditions such as mastoiditis and intracranial abscesses.
 

Most Cases Resolve Without Antibiotics

Ear infections “are the leading reason for antibiotic prescriptions in kids,” Dimo noted, adding that 24% of all pediatric antibiotic prescriptions are for AOM. Amoxicillin is the preferred first-line treatment. “Research supports that 75% of children get better on their own without antibiotics, and when needed, short courses of just 5 days are safe and effective.”

Antibiotics can cause side effects such as diarrhea and rashes. “Each additional day of antibiotics that are not needed leads to more side effects,” Dimo said, as well as contributing to antibiotic resistance.

Dimo’s team implemented new EHR order sets across the University of Colorado/Children’s Hospital Colorado health network’s four emergency departments and four urgent care centers and included 31,929 patients in the study.

Then they conducted a retrospective review of patients 61 days to 18 years old who entered those settings and had confirmed AOM between January 2019 through December 2023, before and after the April 2021 intervention. The researchers also developed a guideline on managing ear infections to support clinicians as part of the intervention in December 2022.
 

Compliance Grew From 3% to 83%

Dimo said they found very few clinicians in their study had been prescribing according to current guidelines. Their results showed a jump from 3% to 83% in providers prescribing 5-day durations of antibiotics for children aged 2 years or older after their intervention.

The intervention did not lead to increased treatment failures or complications, she added. The team looked for diagnostic codes for mastoiditis, subperiosteal abscess, petrositis, labyrinthitis, meningitis, and intracranial abscess, and “none of our patients” developed any of those complications, Dimo said.

Dimo said the overall rate of prescribing, however, increased. Finding out why prescribing rates remained high throughout the study, before and after their intervention, is a question they are investigating in future work, she said.
 

Cost-Effective and Scalable

“The benefit of this strategy to other institutions is that it’s not labor-intensive. It’s cost-effective, and it can result in dramatic changes in antibiotic use,” Dimo said.

“In the outpatient setting, there’s still a lot of antibiotics being given unnecessarily to children with acute otitis media,” said William Schaffner, MD, infectious disease specialist at Vanderbilt University School of Medicine in Nashville, Tennessee, who was not part of the research. “The American Academy of Pediatrics has been working on that for about a decade — to get pediatricians attuned to when you use them. Most of these episodes of acute otitis media — it’s now well-established — are due to viral infections.”

He said that some physicians may still be defaulting to the longer doses — up to 10 days — that they may have learned in medical school or residency.

“The data would indicate that 5 days of treatment — when treatment is appropriate — is, in the vast majority of instances, sufficient,” Schaffner said.

The researchers “were remarkably successful,” he said, adding that another question is ripe for research. “They still have to get to this issue of whether all of these antibiotic starts were necessary.”

Not knowing whether antibiotic prescriptions in this study were warranted is a limitation of the study, Dimo said, as was not being able to track whether patients presented to institutions outside their own for a return visit or for complications.

She said she thinks one of the reasons for such a sharp increase in compliance was that clinicians in their system routinely use order sets, so using the new order sets easily became part of their workflow.

Dimo and Schaffner reported no relevant financial relationships.

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

LOS ANGELES — Embedding a new discharge order set into electronic health records (EHRs) with a preselected 5-day antibiotic course for children aged 2 years or older diagnosed with acute otitis media (AOM) cut antibiotic duration sharply, according to new data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

“We were effectively able to cut antibiotic use in half by shortening the duration of treatment,” said lead author Joana Dimo, DO, a Pediatric Infectious Diseases fellow at the University of Colorado Denver/Children’s Hospital Colorado.

In the United States, 80% of children will experience otitis media during their lifetime. Untreated ear infections can lead to symptoms ranging from mild ear discharge to life-threatening conditions such as mastoiditis and intracranial abscesses.
 

Most Cases Resolve Without Antibiotics

Ear infections “are the leading reason for antibiotic prescriptions in kids,” Dimo noted, adding that 24% of all pediatric antibiotic prescriptions are for AOM. Amoxicillin is the preferred first-line treatment. “Research supports that 75% of children get better on their own without antibiotics, and when needed, short courses of just 5 days are safe and effective.”

Antibiotics can cause side effects such as diarrhea and rashes. “Each additional day of antibiotics that are not needed leads to more side effects,” Dimo said, as well as contributing to antibiotic resistance.

Dimo’s team implemented new EHR order sets across the University of Colorado/Children’s Hospital Colorado health network’s four emergency departments and four urgent care centers and included 31,929 patients in the study.

Then they conducted a retrospective review of patients 61 days to 18 years old who entered those settings and had confirmed AOM between January 2019 through December 2023, before and after the April 2021 intervention. The researchers also developed a guideline on managing ear infections to support clinicians as part of the intervention in December 2022.
 

Compliance Grew From 3% to 83%

Dimo said they found very few clinicians in their study had been prescribing according to current guidelines. Their results showed a jump from 3% to 83% in providers prescribing 5-day durations of antibiotics for children aged 2 years or older after their intervention.

The intervention did not lead to increased treatment failures or complications, she added. The team looked for diagnostic codes for mastoiditis, subperiosteal abscess, petrositis, labyrinthitis, meningitis, and intracranial abscess, and “none of our patients” developed any of those complications, Dimo said.

Dimo said the overall rate of prescribing, however, increased. Finding out why prescribing rates remained high throughout the study, before and after their intervention, is a question they are investigating in future work, she said.
 

Cost-Effective and Scalable

“The benefit of this strategy to other institutions is that it’s not labor-intensive. It’s cost-effective, and it can result in dramatic changes in antibiotic use,” Dimo said.

“In the outpatient setting, there’s still a lot of antibiotics being given unnecessarily to children with acute otitis media,” said William Schaffner, MD, infectious disease specialist at Vanderbilt University School of Medicine in Nashville, Tennessee, who was not part of the research. “The American Academy of Pediatrics has been working on that for about a decade — to get pediatricians attuned to when you use them. Most of these episodes of acute otitis media — it’s now well-established — are due to viral infections.”

He said that some physicians may still be defaulting to the longer doses — up to 10 days — that they may have learned in medical school or residency.

“The data would indicate that 5 days of treatment — when treatment is appropriate — is, in the vast majority of instances, sufficient,” Schaffner said.

The researchers “were remarkably successful,” he said, adding that another question is ripe for research. “They still have to get to this issue of whether all of these antibiotic starts were necessary.”

Not knowing whether antibiotic prescriptions in this study were warranted is a limitation of the study, Dimo said, as was not being able to track whether patients presented to institutions outside their own for a return visit or for complications.

She said she thinks one of the reasons for such a sharp increase in compliance was that clinicians in their system routinely use order sets, so using the new order sets easily became part of their workflow.

Dimo and Schaffner reported no relevant financial relationships.

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

ORLANDO, FLORIDA — Asthma is the most common cause of chronic cough in children, but it’s important to be aware of other differential diagnoses for those patients who have less common concerns, according to Rajeev Bhatia, MD, division chief of pulmonology at Phoenix Children’s in Phoenix, Arizona. Bhatia reviewed both the major causes of chronic cough as well as the rare zebras to watch out for in a presentation at the American Academy of Pediatrics (AAP) 2024 National Conference.

“When you see a patient for cough, the most important thing is, history, history, history,” Bhatia said. “There are many, many, many clues in the history, age of onset, and duration.” That includes starting at birth to ensure you don’t miss key details such as a preterm birth. It’s also important to discuss what the cough sounds like, how frequent it is, what makes it better, what makes it worse, and how it’s affecting the child and others around them — all of which can help narrow the diagnosis.

Jose Quijada, DO, a pediatrician with CommuniCare Pediatrics in San Antonio, found the session “incredibly useful” not only because of the specific pointers about each condition but also because of the realistic case studies he included throughout.

“Sometimes when you’re practicing, you focus on what’s most common,” Quijada said, so it was helpful to get a review of some of the key features and red flags that point to less common causes that may need to be considered. He particularly appreciated the discussion of habitual cough and potential treatments because those can be challenging patients and it can be tough to find a middle ground with how much workup to do.
 

Common Causes of Chronic Cough

The coughing from inadequately controlled asthma tends to be nonproductive and worse at night or in the early morning, Bhatia explained, and it’s often accompanied by wheezing, shortness of breath, and chest tightness. While fractional exhaled nitric oxide can be useful, “studies show that it is more useful for to monitor the symptoms rather than to diagnose the asthma,” Bhatia told attendees, but he also added that spirometry can be normal in patients with asthma. In young patients, the Asthma Predictive Index can be an invaluable tool, he also said.

Another common cause of chronic cough is a postinfectious cough, which lasts more than 3 weeks after resolution of acute upper respiratory infection. It occurs in about one in 10 children after a viral infection such as a rhinovirus or respiratory syncytial virus infection and results from extensive inflammation and disruption of the airway epithelial integrity. Chest x-rays are usually normal in these patients, and the cough will usually resolve on its own. Albuterol has not been shown to be any more effective than placebo for a postinfectious cough, and antibiotics similarly have no clinically useful role.

A wet cough that lasts for at least 4 weeks and appears to have no other specific cause may be protracted bacterial bronchitis (PBB). While the cause of PBB isn’t known, it could be due to frequent illnesses that cause airway inflammation and injury over time, thereby making it easier for bacteria to grow and cause infection. Risk factors include tracheomalacia/bronchomalacia and childcare attendance, and typical pathogens include Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis.

While an x-ray can be done, radiography is often normal in patients with PBB. Bronchoscopy will reveal purulent secretions. PBB should resolve with at least 2 weeks of antibiotics, including amoxicillin-clavulanate, but the course can be extended to 4 weeks if the cough persists. However, about 40% of patients will have recurrence, and those with recurrent PBB or with a chronic cough unresponsive to 4 weeks of antibiotics should be referred to a pediatric pulmonologist.

Upper airway cough syndrome is the updated name for postnasal drip, which can occur with both allergic and nonallergic rhinitis and chronic rhinosinusitis. This is often a dry, throat-clearing cough that can be accompanied by headaches, nasal congestion, and sinus or facial tenderness. An examination will reveal posterior pharynx cobblestoning, Bhatia said, and empirical use of intranasal steroids can be both diagnostic and therapeutic for upper airway cough syndrome. He also emphasized the importance of taking an environmental history and avoiding exposure of environmental triggers.
 

Uncommon Pulmonary Causes of Chronic Cough

After discussing frequent reasons patients may present with a chronic cough, Bhatia went on to discuss the less common things to consider if the provider has eliminated the other possibilities. These include both pulmonary causes as well as congenital malformations, gastrointestinal causes, and habit cough.

A child who presents with a sudden onset of cough or wheeze in the absence of an upper respiratory infection may have a retained foreign body. This cough can be mistaken for bronchiolitis, asthma, croup, and other infectious conditions, especially because a partial obstruction can make diagnosis confusing or challenging. Adding to the challenge is that most foreign bodies will be radiolucent. A decubitus chest x-ray could be useful, but bronchoscopy is necessary for diagnosis. Bhatia stressed that it’s easy to miss a foreign body in younger children and that the wheezing can be more prominent on one side or another.

Cystic fibrosis, another uncommon cause of chronic cough, is ideally diagnosed via newborn screening, but screening is imperfect and can involve missed diagnoses or false negatives. Over 75% of cystic fibrosis cases are diagnosed by age 2, but that means a substantial number of cases still are not diagnosed until older childhood or later. This cough will be a chronic productive/wet cough.

A family history of cystic fibrosis may be present but doesn’t have to be, so signs to look for include poor weight gain, sinusitis, nasal polyps, clubbing, and isolation of suspicious organisms from a respiratory culture, such as Pseudomonas aeruginosa or Burkholderia cepacia complex. Clubbing in the fingers is a particularly telltale symptom of undiagnosed cystic fibrosis, and bronchiectasis of unknown etiology will be present. Suspicion of cystic fibrosis should lead to a referral to a cystic fibrosis center for a sweat test.

