Pediatrics

The Food and Drug Administration has alerted the public to an increased risk of serious heart-related problems and cancer risk associated with the Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR), based on early results from a safety clinical trial comparing tofacitinib and tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA).

The FDA is awaiting further results from the trial, but in a safety communication issued on Feb. 4, the agency advised patients not to discontinue tofacitinib without consulting their health care providers and advised health care professionals to weigh the risks and benefits when prescribing the drug and continue to follow the current prescribing information.

Tofacitinib was approved for treatment of RA in 2012 at a 5-mg dose. After this approval, the FDA required drug manufacturer Pfizer to conduct a safety clinical trial that included the 5-mg twice-daily dose and a 10-mg twice-daily dose that is currently approved only for ulcerative colitis. In addition to RA and ulcerative colitis, tofacitinib is approved for adults with active psoriatic arthritis and patients aged 2 years or older with active polyarticular course juvenile idiopathic arthritis.

Pfizer announced partial results of the study, known as the ORAL Surveillance trial, in a press release on Jan. 27. The randomized trial included 4,362 RA patients aged 50 years and older who received either 5-mg or 10-mg doses of tofacitinib or a TNF inhibitor (adalimumab or etanercept).

The full results have yet to be released, but based on data from approximately 10,000 person-years for the combined tofacitinib groups and approximately 5,000 person-years for the TNF inhibitor group, the rate of major cardiovascular adverse events was significantly higher in the combined tofacitinib group, compared with the TNF inhibitor group (0.98 vs. 0.73 per 100 person-years; hazard ratio, 1.33). In addition, the rate of adjudicated malignancies was significantly higher in the tofacitinib group, compared with the TNF inhibitor group (1.13 vs. 0.77 per 100 person-years; HR, 1.48).

In February 2019, the FDA issued a warning stating an increased risk of pulmonary embolism and death associated with the 10-mg twice-daily dose of tofacitinib, following interims results from the safety study.

In July 2019, the FDA added a boxed warning to tofacitinib advising of the increased risk for pulmonary embolism and death associated with the 10-mg twice-daily dose.

The FDA encouraged health care professionals and patients to report any side effects from tofacitinib or other medications through the FDA MedWatch program online or by phone at 1-800-332-1088.

Until nuances revealed, no change in practice

The preliminary study findings contain some nuances that are a bit complicated from a statistical standpoint, according to Daniel Furst, MD, professor emeritus of medicine at the University of California, Los Angeles; adjunct professor at the University of Washington, Seattle; and research professor at the University of Florence (Italy).

Updated on 2/8/2021.

The Food and Drug Administration has alerted the public to an increased risk of serious heart-related problems and cancer risk associated with the Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR), based on early results from a safety clinical trial comparing tofacitinib and tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA).

The FDA is awaiting further results from the trial, but in a safety communication issued on Feb. 4, the agency advised patients not to discontinue tofacitinib without consulting their health care providers and advised health care professionals to weigh the risks and benefits when prescribing the drug and continue to follow the current prescribing information.

Tofacitinib was approved for treatment of RA in 2012 at a 5-mg dose. After this approval, the FDA required drug manufacturer Pfizer to conduct a safety clinical trial that included the 5-mg twice-daily dose and a 10-mg twice-daily dose that is currently approved only for ulcerative colitis. In addition to RA and ulcerative colitis, tofacitinib is approved for adults with active psoriatic arthritis and patients aged 2 years or older with active polyarticular course juvenile idiopathic arthritis.

Pfizer announced partial results of the study, known as the ORAL Surveillance trial, in a press release on Jan. 27. The randomized trial included 4,362 RA patients aged 50 years and older who received either 5-mg or 10-mg doses of tofacitinib or a TNF inhibitor (adalimumab or etanercept).

The full results have yet to be released, but based on data from approximately 10,000 person-years for the combined tofacitinib groups and approximately 5,000 person-years for the TNF inhibitor group, the rate of major cardiovascular adverse events was significantly higher in the combined tofacitinib group, compared with the TNF inhibitor group (0.98 vs. 0.73 per 100 person-years; hazard ratio, 1.33). In addition, the rate of adjudicated malignancies was significantly higher in the tofacitinib group, compared with the TNF inhibitor group (1.13 vs. 0.77 per 100 person-years; HR, 1.48).

In February 2019, the FDA issued a warning stating an increased risk of pulmonary embolism and death associated with the 10-mg twice-daily dose of tofacitinib, following interims results from the safety study.

In July 2019, the FDA added a boxed warning to tofacitinib advising of the increased risk for pulmonary embolism and death associated with the 10-mg twice-daily dose.

The FDA encouraged health care professionals and patients to report any side effects from tofacitinib or other medications through the FDA MedWatch program online or by phone at 1-800-332-1088.

Until nuances revealed, no change in practice

The preliminary study findings contain some nuances that are a bit complicated from a statistical standpoint, according to Daniel Furst, MD, professor emeritus of medicine at the University of California, Los Angeles; adjunct professor at the University of Washington, Seattle; and research professor at the University of Florence (Italy).

Updated on 2/8/2021.

The Food and Drug Administration has alerted the public to an increased risk of serious heart-related problems and cancer risk associated with the Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR), based on early results from a safety clinical trial comparing tofacitinib and tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA).

The FDA is awaiting further results from the trial, but in a safety communication issued on Feb. 4, the agency advised patients not to discontinue tofacitinib without consulting their health care providers and advised health care professionals to weigh the risks and benefits when prescribing the drug and continue to follow the current prescribing information.

Tofacitinib was approved for treatment of RA in 2012 at a 5-mg dose. After this approval, the FDA required drug manufacturer Pfizer to conduct a safety clinical trial that included the 5-mg twice-daily dose and a 10-mg twice-daily dose that is currently approved only for ulcerative colitis. In addition to RA and ulcerative colitis, tofacitinib is approved for adults with active psoriatic arthritis and patients aged 2 years or older with active polyarticular course juvenile idiopathic arthritis.

Pfizer announced partial results of the study, known as the ORAL Surveillance trial, in a press release on Jan. 27. The randomized trial included 4,362 RA patients aged 50 years and older who received either 5-mg or 10-mg doses of tofacitinib or a TNF inhibitor (adalimumab or etanercept).

The full results have yet to be released, but based on data from approximately 10,000 person-years for the combined tofacitinib groups and approximately 5,000 person-years for the TNF inhibitor group, the rate of major cardiovascular adverse events was significantly higher in the combined tofacitinib group, compared with the TNF inhibitor group (0.98 vs. 0.73 per 100 person-years; hazard ratio, 1.33). In addition, the rate of adjudicated malignancies was significantly higher in the tofacitinib group, compared with the TNF inhibitor group (1.13 vs. 0.77 per 100 person-years; HR, 1.48).

In February 2019, the FDA issued a warning stating an increased risk of pulmonary embolism and death associated with the 10-mg twice-daily dose of tofacitinib, following interims results from the safety study.

In July 2019, the FDA added a boxed warning to tofacitinib advising of the increased risk for pulmonary embolism and death associated with the 10-mg twice-daily dose.

The FDA encouraged health care professionals and patients to report any side effects from tofacitinib or other medications through the FDA MedWatch program online or by phone at 1-800-332-1088.

Until nuances revealed, no change in practice

The preliminary study findings contain some nuances that are a bit complicated from a statistical standpoint, according to Daniel Furst, MD, professor emeritus of medicine at the University of California, Los Angeles; adjunct professor at the University of Washington, Seattle; and research professor at the University of Florence (Italy).

Updated on 2/8/2021.

Adolescents and young adults with mood disorders and cannabis use disorder (CUD) are at significantly increased risk for self-harm, all-cause mortality, homicide, and death by unintentional overdose, new research suggests.

Investigators found the risk for self-harm was three times higher, all-cause mortality was 59% higher, unintentional overdose was 2.5 times higher, and homicide was more than three times higher in those with versus without CUD.

“The take-home message of these findings is that we need to be aware of the perception that cannabis use is harmless, when it’s actually not,” lead author Cynthia Fontanella, PhD, associate professor of psychiatry, Ohio State University Wexner Medical Center, Columbus, said in an interview.

“We need to educate parents and clinicians that there are risks associated with cannabis, including increased risk for self-harm and death, and we need to effectively treat both cannabis use disorder and mood disorders,” she said.

The study was published online Jan. 19, 2021, in JAMA Pediatrics.
 

Little research in youth

“There has been very little research conducted on CUD in the adolescent population, and most studies have been conducted with adults,” Dr. Fontanella said.

Research on adults has shown that, even in people without mood disorders, cannabis use is associated with the early onset of mood disorders, psychosis, and anxiety disorders and has also been linked with suicidal behavior and increased risk for motor vehicle accidents, Dr. Fontanella said.

iStock/ThinkStockPhotos.com

“We were motivated to conduct this study because we treat kids with depression and bipolar disorder and we noticed a high prevalence of CUD in this population, so we were curious about what its negative effects might be,” Dr. Fontanella recounted.

The researchers analyzed 7-year data drawn from Ohio Medicaid claims and linked to data from death certificates in 204,780 youths between the ages of 10 and 24 years (mean age was 17.2 years at the time of mood disorder diagnosis). Most were female, non-Hispanic White, enrolled in Medicaid because of poverty, and living in a metropolitan area (65.0%, 66.9%, 87.6%, and 77.1%, respectively).

Participants were followed up to 1 year from diagnosis until the end of enrollment, a self-harm event, or death.

Researchers included demographic, clinical, and treatment factors as covariates.

Close to three-quarters (72.7%) of the cohort had a depressive disorder, followed by unspecified/persistent mood disorder and bipolar disorder (14.9% and 12.4%, respectively). Comorbidities included ADHD (12.4%), anxiety disorder (12.3%), and other mental disorders (13.1%).

One -tenth of the cohort (10.3%) were diagnosed with CUD.
 

CUD treatment referrals

“Although CUD was associated with suicide in the unadjusted model, it was not significantly associated in adjusted models,” the authors reported.

Dr. Fontanella noted that the risk for these adverse outcomes is greater among those who engage in heavy, frequent use or who use cannabis that has higher-potency tetrahydrocannabinol (THC) content.

Reasons why CUD might be associated with these adverse outcomes are that it can increase impulsivity, poor judgment, and clouded thinking, which may in turn increase the risk for self-harm behaviors, she said.

She recommended that clinicians refer youth with CUD for “effective treatments,” including family-based models and individual approaches, such as cognitive behavioral therapy and motivational enhancement therapy.
 

Open dialogue

In a comment, Wilfrid Noel Raby, MD, PhD, adjunct clinical professor, Albert Einstein College of Medicine, New York, noted that psychosis can occur in patients with CUD and mood disorders – especially bipolar disorder – but was not included as a study outcome. “I would have liked to see more data about that,” he said.

However, a strength of the study was that it included children aged as young as 10 years. “The trend is that cannabis use is starting at younger and younger ages, which has all kinds of ramifications in terms of cerebral development.”

Christopher Hammond, MD, PhD, assistant professor of psychiatry, Johns Hopkins University, Baltimore, said: “Three major strengths of the study are the size of the sample, its longitudinal analysis, and that the authors controlled for a number of potential confounding variables.”

In light of the findings, Dr. Hammond recommended clinicians and other health professionals who work with young people “should screen for cannabis-related problems in youth with mood disorders.”

Dr. Hammond, who is the director of the Co-occurring Disorders in Adolescents and Young Adults Clinical and Research Program, Johns Hopkins Bayview Medical Center, Baltimore, and was not involved with the study, recommended counseling youth with mood disorders and their parents and families “regarding the potential adverse health effects related to cannabis use.”

He also recommended “open dialogue with youth with and without mental health conditions about misleading reports in the national media and advertising about cannabis’ health benefits.”

The study was funded by the National Institute of Mental Health. Dr. Fontanella reported receiving grants from the National Institute of Mental Health during the conduct of the study. Dr. Raby reported no relevant financial relationships. Dr. Hammond reported receiving research grant funding from the National Institutes of Health, the American Academy of Child & Adolescent Psychiatry, Substance Abuse Mental Health Services Administration, the National Network of Depression Centers, and the Armstrong Institute at Johns Hopkins Bayview and serves as a scientific adviser for the National Courts and Science Institute and as a subject matter expert for SAMHSA related to co-occurring substance use disorders and severe emotional disturbance in youth. 
 

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

Adolescents and young adults with mood disorders and cannabis use disorder (CUD) are at significantly increased risk for self-harm, all-cause mortality, homicide, and death by unintentional overdose, new research suggests.

Investigators found the risk for self-harm was three times higher, all-cause mortality was 59% higher, unintentional overdose was 2.5 times higher, and homicide was more than three times higher in those with versus without CUD.

