MDedge Pediatrics

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

Treatment with deuruxolitinib and ritlecitinib, two investigational Janus kinase (JAK) inhibitors, resulted in substantial regrowth of scalp hair for patients with alopecia areata (AA) in separate studies reported at the annual congress of the European Academy of Dermatology and Venereology.

In the THRIVE-AA1 study, the primary endpoint of a Severity of Alopecia Tool (SALT) score of 20 or lower –which indicates that hair regrowth has occurred on at least 80% of the scalp – was achieved among patients taking deuruxolitinib, which was a significantly higher proportion than with placebo (P < .0001). Importantly, the JAK inhibitor’s effects were seen in as early as 4 weeks, and there was significant improvement in both eyelash and eyebrow hair regrowth.

In the unrelated ALLEGRO-LT study, effects from treatment with the JAK inhibitor ritlecitinib appeared to be sustained for 2 years; 69.6% of patients treated with ritlecitinib had a SALT score of 20 or lower by 24 months.

These data are “very exciting for alopecia areata because the patients selected are very severe,” observed Mahtab Samimi, MD, PhD, who cochaired the late-breaking session in which the study findings were discussed.

THRIVE-AA1 included only patients with hair loss of 50% or more. The ALLEGRO-LT study included patients with total scalp or total body hair loss (areata totalis/areata universalis) of 25%-50% at enrollment.

Moreover, “very stringent criteria” were used. SALT scores of 10 or less were evaluated in both studies, observed Dr. Samimi, professor of dermatology at the University of Tours (France).

“We can be ambitious now for our patients with alopecia areata; that’s really good news,” Dr. Samimi added.

Deuruxolitinib and the THRIVE trials

Deuruxolitinib is an oral JAK1/JAK2 inhibitor that has been tested in two similarly designed, multinational, randomized, double-blind, placebo-controlled phase 3 trials in patients with AA, THRIVE-AA1 and THRIVE-AA2.

Two doses of deuruxolitinib, 8 mg and 12 mg given twice daily, were evaluated in the trials, which altogether included just over 1,200 patients.

Results of THRIVE-AA1 have been reported by the manufacturer. Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., presented a more comprehensive review at the EADV meeting.

He reported that at 24 weeks, SALT scores of 20 or lower were achieved by 30% of adults with AA who were treated with deuruxolitinib 8 mg and by 42% of those treated with deuruxolitinib 12 mg. This primary endpoint was seen in only 1% of the placebo-treated patients.

The more stringent endpoint of having a SALT score of 10 or less, which indicates that hair regrowth has occurred over 90% of the scalp, was met by 21% of patients who received deuruxolitinib 8 mg twice a day and by 35% of those who received the 12-mg dose twice a day at 24 weeks. This endpoint was not reached by any of the placebo-treated patients.

“This is truly transformative therapy,” Dr. King said when presenting the findings. “We know that the chances of spontaneous remission when you have severe disease is next to zero,” he added.

There were reasonably high rates of patient satisfaction with the treatment, according to Dr. King. He said that 42% of those who took 8 mg twice a day and 53% of those who took 12 mg twice a day said they were “very satisfied” or “satisfied” with the degree of scalp hair regrowth achieved, compared with 5% for placebo.

Safety was as expected, and there were no signs of any blood clots, said Dr. King. Common treatment-emergent adverse events (TEAEs) that affected 5% or more of patients included acne and headache. Serious TEAEs were reported by 1.1% and 0.5% of those taking the 8-mg and 12-mg twice-daily doses, respectively, compared with 2.9% of those who received placebo.

Overall, the results look promising for deuruxolitinib, he added. He noted that almost all patients included in the trial have opted to continue in the open-label long-term safety study.

Prescribing information of the JAK inhibitors approved by the U.S. Food and Drug Administration includes a boxed warning about risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. The warning is based on experience with another JAK inhibitor for patients with rheumatoid arthritis.
 

Ritlecitinib and the ALLEGRO studies

Interim results of the ongoing, open-label, phase 3 ALLEGRO-LT study with ritlecitinib were presented separately by Athanasios Tsianakas, MD, head of the department of dermatology at Fachklinik Bad Bentheim, Germany.

Ritlecitinib, which targets JAK3 and also the TEC family of tyrosine kinases, had met all of its endpoints in the prior ALLEGRO Phase 2b/3 study, Dr. Tsianakas said. Those included the benchmarks of a SALT score of 20 or less and a SALT score of 10 or less.

“Ritlecitinib showed a very good long-term efficacy and good safety profile in our adolescent and adult patients suffering from alopecia areata,” said Dr. Tsianakas.

A total of 447 patients were included in the trial. They were treated with 50 mg of ritlecitinib every day; some had already participated in the ALLEGRO trial, while others had been newly recruited. The latter group entered the trial after a 4-week run-in period, during which a 200-mg daily loading dose was given for 4 weeks.

Most (86%) patients had been exposed to ritlecitinib for at least 12 months; one-fifth had discontinued treatment at the data cutoff, generally because the patients no longer met the eligibility criteria for the trial.

Safety was paramount, Dr. Tsianakas highlighted. There were few adverse events that led to temporary or permanent discontinuation of the study drug. The most common TEAEs that affected 5% or more of patients included headache and acne. There were two cases of MACE (one nonfatal myocardial infarction and one nonfatal stroke).

The proportion of patients with a SALT score of 20 or less was 2.5% at 1 month, 27.9% at 3 months, 50.1% at 6 months, 59.8% at 9 months, and 65.5% at 12 months. Thereafter, there was little shift in the response. A sustained effect, in which a SALT score of 20 or less was seen out to 24 months, occurred in 69.9% of patients.

A similar pattern was seen for SALT scores of 10 or less, ranging from 16.5% at 3 months to 62.5% at 24 months.
 

Following in baricitinib’s footsteps?

This not the first time that JAK inhibitors have been shown to have beneficial effects for patients with AA. Baricitinib (Olumiant) recently became the first JAK inhibitor to be granted marketing approval for AA in the United States, largely on the basis of two pivotal phase 3 studies, BRAVE-AA1 and BRAVE-AA2.

“This is just such an incredibly exciting time,” said Dr. King. “Our discoveries in the lab are being translated into effective therapies for patients with diseases for which we’ve not previously had therapies,” he commented.

“Our concept of interferon gamma– and interleukin-15–mediated disease is probably not true for everybody,” said, Dr. King, who acknowledged that some patients with AA do not respond to JAK-inhibitor therapy or may need additional or alternative treatment.

“It’s probably not that homogeneous a disease,” he added. “It’s fascinating that the very first drugs for this disease are showing efficacy in as many patients as they are.”

The THRIVE-AAI study was funded by CONCERT Pharmaceuticals. Dr. King has served on advisory boards, has provided consulting services to, or has been a trial investigator for multiple pharmaceutical companies, including CoNCERT Pharmaceuticals. The ALLEGRO-LT study was funded by Pfizer. Dr. Tsianakas has acted as a clinical trial investigator and speaker for Pfizer.

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

Treatment with deuruxolitinib and ritlecitinib, two investigational Janus kinase (JAK) inhibitors, resulted in substantial regrowth of scalp hair for patients with alopecia areata (AA) in separate studies reported at the annual congress of the European Academy of Dermatology and Venereology.

In the THRIVE-AA1 study, the primary endpoint of a Severity of Alopecia Tool (SALT) score of 20 or lower –which indicates that hair regrowth has occurred on at least 80% of the scalp – was achieved among patients taking deuruxolitinib, which was a significantly higher proportion than with placebo (P < .0001). Importantly, the JAK inhibitor’s effects were seen in as early as 4 weeks, and there was significant improvement in both eyelash and eyebrow hair regrowth.

In the unrelated ALLEGRO-LT study, effects from treatment with the JAK inhibitor ritlecitinib appeared to be sustained for 2 years; 69.6% of patients treated with ritlecitinib had a SALT score of 20 or lower by 24 months.

These data are “very exciting for alopecia areata because the patients selected are very severe,” observed Mahtab Samimi, MD, PhD, who cochaired the late-breaking session in which the study findings were discussed.

THRIVE-AA1 included only patients with hair loss of 50% or more. The ALLEGRO-LT study included patients with total scalp or total body hair loss (areata totalis/areata universalis) of 25%-50% at enrollment.

Moreover, “very stringent criteria” were used. SALT scores of 10 or less were evaluated in both studies, observed Dr. Samimi, professor of dermatology at the University of Tours (France).

“We can be ambitious now for our patients with alopecia areata; that’s really good news,” Dr. Samimi added.