Even rarer than cystic fibrosis is primary ciliary dyskinesia (PCD), an inherited autosomal recessive disease that occurs in about one in 20,000 live births and involves a structural or functional defect in the cilia. About half of all patients with PCD will have situs inversus — an arrangement of chest and abdominal organs that is a mirror image of typical human anatomical presentation — but most people with situs inversus do not have PCD. One type of PCD is Kartagener syndrome, identified by the triad of situs inversus totalis, chronic sinusitis, and bronchiectasis.

Children with PCD present with a chronic productive cough and recurrent pneumonias, and nearly all patients will have rhinosinusitis. About 60% of patients will develop respiratory symptoms such as mild distress or cough in their first month, and recurrent otitis media is common in these patients. PCD diagnosis is based on a combination of genetic testing, nasal nitric oxide, and evaluation of ciliary motion and structure. Clinical suspicion of PCD should lead to a specialist referral.

Nearly all people with PCD will eventually develop bronchiectasis, where the priority should be airway clearance using antibiotics for acute exacerbations and chronic azithromycin therapy for recurrent exacerbations. Patients with chronic rhinosinusitis, chronic otitis media, and nasal polyposis should be referred to an ENT specialist.
 

Other Uncommon Causes of Chronic Cough

A non-pulmonary, uncommon cause of chronic cough is a vascular ring, a congenital anomaly in which blood vessels encircle and potentially constrict the esophagus and/or trachea. The most common type is a double aortic arch, but a right aortic arch or pulmonary artery sling is also possible. These coughs sound harsh and are usually accompanied by stridor, dyspnea and feeding problems. Workup includes an echocardiogram, a CT angiogram, and possibly a bronchoscopy to determine the extent of the airway narrowing. In symptomatic patients, surgery is indicated for correction.

Another congenital malformation that can cause chronic cough is a tracheoesophageal fistula, which occurs in about one in 3500 live births, commonly linked to trisomy disorders and VACTERL. Several types of tracheoesophageal fistula exist, and H-type fistula is associated with late onset symptoms. The cough can be wet or dry and sometimes sounds like barking because of the associated airway collapse. Patients often have recurrent pneumonia, bronchitis, and cough or cyanosis with feeding. Workup should include an upper gastrointestinal series but not with barium, Bhatia said, because that can cause pneumonitis. Instead, the series should be done with a thickened water-soluble contrast material, and a bronchoscopy may be indicated as well.

Though common as a condition in adults, gastroesophageal reflux disease (GERD) is a rare, but possible, cause of chronic cough in children. More often, the reflux is the result of the cough rather than the cause. The most sensitive tool for assessing GERD is esophageal 24-hour pH/impedance reflux monitoring. However, treatment of the reflux for cough is not recommended unless the patient has clinical features of GERD, including dystonic neck posturing in infants, heartburn, regurgitation, or other symptoms. If the patient has clinical symptoms, then treatment is acid suppressive therapy for 4-8 weeks, followed by a clinical reassessment.

An uncommon cause of chronic cough with no biological mechanism is habit cough. Habit cough is most easily distinguished from other coughs by its sounds, a “large, loud, honking noise,” Bhatia said. It also lacks a clear trigger and is usually absent during sleep, but it can be continuous during the day. Frustratingly, the patients themselves often don’t seem bothered by the cough, but “it’s very disruptive in the school and everywhere else,” Bhatia said. Families and/providers will often have tried multiple treatments and seen no improvement with habit cough.

The first thing to do with habit cough is reassure the family that there’s nothing serious going on because they are often worried by this point. Several non-pharmaceutical treatments can be effective, such as suggestion therapy or the “warm water technique,” in which the patient takes a sip of warm water every time they feel the urge to cough. “If they’re able to break the cycle, most of the time, they are fine,” Bhatia said. In rarer cases, more involved behavioral interventions may be indicated, such as a psychology referral if an underlying anxiety or other behavioral disorder is contributing.
 

Newer Causes of Cough

Two more recent causes of cough to watch for are long COVID and e-cigarette or vaping product–associated lung injury (EVALI), Bhatia said. The clearest sign of EVALI is a history of e-cigarette/vaping exposure, but clinical symptoms include a dry cough that occurs with dyspnea and chest pain. A chest x-ray may show diffuse, hazy, or consolidative opacities. Sometimes antibiotics or steroids can be helpful, but the evidence isn’t strong, and the most effective treatment is stopping e-cigarette use. Less commonly, passive exposure to vaping can also be associated with EVALI.

The most recent research on long COVID suggests that about 10-20% of children with acute COVID develop long COVID, and about a quarter of these patients develop a chronic dry cough. It’s often associated with fatigue and shortness of breath, which can be assessed with cardiopulmonary exercise testing. Sometimes a short trial of inhaled steroids can help.

Bhatia also mentioned a handful of other uncommon causes of chronic cough that most American pediatricians are unlikely to see: Childhood interstitial lung disease, tuberculosis, use of Angiotensin-Converting Enzyme inhibitors, and a build-up of ear wax via the Arnold’s nerve reflex.
 

Evaluation and Workup

Bhatia also discussed what to cover while taking a history and questions to ask. The history should include the type of cough, the onset timing (sudden vs gradual), associated symptoms, the cough trajectory, medications the patient is taking, and the patient’s past medical history and environmental exposures. Those attributes are included in this more comprehensive list of questions to consider during evaluation, adapted from a list provided in a 2019 article in Paediatric Respiratory Reviews:

• Age of onset and duration?
• Was the onset sudden or associate with an illness?
• Is the cough wet or dry?
• What does the cough sound like?
• How often does the cough occur?
• Is it progressive?
• Is it present during sleep?
• Are there any other associated symptoms, such as wheeze, dyspnea, vomiting, chest pain, etc?
• Are there any exacerbating factors or known triggers?
• Are there any relieving factors, including a trial of bronchodilators?
• Has there been exposure to auto-irritants, such as secondhand smoke?
• What is the cough’s effect on the child and on others around the child?
• Does the child have any other underlying conditions such as neuromuscular disease or asthma?
• What medications is the child taking or has recently taken?
• Is there a family history of atopy and/or respiratory disease?

Bhatia also recommended paying special attention to the following red flags or key features that may help more quickly narrow the diagnosis and often require a specialist referral:

• Digital clubbing, failure to thrive, or low tone
• An abnormal cardiac exam
• Tachypnea, hypoxemia, chest retractions, or hemoptysis
• Abnormal breath sounds such as unilateral wheezing or coarse crackles
• Abnormal spirometry in those aged 5 and older showing reversible obstruction, which often indicates asthma
• An abnormal chest x-ray with, for example, bilateral infiltrates, hyperinflation, right middle lobe syndrome, situs inversus, unilateral hyperlucency, a right aortic arch, etc.

No external funding was used for the presentation. Bhatia and Quijada had no disclosures.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Asthma is the most common cause of chronic cough in children, but it’s important to be aware of other differential diagnoses for those patients who have less common concerns, according to Rajeev Bhatia, MD, division chief of pulmonology at Phoenix Children’s in Phoenix, Arizona. Bhatia reviewed both the major causes of chronic cough as well as the rare zebras to watch out for in a presentation at the American Academy of Pediatrics (AAP) 2024 National Conference.

“When you see a patient for cough, the most important thing is, history, history, history,” Bhatia said. “There are many, many, many clues in the history, age of onset, and duration.” That includes starting at birth to ensure you don’t miss key details such as a preterm birth. It’s also important to discuss what the cough sounds like, how frequent it is, what makes it better, what makes it worse, and how it’s affecting the child and others around them — all of which can help narrow the diagnosis.

Jose Quijada, DO, a pediatrician with CommuniCare Pediatrics in San Antonio, found the session “incredibly useful” not only because of the specific pointers about each condition but also because of the realistic case studies he included throughout.

“Sometimes when you’re practicing, you focus on what’s most common,” Quijada said, so it was helpful to get a review of some of the key features and red flags that point to less common causes that may need to be considered. He particularly appreciated the discussion of habitual cough and potential treatments because those can be challenging patients and it can be tough to find a middle ground with how much workup to do.
 

Common Causes of Chronic Cough

The coughing from inadequately controlled asthma tends to be nonproductive and worse at night or in the early morning, Bhatia explained, and it’s often accompanied by wheezing, shortness of breath, and chest tightness. While fractional exhaled nitric oxide can be useful, “studies show that it is more useful for to monitor the symptoms rather than to diagnose the asthma,” Bhatia told attendees, but he also added that spirometry can be normal in patients with asthma. In young patients, the Asthma Predictive Index can be an invaluable tool, he also said.

Another common cause of chronic cough is a postinfectious cough, which lasts more than 3 weeks after resolution of acute upper respiratory infection. It occurs in about one in 10 children after a viral infection such as a rhinovirus or respiratory syncytial virus infection and results from extensive inflammation and disruption of the airway epithelial integrity. Chest x-rays are usually normal in these patients, and the cough will usually resolve on its own. Albuterol has not been shown to be any more effective than placebo for a postinfectious cough, and antibiotics similarly have no clinically useful role.

A wet cough that lasts for at least 4 weeks and appears to have no other specific cause may be protracted bacterial bronchitis (PBB). While the cause of PBB isn’t known, it could be due to frequent illnesses that cause airway inflammation and injury over time, thereby making it easier for bacteria to grow and cause infection. Risk factors include tracheomalacia/bronchomalacia and childcare attendance, and typical pathogens include Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis.

While an x-ray can be done, radiography is often normal in patients with PBB. Bronchoscopy will reveal purulent secretions. PBB should resolve with at least 2 weeks of antibiotics, including amoxicillin-clavulanate, but the course can be extended to 4 weeks if the cough persists. However, about 40% of patients will have recurrence, and those with recurrent PBB or with a chronic cough unresponsive to 4 weeks of antibiotics should be referred to a pediatric pulmonologist.

Upper airway cough syndrome is the updated name for postnasal drip, which can occur with both allergic and nonallergic rhinitis and chronic rhinosinusitis. This is often a dry, throat-clearing cough that can be accompanied by headaches, nasal congestion, and sinus or facial tenderness. An examination will reveal posterior pharynx cobblestoning, Bhatia said, and empirical use of intranasal steroids can be both diagnostic and therapeutic for upper airway cough syndrome. He also emphasized the importance of taking an environmental history and avoiding exposure of environmental triggers.
 

Uncommon Pulmonary Causes of Chronic Cough

After discussing frequent reasons patients may present with a chronic cough, Bhatia went on to discuss the less common things to consider if the provider has eliminated the other possibilities. These include both pulmonary causes as well as congenital malformations, gastrointestinal causes, and habit cough.

A child who presents with a sudden onset of cough or wheeze in the absence of an upper respiratory infection may have a retained foreign body. This cough can be mistaken for bronchiolitis, asthma, croup, and other infectious conditions, especially because a partial obstruction can make diagnosis confusing or challenging. Adding to the challenge is that most foreign bodies will be radiolucent. A decubitus chest x-ray could be useful, but bronchoscopy is necessary for diagnosis. Bhatia stressed that it’s easy to miss a foreign body in younger children and that the wheezing can be more prominent on one side or another.

Cystic fibrosis, another uncommon cause of chronic cough, is ideally diagnosed via newborn screening, but screening is imperfect and can involve missed diagnoses or false negatives. Over 75% of cystic fibrosis cases are diagnosed by age 2, but that means a substantial number of cases still are not diagnosed until older childhood or later. This cough will be a chronic productive/wet cough.

A family history of cystic fibrosis may be present but doesn’t have to be, so signs to look for include poor weight gain, sinusitis, nasal polyps, clubbing, and isolation of suspicious organisms from a respiratory culture, such as Pseudomonas aeruginosa or Burkholderia cepacia complex. Clubbing in the fingers is a particularly telltale symptom of undiagnosed cystic fibrosis, and bronchiectasis of unknown etiology will be present. Suspicion of cystic fibrosis should lead to a referral to a cystic fibrosis center for a sweat test.