“The take-home message of these findings is that we need to be aware of the perception that cannabis use is harmless, when it’s actually not,” lead author Cynthia Fontanella, PhD, associate professor of psychiatry, Ohio State University Wexner Medical Center, Columbus, said in an interview.

“We need to educate parents and clinicians that there are risks associated with cannabis, including increased risk for self-harm and death, and we need to effectively treat both cannabis use disorder and mood disorders,” she said.

The study was published online Jan. 19, 2021, in JAMA Pediatrics.
 

Little research in youth

“There has been very little research conducted on CUD in the adolescent population, and most studies have been conducted with adults,” Dr. Fontanella said.

Research on adults has shown that, even in people without mood disorders, cannabis use is associated with the early onset of mood disorders, psychosis, and anxiety disorders and has also been linked with suicidal behavior and increased risk for motor vehicle accidents, Dr. Fontanella said.

iStock/ThinkStockPhotos.com

“We were motivated to conduct this study because we treat kids with depression and bipolar disorder and we noticed a high prevalence of CUD in this population, so we were curious about what its negative effects might be,” Dr. Fontanella recounted.

The researchers analyzed 7-year data drawn from Ohio Medicaid claims and linked to data from death certificates in 204,780 youths between the ages of 10 and 24 years (mean age was 17.2 years at the time of mood disorder diagnosis). Most were female, non-Hispanic White, enrolled in Medicaid because of poverty, and living in a metropolitan area (65.0%, 66.9%, 87.6%, and 77.1%, respectively).

Participants were followed up to 1 year from diagnosis until the end of enrollment, a self-harm event, or death.

Researchers included demographic, clinical, and treatment factors as covariates.

Close to three-quarters (72.7%) of the cohort had a depressive disorder, followed by unspecified/persistent mood disorder and bipolar disorder (14.9% and 12.4%, respectively). Comorbidities included ADHD (12.4%), anxiety disorder (12.3%), and other mental disorders (13.1%).

One -tenth of the cohort (10.3%) were diagnosed with CUD.
 

CUD treatment referrals

“Although CUD was associated with suicide in the unadjusted model, it was not significantly associated in adjusted models,” the authors reported.

Dr. Fontanella noted that the risk for these adverse outcomes is greater among those who engage in heavy, frequent use or who use cannabis that has higher-potency tetrahydrocannabinol (THC) content.

Reasons why CUD might be associated with these adverse outcomes are that it can increase impulsivity, poor judgment, and clouded thinking, which may in turn increase the risk for self-harm behaviors, she said.

She recommended that clinicians refer youth with CUD for “effective treatments,” including family-based models and individual approaches, such as cognitive behavioral therapy and motivational enhancement therapy.
 

Open dialogue

In a comment, Wilfrid Noel Raby, MD, PhD, adjunct clinical professor, Albert Einstein College of Medicine, New York, noted that psychosis can occur in patients with CUD and mood disorders – especially bipolar disorder – but was not included as a study outcome. “I would have liked to see more data about that,” he said.

However, a strength of the study was that it included children aged as young as 10 years. “The trend is that cannabis use is starting at younger and younger ages, which has all kinds of ramifications in terms of cerebral development.”

Christopher Hammond, MD, PhD, assistant professor of psychiatry, Johns Hopkins University, Baltimore, said: “Three major strengths of the study are the size of the sample, its longitudinal analysis, and that the authors controlled for a number of potential confounding variables.”

In light of the findings, Dr. Hammond recommended clinicians and other health professionals who work with young people “should screen for cannabis-related problems in youth with mood disorders.”

Dr. Hammond, who is the director of the Co-occurring Disorders in Adolescents and Young Adults Clinical and Research Program, Johns Hopkins Bayview Medical Center, Baltimore, and was not involved with the study, recommended counseling youth with mood disorders and their parents and families “regarding the potential adverse health effects related to cannabis use.”

He also recommended “open dialogue with youth with and without mental health conditions about misleading reports in the national media and advertising about cannabis’ health benefits.”

The study was funded by the National Institute of Mental Health. Dr. Fontanella reported receiving grants from the National Institute of Mental Health during the conduct of the study. Dr. Raby reported no relevant financial relationships. Dr. Hammond reported receiving research grant funding from the National Institutes of Health, the American Academy of Child & Adolescent Psychiatry, Substance Abuse Mental Health Services Administration, the National Network of Depression Centers, and the Armstrong Institute at Johns Hopkins Bayview and serves as a scientific adviser for the National Courts and Science Institute and as a subject matter expert for SAMHSA related to co-occurring substance use disorders and severe emotional disturbance in youth. 
 

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

Adolescents and young adults with mood disorders and cannabis use disorder (CUD) are at significantly increased risk for self-harm, all-cause mortality, homicide, and death by unintentional overdose, new research suggests.

Investigators found the risk for self-harm was three times higher, all-cause mortality was 59% higher, unintentional overdose was 2.5 times higher, and homicide was more than three times higher in those with versus without CUD.

“The take-home message of these findings is that we need to be aware of the perception that cannabis use is harmless, when it’s actually not,” lead author Cynthia Fontanella, PhD, associate professor of psychiatry, Ohio State University Wexner Medical Center, Columbus, said in an interview.

“We need to educate parents and clinicians that there are risks associated with cannabis, including increased risk for self-harm and death, and we need to effectively treat both cannabis use disorder and mood disorders,” she said.

The study was published online Jan. 19, 2021, in JAMA Pediatrics.
 

Little research in youth

“There has been very little research conducted on CUD in the adolescent population, and most studies have been conducted with adults,” Dr. Fontanella said.

Research on adults has shown that, even in people without mood disorders, cannabis use is associated with the early onset of mood disorders, psychosis, and anxiety disorders and has also been linked with suicidal behavior and increased risk for motor vehicle accidents, Dr. Fontanella said.

iStock/ThinkStockPhotos.com

“We were motivated to conduct this study because we treat kids with depression and bipolar disorder and we noticed a high prevalence of CUD in this population, so we were curious about what its negative effects might be,” Dr. Fontanella recounted.

The researchers analyzed 7-year data drawn from Ohio Medicaid claims and linked to data from death certificates in 204,780 youths between the ages of 10 and 24 years (mean age was 17.2 years at the time of mood disorder diagnosis). Most were female, non-Hispanic White, enrolled in Medicaid because of poverty, and living in a metropolitan area (65.0%, 66.9%, 87.6%, and 77.1%, respectively).

Participants were followed up to 1 year from diagnosis until the end of enrollment, a self-harm event, or death.

Researchers included demographic, clinical, and treatment factors as covariates.

Close to three-quarters (72.7%) of the cohort had a depressive disorder, followed by unspecified/persistent mood disorder and bipolar disorder (14.9% and 12.4%, respectively). Comorbidities included ADHD (12.4%), anxiety disorder (12.3%), and other mental disorders (13.1%).

One -tenth of the cohort (10.3%) were diagnosed with CUD.
 

CUD treatment referrals

“Although CUD was associated with suicide in the unadjusted model, it was not significantly associated in adjusted models,” the authors reported.

Dr. Fontanella noted that the risk for these adverse outcomes is greater among those who engage in heavy, frequent use or who use cannabis that has higher-potency tetrahydrocannabinol (THC) content.

Reasons why CUD might be associated with these adverse outcomes are that it can increase impulsivity, poor judgment, and clouded thinking, which may in turn increase the risk for self-harm behaviors, she said.

She recommended that clinicians refer youth with CUD for “effective treatments,” including family-based models and individual approaches, such as cognitive behavioral therapy and motivational enhancement therapy.
 

Open dialogue

In a comment, Wilfrid Noel Raby, MD, PhD, adjunct clinical professor, Albert Einstein College of Medicine, New York, noted that psychosis can occur in patients with CUD and mood disorders – especially bipolar disorder – but was not included as a study outcome. “I would have liked to see more data about that,” he said.

However, a strength of the study was that it included children aged as young as 10 years. “The trend is that cannabis use is starting at younger and younger ages, which has all kinds of ramifications in terms of cerebral development.”

Christopher Hammond, MD, PhD, assistant professor of psychiatry, Johns Hopkins University, Baltimore, said: “Three major strengths of the study are the size of the sample, its longitudinal analysis, and that the authors controlled for a number of potential confounding variables.”

In light of the findings, Dr. Hammond recommended clinicians and other health professionals who work with young people “should screen for cannabis-related problems in youth with mood disorders.”

Dr. Hammond, who is the director of the Co-occurring Disorders in Adolescents and Young Adults Clinical and Research Program, Johns Hopkins Bayview Medical Center, Baltimore, and was not involved with the study, recommended counseling youth with mood disorders and their parents and families “regarding the potential adverse health effects related to cannabis use.”

He also recommended “open dialogue with youth with and without mental health conditions about misleading reports in the national media and advertising about cannabis’ health benefits.”

The study was funded by the National Institute of Mental Health. Dr. Fontanella reported receiving grants from the National Institute of Mental Health during the conduct of the study. Dr. Raby reported no relevant financial relationships. Dr. Hammond reported receiving research grant funding from the National Institutes of Health, the American Academy of Child & Adolescent Psychiatry, Substance Abuse Mental Health Services Administration, the National Network of Depression Centers, and the Armstrong Institute at Johns Hopkins Bayview and serves as a scientific adviser for the National Courts and Science Institute and as a subject matter expert for SAMHSA related to co-occurring substance use disorders and severe emotional disturbance in youth. 
 

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

For now at least, total body irradiation (TBI) plus etoposide remains the conditioning regimen of choice for children undergoing allogeneic hematopoietic stem cell transplant for acute lymphoblastic leukemia (ALL), according to an open-label, phase 3 trial from Europe.

The investigators sought to answer a question many physicians have raised: With improvements in human leukocyte antigen typing, better graft-versus-host disease prophylaxis, and other advances, can myeloablative chemotherapy conditioning replace TBI, which is more toxic?

The downstream effects of TBI can include secondary malignancies and cataracts, as well as impaired growth and impaired gonadal and cognitive function.

But the answer to that question is no, or at least, not yet.

The phase 3 trial included individuals with ALL who were aged 4-21 years at time of transplant. They were randomly assigned to receive either fractionated TBI at 12 Gy plus etoposide or chemotherapy based on a myeloablative regimen: fludarabine, thiotepa, and either busulfan or treosulfan.

The trial was stopped after 413 patients had undergone randomization – quite a bit short of the 1,000-patient goal. The trial was terminated because TBI proved clearly superior on an interim analysis at a median follow-up of 2.1 years.

The results showed that 72% of the TBI group – but only 51% of the chemotherapy arm – were relapse free at 2 years with no graft-versus-host disease (P = .0003).

The 2-year treatment-related mortality rate was 2% in the TBI group but 9% with chemotherapy conditioning (P = .03).

The study was published Feb. 1, 2020, in the Journal of Clinical Oncology.

“We recommend TBI plus etoposide conditioning for patients [aged over] 4 years old with high-risk ALL undergoing allogeneic HSCT [hematopoietic stem cell transplant],” they concluded. The investigators were led by Christina Peters, MD, a pediatrics professor at the St. Anna Children’s Cancer Research Institute, Vienna.

The benefits of TBI held on multivariate analysis and across subgroups, including children in their first and second remissions and among those with high-risk cytogenetics. Relapse risk factors, such as age at transplant, leukemic phenotype, and molecular aberrations, did not significantly affect outcomes, the authors reported.

Given that relapses plateaued with TBI at 2.5 years but were still on the upswing for patients who underwent chemoconditioning, “it is unlikely that secondary malignancies after TBI could jeopardize the survival advantage,” they wrote.

“So does this mean that the HCT community is forever chained to TBI as a standard of care? Certainly, it means that without very sound rationale to deviate, a TBI-based preparative regimen is the preferred therapy at present,” Michael Pulsipher, MD, head of blood and marrow transplantation at Children’s Hospital Los Angeles, commented in an accompanying editorial.

However, “there are approaches under study currently that may define patients who do not need TBI for high rates of cure,” he suggested. Those approaches include selecting patients with the deepest remissions and using KIR-favorable haplotype to harness natural killer cell activity.

“In our new world of chimeric antigen receptor T-cells and immunotherapies, surely we can find safer paths to success,” Dr. Pulsipher wrote.

With regard to patient selection, the investigators noted that a recent review that included more than 3,000 children with ALL found no overall survival benefit with TBI versus chemoconditioning for patients in first complete remission but worse outcomes with chemoconditioning among patients in second complete remission. “A similar trend was observed in our subgroup analyses; however, our study was not powered to assess statistical significance in a sample size of 413 patients,” they wrote.

Minimal residual disease did not influence survival outcomes, probably because the investigators were aggressive in inducing deep remission in their patients before transplant, so for most patients, MRD was undetectable or very low beforehand.