Deuruxolitinib and the THRIVE trials

Deuruxolitinib is an oral JAK1/JAK2 inhibitor that has been tested in two similarly designed, multinational, randomized, double-blind, placebo-controlled phase 3 trials in patients with AA, THRIVE-AA1 and THRIVE-AA2.

Two doses of deuruxolitinib, 8 mg and 12 mg given twice daily, were evaluated in the trials, which altogether included just over 1,200 patients.

Results of THRIVE-AA1 have been reported by the manufacturer. Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., presented a more comprehensive review at the EADV meeting.

He reported that at 24 weeks, SALT scores of 20 or lower were achieved by 30% of adults with AA who were treated with deuruxolitinib 8 mg and by 42% of those treated with deuruxolitinib 12 mg. This primary endpoint was seen in only 1% of the placebo-treated patients.

The more stringent endpoint of having a SALT score of 10 or less, which indicates that hair regrowth has occurred over 90% of the scalp, was met by 21% of patients who received deuruxolitinib 8 mg twice a day and by 35% of those who received the 12-mg dose twice a day at 24 weeks. This endpoint was not reached by any of the placebo-treated patients.

“This is truly transformative therapy,” Dr. King said when presenting the findings. “We know that the chances of spontaneous remission when you have severe disease is next to zero,” he added.

There were reasonably high rates of patient satisfaction with the treatment, according to Dr. King. He said that 42% of those who took 8 mg twice a day and 53% of those who took 12 mg twice a day said they were “very satisfied” or “satisfied” with the degree of scalp hair regrowth achieved, compared with 5% for placebo.

Safety was as expected, and there were no signs of any blood clots, said Dr. King. Common treatment-emergent adverse events (TEAEs) that affected 5% or more of patients included acne and headache. Serious TEAEs were reported by 1.1% and 0.5% of those taking the 8-mg and 12-mg twice-daily doses, respectively, compared with 2.9% of those who received placebo.

Overall, the results look promising for deuruxolitinib, he added. He noted that almost all patients included in the trial have opted to continue in the open-label long-term safety study.

Prescribing information of the JAK inhibitors approved by the U.S. Food and Drug Administration includes a boxed warning about risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. The warning is based on experience with another JAK inhibitor for patients with rheumatoid arthritis.
 

Ritlecitinib and the ALLEGRO studies

Interim results of the ongoing, open-label, phase 3 ALLEGRO-LT study with ritlecitinib were presented separately by Athanasios Tsianakas, MD, head of the department of dermatology at Fachklinik Bad Bentheim, Germany.

Ritlecitinib, which targets JAK3 and also the TEC family of tyrosine kinases, had met all of its endpoints in the prior ALLEGRO Phase 2b/3 study, Dr. Tsianakas said. Those included the benchmarks of a SALT score of 20 or less and a SALT score of 10 or less.

“Ritlecitinib showed a very good long-term efficacy and good safety profile in our adolescent and adult patients suffering from alopecia areata,” said Dr. Tsianakas.

A total of 447 patients were included in the trial. They were treated with 50 mg of ritlecitinib every day; some had already participated in the ALLEGRO trial, while others had been newly recruited. The latter group entered the trial after a 4-week run-in period, during which a 200-mg daily loading dose was given for 4 weeks.

Most (86%) patients had been exposed to ritlecitinib for at least 12 months; one-fifth had discontinued treatment at the data cutoff, generally because the patients no longer met the eligibility criteria for the trial.

Safety was paramount, Dr. Tsianakas highlighted. There were few adverse events that led to temporary or permanent discontinuation of the study drug. The most common TEAEs that affected 5% or more of patients included headache and acne. There were two cases of MACE (one nonfatal myocardial infarction and one nonfatal stroke).

The proportion of patients with a SALT score of 20 or less was 2.5% at 1 month, 27.9% at 3 months, 50.1% at 6 months, 59.8% at 9 months, and 65.5% at 12 months. Thereafter, there was little shift in the response. A sustained effect, in which a SALT score of 20 or less was seen out to 24 months, occurred in 69.9% of patients.

A similar pattern was seen for SALT scores of 10 or less, ranging from 16.5% at 3 months to 62.5% at 24 months.
 

Following in baricitinib’s footsteps?

This not the first time that JAK inhibitors have been shown to have beneficial effects for patients with AA. Baricitinib (Olumiant) recently became the first JAK inhibitor to be granted marketing approval for AA in the United States, largely on the basis of two pivotal phase 3 studies, BRAVE-AA1 and BRAVE-AA2.

“This is just such an incredibly exciting time,” said Dr. King. “Our discoveries in the lab are being translated into effective therapies for patients with diseases for which we’ve not previously had therapies,” he commented.

“Our concept of interferon gamma– and interleukin-15–mediated disease is probably not true for everybody,” said, Dr. King, who acknowledged that some patients with AA do not respond to JAK-inhibitor therapy or may need additional or alternative treatment.

“It’s probably not that homogeneous a disease,” he added. “It’s fascinating that the very first drugs for this disease are showing efficacy in as many patients as they are.”

The THRIVE-AAI study was funded by CONCERT Pharmaceuticals. Dr. King has served on advisory boards, has provided consulting services to, or has been a trial investigator for multiple pharmaceutical companies, including CoNCERT Pharmaceuticals. The ALLEGRO-LT study was funded by Pfizer. Dr. Tsianakas has acted as a clinical trial investigator and speaker for Pfizer.

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

Treatment with deuruxolitinib and ritlecitinib, two investigational Janus kinase (JAK) inhibitors, resulted in substantial regrowth of scalp hair for patients with alopecia areata (AA) in separate studies reported at the annual congress of the European Academy of Dermatology and Venereology.

In the THRIVE-AA1 study, the primary endpoint of a Severity of Alopecia Tool (SALT) score of 20 or lower –which indicates that hair regrowth has occurred on at least 80% of the scalp – was achieved among patients taking deuruxolitinib, which was a significantly higher proportion than with placebo (P < .0001). Importantly, the JAK inhibitor’s effects were seen in as early as 4 weeks, and there was significant improvement in both eyelash and eyebrow hair regrowth.

In the unrelated ALLEGRO-LT study, effects from treatment with the JAK inhibitor ritlecitinib appeared to be sustained for 2 years; 69.6% of patients treated with ritlecitinib had a SALT score of 20 or lower by 24 months.

These data are “very exciting for alopecia areata because the patients selected are very severe,” observed Mahtab Samimi, MD, PhD, who cochaired the late-breaking session in which the study findings were discussed.

THRIVE-AA1 included only patients with hair loss of 50% or more. The ALLEGRO-LT study included patients with total scalp or total body hair loss (areata totalis/areata universalis) of 25%-50% at enrollment.

Moreover, “very stringent criteria” were used. SALT scores of 10 or less were evaluated in both studies, observed Dr. Samimi, professor of dermatology at the University of Tours (France).

“We can be ambitious now for our patients with alopecia areata; that’s really good news,” Dr. Samimi added.

Deuruxolitinib and the THRIVE trials

Deuruxolitinib is an oral JAK1/JAK2 inhibitor that has been tested in two similarly designed, multinational, randomized, double-blind, placebo-controlled phase 3 trials in patients with AA, THRIVE-AA1 and THRIVE-AA2.

Two doses of deuruxolitinib, 8 mg and 12 mg given twice daily, were evaluated in the trials, which altogether included just over 1,200 patients.

Results of THRIVE-AA1 have been reported by the manufacturer. Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., presented a more comprehensive review at the EADV meeting.

He reported that at 24 weeks, SALT scores of 20 or lower were achieved by 30% of adults with AA who were treated with deuruxolitinib 8 mg and by 42% of those treated with deuruxolitinib 12 mg. This primary endpoint was seen in only 1% of the placebo-treated patients.

The more stringent endpoint of having a SALT score of 10 or less, which indicates that hair regrowth has occurred over 90% of the scalp, was met by 21% of patients who received deuruxolitinib 8 mg twice a day and by 35% of those who received the 12-mg dose twice a day at 24 weeks. This endpoint was not reached by any of the placebo-treated patients.

“This is truly transformative therapy,” Dr. King said when presenting the findings. “We know that the chances of spontaneous remission when you have severe disease is next to zero,” he added.

There were reasonably high rates of patient satisfaction with the treatment, according to Dr. King. He said that 42% of those who took 8 mg twice a day and 53% of those who took 12 mg twice a day said they were “very satisfied” or “satisfied” with the degree of scalp hair regrowth achieved, compared with 5% for placebo.