Even rarer than cystic fibrosis is primary ciliary dyskinesia (PCD), an inherited autosomal recessive disease that occurs in about one in 20,000 live births and involves a structural or functional defect in the cilia. About half of all patients with PCD will have situs inversus — an arrangement of chest and abdominal organs that is a mirror image of typical human anatomical presentation — but most people with situs inversus do not have PCD. One type of PCD is Kartagener syndrome, identified by the triad of situs inversus totalis, chronic sinusitis, and bronchiectasis.

Children with PCD present with a chronic productive cough and recurrent pneumonias, and nearly all patients will have rhinosinusitis. About 60% of patients will develop respiratory symptoms such as mild distress or cough in their first month, and recurrent otitis media is common in these patients. PCD diagnosis is based on a combination of genetic testing, nasal nitric oxide, and evaluation of ciliary motion and structure. Clinical suspicion of PCD should lead to a specialist referral.

Nearly all people with PCD will eventually develop bronchiectasis, where the priority should be airway clearance using antibiotics for acute exacerbations and chronic azithromycin therapy for recurrent exacerbations. Patients with chronic rhinosinusitis, chronic otitis media, and nasal polyposis should be referred to an ENT specialist.
 

Other Uncommon Causes of Chronic Cough

A non-pulmonary, uncommon cause of chronic cough is a vascular ring, a congenital anomaly in which blood vessels encircle and potentially constrict the esophagus and/or trachea. The most common type is a double aortic arch, but a right aortic arch or pulmonary artery sling is also possible. These coughs sound harsh and are usually accompanied by stridor, dyspnea and feeding problems. Workup includes an echocardiogram, a CT angiogram, and possibly a bronchoscopy to determine the extent of the airway narrowing. In symptomatic patients, surgery is indicated for correction.

Another congenital malformation that can cause chronic cough is a tracheoesophageal fistula, which occurs in about one in 3500 live births, commonly linked to trisomy disorders and VACTERL. Several types of tracheoesophageal fistula exist, and H-type fistula is associated with late onset symptoms. The cough can be wet or dry and sometimes sounds like barking because of the associated airway collapse. Patients often have recurrent pneumonia, bronchitis, and cough or cyanosis with feeding. Workup should include an upper gastrointestinal series but not with barium, Bhatia said, because that can cause pneumonitis. Instead, the series should be done with a thickened water-soluble contrast material, and a bronchoscopy may be indicated as well.

Though common as a condition in adults, gastroesophageal reflux disease (GERD) is a rare, but possible, cause of chronic cough in children. More often, the reflux is the result of the cough rather than the cause. The most sensitive tool for assessing GERD is esophageal 24-hour pH/impedance reflux monitoring. However, treatment of the reflux for cough is not recommended unless the patient has clinical features of GERD, including dystonic neck posturing in infants, heartburn, regurgitation, or other symptoms. If the patient has clinical symptoms, then treatment is acid suppressive therapy for 4-8 weeks, followed by a clinical reassessment.

An uncommon cause of chronic cough with no biological mechanism is habit cough. Habit cough is most easily distinguished from other coughs by its sounds, a “large, loud, honking noise,” Bhatia said. It also lacks a clear trigger and is usually absent during sleep, but it can be continuous during the day. Frustratingly, the patients themselves often don’t seem bothered by the cough, but “it’s very disruptive in the school and everywhere else,” Bhatia said. Families and/providers will often have tried multiple treatments and seen no improvement with habit cough.

The first thing to do with habit cough is reassure the family that there’s nothing serious going on because they are often worried by this point. Several non-pharmaceutical treatments can be effective, such as suggestion therapy or the “warm water technique,” in which the patient takes a sip of warm water every time they feel the urge to cough. “If they’re able to break the cycle, most of the time, they are fine,” Bhatia said. In rarer cases, more involved behavioral interventions may be indicated, such as a psychology referral if an underlying anxiety or other behavioral disorder is contributing.
 

Newer Causes of Cough

Two more recent causes of cough to watch for are long COVID and e-cigarette or vaping product–associated lung injury (EVALI), Bhatia said. The clearest sign of EVALI is a history of e-cigarette/vaping exposure, but clinical symptoms include a dry cough that occurs with dyspnea and chest pain. A chest x-ray may show diffuse, hazy, or consolidative opacities. Sometimes antibiotics or steroids can be helpful, but the evidence isn’t strong, and the most effective treatment is stopping e-cigarette use. Less commonly, passive exposure to vaping can also be associated with EVALI.

The most recent research on long COVID suggests that about 10-20% of children with acute COVID develop long COVID, and about a quarter of these patients develop a chronic dry cough. It’s often associated with fatigue and shortness of breath, which can be assessed with cardiopulmonary exercise testing. Sometimes a short trial of inhaled steroids can help.

Bhatia also mentioned a handful of other uncommon causes of chronic cough that most American pediatricians are unlikely to see: Childhood interstitial lung disease, tuberculosis, use of Angiotensin-Converting Enzyme inhibitors, and a build-up of ear wax via the Arnold’s nerve reflex.
 

Evaluation and Workup

Bhatia also discussed what to cover while taking a history and questions to ask. The history should include the type of cough, the onset timing (sudden vs gradual), associated symptoms, the cough trajectory, medications the patient is taking, and the patient’s past medical history and environmental exposures. Those attributes are included in this more comprehensive list of questions to consider during evaluation, adapted from a list provided in a 2019 article in Paediatric Respiratory Reviews:

• Age of onset and duration?
• Was the onset sudden or associate with an illness?
• Is the cough wet or dry?
• What does the cough sound like?
• How often does the cough occur?
• Is it progressive?
• Is it present during sleep?
• Are there any other associated symptoms, such as wheeze, dyspnea, vomiting, chest pain, etc?
• Are there any exacerbating factors or known triggers?
• Are there any relieving factors, including a trial of bronchodilators?
• Has there been exposure to auto-irritants, such as secondhand smoke?
• What is the cough’s effect on the child and on others around the child?
• Does the child have any other underlying conditions such as neuromuscular disease or asthma?
• What medications is the child taking or has recently taken?
• Is there a family history of atopy and/or respiratory disease?

Bhatia also recommended paying special attention to the following red flags or key features that may help more quickly narrow the diagnosis and often require a specialist referral:

• Digital clubbing, failure to thrive, or low tone
• An abnormal cardiac exam
• Tachypnea, hypoxemia, chest retractions, or hemoptysis
• Abnormal breath sounds such as unilateral wheezing or coarse crackles
• Abnormal spirometry in those aged 5 and older showing reversible obstruction, which often indicates asthma
• An abnormal chest x-ray with, for example, bilateral infiltrates, hyperinflation, right middle lobe syndrome, situs inversus, unilateral hyperlucency, a right aortic arch, etc.

No external funding was used for the presentation. Bhatia and Quijada had no disclosures.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Asthma is the most common cause of chronic cough in children, but it’s important to be aware of other differential diagnoses for those patients who have less common concerns, according to Rajeev Bhatia, MD, division chief of pulmonology at Phoenix Children’s in Phoenix, Arizona. Bhatia reviewed both the major causes of chronic cough as well as the rare zebras to watch out for in a presentation at the American Academy of Pediatrics (AAP) 2024 National Conference.

“When you see a patient for cough, the most important thing is, history, history, history,” Bhatia said. “There are many, many, many clues in the history, age of onset, and duration.” That includes starting at birth to ensure you don’t miss key details such as a preterm birth. It’s also important to discuss what the cough sounds like, how frequent it is, what makes it better, what makes it worse, and how it’s affecting the child and others around them — all of which can help narrow the diagnosis.

Jose Quijada, DO, a pediatrician with CommuniCare Pediatrics in San Antonio, found the session “incredibly useful” not only because of the specific pointers about each condition but also because of the realistic case studies he included throughout.

“Sometimes when you’re practicing, you focus on what’s most common,” Quijada said, so it was helpful to get a review of some of the key features and red flags that point to less common causes that may need to be considered. He particularly appreciated the discussion of habitual cough and potential treatments because those can be challenging patients and it can be tough to find a middle ground with how much workup to do.
 

Common Causes of Chronic Cough

The coughing from inadequately controlled asthma tends to be nonproductive and worse at night or in the early morning, Bhatia explained, and it’s often accompanied by wheezing, shortness of breath, and chest tightness. While fractional exhaled nitric oxide can be useful, “studies show that it is more useful for to monitor the symptoms rather than to diagnose the asthma,” Bhatia told attendees, but he also added that spirometry can be normal in patients with asthma. In young patients, the Asthma Predictive Index can be an invaluable tool, he also said.

Another common cause of chronic cough is a postinfectious cough, which lasts more than 3 weeks after resolution of acute upper respiratory infection. It occurs in about one in 10 children after a viral infection such as a rhinovirus or respiratory syncytial virus infection and results from extensive inflammation and disruption of the airway epithelial integrity. Chest x-rays are usually normal in these patients, and the cough will usually resolve on its own. Albuterol has not been shown to be any more effective than placebo for a postinfectious cough, and antibiotics similarly have no clinically useful role.

A wet cough that lasts for at least 4 weeks and appears to have no other specific cause may be protracted bacterial bronchitis (PBB). While the cause of PBB isn’t known, it could be due to frequent illnesses that cause airway inflammation and injury over time, thereby making it easier for bacteria to grow and cause infection. Risk factors include tracheomalacia/bronchomalacia and childcare attendance, and typical pathogens include Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis.

While an x-ray can be done, radiography is often normal in patients with PBB. Bronchoscopy will reveal purulent secretions. PBB should resolve with at least 2 weeks of antibiotics, including amoxicillin-clavulanate, but the course can be extended to 4 weeks if the cough persists. However, about 40% of patients will have recurrence, and those with recurrent PBB or with a chronic cough unresponsive to 4 weeks of antibiotics should be referred to a pediatric pulmonologist.

Upper airway cough syndrome is the updated name for postnasal drip, which can occur with both allergic and nonallergic rhinitis and chronic rhinosinusitis. This is often a dry, throat-clearing cough that can be accompanied by headaches, nasal congestion, and sinus or facial tenderness. An examination will reveal posterior pharynx cobblestoning, Bhatia said, and empirical use of intranasal steroids can be both diagnostic and therapeutic for upper airway cough syndrome. He also emphasized the importance of taking an environmental history and avoiding exposure of environmental triggers.
 

Uncommon Pulmonary Causes of Chronic Cough

After discussing frequent reasons patients may present with a chronic cough, Bhatia went on to discuss the less common things to consider if the provider has eliminated the other possibilities. These include both pulmonary causes as well as congenital malformations, gastrointestinal causes, and habit cough.

A child who presents with a sudden onset of cough or wheeze in the absence of an upper respiratory infection may have a retained foreign body. This cough can be mistaken for bronchiolitis, asthma, croup, and other infectious conditions, especially because a partial obstruction can make diagnosis confusing or challenging. Adding to the challenge is that most foreign bodies will be radiolucent. A decubitus chest x-ray could be useful, but bronchoscopy is necessary for diagnosis. Bhatia stressed that it’s easy to miss a foreign body in younger children and that the wheezing can be more prominent on one side or another.

Cystic fibrosis, another uncommon cause of chronic cough, is ideally diagnosed via newborn screening, but screening is imperfect and can involve missed diagnoses or false negatives. Over 75% of cystic fibrosis cases are diagnosed by age 2, but that means a substantial number of cases still are not diagnosed until older childhood or later. This cough will be a chronic productive/wet cough.

A family history of cystic fibrosis may be present but doesn’t have to be, so signs to look for include poor weight gain, sinusitis, nasal polyps, clubbing, and isolation of suspicious organisms from a respiratory culture, such as Pseudomonas aeruginosa or Burkholderia cepacia complex. Clubbing in the fingers is a particularly telltale symptom of undiagnosed cystic fibrosis, and bronchiectasis of unknown etiology will be present. Suspicion of cystic fibrosis should lead to a referral to a cystic fibrosis center for a sweat test.

Even rarer than cystic fibrosis is primary ciliary dyskinesia (PCD), an inherited autosomal recessive disease that occurs in about one in 20,000 live births and involves a structural or functional defect in the cilia. About half of all patients with PCD will have situs inversus — an arrangement of chest and abdominal organs that is a mirror image of typical human anatomical presentation — but most people with situs inversus do not have PCD. One type of PCD is Kartagener syndrome, identified by the triad of situs inversus totalis, chronic sinusitis, and bronchiectasis.