The study was funded by Amgen, Jazz Pharmaceuticals, Neovii, Medac, and others. Dr. Peters and coauthors, as well as Dr. Pulsipher have disclosed numerous ties with those and/or other companies.

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

For now at least, total body irradiation (TBI) plus etoposide remains the conditioning regimen of choice for children undergoing allogeneic hematopoietic stem cell transplant for acute lymphoblastic leukemia (ALL), according to an open-label, phase 3 trial from Europe.

The investigators sought to answer a question many physicians have raised: With improvements in human leukocyte antigen typing, better graft-versus-host disease prophylaxis, and other advances, can myeloablative chemotherapy conditioning replace TBI, which is more toxic?

The downstream effects of TBI can include secondary malignancies and cataracts, as well as impaired growth and impaired gonadal and cognitive function.

But the answer to that question is no, or at least, not yet.

The phase 3 trial included individuals with ALL who were aged 4-21 years at time of transplant. They were randomly assigned to receive either fractionated TBI at 12 Gy plus etoposide or chemotherapy based on a myeloablative regimen: fludarabine, thiotepa, and either busulfan or treosulfan.

The trial was stopped after 413 patients had undergone randomization – quite a bit short of the 1,000-patient goal. The trial was terminated because TBI proved clearly superior on an interim analysis at a median follow-up of 2.1 years.

The results showed that 72% of the TBI group – but only 51% of the chemotherapy arm – were relapse free at 2 years with no graft-versus-host disease (P = .0003).

The 2-year treatment-related mortality rate was 2% in the TBI group but 9% with chemotherapy conditioning (P = .03).

The study was published Feb. 1, 2020, in the Journal of Clinical Oncology.

“We recommend TBI plus etoposide conditioning for patients [aged over] 4 years old with high-risk ALL undergoing allogeneic HSCT [hematopoietic stem cell transplant],” they concluded. The investigators were led by Christina Peters, MD, a pediatrics professor at the St. Anna Children’s Cancer Research Institute, Vienna.

The benefits of TBI held on multivariate analysis and across subgroups, including children in their first and second remissions and among those with high-risk cytogenetics. Relapse risk factors, such as age at transplant, leukemic phenotype, and molecular aberrations, did not significantly affect outcomes, the authors reported.

Given that relapses plateaued with TBI at 2.5 years but were still on the upswing for patients who underwent chemoconditioning, “it is unlikely that secondary malignancies after TBI could jeopardize the survival advantage,” they wrote.

“So does this mean that the HCT community is forever chained to TBI as a standard of care? Certainly, it means that without very sound rationale to deviate, a TBI-based preparative regimen is the preferred therapy at present,” Michael Pulsipher, MD, head of blood and marrow transplantation at Children’s Hospital Los Angeles, commented in an accompanying editorial.

However, “there are approaches under study currently that may define patients who do not need TBI for high rates of cure,” he suggested. Those approaches include selecting patients with the deepest remissions and using KIR-favorable haplotype to harness natural killer cell activity.

“In our new world of chimeric antigen receptor T-cells and immunotherapies, surely we can find safer paths to success,” Dr. Pulsipher wrote.

With regard to patient selection, the investigators noted that a recent review that included more than 3,000 children with ALL found no overall survival benefit with TBI versus chemoconditioning for patients in first complete remission but worse outcomes with chemoconditioning among patients in second complete remission. “A similar trend was observed in our subgroup analyses; however, our study was not powered to assess statistical significance in a sample size of 413 patients,” they wrote.

Minimal residual disease did not influence survival outcomes, probably because the investigators were aggressive in inducing deep remission in their patients before transplant, so for most patients, MRD was undetectable or very low beforehand.

The study was funded by Amgen, Jazz Pharmaceuticals, Neovii, Medac, and others. Dr. Peters and coauthors, as well as Dr. Pulsipher have disclosed numerous ties with those and/or other companies.

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

For now at least, total body irradiation (TBI) plus etoposide remains the conditioning regimen of choice for children undergoing allogeneic hematopoietic stem cell transplant for acute lymphoblastic leukemia (ALL), according to an open-label, phase 3 trial from Europe.

The investigators sought to answer a question many physicians have raised: With improvements in human leukocyte antigen typing, better graft-versus-host disease prophylaxis, and other advances, can myeloablative chemotherapy conditioning replace TBI, which is more toxic?

The downstream effects of TBI can include secondary malignancies and cataracts, as well as impaired growth and impaired gonadal and cognitive function.

But the answer to that question is no, or at least, not yet.

The phase 3 trial included individuals with ALL who were aged 4-21 years at time of transplant. They were randomly assigned to receive either fractionated TBI at 12 Gy plus etoposide or chemotherapy based on a myeloablative regimen: fludarabine, thiotepa, and either busulfan or treosulfan.

The trial was stopped after 413 patients had undergone randomization – quite a bit short of the 1,000-patient goal. The trial was terminated because TBI proved clearly superior on an interim analysis at a median follow-up of 2.1 years.

The results showed that 72% of the TBI group – but only 51% of the chemotherapy arm – were relapse free at 2 years with no graft-versus-host disease (P = .0003).

The 2-year treatment-related mortality rate was 2% in the TBI group but 9% with chemotherapy conditioning (P = .03).

The study was published Feb. 1, 2020, in the Journal of Clinical Oncology.

“We recommend TBI plus etoposide conditioning for patients [aged over] 4 years old with high-risk ALL undergoing allogeneic HSCT [hematopoietic stem cell transplant],” they concluded. The investigators were led by Christina Peters, MD, a pediatrics professor at the St. Anna Children’s Cancer Research Institute, Vienna.

The benefits of TBI held on multivariate analysis and across subgroups, including children in their first and second remissions and among those with high-risk cytogenetics. Relapse risk factors, such as age at transplant, leukemic phenotype, and molecular aberrations, did not significantly affect outcomes, the authors reported.

Given that relapses plateaued with TBI at 2.5 years but were still on the upswing for patients who underwent chemoconditioning, “it is unlikely that secondary malignancies after TBI could jeopardize the survival advantage,” they wrote.

“So does this mean that the HCT community is forever chained to TBI as a standard of care? Certainly, it means that without very sound rationale to deviate, a TBI-based preparative regimen is the preferred therapy at present,” Michael Pulsipher, MD, head of blood and marrow transplantation at Children’s Hospital Los Angeles, commented in an accompanying editorial.

However, “there are approaches under study currently that may define patients who do not need TBI for high rates of cure,” he suggested. Those approaches include selecting patients with the deepest remissions and using KIR-favorable haplotype to harness natural killer cell activity.

“In our new world of chimeric antigen receptor T-cells and immunotherapies, surely we can find safer paths to success,” Dr. Pulsipher wrote.

With regard to patient selection, the investigators noted that a recent review that included more than 3,000 children with ALL found no overall survival benefit with TBI versus chemoconditioning for patients in first complete remission but worse outcomes with chemoconditioning among patients in second complete remission. “A similar trend was observed in our subgroup analyses; however, our study was not powered to assess statistical significance in a sample size of 413 patients,” they wrote.

Minimal residual disease did not influence survival outcomes, probably because the investigators were aggressive in inducing deep remission in their patients before transplant, so for most patients, MRD was undetectable or very low beforehand.

The study was funded by Amgen, Jazz Pharmaceuticals, Neovii, Medac, and others. Dr. Peters and coauthors, as well as Dr. Pulsipher have disclosed numerous ties with those and/or other companies.

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

Does the name Bruce Lipton sound familiar to you? Until a few years ago the only bell that it rang with me was that I had a high school classmate named Bruce Lipton. I recall that his father owned the local grocery store and he was one of the most prolific pranksters in a class with a long history of prank playing. If the name dredges up any associations for you it may because you have heard of a PhD biologist who has written and lectured extensively on epigenetics. You may have even read his most widely published book, “The Biology of Belief.” It turns out the Epigenetics Guy and my high school prankster classmate are one and the same.

After decades of separation – he is in California and I’m here in Maine – we have reconnected via Zoom mini reunions that our class has organized to combat the isolation that has descended on us with the pandemic. While I haven’t read his books, I have watched and listened to some of his podcasts and lectures. The devilish twinkle in his eye in the 1950s and 1960s has provided the scaffolding on which he has built a charismatic and persuasive presentation style.

Bruce was no dummy in school but his early career as a cell biologist doing research in stem-cell function was a surprise to all of us. But then high school reunions are often full of surprises and should serve as good reminders of the danger of profiling and pigeon-holing adolescents.

Professor Lipton’s take on epigenetics boils down to the notion that our genome should merely be considered a blueprint and not the final determinant of who we are and what illnesses befall us. His research and observations suggest to him that there are an uncountable number extragenomic factors, including environmental conditions and our belief systems, that can influence how that blueprint is read and the resulting expression of the genes we have inherited.

At face value, Bruce’s basic premise falls very close to some of the conclusions I have toyed with in an attempt to explain what I have observed doing primary care pediatrics. For example, I have trouble blaming the meteoric rise of the ADHD phenomenon on a genetic mutation. I suspect there are likely to be extragenomic forces coming into play, such as sleep deprivation and changing child-rearing practices. In my Oct. 9, 2020, Letters from Maine column I referred to a Swedish twins study that suggested children from a family with a strong history of depression were more likely to develop depression when raised in an adopted family that experienced domestic turmoil. His philosophy also fits with my sense that I have more control over my own health outcomes than many other people.

However, Professor Lipton and I part company (just philosophically that is) when he slips into hyperbole and applies what he terms as the New Biology too broadly. He may be correct that the revolutionary changes which came in the wake of Watson and Crick’s double helix discovery have resulted in a view of pathophysiology that is overly focused on what we are learning about our genome. On the other hand it is refreshing to hear someone with his charismatic and persuasive skills question the status quo.

If you haven’t listened to what he has to say I urge you to browse the Internet and sample some of his talks. I am sure you will find what he has to say stimulating. I doubt you will buy his whole package but I suspect you may find some bits you can agree with.

It still boils down to the old nature versus nurture argument. He’s all in for nurture. I’m still more comfortable straddling the fence.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Does the name Bruce Lipton sound familiar to you? Until a few years ago the only bell that it rang with me was that I had a high school classmate named Bruce Lipton. I recall that his father owned the local grocery store and he was one of the most prolific pranksters in a class with a long history of prank playing. If the name dredges up any associations for you it may because you have heard of a PhD biologist who has written and lectured extensively on epigenetics. You may have even read his most widely published book, “The Biology of Belief.” It turns out the Epigenetics Guy and my high school prankster classmate are one and the same.

After decades of separation – he is in California and I’m here in Maine – we have reconnected via Zoom mini reunions that our class has organized to combat the isolation that has descended on us with the pandemic. While I haven’t read his books, I have watched and listened to some of his podcasts and lectures. The devilish twinkle in his eye in the 1950s and 1960s has provided the scaffolding on which he has built a charismatic and persuasive presentation style.

Bruce was no dummy in school but his early career as a cell biologist doing research in stem-cell function was a surprise to all of us. But then high school reunions are often full of surprises and should serve as good reminders of the danger of profiling and pigeon-holing adolescents.

Professor Lipton’s take on epigenetics boils down to the notion that our genome should merely be considered a blueprint and not the final determinant of who we are and what illnesses befall us. His research and observations suggest to him that there are an uncountable number extragenomic factors, including environmental conditions and our belief systems, that can influence how that blueprint is read and the resulting expression of the genes we have inherited.

At face value, Bruce’s basic premise falls very close to some of the conclusions I have toyed with in an attempt to explain what I have observed doing primary care pediatrics. For example, I have trouble blaming the meteoric rise of the ADHD phenomenon on a genetic mutation. I suspect there are likely to be extragenomic forces coming into play, such as sleep deprivation and changing child-rearing practices. In my Oct. 9, 2020, Letters from Maine column I referred to a Swedish twins study that suggested children from a family with a strong history of depression were more likely to develop depression when raised in an adopted family that experienced domestic turmoil. His philosophy also fits with my sense that I have more control over my own health outcomes than many other people.

However, Professor Lipton and I part company (just philosophically that is) when he slips into hyperbole and applies what he terms as the New Biology too broadly. He may be correct that the revolutionary changes which came in the wake of Watson and Crick’s double helix discovery have resulted in a view of pathophysiology that is overly focused on what we are learning about our genome. On the other hand it is refreshing to hear someone with his charismatic and persuasive skills question the status quo.

If you haven’t listened to what he has to say I urge you to browse the Internet and sample some of his talks. I am sure you will find what he has to say stimulating. I doubt you will buy his whole package but I suspect you may find some bits you can agree with.