Safety was as expected, and there were no signs of any blood clots, said Dr. King. Common treatment-emergent adverse events (TEAEs) that affected 5% or more of patients included acne and headache. Serious TEAEs were reported by 1.1% and 0.5% of those taking the 8-mg and 12-mg twice-daily doses, respectively, compared with 2.9% of those who received placebo.

Overall, the results look promising for deuruxolitinib, he added. He noted that almost all patients included in the trial have opted to continue in the open-label long-term safety study.

Prescribing information of the JAK inhibitors approved by the U.S. Food and Drug Administration includes a boxed warning about risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. The warning is based on experience with another JAK inhibitor for patients with rheumatoid arthritis.
 

Ritlecitinib and the ALLEGRO studies

Interim results of the ongoing, open-label, phase 3 ALLEGRO-LT study with ritlecitinib were presented separately by Athanasios Tsianakas, MD, head of the department of dermatology at Fachklinik Bad Bentheim, Germany.

Ritlecitinib, which targets JAK3 and also the TEC family of tyrosine kinases, had met all of its endpoints in the prior ALLEGRO Phase 2b/3 study, Dr. Tsianakas said. Those included the benchmarks of a SALT score of 20 or less and a SALT score of 10 or less.

“Ritlecitinib showed a very good long-term efficacy and good safety profile in our adolescent and adult patients suffering from alopecia areata,” said Dr. Tsianakas.

A total of 447 patients were included in the trial. They were treated with 50 mg of ritlecitinib every day; some had already participated in the ALLEGRO trial, while others had been newly recruited. The latter group entered the trial after a 4-week run-in period, during which a 200-mg daily loading dose was given for 4 weeks.

Most (86%) patients had been exposed to ritlecitinib for at least 12 months; one-fifth had discontinued treatment at the data cutoff, generally because the patients no longer met the eligibility criteria for the trial.

Safety was paramount, Dr. Tsianakas highlighted. There were few adverse events that led to temporary or permanent discontinuation of the study drug. The most common TEAEs that affected 5% or more of patients included headache and acne. There were two cases of MACE (one nonfatal myocardial infarction and one nonfatal stroke).

The proportion of patients with a SALT score of 20 or less was 2.5% at 1 month, 27.9% at 3 months, 50.1% at 6 months, 59.8% at 9 months, and 65.5% at 12 months. Thereafter, there was little shift in the response. A sustained effect, in which a SALT score of 20 or less was seen out to 24 months, occurred in 69.9% of patients.

A similar pattern was seen for SALT scores of 10 or less, ranging from 16.5% at 3 months to 62.5% at 24 months.
 

Following in baricitinib’s footsteps?

This not the first time that JAK inhibitors have been shown to have beneficial effects for patients with AA. Baricitinib (Olumiant) recently became the first JAK inhibitor to be granted marketing approval for AA in the United States, largely on the basis of two pivotal phase 3 studies, BRAVE-AA1 and BRAVE-AA2.

“This is just such an incredibly exciting time,” said Dr. King. “Our discoveries in the lab are being translated into effective therapies for patients with diseases for which we’ve not previously had therapies,” he commented.

“Our concept of interferon gamma– and interleukin-15–mediated disease is probably not true for everybody,” said, Dr. King, who acknowledged that some patients with AA do not respond to JAK-inhibitor therapy or may need additional or alternative treatment.

“It’s probably not that homogeneous a disease,” he added. “It’s fascinating that the very first drugs for this disease are showing efficacy in as many patients as they are.”

The THRIVE-AAI study was funded by CONCERT Pharmaceuticals. Dr. King has served on advisory boards, has provided consulting services to, or has been a trial investigator for multiple pharmaceutical companies, including CoNCERT Pharmaceuticals. The ALLEGRO-LT study was funded by Pfizer. Dr. Tsianakas has acted as a clinical trial investigator and speaker for Pfizer.

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

It might be possible to develop a simple test to identify newborn children who are at risk of later developing atopic dermatitis (AD), according to findings from a Danish prospective birth cohort study.

In the study, the Barrier Dysfunction in Atopic Newborns Study (BABY), several biomarkers were found in the skin cells of newborns that were predictive not only for having AD but also for having more severe disease.

“We are able to identify predictive immune biomarkers of atopic dermatitis using a noninvasive method that was not associated with any pain,” one of the study’s investigators, Anne-Sofie Halling, MD, said at a press briefing at the annual congress of the European Academy of Dermatology and Venereology.

“Importantly, we were able to predict atopic dermatitis occurring months after [sample] collection,” said Dr. Halling, who works at Bispebjerg Hospital and is a PhD student at the University of Copenhagen.

These findings could hopefully be used to help identify children “so that preventive strategies can target these children ... and decrease the incidence of this common disease,” she added.

AD is caused “by a complex interplay between skin barrier dysfunction and immune dysregulation,” Dr. Halling said, and it is “the first step in the so-called atopic march, where children also develop food allergy, asthma, and rhinitis.” Almost all cases of AD begin during the first years of life. Approximately 15%-20% of children can be affected, she noted, emphasizing the high burden of the disease and pointing out that strategies are shifting toward trying to prevent the disease in those at risk.

Copenhagen BABY cohort

This is where the BABY study comes in, Dr. Halling said. The study enrolled 450 children at birth and followed them until age 2 years. Gene mutation testing was performed at enrollment. All children underwent skin examination, and skin samples were taken using tape strips. Tape strips were applied to the back of the hand of children born at term and between the shoulder blades on the back of children who were premature.

Skin examinations were repeated, and skin samples were obtained again at age 2 months. They were taken again only if there were any signs of AD. For those diagnosed with AD, disease severity was assessed using the Eczema Area and Severity Index (EASI) by the treating physician. Children were excluded if they had AD at the time the tape strip testing was due to be performed.
 

Comparing term and preterm children

Dr. Halling noted that analyses were performed separately for the 300 children born at term and for the 150 who were preterm.

The prevalence of AD was higher among children born at term than among the preterm children (34.6% vs. 21.2%), and the median time to onset was shorter (6 months vs. 8 months). There were also differences in the EASI scores among those who developed AD; median scores were higher in the children born at term than in the preterm children (4.1 vs. 1.6).

More children born at term than preterm children had moderate to severe AD (23.3% vs. 8%), Dr. Halling reported.
 

TARC, IL-8, and IL-18 predictive of AD

Multiple immune biomarkers were tested, including various cytokines and filaggrin degradation products. On examination of skin samples collected at birth, no particular biomarkers were found at higher levels among children who developed AD in comparison with those who did not develop AD.

With regard to biomarkers examined in skin samples at 2 months of age, however, the results were different, Dr. Halling said. One particular cytokine, thymus and activation-regulated chemokine (TARC), was seen to double the risk of AD in the first 2 years of a child’s life.

This doubled risk was seen not only among the children born at term but also among those born preterm, although the data were only significant with regard to the children born at term.

The unadjusted hazard ratios and adjusted HRs (adjusted for parental atopy and filaggrin gene mutations) in term children were 2.11 (95% confidence interval, 1.36-3.26; P = .0008) and 1.85 (95% CI, 1.18-2.89; P = .007), respectively.

For preterm children, the HRs were 2.23 (95% CI, 0.85-5.86; P = .1) and 2.60 (95% CI, 0.98-6.85; P =.05), respectively.

These findings were in line with findings of other studies, Dr. Halling said. “It is well recognized that TARC is currently the best biomarker in patients with established atopic dermatitis.” Moreover, she reported that TARC was associated with a cumulative increase in the risk for AD and that levels were found to be higher in children in whom onset occurred at a later age than among those diagnosed before 6 months of age.

“This is important, as these findings shows that TARC levels predict atopic dermatitis that occurred many months later,” Dr. Halling said.

And, in term-born children at least, TARC upped the chances that the severity of AD would be greater than had it not been present (adjusted HR, 4.65; 95% CI, 1.91-11.31; P = .0007).

Increased levels of interleukin-8 (IL-8) and IL-18 at 2 months of age were also found to be predictive of having moderate to severe AD. The risk was more than double in comparison with those in whom levels were not increased, again only in term-born children.

‘Stimulating and interesting findings’

These data are “very stimulating and interesting,” Dedee Murrell, MD, professor and head of the department of dermatology at St. George Hospital, University of New South Wales, Sydney, observed at the press briefing.

“You found this significant association mainly in the newborn children born at term, and the association in the preterm babies wasn’t as high. Is that anything to do with how they were taken care of in the hospital?” Dr. Murrell asked.

“That’s a really good question,” Dr. Halling said. “Maybe they need to be exposed for a month or two before we are actually able to identify which children will develop atopic dermatitis.”