Children with PCD present with a chronic productive cough and recurrent pneumonias, and nearly all patients will have rhinosinusitis. About 60% of patients will develop respiratory symptoms such as mild distress or cough in their first month, and recurrent otitis media is common in these patients. PCD diagnosis is based on a combination of genetic testing, nasal nitric oxide, and evaluation of ciliary motion and structure. Clinical suspicion of PCD should lead to a specialist referral.

Nearly all people with PCD will eventually develop bronchiectasis, where the priority should be airway clearance using antibiotics for acute exacerbations and chronic azithromycin therapy for recurrent exacerbations. Patients with chronic rhinosinusitis, chronic otitis media, and nasal polyposis should be referred to an ENT specialist.
 

Other Uncommon Causes of Chronic Cough

A non-pulmonary, uncommon cause of chronic cough is a vascular ring, a congenital anomaly in which blood vessels encircle and potentially constrict the esophagus and/or trachea. The most common type is a double aortic arch, but a right aortic arch or pulmonary artery sling is also possible. These coughs sound harsh and are usually accompanied by stridor, dyspnea and feeding problems. Workup includes an echocardiogram, a CT angiogram, and possibly a bronchoscopy to determine the extent of the airway narrowing. In symptomatic patients, surgery is indicated for correction.

Another congenital malformation that can cause chronic cough is a tracheoesophageal fistula, which occurs in about one in 3500 live births, commonly linked to trisomy disorders and VACTERL. Several types of tracheoesophageal fistula exist, and H-type fistula is associated with late onset symptoms. The cough can be wet or dry and sometimes sounds like barking because of the associated airway collapse. Patients often have recurrent pneumonia, bronchitis, and cough or cyanosis with feeding. Workup should include an upper gastrointestinal series but not with barium, Bhatia said, because that can cause pneumonitis. Instead, the series should be done with a thickened water-soluble contrast material, and a bronchoscopy may be indicated as well.

Though common as a condition in adults, gastroesophageal reflux disease (GERD) is a rare, but possible, cause of chronic cough in children. More often, the reflux is the result of the cough rather than the cause. The most sensitive tool for assessing GERD is esophageal 24-hour pH/impedance reflux monitoring. However, treatment of the reflux for cough is not recommended unless the patient has clinical features of GERD, including dystonic neck posturing in infants, heartburn, regurgitation, or other symptoms. If the patient has clinical symptoms, then treatment is acid suppressive therapy for 4-8 weeks, followed by a clinical reassessment.

An uncommon cause of chronic cough with no biological mechanism is habit cough. Habit cough is most easily distinguished from other coughs by its sounds, a “large, loud, honking noise,” Bhatia said. It also lacks a clear trigger and is usually absent during sleep, but it can be continuous during the day. Frustratingly, the patients themselves often don’t seem bothered by the cough, but “it’s very disruptive in the school and everywhere else,” Bhatia said. Families and/providers will often have tried multiple treatments and seen no improvement with habit cough.

The first thing to do with habit cough is reassure the family that there’s nothing serious going on because they are often worried by this point. Several non-pharmaceutical treatments can be effective, such as suggestion therapy or the “warm water technique,” in which the patient takes a sip of warm water every time they feel the urge to cough. “If they’re able to break the cycle, most of the time, they are fine,” Bhatia said. In rarer cases, more involved behavioral interventions may be indicated, such as a psychology referral if an underlying anxiety or other behavioral disorder is contributing.
 

Newer Causes of Cough

Two more recent causes of cough to watch for are long COVID and e-cigarette or vaping product–associated lung injury (EVALI), Bhatia said. The clearest sign of EVALI is a history of e-cigarette/vaping exposure, but clinical symptoms include a dry cough that occurs with dyspnea and chest pain. A chest x-ray may show diffuse, hazy, or consolidative opacities. Sometimes antibiotics or steroids can be helpful, but the evidence isn’t strong, and the most effective treatment is stopping e-cigarette use. Less commonly, passive exposure to vaping can also be associated with EVALI.

The most recent research on long COVID suggests that about 10-20% of children with acute COVID develop long COVID, and about a quarter of these patients develop a chronic dry cough. It’s often associated with fatigue and shortness of breath, which can be assessed with cardiopulmonary exercise testing. Sometimes a short trial of inhaled steroids can help.

Bhatia also mentioned a handful of other uncommon causes of chronic cough that most American pediatricians are unlikely to see: Childhood interstitial lung disease, tuberculosis, use of Angiotensin-Converting Enzyme inhibitors, and a build-up of ear wax via the Arnold’s nerve reflex.
 

Evaluation and Workup

Bhatia also discussed what to cover while taking a history and questions to ask. The history should include the type of cough, the onset timing (sudden vs gradual), associated symptoms, the cough trajectory, medications the patient is taking, and the patient’s past medical history and environmental exposures. Those attributes are included in this more comprehensive list of questions to consider during evaluation, adapted from a list provided in a 2019 article in Paediatric Respiratory Reviews:

• Age of onset and duration?
• Was the onset sudden or associate with an illness?
• Is the cough wet or dry?
• What does the cough sound like?
• How often does the cough occur?
• Is it progressive?
• Is it present during sleep?
• Are there any other associated symptoms, such as wheeze, dyspnea, vomiting, chest pain, etc?
• Are there any exacerbating factors or known triggers?
• Are there any relieving factors, including a trial of bronchodilators?
• Has there been exposure to auto-irritants, such as secondhand smoke?
• What is the cough’s effect on the child and on others around the child?
• Does the child have any other underlying conditions such as neuromuscular disease or asthma?
• What medications is the child taking or has recently taken?
• Is there a family history of atopy and/or respiratory disease?

Bhatia also recommended paying special attention to the following red flags or key features that may help more quickly narrow the diagnosis and often require a specialist referral:

• Digital clubbing, failure to thrive, or low tone
• An abnormal cardiac exam
• Tachypnea, hypoxemia, chest retractions, or hemoptysis
• Abnormal breath sounds such as unilateral wheezing or coarse crackles
• Abnormal spirometry in those aged 5 and older showing reversible obstruction, which often indicates asthma
• An abnormal chest x-ray with, for example, bilateral infiltrates, hyperinflation, right middle lobe syndrome, situs inversus, unilateral hyperlucency, a right aortic arch, etc.

No external funding was used for the presentation. Bhatia and Quijada had no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Fetuses exposed in utero to SARS-CoV-2 are not at an increased risk for neurodevelopmental problems in early childhood.

METHODOLOGY:

• This prospective study aimed to assess whether in utero exposure to SARS-CoV-2, which causes COVID-19, is associated with abnormal neurodevelopment among children at ages 12, 18, and 24 months.
• It included 2003 pregnant individuals (mean age, 33.3 years) from the ASPIRE cohort who were enrolled before 10 weeks’ gestation and followed through 24 months post partum; 10.8% of them were exposed to SARS-CoV-2 during pregnancy, as determined via self-reported data or dried blood spot cards.
• The birth mothers were required to complete the Ages & Stages Questionnaires, Third Edition (ASQ-3), a validated screening tool for neurodevelopmental delays, at 12, 18, and 24 months postpartum.
• Neurodevelopmental outcomes were available for 1757, 1522, and 1523 children at ages 12, 18, and 24 months, respectively.
• The primary outcome was a score below the cutoff on the ASQ-3 across any of the following developmental domains: Communication, gross motor, fine motor, problem-solving, and social skills.

TAKEAWAY:

• The prevalence of abnormal ASQ-3 scores did not differ between children who were exposed to SARS-CoV-2 in utero and those who were not, at ages 12 (P = .39), 18 (P = .58), and 24 (P = .45) months.
• No association was observed between in utero exposure to SARS-CoV-2 and abnormal ASQ-3 scores among children in any of the age groups.
• The lack of an association between exposure to SARS-CoV-2 during pregnancy and abnormal neurodevelopment remained unchanged even when factors such as preterm delivery and the sex of the infant were considered.
• Supplemental analyses found no difference in risk based on the trimester of infection, presence of fever, or incidence of breakthrough infection following vaccination.

IN PRACTICE:

“In this prospective cohort study of pregnant individuals and offspring, in utero exposure to maternal SARS-CoV-2 infection was not associated with abnormal neurodevelopmental screening scores of children through age 24 months. These findings are critical considering the novelty of the SARS-CoV-2 virus to the human species, the global scale of the initial COVID-19 outbreak, the now-endemic nature of the virus indicating ongoing relevance for pregnant individuals,” the authors of the study wrote. 

“While the scientific consensus resists a link between in utero COVID-19 exposure and impaired offspring neurodevelopment, the question remains whether societal responses to the pandemic impacted developmental trajectories,” the researchers added. “Certain studies comparing infants from a pandemic cohort with historic controls have raised concerns about lower ASQ-3 scores among children living during the pandemic. Critically, socioeconomic factors influence vulnerability, not only to infection itself but also regarding the ability to deploy resources in times of stress (eg, school closures) to mitigate sources of developmental harm. Our data support this theory, with the observed independent protective association of increasing household income with childhood ASQ-3 scores. Additional research is warranted to clarify the potential impact of societal measures on early development and the differential impact of these measures on different communities.”
 

SOURCE:

The study was led by Eleni G. Jaswa, MD, MSc, of the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS: 

Limitations of the research included the use of self-reported data and dried blood spot cards for determining exposure to SARS-CoV-2, which may have led to misclassification. The ASQ-3 is a modestly sensitive tool for detecting developmental delays that may have affected the study’s power to detect associations. The sample size of this study, while larger than many, may still have been underpowered to detect small differences in neurodevelopmental outcomes.

DISCLOSURES:

The ASPIRE cohort was supported by research grants provided to the University of California, San Francisco, and by the Start Small Foundation, the California Breast Cancer Research Program, the COVID Catalyst Award, and other sources. Some authors reported receiving grants, royalties, and personal fees, serving on medical advisory boards, and having other ties with several institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Fetuses exposed in utero to SARS-CoV-2 are not at an increased risk for neurodevelopmental problems in early childhood.

METHODOLOGY:

• This prospective study aimed to assess whether in utero exposure to SARS-CoV-2, which causes COVID-19, is associated with abnormal neurodevelopment among children at ages 12, 18, and 24 months.
• It included 2003 pregnant individuals (mean age, 33.3 years) from the ASPIRE cohort who were enrolled before 10 weeks’ gestation and followed through 24 months post partum; 10.8% of them were exposed to SARS-CoV-2 during pregnancy, as determined via self-reported data or dried blood spot cards.
• The birth mothers were required to complete the Ages & Stages Questionnaires, Third Edition (ASQ-3), a validated screening tool for neurodevelopmental delays, at 12, 18, and 24 months postpartum.
• Neurodevelopmental outcomes were available for 1757, 1522, and 1523 children at ages 12, 18, and 24 months, respectively.
• The primary outcome was a score below the cutoff on the ASQ-3 across any of the following developmental domains: Communication, gross motor, fine motor, problem-solving, and social skills.

TAKEAWAY:

• The prevalence of abnormal ASQ-3 scores did not differ between children who were exposed to SARS-CoV-2 in utero and those who were not, at ages 12 (P = .39), 18 (P = .58), and 24 (P = .45) months.
• No association was observed between in utero exposure to SARS-CoV-2 and abnormal ASQ-3 scores among children in any of the age groups.
• The lack of an association between exposure to SARS-CoV-2 during pregnancy and abnormal neurodevelopment remained unchanged even when factors such as preterm delivery and the sex of the infant were considered.
• Supplemental analyses found no difference in risk based on the trimester of infection, presence of fever, or incidence of breakthrough infection following vaccination.

IN PRACTICE:

“In this prospective cohort study of pregnant individuals and offspring, in utero exposure to maternal SARS-CoV-2 infection was not associated with abnormal neurodevelopmental screening scores of children through age 24 months. These findings are critical considering the novelty of the SARS-CoV-2 virus to the human species, the global scale of the initial COVID-19 outbreak, the now-endemic nature of the virus indicating ongoing relevance for pregnant individuals,” the authors of the study wrote. 