It still boils down to the old nature versus nurture argument. He’s all in for nurture. I’m still more comfortable straddling the fence.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Does the name Bruce Lipton sound familiar to you? Until a few years ago the only bell that it rang with me was that I had a high school classmate named Bruce Lipton. I recall that his father owned the local grocery store and he was one of the most prolific pranksters in a class with a long history of prank playing. If the name dredges up any associations for you it may because you have heard of a PhD biologist who has written and lectured extensively on epigenetics. You may have even read his most widely published book, “The Biology of Belief.” It turns out the Epigenetics Guy and my high school prankster classmate are one and the same.

After decades of separation – he is in California and I’m here in Maine – we have reconnected via Zoom mini reunions that our class has organized to combat the isolation that has descended on us with the pandemic. While I haven’t read his books, I have watched and listened to some of his podcasts and lectures. The devilish twinkle in his eye in the 1950s and 1960s has provided the scaffolding on which he has built a charismatic and persuasive presentation style.

Bruce was no dummy in school but his early career as a cell biologist doing research in stem-cell function was a surprise to all of us. But then high school reunions are often full of surprises and should serve as good reminders of the danger of profiling and pigeon-holing adolescents.

Professor Lipton’s take on epigenetics boils down to the notion that our genome should merely be considered a blueprint and not the final determinant of who we are and what illnesses befall us. His research and observations suggest to him that there are an uncountable number extragenomic factors, including environmental conditions and our belief systems, that can influence how that blueprint is read and the resulting expression of the genes we have inherited.

At face value, Bruce’s basic premise falls very close to some of the conclusions I have toyed with in an attempt to explain what I have observed doing primary care pediatrics. For example, I have trouble blaming the meteoric rise of the ADHD phenomenon on a genetic mutation. I suspect there are likely to be extragenomic forces coming into play, such as sleep deprivation and changing child-rearing practices. In my Oct. 9, 2020, Letters from Maine column I referred to a Swedish twins study that suggested children from a family with a strong history of depression were more likely to develop depression when raised in an adopted family that experienced domestic turmoil. His philosophy also fits with my sense that I have more control over my own health outcomes than many other people.

However, Professor Lipton and I part company (just philosophically that is) when he slips into hyperbole and applies what he terms as the New Biology too broadly. He may be correct that the revolutionary changes which came in the wake of Watson and Crick’s double helix discovery have resulted in a view of pathophysiology that is overly focused on what we are learning about our genome. On the other hand it is refreshing to hear someone with his charismatic and persuasive skills question the status quo.

If you haven’t listened to what he has to say I urge you to browse the Internet and sample some of his talks. I am sure you will find what he has to say stimulating. I doubt you will buy his whole package but I suspect you may find some bits you can agree with.

It still boils down to the old nature versus nurture argument. He’s all in for nurture. I’m still more comfortable straddling the fence.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Despite a drop in the number of weekly COVID-19 cases, children made up a larger share of cases for the fourth consecutive week, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Just over 140,000 new cases of COVID-19 in children were reported for the week of Jan. 22-28, down from 165,000 the week before and down from the record high of 211,000 2 weeks earlier, the AAP and the CHA said in their weekly COVID-19 report.

Since the beginning of January, however, the proportion of weekly cases occurring in children has risen from 12.9% to 15.1%, based on data collected by the AAP/CHA from the health department websites of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Since the beginning of the pandemic, 2.81 million children have been infected by the coronavirus, representing 12.8% of the total for all ages, which is almost 22 million. The cumulative rate since the start of the pandemic passed 3,700 cases per 100,000 children after increasing by 5.2% over the previous week, the AAP and CHA said in their report.

Cumulative hospitalizations in children just passed 11,000 in the 24 states (and New York City) that are reporting data for children, which represents 1.8% of COVID-19–related admissions for all ages, a proportion that has not changed since mid-November. Ten more deaths in children were reported during Jan. 22-28, bringing the total to 215 in the 43 states, along with New York City and Guam, that are tracking mortality.

In the 10 states that are reporting data on testing, rates of positive results in children range from 7.1% in Indiana, in which children make up the largest proportion of total tests performed (18.1%) to 28.4% in Iowa, where children make up the smallest proportion of tests (6.0%), the AAP and CHA said.

[email protected]

Despite a drop in the number of weekly COVID-19 cases, children made up a larger share of cases for the fourth consecutive week, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Just over 140,000 new cases of COVID-19 in children were reported for the week of Jan. 22-28, down from 165,000 the week before and down from the record high of 211,000 2 weeks earlier, the AAP and the CHA said in their weekly COVID-19 report.

Since the beginning of January, however, the proportion of weekly cases occurring in children has risen from 12.9% to 15.1%, based on data collected by the AAP/CHA from the health department websites of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Since the beginning of the pandemic, 2.81 million children have been infected by the coronavirus, representing 12.8% of the total for all ages, which is almost 22 million. The cumulative rate since the start of the pandemic passed 3,700 cases per 100,000 children after increasing by 5.2% over the previous week, the AAP and CHA said in their report.

Cumulative hospitalizations in children just passed 11,000 in the 24 states (and New York City) that are reporting data for children, which represents 1.8% of COVID-19–related admissions for all ages, a proportion that has not changed since mid-November. Ten more deaths in children were reported during Jan. 22-28, bringing the total to 215 in the 43 states, along with New York City and Guam, that are tracking mortality.

In the 10 states that are reporting data on testing, rates of positive results in children range from 7.1% in Indiana, in which children make up the largest proportion of total tests performed (18.1%) to 28.4% in Iowa, where children make up the smallest proportion of tests (6.0%), the AAP and CHA said.

[email protected]

Despite a drop in the number of weekly COVID-19 cases, children made up a larger share of cases for the fourth consecutive week, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Just over 140,000 new cases of COVID-19 in children were reported for the week of Jan. 22-28, down from 165,000 the week before and down from the record high of 211,000 2 weeks earlier, the AAP and the CHA said in their weekly COVID-19 report.

Since the beginning of January, however, the proportion of weekly cases occurring in children has risen from 12.9% to 15.1%, based on data collected by the AAP/CHA from the health department websites of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Since the beginning of the pandemic, 2.81 million children have been infected by the coronavirus, representing 12.8% of the total for all ages, which is almost 22 million. The cumulative rate since the start of the pandemic passed 3,700 cases per 100,000 children after increasing by 5.2% over the previous week, the AAP and CHA said in their report.

Cumulative hospitalizations in children just passed 11,000 in the 24 states (and New York City) that are reporting data for children, which represents 1.8% of COVID-19–related admissions for all ages, a proportion that has not changed since mid-November. Ten more deaths in children were reported during Jan. 22-28, bringing the total to 215 in the 43 states, along with New York City and Guam, that are tracking mortality.

In the 10 states that are reporting data on testing, rates of positive results in children range from 7.1% in Indiana, in which children make up the largest proportion of total tests performed (18.1%) to 28.4% in Iowa, where children make up the smallest proportion of tests (6.0%), the AAP and CHA said.

[email protected]

Younger adolescents who underwent metabolic and bariatric surgery had outcomes similar to those of older adolescents undergoing the same procedure, according to recent research in Pediatrics.

Five years after metabolic and bariatric surgery (MBS), adolescents between ages 13 and 15 years had similar outcomes with regard to reduction in body mass index percentage, hypertension and dyslipidemia, and improved quality of life, compared with adolescents between ages 16 and 19 years, according to Sarah B. Ogle, DO, MS, of Children’s Hospital Colorado at the University of Colorado at Denver, Aurora, and colleagues.

“These results appear promising for the treatment of severe obesity in young patients,” Dr. Ogle and colleagues wrote, “however, further controlled studies are needed to fully evaluate the timing of surgery and extended long-term durability.”

The researchers analyzed the outcomes of adolescents enrolled in the Teen–Longitudinal Assessment of Bariatric Surgery who were aged 19 years or younger and underwent MBS between March 2007 and December 2011 at five U.S. centers. In the group of younger adolescents (66 participants), the mean age at surgery was 15.1 years, while the group of older adolescents (162 participants) had a mean age of 17.7 years at the time of surgery. Both groups consisted mostly of White (71.6%-72.7%) girls (72.7%-75.9%) who were morbidly obese (mean BMI, 52.4-53.1 kg/m²). With regard to baseline comorbidities, about three-quarters of participants in the younger (72.4%) and older (77.0%) adolescent groups had dyslipidemia. More than one-quarter of younger adolescents had hypertension (27.3%) compared with more than one-third of older adolescents (37.1%). The prevalence of type 2 diabetes was 10.6% in the younger adolescent group and 13.6% among older adolescents.

At 5-year follow-up, there was a similar BMI reduction maintained from baseline in the younger adolescent group (–22.2%; 95% confidence interval, –26.2% to –18.2%) and the older adolescent group (–24.6%; 95% CI, –27.7% to –22.5%; P = .59). There was a similar number of participants who had remission of dyslipidemia at 5 years in the younger adolescent group (61%; 95% CI, 46.3%-81.1%) and older adolescent group (58%; 95% CI, 48.0%-68.9%; P = .74). In participants with hypertension, 77% of younger adolescents (95% CI, 57.1%-100.0%) and 67% of older adolescents (95% CI, 54.5%-81.5%) achieved remission at 5 years after MBS, which showed no significant differences after adjustment (P = .84). For participants with type 2 diabetes at baseline, 83% of younger adolescents (6 participants) and 87% of older adolescents (15 participants) experienced remission by 5 years after surgery. Participants in both younger and older adolescent groups had similar quality of life scores at 5 years after surgery. When analyzing nutritional abnormalities, the researchers found younger adolescents in the group were less at risk for elevated transferrin levels (prevalence ratio, 0.52; P = .048) as well as less likely to have low vitamin D levels (prevalence ratio, 0.8; P = .034).
 

Pediatricians still concerned about safety

In an interview, Kelly A. Curran, MD, MA, assistant professor of pediatrics at University of Oklahoma Children’s Hospital in Oklahoma City, said that the findings by Dr. Ogle and colleagues add to a “growing body of literature about the importance of bariatric surgery for both younger and older adolescents.

“While many often see bariatric surgery as a ‘last resort,’ this study shows good outcomes in resolving obesity-related health conditions in both young and older teens over time – and something that should be considered more frequently than it is currently being used,” she said.

Guidelines from the American Society for Metabolic and Bariatric Surgery removed a restriction for younger age before a patient undergoes MBS, and a policy statement from the American Academy of Pediatrics encouraged increased use and access to MBS for younger adolescents. However, Dr. Curran noted that many pediatricians are still concerned about performing MBS on younger adolescents.

“Despite growing evidence of safety, I think many pediatricians worry about the potential for unintended consequences and potential impact on adolescent development or for lifelong micronutrition deficiencies – especially as there are no longitudinal studies over a lifetime,” she said.

“[W]ith the growing obesity epidemic and the long-term consequences of obesity on health and quality of life – the potential to help impact adolescents’ lives – for now and for the future – is impressive,” Dr. Curran said, acknowledging the ethical challenges involved with performing MBS on a patient who may be too young to understand the full risks and benefits of surgery.

“There are always inherent ethical challenges in providing surgery for patients too young to understand – we are asking parents to act in their child’s best interests, which may be murky to elucidate,” she explained. “While there is [a] growing body of literature around the safety and efficacy in bariatric surgery for children and adolescents, there are still many unanswered questions that remain – especially for parents. Parents can feel trapped in between these two choices – have children undergo surgery or stick with potentially less effective medical management.”

The limitations of the study include its observational nature, small sample size of some comorbidities, and a lack of diversity among participants, most of whom were White and female. In addition, “long-term studies examining the impact of bariatric surgery during adolescence would be important to give more perspective and guidance on the risks and benefits for teens,” Dr. Curran said.

The study was funded by the National Institutes of Health and grants from the National Institute of Diabetes and Digestive and Kidney Diseases as well as grants from Cincinnati Children’s Hospital Medical Center, Nationwide Children’s Hospital, Texas Children’s Hospital and Baylor College of Medicine, University of Pittsburgh, and the University of Alabama at Birmingham. The authors and Dr. Curran reported no conflicts of interest.
 

Younger adolescents who underwent metabolic and bariatric surgery had outcomes similar to those of older adolescents undergoing the same procedure, according to recent research in Pediatrics.

Five years after metabolic and bariatric surgery (MBS), adolescents between ages 13 and 15 years had similar outcomes with regard to reduction in body mass index percentage, hypertension and dyslipidemia, and improved quality of life, compared with adolescents between ages 16 and 19 years, according to Sarah B. Ogle, DO, MS, of Children’s Hospital Colorado at the University of Colorado at Denver, Aurora, and colleagues.

“These results appear promising for the treatment of severe obesity in young patients,” Dr. Ogle and colleagues wrote, “however, further controlled studies are needed to fully evaluate the timing of surgery and extended long-term durability.”