The study was funded by the Lundbeck Foundation. Dr. Halling has acted as a consultant for Coloplast and as a speaker for Leo Pharma. Dr. Murrell has disclosed no relevant financial relationships.

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

It might be possible to develop a simple test to identify newborn children who are at risk of later developing atopic dermatitis (AD), according to findings from a Danish prospective birth cohort study.

In the study, the Barrier Dysfunction in Atopic Newborns Study (BABY), several biomarkers were found in the skin cells of newborns that were predictive not only for having AD but also for having more severe disease.

“We are able to identify predictive immune biomarkers of atopic dermatitis using a noninvasive method that was not associated with any pain,” one of the study’s investigators, Anne-Sofie Halling, MD, said at a press briefing at the annual congress of the European Academy of Dermatology and Venereology.

“Importantly, we were able to predict atopic dermatitis occurring months after [sample] collection,” said Dr. Halling, who works at Bispebjerg Hospital and is a PhD student at the University of Copenhagen.

These findings could hopefully be used to help identify children “so that preventive strategies can target these children ... and decrease the incidence of this common disease,” she added.

AD is caused “by a complex interplay between skin barrier dysfunction and immune dysregulation,” Dr. Halling said, and it is “the first step in the so-called atopic march, where children also develop food allergy, asthma, and rhinitis.” Almost all cases of AD begin during the first years of life. Approximately 15%-20% of children can be affected, she noted, emphasizing the high burden of the disease and pointing out that strategies are shifting toward trying to prevent the disease in those at risk.

Copenhagen BABY cohort

This is where the BABY study comes in, Dr. Halling said. The study enrolled 450 children at birth and followed them until age 2 years. Gene mutation testing was performed at enrollment. All children underwent skin examination, and skin samples were taken using tape strips. Tape strips were applied to the back of the hand of children born at term and between the shoulder blades on the back of children who were premature.

Skin examinations were repeated, and skin samples were obtained again at age 2 months. They were taken again only if there were any signs of AD. For those diagnosed with AD, disease severity was assessed using the Eczema Area and Severity Index (EASI) by the treating physician. Children were excluded if they had AD at the time the tape strip testing was due to be performed.
 

Comparing term and preterm children

Dr. Halling noted that analyses were performed separately for the 300 children born at term and for the 150 who were preterm.

The prevalence of AD was higher among children born at term than among the preterm children (34.6% vs. 21.2%), and the median time to onset was shorter (6 months vs. 8 months). There were also differences in the EASI scores among those who developed AD; median scores were higher in the children born at term than in the preterm children (4.1 vs. 1.6).

More children born at term than preterm children had moderate to severe AD (23.3% vs. 8%), Dr. Halling reported.
 

TARC, IL-8, and IL-18 predictive of AD

Multiple immune biomarkers were tested, including various cytokines and filaggrin degradation products. On examination of skin samples collected at birth, no particular biomarkers were found at higher levels among children who developed AD in comparison with those who did not develop AD.

With regard to biomarkers examined in skin samples at 2 months of age, however, the results were different, Dr. Halling said. One particular cytokine, thymus and activation-regulated chemokine (TARC), was seen to double the risk of AD in the first 2 years of a child’s life.

This doubled risk was seen not only among the children born at term but also among those born preterm, although the data were only significant with regard to the children born at term.

The unadjusted hazard ratios and adjusted HRs (adjusted for parental atopy and filaggrin gene mutations) in term children were 2.11 (95% confidence interval, 1.36-3.26; P = .0008) and 1.85 (95% CI, 1.18-2.89; P = .007), respectively.

For preterm children, the HRs were 2.23 (95% CI, 0.85-5.86; P = .1) and 2.60 (95% CI, 0.98-6.85; P =.05), respectively.

These findings were in line with findings of other studies, Dr. Halling said. “It is well recognized that TARC is currently the best biomarker in patients with established atopic dermatitis.” Moreover, she reported that TARC was associated with a cumulative increase in the risk for AD and that levels were found to be higher in children in whom onset occurred at a later age than among those diagnosed before 6 months of age.

“This is important, as these findings shows that TARC levels predict atopic dermatitis that occurred many months later,” Dr. Halling said.

And, in term-born children at least, TARC upped the chances that the severity of AD would be greater than had it not been present (adjusted HR, 4.65; 95% CI, 1.91-11.31; P = .0007).

Increased levels of interleukin-8 (IL-8) and IL-18 at 2 months of age were also found to be predictive of having moderate to severe AD. The risk was more than double in comparison with those in whom levels were not increased, again only in term-born children.

‘Stimulating and interesting findings’

These data are “very stimulating and interesting,” Dedee Murrell, MD, professor and head of the department of dermatology at St. George Hospital, University of New South Wales, Sydney, observed at the press briefing.

“You found this significant association mainly in the newborn children born at term, and the association in the preterm babies wasn’t as high. Is that anything to do with how they were taken care of in the hospital?” Dr. Murrell asked.

“That’s a really good question,” Dr. Halling said. “Maybe they need to be exposed for a month or two before we are actually able to identify which children will develop atopic dermatitis.”

The study was funded by the Lundbeck Foundation. Dr. Halling has acted as a consultant for Coloplast and as a speaker for Leo Pharma. Dr. Murrell has disclosed no relevant financial relationships.

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

It might be possible to develop a simple test to identify newborn children who are at risk of later developing atopic dermatitis (AD), according to findings from a Danish prospective birth cohort study.

In the study, the Barrier Dysfunction in Atopic Newborns Study (BABY), several biomarkers were found in the skin cells of newborns that were predictive not only for having AD but also for having more severe disease.

“We are able to identify predictive immune biomarkers of atopic dermatitis using a noninvasive method that was not associated with any pain,” one of the study’s investigators, Anne-Sofie Halling, MD, said at a press briefing at the annual congress of the European Academy of Dermatology and Venereology.

“Importantly, we were able to predict atopic dermatitis occurring months after [sample] collection,” said Dr. Halling, who works at Bispebjerg Hospital and is a PhD student at the University of Copenhagen.

These findings could hopefully be used to help identify children “so that preventive strategies can target these children ... and decrease the incidence of this common disease,” she added.

AD is caused “by a complex interplay between skin barrier dysfunction and immune dysregulation,” Dr. Halling said, and it is “the first step in the so-called atopic march, where children also develop food allergy, asthma, and rhinitis.” Almost all cases of AD begin during the first years of life. Approximately 15%-20% of children can be affected, she noted, emphasizing the high burden of the disease and pointing out that strategies are shifting toward trying to prevent the disease in those at risk.

Copenhagen BABY cohort

This is where the BABY study comes in, Dr. Halling said. The study enrolled 450 children at birth and followed them until age 2 years. Gene mutation testing was performed at enrollment. All children underwent skin examination, and skin samples were taken using tape strips. Tape strips were applied to the back of the hand of children born at term and between the shoulder blades on the back of children who were premature.

Skin examinations were repeated, and skin samples were obtained again at age 2 months. They were taken again only if there were any signs of AD. For those diagnosed with AD, disease severity was assessed using the Eczema Area and Severity Index (EASI) by the treating physician. Children were excluded if they had AD at the time the tape strip testing was due to be performed.
 

Comparing term and preterm children

Dr. Halling noted that analyses were performed separately for the 300 children born at term and for the 150 who were preterm.

The prevalence of AD was higher among children born at term than among the preterm children (34.6% vs. 21.2%), and the median time to onset was shorter (6 months vs. 8 months). There were also differences in the EASI scores among those who developed AD; median scores were higher in the children born at term than in the preterm children (4.1 vs. 1.6).

More children born at term than preterm children had moderate to severe AD (23.3% vs. 8%), Dr. Halling reported.
 

TARC, IL-8, and IL-18 predictive of AD

Multiple immune biomarkers were tested, including various cytokines and filaggrin degradation products. On examination of skin samples collected at birth, no particular biomarkers were found at higher levels among children who developed AD in comparison with those who did not develop AD.

With regard to biomarkers examined in skin samples at 2 months of age, however, the results were different, Dr. Halling said. One particular cytokine, thymus and activation-regulated chemokine (TARC), was seen to double the risk of AD in the first 2 years of a child’s life.

This doubled risk was seen not only among the children born at term but also among those born preterm, although the data were only significant with regard to the children born at term.

The unadjusted hazard ratios and adjusted HRs (adjusted for parental atopy and filaggrin gene mutations) in term children were 2.11 (95% confidence interval, 1.36-3.26; P = .0008) and 1.85 (95% CI, 1.18-2.89; P = .007), respectively.

For preterm children, the HRs were 2.23 (95% CI, 0.85-5.86; P = .1) and 2.60 (95% CI, 0.98-6.85; P =.05), respectively.