“While the scientific consensus resists a link between in utero COVID-19 exposure and impaired offspring neurodevelopment, the question remains whether societal responses to the pandemic impacted developmental trajectories,” the researchers added. “Certain studies comparing infants from a pandemic cohort with historic controls have raised concerns about lower ASQ-3 scores among children living during the pandemic. Critically, socioeconomic factors influence vulnerability, not only to infection itself but also regarding the ability to deploy resources in times of stress (eg, school closures) to mitigate sources of developmental harm. Our data support this theory, with the observed independent protective association of increasing household income with childhood ASQ-3 scores. Additional research is warranted to clarify the potential impact of societal measures on early development and the differential impact of these measures on different communities.”
 

SOURCE:

The study was led by Eleni G. Jaswa, MD, MSc, of the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS: 

Limitations of the research included the use of self-reported data and dried blood spot cards for determining exposure to SARS-CoV-2, which may have led to misclassification. The ASQ-3 is a modestly sensitive tool for detecting developmental delays that may have affected the study’s power to detect associations. The sample size of this study, while larger than many, may still have been underpowered to detect small differences in neurodevelopmental outcomes.

DISCLOSURES:

The ASPIRE cohort was supported by research grants provided to the University of California, San Francisco, and by the Start Small Foundation, the California Breast Cancer Research Program, the COVID Catalyst Award, and other sources. Some authors reported receiving grants, royalties, and personal fees, serving on medical advisory boards, and having other ties with several institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Fetuses exposed in utero to SARS-CoV-2 are not at an increased risk for neurodevelopmental problems in early childhood.

METHODOLOGY:

• This prospective study aimed to assess whether in utero exposure to SARS-CoV-2, which causes COVID-19, is associated with abnormal neurodevelopment among children at ages 12, 18, and 24 months.
• It included 2003 pregnant individuals (mean age, 33.3 years) from the ASPIRE cohort who were enrolled before 10 weeks’ gestation and followed through 24 months post partum; 10.8% of them were exposed to SARS-CoV-2 during pregnancy, as determined via self-reported data or dried blood spot cards.
• The birth mothers were required to complete the Ages & Stages Questionnaires, Third Edition (ASQ-3), a validated screening tool for neurodevelopmental delays, at 12, 18, and 24 months postpartum.
• Neurodevelopmental outcomes were available for 1757, 1522, and 1523 children at ages 12, 18, and 24 months, respectively.
• The primary outcome was a score below the cutoff on the ASQ-3 across any of the following developmental domains: Communication, gross motor, fine motor, problem-solving, and social skills.

TAKEAWAY:

• The prevalence of abnormal ASQ-3 scores did not differ between children who were exposed to SARS-CoV-2 in utero and those who were not, at ages 12 (P = .39), 18 (P = .58), and 24 (P = .45) months.
• No association was observed between in utero exposure to SARS-CoV-2 and abnormal ASQ-3 scores among children in any of the age groups.
• The lack of an association between exposure to SARS-CoV-2 during pregnancy and abnormal neurodevelopment remained unchanged even when factors such as preterm delivery and the sex of the infant were considered.
• Supplemental analyses found no difference in risk based on the trimester of infection, presence of fever, or incidence of breakthrough infection following vaccination.

IN PRACTICE:

“In this prospective cohort study of pregnant individuals and offspring, in utero exposure to maternal SARS-CoV-2 infection was not associated with abnormal neurodevelopmental screening scores of children through age 24 months. These findings are critical considering the novelty of the SARS-CoV-2 virus to the human species, the global scale of the initial COVID-19 outbreak, the now-endemic nature of the virus indicating ongoing relevance for pregnant individuals,” the authors of the study wrote. 

“While the scientific consensus resists a link between in utero COVID-19 exposure and impaired offspring neurodevelopment, the question remains whether societal responses to the pandemic impacted developmental trajectories,” the researchers added. “Certain studies comparing infants from a pandemic cohort with historic controls have raised concerns about lower ASQ-3 scores among children living during the pandemic. Critically, socioeconomic factors influence vulnerability, not only to infection itself but also regarding the ability to deploy resources in times of stress (eg, school closures) to mitigate sources of developmental harm. Our data support this theory, with the observed independent protective association of increasing household income with childhood ASQ-3 scores. Additional research is warranted to clarify the potential impact of societal measures on early development and the differential impact of these measures on different communities.”
 

SOURCE:

The study was led by Eleni G. Jaswa, MD, MSc, of the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS: 

Limitations of the research included the use of self-reported data and dried blood spot cards for determining exposure to SARS-CoV-2, which may have led to misclassification. The ASQ-3 is a modestly sensitive tool for detecting developmental delays that may have affected the study’s power to detect associations. The sample size of this study, while larger than many, may still have been underpowered to detect small differences in neurodevelopmental outcomes.

DISCLOSURES:

The ASPIRE cohort was supported by research grants provided to the University of California, San Francisco, and by the Start Small Foundation, the California Breast Cancer Research Program, the COVID Catalyst Award, and other sources. Some authors reported receiving grants, royalties, and personal fees, serving on medical advisory boards, and having other ties with several institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

AMSTERDAM — For patients with atopic dermatitis (AD) who responded to the anti–interleukin (IL)–13 monoclonal antibody lebrikizumab in the pivotal trials, the level of response, including 90% skin clearance, has generally remained unchanged among those followed up for an additional 2 years, according to the latest data from an extension study. 

At the end of the maintenance phase of the pivotal trials at 12 months, 84% of the patients enrolled into the extension had clear or almost clear skin, as per the Investigator Global Assessment (IGA). This overall figure as well as the proportion with even better responses have persisted unchanged, reported Diamant Thaçi, MD, PhD, professor and head of the Comprehensive Center for Inflammatory Medicine, University of Lübeck in Germany. 
 

Responses at 3 Years Maintained

“This is really quite remarkable,” Dr. Thaçi said. “Roughly all the patients maintained their response.” These results became even more remarkable when patients were assessed for their use of adjunctive therapy to control flares. 

“Over the whole follow-up, 90% had no need for topical corticosteroids or any other rescue therapy,” Dr. Thaçi reported, providing data from the ADjoin lebrikizumab extension study during a late-breaking news session at the annual meeting of the European Academy of Dermatology and Venereology. 

The patients in ADjoin were enrolled from the pivotal phase 3 ADvocate 1 and 2 trials completed almost 2 years ago and published together in March 2023. Lebrikizumab was approved in the United States in September 2024 for moderate to severe AD in patients aged ≥ 12 years, following previous approvals in Europe in 2023 and in Japan in January 2024.

In these two identical trials with a total of 564 patients, the primary endpoint was an IGA of 0 or 1, signifying clear or almost clear skin. At nearly 40%, the proportion of patients reaching this outcome at 16 weeks was about threefold greater (P < .001) on lebrikizumab than on placebo. The benefit was similar on secondary endpoints, such as 75% improvement in the Eczema Area and Severity Index (EASI75) score. 

At the end of the double-blind, placebo-controlled 16-week phase of the ADvocate 1 and 2 trials, which enrolled adults and adolescents aged ≥ 12 years, responders were enrolled into a maintenance phase in which they were rerandomized to 250 mg lebrikizumab every 2 weeks (Q2W) or every 4 weeks (Q4W). The latter is the approved maintenance dose. 

At the end of the maintenance phase, which lasted another 32 weeks (total exposure of 52 weeks for those initially randomized to lebrikizumab), patients were invited into the ADjoin extension. The only exclusions from the extension were serious adverse events related to lebrikizumab and noncompliance. 
 

Response Curves Appear as Straight Lines

Over the next 2 years of ADjoin, response curves appeared as straight lines not only for the overall response but when patients were stratified for different levels of response at the extension study entry. Specifically, 81.5% and 83.3% had an IGA score of 0 or 1 in the Q2W and Q4W arms at completion of the ADvocate 16-week double-blind phase. At 3 years, the rates were 84.0% and 82.9%, respectively. 

For the subgroup who entered ADjoin with an EASI75 or an EASI90 response, the persistence of this level of response over 2 years was similar, although there was some gain observed among those who entered the trial with an EASI75 response. 

“Not only did these patients maintain their response, but the response on average slowly improved, so that there were more patients with an EASI90 response at the 3-year timepoint,” Dr. Thaçi said.

Of the 181 patients in the ADjoin extension, 82 patients were maintained on Q2W dosing and 99 were maintained on Q4W lebrikizumab. Their mean age was about 35 years, more than half were women, and nearly 40% had severe AD at the time they enrolled in the ADvocate trials. There was essentially no difference in response rates among those in the Q2W and Q4W arms over time in ADjoin. 
 

Side Effect Profile Essentially Unchanged

The side effect and tolerability profiles, which were favorable in the original 16-week placebo-controlled study, have remained unchanged over the subsequent maintenance phase and through the additional 2 years of the ADjoin extension.

“There continued to be reports of conjunctivitis, which is very specific for anti–IL-13 therapies,” Dr. Thaçi said. However, he said that the incidence did not increase over time, and because it was easy to treat, “most patients do not discontinue lebrikizumab for this reason.” Moreover, he said the impression was that “the number of patients experiencing adverse effects has been decreasing over time.” 

Calling these long-term results “very exciting,” Dr. Thaçi called lebrikizumab “a very valuable option for long-term AD care.” 

Asked for his perspective on the results, Jonathan I. Silverberg, MD, PhD, Director of Clinical Research, Department of Dermatology, George Washington University, Washington, DC, said that it is important to study long-term efficacy, and these results are positive. Without direct comparisons to other biologics available for AD, nothing can be implied about the relative efficacy of monoclonal antibodies approved for AD. 

“These data are important both from an efficacy and safety perspective” for those advising patients who need chronic AD treatment, said Dr. Silverberg, who was the principal investigator of the ADvocate trials. 

Earlier this year, 5-year follow-up data were published for dupilumab. Of 326 patients who remained on therapy this long, 220 (67%) maintained an IGA of 0 or 1 at the end of the study. There were no unexpected adverse events, which were generally stable or declined throughout the study. 

Dr. Thaçi has financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Leo Pharma, L’Oreal, Janssen-Cilag, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sun Pharma, UCB, and Vichy. Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies including those that make drugs for AD.

A version of this article appeared on Medscape.com.

AMSTERDAM — For patients with atopic dermatitis (AD) who responded to the anti–interleukin (IL)–13 monoclonal antibody lebrikizumab in the pivotal trials, the level of response, including 90% skin clearance, has generally remained unchanged among those followed up for an additional 2 years, according to the latest data from an extension study. 

At the end of the maintenance phase of the pivotal trials at 12 months, 84% of the patients enrolled into the extension had clear or almost clear skin, as per the Investigator Global Assessment (IGA). This overall figure as well as the proportion with even better responses have persisted unchanged, reported Diamant Thaçi, MD, PhD, professor and head of the Comprehensive Center for Inflammatory Medicine, University of Lübeck in Germany. 
 

Responses at 3 Years Maintained

“This is really quite remarkable,” Dr. Thaçi said. “Roughly all the patients maintained their response.” These results became even more remarkable when patients were assessed for their use of adjunctive therapy to control flares. 

“Over the whole follow-up, 90% had no need for topical corticosteroids or any other rescue therapy,” Dr. Thaçi reported, providing data from the ADjoin lebrikizumab extension study during a late-breaking news session at the annual meeting of the European Academy of Dermatology and Venereology. 

The patients in ADjoin were enrolled from the pivotal phase 3 ADvocate 1 and 2 trials completed almost 2 years ago and published together in March 2023. Lebrikizumab was approved in the United States in September 2024 for moderate to severe AD in patients aged ≥ 12 years, following previous approvals in Europe in 2023 and in Japan in January 2024.

In these two identical trials with a total of 564 patients, the primary endpoint was an IGA of 0 or 1, signifying clear or almost clear skin. At nearly 40%, the proportion of patients reaching this outcome at 16 weeks was about threefold greater (P < .001) on lebrikizumab than on placebo. The benefit was similar on secondary endpoints, such as 75% improvement in the Eczema Area and Severity Index (EASI75) score. 

