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Rules for performing research with children
The road to hell is paved with good intentions – especially true in clinical research. A Food and Drug Administration press release notes, “Historically, children were not included in clinical trials because of a misperception that excluding them from research was in fact protecting them. This resulted in many FDA-approved, licensed, cleared, or authorized drugs, biological products, and medical devices lacking pediatric-specific labeling information.” In an effort to improve on this situation, the FDA published in September 2022 a proposed new draft guidance on performing research with children that is open for public comment for 3 months.
There is a long history of government attempts to promote research and development for the benefit of society. Sometimes government succeeds and sometimes not. For instance, when the U.S. federal government funded scientific research in the 1960s, it sought to increase the common good by promulgating those discoveries. The government insisted that all federally funded research be in the public domain. The funding produced a spectacular number of technological advancements that have enriched society. However, a decade later, the government concluded that too many good research ideas were never developed into beneficial products because without the ability to patent the results, the costs and risks of product development were not profitable for industry. By the late 1970s, new laws were enacted to enable universities and their faculty to patent the results of government-funded research and share in any wealth created.
Pharmaceutical research in the 1970s and 1980s was mostly performed on men in order to reduce the risk of giving treatments of unknown safety to pregnant women. The unintended consequence was that the new drugs frequently were less effective for women. This was particularly true for cardiac medications for which lifestyle risk factors differed between the sexes.
Similarly, children were often excluded from research because of the unknown risks of new drugs on growing bodies and brains. Children were also seen as a vulnerable population for whom informed consent was problematic. The result of these well-intentioned restrictions was the creation of new products that did not have pediatric dosing recommendations, pediatric safety assessments, or approval for pediatric indications. To remediate these deficiencies, in 1997 and 2007 the FDA offered a 6-month extension on patent protection as motivation for companies to develop those pediatric recommendations. Alas, those laws were primarily used to extend the profitability of blockbuster products rather than truly benefit children.
Over the past 4 decades, pediatric ethicists proposed and refined rules to govern research on children. The Common Rule used by institutional review boards (IRBs) to protect human research subjects was expanded with guidelines covering children. The new draft guidance is the latest iteration of this effort. Nothing in the 14 pages of draft regulation appears revolutionary to me. The ideas are tweaks, based on theory and experience, of principles agreed upon 30 years ago. Finding the optimal social moral contract involves some empirical assessment of praxis and effectiveness.
I am loathe to summarize this new document, which itself is a summary of a vast body of literature, that supports the Code of Federal Regulations Title 21 Part 50 and 45 CFR Part 46. The draft document is well organized and I recommend it as an excellent primer for the area of pediatric research ethics if the subject is new to you. I also recommend it as required reading for anyone serving on an IRB.
IRBs usually review and approve any research on people. Generally, the selection of people for research should be done equitably. However, children should not be enrolled unless it is necessary to answer an important question relevant to children. For the past 2 decades, there has been an emphasis on obtaining the assent of the child as well as informed consent by the parents.
An important determination is whether the research is likely to help that particular child or whether it is aimed at advancing general knowledge. If there is no prospect of direct benefit, research is still permissible but more restricted for safety and comfort reasons. Next is determining whether the research carries only minimal risk or a minor increase over minimal risk. The draft defines and provides anchor examples of these situations. For instance, oral placebos and single blood draws are typically minimal risk. Multiple injections and blood draws over a year fall into the second category. One MRI is minimal risk but a minor increase in risk if it involves sedation or contrast.
I strongly support the ideals expressed in these guidelines. They represent the best blend of intentions and practical experience. They will become the law of the land. In ethics, there is merit in striving to do things properly, orderly, and enforceably.
The cynic in me sees two weaknesses in the stated approach. First, the volume of harm to children occurring during organized clinical research is extremely small. The greater harms come from off-label use, nonsystematic research, and the ignorance resulting from a lack of research. Second, my observation in all endeavors of morality is, “Raise the bar high enough and people walk under it.”
Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
The road to hell is paved with good intentions – especially true in clinical research. A Food and Drug Administration press release notes, “Historically, children were not included in clinical trials because of a misperception that excluding them from research was in fact protecting them. This resulted in many FDA-approved, licensed, cleared, or authorized drugs, biological products, and medical devices lacking pediatric-specific labeling information.” In an effort to improve on this situation, the FDA published in September 2022 a proposed new draft guidance on performing research with children that is open for public comment for 3 months.
There is a long history of government attempts to promote research and development for the benefit of society. Sometimes government succeeds and sometimes not. For instance, when the U.S. federal government funded scientific research in the 1960s, it sought to increase the common good by promulgating those discoveries. The government insisted that all federally funded research be in the public domain. The funding produced a spectacular number of technological advancements that have enriched society. However, a decade later, the government concluded that too many good research ideas were never developed into beneficial products because without the ability to patent the results, the costs and risks of product development were not profitable for industry. By the late 1970s, new laws were enacted to enable universities and their faculty to patent the results of government-funded research and share in any wealth created.
Pharmaceutical research in the 1970s and 1980s was mostly performed on men in order to reduce the risk of giving treatments of unknown safety to pregnant women. The unintended consequence was that the new drugs frequently were less effective for women. This was particularly true for cardiac medications for which lifestyle risk factors differed between the sexes.
Similarly, children were often excluded from research because of the unknown risks of new drugs on growing bodies and brains. Children were also seen as a vulnerable population for whom informed consent was problematic. The result of these well-intentioned restrictions was the creation of new products that did not have pediatric dosing recommendations, pediatric safety assessments, or approval for pediatric indications. To remediate these deficiencies, in 1997 and 2007 the FDA offered a 6-month extension on patent protection as motivation for companies to develop those pediatric recommendations. Alas, those laws were primarily used to extend the profitability of blockbuster products rather than truly benefit children.
Over the past 4 decades, pediatric ethicists proposed and refined rules to govern research on children. The Common Rule used by institutional review boards (IRBs) to protect human research subjects was expanded with guidelines covering children. The new draft guidance is the latest iteration of this effort. Nothing in the 14 pages of draft regulation appears revolutionary to me. The ideas are tweaks, based on theory and experience, of principles agreed upon 30 years ago. Finding the optimal social moral contract involves some empirical assessment of praxis and effectiveness.
I am loathe to summarize this new document, which itself is a summary of a vast body of literature, that supports the Code of Federal Regulations Title 21 Part 50 and 45 CFR Part 46. The draft document is well organized and I recommend it as an excellent primer for the area of pediatric research ethics if the subject is new to you. I also recommend it as required reading for anyone serving on an IRB.
IRBs usually review and approve any research on people. Generally, the selection of people for research should be done equitably. However, children should not be enrolled unless it is necessary to answer an important question relevant to children. For the past 2 decades, there has been an emphasis on obtaining the assent of the child as well as informed consent by the parents.
An important determination is whether the research is likely to help that particular child or whether it is aimed at advancing general knowledge. If there is no prospect of direct benefit, research is still permissible but more restricted for safety and comfort reasons. Next is determining whether the research carries only minimal risk or a minor increase over minimal risk. The draft defines and provides anchor examples of these situations. For instance, oral placebos and single blood draws are typically minimal risk. Multiple injections and blood draws over a year fall into the second category. One MRI is minimal risk but a minor increase in risk if it involves sedation or contrast.
I strongly support the ideals expressed in these guidelines. They represent the best blend of intentions and practical experience. They will become the law of the land. In ethics, there is merit in striving to do things properly, orderly, and enforceably.
The cynic in me sees two weaknesses in the stated approach. First, the volume of harm to children occurring during organized clinical research is extremely small. The greater harms come from off-label use, nonsystematic research, and the ignorance resulting from a lack of research. Second, my observation in all endeavors of morality is, “Raise the bar high enough and people walk under it.”
Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
The road to hell is paved with good intentions – especially true in clinical research. A Food and Drug Administration press release notes, “Historically, children were not included in clinical trials because of a misperception that excluding them from research was in fact protecting them. This resulted in many FDA-approved, licensed, cleared, or authorized drugs, biological products, and medical devices lacking pediatric-specific labeling information.” In an effort to improve on this situation, the FDA published in September 2022 a proposed new draft guidance on performing research with children that is open for public comment for 3 months.
There is a long history of government attempts to promote research and development for the benefit of society. Sometimes government succeeds and sometimes not. For instance, when the U.S. federal government funded scientific research in the 1960s, it sought to increase the common good by promulgating those discoveries. The government insisted that all federally funded research be in the public domain. The funding produced a spectacular number of technological advancements that have enriched society. However, a decade later, the government concluded that too many good research ideas were never developed into beneficial products because without the ability to patent the results, the costs and risks of product development were not profitable for industry. By the late 1970s, new laws were enacted to enable universities and their faculty to patent the results of government-funded research and share in any wealth created.
Pharmaceutical research in the 1970s and 1980s was mostly performed on men in order to reduce the risk of giving treatments of unknown safety to pregnant women. The unintended consequence was that the new drugs frequently were less effective for women. This was particularly true for cardiac medications for which lifestyle risk factors differed between the sexes.
Similarly, children were often excluded from research because of the unknown risks of new drugs on growing bodies and brains. Children were also seen as a vulnerable population for whom informed consent was problematic. The result of these well-intentioned restrictions was the creation of new products that did not have pediatric dosing recommendations, pediatric safety assessments, or approval for pediatric indications. To remediate these deficiencies, in 1997 and 2007 the FDA offered a 6-month extension on patent protection as motivation for companies to develop those pediatric recommendations. Alas, those laws were primarily used to extend the profitability of blockbuster products rather than truly benefit children.
Over the past 4 decades, pediatric ethicists proposed and refined rules to govern research on children. The Common Rule used by institutional review boards (IRBs) to protect human research subjects was expanded with guidelines covering children. The new draft guidance is the latest iteration of this effort. Nothing in the 14 pages of draft regulation appears revolutionary to me. The ideas are tweaks, based on theory and experience, of principles agreed upon 30 years ago. Finding the optimal social moral contract involves some empirical assessment of praxis and effectiveness.
I am loathe to summarize this new document, which itself is a summary of a vast body of literature, that supports the Code of Federal Regulations Title 21 Part 50 and 45 CFR Part 46. The draft document is well organized and I recommend it as an excellent primer for the area of pediatric research ethics if the subject is new to you. I also recommend it as required reading for anyone serving on an IRB.
IRBs usually review and approve any research on people. Generally, the selection of people for research should be done equitably. However, children should not be enrolled unless it is necessary to answer an important question relevant to children. For the past 2 decades, there has been an emphasis on obtaining the assent of the child as well as informed consent by the parents.
An important determination is whether the research is likely to help that particular child or whether it is aimed at advancing general knowledge. If there is no prospect of direct benefit, research is still permissible but more restricted for safety and comfort reasons. Next is determining whether the research carries only minimal risk or a minor increase over minimal risk. The draft defines and provides anchor examples of these situations. For instance, oral placebos and single blood draws are typically minimal risk. Multiple injections and blood draws over a year fall into the second category. One MRI is minimal risk but a minor increase in risk if it involves sedation or contrast.
I strongly support the ideals expressed in these guidelines. They represent the best blend of intentions and practical experience. They will become the law of the land. In ethics, there is merit in striving to do things properly, orderly, and enforceably.
The cynic in me sees two weaknesses in the stated approach. First, the volume of harm to children occurring during organized clinical research is extremely small. The greater harms come from off-label use, nonsystematic research, and the ignorance resulting from a lack of research. Second, my observation in all endeavors of morality is, “Raise the bar high enough and people walk under it.”
Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
NICU signs hint at cerebral palsy risk
CINCINNATI – Cerebral palsy affects about 3 in every 1,000 children, but there is usually little sign of the condition at birth. Instead, it usually shows clinical manifestation between ages 2 and 5, and a diagnosis can trigger early interventions that can improve long-term outcomes.
Physicians and patients would benefit from a screening method for cerebral palsy at birth, but that has so far eluded researchers.
At the 2022 annual meeting of the Child Neurology Society, researchers presented evidence that , with higher variability associated with increased cerebral palsy risk.
The study results were promising, according to Marc Patterson, MD, who comoderated the session. “It gives us more confidence in predicting the children at risk and making sure that they’re going to be followed closely to get the interventions they need to help them,” said Dr. Patterson, who is a professor of neurology, pediatrics, and medical genetics at Mayo Medical School in Rochester, Minn.