The researchers analyzed the outcomes of adolescents enrolled in the Teen–Longitudinal Assessment of Bariatric Surgery who were aged 19 years or younger and underwent MBS between March 2007 and December 2011 at five U.S. centers. In the group of younger adolescents (66 participants), the mean age at surgery was 15.1 years, while the group of older adolescents (162 participants) had a mean age of 17.7 years at the time of surgery. Both groups consisted mostly of White (71.6%-72.7%) girls (72.7%-75.9%) who were morbidly obese (mean BMI, 52.4-53.1 kg/m²). With regard to baseline comorbidities, about three-quarters of participants in the younger (72.4%) and older (77.0%) adolescent groups had dyslipidemia. More than one-quarter of younger adolescents had hypertension (27.3%) compared with more than one-third of older adolescents (37.1%). The prevalence of type 2 diabetes was 10.6% in the younger adolescent group and 13.6% among older adolescents.

At 5-year follow-up, there was a similar BMI reduction maintained from baseline in the younger adolescent group (–22.2%; 95% confidence interval, –26.2% to –18.2%) and the older adolescent group (–24.6%; 95% CI, –27.7% to –22.5%; P = .59). There was a similar number of participants who had remission of dyslipidemia at 5 years in the younger adolescent group (61%; 95% CI, 46.3%-81.1%) and older adolescent group (58%; 95% CI, 48.0%-68.9%; P = .74). In participants with hypertension, 77% of younger adolescents (95% CI, 57.1%-100.0%) and 67% of older adolescents (95% CI, 54.5%-81.5%) achieved remission at 5 years after MBS, which showed no significant differences after adjustment (P = .84). For participants with type 2 diabetes at baseline, 83% of younger adolescents (6 participants) and 87% of older adolescents (15 participants) experienced remission by 5 years after surgery. Participants in both younger and older adolescent groups had similar quality of life scores at 5 years after surgery. When analyzing nutritional abnormalities, the researchers found younger adolescents in the group were less at risk for elevated transferrin levels (prevalence ratio, 0.52; P = .048) as well as less likely to have low vitamin D levels (prevalence ratio, 0.8; P = .034).
 

Pediatricians still concerned about safety

In an interview, Kelly A. Curran, MD, MA, assistant professor of pediatrics at University of Oklahoma Children’s Hospital in Oklahoma City, said that the findings by Dr. Ogle and colleagues add to a “growing body of literature about the importance of bariatric surgery for both younger and older adolescents.

“While many often see bariatric surgery as a ‘last resort,’ this study shows good outcomes in resolving obesity-related health conditions in both young and older teens over time – and something that should be considered more frequently than it is currently being used,” she said.

Guidelines from the American Society for Metabolic and Bariatric Surgery removed a restriction for younger age before a patient undergoes MBS, and a policy statement from the American Academy of Pediatrics encouraged increased use and access to MBS for younger adolescents. However, Dr. Curran noted that many pediatricians are still concerned about performing MBS on younger adolescents.

“Despite growing evidence of safety, I think many pediatricians worry about the potential for unintended consequences and potential impact on adolescent development or for lifelong micronutrition deficiencies – especially as there are no longitudinal studies over a lifetime,” she said.

“[W]ith the growing obesity epidemic and the long-term consequences of obesity on health and quality of life – the potential to help impact adolescents’ lives – for now and for the future – is impressive,” Dr. Curran said, acknowledging the ethical challenges involved with performing MBS on a patient who may be too young to understand the full risks and benefits of surgery.

“There are always inherent ethical challenges in providing surgery for patients too young to understand – we are asking parents to act in their child’s best interests, which may be murky to elucidate,” she explained. “While there is [a] growing body of literature around the safety and efficacy in bariatric surgery for children and adolescents, there are still many unanswered questions that remain – especially for parents. Parents can feel trapped in between these two choices – have children undergo surgery or stick with potentially less effective medical management.”

The limitations of the study include its observational nature, small sample size of some comorbidities, and a lack of diversity among participants, most of whom were White and female. In addition, “long-term studies examining the impact of bariatric surgery during adolescence would be important to give more perspective and guidance on the risks and benefits for teens,” Dr. Curran said.

The study was funded by the National Institutes of Health and grants from the National Institute of Diabetes and Digestive and Kidney Diseases as well as grants from Cincinnati Children’s Hospital Medical Center, Nationwide Children’s Hospital, Texas Children’s Hospital and Baylor College of Medicine, University of Pittsburgh, and the University of Alabama at Birmingham. The authors and Dr. Curran reported no conflicts of interest.
 

Younger adolescents who underwent metabolic and bariatric surgery had outcomes similar to those of older adolescents undergoing the same procedure, according to recent research in Pediatrics.

Five years after metabolic and bariatric surgery (MBS), adolescents between ages 13 and 15 years had similar outcomes with regard to reduction in body mass index percentage, hypertension and dyslipidemia, and improved quality of life, compared with adolescents between ages 16 and 19 years, according to Sarah B. Ogle, DO, MS, of Children’s Hospital Colorado at the University of Colorado at Denver, Aurora, and colleagues.

“These results appear promising for the treatment of severe obesity in young patients,” Dr. Ogle and colleagues wrote, “however, further controlled studies are needed to fully evaluate the timing of surgery and extended long-term durability.”

The researchers analyzed the outcomes of adolescents enrolled in the Teen–Longitudinal Assessment of Bariatric Surgery who were aged 19 years or younger and underwent MBS between March 2007 and December 2011 at five U.S. centers. In the group of younger adolescents (66 participants), the mean age at surgery was 15.1 years, while the group of older adolescents (162 participants) had a mean age of 17.7 years at the time of surgery. Both groups consisted mostly of White (71.6%-72.7%) girls (72.7%-75.9%) who were morbidly obese (mean BMI, 52.4-53.1 kg/m²). With regard to baseline comorbidities, about three-quarters of participants in the younger (72.4%) and older (77.0%) adolescent groups had dyslipidemia. More than one-quarter of younger adolescents had hypertension (27.3%) compared with more than one-third of older adolescents (37.1%). The prevalence of type 2 diabetes was 10.6% in the younger adolescent group and 13.6% among older adolescents.

At 5-year follow-up, there was a similar BMI reduction maintained from baseline in the younger adolescent group (–22.2%; 95% confidence interval, –26.2% to –18.2%) and the older adolescent group (–24.6%; 95% CI, –27.7% to –22.5%; P = .59). There was a similar number of participants who had remission of dyslipidemia at 5 years in the younger adolescent group (61%; 95% CI, 46.3%-81.1%) and older adolescent group (58%; 95% CI, 48.0%-68.9%; P = .74). In participants with hypertension, 77% of younger adolescents (95% CI, 57.1%-100.0%) and 67% of older adolescents (95% CI, 54.5%-81.5%) achieved remission at 5 years after MBS, which showed no significant differences after adjustment (P = .84). For participants with type 2 diabetes at baseline, 83% of younger adolescents (6 participants) and 87% of older adolescents (15 participants) experienced remission by 5 years after surgery. Participants in both younger and older adolescent groups had similar quality of life scores at 5 years after surgery. When analyzing nutritional abnormalities, the researchers found younger adolescents in the group were less at risk for elevated transferrin levels (prevalence ratio, 0.52; P = .048) as well as less likely to have low vitamin D levels (prevalence ratio, 0.8; P = .034).
 

Pediatricians still concerned about safety

In an interview, Kelly A. Curran, MD, MA, assistant professor of pediatrics at University of Oklahoma Children’s Hospital in Oklahoma City, said that the findings by Dr. Ogle and colleagues add to a “growing body of literature about the importance of bariatric surgery for both younger and older adolescents.

“While many often see bariatric surgery as a ‘last resort,’ this study shows good outcomes in resolving obesity-related health conditions in both young and older teens over time – and something that should be considered more frequently than it is currently being used,” she said.

Guidelines from the American Society for Metabolic and Bariatric Surgery removed a restriction for younger age before a patient undergoes MBS, and a policy statement from the American Academy of Pediatrics encouraged increased use and access to MBS for younger adolescents. However, Dr. Curran noted that many pediatricians are still concerned about performing MBS on younger adolescents.

“Despite growing evidence of safety, I think many pediatricians worry about the potential for unintended consequences and potential impact on adolescent development or for lifelong micronutrition deficiencies – especially as there are no longitudinal studies over a lifetime,” she said.

“[W]ith the growing obesity epidemic and the long-term consequences of obesity on health and quality of life – the potential to help impact adolescents’ lives – for now and for the future – is impressive,” Dr. Curran said, acknowledging the ethical challenges involved with performing MBS on a patient who may be too young to understand the full risks and benefits of surgery.

“There are always inherent ethical challenges in providing surgery for patients too young to understand – we are asking parents to act in their child’s best interests, which may be murky to elucidate,” she explained. “While there is [a] growing body of literature around the safety and efficacy in bariatric surgery for children and adolescents, there are still many unanswered questions that remain – especially for parents. Parents can feel trapped in between these two choices – have children undergo surgery or stick with potentially less effective medical management.”

The limitations of the study include its observational nature, small sample size of some comorbidities, and a lack of diversity among participants, most of whom were White and female. In addition, “long-term studies examining the impact of bariatric surgery during adolescence would be important to give more perspective and guidance on the risks and benefits for teens,” Dr. Curran said.

The study was funded by the National Institutes of Health and grants from the National Institute of Diabetes and Digestive and Kidney Diseases as well as grants from Cincinnati Children’s Hospital Medical Center, Nationwide Children’s Hospital, Texas Children’s Hospital and Baylor College of Medicine, University of Pittsburgh, and the University of Alabama at Birmingham. The authors and Dr. Curran reported no conflicts of interest.
 

The Royal Swedish Academy of Sciences and the Crafoord Foundation in Lund has awarded Daniel Kastner, MD, PhD, its 2021 Crafoord Prize in Polyarthritis, “for establishing the concept of autoinflammatory diseases.” The prize, named after the donor Holger Crafoord because of his bout with severe rheumatoid arthritis toward the end of his life, is for 6 million Swedish kronor (approximately USD $700,000).

Dr. Kastner, scientific director at the U.S. National Human Genome Research Institute’s division of intramural research, received the award for identifying the mechanisms responsible for familial Mediterranean fever, tumor necrosis factor receptor–associated periodic syndrome, and other diagnoses within the group of autoinflammatory diseases.

“Dan Kastner is often called the father of autoinflammatory diseases, a title that he thoroughly deserves. His discoveries have taught us a great deal about the immune system and its functions, contributing to effective treatments that reduce the symptoms of diseases from which patients previously suffered enormously, sometimes leading to premature death,” Olle Kämpe, chair of the prize committee, said in a press announcement.

While the Crafoord Prize normally is awarded on a 3-year rotating basis for achievements in mathematics and astronomy, geosciences, and biosciences, the prize in polyarthritis is “only awarded when there has been scientific progress that motivates a prize,” according to the press release.

[email protected]

The Royal Swedish Academy of Sciences and the Crafoord Foundation in Lund has awarded Daniel Kastner, MD, PhD, its 2021 Crafoord Prize in Polyarthritis, “for establishing the concept of autoinflammatory diseases.” The prize, named after the donor Holger Crafoord because of his bout with severe rheumatoid arthritis toward the end of his life, is for 6 million Swedish kronor (approximately USD $700,000).

Dr. Kastner, scientific director at the U.S. National Human Genome Research Institute’s division of intramural research, received the award for identifying the mechanisms responsible for familial Mediterranean fever, tumor necrosis factor receptor–associated periodic syndrome, and other diagnoses within the group of autoinflammatory diseases.

“Dan Kastner is often called the father of autoinflammatory diseases, a title that he thoroughly deserves. His discoveries have taught us a great deal about the immune system and its functions, contributing to effective treatments that reduce the symptoms of diseases from which patients previously suffered enormously, sometimes leading to premature death,” Olle Kämpe, chair of the prize committee, said in a press announcement.

While the Crafoord Prize normally is awarded on a 3-year rotating basis for achievements in mathematics and astronomy, geosciences, and biosciences, the prize in polyarthritis is “only awarded when there has been scientific progress that motivates a prize,” according to the press release.

[email protected]

The Royal Swedish Academy of Sciences and the Crafoord Foundation in Lund has awarded Daniel Kastner, MD, PhD, its 2021 Crafoord Prize in Polyarthritis, “for establishing the concept of autoinflammatory diseases.” The prize, named after the donor Holger Crafoord because of his bout with severe rheumatoid arthritis toward the end of his life, is for 6 million Swedish kronor (approximately USD $700,000).