At the end of the double-blind, placebo-controlled 16-week phase of the ADvocate 1 and 2 trials, which enrolled adults and adolescents aged ≥ 12 years, responders were enrolled into a maintenance phase in which they were rerandomized to 250 mg lebrikizumab every 2 weeks (Q2W) or every 4 weeks (Q4W). The latter is the approved maintenance dose. 

At the end of the maintenance phase, which lasted another 32 weeks (total exposure of 52 weeks for those initially randomized to lebrikizumab), patients were invited into the ADjoin extension. The only exclusions from the extension were serious adverse events related to lebrikizumab and noncompliance. 
 

Response Curves Appear as Straight Lines

Over the next 2 years of ADjoin, response curves appeared as straight lines not only for the overall response but when patients were stratified for different levels of response at the extension study entry. Specifically, 81.5% and 83.3% had an IGA score of 0 or 1 in the Q2W and Q4W arms at completion of the ADvocate 16-week double-blind phase. At 3 years, the rates were 84.0% and 82.9%, respectively. 

For the subgroup who entered ADjoin with an EASI75 or an EASI90 response, the persistence of this level of response over 2 years was similar, although there was some gain observed among those who entered the trial with an EASI75 response. 

“Not only did these patients maintain their response, but the response on average slowly improved, so that there were more patients with an EASI90 response at the 3-year timepoint,” Dr. Thaçi said.

Of the 181 patients in the ADjoin extension, 82 patients were maintained on Q2W dosing and 99 were maintained on Q4W lebrikizumab. Their mean age was about 35 years, more than half were women, and nearly 40% had severe AD at the time they enrolled in the ADvocate trials. There was essentially no difference in response rates among those in the Q2W and Q4W arms over time in ADjoin. 
 

Side Effect Profile Essentially Unchanged

The side effect and tolerability profiles, which were favorable in the original 16-week placebo-controlled study, have remained unchanged over the subsequent maintenance phase and through the additional 2 years of the ADjoin extension.

“There continued to be reports of conjunctivitis, which is very specific for anti–IL-13 therapies,” Dr. Thaçi said. However, he said that the incidence did not increase over time, and because it was easy to treat, “most patients do not discontinue lebrikizumab for this reason.” Moreover, he said the impression was that “the number of patients experiencing adverse effects has been decreasing over time.” 

Calling these long-term results “very exciting,” Dr. Thaçi called lebrikizumab “a very valuable option for long-term AD care.” 

Asked for his perspective on the results, Jonathan I. Silverberg, MD, PhD, Director of Clinical Research, Department of Dermatology, George Washington University, Washington, DC, said that it is important to study long-term efficacy, and these results are positive. Without direct comparisons to other biologics available for AD, nothing can be implied about the relative efficacy of monoclonal antibodies approved for AD. 

“These data are important both from an efficacy and safety perspective” for those advising patients who need chronic AD treatment, said Dr. Silverberg, who was the principal investigator of the ADvocate trials. 

Earlier this year, 5-year follow-up data were published for dupilumab. Of 326 patients who remained on therapy this long, 220 (67%) maintained an IGA of 0 or 1 at the end of the study. There were no unexpected adverse events, which were generally stable or declined throughout the study. 

Dr. Thaçi has financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Leo Pharma, L’Oreal, Janssen-Cilag, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sun Pharma, UCB, and Vichy. Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies including those that make drugs for AD.

A version of this article appeared on Medscape.com.

AMSTERDAM — For patients with atopic dermatitis (AD) who responded to the anti–interleukin (IL)–13 monoclonal antibody lebrikizumab in the pivotal trials, the level of response, including 90% skin clearance, has generally remained unchanged among those followed up for an additional 2 years, according to the latest data from an extension study. 

At the end of the maintenance phase of the pivotal trials at 12 months, 84% of the patients enrolled into the extension had clear or almost clear skin, as per the Investigator Global Assessment (IGA). This overall figure as well as the proportion with even better responses have persisted unchanged, reported Diamant Thaçi, MD, PhD, professor and head of the Comprehensive Center for Inflammatory Medicine, University of Lübeck in Germany. 
 

Responses at 3 Years Maintained

“This is really quite remarkable,” Dr. Thaçi said. “Roughly all the patients maintained their response.” These results became even more remarkable when patients were assessed for their use of adjunctive therapy to control flares. 

“Over the whole follow-up, 90% had no need for topical corticosteroids or any other rescue therapy,” Dr. Thaçi reported, providing data from the ADjoin lebrikizumab extension study during a late-breaking news session at the annual meeting of the European Academy of Dermatology and Venereology. 

The patients in ADjoin were enrolled from the pivotal phase 3 ADvocate 1 and 2 trials completed almost 2 years ago and published together in March 2023. Lebrikizumab was approved in the United States in September 2024 for moderate to severe AD in patients aged ≥ 12 years, following previous approvals in Europe in 2023 and in Japan in January 2024.

In these two identical trials with a total of 564 patients, the primary endpoint was an IGA of 0 or 1, signifying clear or almost clear skin. At nearly 40%, the proportion of patients reaching this outcome at 16 weeks was about threefold greater (P < .001) on lebrikizumab than on placebo. The benefit was similar on secondary endpoints, such as 75% improvement in the Eczema Area and Severity Index (EASI75) score. 

At the end of the double-blind, placebo-controlled 16-week phase of the ADvocate 1 and 2 trials, which enrolled adults and adolescents aged ≥ 12 years, responders were enrolled into a maintenance phase in which they were rerandomized to 250 mg lebrikizumab every 2 weeks (Q2W) or every 4 weeks (Q4W). The latter is the approved maintenance dose. 

At the end of the maintenance phase, which lasted another 32 weeks (total exposure of 52 weeks for those initially randomized to lebrikizumab), patients were invited into the ADjoin extension. The only exclusions from the extension were serious adverse events related to lebrikizumab and noncompliance. 
 

Response Curves Appear as Straight Lines

Over the next 2 years of ADjoin, response curves appeared as straight lines not only for the overall response but when patients were stratified for different levels of response at the extension study entry. Specifically, 81.5% and 83.3% had an IGA score of 0 or 1 in the Q2W and Q4W arms at completion of the ADvocate 16-week double-blind phase. At 3 years, the rates were 84.0% and 82.9%, respectively. 

For the subgroup who entered ADjoin with an EASI75 or an EASI90 response, the persistence of this level of response over 2 years was similar, although there was some gain observed among those who entered the trial with an EASI75 response. 

“Not only did these patients maintain their response, but the response on average slowly improved, so that there were more patients with an EASI90 response at the 3-year timepoint,” Dr. Thaçi said.

Of the 181 patients in the ADjoin extension, 82 patients were maintained on Q2W dosing and 99 were maintained on Q4W lebrikizumab. Their mean age was about 35 years, more than half were women, and nearly 40% had severe AD at the time they enrolled in the ADvocate trials. There was essentially no difference in response rates among those in the Q2W and Q4W arms over time in ADjoin. 
 

Side Effect Profile Essentially Unchanged

The side effect and tolerability profiles, which were favorable in the original 16-week placebo-controlled study, have remained unchanged over the subsequent maintenance phase and through the additional 2 years of the ADjoin extension.

“There continued to be reports of conjunctivitis, which is very specific for anti–IL-13 therapies,” Dr. Thaçi said. However, he said that the incidence did not increase over time, and because it was easy to treat, “most patients do not discontinue lebrikizumab for this reason.” Moreover, he said the impression was that “the number of patients experiencing adverse effects has been decreasing over time.” 

Calling these long-term results “very exciting,” Dr. Thaçi called lebrikizumab “a very valuable option for long-term AD care.” 

Asked for his perspective on the results, Jonathan I. Silverberg, MD, PhD, Director of Clinical Research, Department of Dermatology, George Washington University, Washington, DC, said that it is important to study long-term efficacy, and these results are positive. Without direct comparisons to other biologics available for AD, nothing can be implied about the relative efficacy of monoclonal antibodies approved for AD. 

“These data are important both from an efficacy and safety perspective” for those advising patients who need chronic AD treatment, said Dr. Silverberg, who was the principal investigator of the ADvocate trials. 

Earlier this year, 5-year follow-up data were published for dupilumab. Of 326 patients who remained on therapy this long, 220 (67%) maintained an IGA of 0 or 1 at the end of the study. There were no unexpected adverse events, which were generally stable or declined throughout the study. 

Dr. Thaçi has financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Leo Pharma, L’Oreal, Janssen-Cilag, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sun Pharma, UCB, and Vichy. Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies including those that make drugs for AD.

A version of this article appeared on Medscape.com.

AMSTERDAM — A proteomics study designed to determine why some patients with atopic dermatitis (AD) respond quickly to dupilumab, others respond more slowly, and the remainder do not respond at all demonstrated that molecular responses in these three groups are very different.

A discovery that could lead to personalizing therapies, the data identified “distinct systemic biomarker profiles,” according to Ester Del Duca, MD, an instructor in the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York City.

The study was conducted with 67 patients with AD and 16 healthy controls. Serum was collected at two timepoints: An average of 20 weeks after starting dupilumab, then at a mean interval of about 9 months later. At these timepoints, called follow-up 1 and 2, a panel of more than 600 proteins, including unique markers for immunologic, cardiovascular, and neurologic activity, were evaluated.

The criterion for differentiating the three response groups was an Investigator Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (or at least a 2-point IGA reduction from baseline). Early responders were those who met the criterion at both follow-ups, late responders were those who met this criterion only at the second follow-up, and nonresponders never met the criterion.

“There were no significant differences at baseline in clinical severity, past medical history, or patient characteristics,” said Del Duca, who presented these data in a late breaking news session at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Of the 67 patients with AD, 39 were early responders, 11 were late responders, and 17 were nonresponders.

The differences in proteomics were marked. For early responders, there was an early normalization of the proteome, reported Del Duca, illustrating the differences in the proteome of the three groups with a color-coded chart of protein up-regulation and down-regulation relative to healthy controls. The normalization of the proteome persisted in early responders when assessed at the second follow-up.

In the late responders, the proteome dysregulation was substantial relative to healthy controls at the first follow-up, but there was considerable improvement by the second follow-up. Although the change at the second follow-up was still not as robust as that seen in the early responders at either follow-up, Del Duca described the proteomic profile as a 45% improvement from the first follow-up.

In contrast, nonresponders showed worsening in their blood proteome from follow-up 1 to 2. Nonresponders at first follow-up showed up-regulation relative to healthy controls for many proteins associated with the Th1 response, such as interferon gamma, CXCL9, and CXCL10, and Th2 response, such as interleukin-4 and Th17/22, and these did not normalize or worsen by the second follow-up.

“Uniquely to nonresponders, key Th1 biomarkers remained significantly up-regulated relative to controls at both follow-up 1 and 2,” with a P value < .05, Del Duca reported.

To achieve normalization of the proteome as defined by healthy controls, both up-regulation and down-regulation of protein activity were required, although more up-regulations than down-regulations were observed.

When evaluating the proteome changes most implicated in immunoregulation, the investigators were able to show a correlation between worsening in the proteome and greater severity of AD as defined by IGA, Eczema Area and Severity Index, and body surface area involvement.

“Spearman analysis revealed strong and positive correlations between improvements in biomarkers at follow-up 1 and 2 with improvements in clinical markers,” Del Duca said. As examples, she noted favorable changes in biomarkers specifically associated with T cells, dendritic cells, and natural killer cells as clinical outcomes improved.

Conversely, the worsening in T-cell activation among nonresponders, particularly Th1 biomarkers, also tracked with increasing AD symptoms over time.

The implications of the research are broad, and most importantly, it shows that therapeutic targets are likely to differ between patients with AD, according to Del Duca. Although proteomic studies have not yet been conducted with other treatments, these might provide further insight about how patients with AD differ in response across other drugs.