“By the time a child is 5 or 6, the symptoms are usually very obvious, but you really want to intervene as soon as possible before their brain’s plasticity decreases over time, so the earlier you can intervene in general, the better your results are going to be,” said Dr. Patterson.
There are tools available to diagnose cerebral palsy at an earlier age, including the Prechtl General Movements Assessment (GMA), which can be done up to 5 months of corrected age. It has 97% sensitivity and 89% specificity for cerebral palsy. The Hammersmith Infant Neurological Examination (HINE), which can be used in the same age range, and has 72-91% sensitivity and 100% specificity.
Both of the available tools are resource intensive and require trained clinicians, and may be unavailable in many areas. Despite these tools, early diagnosis of cerebral palsy is still underemployed, according to Arohi Saxena, a third-year medical student at Washington University in St. Louis, who presented the study results.
Respiratory rate variability may indicate increased risk
The researchers set out to identify objective metrics that correlated with HINE and GMA scores. They looked at kinematic data from practical assessments carried out by their physical therapists, as well as vital sign instability obtained at NICU discharge, which was based on suggestions that hemodynamic instability may be linked to later risk of cerebral palsy, according to Ms. Saxena.
They analyzed data from 31 infants with a corrected age of 8-25 weeks at a tertiary NICU follow-up clinic. Of these, 18 displayed fidgety movements on their Prechtl assessment, and 13 did not.
They used DeepLabCut software to analyze data from videos of the Prechtl assessment, with a focus on range and variance of hand and foot movements normalized to nose-to-umbilicus distance. They also analyzed pulse and respiratory data from the final 24 hours before NICU discharge.
They found that infants without fidgety movements had decreased hand and foot movement ranges (P = .04). There was no significant difference between the two groups with respect to pulse measurements. However, the respiratory rate range and variance was significantly higher in infants without fidgety movements. “Infants who are at higher risk for developing cerebral palsy had more respiratory instability early on in life,” said Ms. Saxena during her talk.
When they compared values to HINE scores, they found a correlation with less foot movement and a predisposition to develop cerebral palsy, but no correlation with hand movement. A lower HINE sore also correlated to larger respiratory rate range and variance (P < .01 for both).
“Our hypothesis to explain this link is that respiratory rate variability is likely driven by neonatal injury in the brainstem, where the respiratory centers are located. In some infants, this may correlate with more extensive cerebral injury that could predict the development of cerebral palsy,” said Ms. Saxena.
The group plans to increase its sample size as well as to conduct long-term follow-up on the infants to see how many receive formal diagnoses of cerebral palsy.
After her talk, asked by a moderator why motor assessments were not a reliable predictor in their study, Ms. Saxena pointed to the inexperience of assessors at the institution, where Prechtl testing had only recently begun.
“I think a lot of it is to do with the more subjective nature of the motor assessment. We definitely saw kind of a trend where in the earlier data that was collected, right when our institutions started doing these Prechtls, it was even less of a reliable effect. So I think possibly as clinicians continue to get more familiar with this assessment and there’s more like a validated and robust scoring system, maybe we’ll see a stronger correlation,” she said.
Ms. Saxena had no relevant disclosures. Coauthor Boomah Aravamuthan, MD, DPhil, is a consultant for Neurocrine Biosciences and has received royalties from UpToDate and funding from the National Institute of Neurological Disorders and Stroke.
CINCINNATI – Cerebral palsy affects about 3 in every 1,000 children, but there is usually little sign of the condition at birth. Instead, it usually shows clinical manifestation between ages 2 and 5, and a diagnosis can trigger early interventions that can improve long-term outcomes.
Physicians and patients would benefit from a screening method for cerebral palsy at birth, but that has so far eluded researchers.
At the 2022 annual meeting of the Child Neurology Society, researchers presented evidence that , with higher variability associated with increased cerebral palsy risk.
The study results were promising, according to Marc Patterson, MD, who comoderated the session. “It gives us more confidence in predicting the children at risk and making sure that they’re going to be followed closely to get the interventions they need to help them,” said Dr. Patterson, who is a professor of neurology, pediatrics, and medical genetics at Mayo Medical School in Rochester, Minn.
“By the time a child is 5 or 6, the symptoms are usually very obvious, but you really want to intervene as soon as possible before their brain’s plasticity decreases over time, so the earlier you can intervene in general, the better your results are going to be,” said Dr. Patterson.
There are tools available to diagnose cerebral palsy at an earlier age, including the Prechtl General Movements Assessment (GMA), which can be done up to 5 months of corrected age. It has 97% sensitivity and 89% specificity for cerebral palsy. The Hammersmith Infant Neurological Examination (HINE), which can be used in the same age range, and has 72-91% sensitivity and 100% specificity.
Both of the available tools are resource intensive and require trained clinicians, and may be unavailable in many areas. Despite these tools, early diagnosis of cerebral palsy is still underemployed, according to Arohi Saxena, a third-year medical student at Washington University in St. Louis, who presented the study results.
Respiratory rate variability may indicate increased risk
The researchers set out to identify objective metrics that correlated with HINE and GMA scores. They looked at kinematic data from practical assessments carried out by their physical therapists, as well as vital sign instability obtained at NICU discharge, which was based on suggestions that hemodynamic instability may be linked to later risk of cerebral palsy, according to Ms. Saxena.
They analyzed data from 31 infants with a corrected age of 8-25 weeks at a tertiary NICU follow-up clinic. Of these, 18 displayed fidgety movements on their Prechtl assessment, and 13 did not.
They used DeepLabCut software to analyze data from videos of the Prechtl assessment, with a focus on range and variance of hand and foot movements normalized to nose-to-umbilicus distance. They also analyzed pulse and respiratory data from the final 24 hours before NICU discharge.
They found that infants without fidgety movements had decreased hand and foot movement ranges (P = .04). There was no significant difference between the two groups with respect to pulse measurements. However, the respiratory rate range and variance was significantly higher in infants without fidgety movements. “Infants who are at higher risk for developing cerebral palsy had more respiratory instability early on in life,” said Ms. Saxena during her talk.
When they compared values to HINE scores, they found a correlation with less foot movement and a predisposition to develop cerebral palsy, but no correlation with hand movement. A lower HINE sore also correlated to larger respiratory rate range and variance (P < .01 for both).
“Our hypothesis to explain this link is that respiratory rate variability is likely driven by neonatal injury in the brainstem, where the respiratory centers are located. In some infants, this may correlate with more extensive cerebral injury that could predict the development of cerebral palsy,” said Ms. Saxena.
The group plans to increase its sample size as well as to conduct long-term follow-up on the infants to see how many receive formal diagnoses of cerebral palsy.
After her talk, asked by a moderator why motor assessments were not a reliable predictor in their study, Ms. Saxena pointed to the inexperience of assessors at the institution, where Prechtl testing had only recently begun.
“I think a lot of it is to do with the more subjective nature of the motor assessment. We definitely saw kind of a trend where in the earlier data that was collected, right when our institutions started doing these Prechtls, it was even less of a reliable effect. So I think possibly as clinicians continue to get more familiar with this assessment and there’s more like a validated and robust scoring system, maybe we’ll see a stronger correlation,” she said.
Ms. Saxena had no relevant disclosures. Coauthor Boomah Aravamuthan, MD, DPhil, is a consultant for Neurocrine Biosciences and has received royalties from UpToDate and funding from the National Institute of Neurological Disorders and Stroke.
CINCINNATI – Cerebral palsy affects about 3 in every 1,000 children, but there is usually little sign of the condition at birth. Instead, it usually shows clinical manifestation between ages 2 and 5, and a diagnosis can trigger early interventions that can improve long-term outcomes.
Physicians and patients would benefit from a screening method for cerebral palsy at birth, but that has so far eluded researchers.
At the 2022 annual meeting of the Child Neurology Society, researchers presented evidence that , with higher variability associated with increased cerebral palsy risk.
The study results were promising, according to Marc Patterson, MD, who comoderated the session. “It gives us more confidence in predicting the children at risk and making sure that they’re going to be followed closely to get the interventions they need to help them,” said Dr. Patterson, who is a professor of neurology, pediatrics, and medical genetics at Mayo Medical School in Rochester, Minn.
“By the time a child is 5 or 6, the symptoms are usually very obvious, but you really want to intervene as soon as possible before their brain’s plasticity decreases over time, so the earlier you can intervene in general, the better your results are going to be,” said Dr. Patterson.
There are tools available to diagnose cerebral palsy at an earlier age, including the Prechtl General Movements Assessment (GMA), which can be done up to 5 months of corrected age. It has 97% sensitivity and 89% specificity for cerebral palsy. The Hammersmith Infant Neurological Examination (HINE), which can be used in the same age range, and has 72-91% sensitivity and 100% specificity.
Both of the available tools are resource intensive and require trained clinicians, and may be unavailable in many areas. Despite these tools, early diagnosis of cerebral palsy is still underemployed, according to Arohi Saxena, a third-year medical student at Washington University in St. Louis, who presented the study results.
Respiratory rate variability may indicate increased risk
The researchers set out to identify objective metrics that correlated with HINE and GMA scores. They looked at kinematic data from practical assessments carried out by their physical therapists, as well as vital sign instability obtained at NICU discharge, which was based on suggestions that hemodynamic instability may be linked to later risk of cerebral palsy, according to Ms. Saxena.
They analyzed data from 31 infants with a corrected age of 8-25 weeks at a tertiary NICU follow-up clinic. Of these, 18 displayed fidgety movements on their Prechtl assessment, and 13 did not.
They used DeepLabCut software to analyze data from videos of the Prechtl assessment, with a focus on range and variance of hand and foot movements normalized to nose-to-umbilicus distance. They also analyzed pulse and respiratory data from the final 24 hours before NICU discharge.
They found that infants without fidgety movements had decreased hand and foot movement ranges (P = .04). There was no significant difference between the two groups with respect to pulse measurements. However, the respiratory rate range and variance was significantly higher in infants without fidgety movements. “Infants who are at higher risk for developing cerebral palsy had more respiratory instability early on in life,” said Ms. Saxena during her talk.
When they compared values to HINE scores, they found a correlation with less foot movement and a predisposition to develop cerebral palsy, but no correlation with hand movement. A lower HINE sore also correlated to larger respiratory rate range and variance (P < .01 for both).
“Our hypothesis to explain this link is that respiratory rate variability is likely driven by neonatal injury in the brainstem, where the respiratory centers are located. In some infants, this may correlate with more extensive cerebral injury that could predict the development of cerebral palsy,” said Ms. Saxena.
The group plans to increase its sample size as well as to conduct long-term follow-up on the infants to see how many receive formal diagnoses of cerebral palsy.
After her talk, asked by a moderator why motor assessments were not a reliable predictor in their study, Ms. Saxena pointed to the inexperience of assessors at the institution, where Prechtl testing had only recently begun.
“I think a lot of it is to do with the more subjective nature of the motor assessment. We definitely saw kind of a trend where in the earlier data that was collected, right when our institutions started doing these Prechtls, it was even less of a reliable effect. So I think possibly as clinicians continue to get more familiar with this assessment and there’s more like a validated and robust scoring system, maybe we’ll see a stronger correlation,” she said.
Ms. Saxena had no relevant disclosures. Coauthor Boomah Aravamuthan, MD, DPhil, is a consultant for Neurocrine Biosciences and has received royalties from UpToDate and funding from the National Institute of Neurological Disorders and Stroke.
FROM CNS 2022
JAK inhibitors show no excess cardiovascular safety signal in French nationwide cohort
Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.
The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.
These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.
More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.
“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.
Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.
Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).
These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
Findings from Echo ORAL Surveillance
“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”
Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.
He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.
“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”
Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.
“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.
Boxed warnings encourage caution, lock treatment sequence
Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.
“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”
If these risks aren’t discussed, he noted, patient trust may falter.
“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”
Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.
Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.
“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”
The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.
The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.
These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.
More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.
“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.
Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.
Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).
These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
Findings from Echo ORAL Surveillance
“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”
Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.
He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.
“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”
Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.
“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.
Boxed warnings encourage caution, lock treatment sequence
Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.
“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”
If these risks aren’t discussed, he noted, patient trust may falter.
“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”
Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.
Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.
“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”
The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.
The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.
These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.
More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.
“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.
Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.
Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).
These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
Findings from Echo ORAL Surveillance
“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”
Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.
He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.
“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”
Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.
“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.
Boxed warnings encourage caution, lock treatment sequence
Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.
“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”
If these risks aren’t discussed, he noted, patient trust may falter.
“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”
Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.
Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.