Dr. Kastner, scientific director at the U.S. National Human Genome Research Institute’s division of intramural research, received the award for identifying the mechanisms responsible for familial Mediterranean fever, tumor necrosis factor receptor–associated periodic syndrome, and other diagnoses within the group of autoinflammatory diseases.

“Dan Kastner is often called the father of autoinflammatory diseases, a title that he thoroughly deserves. His discoveries have taught us a great deal about the immune system and its functions, contributing to effective treatments that reduce the symptoms of diseases from which patients previously suffered enormously, sometimes leading to premature death,” Olle Kämpe, chair of the prize committee, said in a press announcement.

While the Crafoord Prize normally is awarded on a 3-year rotating basis for achievements in mathematics and astronomy, geosciences, and biosciences, the prize in polyarthritis is “only awarded when there has been scientific progress that motivates a prize,” according to the press release.

[email protected]

Oral antibiotic treatment for 7-10 days works for most feverish children with uncomplicated urinary tract infection (UTI), reported Tej K. Mattoo, MD, of Wayne State University, Detroit, and associates.

A good clinical assessment supported by laboratory results using a clean urine specimen is crucial to accurately diagnosing UTI in children, Dr. Mattoo and colleagues reported in a state-of-the-art review article in Pediatrics.

The authors set out to summarize the current literature on UTI in children with the goal of guiding clinical management. They provide a thorough summary of the research on a wide range of issues, including pathogenesis of acute pyelonephritis and renal scarring, risk factors for UTI and renal scarring, diagnosis and common errors in diagnosis, complications of UTI and post-UTI renal imaging, antibiotics, antimicrobial prophylaxis, surgical interventions, and prevention of recurrent UTIs.
 

What key steps make all the difference?

To help guide practicing physicians through this wealth of information, Dr. Mattoo noted in an interview that, although the review article offers “many takeaway messages,” there are several issues of crucial importance. Notably, urine collection in young children who are not yet toilet trained can present considerable challenges in achieving an accurate assessment. A contaminated urine specimen leads to unnecessary antibiotic treatment, and in some cases unwarranted hospitalization, intravenous lines, renal imaging, and follow-up investigations, Dr. Mattoo said.

Ureteral catheterization or suprapubic bladder aspiration are the preferred methods of specimen collection, especially in cases where specimens collected with a perineal bag are dipstick positive, the authors explained. Midstream collection (known as the Quick-Wee method) can also be used following stimulation of the suprapubic area with cold fluid-soaked gauze.

Also of considerable importance is distinguishing bladder infections from kidney infections whenever possible, Dr. Mattoo noted. The antibiotic treatment, complications, and follow-up plans can be different for each, he cautioned. The authors have provided a helpful table within the article to help make this differentiation.
 

Timing is crucial

Prescribing treatment with an antibiotic within 48 hours of fever onset is essential for the prevention of renal scarring, Dr. Mattoo advised. The key is to treat with the goal of avoiding long-term complications. Although there are some exceptions, most cases of UTI can be treated with oral antibiotics and do not require hospitalization.

Some children with first UTI need additional testing, such as renal imaging, to ensure that there are no underlying risk factors for UTI. These children, in particular, can be at an increased risk of recurrent UTI and renal scarring, Dr. Mattoo explained.

Antibiotic resistance is a major emerging problem in patients with UTI at all ages and we should use antibiotics only in patients who truly have a UTI that requires such treatment, he urged.

In an interview, Timothy Joos, MD, a Seattle internist and pediatrician in private practice, noted: “In the words of the British novelist Tom Holt, ‘There are few moments of clarity more profound than those that follow the emptying of an overcharged bladder. The world slows down, the focus sharpens, the brain comes back online. Huge nebulous difficulties prove on close calm examination to be merely cloud giants.’ Thank you to Drs. Mattoo, Nelson, and Shaikh for providing this clarity of current UTI diagnosis and management,” Dr. Joos said.

“It bears repeating that because of the rare prevalence of grade 4 to 5 vesicoureteral reflux in children with their first UTI, current guidelines recommend that a voiding cystourethrogram can be reserved for children with an abnormal ultrasound, atypical pathogen, complicated clinical course, or known renal scarring,” added Dr. Joos.

The authors had no relevant disclosures. Dr. Joos is a member of the Pediatric News editorial advisory board but had no other disclosures.

Oral antibiotic treatment for 7-10 days works for most feverish children with uncomplicated urinary tract infection (UTI), reported Tej K. Mattoo, MD, of Wayne State University, Detroit, and associates.

A good clinical assessment supported by laboratory results using a clean urine specimen is crucial to accurately diagnosing UTI in children, Dr. Mattoo and colleagues reported in a state-of-the-art review article in Pediatrics.

The authors set out to summarize the current literature on UTI in children with the goal of guiding clinical management. They provide a thorough summary of the research on a wide range of issues, including pathogenesis of acute pyelonephritis and renal scarring, risk factors for UTI and renal scarring, diagnosis and common errors in diagnosis, complications of UTI and post-UTI renal imaging, antibiotics, antimicrobial prophylaxis, surgical interventions, and prevention of recurrent UTIs.
 

What key steps make all the difference?

To help guide practicing physicians through this wealth of information, Dr. Mattoo noted in an interview that, although the review article offers “many takeaway messages,” there are several issues of crucial importance. Notably, urine collection in young children who are not yet toilet trained can present considerable challenges in achieving an accurate assessment. A contaminated urine specimen leads to unnecessary antibiotic treatment, and in some cases unwarranted hospitalization, intravenous lines, renal imaging, and follow-up investigations, Dr. Mattoo said.

Ureteral catheterization or suprapubic bladder aspiration are the preferred methods of specimen collection, especially in cases where specimens collected with a perineal bag are dipstick positive, the authors explained. Midstream collection (known as the Quick-Wee method) can also be used following stimulation of the suprapubic area with cold fluid-soaked gauze.

Also of considerable importance is distinguishing bladder infections from kidney infections whenever possible, Dr. Mattoo noted. The antibiotic treatment, complications, and follow-up plans can be different for each, he cautioned. The authors have provided a helpful table within the article to help make this differentiation.
 

Timing is crucial

Prescribing treatment with an antibiotic within 48 hours of fever onset is essential for the prevention of renal scarring, Dr. Mattoo advised. The key is to treat with the goal of avoiding long-term complications. Although there are some exceptions, most cases of UTI can be treated with oral antibiotics and do not require hospitalization.

Some children with first UTI need additional testing, such as renal imaging, to ensure that there are no underlying risk factors for UTI. These children, in particular, can be at an increased risk of recurrent UTI and renal scarring, Dr. Mattoo explained.

Antibiotic resistance is a major emerging problem in patients with UTI at all ages and we should use antibiotics only in patients who truly have a UTI that requires such treatment, he urged.

In an interview, Timothy Joos, MD, a Seattle internist and pediatrician in private practice, noted: “In the words of the British novelist Tom Holt, ‘There are few moments of clarity more profound than those that follow the emptying of an overcharged bladder. The world slows down, the focus sharpens, the brain comes back online. Huge nebulous difficulties prove on close calm examination to be merely cloud giants.’ Thank you to Drs. Mattoo, Nelson, and Shaikh for providing this clarity of current UTI diagnosis and management,” Dr. Joos said.

“It bears repeating that because of the rare prevalence of grade 4 to 5 vesicoureteral reflux in children with their first UTI, current guidelines recommend that a voiding cystourethrogram can be reserved for children with an abnormal ultrasound, atypical pathogen, complicated clinical course, or known renal scarring,” added Dr. Joos.

The authors had no relevant disclosures. Dr. Joos is a member of the Pediatric News editorial advisory board but had no other disclosures.

Oral antibiotic treatment for 7-10 days works for most feverish children with uncomplicated urinary tract infection (UTI), reported Tej K. Mattoo, MD, of Wayne State University, Detroit, and associates.

A good clinical assessment supported by laboratory results using a clean urine specimen is crucial to accurately diagnosing UTI in children, Dr. Mattoo and colleagues reported in a state-of-the-art review article in Pediatrics.

The authors set out to summarize the current literature on UTI in children with the goal of guiding clinical management. They provide a thorough summary of the research on a wide range of issues, including pathogenesis of acute pyelonephritis and renal scarring, risk factors for UTI and renal scarring, diagnosis and common errors in diagnosis, complications of UTI and post-UTI renal imaging, antibiotics, antimicrobial prophylaxis, surgical interventions, and prevention of recurrent UTIs.
 

What key steps make all the difference?

To help guide practicing physicians through this wealth of information, Dr. Mattoo noted in an interview that, although the review article offers “many takeaway messages,” there are several issues of crucial importance. Notably, urine collection in young children who are not yet toilet trained can present considerable challenges in achieving an accurate assessment. A contaminated urine specimen leads to unnecessary antibiotic treatment, and in some cases unwarranted hospitalization, intravenous lines, renal imaging, and follow-up investigations, Dr. Mattoo said.

Ureteral catheterization or suprapubic bladder aspiration are the preferred methods of specimen collection, especially in cases where specimens collected with a perineal bag are dipstick positive, the authors explained. Midstream collection (known as the Quick-Wee method) can also be used following stimulation of the suprapubic area with cold fluid-soaked gauze.

Also of considerable importance is distinguishing bladder infections from kidney infections whenever possible, Dr. Mattoo noted. The antibiotic treatment, complications, and follow-up plans can be different for each, he cautioned. The authors have provided a helpful table within the article to help make this differentiation.
 

Timing is crucial

Prescribing treatment with an antibiotic within 48 hours of fever onset is essential for the prevention of renal scarring, Dr. Mattoo advised. The key is to treat with the goal of avoiding long-term complications. Although there are some exceptions, most cases of UTI can be treated with oral antibiotics and do not require hospitalization.

Some children with first UTI need additional testing, such as renal imaging, to ensure that there are no underlying risk factors for UTI. These children, in particular, can be at an increased risk of recurrent UTI and renal scarring, Dr. Mattoo explained.

Antibiotic resistance is a major emerging problem in patients with UTI at all ages and we should use antibiotics only in patients who truly have a UTI that requires such treatment, he urged.

In an interview, Timothy Joos, MD, a Seattle internist and pediatrician in private practice, noted: “In the words of the British novelist Tom Holt, ‘There are few moments of clarity more profound than those that follow the emptying of an overcharged bladder. The world slows down, the focus sharpens, the brain comes back online. Huge nebulous difficulties prove on close calm examination to be merely cloud giants.’ Thank you to Drs. Mattoo, Nelson, and Shaikh for providing this clarity of current UTI diagnosis and management,” Dr. Joos said.

“It bears repeating that because of the rare prevalence of grade 4 to 5 vesicoureteral reflux in children with their first UTI, current guidelines recommend that a voiding cystourethrogram can be reserved for children with an abnormal ultrasound, atypical pathogen, complicated clinical course, or known renal scarring,” added Dr. Joos.

The authors had no relevant disclosures. Dr. Joos is a member of the Pediatric News editorial advisory board but had no other disclosures.

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

A bag of Doritos, that’s all Princess wanted.

StHelena/Getty Images

Her mom calls her Princess, but her real name is Lindsey. She’s 17 and lives with her mom, Sandra, a nurse, outside Atlanta. On May 17, 2020, a Sunday, Lindsey decided she didn’t want breakfast; she wanted Doritos. So she left home and walked to Family Dollar, taking her pants off on the way, while her mom followed on foot, talking to the police on her phone as they went.

Lindsey has autism. It can be hard for her to communicate and navigate social situations. She thrives on routine and gets special help at school. Or got help, before the coronavirus pandemic closed schools and forced tens of millions of children to stay home. Sandra said that’s when their living hell started.

“It’s like her brain was wired,” she said. “She’d just put on her jacket, and she’s out the door. And I’m chasing her.”

On May 17, Sandra chased her all the way to Family Dollar. Hours later, Lindsey was in jail, charged with assaulting her mom. (KHN and NPR are not using the family’s last name.)

Lindsey is 1 of almost 3 million children in the United States who have a serious emotional or behavioral health condition. When the pandemic forced schools and doctors’ offices to close last spring, it also cut children off from the trained teachers and therapists who understand their needs.

As a result, many, like Lindsey, spiraled into EDs and even police custody. Federal data shows a nationwide surge of children in mental health crisis during the pandemic – a surge that’s further taxing an already overstretched safety net.
 

‘Take her’

Even after schools closed, Lindsey continued to wake up early, get dressed and wait for the bus. When she realized it had stopped coming, Sandra said, her daughter just started walking out of the house, wandering, a few times a week.

In those situations, Sandra did what many families in crisis report they’ve had to do since the pandemic began: Race through the short list of places she could call for help.

First, her state’s mental health crisis hotline. But they often put Sandra on hold.

“This is ridiculous,” she said of the wait. “It’s supposed to be a crisis team. But I’m on hold for 40, 50 minutes. And by the time you get on the phone, [the crisis] is done!”