This is important work, according to Brigitte Dréno, MD, PhD, head of the Department of Dermatology, Nantes University Hospital in France. As moderator of the late-breaking news session, she suggested that there are many potential messages from these data, not least that treatment of AD likely involves targeting cytokines beyond those affected by dupilumab in at least some patients.

When Dréno asked Del Duca about what could be surmised about changes from baseline before treatment to the first follow-up, Del Duca said that the study was retrospective, so baseline data were not available.

This is an important missing piece of this investigation, according to Dréno.

“As you move this work forward,” she said that it would be “very important” to determine “if there are predictive markers for evaluating which patients will respond.”

This is a small study with many additional variables to consider in order to develop a clinically useful tool, Del Duca noted. However, this work not only has the potential to guide treatment selection but the biomarkers up-regulated in nonresponders are already “suggesting potential targets for refining therapeutic strategies,” she said.

The study received funding from Bristol-Myers Squibb. Del Duca reported no financial relationships with industry. Dréno reported financial relationships with La Roche–Posay, Pierre Fabré, and Galderma.

A version of this article appeared on Medscape.com.

AMSTERDAM — A proteomics study designed to determine why some patients with atopic dermatitis (AD) respond quickly to dupilumab, others respond more slowly, and the remainder do not respond at all demonstrated that molecular responses in these three groups are very different.

A discovery that could lead to personalizing therapies, the data identified “distinct systemic biomarker profiles,” according to Ester Del Duca, MD, an instructor in the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York City.

The study was conducted with 67 patients with AD and 16 healthy controls. Serum was collected at two timepoints: An average of 20 weeks after starting dupilumab, then at a mean interval of about 9 months later. At these timepoints, called follow-up 1 and 2, a panel of more than 600 proteins, including unique markers for immunologic, cardiovascular, and neurologic activity, were evaluated.

The criterion for differentiating the three response groups was an Investigator Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (or at least a 2-point IGA reduction from baseline). Early responders were those who met the criterion at both follow-ups, late responders were those who met this criterion only at the second follow-up, and nonresponders never met the criterion.

“There were no significant differences at baseline in clinical severity, past medical history, or patient characteristics,” said Del Duca, who presented these data in a late breaking news session at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Of the 67 patients with AD, 39 were early responders, 11 were late responders, and 17 were nonresponders.

The differences in proteomics were marked. For early responders, there was an early normalization of the proteome, reported Del Duca, illustrating the differences in the proteome of the three groups with a color-coded chart of protein up-regulation and down-regulation relative to healthy controls. The normalization of the proteome persisted in early responders when assessed at the second follow-up.

In the late responders, the proteome dysregulation was substantial relative to healthy controls at the first follow-up, but there was considerable improvement by the second follow-up. Although the change at the second follow-up was still not as robust as that seen in the early responders at either follow-up, Del Duca described the proteomic profile as a 45% improvement from the first follow-up.

In contrast, nonresponders showed worsening in their blood proteome from follow-up 1 to 2. Nonresponders at first follow-up showed up-regulation relative to healthy controls for many proteins associated with the Th1 response, such as interferon gamma, CXCL9, and CXCL10, and Th2 response, such as interleukin-4 and Th17/22, and these did not normalize or worsen by the second follow-up.

“Uniquely to nonresponders, key Th1 biomarkers remained significantly up-regulated relative to controls at both follow-up 1 and 2,” with a P value < .05, Del Duca reported.

To achieve normalization of the proteome as defined by healthy controls, both up-regulation and down-regulation of protein activity were required, although more up-regulations than down-regulations were observed.

When evaluating the proteome changes most implicated in immunoregulation, the investigators were able to show a correlation between worsening in the proteome and greater severity of AD as defined by IGA, Eczema Area and Severity Index, and body surface area involvement.

“Spearman analysis revealed strong and positive correlations between improvements in biomarkers at follow-up 1 and 2 with improvements in clinical markers,” Del Duca said. As examples, she noted favorable changes in biomarkers specifically associated with T cells, dendritic cells, and natural killer cells as clinical outcomes improved.

Conversely, the worsening in T-cell activation among nonresponders, particularly Th1 biomarkers, also tracked with increasing AD symptoms over time.

The implications of the research are broad, and most importantly, it shows that therapeutic targets are likely to differ between patients with AD, according to Del Duca. Although proteomic studies have not yet been conducted with other treatments, these might provide further insight about how patients with AD differ in response across other drugs.

This is important work, according to Brigitte Dréno, MD, PhD, head of the Department of Dermatology, Nantes University Hospital in France. As moderator of the late-breaking news session, she suggested that there are many potential messages from these data, not least that treatment of AD likely involves targeting cytokines beyond those affected by dupilumab in at least some patients.

When Dréno asked Del Duca about what could be surmised about changes from baseline before treatment to the first follow-up, Del Duca said that the study was retrospective, so baseline data were not available.

This is an important missing piece of this investigation, according to Dréno.

“As you move this work forward,” she said that it would be “very important” to determine “if there are predictive markers for evaluating which patients will respond.”

This is a small study with many additional variables to consider in order to develop a clinically useful tool, Del Duca noted. However, this work not only has the potential to guide treatment selection but the biomarkers up-regulated in nonresponders are already “suggesting potential targets for refining therapeutic strategies,” she said.

The study received funding from Bristol-Myers Squibb. Del Duca reported no financial relationships with industry. Dréno reported financial relationships with La Roche–Posay, Pierre Fabré, and Galderma.

A version of this article appeared on Medscape.com.

AMSTERDAM — A proteomics study designed to determine why some patients with atopic dermatitis (AD) respond quickly to dupilumab, others respond more slowly, and the remainder do not respond at all demonstrated that molecular responses in these three groups are very different.

A discovery that could lead to personalizing therapies, the data identified “distinct systemic biomarker profiles,” according to Ester Del Duca, MD, an instructor in the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York City.

The study was conducted with 67 patients with AD and 16 healthy controls. Serum was collected at two timepoints: An average of 20 weeks after starting dupilumab, then at a mean interval of about 9 months later. At these timepoints, called follow-up 1 and 2, a panel of more than 600 proteins, including unique markers for immunologic, cardiovascular, and neurologic activity, were evaluated.

The criterion for differentiating the three response groups was an Investigator Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (or at least a 2-point IGA reduction from baseline). Early responders were those who met the criterion at both follow-ups, late responders were those who met this criterion only at the second follow-up, and nonresponders never met the criterion.

“There were no significant differences at baseline in clinical severity, past medical history, or patient characteristics,” said Del Duca, who presented these data in a late breaking news session at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Of the 67 patients with AD, 39 were early responders, 11 were late responders, and 17 were nonresponders.

The differences in proteomics were marked. For early responders, there was an early normalization of the proteome, reported Del Duca, illustrating the differences in the proteome of the three groups with a color-coded chart of protein up-regulation and down-regulation relative to healthy controls. The normalization of the proteome persisted in early responders when assessed at the second follow-up.

In the late responders, the proteome dysregulation was substantial relative to healthy controls at the first follow-up, but there was considerable improvement by the second follow-up. Although the change at the second follow-up was still not as robust as that seen in the early responders at either follow-up, Del Duca described the proteomic profile as a 45% improvement from the first follow-up.

In contrast, nonresponders showed worsening in their blood proteome from follow-up 1 to 2. Nonresponders at first follow-up showed up-regulation relative to healthy controls for many proteins associated with the Th1 response, such as interferon gamma, CXCL9, and CXCL10, and Th2 response, such as interleukin-4 and Th17/22, and these did not normalize or worsen by the second follow-up.

“Uniquely to nonresponders, key Th1 biomarkers remained significantly up-regulated relative to controls at both follow-up 1 and 2,” with a P value < .05, Del Duca reported.

To achieve normalization of the proteome as defined by healthy controls, both up-regulation and down-regulation of protein activity were required, although more up-regulations than down-regulations were observed.

When evaluating the proteome changes most implicated in immunoregulation, the investigators were able to show a correlation between worsening in the proteome and greater severity of AD as defined by IGA, Eczema Area and Severity Index, and body surface area involvement.

“Spearman analysis revealed strong and positive correlations between improvements in biomarkers at follow-up 1 and 2 with improvements in clinical markers,” Del Duca said. As examples, she noted favorable changes in biomarkers specifically associated with T cells, dendritic cells, and natural killer cells as clinical outcomes improved.

Conversely, the worsening in T-cell activation among nonresponders, particularly Th1 biomarkers, also tracked with increasing AD symptoms over time.

The implications of the research are broad, and most importantly, it shows that therapeutic targets are likely to differ between patients with AD, according to Del Duca. Although proteomic studies have not yet been conducted with other treatments, these might provide further insight about how patients with AD differ in response across other drugs.

This is important work, according to Brigitte Dréno, MD, PhD, head of the Department of Dermatology, Nantes University Hospital in France. As moderator of the late-breaking news session, she suggested that there are many potential messages from these data, not least that treatment of AD likely involves targeting cytokines beyond those affected by dupilumab in at least some patients.

When Dréno asked Del Duca about what could be surmised about changes from baseline before treatment to the first follow-up, Del Duca said that the study was retrospective, so baseline data were not available.

This is an important missing piece of this investigation, according to Dréno.

“As you move this work forward,” she said that it would be “very important” to determine “if there are predictive markers for evaluating which patients will respond.”

This is a small study with many additional variables to consider in order to develop a clinically useful tool, Del Duca noted. However, this work not only has the potential to guide treatment selection but the biomarkers up-regulated in nonresponders are already “suggesting potential targets for refining therapeutic strategies,” she said.

The study received funding from Bristol-Myers Squibb. Del Duca reported no financial relationships with industry. Dréno reported financial relationships with La Roche–Posay, Pierre Fabré, and Galderma.

A version of this article appeared on Medscape.com.

Clinicians receive conflicting advice on whether to order blood tests to screen for lipids in children. A new study could add to the confusion. Researchers found that a combination of physical proxy measures such as hypertension and body mass index (BMI) predicted the risk for future cardiovascular events as well as the physical model plus lipid labs, questioning the value of those blood tests.

Some medical organizations advise screening only for high-risk children because more research is needed to define the harms and benefits of universal screening. Diet and behavioral changes are sufficient for most children, and universal screening could lead to false positives and unnecessary further testing, they said.

Groups that favor lipid tests for all children say these measurements detect familial hypercholesterolemia (FH) that would not otherwise be diagnosed, leading to treatment with drugs like statins and a greater chance of preventing cardiovascular disease (CVD) in adulthood.

Researchers from the new study said their findings do not address screenings for FH, which affects 1 in 250 US children and puts them at a risk for atherosclerotic CVD.
 

Recommending Blood Tests in Age Groups

One of the seminal guidelines on screening lipids in children came from the National Heart, Lung, and Blood Institute (NHLBI), which in 2011 recommended children undergo dyslipidemia screening between the ages of 9 and 11 years and again between 17 and 21 years. Children should receive a screening starting at age 2 years if they have a family history of CVD or dyslipidemia or have diabetes, an elevated BMI, or hypertension. The American Academy of Pediatrics shortly followed suit, issuing similar recommendations.

Screening for the two subsets of ages was an expansion from the original 1992 guidelines from the National Cholesterol Education Program, which recommended screening only for children with either a family history of early CVD or elevated total cholesterol levels.

A 2011 panel for the NHLBI said the older approach identified significantly fewer children with abnormal levels of low-density lipoprotein cholesterol (LDL-C) than the addition of two age groups for screening, adding that many children do not have a complete family history. The American College of Cardiology and American Heart Association later supported NHLBI’s stance in their joint guidelines on the management of cholesterol.

Mark Corkins, MD, chair of the AAP’s Committee on Nutrition, told Medscape Medical News that if children are screened only because they have obesity or a family history of FH, some with elevated lipid levels will be missed. For instance, studies indicate caregiver recall of FH often is inaccurate, and the genetic disorder that causes the condition is not related to obesity.

“The screening is to find familial hypercholesterolemia, to try to find the ones that need therapy,” that would not be caught by the risk-based screening earlier on in childhood, Corkins said.
 

Only Screen Children With Risk Factors

But other groups do not agree. The US Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for lipid disorders in asymptomatic children and teens.