“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”
The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF THE RHEUMATIC DISEASES
Preexisting mental illness symptoms spiked during pandemic
“Those with preexisting mental health conditions may be particularly vulnerable to these effects because they are more susceptible to experiencing high levels of stress during a crisis and are more likely to experience isolation/despair during confinement compared to the general population,” wrote Danna Ramirez of The Menninger Clinic, Houston, and colleagues.
In a study published in Psychiatry Research , the investigators compared data from 142 adolescents aged 12-17 years and 470 adults aged 18-79 years who were admitted to an inpatient psychiatric hospital in Houston. Of these, 65 adolescents and 235 adults were admitted before the pandemic, and 77 adolescents and 235 adults were admitted during the pandemic.
Clinical outcomes were scores on the Generalized Anxiety Disorder Scale (GAD-7), the Patient Health Questionnaire (PHQ-9), the Patient Health Questionnaire for Adolescents (PHQ-A), the Difficulties in Emotion Regulation Scale–Short Form (DERS-SF), the World Health Organization Disability Assessment Scale (WHODAS), the World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test (WHOASSIST), the Pittsburgh Sleep Quality Index (PSQI), the Disturbing Dream and Nightmare Severity Index (DDNSI), and the Suicide Behaviors Questionnaire–Revised (SBQ-R).
Overall, adults admitted during the pandemic had significantly higher levels of anxiety, depression, emotional dysregulation, and disability (P < .001 for all) as well as nightmares (P = .013) compared to those admitted prior to the pandemic.
Among adolescents, measures of anxiety, depression, and sleep quality were significantly higher at admission during the pandemic compared to prior to the pandemic (P = .005, P = .005, and P = .011, respectively)
Reasons for the increase in symptom severity remain unclear, but include the possibility that individuals with preexisting mental illness simply became more ill; or that individuals with symptoms delayed hospital admission out of fear of exposure to COVID-19, which resulted in more severe symptoms at admission, the researchers wrote in their discussion.
The findings were limited by several factors, including the primarily White population and the reliance on self-reports, the researchers noted. Another limitation was the lack of differentiation between patients who may have had COVID-19 before hospitalization and those who did not, so the researchers could not determine whether the virus itself played a biological role in symptom severity.
However, the results support data from previous studies and identify increased psychiatry symptom severity for patients admitted for inpatient psychiatry care during the pandemic, they said. Although resources are scarce, the findings emphasize that mental health needs, especially for those with preexisting conditions, should not be overlooked, and continuity and expansion of access to mental health care for all should be prioritized, they concluded.
The study was supported by The Menninger Clinic and The Menninger Clinic Foundation. The researchers had no financial conflicts to disclose.
“Those with preexisting mental health conditions may be particularly vulnerable to these effects because they are more susceptible to experiencing high levels of stress during a crisis and are more likely to experience isolation/despair during confinement compared to the general population,” wrote Danna Ramirez of The Menninger Clinic, Houston, and colleagues.
In a study published in Psychiatry Research , the investigators compared data from 142 adolescents aged 12-17 years and 470 adults aged 18-79 years who were admitted to an inpatient psychiatric hospital in Houston. Of these, 65 adolescents and 235 adults were admitted before the pandemic, and 77 adolescents and 235 adults were admitted during the pandemic.
Clinical outcomes were scores on the Generalized Anxiety Disorder Scale (GAD-7), the Patient Health Questionnaire (PHQ-9), the Patient Health Questionnaire for Adolescents (PHQ-A), the Difficulties in Emotion Regulation Scale–Short Form (DERS-SF), the World Health Organization Disability Assessment Scale (WHODAS), the World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test (WHOASSIST), the Pittsburgh Sleep Quality Index (PSQI), the Disturbing Dream and Nightmare Severity Index (DDNSI), and the Suicide Behaviors Questionnaire–Revised (SBQ-R).
Overall, adults admitted during the pandemic had significantly higher levels of anxiety, depression, emotional dysregulation, and disability (P < .001 for all) as well as nightmares (P = .013) compared to those admitted prior to the pandemic.
Among adolescents, measures of anxiety, depression, and sleep quality were significantly higher at admission during the pandemic compared to prior to the pandemic (P = .005, P = .005, and P = .011, respectively)
Reasons for the increase in symptom severity remain unclear, but include the possibility that individuals with preexisting mental illness simply became more ill; or that individuals with symptoms delayed hospital admission out of fear of exposure to COVID-19, which resulted in more severe symptoms at admission, the researchers wrote in their discussion.
The findings were limited by several factors, including the primarily White population and the reliance on self-reports, the researchers noted. Another limitation was the lack of differentiation between patients who may have had COVID-19 before hospitalization and those who did not, so the researchers could not determine whether the virus itself played a biological role in symptom severity.
However, the results support data from previous studies and identify increased psychiatry symptom severity for patients admitted for inpatient psychiatry care during the pandemic, they said. Although resources are scarce, the findings emphasize that mental health needs, especially for those with preexisting conditions, should not be overlooked, and continuity and expansion of access to mental health care for all should be prioritized, they concluded.
The study was supported by The Menninger Clinic and The Menninger Clinic Foundation. The researchers had no financial conflicts to disclose.
“Those with preexisting mental health conditions may be particularly vulnerable to these effects because they are more susceptible to experiencing high levels of stress during a crisis and are more likely to experience isolation/despair during confinement compared to the general population,” wrote Danna Ramirez of The Menninger Clinic, Houston, and colleagues.
In a study published in Psychiatry Research , the investigators compared data from 142 adolescents aged 12-17 years and 470 adults aged 18-79 years who were admitted to an inpatient psychiatric hospital in Houston. Of these, 65 adolescents and 235 adults were admitted before the pandemic, and 77 adolescents and 235 adults were admitted during the pandemic.
Clinical outcomes were scores on the Generalized Anxiety Disorder Scale (GAD-7), the Patient Health Questionnaire (PHQ-9), the Patient Health Questionnaire for Adolescents (PHQ-A), the Difficulties in Emotion Regulation Scale–Short Form (DERS-SF), the World Health Organization Disability Assessment Scale (WHODAS), the World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test (WHOASSIST), the Pittsburgh Sleep Quality Index (PSQI), the Disturbing Dream and Nightmare Severity Index (DDNSI), and the Suicide Behaviors Questionnaire–Revised (SBQ-R).
Overall, adults admitted during the pandemic had significantly higher levels of anxiety, depression, emotional dysregulation, and disability (P < .001 for all) as well as nightmares (P = .013) compared to those admitted prior to the pandemic.
Among adolescents, measures of anxiety, depression, and sleep quality were significantly higher at admission during the pandemic compared to prior to the pandemic (P = .005, P = .005, and P = .011, respectively)
Reasons for the increase in symptom severity remain unclear, but include the possibility that individuals with preexisting mental illness simply became more ill; or that individuals with symptoms delayed hospital admission out of fear of exposure to COVID-19, which resulted in more severe symptoms at admission, the researchers wrote in their discussion.
The findings were limited by several factors, including the primarily White population and the reliance on self-reports, the researchers noted. Another limitation was the lack of differentiation between patients who may have had COVID-19 before hospitalization and those who did not, so the researchers could not determine whether the virus itself played a biological role in symptom severity.
However, the results support data from previous studies and identify increased psychiatry symptom severity for patients admitted for inpatient psychiatry care during the pandemic, they said. Although resources are scarce, the findings emphasize that mental health needs, especially for those with preexisting conditions, should not be overlooked, and continuity and expansion of access to mental health care for all should be prioritized, they concluded.
The study was supported by The Menninger Clinic and The Menninger Clinic Foundation. The researchers had no financial conflicts to disclose.
FROM PSYCHIATRY RESEARCH
An infant with a tender bump on her ear
A biopsy of the lesion was performed that showed a well-defined nodulocystic tumor composed of nests of basaloid cells that are undergoing trichilemmal keratinization. Shadow cells are seen as well as small areas of calcification. There is also a histiocytic infiltrate with multinucleated giant cells. The histologic diagnosis is of a pilomatrixoma.
Pilomatrixoma, also known as calcifying epithelioma of Malherbe, was first described in 1880, as a tumor of sebaceous gland origin. Later, in 1961, Robert Forbis Jr, MD, and Elson B. Helwig, MD, coined the term pilomatrixoma to describe the hair follicle matrix as the source of the tumor. Pilomatrixomas are commonly seen in the pediatric population, usually in children between 8 and 13 years of age. Our patient is one of the youngest described. The lesions are commonly seen on the face and neck in about 70% of the cases followed by the upper extremities, back, and legs. Clinically, the lesions appear as a firm dermal papule or nodule, which moves freely and may have associated erythema on the skin surface or a blueish gray hue on the underlying skin.
Most pilomatrixomas that have been studied have shown a mutation in Exon 3 of the beta-catenin gene (CTNNB1). The beta-catenin molecule is a subunit of the cadherin protein, which is part of an important pathway in the terminal hair follicle differentiation. Beta-catenin also plays an important role in the Wnt pathway, which regulates cell fate as well as early embryonic patterning. Beta-catenin is responsible for forming adhesion junctions among cells. There have also been immunohistochemical studies that have shown a BCL2 proto-oncogene overexpression to pilomatrixoma.
There are several genetic syndromes that have been associated with the presence of pilomatrixomas: Turner syndrome (XO chromosome abnormality associated with short stature and cardiac defects), Gardner syndrome (polyposis coli and colon and rectal cancer), myotonic dystrophy, Rubinstein-Taybi syndrome (characterized by broad thumbs and toes, short stature, distinctive facial features, and varying degrees of intellectual disability), and trisomy 9. On physical examination our patient didn’t present with any of the typical features or history that could suggest any of these syndromes. A close follow-up and evaluation by a geneticist was recommended because after the initial visit she developed a second lesion on the forehead.
The differential diagnosis for this lesion includes other cysts that may occur on the ear such as epidermal inclusion cyst or dermoid cysts, though these lesions do not tend to be as firm as pilomatrixomas are, which can help with the diagnosis. Dermoid cysts are made of dermal and epidermal components. They are usually present at birth and are commonly seen on the scalp and the periorbital face.
Keloids are rubbery nodules of scar tissue that can form on sites of trauma, and although the lesion occurred after she had her ears pierced, the consistency and rapid growth of the lesion as well as the pathological description made this benign fibrous growth less likely.
When pilomatrixomas are inflamed they can be confused with vascular growths: in this particular case, a hemangioma or another vascular tumor such as a tufted angioma or kaposiform hemangioendothelioma. An ultrasound of the lesion could have helped in the differential diagnosis of the lesion.
Pilomatrixomas can grow significantly and in some cases get inflamed or infected. Surgical management of pilomatrixomas is often required because the lesions do not regress spontaneously.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
Forbis R Jr and Helwig EB. Arch Dermatol 1961;83:606-18.
Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016 Jun;85:148-53.
A biopsy of the lesion was performed that showed a well-defined nodulocystic tumor composed of nests of basaloid cells that are undergoing trichilemmal keratinization. Shadow cells are seen as well as small areas of calcification. There is also a histiocytic infiltrate with multinucleated giant cells. The histologic diagnosis is of a pilomatrixoma.
Pilomatrixoma, also known as calcifying epithelioma of Malherbe, was first described in 1880, as a tumor of sebaceous gland origin. Later, in 1961, Robert Forbis Jr, MD, and Elson B. Helwig, MD, coined the term pilomatrixoma to describe the hair follicle matrix as the source of the tumor. Pilomatrixomas are commonly seen in the pediatric population, usually in children between 8 and 13 years of age. Our patient is one of the youngest described. The lesions are commonly seen on the face and neck in about 70% of the cases followed by the upper extremities, back, and legs. Clinically, the lesions appear as a firm dermal papule or nodule, which moves freely and may have associated erythema on the skin surface or a blueish gray hue on the underlying skin.
Most pilomatrixomas that have been studied have shown a mutation in Exon 3 of the beta-catenin gene (CTNNB1). The beta-catenin molecule is a subunit of the cadherin protein, which is part of an important pathway in the terminal hair follicle differentiation. Beta-catenin also plays an important role in the Wnt pathway, which regulates cell fate as well as early embryonic patterning. Beta-catenin is responsible for forming adhesion junctions among cells. There have also been immunohistochemical studies that have shown a BCL2 proto-oncogene overexpression to pilomatrixoma.