These findings were in line with findings of other studies, Dr. Halling said. “It is well recognized that TARC is currently the best biomarker in patients with established atopic dermatitis.” Moreover, she reported that TARC was associated with a cumulative increase in the risk for AD and that levels were found to be higher in children in whom onset occurred at a later age than among those diagnosed before 6 months of age.

“This is important, as these findings shows that TARC levels predict atopic dermatitis that occurred many months later,” Dr. Halling said.

And, in term-born children at least, TARC upped the chances that the severity of AD would be greater than had it not been present (adjusted HR, 4.65; 95% CI, 1.91-11.31; P = .0007).

Increased levels of interleukin-8 (IL-8) and IL-18 at 2 months of age were also found to be predictive of having moderate to severe AD. The risk was more than double in comparison with those in whom levels were not increased, again only in term-born children.

‘Stimulating and interesting findings’

These data are “very stimulating and interesting,” Dedee Murrell, MD, professor and head of the department of dermatology at St. George Hospital, University of New South Wales, Sydney, observed at the press briefing.

“You found this significant association mainly in the newborn children born at term, and the association in the preterm babies wasn’t as high. Is that anything to do with how they were taken care of in the hospital?” Dr. Murrell asked.

“That’s a really good question,” Dr. Halling said. “Maybe they need to be exposed for a month or two before we are actually able to identify which children will develop atopic dermatitis.”

The study was funded by the Lundbeck Foundation. Dr. Halling has acted as a consultant for Coloplast and as a speaker for Leo Pharma. Dr. Murrell has disclosed no relevant financial relationships.

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

STOCKHOLM – It remains inconclusive whether SARS-CoV-2 infection predisposes children and adolescents to a higher risk of type 1 diabetes. Data from two new studies and a recently published research letter add to the growing body of knowledge on the subject, but still can’t draw any definitive conclusions.

The latest results from a Norwegian and a Scottish study both examine incidence of type 1 diabetes in young people with a history of SARS-CoV-2 infection and were reported at the annual meeting of the European Association for the Study of Diabetes.

A 60% increased risk for type 1 diabetes at least 31 days after SARS-CoV-2 infection (adjusted hazard ratio, 1.63) was found in the Norwegian study, while in contrast, the Scottish study only found an increased risk in the first few months of the pandemic, in 2020, but importantly, no association over a much longer time period (March 2020–November 2021).

In a comment on Twitter on the two studies presented at EASD, session moderator Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, (England), said: “In summary, two studies showing no or weak association of type 1 diabetes with COVID.”

But new data in the research letter published in JAMA Network Open, based on U.S. figures, also found an almost doubling of type 1 diabetes in children in the first few months after COVID-19 infection relative to infection with other respiratory viruses.

Lead author of the Scottish study, Helen Colhoun, PhD, honorary public health consultant at Public Health Scotland, commented: “Data in children are variable year on year, which emphasizes the need to be cautious over taking a tiny snapshot.”

Nevertheless, this is “a hugely important question and we must not drop the ball. [We must] keep looking at it and maintain scientific equipoise. ... [This] reinforces the need to carry on this analysis into the future to obtain an unequivocal picture,” she emphasized.
 

Norwegian study: If there is an association, the risk is small

German Tapia, PhD, from the Norwegian Institute of Public Health, Oslo, presented the results of a study of SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children in Norway.

Of these, 424,354 children had been infected with SARS-CoV-2, and there were 990 incident cases of type 1 diabetes.

“What we do know about COVID-19 in children is that the symptoms are mild and only a small proportion are hospitalized with more serious symptoms. But we do not know the long-term effects of COVID-19 infection because this requires a longer follow-up period,” remarked Dr. Tapia, adding that other viral infections are thought to be linked to the development of type 1 diabetes, in particular, respiratory infections.

The data were sourced from the Norwegian Emergency Preparedness Register for COVID-19, which gathers daily data updates including infections (positive and negative results for free-of-charge testing), diagnoses (primary and secondary care), vaccinations (also free of charge), prescribed medications, and basic demographics.

“We link these data using the personal identification number that every Norwegian citizen has,” explained Dr. Tapia.

He presented results from two cohorts: firstly, results in children only, including those tested for SARS-CoV-2 infection, and secondly, a full national Norwegian population cohort.

Regarding the first cohort, those under 18 years who tested positive for SARS-CoV-2 infection, from March 2020 to March 2022, had a significantly increased risk of type 1 diabetes at least 31 days after infection, with an adjusted hazard ratio of 1.63 (95% confidence interval, 1.08-2.47; P = .02). Adjustments were made for age, sex, non-Nordic country of origin, geographic area, and socioeconomic factors.

For children who developed type 1 diabetes within 30 days of a SARS-CoV-2 infection, the HR was 1.26 (95% CI, 0.72-2.19; P = .42), which did not reach statistical significance.

“The fact that fewer people developed type 1 diabetes within 30 days is not surprising because we know that type 1 diabetes develops over a long period of time,” Dr. Tapia said.

“For this reason, we would not expect to find new cases of those people who develop type 1 diabetes within 30 days of COVID-19 infection,” he explained. In these cases, “it is most likely that they already had [type 1 diabetes], and the infection probably triggered clinical symptoms, so their type 1 diabetes was discovered.”

Turning to the full population cohort and diagnoses of type 1 diabetes over 30 days after SARS-CoV-2 infection, the Norwegian researchers found an association, with an HR of 1.57 (95% CI, 1.06-2.33; P = .03), while diagnosis of type 1 diabetes at 30 days or less generated a hazard ratio of 1.22 (95% CI, 0.72-2.19; P = .42).

“So very similar results were found, and after adjustment for confounders, results were still similar,” reported Dr. Tapia.

He also conducted a similar analysis with vaccination as an exposure but found no association between vaccination against SARS-CoV-2 and diagnosis of type 1 diabetes.

“From these results, we conclude that this suggests an increase in diagnosis of type 1 diabetes after SARS-CoV-2 infection, but it must be noted that the absolute risk of developing type 1 diabetes after infection in children is low, with most children not developing the disease,” he emphasized. “There are nearly half a million children who have been infected with SARS-CoV-2 in Norway, but only a very small proportion develop type 1 diabetes.”
 

Scottish study: No association found over longer term

Dr. Colhoun and colleagues looked at the relationship between incident type 1 diabetes and SARS-CoV-2 infection in children in Scotland using e-health record linkage.

The study involved 1.8 million people under 35 years of age and found very weak, if any, evidence of an association between incident type 1 diabetes and SARS-CoV-2.

Examining data between March 2020 and November 2021, Dr. Colhoun and colleagues identified 365,080 individuals up to age 35 with at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes.

“In children under 16 years, suspected cases of type 1 diabetes are admitted to hospital, and 97% of diagnosis dates are recorded in the Scottish Care Information – Diabetes Collaboration register [SCI-Diabetes] prior to or within 2 days of the first hospital admission for type 1 diabetes,” Dr. Colhoun said, stressing the timeliness of the data.

“We found the incidence of type 1 diabetes diagnosis increased 1.2-fold in those aged 0-14 years, but we did not find any association at an individual level of COVID-19 infection over 30 days prior to a type 1 diabetes diagnosis, in this particular dataset,” she reported. In young people aged 15-34, there was a linear increase in incident type 1 diabetes from 2015 to 2021 with no pandemic increase.

Referring to the 1.2-fold increase soon after the pandemic started, she explained that, in 0- to 14-year-olds, the increase followed a drop in the preceding months prepandemic in 2019. They also found that the seasonal pattern of type 1 diabetes diagnoses remained roughly the same across the pandemic months, with typical peaks in February and September.

In the cohort of under 35s, researchers also found a rate ratio of 2.62 (95% CI, 1.81-3.78) within a 30-day window of SARS-CoV-2 infection, but beyond 30 days, no evidence was seen of an association, with a RR of 0.86 (95% CI, 0.62-1.21; P = .40), she reported.

She explained her reasons for not considering diagnoses within 30 days of COVID-19 as causative. Echoing Dr. Tapia, Dr. Colhoun said the median time from symptom onset to diagnosis of type 1 diabetes is 25 days. “This suggests that 50% have had symptoms for over 25 days at diagnosis.”

She also stressed that when they compared the timing of SARS-CoV-2 testing with diagnosis, they found a much higher rate of COVID-19 testing around diagnosis. “This was not least because everyone admitted to hospital had to have a COVID-19 test.”
 