Then there’s the local hospital’s ED, but Sandra said she had taken Lindsey there for previous crises and been told there isn’t much they can do.

That’s why, on May 17, when Lindsey walked to Family Dollar in just a red T-shirt and underwear to get that bag of Doritos, Sandra called the last option on her list: the police.

Sandra arrived at the store before the police and paid for the chips. According to Sandra and police records, when an officer approached, Lindsey grew agitated and hit her mom on the back, hard.

Sandra said she explained to the officer: “‘She’s autistic. You know, I’m okay. I’m a nurse. I just need to take her home and give her her medication.’ ”

Lindsey takes a mood stabilizer, but because she left home before breakfast, she hadn’t taken it that morning. The officer asked if Sandra wanted to take her to the nearest hospital.

The hospital wouldn’t be able to help Lindsey, Sandra said. It hadn’t before. “They already told me: ‘Ma’am, there’s nothing we can do.’ They just check her labs, it’s fine, and they ship her back home. There’s nothing [the hospital] can do,” she recalled telling the officer.

Sandra asked if the police could drive her daughter home so the teen could take her medication, but the officer said no, they couldn’t. The only other thing they could do, the officer said, was take Lindsey to jail for hitting her mom.

“I’ve tried everything,” Sandra said, exasperated. She paced the parking lot, feeling hopeless, sad and out of options. Finally, in tears, she told the officers: “Take her.”

Lindsey does not like to be touched and fought back when authorities tried to handcuff her. Several officers wrestled her to the ground. At that point, Sandra protested and said an officer threatened to arrest her, too, if she didn’t back away. Lindsey was taken to jail, where she spent much of the night until Sandra was able to post bail.

Clayton County Solicitor-General Charles Brooks denied that Sandra was threatened with arrest and said that, while Lindsey’s case is still pending, his office “is working to ensure that the resolution in this matter involves a plan for medication compliance and not punitive action.”

Sandra isn’t alone in her experience. Multiple families interviewed for this story reported similar experiences of calling in the police when a child was in crisis because caretakers didn’t feel they had any other option.
 

‘The whole system is really grinding to a halt’

Roughly 6% of U.S. children ages 6-17 years are living with serious emotional or behavioral difficulties, including children with autism, severe anxiety, depression and trauma-related mental health conditions.

Many of these children depend on schools for access to vital therapies. When schools and doctors’ offices stopped providing in-person services last spring, kids were untethered from the people and supports they rely on.

“The lack of in-person services is really detrimental,” said Susan Duffy, MD,a pediatrician and professor of emergency medicine at Brown University, Providence, R.I.

Marjorie, a mother in Florida, said her 15-year-old son has suffered during these disruptions. He has ADHD and oppositional defiant disorder, a condition marked by frequent and persistent hostility. Little things – like being asked to do schoolwork – can send him into a rage, leading to holes punched in walls, broken doors and violent threats. (The family’s last name or her son’s first name are not used to protect her son’s privacy and future prospects.)

The pandemic has shifted both school and her son’s therapy sessions online. But Marjorie said virtual therapy isn’t working because her son doesn’t focus well during sessions and tries to watch television instead. Lately, she has simply been canceling them.

“I was paying for appointments and there was no therapeutic value,” Marjorie said.

The issues cut across socioeconomic lines – affecting families with private insurance, like Marjorie, as well as those who receive coverage through Medicaid, a federal-state program that provides health insurance to low-income people and those with disabilities.

In the first few months of the pandemic, between March and May, children on Medicaid received 44% fewer outpatient mental health services – including therapy and in-home support – compared with the same time period in 2019, according to the Centers for Medicare & Medicaid Services. That’s even after accounting for increased telehealth appointments.

And while the nation’s EDs have seen a decline in overall visits, there was a relative increase in mental health visits for kids in 2020, compared with 2019.

The Centers for Disease Control and Prevention found that, from April to October 2020, hospitals across the United States saw a 24% increase in the proportion of mental health emergency visits for children aged 5-11 years, and a 31% increase for children aged 12-17.

“Proportionally, the number of mental health visits is far more significant than it has been in the past,” said Dr. Duffy. “Not only are we seeing more children, more children are being admitted” to inpatient care.

That’s because there are fewer outpatient services now available to children, she said, and because the conditions of the children showing up at EDs “are more serious.”

This crisis is not only making life harder for these kids and their families, but it’s also stressing the entire health care system.

Child and adolescent psychiatrists working in hospitals around the country said children are increasingly “boarding” in EDs for days, waiting for inpatient admission to a regular hospital or psychiatric hospital.

Before the pandemic, there was already a shortage of inpatient psychiatric beds for children, said Christopher Bellonci, MD, a child psychiatrist at Judge Baker Children’s Center in Boston. That shortage has only gotten worse as hospitals cut capacity to allow for more physical distancing within psychiatric units.

“The whole system is really grinding to a halt at a time when we have unprecedented need,” Dr. Bellonci said.
 

‘A signal that the rest of your system doesn’t work’

Psychiatrists on the front lines share the frustrations of parents struggling to find help for their children.

Part of the problem is there have never been enough psychiatrists and therapists trained to work with children, intervening in the early stages of their illness, said Jennifer Havens, MD, a child psychiatrist at New York University.

“Tons of people showing up in emergency rooms in bad shape is a signal that the rest of your system doesn’t work,” she said.

Too often, Dr. Havens said, services aren’t available until children are older – and in crisis. “Often for people who don’t have access to services, we wait until they’re too big to be managed.”

While the pandemic has made life harder for Marjorie and her son in Florida, she said it has always been difficult to find the support and care he needs. Last fall, he needed a psychiatric evaluation, but the nearest specialist who would accept her commercial insurance was 100 miles away, in Alabama.

“Even when you have the money or you have the insurance, it is still a travesty,” Marjorie said. “You cannot get help for these kids.”

Parents are frustrated, and so are psychiatrists on the front lines. C.J. Glawe, MD, who leads the psychiatric crisis department at Nationwide Children’s Hospital in Columbus, Ohio, said that once a child is stabilized after a crisis it can be hard to explain to parents that they may not be able to find follow-up care anywhere near their home.

“Especially when I can clearly tell you I know exactly what you need, I just can’t give it to you,” Dr. Glawe said. “It’s demoralizing.”

When states and communities fail to provide children the services they need to live at home, kids can deteriorate and even wind up in jail, like Lindsey. At that point, Dr. Glawe said, the cost and level of care required will be even higher, whether that’s hospitalization or long stays in residential treatment facilities.

That’s exactly the scenario Sandra, Lindsey’s mom, is hoping to avoid for her Princess.

“For me, as a nurse and as a provider, that will be the last thing for my daughter,” she said. “It’s like [state and local leaders] leave it to the school and the parent to deal with, and they don’t care. And that’s the problem. It’s sad because, if I’m not here...”

Her voice trailed off as tears welled.

“She didn’t ask to have autism.”

To help families like Sandra’s and Marjorie’s, advocates said, all levels of government need to invest in creating a mental health system that’s accessible to anyone who needs it.

But given that many states have seen their revenues drop because of the pandemic, there’s a concern services will instead be cut – at a time when the need has never been greater.

This story is part of a reporting partnership that includes NPR, Illinois Public Media and Kaiser Health News. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

A bag of Doritos, that’s all Princess wanted.

StHelena/Getty Images

Her mom calls her Princess, but her real name is Lindsey. She’s 17 and lives with her mom, Sandra, a nurse, outside Atlanta. On May 17, 2020, a Sunday, Lindsey decided she didn’t want breakfast; she wanted Doritos. So she left home and walked to Family Dollar, taking her pants off on the way, while her mom followed on foot, talking to the police on her phone as they went.

Lindsey has autism. It can be hard for her to communicate and navigate social situations. She thrives on routine and gets special help at school. Or got help, before the coronavirus pandemic closed schools and forced tens of millions of children to stay home. Sandra said that’s when their living hell started.

“It’s like her brain was wired,” she said. “She’d just put on her jacket, and she’s out the door. And I’m chasing her.”

On May 17, Sandra chased her all the way to Family Dollar. Hours later, Lindsey was in jail, charged with assaulting her mom. (KHN and NPR are not using the family’s last name.)

Lindsey is 1 of almost 3 million children in the United States who have a serious emotional or behavioral health condition. When the pandemic forced schools and doctors’ offices to close last spring, it also cut children off from the trained teachers and therapists who understand their needs.

As a result, many, like Lindsey, spiraled into EDs and even police custody. Federal data shows a nationwide surge of children in mental health crisis during the pandemic – a surge that’s further taxing an already overstretched safety net.
 

‘Take her’

Even after schools closed, Lindsey continued to wake up early, get dressed and wait for the bus. When she realized it had stopped coming, Sandra said, her daughter just started walking out of the house, wandering, a few times a week.

In those situations, Sandra did what many families in crisis report they’ve had to do since the pandemic began: Race through the short list of places she could call for help.

First, her state’s mental health crisis hotline. But they often put Sandra on hold.

“This is ridiculous,” she said of the wait. “It’s supposed to be a crisis team. But I’m on hold for 40, 50 minutes. And by the time you get on the phone, [the crisis] is done!”

Then there’s the local hospital’s ED, but Sandra said she had taken Lindsey there for previous crises and been told there isn’t much they can do.

That’s why, on May 17, when Lindsey walked to Family Dollar in just a red T-shirt and underwear to get that bag of Doritos, Sandra called the last option on her list: the police.

Sandra arrived at the store before the police and paid for the chips. According to Sandra and police records, when an officer approached, Lindsey grew agitated and hit her mom on the back, hard.

Sandra said she explained to the officer: “‘She’s autistic. You know, I’m okay. I’m a nurse. I just need to take her home and give her her medication.’ ”

Lindsey takes a mood stabilizer, but because she left home before breakfast, she hadn’t taken it that morning. The officer asked if Sandra wanted to take her to the nearest hospital.

The hospital wouldn’t be able to help Lindsey, Sandra said. It hadn’t before. “They already told me: ‘Ma’am, there’s nothing we can do.’ They just check her labs, it’s fine, and they ship her back home. There’s nothing [the hospital] can do,” she recalled telling the officer.

Sandra asked if the police could drive her daughter home so the teen could take her medication, but the officer said no, they couldn’t. The only other thing they could do, the officer said, was take Lindsey to jail for hitting her mom.

“I’ve tried everything,” Sandra said, exasperated. She paced the parking lot, feeling hopeless, sad and out of options. Finally, in tears, she told the officers: “Take her.”

Lindsey does not like to be touched and fought back when authorities tried to handcuff her. Several officers wrestled her to the ground. At that point, Sandra protested and said an officer threatened to arrest her, too, if she didn’t back away. Lindsey was taken to jail, where she spent much of the night until Sandra was able to post bail.

Clayton County Solicitor-General Charles Brooks denied that Sandra was threatened with arrest and said that, while Lindsey’s case is still pending, his office “is working to ensure that the resolution in this matter involves a plan for medication compliance and not punitive action.”

Sandra isn’t alone in her experience. Multiple families interviewed for this story reported similar experiences of calling in the police when a child was in crisis because caretakers didn’t feel they had any other option.
 

‘The whole system is really grinding to a halt’

Roughly 6% of U.S. children ages 6-17 years are living with serious emotional or behavioral difficulties, including children with autism, severe anxiety, depression and trauma-related mental health conditions.

Many of these children depend on schools for access to vital therapies. When schools and doctors’ offices stopped providing in-person services last spring, kids were untethered from the people and supports they rely on.

“The lack of in-person services is really detrimental,” said Susan Duffy, MD,a pediatrician and professor of emergency medicine at Brown University, Providence, R.I.

Marjorie, a mother in Florida, said her 15-year-old son has suffered during these disruptions. He has ADHD and oppositional defiant disorder, a condition marked by frequent and persistent hostility. Little things – like being asked to do schoolwork – can send him into a rage, leading to holes punched in walls, broken doors and violent threats. (The family’s last name or her son’s first name are not used to protect her son’s privacy and future prospects.)

The pandemic has shifted both school and her son’s therapy sessions online. But Marjorie said virtual therapy isn’t working because her son doesn’t focus well during sessions and tries to watch television instead. Lately, she has simply been canceling them.

“I was paying for appointments and there was no therapeutic value,” Marjorie said.

The issues cut across socioeconomic lines – affecting families with private insurance, like Marjorie, as well as those who receive coverage through Medicaid, a federal-state program that provides health insurance to low-income people and those with disabilities.

In the first few months of the pandemic, between March and May, children on Medicaid received 44% fewer outpatient mental health services – including therapy and in-home support – compared with the same time period in 2019, according to the Centers for Medicare & Medicaid Services. That’s even after accounting for increased telehealth appointments.