There are several genetic syndromes that have been associated with the presence of pilomatrixomas: Turner syndrome (XO chromosome abnormality associated with short stature and cardiac defects), Gardner syndrome (polyposis coli and colon and rectal cancer), myotonic dystrophy, Rubinstein-Taybi syndrome (characterized by broad thumbs and toes, short stature, distinctive facial features, and varying degrees of intellectual disability), and trisomy 9. On physical examination our patient didn’t present with any of the typical features or history that could suggest any of these syndromes. A close follow-up and evaluation by a geneticist was recommended because after the initial visit she developed a second lesion on the forehead.
The differential diagnosis for this lesion includes other cysts that may occur on the ear such as epidermal inclusion cyst or dermoid cysts, though these lesions do not tend to be as firm as pilomatrixomas are, which can help with the diagnosis. Dermoid cysts are made of dermal and epidermal components. They are usually present at birth and are commonly seen on the scalp and the periorbital face.
Keloids are rubbery nodules of scar tissue that can form on sites of trauma, and although the lesion occurred after she had her ears pierced, the consistency and rapid growth of the lesion as well as the pathological description made this benign fibrous growth less likely.
When pilomatrixomas are inflamed they can be confused with vascular growths: in this particular case, a hemangioma or another vascular tumor such as a tufted angioma or kaposiform hemangioendothelioma. An ultrasound of the lesion could have helped in the differential diagnosis of the lesion.
Pilomatrixomas can grow significantly and in some cases get inflamed or infected. Surgical management of pilomatrixomas is often required because the lesions do not regress spontaneously.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
Forbis R Jr and Helwig EB. Arch Dermatol 1961;83:606-18.
Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016 Jun;85:148-53.
A biopsy of the lesion was performed that showed a well-defined nodulocystic tumor composed of nests of basaloid cells that are undergoing trichilemmal keratinization. Shadow cells are seen as well as small areas of calcification. There is also a histiocytic infiltrate with multinucleated giant cells. The histologic diagnosis is of a pilomatrixoma.
Pilomatrixoma, also known as calcifying epithelioma of Malherbe, was first described in 1880, as a tumor of sebaceous gland origin. Later, in 1961, Robert Forbis Jr, MD, and Elson B. Helwig, MD, coined the term pilomatrixoma to describe the hair follicle matrix as the source of the tumor. Pilomatrixomas are commonly seen in the pediatric population, usually in children between 8 and 13 years of age. Our patient is one of the youngest described. The lesions are commonly seen on the face and neck in about 70% of the cases followed by the upper extremities, back, and legs. Clinically, the lesions appear as a firm dermal papule or nodule, which moves freely and may have associated erythema on the skin surface or a blueish gray hue on the underlying skin.
Most pilomatrixomas that have been studied have shown a mutation in Exon 3 of the beta-catenin gene (CTNNB1). The beta-catenin molecule is a subunit of the cadherin protein, which is part of an important pathway in the terminal hair follicle differentiation. Beta-catenin also plays an important role in the Wnt pathway, which regulates cell fate as well as early embryonic patterning. Beta-catenin is responsible for forming adhesion junctions among cells. There have also been immunohistochemical studies that have shown a BCL2 proto-oncogene overexpression to pilomatrixoma.
There are several genetic syndromes that have been associated with the presence of pilomatrixomas: Turner syndrome (XO chromosome abnormality associated with short stature and cardiac defects), Gardner syndrome (polyposis coli and colon and rectal cancer), myotonic dystrophy, Rubinstein-Taybi syndrome (characterized by broad thumbs and toes, short stature, distinctive facial features, and varying degrees of intellectual disability), and trisomy 9. On physical examination our patient didn’t present with any of the typical features or history that could suggest any of these syndromes. A close follow-up and evaluation by a geneticist was recommended because after the initial visit she developed a second lesion on the forehead.
The differential diagnosis for this lesion includes other cysts that may occur on the ear such as epidermal inclusion cyst or dermoid cysts, though these lesions do not tend to be as firm as pilomatrixomas are, which can help with the diagnosis. Dermoid cysts are made of dermal and epidermal components. They are usually present at birth and are commonly seen on the scalp and the periorbital face.
Keloids are rubbery nodules of scar tissue that can form on sites of trauma, and although the lesion occurred after she had her ears pierced, the consistency and rapid growth of the lesion as well as the pathological description made this benign fibrous growth less likely.
When pilomatrixomas are inflamed they can be confused with vascular growths: in this particular case, a hemangioma or another vascular tumor such as a tufted angioma or kaposiform hemangioendothelioma. An ultrasound of the lesion could have helped in the differential diagnosis of the lesion.
Pilomatrixomas can grow significantly and in some cases get inflamed or infected. Surgical management of pilomatrixomas is often required because the lesions do not regress spontaneously.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
Forbis R Jr and Helwig EB. Arch Dermatol 1961;83:606-18.
Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016 Jun;85:148-53.
A 4-month-old female was referred to our clinic for evaluation of a bump on the right ear. The lesion was first noted at 2 months of age as a little pimple. She was evaluated by her pediatrician and was treated with topical and oral antibiotics without resolution of the lesion. The bump continued to grow and seemed tender to palpation, so she was referred to dermatology for evaluation.
She was born via normal vaginal delivery at 40 weeks. Her mother has no medical conditions and the pregnancy was uneventful. She has been growing and developing well. She takes vitamin D and is currently breast fed.
There have been no other family members with similar lesions. She had her ears pierced at a month of age without any complications.
On skin examination she has a firm red nodule on the right ear that appears slightly tender to touch. She has no other skin lesions of concern. She has normal muscle tone and there are no other abnormalities noted on the physical exam. She has no hepatomegaly, splenomegaly, or lymphadenopathy.
Bipolar risk and parental age: What’s the relationship?
VIENNA –
Results from a meta-analysis of more than 210,000 patients with bipolar disorder and over 13 million healthy individuals showed that children of mothers younger than 20 years had a 23% increased risk for bipolar disorder vs. those whose parents were aged 25-29 years. For participants whose mothers were aged 35-39 years, there was a 10% increased risk for bipolar disorder, which rose to 20% if the mother was aged 40 or older.
Having a father younger than 20 years conferred a 29% increased risk for bipolar disorder, which was the same increase in risk found in individuals whose fathers were aged 45 years or older.
These findings, which are an update of data published in the journal European Pharmacology, were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
Fourteen studies included
Previous studies have suggested that parental age at birth is a risk factor for several psychiatric disorders in offspring, including bipolar disorder, and that advanced parental age, specifically, is associated with earlier onset schizophrenia.
To investigate further, the current researchers conducted a systematic review and meta-analysis, searching the PubMed/MEDLINE, EMBASE, Scopus, and PsychINFO databases for relevant studies published to Dec. 1, 2021.
From 712 studies initially identified, 16 met all the inclusion criteria and 14 were included in the quantitative analysis.
Five studies reported only paternal age and risk for bipolar disorder in their offspring, one included just maternal age, and eight reported both maternal and paternal age in relation to the risk for offspring bipolar disorder.
Individuals with a history of any psychiatric disorders were excluded, leaving a total of 13.4 million individuals without bipolar disorder and 217,089 who had received a diagnosis for the disorder.
The investigators also corrected for both socioeconomic status and, when assessing the impact of maternal or paternal age at birth, corrected for the age of the other parent. However, they were unable to correct for the number of children in a family.
Results after stratifying maternal and paternal age showed that, compared with those born to parents aged 25-29 years, there was an increased risk for bipolar disorder in the offspring of both fathers and mothers younger than 20 years of age, with adjusted odds ratios of 1.29 (95% confidence interval, 1.13-1.48) and 1.23 (95% CI, 1.14-1.33), respectively.
Compared with those aged 25-29 years, there was also an increased risk for bipolar disorder in children born to mothers aged 35-39 years (adjusted OR, 1.1; 95% CI, 1.01-1.19) and aged 40 or older (OR, 1.2; 95% CI, 1.02-1.40).
Among fathers, there was increased risk for offspring bipolar disorder in those aged 45 or older vs. those aged 25-29 years (adjusted OR, 1.29; 95% CI, 1.15-1.46).
Several hypotheses
There are several hypotheses that could explain the results, lead study author Giovanna Fico, MD, bipolar and depressive disorders unit, Hospital Clínic Barcelona, told this news organization.
In older age, it may be “more related to genetic or epigenetic modification, especially in fathers,” Dr. Fico said. “Some studies have shown that there are de novo mutations in the germ lines, which increase the risk of several diseases, including schizophrenia.”
In younger individuals, there could be a “mixed effect between sociocultural factors, such as substance abuse, low educational status,” and other issues, Dr. Fico noted.
Moreover, as bipolar disorder onset can be as late as 30 years of age, the younger group could include “undiagnosed patients with bipolar disorder, which would increase the risk” of the disease in their offspring, she added.
Dr. Fico noted the investigators are now planning on studying the impact of environmental factors such as pollution, climate change, and urbanization on risk for bipolar disorder, with the aim of being better able to inform parents or to develop prevention strategies.
Psychoeducation is “very common for infertility, birth defects, and Down syndrome, but it’s not so common for psychiatric disorders because we need more data. But I think it’s important that parents know they have an increased risk,” she said.
Nevertheless, “We must stress that this risk is moderate, and it must be kept in perspective,” Dr. Fico said in a news release.
‘Exciting’ questions raised
The study “raises several exciting research questions, including the possibility of early prevention and intervention,” Maj Vinberg, MD, PhD, clinical professor, department of clinical medicine, University of Copenhagen, said in the release.
She said she agrees there are likely to be different factors at play at different ages, with the risk for bipolar disorder associated with younger-age parenthood more likely to be related to socioeconomic status.
For older parents, “there has been a lot of speculation around the father’s age especially, which everybody thought didn’t matter,” said Dr. Vinberg, who was not involved with the research.
“But you might have some epigenetic changes as you grow older that might transfer into the next generation,” given that there is 20 years of additional exposure to potential epigenetic changes between a man aged 25 years and one aged 45 years, she noted.
Dr. Vinberg also highlighted that there could be cases of undiagnosed bipolar disorder among the younger parents, and she noted that “men with bipolar disorder tend to have more children,” particularly during manic phases.
She explained that if someone were to get divorced at 35 years of age, then have a new manic episode at 45 “and have a new wife and children, I don’t know whether it’s possible to correct for that.”
The research is supported by a fellowship from “la Caixa” Foundation. The investigators have reported no relevant financial relationships. Dr. Vinberg reported having relationships with Lundbeck and Janssen.
A version of this article first appeared on Medscape.com.
VIENNA –
Results from a meta-analysis of more than 210,000 patients with bipolar disorder and over 13 million healthy individuals showed that children of mothers younger than 20 years had a 23% increased risk for bipolar disorder vs. those whose parents were aged 25-29 years. For participants whose mothers were aged 35-39 years, there was a 10% increased risk for bipolar disorder, which rose to 20% if the mother was aged 40 or older.
Having a father younger than 20 years conferred a 29% increased risk for bipolar disorder, which was the same increase in risk found in individuals whose fathers were aged 45 years or older.
These findings, which are an update of data published in the journal European Pharmacology, were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
Fourteen studies included
Previous studies have suggested that parental age at birth is a risk factor for several psychiatric disorders in offspring, including bipolar disorder, and that advanced parental age, specifically, is associated with earlier onset schizophrenia.
To investigate further, the current researchers conducted a systematic review and meta-analysis, searching the PubMed/MEDLINE, EMBASE, Scopus, and PsychINFO databases for relevant studies published to Dec. 1, 2021.
From 712 studies initially identified, 16 met all the inclusion criteria and 14 were included in the quantitative analysis.
Five studies reported only paternal age and risk for bipolar disorder in their offspring, one included just maternal age, and eight reported both maternal and paternal age in relation to the risk for offspring bipolar disorder.
Individuals with a history of any psychiatric disorders were excluded, leaving a total of 13.4 million individuals without bipolar disorder and 217,089 who had received a diagnosis for the disorder.
The investigators also corrected for both socioeconomic status and, when assessing the impact of maternal or paternal age at birth, corrected for the age of the other parent. However, they were unable to correct for the number of children in a family.
Results after stratifying maternal and paternal age showed that, compared with those born to parents aged 25-29 years, there was an increased risk for bipolar disorder in the offspring of both fathers and mothers younger than 20 years of age, with adjusted odds ratios of 1.29 (95% confidence interval, 1.13-1.48) and 1.23 (95% CI, 1.14-1.33), respectively.