Latest U.S. data point to a link

Meanwhile, for the new data reported in JAMA Network Open, medical student Ellen K. Kendall of Case Western Reserve University, Cleveland, matched 571,256 pediatric patients: 285,628 with COVID-19 and 285,628 with non–COVID-19 respiratory infections.

By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of type 1 diabetes, but only 72 (0.025%) were diagnosed with type 1 diabetes within 6 months after non–COVID-19 respiratory infection.

At 1, 3, and 6 months after infection, risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2, compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96; 3 months: HR, 2.10; and 6 months: HR, 1.83), and in subgroups of patients aged 0-9 years, a group unlikely to develop type 2 diabetes.

“In this study, new type 1 diabetes diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems),” noted Ms. Kendall and coauthors. “Respiratory infections have previously been associated with onset of type 1 diabetes, but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths.”

“The increased risk of new-onset type 1 diabetes after COVID-19 adds an important consideration for risk–benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A study from the Centers for Disease Control and Prevention published in January 2022, also concluded there was a link between COVID-19 and diabetes in children, but not with other acute respiratory infections. Children were 2.5 times more likely to be diagnosed with diabetes following a SARS-CoV-2 infection, it found.

However, the study has been criticized because it pooled all types of diabetes together and did not account for other health conditions, medications that can increase blood glucose levels, race, obesity, and other social determinants of health that might influence a child’s risk of acquiring COVID-19 or diabetes.

“I’ve no doubt that the CDC data were incorrect because the incidence rate for ... diabetes, even in those never exposed to COVID-19 infection, was 10 times the rate ever reported in the U.S.,” Dr. Colhoun said. “There’s no way these data are correct. I believe there was a confusion between incidence and prevalence of diabetes.”

“This paper caused a great deal of panic, especially among those who have a child with type 1diabetes, so we need to be very careful not to cause undue alarm until we have more definitive evidence in this arena,” she stressed.

However, she also acknowledged that the new Norwegian study was well conducted, and she has no methodological concerns about it, so “I think we just have to wait and see.”

Given the inconclusiveness on the issue, there is an ongoing CoviDiab registry collecting data on this very subject.

Dr. Tapia presented on behalf of lead author Dr. Gulseth, who has reported no relevant financial relationships. Dr. Colhoun also reported no relevant financial relationships.

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

STOCKHOLM – It remains inconclusive whether SARS-CoV-2 infection predisposes children and adolescents to a higher risk of type 1 diabetes. Data from two new studies and a recently published research letter add to the growing body of knowledge on the subject, but still can’t draw any definitive conclusions.

The latest results from a Norwegian and a Scottish study both examine incidence of type 1 diabetes in young people with a history of SARS-CoV-2 infection and were reported at the annual meeting of the European Association for the Study of Diabetes.

A 60% increased risk for type 1 diabetes at least 31 days after SARS-CoV-2 infection (adjusted hazard ratio, 1.63) was found in the Norwegian study, while in contrast, the Scottish study only found an increased risk in the first few months of the pandemic, in 2020, but importantly, no association over a much longer time period (March 2020–November 2021).

In a comment on Twitter on the two studies presented at EASD, session moderator Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, (England), said: “In summary, two studies showing no or weak association of type 1 diabetes with COVID.”

But new data in the research letter published in JAMA Network Open, based on U.S. figures, also found an almost doubling of type 1 diabetes in children in the first few months after COVID-19 infection relative to infection with other respiratory viruses.

Lead author of the Scottish study, Helen Colhoun, PhD, honorary public health consultant at Public Health Scotland, commented: “Data in children are variable year on year, which emphasizes the need to be cautious over taking a tiny snapshot.”

Nevertheless, this is “a hugely important question and we must not drop the ball. [We must] keep looking at it and maintain scientific equipoise. ... [This] reinforces the need to carry on this analysis into the future to obtain an unequivocal picture,” she emphasized.
 

Norwegian study: If there is an association, the risk is small

German Tapia, PhD, from the Norwegian Institute of Public Health, Oslo, presented the results of a study of SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children in Norway.

Of these, 424,354 children had been infected with SARS-CoV-2, and there were 990 incident cases of type 1 diabetes.

“What we do know about COVID-19 in children is that the symptoms are mild and only a small proportion are hospitalized with more serious symptoms. But we do not know the long-term effects of COVID-19 infection because this requires a longer follow-up period,” remarked Dr. Tapia, adding that other viral infections are thought to be linked to the development of type 1 diabetes, in particular, respiratory infections.

The data were sourced from the Norwegian Emergency Preparedness Register for COVID-19, which gathers daily data updates including infections (positive and negative results for free-of-charge testing), diagnoses (primary and secondary care), vaccinations (also free of charge), prescribed medications, and basic demographics.

“We link these data using the personal identification number that every Norwegian citizen has,” explained Dr. Tapia.

He presented results from two cohorts: firstly, results in children only, including those tested for SARS-CoV-2 infection, and secondly, a full national Norwegian population cohort.

Regarding the first cohort, those under 18 years who tested positive for SARS-CoV-2 infection, from March 2020 to March 2022, had a significantly increased risk of type 1 diabetes at least 31 days after infection, with an adjusted hazard ratio of 1.63 (95% confidence interval, 1.08-2.47; P = .02). Adjustments were made for age, sex, non-Nordic country of origin, geographic area, and socioeconomic factors.

For children who developed type 1 diabetes within 30 days of a SARS-CoV-2 infection, the HR was 1.26 (95% CI, 0.72-2.19; P = .42), which did not reach statistical significance.

“The fact that fewer people developed type 1 diabetes within 30 days is not surprising because we know that type 1 diabetes develops over a long period of time,” Dr. Tapia said.

“For this reason, we would not expect to find new cases of those people who develop type 1 diabetes within 30 days of COVID-19 infection,” he explained. In these cases, “it is most likely that they already had [type 1 diabetes], and the infection probably triggered clinical symptoms, so their type 1 diabetes was discovered.”

Turning to the full population cohort and diagnoses of type 1 diabetes over 30 days after SARS-CoV-2 infection, the Norwegian researchers found an association, with an HR of 1.57 (95% CI, 1.06-2.33; P = .03), while diagnosis of type 1 diabetes at 30 days or less generated a hazard ratio of 1.22 (95% CI, 0.72-2.19; P = .42).

“So very similar results were found, and after adjustment for confounders, results were still similar,” reported Dr. Tapia.

He also conducted a similar analysis with vaccination as an exposure but found no association between vaccination against SARS-CoV-2 and diagnosis of type 1 diabetes.

“From these results, we conclude that this suggests an increase in diagnosis of type 1 diabetes after SARS-CoV-2 infection, but it must be noted that the absolute risk of developing type 1 diabetes after infection in children is low, with most children not developing the disease,” he emphasized. “There are nearly half a million children who have been infected with SARS-CoV-2 in Norway, but only a very small proportion develop type 1 diabetes.”
 

Scottish study: No association found over longer term

Dr. Colhoun and colleagues looked at the relationship between incident type 1 diabetes and SARS-CoV-2 infection in children in Scotland using e-health record linkage.

The study involved 1.8 million people under 35 years of age and found very weak, if any, evidence of an association between incident type 1 diabetes and SARS-CoV-2.

Examining data between March 2020 and November 2021, Dr. Colhoun and colleagues identified 365,080 individuals up to age 35 with at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes.

“In children under 16 years, suspected cases of type 1 diabetes are admitted to hospital, and 97% of diagnosis dates are recorded in the Scottish Care Information – Diabetes Collaboration register [SCI-Diabetes] prior to or within 2 days of the first hospital admission for type 1 diabetes,” Dr. Colhoun said, stressing the timeliness of the data.

“We found the incidence of type 1 diabetes diagnosis increased 1.2-fold in those aged 0-14 years, but we did not find any association at an individual level of COVID-19 infection over 30 days prior to a type 1 diabetes diagnosis, in this particular dataset,” she reported. In young people aged 15-34, there was a linear increase in incident type 1 diabetes from 2015 to 2021 with no pandemic increase.

Referring to the 1.2-fold increase soon after the pandemic started, she explained that, in 0- to 14-year-olds, the increase followed a drop in the preceding months prepandemic in 2019. They also found that the seasonal pattern of type 1 diabetes diagnoses remained roughly the same across the pandemic months, with typical peaks in February and September.

In the cohort of under 35s, researchers also found a rate ratio of 2.62 (95% CI, 1.81-3.78) within a 30-day window of SARS-CoV-2 infection, but beyond 30 days, no evidence was seen of an association, with a RR of 0.86 (95% CI, 0.62-1.21; P = .40), she reported.