And while the nation’s EDs have seen a decline in overall visits, there was a relative increase in mental health visits for kids in 2020, compared with 2019.

The Centers for Disease Control and Prevention found that, from April to October 2020, hospitals across the United States saw a 24% increase in the proportion of mental health emergency visits for children aged 5-11 years, and a 31% increase for children aged 12-17.

“Proportionally, the number of mental health visits is far more significant than it has been in the past,” said Dr. Duffy. “Not only are we seeing more children, more children are being admitted” to inpatient care.

That’s because there are fewer outpatient services now available to children, she said, and because the conditions of the children showing up at EDs “are more serious.”

This crisis is not only making life harder for these kids and their families, but it’s also stressing the entire health care system.

Child and adolescent psychiatrists working in hospitals around the country said children are increasingly “boarding” in EDs for days, waiting for inpatient admission to a regular hospital or psychiatric hospital.

Before the pandemic, there was already a shortage of inpatient psychiatric beds for children, said Christopher Bellonci, MD, a child psychiatrist at Judge Baker Children’s Center in Boston. That shortage has only gotten worse as hospitals cut capacity to allow for more physical distancing within psychiatric units.

“The whole system is really grinding to a halt at a time when we have unprecedented need,” Dr. Bellonci said.
 

‘A signal that the rest of your system doesn’t work’

Psychiatrists on the front lines share the frustrations of parents struggling to find help for their children.

Part of the problem is there have never been enough psychiatrists and therapists trained to work with children, intervening in the early stages of their illness, said Jennifer Havens, MD, a child psychiatrist at New York University.

“Tons of people showing up in emergency rooms in bad shape is a signal that the rest of your system doesn’t work,” she said.

Too often, Dr. Havens said, services aren’t available until children are older – and in crisis. “Often for people who don’t have access to services, we wait until they’re too big to be managed.”

While the pandemic has made life harder for Marjorie and her son in Florida, she said it has always been difficult to find the support and care he needs. Last fall, he needed a psychiatric evaluation, but the nearest specialist who would accept her commercial insurance was 100 miles away, in Alabama.

“Even when you have the money or you have the insurance, it is still a travesty,” Marjorie said. “You cannot get help for these kids.”

Parents are frustrated, and so are psychiatrists on the front lines. C.J. Glawe, MD, who leads the psychiatric crisis department at Nationwide Children’s Hospital in Columbus, Ohio, said that once a child is stabilized after a crisis it can be hard to explain to parents that they may not be able to find follow-up care anywhere near their home.

“Especially when I can clearly tell you I know exactly what you need, I just can’t give it to you,” Dr. Glawe said. “It’s demoralizing.”

When states and communities fail to provide children the services they need to live at home, kids can deteriorate and even wind up in jail, like Lindsey. At that point, Dr. Glawe said, the cost and level of care required will be even higher, whether that’s hospitalization or long stays in residential treatment facilities.

That’s exactly the scenario Sandra, Lindsey’s mom, is hoping to avoid for her Princess.

“For me, as a nurse and as a provider, that will be the last thing for my daughter,” she said. “It’s like [state and local leaders] leave it to the school and the parent to deal with, and they don’t care. And that’s the problem. It’s sad because, if I’m not here...”

Her voice trailed off as tears welled.

“She didn’t ask to have autism.”

To help families like Sandra’s and Marjorie’s, advocates said, all levels of government need to invest in creating a mental health system that’s accessible to anyone who needs it.

But given that many states have seen their revenues drop because of the pandemic, there’s a concern services will instead be cut – at a time when the need has never been greater.

This story is part of a reporting partnership that includes NPR, Illinois Public Media and Kaiser Health News. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

A bag of Doritos, that’s all Princess wanted.

StHelena/Getty Images

Her mom calls her Princess, but her real name is Lindsey. She’s 17 and lives with her mom, Sandra, a nurse, outside Atlanta. On May 17, 2020, a Sunday, Lindsey decided she didn’t want breakfast; she wanted Doritos. So she left home and walked to Family Dollar, taking her pants off on the way, while her mom followed on foot, talking to the police on her phone as they went.

Lindsey has autism. It can be hard for her to communicate and navigate social situations. She thrives on routine and gets special help at school. Or got help, before the coronavirus pandemic closed schools and forced tens of millions of children to stay home. Sandra said that’s when their living hell started.

“It’s like her brain was wired,” she said. “She’d just put on her jacket, and she’s out the door. And I’m chasing her.”

On May 17, Sandra chased her all the way to Family Dollar. Hours later, Lindsey was in jail, charged with assaulting her mom. (KHN and NPR are not using the family’s last name.)

Lindsey is 1 of almost 3 million children in the United States who have a serious emotional or behavioral health condition. When the pandemic forced schools and doctors’ offices to close last spring, it also cut children off from the trained teachers and therapists who understand their needs.

As a result, many, like Lindsey, spiraled into EDs and even police custody. Federal data shows a nationwide surge of children in mental health crisis during the pandemic – a surge that’s further taxing an already overstretched safety net.
 

‘Take her’

Even after schools closed, Lindsey continued to wake up early, get dressed and wait for the bus. When she realized it had stopped coming, Sandra said, her daughter just started walking out of the house, wandering, a few times a week.

In those situations, Sandra did what many families in crisis report they’ve had to do since the pandemic began: Race through the short list of places she could call for help.

First, her state’s mental health crisis hotline. But they often put Sandra on hold.

“This is ridiculous,” she said of the wait. “It’s supposed to be a crisis team. But I’m on hold for 40, 50 minutes. And by the time you get on the phone, [the crisis] is done!”

Then there’s the local hospital’s ED, but Sandra said she had taken Lindsey there for previous crises and been told there isn’t much they can do.

That’s why, on May 17, when Lindsey walked to Family Dollar in just a red T-shirt and underwear to get that bag of Doritos, Sandra called the last option on her list: the police.

Sandra arrived at the store before the police and paid for the chips. According to Sandra and police records, when an officer approached, Lindsey grew agitated and hit her mom on the back, hard.

Sandra said she explained to the officer: “‘She’s autistic. You know, I’m okay. I’m a nurse. I just need to take her home and give her her medication.’ ”

Lindsey takes a mood stabilizer, but because she left home before breakfast, she hadn’t taken it that morning. The officer asked if Sandra wanted to take her to the nearest hospital.

The hospital wouldn’t be able to help Lindsey, Sandra said. It hadn’t before. “They already told me: ‘Ma’am, there’s nothing we can do.’ They just check her labs, it’s fine, and they ship her back home. There’s nothing [the hospital] can do,” she recalled telling the officer.

Sandra asked if the police could drive her daughter home so the teen could take her medication, but the officer said no, they couldn’t. The only other thing they could do, the officer said, was take Lindsey to jail for hitting her mom.

“I’ve tried everything,” Sandra said, exasperated. She paced the parking lot, feeling hopeless, sad and out of options. Finally, in tears, she told the officers: “Take her.”

Lindsey does not like to be touched and fought back when authorities tried to handcuff her. Several officers wrestled her to the ground. At that point, Sandra protested and said an officer threatened to arrest her, too, if she didn’t back away. Lindsey was taken to jail, where she spent much of the night until Sandra was able to post bail.

Clayton County Solicitor-General Charles Brooks denied that Sandra was threatened with arrest and said that, while Lindsey’s case is still pending, his office “is working to ensure that the resolution in this matter involves a plan for medication compliance and not punitive action.”

Sandra isn’t alone in her experience. Multiple families interviewed for this story reported similar experiences of calling in the police when a child was in crisis because caretakers didn’t feel they had any other option.
 

‘The whole system is really grinding to a halt’

Roughly 6% of U.S. children ages 6-17 years are living with serious emotional or behavioral difficulties, including children with autism, severe anxiety, depression and trauma-related mental health conditions.

Many of these children depend on schools for access to vital therapies. When schools and doctors’ offices stopped providing in-person services last spring, kids were untethered from the people and supports they rely on.

“The lack of in-person services is really detrimental,” said Susan Duffy, MD,a pediatrician and professor of emergency medicine at Brown University, Providence, R.I.

Marjorie, a mother in Florida, said her 15-year-old son has suffered during these disruptions. He has ADHD and oppositional defiant disorder, a condition marked by frequent and persistent hostility. Little things – like being asked to do schoolwork – can send him into a rage, leading to holes punched in walls, broken doors and violent threats. (The family’s last name or her son’s first name are not used to protect her son’s privacy and future prospects.)

The pandemic has shifted both school and her son’s therapy sessions online. But Marjorie said virtual therapy isn’t working because her son doesn’t focus well during sessions and tries to watch television instead. Lately, she has simply been canceling them.

“I was paying for appointments and there was no therapeutic value,” Marjorie said.

The issues cut across socioeconomic lines – affecting families with private insurance, like Marjorie, as well as those who receive coverage through Medicaid, a federal-state program that provides health insurance to low-income people and those with disabilities.

In the first few months of the pandemic, between March and May, children on Medicaid received 44% fewer outpatient mental health services – including therapy and in-home support – compared with the same time period in 2019, according to the Centers for Medicare & Medicaid Services. That’s even after accounting for increased telehealth appointments.

And while the nation’s EDs have seen a decline in overall visits, there was a relative increase in mental health visits for kids in 2020, compared with 2019.

The Centers for Disease Control and Prevention found that, from April to October 2020, hospitals across the United States saw a 24% increase in the proportion of mental health emergency visits for children aged 5-11 years, and a 31% increase for children aged 12-17.

“Proportionally, the number of mental health visits is far more significant than it has been in the past,” said Dr. Duffy. “Not only are we seeing more children, more children are being admitted” to inpatient care.

That’s because there are fewer outpatient services now available to children, she said, and because the conditions of the children showing up at EDs “are more serious.”

This crisis is not only making life harder for these kids and their families, but it’s also stressing the entire health care system.

Child and adolescent psychiatrists working in hospitals around the country said children are increasingly “boarding” in EDs for days, waiting for inpatient admission to a regular hospital or psychiatric hospital.

Before the pandemic, there was already a shortage of inpatient psychiatric beds for children, said Christopher Bellonci, MD, a child psychiatrist at Judge Baker Children’s Center in Boston. That shortage has only gotten worse as hospitals cut capacity to allow for more physical distancing within psychiatric units.

“The whole system is really grinding to a halt at a time when we have unprecedented need,” Dr. Bellonci said.
 

‘A signal that the rest of your system doesn’t work’

Psychiatrists on the front lines share the frustrations of parents struggling to find help for their children.

Part of the problem is there have never been enough psychiatrists and therapists trained to work with children, intervening in the early stages of their illness, said Jennifer Havens, MD, a child psychiatrist at New York University.

“Tons of people showing up in emergency rooms in bad shape is a signal that the rest of your system doesn’t work,” she said.

Too often, Dr. Havens said, services aren’t available until children are older – and in crisis. “Often for people who don’t have access to services, we wait until they’re too big to be managed.”

While the pandemic has made life harder for Marjorie and her son in Florida, she said it has always been difficult to find the support and care he needs. Last fall, he needed a psychiatric evaluation, but the nearest specialist who would accept her commercial insurance was 100 miles away, in Alabama.

“Even when you have the money or you have the insurance, it is still a travesty,” Marjorie said. “You cannot get help for these kids.”

Parents are frustrated, and so are psychiatrists on the front lines. C.J. Glawe, MD, who leads the psychiatric crisis department at Nationwide Children’s Hospital in Columbus, Ohio, said that once a child is stabilized after a crisis it can be hard to explain to parents that they may not be able to find follow-up care anywhere near their home.

“Especially when I can clearly tell you I know exactly what you need, I just can’t give it to you,” Dr. Glawe said. “It’s demoralizing.”

When states and communities fail to provide children the services they need to live at home, kids can deteriorate and even wind up in jail, like Lindsey. At that point, Dr. Glawe said, the cost and level of care required will be even higher, whether that’s hospitalization or long stays in residential treatment facilities.

That’s exactly the scenario Sandra, Lindsey’s mom, is hoping to avoid for her Princess.

“For me, as a nurse and as a provider, that will be the last thing for my daughter,” she said. “It’s like [state and local leaders] leave it to the school and the parent to deal with, and they don’t care. And that’s the problem. It’s sad because, if I’m not here...”

Her voice trailed off as tears welled.

“She didn’t ask to have autism.”

To help families like Sandra’s and Marjorie’s, advocates said, all levels of government need to invest in creating a mental health system that’s accessible to anyone who needs it.

But given that many states have seen their revenues drop because of the pandemic, there’s a concern services will instead be cut – at a time when the need has never been greater.

This story is part of a reporting partnership that includes NPR, Illinois Public Media and Kaiser Health News. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.