Compared with those aged 25-29 years, there was also an increased risk for bipolar disorder in children born to mothers aged 35-39 years (adjusted OR, 1.1; 95% CI, 1.01-1.19) and aged 40 or older (OR, 1.2; 95% CI, 1.02-1.40).
Among fathers, there was increased risk for offspring bipolar disorder in those aged 45 or older vs. those aged 25-29 years (adjusted OR, 1.29; 95% CI, 1.15-1.46).
Several hypotheses
There are several hypotheses that could explain the results, lead study author Giovanna Fico, MD, bipolar and depressive disorders unit, Hospital Clínic Barcelona, told this news organization.
In older age, it may be “more related to genetic or epigenetic modification, especially in fathers,” Dr. Fico said. “Some studies have shown that there are de novo mutations in the germ lines, which increase the risk of several diseases, including schizophrenia.”
In younger individuals, there could be a “mixed effect between sociocultural factors, such as substance abuse, low educational status,” and other issues, Dr. Fico noted.
Moreover, as bipolar disorder onset can be as late as 30 years of age, the younger group could include “undiagnosed patients with bipolar disorder, which would increase the risk” of the disease in their offspring, she added.
Dr. Fico noted the investigators are now planning on studying the impact of environmental factors such as pollution, climate change, and urbanization on risk for bipolar disorder, with the aim of being better able to inform parents or to develop prevention strategies.
Psychoeducation is “very common for infertility, birth defects, and Down syndrome, but it’s not so common for psychiatric disorders because we need more data. But I think it’s important that parents know they have an increased risk,” she said.
Nevertheless, “We must stress that this risk is moderate, and it must be kept in perspective,” Dr. Fico said in a news release.
‘Exciting’ questions raised
The study “raises several exciting research questions, including the possibility of early prevention and intervention,” Maj Vinberg, MD, PhD, clinical professor, department of clinical medicine, University of Copenhagen, said in the release.
She said she agrees there are likely to be different factors at play at different ages, with the risk for bipolar disorder associated with younger-age parenthood more likely to be related to socioeconomic status.
For older parents, “there has been a lot of speculation around the father’s age especially, which everybody thought didn’t matter,” said Dr. Vinberg, who was not involved with the research.
“But you might have some epigenetic changes as you grow older that might transfer into the next generation,” given that there is 20 years of additional exposure to potential epigenetic changes between a man aged 25 years and one aged 45 years, she noted.
Dr. Vinberg also highlighted that there could be cases of undiagnosed bipolar disorder among the younger parents, and she noted that “men with bipolar disorder tend to have more children,” particularly during manic phases.
She explained that if someone were to get divorced at 35 years of age, then have a new manic episode at 45 “and have a new wife and children, I don’t know whether it’s possible to correct for that.”
The research is supported by a fellowship from “la Caixa” Foundation. The investigators have reported no relevant financial relationships. Dr. Vinberg reported having relationships with Lundbeck and Janssen.
A version of this article first appeared on Medscape.com.
VIENNA –
Results from a meta-analysis of more than 210,000 patients with bipolar disorder and over 13 million healthy individuals showed that children of mothers younger than 20 years had a 23% increased risk for bipolar disorder vs. those whose parents were aged 25-29 years. For participants whose mothers were aged 35-39 years, there was a 10% increased risk for bipolar disorder, which rose to 20% if the mother was aged 40 or older.
Having a father younger than 20 years conferred a 29% increased risk for bipolar disorder, which was the same increase in risk found in individuals whose fathers were aged 45 years or older.
These findings, which are an update of data published in the journal European Pharmacology, were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
Fourteen studies included
Previous studies have suggested that parental age at birth is a risk factor for several psychiatric disorders in offspring, including bipolar disorder, and that advanced parental age, specifically, is associated with earlier onset schizophrenia.
To investigate further, the current researchers conducted a systematic review and meta-analysis, searching the PubMed/MEDLINE, EMBASE, Scopus, and PsychINFO databases for relevant studies published to Dec. 1, 2021.
From 712 studies initially identified, 16 met all the inclusion criteria and 14 were included in the quantitative analysis.
Five studies reported only paternal age and risk for bipolar disorder in their offspring, one included just maternal age, and eight reported both maternal and paternal age in relation to the risk for offspring bipolar disorder.
Individuals with a history of any psychiatric disorders were excluded, leaving a total of 13.4 million individuals without bipolar disorder and 217,089 who had received a diagnosis for the disorder.
The investigators also corrected for both socioeconomic status and, when assessing the impact of maternal or paternal age at birth, corrected for the age of the other parent. However, they were unable to correct for the number of children in a family.
Results after stratifying maternal and paternal age showed that, compared with those born to parents aged 25-29 years, there was an increased risk for bipolar disorder in the offspring of both fathers and mothers younger than 20 years of age, with adjusted odds ratios of 1.29 (95% confidence interval, 1.13-1.48) and 1.23 (95% CI, 1.14-1.33), respectively.
Compared with those aged 25-29 years, there was also an increased risk for bipolar disorder in children born to mothers aged 35-39 years (adjusted OR, 1.1; 95% CI, 1.01-1.19) and aged 40 or older (OR, 1.2; 95% CI, 1.02-1.40).
Among fathers, there was increased risk for offspring bipolar disorder in those aged 45 or older vs. those aged 25-29 years (adjusted OR, 1.29; 95% CI, 1.15-1.46).
Several hypotheses
There are several hypotheses that could explain the results, lead study author Giovanna Fico, MD, bipolar and depressive disorders unit, Hospital Clínic Barcelona, told this news organization.
In older age, it may be “more related to genetic or epigenetic modification, especially in fathers,” Dr. Fico said. “Some studies have shown that there are de novo mutations in the germ lines, which increase the risk of several diseases, including schizophrenia.”
In younger individuals, there could be a “mixed effect between sociocultural factors, such as substance abuse, low educational status,” and other issues, Dr. Fico noted.
Moreover, as bipolar disorder onset can be as late as 30 years of age, the younger group could include “undiagnosed patients with bipolar disorder, which would increase the risk” of the disease in their offspring, she added.
Dr. Fico noted the investigators are now planning on studying the impact of environmental factors such as pollution, climate change, and urbanization on risk for bipolar disorder, with the aim of being better able to inform parents or to develop prevention strategies.
Psychoeducation is “very common for infertility, birth defects, and Down syndrome, but it’s not so common for psychiatric disorders because we need more data. But I think it’s important that parents know they have an increased risk,” she said.
Nevertheless, “We must stress that this risk is moderate, and it must be kept in perspective,” Dr. Fico said in a news release.
‘Exciting’ questions raised
The study “raises several exciting research questions, including the possibility of early prevention and intervention,” Maj Vinberg, MD, PhD, clinical professor, department of clinical medicine, University of Copenhagen, said in the release.
She said she agrees there are likely to be different factors at play at different ages, with the risk for bipolar disorder associated with younger-age parenthood more likely to be related to socioeconomic status.
For older parents, “there has been a lot of speculation around the father’s age especially, which everybody thought didn’t matter,” said Dr. Vinberg, who was not involved with the research.
“But you might have some epigenetic changes as you grow older that might transfer into the next generation,” given that there is 20 years of additional exposure to potential epigenetic changes between a man aged 25 years and one aged 45 years, she noted.
Dr. Vinberg also highlighted that there could be cases of undiagnosed bipolar disorder among the younger parents, and she noted that “men with bipolar disorder tend to have more children,” particularly during manic phases.
She explained that if someone were to get divorced at 35 years of age, then have a new manic episode at 45 “and have a new wife and children, I don’t know whether it’s possible to correct for that.”
The research is supported by a fellowship from “la Caixa” Foundation. The investigators have reported no relevant financial relationships. Dr. Vinberg reported having relationships with Lundbeck and Janssen.
A version of this article first appeared on Medscape.com.
AT ECNP CONGRESS 2022
Chest reconstruction surgeries up nearly fourfold among adolescents
The number of chest reconstruction surgeries performed for adolescents rose nearly fourfold between 2016 and 2019, researchers report in a study published in JAMA Pediatrics.
“To our knowledge, this study is the largest investigation to date of gender-affirming chest reconstruction in a pediatric population. The results demonstrate substantial increases in gender-affirming chest reconstruction for adolescents,” the authors report.
The researchers, from Vanderbilt University School of Medicine, Nashville, Tenn., used the Nationwide Ambulatory Surgery Sample to identify youth with gender dysphoria who underwent top surgery to remove, or, in rare cases, to add breasts.
The authors identified 829 chest surgeries. They adjusted the number to a weighted figure of 1,130 patients who underwent chest reconstruction during the study period. Of those, 98.6% underwent masculinizing surgery to remove breasts, and 1.4% underwent feminizing surgery. Roughly 100 individuals received gender-affirming chest surgeries in 2016. In 2019, the number had risen to 489 – a 389% increase, the authors reported.
Approximately 44% of the patients in the study were aged 17 years at the time of surgery, while 5.5% were younger than 14.
Around 78% of the individuals who underwent chest surgeries in 2019 were White, 2.7% were Black, 12.2% were Hispanic, and 2.5% were Asian or Pacific Islander. Half of the patients who underwent surgery had a household income of $82,000 or more, according to the researchers.
“Most transgender adolescents had either public or private health insurance coverage for these procedures, contrasting with the predominance of self-payers reported in earlier studies on transgender adults,” write the researchers, citing a 2018 study of trends in transgender surgery.
Masculinizing chest reconstruction, such as mastectomy, and feminizing chest reconstruction, such as augmentation mammaplasty, can be performed as outpatient procedures or as ambulatory surgeries, according to another study .
The study was supported by a grant from the National Center for Advancing Translational Sciences Clinical and Translational Science Awards Program. One author has reported receiving grant funding from Merck.
A version of this article first appeared on Medscape.com.
The number of chest reconstruction surgeries performed for adolescents rose nearly fourfold between 2016 and 2019, researchers report in a study published in JAMA Pediatrics.
“To our knowledge, this study is the largest investigation to date of gender-affirming chest reconstruction in a pediatric population. The results demonstrate substantial increases in gender-affirming chest reconstruction for adolescents,” the authors report.
The researchers, from Vanderbilt University School of Medicine, Nashville, Tenn., used the Nationwide Ambulatory Surgery Sample to identify youth with gender dysphoria who underwent top surgery to remove, or, in rare cases, to add breasts.
The authors identified 829 chest surgeries. They adjusted the number to a weighted figure of 1,130 patients who underwent chest reconstruction during the study period. Of those, 98.6% underwent masculinizing surgery to remove breasts, and 1.4% underwent feminizing surgery. Roughly 100 individuals received gender-affirming chest surgeries in 2016. In 2019, the number had risen to 489 – a 389% increase, the authors reported.
Approximately 44% of the patients in the study were aged 17 years at the time of surgery, while 5.5% were younger than 14.
Around 78% of the individuals who underwent chest surgeries in 2019 were White, 2.7% were Black, 12.2% were Hispanic, and 2.5% were Asian or Pacific Islander. Half of the patients who underwent surgery had a household income of $82,000 or more, according to the researchers.
“Most transgender adolescents had either public or private health insurance coverage for these procedures, contrasting with the predominance of self-payers reported in earlier studies on transgender adults,” write the researchers, citing a 2018 study of trends in transgender surgery.
Masculinizing chest reconstruction, such as mastectomy, and feminizing chest reconstruction, such as augmentation mammaplasty, can be performed as outpatient procedures or as ambulatory surgeries, according to another study .
The study was supported by a grant from the National Center for Advancing Translational Sciences Clinical and Translational Science Awards Program. One author has reported receiving grant funding from Merck.
A version of this article first appeared on Medscape.com.
The number of chest reconstruction surgeries performed for adolescents rose nearly fourfold between 2016 and 2019, researchers report in a study published in JAMA Pediatrics.
“To our knowledge, this study is the largest investigation to date of gender-affirming chest reconstruction in a pediatric population. The results demonstrate substantial increases in gender-affirming chest reconstruction for adolescents,” the authors report.
The researchers, from Vanderbilt University School of Medicine, Nashville, Tenn., used the Nationwide Ambulatory Surgery Sample to identify youth with gender dysphoria who underwent top surgery to remove, or, in rare cases, to add breasts.
The authors identified 829 chest surgeries. They adjusted the number to a weighted figure of 1,130 patients who underwent chest reconstruction during the study period. Of those, 98.6% underwent masculinizing surgery to remove breasts, and 1.4% underwent feminizing surgery. Roughly 100 individuals received gender-affirming chest surgeries in 2016. In 2019, the number had risen to 489 – a 389% increase, the authors reported.