She explained her reasons for not considering diagnoses within 30 days of COVID-19 as causative. Echoing Dr. Tapia, Dr. Colhoun said the median time from symptom onset to diagnosis of type 1 diabetes is 25 days. “This suggests that 50% have had symptoms for over 25 days at diagnosis.”

She also stressed that when they compared the timing of SARS-CoV-2 testing with diagnosis, they found a much higher rate of COVID-19 testing around diagnosis. “This was not least because everyone admitted to hospital had to have a COVID-19 test.”
 

Latest U.S. data point to a link

Meanwhile, for the new data reported in JAMA Network Open, medical student Ellen K. Kendall of Case Western Reserve University, Cleveland, matched 571,256 pediatric patients: 285,628 with COVID-19 and 285,628 with non–COVID-19 respiratory infections.

By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of type 1 diabetes, but only 72 (0.025%) were diagnosed with type 1 diabetes within 6 months after non–COVID-19 respiratory infection.

At 1, 3, and 6 months after infection, risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2, compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96; 3 months: HR, 2.10; and 6 months: HR, 1.83), and in subgroups of patients aged 0-9 years, a group unlikely to develop type 2 diabetes.

“In this study, new type 1 diabetes diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems),” noted Ms. Kendall and coauthors. “Respiratory infections have previously been associated with onset of type 1 diabetes, but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths.”

“The increased risk of new-onset type 1 diabetes after COVID-19 adds an important consideration for risk–benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A study from the Centers for Disease Control and Prevention published in January 2022, also concluded there was a link between COVID-19 and diabetes in children, but not with other acute respiratory infections. Children were 2.5 times more likely to be diagnosed with diabetes following a SARS-CoV-2 infection, it found.

However, the study has been criticized because it pooled all types of diabetes together and did not account for other health conditions, medications that can increase blood glucose levels, race, obesity, and other social determinants of health that might influence a child’s risk of acquiring COVID-19 or diabetes.

“I’ve no doubt that the CDC data were incorrect because the incidence rate for ... diabetes, even in those never exposed to COVID-19 infection, was 10 times the rate ever reported in the U.S.,” Dr. Colhoun said. “There’s no way these data are correct. I believe there was a confusion between incidence and prevalence of diabetes.”

“This paper caused a great deal of panic, especially among those who have a child with type 1diabetes, so we need to be very careful not to cause undue alarm until we have more definitive evidence in this arena,” she stressed.

However, she also acknowledged that the new Norwegian study was well conducted, and she has no methodological concerns about it, so “I think we just have to wait and see.”

Given the inconclusiveness on the issue, there is an ongoing CoviDiab registry collecting data on this very subject.

Dr. Tapia presented on behalf of lead author Dr. Gulseth, who has reported no relevant financial relationships. Dr. Colhoun also reported no relevant financial relationships.

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

STOCKHOLM – It remains inconclusive whether SARS-CoV-2 infection predisposes children and adolescents to a higher risk of type 1 diabetes. Data from two new studies and a recently published research letter add to the growing body of knowledge on the subject, but still can’t draw any definitive conclusions.

The latest results from a Norwegian and a Scottish study both examine incidence of type 1 diabetes in young people with a history of SARS-CoV-2 infection and were reported at the annual meeting of the European Association for the Study of Diabetes.

A 60% increased risk for type 1 diabetes at least 31 days after SARS-CoV-2 infection (adjusted hazard ratio, 1.63) was found in the Norwegian study, while in contrast, the Scottish study only found an increased risk in the first few months of the pandemic, in 2020, but importantly, no association over a much longer time period (March 2020–November 2021).

In a comment on Twitter on the two studies presented at EASD, session moderator Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, (England), said: “In summary, two studies showing no or weak association of type 1 diabetes with COVID.”

But new data in the research letter published in JAMA Network Open, based on U.S. figures, also found an almost doubling of type 1 diabetes in children in the first few months after COVID-19 infection relative to infection with other respiratory viruses.

Lead author of the Scottish study, Helen Colhoun, PhD, honorary public health consultant at Public Health Scotland, commented: “Data in children are variable year on year, which emphasizes the need to be cautious over taking a tiny snapshot.”

Nevertheless, this is “a hugely important question and we must not drop the ball. [We must] keep looking at it and maintain scientific equipoise. ... [This] reinforces the need to carry on this analysis into the future to obtain an unequivocal picture,” she emphasized.
 

Norwegian study: If there is an association, the risk is small

German Tapia, PhD, from the Norwegian Institute of Public Health, Oslo, presented the results of a study of SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children in Norway.

Of these, 424,354 children had been infected with SARS-CoV-2, and there were 990 incident cases of type 1 diabetes.

“What we do know about COVID-19 in children is that the symptoms are mild and only a small proportion are hospitalized with more serious symptoms. But we do not know the long-term effects of COVID-19 infection because this requires a longer follow-up period,” remarked Dr. Tapia, adding that other viral infections are thought to be linked to the development of type 1 diabetes, in particular, respiratory infections.

The data were sourced from the Norwegian Emergency Preparedness Register for COVID-19, which gathers daily data updates including infections (positive and negative results for free-of-charge testing), diagnoses (primary and secondary care), vaccinations (also free of charge), prescribed medications, and basic demographics.

“We link these data using the personal identification number that every Norwegian citizen has,” explained Dr. Tapia.

He presented results from two cohorts: firstly, results in children only, including those tested for SARS-CoV-2 infection, and secondly, a full national Norwegian population cohort.

Regarding the first cohort, those under 18 years who tested positive for SARS-CoV-2 infection, from March 2020 to March 2022, had a significantly increased risk of type 1 diabetes at least 31 days after infection, with an adjusted hazard ratio of 1.63 (95% confidence interval, 1.08-2.47; P = .02). Adjustments were made for age, sex, non-Nordic country of origin, geographic area, and socioeconomic factors.

For children who developed type 1 diabetes within 30 days of a SARS-CoV-2 infection, the HR was 1.26 (95% CI, 0.72-2.19; P = .42), which did not reach statistical significance.

“The fact that fewer people developed type 1 diabetes within 30 days is not surprising because we know that type 1 diabetes develops over a long period of time,” Dr. Tapia said.

“For this reason, we would not expect to find new cases of those people who develop type 1 diabetes within 30 days of COVID-19 infection,” he explained. In these cases, “it is most likely that they already had [type 1 diabetes], and the infection probably triggered clinical symptoms, so their type 1 diabetes was discovered.”

Turning to the full population cohort and diagnoses of type 1 diabetes over 30 days after SARS-CoV-2 infection, the Norwegian researchers found an association, with an HR of 1.57 (95% CI, 1.06-2.33; P = .03), while diagnosis of type 1 diabetes at 30 days or less generated a hazard ratio of 1.22 (95% CI, 0.72-2.19; P = .42).

“So very similar results were found, and after adjustment for confounders, results were still similar,” reported Dr. Tapia.

He also conducted a similar analysis with vaccination as an exposure but found no association between vaccination against SARS-CoV-2 and diagnosis of type 1 diabetes.

“From these results, we conclude that this suggests an increase in diagnosis of type 1 diabetes after SARS-CoV-2 infection, but it must be noted that the absolute risk of developing type 1 diabetes after infection in children is low, with most children not developing the disease,” he emphasized. “There are nearly half a million children who have been infected with SARS-CoV-2 in Norway, but only a very small proportion develop type 1 diabetes.”
 

Scottish study: No association found over longer term

Dr. Colhoun and colleagues looked at the relationship between incident type 1 diabetes and SARS-CoV-2 infection in children in Scotland using e-health record linkage.

The study involved 1.8 million people under 35 years of age and found very weak, if any, evidence of an association between incident type 1 diabetes and SARS-CoV-2.

Examining data between March 2020 and November 2021, Dr. Colhoun and colleagues identified 365,080 individuals up to age 35 with at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes.

“In children under 16 years, suspected cases of type 1 diabetes are admitted to hospital, and 97% of diagnosis dates are recorded in the Scottish Care Information – Diabetes Collaboration register [SCI-Diabetes] prior to or within 2 days of the first hospital admission for type 1 diabetes,” Dr. Colhoun said, stressing the timeliness of the data.

“We found the incidence of type 1 diabetes diagnosis increased 1.2-fold in those aged 0-14 years, but we did not find any association at an individual level of COVID-19 infection over 30 days prior to a type 1 diabetes diagnosis, in this particular dataset,” she reported. In young people aged 15-34, there was a linear increase in incident type 1 diabetes from 2015 to 2021 with no pandemic increase.