The group also said it found inadequate evidence that lipid-lowering interventions in the general pediatric population lead to reductions in cardiovascular events or all-cause mortality once they reached adulthood. USPSTF also raised questions about the safety of lipid-lowering drugs in children.

“The current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger,” the panel wrote.

The American Academy of Family Physicians supports USPSTF’s recommendations.
 

Low Rate of Screening

While the uncertainty over screening in children continues, the practice has been adopted by a minority of clinicians.

A study published in JAMA Network Open in July found 9% of 700,000 9- to 11-year-olds had a documented result from a lipid screening. Among more than 1.3 million 17- to 21-year-olds, 13% had received a screening.

As BMI went up, so did screening rates. A little over 9% children and teens with a healthy weight were screened compared with 14.7% of those with moderate obesity and 21.9% of those with severe obesity.

Among those screened, 32.3% of 9- to 11-year-olds and 30.2% of 17- to 21-year-olds had abnormal lipid levels, defined as having one elevated measure out of five, including total cholesterol of 200 mg/dL or higher or LDL-C levels of 130 mg/dL or higher.

Justin Zachariah, MD, MPH, an associate professor of pediatrics-cardiology at Baylor College of Medicine in Houston, spoke about physicians screening children based only on factors like obesity during a presentation at the recent annual meeting of the American Academy of Pediatrics. He cited research showing roughly one in four children with abnormal lipids had a normal weight.

If a clinician is reserving a lipid screening for a child who is overweight or has obesity, “you’re missing nearly half the problem,” Zachariah said during his presentation.

One reason for the low rate of universal screening may be inattention to FH by clinicians, according to Samuel S. Gidding, MD, a professor in the Department of Genomic Health at Geisinger College of Health Sciences in Bridgewater Corners, Vermont.

For instance, a clinician has only a set amount of time during a well-child visit and other issues may take precedence, “so it doesn’t make sense to broach preventive screening for something that could happen 30 or 40 years from now, vs this [other] very immediate problem,” he said.

Clinicians “are triggered to act on the LDL level, but don’t think about FH as a possible diagnosis,” Gidding told Medscape Medical News.

Another barrier is that in some settings, caregivers must take children and teens to another facility on a different day to fulfill an order for a lipid test.

“It’s reluctance of doctors to order it, knowing patients won’t go through with it,” Gidding said.

Gidding is a consultant for Esperion Therapeutics. Other sources in this story reported no relevant financial conflicts of interest.
 

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

Clinicians receive conflicting advice on whether to order blood tests to screen for lipids in children. A new study could add to the confusion. Researchers found that a combination of physical proxy measures such as hypertension and body mass index (BMI) predicted the risk for future cardiovascular events as well as the physical model plus lipid labs, questioning the value of those blood tests.

Some medical organizations advise screening only for high-risk children because more research is needed to define the harms and benefits of universal screening. Diet and behavioral changes are sufficient for most children, and universal screening could lead to false positives and unnecessary further testing, they said.

Groups that favor lipid tests for all children say these measurements detect familial hypercholesterolemia (FH) that would not otherwise be diagnosed, leading to treatment with drugs like statins and a greater chance of preventing cardiovascular disease (CVD) in adulthood.

Researchers from the new study said their findings do not address screenings for FH, which affects 1 in 250 US children and puts them at a risk for atherosclerotic CVD.
 

Recommending Blood Tests in Age Groups

One of the seminal guidelines on screening lipids in children came from the National Heart, Lung, and Blood Institute (NHLBI), which in 2011 recommended children undergo dyslipidemia screening between the ages of 9 and 11 years and again between 17 and 21 years. Children should receive a screening starting at age 2 years if they have a family history of CVD or dyslipidemia or have diabetes, an elevated BMI, or hypertension. The American Academy of Pediatrics shortly followed suit, issuing similar recommendations.

Screening for the two subsets of ages was an expansion from the original 1992 guidelines from the National Cholesterol Education Program, which recommended screening only for children with either a family history of early CVD or elevated total cholesterol levels.

A 2011 panel for the NHLBI said the older approach identified significantly fewer children with abnormal levels of low-density lipoprotein cholesterol (LDL-C) than the addition of two age groups for screening, adding that many children do not have a complete family history. The American College of Cardiology and American Heart Association later supported NHLBI’s stance in their joint guidelines on the management of cholesterol.

Mark Corkins, MD, chair of the AAP’s Committee on Nutrition, told Medscape Medical News that if children are screened only because they have obesity or a family history of FH, some with elevated lipid levels will be missed. For instance, studies indicate caregiver recall of FH often is inaccurate, and the genetic disorder that causes the condition is not related to obesity.

“The screening is to find familial hypercholesterolemia, to try to find the ones that need therapy,” that would not be caught by the risk-based screening earlier on in childhood, Corkins said.
 

Only Screen Children With Risk Factors

But other groups do not agree. The US Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for lipid disorders in asymptomatic children and teens.

The group also said it found inadequate evidence that lipid-lowering interventions in the general pediatric population lead to reductions in cardiovascular events or all-cause mortality once they reached adulthood. USPSTF also raised questions about the safety of lipid-lowering drugs in children.

“The current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger,” the panel wrote.

The American Academy of Family Physicians supports USPSTF’s recommendations.
 

Low Rate of Screening

While the uncertainty over screening in children continues, the practice has been adopted by a minority of clinicians.

A study published in JAMA Network Open in July found 9% of 700,000 9- to 11-year-olds had a documented result from a lipid screening. Among more than 1.3 million 17- to 21-year-olds, 13% had received a screening.

As BMI went up, so did screening rates. A little over 9% children and teens with a healthy weight were screened compared with 14.7% of those with moderate obesity and 21.9% of those with severe obesity.

Among those screened, 32.3% of 9- to 11-year-olds and 30.2% of 17- to 21-year-olds had abnormal lipid levels, defined as having one elevated measure out of five, including total cholesterol of 200 mg/dL or higher or LDL-C levels of 130 mg/dL or higher.

Justin Zachariah, MD, MPH, an associate professor of pediatrics-cardiology at Baylor College of Medicine in Houston, spoke about physicians screening children based only on factors like obesity during a presentation at the recent annual meeting of the American Academy of Pediatrics. He cited research showing roughly one in four children with abnormal lipids had a normal weight.

If a clinician is reserving a lipid screening for a child who is overweight or has obesity, “you’re missing nearly half the problem,” Zachariah said during his presentation.

One reason for the low rate of universal screening may be inattention to FH by clinicians, according to Samuel S. Gidding, MD, a professor in the Department of Genomic Health at Geisinger College of Health Sciences in Bridgewater Corners, Vermont.

For instance, a clinician has only a set amount of time during a well-child visit and other issues may take precedence, “so it doesn’t make sense to broach preventive screening for something that could happen 30 or 40 years from now, vs this [other] very immediate problem,” he said.

Clinicians “are triggered to act on the LDL level, but don’t think about FH as a possible diagnosis,” Gidding told Medscape Medical News.

Another barrier is that in some settings, caregivers must take children and teens to another facility on a different day to fulfill an order for a lipid test.

“It’s reluctance of doctors to order it, knowing patients won’t go through with it,” Gidding said.

Gidding is a consultant for Esperion Therapeutics. Other sources in this story reported no relevant financial conflicts of interest.
 

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

Clinicians receive conflicting advice on whether to order blood tests to screen for lipids in children. A new study could add to the confusion. Researchers found that a combination of physical proxy measures such as hypertension and body mass index (BMI) predicted the risk for future cardiovascular events as well as the physical model plus lipid labs, questioning the value of those blood tests.

Some medical organizations advise screening only for high-risk children because more research is needed to define the harms and benefits of universal screening. Diet and behavioral changes are sufficient for most children, and universal screening could lead to false positives and unnecessary further testing, they said.

Groups that favor lipid tests for all children say these measurements detect familial hypercholesterolemia (FH) that would not otherwise be diagnosed, leading to treatment with drugs like statins and a greater chance of preventing cardiovascular disease (CVD) in adulthood.

Researchers from the new study said their findings do not address screenings for FH, which affects 1 in 250 US children and puts them at a risk for atherosclerotic CVD.
 

Recommending Blood Tests in Age Groups

One of the seminal guidelines on screening lipids in children came from the National Heart, Lung, and Blood Institute (NHLBI), which in 2011 recommended children undergo dyslipidemia screening between the ages of 9 and 11 years and again between 17 and 21 years. Children should receive a screening starting at age 2 years if they have a family history of CVD or dyslipidemia or have diabetes, an elevated BMI, or hypertension. The American Academy of Pediatrics shortly followed suit, issuing similar recommendations.

Screening for the two subsets of ages was an expansion from the original 1992 guidelines from the National Cholesterol Education Program, which recommended screening only for children with either a family history of early CVD or elevated total cholesterol levels.

A 2011 panel for the NHLBI said the older approach identified significantly fewer children with abnormal levels of low-density lipoprotein cholesterol (LDL-C) than the addition of two age groups for screening, adding that many children do not have a complete family history. The American College of Cardiology and American Heart Association later supported NHLBI’s stance in their joint guidelines on the management of cholesterol.

Mark Corkins, MD, chair of the AAP’s Committee on Nutrition, told Medscape Medical News that if children are screened only because they have obesity or a family history of FH, some with elevated lipid levels will be missed. For instance, studies indicate caregiver recall of FH often is inaccurate, and the genetic disorder that causes the condition is not related to obesity.

“The screening is to find familial hypercholesterolemia, to try to find the ones that need therapy,” that would not be caught by the risk-based screening earlier on in childhood, Corkins said.
 

Only Screen Children With Risk Factors

But other groups do not agree. The US Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for lipid disorders in asymptomatic children and teens.

The group also said it found inadequate evidence that lipid-lowering interventions in the general pediatric population lead to reductions in cardiovascular events or all-cause mortality once they reached adulthood. USPSTF also raised questions about the safety of lipid-lowering drugs in children.

“The current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger,” the panel wrote.

The American Academy of Family Physicians supports USPSTF’s recommendations.
 

Low Rate of Screening

While the uncertainty over screening in children continues, the practice has been adopted by a minority of clinicians.

A study published in JAMA Network Open in July found 9% of 700,000 9- to 11-year-olds had a documented result from a lipid screening. Among more than 1.3 million 17- to 21-year-olds, 13% had received a screening.

As BMI went up, so did screening rates. A little over 9% children and teens with a healthy weight were screened compared with 14.7% of those with moderate obesity and 21.9% of those with severe obesity.

Among those screened, 32.3% of 9- to 11-year-olds and 30.2% of 17- to 21-year-olds had abnormal lipid levels, defined as having one elevated measure out of five, including total cholesterol of 200 mg/dL or higher or LDL-C levels of 130 mg/dL or higher.

Justin Zachariah, MD, MPH, an associate professor of pediatrics-cardiology at Baylor College of Medicine in Houston, spoke about physicians screening children based only on factors like obesity during a presentation at the recent annual meeting of the American Academy of Pediatrics. He cited research showing roughly one in four children with abnormal lipids had a normal weight.

If a clinician is reserving a lipid screening for a child who is overweight or has obesity, “you’re missing nearly half the problem,” Zachariah said during his presentation.

One reason for the low rate of universal screening may be inattention to FH by clinicians, according to Samuel S. Gidding, MD, a professor in the Department of Genomic Health at Geisinger College of Health Sciences in Bridgewater Corners, Vermont.

For instance, a clinician has only a set amount of time during a well-child visit and other issues may take precedence, “so it doesn’t make sense to broach preventive screening for something that could happen 30 or 40 years from now, vs this [other] very immediate problem,” he said.

Clinicians “are triggered to act on the LDL level, but don’t think about FH as a possible diagnosis,” Gidding told Medscape Medical News.

Another barrier is that in some settings, caregivers must take children and teens to another facility on a different day to fulfill an order for a lipid test.

“It’s reluctance of doctors to order it, knowing patients won’t go through with it,” Gidding said.

Gidding is a consultant for Esperion Therapeutics. Other sources in this story reported no relevant financial conflicts of interest.
 

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

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

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

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

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

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

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