Approximately 44% of the patients in the study were aged 17 years at the time of surgery, while 5.5% were younger than 14.
Around 78% of the individuals who underwent chest surgeries in 2019 were White, 2.7% were Black, 12.2% were Hispanic, and 2.5% were Asian or Pacific Islander. Half of the patients who underwent surgery had a household income of $82,000 or more, according to the researchers.
“Most transgender adolescents had either public or private health insurance coverage for these procedures, contrasting with the predominance of self-payers reported in earlier studies on transgender adults,” write the researchers, citing a 2018 study of trends in transgender surgery.
Masculinizing chest reconstruction, such as mastectomy, and feminizing chest reconstruction, such as augmentation mammaplasty, can be performed as outpatient procedures or as ambulatory surgeries, according to another study .
The study was supported by a grant from the National Center for Advancing Translational Sciences Clinical and Translational Science Awards Program. One author has reported receiving grant funding from Merck.
A version of this article first appeared on Medscape.com.
FROM JAMA PEDIATRICS
Screening gaps miss childhood heart problems
People with a rare genetic condition that causes extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) may miss out on decades of treatment because of a lack of lipid screening in childhood, researchers reported at the annual meeting of the American Academy of Pediatrics.
The condition, homozygous familial hypercholesterolemia (FH), raises the risk for atherosclerotic cardiovascular disease (ASCVD) as early as the first decade of life.
Routine screening for FH is uncommon, however, the researchers said. Lack of familiarity with guidelines and limited access to lipid specialists have been cited as possible reasons for inconsistent screening practices.
“These findings and recent improvement in lipid lowering therapies make a compelling case for rigorous compliance with AAP’s guidelines on lipid screening for children with a family history of FH or ASCVD at age 2,” study coauthor Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation, said in a statement about the new study.
Early consequences
To characterize patients with homozygous FH, Dr. McGowan and her colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation created the registry in 2013, and 40 medical centers in the United States contribute data to the repository. The researchers had access to data about patients with homozygous FH from 20 centers in the registry.
Dr. McGowan’s group compared 16 patients with homozygous FH who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.
Patients enrolled as children had a median age at diagnosis of 2 years (interquartile range [IQR], 2-3.5), whereas patients enrolled as adults had a median age at diagnosis of 12.6 years (IQR, 4.1-26.5).
The median untreated level of LDL-C in those enrolled as children was 776 mg/dL (IQR, 704-892). Among those enrolled as adults, it was 533 mg/dL (IQR, 467-702).
Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The median age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at age 2 years and underwent liver transplant at age 4 years. Another was diagnosed with the condition at age 3 years and underwent liver transplant at age 8 years. Two children underwent coronary artery bypass grafting at ages 6 years and 14 years. Five participants underwent liver transplant before age 18 years.
About 56% of participants who enrolled as children had xanthomas, or fat deposits in tendons, and none had corneal arcus — a gray-white line of fat deposits around the edge of the cornea, both of which can indicate homozygous FH in children.
Treatment reduced LDL-C substantially, but only 25% of children achieved goal levels of cholesterol, the researchers reported. Patients who received more lipid-lowering therapies had a better chance of reaching their target levels, they found.
The data raise “the possibility that only children with the most severe phenotypes are diagnosed before adulthood,” the researchers said.
Clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthomas, the researchers noted. Many children do not have physical findings, however, and a lipid panel or genetic testing may be necessary.
“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, Dr. McGowan said.
Possible missed cases
As many as 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, levels of LDL-C levels typically range between 400 and 1,000 mg/dL without treatment, which is four to 10 times higher than normal concentrations of the blood fat, according to the Family Heart Foundation.
“This study adds to a growing body of literature – including our own work – demonstrating that recommended universal screening occurs in barely 1 in 5 children. This means some patients are not being recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.
Even among children who are at the highest risk for early onset adult-type heart disease, only a quarter to two-thirds receive recommended screening, said Dr. Berger, who was not a member of the study team.
While Dr. Berger advocates universal lipid screening, improving screening rates in practice probably isn’t as simple as telling clinicians to screen more, he said. “Increasing testing will increase health care spending and the burden on busy primary care providers without addressing who will subsequently evaluate and manage children with abnormal lipid screening results,” Dr. Berger said.
Instead, clinicians may want to focus on screening patients who are at risk, which “could have dramatic benefits for their life-long cardiovascular health,” he said.
Dr. McGowan disclosed ties to Abbott and Regeneron, and her coauthors disclosed ties to Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Dr. Berger disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People with a rare genetic condition that causes extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) may miss out on decades of treatment because of a lack of lipid screening in childhood, researchers reported at the annual meeting of the American Academy of Pediatrics.
The condition, homozygous familial hypercholesterolemia (FH), raises the risk for atherosclerotic cardiovascular disease (ASCVD) as early as the first decade of life.
Routine screening for FH is uncommon, however, the researchers said. Lack of familiarity with guidelines and limited access to lipid specialists have been cited as possible reasons for inconsistent screening practices.
“These findings and recent improvement in lipid lowering therapies make a compelling case for rigorous compliance with AAP’s guidelines on lipid screening for children with a family history of FH or ASCVD at age 2,” study coauthor Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation, said in a statement about the new study.
Early consequences
To characterize patients with homozygous FH, Dr. McGowan and her colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation created the registry in 2013, and 40 medical centers in the United States contribute data to the repository. The researchers had access to data about patients with homozygous FH from 20 centers in the registry.
Dr. McGowan’s group compared 16 patients with homozygous FH who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.
Patients enrolled as children had a median age at diagnosis of 2 years (interquartile range [IQR], 2-3.5), whereas patients enrolled as adults had a median age at diagnosis of 12.6 years (IQR, 4.1-26.5).
The median untreated level of LDL-C in those enrolled as children was 776 mg/dL (IQR, 704-892). Among those enrolled as adults, it was 533 mg/dL (IQR, 467-702).
Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The median age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at age 2 years and underwent liver transplant at age 4 years. Another was diagnosed with the condition at age 3 years and underwent liver transplant at age 8 years. Two children underwent coronary artery bypass grafting at ages 6 years and 14 years. Five participants underwent liver transplant before age 18 years.
About 56% of participants who enrolled as children had xanthomas, or fat deposits in tendons, and none had corneal arcus — a gray-white line of fat deposits around the edge of the cornea, both of which can indicate homozygous FH in children.
Treatment reduced LDL-C substantially, but only 25% of children achieved goal levels of cholesterol, the researchers reported. Patients who received more lipid-lowering therapies had a better chance of reaching their target levels, they found.
The data raise “the possibility that only children with the most severe phenotypes are diagnosed before adulthood,” the researchers said.
Clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthomas, the researchers noted. Many children do not have physical findings, however, and a lipid panel or genetic testing may be necessary.
“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, Dr. McGowan said.
Possible missed cases
As many as 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, levels of LDL-C levels typically range between 400 and 1,000 mg/dL without treatment, which is four to 10 times higher than normal concentrations of the blood fat, according to the Family Heart Foundation.
“This study adds to a growing body of literature – including our own work – demonstrating that recommended universal screening occurs in barely 1 in 5 children. This means some patients are not being recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.
Even among children who are at the highest risk for early onset adult-type heart disease, only a quarter to two-thirds receive recommended screening, said Dr. Berger, who was not a member of the study team.
While Dr. Berger advocates universal lipid screening, improving screening rates in practice probably isn’t as simple as telling clinicians to screen more, he said. “Increasing testing will increase health care spending and the burden on busy primary care providers without addressing who will subsequently evaluate and manage children with abnormal lipid screening results,” Dr. Berger said.
Instead, clinicians may want to focus on screening patients who are at risk, which “could have dramatic benefits for their life-long cardiovascular health,” he said.
Dr. McGowan disclosed ties to Abbott and Regeneron, and her coauthors disclosed ties to Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Dr. Berger disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People with a rare genetic condition that causes extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) may miss out on decades of treatment because of a lack of lipid screening in childhood, researchers reported at the annual meeting of the American Academy of Pediatrics.
The condition, homozygous familial hypercholesterolemia (FH), raises the risk for atherosclerotic cardiovascular disease (ASCVD) as early as the first decade of life.
Routine screening for FH is uncommon, however, the researchers said. Lack of familiarity with guidelines and limited access to lipid specialists have been cited as possible reasons for inconsistent screening practices.
“These findings and recent improvement in lipid lowering therapies make a compelling case for rigorous compliance with AAP’s guidelines on lipid screening for children with a family history of FH or ASCVD at age 2,” study coauthor Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation, said in a statement about the new study.
Early consequences
To characterize patients with homozygous FH, Dr. McGowan and her colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation created the registry in 2013, and 40 medical centers in the United States contribute data to the repository. The researchers had access to data about patients with homozygous FH from 20 centers in the registry.
Dr. McGowan’s group compared 16 patients with homozygous FH who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.
Patients enrolled as children had a median age at diagnosis of 2 years (interquartile range [IQR], 2-3.5), whereas patients enrolled as adults had a median age at diagnosis of 12.6 years (IQR, 4.1-26.5).
The median untreated level of LDL-C in those enrolled as children was 776 mg/dL (IQR, 704-892). Among those enrolled as adults, it was 533 mg/dL (IQR, 467-702).
Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The median age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at age 2 years and underwent liver transplant at age 4 years. Another was diagnosed with the condition at age 3 years and underwent liver transplant at age 8 years. Two children underwent coronary artery bypass grafting at ages 6 years and 14 years. Five participants underwent liver transplant before age 18 years.
About 56% of participants who enrolled as children had xanthomas, or fat deposits in tendons, and none had corneal arcus — a gray-white line of fat deposits around the edge of the cornea, both of which can indicate homozygous FH in children.
Treatment reduced LDL-C substantially, but only 25% of children achieved goal levels of cholesterol, the researchers reported. Patients who received more lipid-lowering therapies had a better chance of reaching their target levels, they found.
The data raise “the possibility that only children with the most severe phenotypes are diagnosed before adulthood,” the researchers said.
Clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthomas, the researchers noted. Many children do not have physical findings, however, and a lipid panel or genetic testing may be necessary.
“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, Dr. McGowan said.
Possible missed cases
As many as 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, levels of LDL-C levels typically range between 400 and 1,000 mg/dL without treatment, which is four to 10 times higher than normal concentrations of the blood fat, according to the Family Heart Foundation.
“This study adds to a growing body of literature – including our own work – demonstrating that recommended universal screening occurs in barely 1 in 5 children. This means some patients are not being recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.
Even among children who are at the highest risk for early onset adult-type heart disease, only a quarter to two-thirds receive recommended screening, said Dr. Berger, who was not a member of the study team.
While Dr. Berger advocates universal lipid screening, improving screening rates in practice probably isn’t as simple as telling clinicians to screen more, he said. “Increasing testing will increase health care spending and the burden on busy primary care providers without addressing who will subsequently evaluate and manage children with abnormal lipid screening results,” Dr. Berger said.
Instead, clinicians may want to focus on screening patients who are at risk, which “could have dramatic benefits for their life-long cardiovascular health,” he said.
Dr. McGowan disclosed ties to Abbott and Regeneron, and her coauthors disclosed ties to Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Dr. Berger disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAP 2022
Sleep kits help foster children manage effects of trauma
A stuffed animal, aromatherapy, a night light. A kit containing these and other items can help children in foster care who have experienced trauma sleep more soundly, a critical step in helping them cope with their emotional distress.
In a new study, researchers at the Children’s Hospital of Philadelphia reported that sleep kits specially tailored to foster children appeared to be helpful in most cases. The kits can be distributed by pediatricians in the office or clinic setting.
“Children who have experienced trauma can have issues with behavior, it can impact their school, and they have difficulties sleeping,” said Kristine Fortin, MD, MPH, director of the fostering health program at Safe Place: Center for Child Protection and Health at CHOP. “I thought, what could a pediatrician do in the office in one visit to help children with sleep?”
Dr. Fortin and colleagues designed sleep kits for both younger children and adolescents.
The version for teenagers contained a sound machine, aromatherapy spray, and a sleep mask. The kits for younger children contained matching stuffed toys to share with someone they felt connected to, and a rechargeable night-light. All kits included written materials about sleep hygiene, a journal, and directions for downloading a free age-appropriate relaxation app for belly breathing or a PTSD Coach app from the Department of Veterans Affairs to manage symptoms of trauma.
In a pilot study presented at the annual meeting of the American Academy of Pediatrics, Dr. Fortin and colleagues surveyed caregivers in foster homes about their use of the kits.
Of the 20 foster parents who responded to the survey, 11 said the kits helped “very much,” 5 others reported they helped “somewhat,” another 2 reported no improvements in sleep, and 2 said they didn’t know the effect. The children for whom results were unknown moved from the home without the sleep kit or had difficulties communicating with the foster parents, resulting in incomplete assessment, according to the researchers.
Night-lights were used most in the kits, followed by the stuffed toys, sound machines, and sleep journals.
Dr. Fortin said existing resources like sleep therapy or medication can be costly or difficult to find, and many pediatricians don’t have enough time during wellness visits to address symptoms like sleep deprivation. She said the sleep kits could be an alternative to other forms of sleep therapy. “If these sleep kits were effective, and could really help them sleep, then maybe less children would need something like medication.”
Dr. Fortin said the kits her group has designed are tailored specifically for children with symptoms of trauma, or with difficult emotions associated with foster care.
“We’ve tried to design something that can be really practical and easy to use in a pediatric visit, where there’s a lot of written information that can be discussed with the child and their family,” Dr. Fortin said.
She added that she would like to see clinicians give out the sleep kits during in-office visits.
“These sleep issues are common in foster children,” she said. “We felt it was important to do an intervention.”
Kristina Lenker, PhD, a sleep psychologist at Penn State Health, Hershey, said children in foster care often struggle with falling or staying asleep, an inability to sleep alone, nightmares, and bed wetting.
“Sleep kits can be particularly helpful for these children, given how they can help caregivers to provide a safe sleep environment and predictable routine, and send messages of safety and comfort at bedtime, with tangible objects, and enable children to feel a sense of control,” she said.
Charitable organizations like Pajama Program and Sleeping Children Around the World provide sleep kits to children from underserved backgrounds. But Candice Alfano, PhD, director of the University of Houston’s Sleep and Anxiety Center of Houston, said the CHOP kits are the first to specifically target sleeping difficulties in foster children.
“Sleep is a largely neglected yet essential area of health, development, and well-being in this highly-vulnerable population of youth, so I am very excited to see this work being done,” Dr. Alfano said in an interview.
Dr. Fortin and Dr. Lenker reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A stuffed animal, aromatherapy, a night light. A kit containing these and other items can help children in foster care who have experienced trauma sleep more soundly, a critical step in helping them cope with their emotional distress.
In a new study, researchers at the Children’s Hospital of Philadelphia reported that sleep kits specially tailored to foster children appeared to be helpful in most cases. The kits can be distributed by pediatricians in the office or clinic setting.
“Children who have experienced trauma can have issues with behavior, it can impact their school, and they have difficulties sleeping,” said Kristine Fortin, MD, MPH, director of the fostering health program at Safe Place: Center for Child Protection and Health at CHOP. “I thought, what could a pediatrician do in the office in one visit to help children with sleep?”
Dr. Fortin and colleagues designed sleep kits for both younger children and adolescents.
The version for teenagers contained a sound machine, aromatherapy spray, and a sleep mask. The kits for younger children contained matching stuffed toys to share with someone they felt connected to, and a rechargeable night-light. All kits included written materials about sleep hygiene, a journal, and directions for downloading a free age-appropriate relaxation app for belly breathing or a PTSD Coach app from the Department of Veterans Affairs to manage symptoms of trauma.
In a pilot study presented at the annual meeting of the American Academy of Pediatrics, Dr. Fortin and colleagues surveyed caregivers in foster homes about their use of the kits.
Of the 20 foster parents who responded to the survey, 11 said the kits helped “very much,” 5 others reported they helped “somewhat,” another 2 reported no improvements in sleep, and 2 said they didn’t know the effect. The children for whom results were unknown moved from the home without the sleep kit or had difficulties communicating with the foster parents, resulting in incomplete assessment, according to the researchers.
Night-lights were used most in the kits, followed by the stuffed toys, sound machines, and sleep journals.
Dr. Fortin said existing resources like sleep therapy or medication can be costly or difficult to find, and many pediatricians don’t have enough time during wellness visits to address symptoms like sleep deprivation. She said the sleep kits could be an alternative to other forms of sleep therapy. “If these sleep kits were effective, and could really help them sleep, then maybe less children would need something like medication.”
Dr. Fortin said the kits her group has designed are tailored specifically for children with symptoms of trauma, or with difficult emotions associated with foster care.
“We’ve tried to design something that can be really practical and easy to use in a pediatric visit, where there’s a lot of written information that can be discussed with the child and their family,” Dr. Fortin said.
She added that she would like to see clinicians give out the sleep kits during in-office visits.
“These sleep issues are common in foster children,” she said. “We felt it was important to do an intervention.”
Kristina Lenker, PhD, a sleep psychologist at Penn State Health, Hershey, said children in foster care often struggle with falling or staying asleep, an inability to sleep alone, nightmares, and bed wetting.
“Sleep kits can be particularly helpful for these children, given how they can help caregivers to provide a safe sleep environment and predictable routine, and send messages of safety and comfort at bedtime, with tangible objects, and enable children to feel a sense of control,” she said.
Charitable organizations like Pajama Program and Sleeping Children Around the World provide sleep kits to children from underserved backgrounds. But Candice Alfano, PhD, director of the University of Houston’s Sleep and Anxiety Center of Houston, said the CHOP kits are the first to specifically target sleeping difficulties in foster children.
“Sleep is a largely neglected yet essential area of health, development, and well-being in this highly-vulnerable population of youth, so I am very excited to see this work being done,” Dr. Alfano said in an interview.
Dr. Fortin and Dr. Lenker reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A stuffed animal, aromatherapy, a night light. A kit containing these and other items can help children in foster care who have experienced trauma sleep more soundly, a critical step in helping them cope with their emotional distress.
In a new study, researchers at the Children’s Hospital of Philadelphia reported that sleep kits specially tailored to foster children appeared to be helpful in most cases. The kits can be distributed by pediatricians in the office or clinic setting.
“Children who have experienced trauma can have issues with behavior, it can impact their school, and they have difficulties sleeping,” said Kristine Fortin, MD, MPH, director of the fostering health program at Safe Place: Center for Child Protection and Health at CHOP. “I thought, what could a pediatrician do in the office in one visit to help children with sleep?”
Dr. Fortin and colleagues designed sleep kits for both younger children and adolescents.
The version for teenagers contained a sound machine, aromatherapy spray, and a sleep mask. The kits for younger children contained matching stuffed toys to share with someone they felt connected to, and a rechargeable night-light. All kits included written materials about sleep hygiene, a journal, and directions for downloading a free age-appropriate relaxation app for belly breathing or a PTSD Coach app from the Department of Veterans Affairs to manage symptoms of trauma.
In a pilot study presented at the annual meeting of the American Academy of Pediatrics, Dr. Fortin and colleagues surveyed caregivers in foster homes about their use of the kits.
Of the 20 foster parents who responded to the survey, 11 said the kits helped “very much,” 5 others reported they helped “somewhat,” another 2 reported no improvements in sleep, and 2 said they didn’t know the effect. The children for whom results were unknown moved from the home without the sleep kit or had difficulties communicating with the foster parents, resulting in incomplete assessment, according to the researchers.
Night-lights were used most in the kits, followed by the stuffed toys, sound machines, and sleep journals.
Dr. Fortin said existing resources like sleep therapy or medication can be costly or difficult to find, and many pediatricians don’t have enough time during wellness visits to address symptoms like sleep deprivation. She said the sleep kits could be an alternative to other forms of sleep therapy. “If these sleep kits were effective, and could really help them sleep, then maybe less children would need something like medication.”
Dr. Fortin said the kits her group has designed are tailored specifically for children with symptoms of trauma, or with difficult emotions associated with foster care.
“We’ve tried to design something that can be really practical and easy to use in a pediatric visit, where there’s a lot of written information that can be discussed with the child and their family,” Dr. Fortin said.
She added that she would like to see clinicians give out the sleep kits during in-office visits.
“These sleep issues are common in foster children,” she said. “We felt it was important to do an intervention.”
Kristina Lenker, PhD, a sleep psychologist at Penn State Health, Hershey, said children in foster care often struggle with falling or staying asleep, an inability to sleep alone, nightmares, and bed wetting.
“Sleep kits can be particularly helpful for these children, given how they can help caregivers to provide a safe sleep environment and predictable routine, and send messages of safety and comfort at bedtime, with tangible objects, and enable children to feel a sense of control,” she said.
Charitable organizations like Pajama Program and Sleeping Children Around the World provide sleep kits to children from underserved backgrounds. But Candice Alfano, PhD, director of the University of Houston’s Sleep and Anxiety Center of Houston, said the CHOP kits are the first to specifically target sleeping difficulties in foster children.
“Sleep is a largely neglected yet essential area of health, development, and well-being in this highly-vulnerable population of youth, so I am very excited to see this work being done,” Dr. Alfano said in an interview.
Dr. Fortin and Dr. Lenker reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAP 2022
Connected: Preterm infant program makes progress
Martha Welch, MD, spent the better part of three decades in private practice treating children with emotional, behavioral, and developmental disorders before accepting a job on the faculty of Columbia University, New York, in 1997.
She took the position, she said, with a mission: to find evidence to support what she’d observed in her practice – that parents could, by making stronger emotional connections, change the trajectory of development for preemie infants.
With that understanding, Dr. Welch created Family Nurture Intervention (FNI), which has been shown to improve the development of premature babies.
“We saw that no matter what happened to the baby, no matter how avoidant the baby might be, we’re able to overcome this with emotional expression,” Dr. Welch said.
Over the course of the intervention, families work with a specialist who helps bring mother and baby together – both physically and emotionally – until both are calm, which can initially take several hours and over time, minutes.
FNI appears to help families – especially mothers – re-establish an emotional connection often interrupted by their babies’ stressful and uncertain stay in a neonatal intensive care unit (NICU). In turn, both the infant and maternal nervous systems become better regulated, according to researchers.
Early challenges
Babies born preterm can face a range of short-term and long-term challenges, such as breathing problems due to an underdeveloped respiratory system, an increased risk of infection from an underdeveloped immune system, and learning difficulties, according to the Mayo Clinic.
Many aspects of FNI are not new: The neonatal intensive care unit has long incorporated activities such as scent cloth exchanges, talking to the baby, and skin-to-skin contact. But the approach Dr. Welch and her colleagues advocate emphasizes building a bond between the mother and the infant.
Mounting evidence shows that FNI can improve a wide range of outcomes for premature babies. In a 2021 study, for example, Dr. Welch’s group showed that FNI was associated with lower heart rates among preemies in the NICU. A 2016 study linked the intervention to reduced depression and anxiety symptoms in mothers of preterm infants. And a 2015 randomized controlled trial showed FNI improved development and behavioral outcomes in infants up to 18 months.
A new study published in Science Translational Medicine showed that the intervention led to a greater likelihood that babies had improved cognitive development later on, narrowing the developmental gap between healthy, full-term babies.
Dr. Welch and her colleagues tested to see if FNI measurably changed brain development in preterm infants who were born at 26-34 weeks of a pregnancy.
“We were blown away by the strength of the effect,” said Pauliina Yrjölä, MSc, a doctoral student and medical physicist at the University of Helsinki, who led the study on which Dr. Welch is a co-author.
Mothers in the intervention group made as much eye contact with the infants as possible and spoke with infants about their feelings.
Intimate sensory interactions between mothers and infants physically altered infants’ cortical networks in the brain and was later correlated to improved neurocognitive performance, according to the researchers.
“I was convinced there were physiological changes; I knew that from my clinical work,” Dr. Welch said. “I wanted to show it in this concrete, scientific way.”
Preterm babies face many hurdles
“If we can prevent problems in brain network organization to the extent that’s shown in this study and improve their outcomes, this is worth millions of dollars in terms of cost to society, schooling, health care, especially education, and families,” said Ruth Grunau, PhD, a professor in the Division of Neonatology in the department of pediatrics at the University of British Columbia, Vancouver, who was not involved with the most recent study but has worked with Dr. Welch previously.
Babies born too early, especially before 32 weeks, have higher rates of death and disability, according to the Centers for Disease Control and Prevention.
And preterm babies overall may experience breathing problems and feeding difficulties almost immediately following birth. They may also experience long-term problems such as developmental delays, vision problems, and hearing problems.
Dr. Grunau said that while many other programs and interventions have been used in the neonatal intensive care unit to help infants and mothers, the results from FNI stand out.
Ms. Yrjölä said she was surprised by the strength of the correlation as the infants continued to develop. The infants receiving the Family Nurture Intervention showed brain development close to the control group, which was infants born at full-term.
“Emotional connection is a state, not a trait – and a state can be changed,” said Dr. Welch. “And in this case, it can be changed by the parent through emotional expression.”
Steps clinicians can take
Dr. Welch said the approach is highly scalable, and two NICUs that participated in the FNI studies have implemented the program as standard care.
The approach is also gaining interest outside of the clinical setting, as preschool partners have expressed interest in implementing some of the methods to promote development.
Parents, family members, and teachers can use many of the FNI techniques – such as eye contact and emotional expression – to continue to develop and strengthen connection.
For clinicians who want to implement parts of the intervention on their own, Dr. Welch said doctors can observe if the baby looks at or turns toward their mother.
Clinicians can encourage mothers to express deep, emotional feelings toward the infant. Dr. Welch stressed that feelings don’t have to be positive, as many mothers with babies in the NICU have a hard time expressing positive emotions. Crying or talking about the difficulties of their childbirth experience count as expressing emotion. The important part is that the baby hears emotion, of any kind, in the mother’s voice, Dr. Welch said.
As the connection develops, it will eventually take less time for the mother and the baby to form a bond, and eventually the pair will become autonomically regulated.
“This is what gives us hope,” she said. “We affect each other in our autonomic nervous systems. It’s why this treatment works.”
The study was funded by the Finnish Pediatric Foundation, The Finnish Academy, the Juselius Foundation, Aivosäätiö, Neuroscience Center at University of Helsinki and Helsinki University Central Hospital, gifts from the Einhorn Family Charitable Trust, the Fleur Fairman Family, M. D. Stephenson, and The National Health and Medical Research Council of Australia. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Martha Welch, MD, spent the better part of three decades in private practice treating children with emotional, behavioral, and developmental disorders before accepting a job on the faculty of Columbia University, New York, in 1997.
She took the position, she said, with a mission: to find evidence to support what she’d observed in her practice – that parents could, by making stronger emotional connections, change the trajectory of development for preemie infants.
With that understanding, Dr. Welch created Family Nurture Intervention (FNI), which has been shown to improve the development of premature babies.
“We saw that no matter what happened to the baby, no matter how avoidant the baby might be, we’re able to overcome this with emotional expression,” Dr. Welch said.
Over the course of the intervention, families work with a specialist who helps bring mother and baby together – both physically and emotionally – until both are calm, which can initially take several hours and over time, minutes.
FNI appears to help families – especially mothers – re-establish an emotional connection often interrupted by their babies’ stressful and uncertain stay in a neonatal intensive care unit (NICU). In turn, both the infant and maternal nervous systems become better regulated, according to researchers.
Early challenges
Babies born preterm can face a range of short-term and long-term challenges, such as breathing problems due to an underdeveloped respiratory system, an increased risk of infection from an underdeveloped immune system, and learning difficulties, according to the Mayo Clinic.
Many aspects of FNI are not new: The neonatal intensive care unit has long incorporated activities such as scent cloth exchanges, talking to the baby, and skin-to-skin contact. But the approach Dr. Welch and her colleagues advocate emphasizes building a bond between the mother and the infant.
Mounting evidence shows that FNI can improve a wide range of outcomes for premature babies. In a 2021 study, for example, Dr. Welch’s group showed that FNI was associated with lower heart rates among preemies in the NICU. A 2016 study linked the intervention to reduced depression and anxiety symptoms in mothers of preterm infants. And a 2015 randomized controlled trial showed FNI improved development and behavioral outcomes in infants up to 18 months.
A new study published in Science Translational Medicine showed that the intervention led to a greater likelihood that babies had improved cognitive development later on, narrowing the developmental gap between healthy, full-term babies.
Dr. Welch and her colleagues tested to see if FNI measurably changed brain development in preterm infants who were born at 26-34 weeks of a pregnancy.
“We were blown away by the strength of the effect,” said Pauliina Yrjölä, MSc, a doctoral student and medical physicist at the University of Helsinki, who led the study on which Dr. Welch is a co-author.
Mothers in the intervention group made as much eye contact with the infants as possible and spoke with infants about their feelings.
Intimate sensory interactions between mothers and infants physically altered infants’ cortical networks in the brain and was later correlated to improved neurocognitive performance, according to the researchers.
“I was convinced there were physiological changes; I knew that from my clinical work,” Dr. Welch said. “I wanted to show it in this concrete, scientific way.”
Preterm babies face many hurdles
“If we can prevent problems in brain network organization to the extent that’s shown in this study and improve their outcomes, this is worth millions of dollars in terms of cost to society, schooling, health care, especially education, and families,” said Ruth Grunau, PhD, a professor in the Division of Neonatology in the department of pediatrics at the University of British Columbia, Vancouver, who was not involved with the most recent study but has worked with Dr. Welch previously.
Babies born too early, especially before 32 weeks, have higher rates of death and disability, according to the Centers for Disease Control and Prevention.
And preterm babies overall may experience breathing problems and feeding difficulties almost immediately following birth. They may also experience long-term problems such as developmental delays, vision problems, and hearing problems.
Dr. Grunau said that while many other programs and interventions have been used in the neonatal intensive care unit to help infants and mothers, the results from FNI stand out.
Ms. Yrjölä said she was surprised by the strength of the correlation as the infants continued to develop. The infants receiving the Family Nurture Intervention showed brain development close to the control group, which was infants born at full-term.
“Emotional connection is a state, not a trait – and a state can be changed,” said Dr. Welch. “And in this case, it can be changed by the parent through emotional expression.”
Steps clinicians can take
Dr. Welch said the approach is highly scalable, and two NICUs that participated in the FNI studies have implemented the program as standard care.
The approach is also gaining interest outside of the clinical setting, as preschool partners have expressed interest in implementing some of the methods to promote development.
Parents, family members, and teachers can use many of the FNI techniques – such as eye contact and emotional expression – to continue to develop and strengthen connection.
For clinicians who want to implement parts of the intervention on their own, Dr. Welch said doctors can observe if the baby looks at or turns toward their mother.
Clinicians can encourage mothers to express deep, emotional feelings toward the infant. Dr. Welch stressed that feelings don’t have to be positive, as many mothers with babies in the NICU have a hard time expressing positive emotions. Crying or talking about the difficulties of their childbirth experience count as expressing emotion. The important part is that the baby hears emotion, of any kind, in the mother’s voice, Dr. Welch said.
As the connection develops, it will eventually take less time for the mother and the baby to form a bond, and eventually the pair will become autonomically regulated.
“This is what gives us hope,” she said. “We affect each other in our autonomic nervous systems. It’s why this treatment works.”
The study was funded by the Finnish Pediatric Foundation, The Finnish Academy, the Juselius Foundation, Aivosäätiö, Neuroscience Center at University of Helsinki and Helsinki University Central Hospital, gifts from the Einhorn Family Charitable Trust, the Fleur Fairman Family, M. D. Stephenson, and The National Health and Medical Research Council of Australia. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Martha Welch, MD, spent the better part of three decades in private practice treating children with emotional, behavioral, and developmental disorders before accepting a job on the faculty of Columbia University, New York, in 1997.
She took the position, she said, with a mission: to find evidence to support what she’d observed in her practice – that parents could, by making stronger emotional connections, change the trajectory of development for preemie infants.
With that understanding, Dr. Welch created Family Nurture Intervention (FNI), which has been shown to improve the development of premature babies.
“We saw that no matter what happened to the baby, no matter how avoidant the baby might be, we’re able to overcome this with emotional expression,” Dr. Welch said.
Over the course of the intervention, families work with a specialist who helps bring mother and baby together – both physically and emotionally – until both are calm, which can initially take several hours and over time, minutes.
FNI appears to help families – especially mothers – re-establish an emotional connection often interrupted by their babies’ stressful and uncertain stay in a neonatal intensive care unit (NICU). In turn, both the infant and maternal nervous systems become better regulated, according to researchers.
Early challenges
Babies born preterm can face a range of short-term and long-term challenges, such as breathing problems due to an underdeveloped respiratory system, an increased risk of infection from an underdeveloped immune system, and learning difficulties, according to the Mayo Clinic.
Many aspects of FNI are not new: The neonatal intensive care unit has long incorporated activities such as scent cloth exchanges, talking to the baby, and skin-to-skin contact. But the approach Dr. Welch and her colleagues advocate emphasizes building a bond between the mother and the infant.
Mounting evidence shows that FNI can improve a wide range of outcomes for premature babies. In a 2021 study, for example, Dr. Welch’s group showed that FNI was associated with lower heart rates among preemies in the NICU. A 2016 study linked the intervention to reduced depression and anxiety symptoms in mothers of preterm infants. And a 2015 randomized controlled trial showed FNI improved development and behavioral outcomes in infants up to 18 months.
A new study published in Science Translational Medicine showed that the intervention led to a greater likelihood that babies had improved cognitive development later on, narrowing the developmental gap between healthy, full-term babies.
Dr. Welch and her colleagues tested to see if FNI measurably changed brain development in preterm infants who were born at 26-34 weeks of a pregnancy.
“We were blown away by the strength of the effect,” said Pauliina Yrjölä, MSc, a doctoral student and medical physicist at the University of Helsinki, who led the study on which Dr. Welch is a co-author.
Mothers in the intervention group made as much eye contact with the infants as possible and spoke with infants about their feelings.
Intimate sensory interactions between mothers and infants physically altered infants’ cortical networks in the brain and was later correlated to improved neurocognitive performance, according to the researchers.
“I was convinced there were physiological changes; I knew that from my clinical work,” Dr. Welch said. “I wanted to show it in this concrete, scientific way.”
Preterm babies face many hurdles
“If we can prevent problems in brain network organization to the extent that’s shown in this study and improve their outcomes, this is worth millions of dollars in terms of cost to society, schooling, health care, especially education, and families,” said Ruth Grunau, PhD, a professor in the Division of Neonatology in the department of pediatrics at the University of British Columbia, Vancouver, who was not involved with the most recent study but has worked with Dr. Welch previously.
Babies born too early, especially before 32 weeks, have higher rates of death and disability, according to the Centers for Disease Control and Prevention.
And preterm babies overall may experience breathing problems and feeding difficulties almost immediately following birth. They may also experience long-term problems such as developmental delays, vision problems, and hearing problems.
Dr. Grunau said that while many other programs and interventions have been used in the neonatal intensive care unit to help infants and mothers, the results from FNI stand out.
Ms. Yrjölä said she was surprised by the strength of the correlation as the infants continued to develop. The infants receiving the Family Nurture Intervention showed brain development close to the control group, which was infants born at full-term.
“Emotional connection is a state, not a trait – and a state can be changed,” said Dr. Welch. “And in this case, it can be changed by the parent through emotional expression.”
Steps clinicians can take
Dr. Welch said the approach is highly scalable, and two NICUs that participated in the FNI studies have implemented the program as standard care.
The approach is also gaining interest outside of the clinical setting, as preschool partners have expressed interest in implementing some of the methods to promote development.
Parents, family members, and teachers can use many of the FNI techniques – such as eye contact and emotional expression – to continue to develop and strengthen connection.
For clinicians who want to implement parts of the intervention on their own, Dr. Welch said doctors can observe if the baby looks at or turns toward their mother.
Clinicians can encourage mothers to express deep, emotional feelings toward the infant. Dr. Welch stressed that feelings don’t have to be positive, as many mothers with babies in the NICU have a hard time expressing positive emotions. Crying or talking about the difficulties of their childbirth experience count as expressing emotion. The important part is that the baby hears emotion, of any kind, in the mother’s voice, Dr. Welch said.
As the connection develops, it will eventually take less time for the mother and the baby to form a bond, and eventually the pair will become autonomically regulated.
“This is what gives us hope,” she said. “We affect each other in our autonomic nervous systems. It’s why this treatment works.”
The study was funded by the Finnish Pediatric Foundation, The Finnish Academy, the Juselius Foundation, Aivosäätiö, Neuroscience Center at University of Helsinki and Helsinki University Central Hospital, gifts from the Einhorn Family Charitable Trust, the Fleur Fairman Family, M. D. Stephenson, and The National Health and Medical Research Council of Australia. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.