Referring to the 1.2-fold increase soon after the pandemic started, she explained that, in 0- to 14-year-olds, the increase followed a drop in the preceding months prepandemic in 2019. They also found that the seasonal pattern of type 1 diabetes diagnoses remained roughly the same across the pandemic months, with typical peaks in February and September.

In the cohort of under 35s, researchers also found a rate ratio of 2.62 (95% CI, 1.81-3.78) within a 30-day window of SARS-CoV-2 infection, but beyond 30 days, no evidence was seen of an association, with a RR of 0.86 (95% CI, 0.62-1.21; P = .40), she reported.

She explained her reasons for not considering diagnoses within 30 days of COVID-19 as causative. Echoing Dr. Tapia, Dr. Colhoun said the median time from symptom onset to diagnosis of type 1 diabetes is 25 days. “This suggests that 50% have had symptoms for over 25 days at diagnosis.”

She also stressed that when they compared the timing of SARS-CoV-2 testing with diagnosis, they found a much higher rate of COVID-19 testing around diagnosis. “This was not least because everyone admitted to hospital had to have a COVID-19 test.”
 

Latest U.S. data point to a link

Meanwhile, for the new data reported in JAMA Network Open, medical student Ellen K. Kendall of Case Western Reserve University, Cleveland, matched 571,256 pediatric patients: 285,628 with COVID-19 and 285,628 with non–COVID-19 respiratory infections.

By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of type 1 diabetes, but only 72 (0.025%) were diagnosed with type 1 diabetes within 6 months after non–COVID-19 respiratory infection.

At 1, 3, and 6 months after infection, risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2, compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96; 3 months: HR, 2.10; and 6 months: HR, 1.83), and in subgroups of patients aged 0-9 years, a group unlikely to develop type 2 diabetes.

“In this study, new type 1 diabetes diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems),” noted Ms. Kendall and coauthors. “Respiratory infections have previously been associated with onset of type 1 diabetes, but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths.”

“The increased risk of new-onset type 1 diabetes after COVID-19 adds an important consideration for risk–benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A study from the Centers for Disease Control and Prevention published in January 2022, also concluded there was a link between COVID-19 and diabetes in children, but not with other acute respiratory infections. Children were 2.5 times more likely to be diagnosed with diabetes following a SARS-CoV-2 infection, it found.

However, the study has been criticized because it pooled all types of diabetes together and did not account for other health conditions, medications that can increase blood glucose levels, race, obesity, and other social determinants of health that might influence a child’s risk of acquiring COVID-19 or diabetes.

“I’ve no doubt that the CDC data were incorrect because the incidence rate for ... diabetes, even in those never exposed to COVID-19 infection, was 10 times the rate ever reported in the U.S.,” Dr. Colhoun said. “There’s no way these data are correct. I believe there was a confusion between incidence and prevalence of diabetes.”

“This paper caused a great deal of panic, especially among those who have a child with type 1diabetes, so we need to be very careful not to cause undue alarm until we have more definitive evidence in this arena,” she stressed.

However, she also acknowledged that the new Norwegian study was well conducted, and she has no methodological concerns about it, so “I think we just have to wait and see.”

Given the inconclusiveness on the issue, there is an ongoing CoviDiab registry collecting data on this very subject.

Dr. Tapia presented on behalf of lead author Dr. Gulseth, who has reported no relevant financial relationships. Dr. Colhoun also reported no relevant financial relationships.

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

The diagnosis and management of refractory celiac disease remains challenging, but ongoing studies can provide the proper diagnostic criteria and identify the optimal management strategies, according to a new American Gastroenterological Association expert review published in Gastroenterology.

Celiac disease is present in about 1% of the U.S. population and can cause various symptoms, wrote Peter H. R. Green, MD, director of the Celiac Disease Center at Columbia University, New York, and colleagues. Adhering to a strict gluten-free diet can improve symptoms, normalize serum antibody levels, and reverse small bowel villous atrophy. However, persistent or recurrent symptoms and elevated celiac antibodies can persist in some patients after a year of trying a gluten-free diet, a condition called nonresponsive celiac disease. In some patients, this raises concern for refractory celiac disease, or RCD.

“RCD is believed to occur in only approximately 1% of patients with celiac disease, although this may be an overestimate, as data are obtained from referral centers,” the authors wrote.

RCD can be classified into two subtypes with different diagnostic criteria, prognoses, and therapy responses. The first, called RCD1, is characterized by villous atrophy but has intraepithelial lymphocytes similar to conventional celiac disease. The other, called RCD2, is characterized by aberrant clonal T-cell expansion in the intestinal tract and other organs, has a poorer prognosis than RCD1, and has a risk of developing ulcerative jejunoileitis or enteropathy-associated T-cell lymphoma.

The experts developed 10 clinical practice advice statements based on a review of the published literature and expert opinion.

First, in patients who have persistent or recurring symptoms, an initial celiac disease diagnosis should be confirmed through review of prior diagnostic testing, including serologies, endoscopies, and histologic findings. Celiac disease can overlap with other gastrointestinal conditions, and some pathologic findings aren’t specific to celiac disease. Results of serologic testing with tissue transglutaminase immunoglobulin A, deamidated gliadin peptide IgA and IgG, and endomysial antibodies should be reviewed or obtained if not previously performed.

Next, in those with confirmed but nonresponsive celiac disease, ongoing gluten ingestion should be excluded as a cause of symptoms with serologic testing, dietitian review, and potentially detection of immunogenic peptides in stool or urine samples. The authors noted that persistent gluten ingestion, whether intentional or inadvertent, accounts for 40%-50% of patients with nonresponsive celiac disease. In these cases, esophagogastroduodenoscopy and small bowel biopsies should be performed to look for persistent villous atrophy, which can also be caused by common variable immunodeficiency, autoimmune enteropathy, tropical sprue, and medication-induced enteropathy. Patients with villous atrophy due to other causes won’t respond to a gluten-free diet.

After excluding gluten, clinicians should perform a systematic evaluation for other potential causes of symptoms, including functional bowel disorders, lactose or fructose intolerance, microscopic colitis, pancreatic insufficiency, inflammatory bowel disease, and small intestinal bacterial growth. Irritable bowel syndrome, for instance, may contribute to persistent symptoms and respond to fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) restriction. RCD should be strongly considered in patients with persistent symptoms or signs of malabsorption after the exclusion of the other causes.

To distinguish between the two subtypes of RCD and exclude enteropathy-associated T-cell lymphoma, clinicians should use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies. RCD1 has a normal intraepithelial lymphocyte population, and RCD2 has an aberrant, clonal intraepithelial lymphocyte population. Consulting with a hematopathologist may be necessary to interpret these studies.

After RCD2 is diagnosed, complications such as enteropathy-associated T-cell lymphoma and ulcerative jejunoileitis should be excluded through small bowel imaging with capsule endoscopy and either computed tomography (CT) or magnetic resonance enterography. In general, the extent and severity of villous atrophy is greater in patients with RCD2, compared with RCD1.

In patients diagnosed with RCD, clinicians should complete a detailed nutritional assessment with investigation of micronutrient and macronutrient deficiencies. Check albumin as an independent prognostic factor. Then, try to correct deficiencies with oral supplements. Malnourished patients may need enteral support, and those with severe malnutrition due to malabsorption may need parenteral support.

So far, RCD management suggestions are based on small retrospective studies and expert opinion, with minimal prospective data and no Food and Drug Administration–approved therapies. The goals should be to improve symptoms and duodenal mucosal abnormalities, manage malnutrition, and prevent lymphoma. Glucocorticoids are considered first-line therapy, typically open-capsule budesonide given as 3 mg three times daily. Prednisone serves as an alternative with proven efficacy but a higher risk for adverse effects.

The optimal choice for second-line therapy is unknown, but the addition of an immunosuppressant agent to steroids appears to be effective in RCD1, including azathioprine, mercaptopurine, and tioguanine. The best treatment for RCD2 is unknown, though clinical response has been reported with steroids, and cladribine has been well tolerated in some patients.

Patients with RCD who don’t respond to steroids may benefit from referral to a center with expertise for management or evaluation for inclusion in clinical trials. Frequent medical visits are advised until the disease is well controlled, with regular follow-up after that. 

Ultimately, “patients with RCD benefit from evaluation and regular follow-up by a multidisciplinary team, including gastroenterologists and dietitians, to assess clinical and histologic response to therapy,” the authors wrote. “Identify local experts with expertise in celiac disease to assist with management.”

The authors reported no grant support or funding sources for this study. One author has received research report from Freenome, and another is on the celiac disease advisory board for Takeda. The remaining authors disclosed no conflicts.

The diagnosis and management of refractory celiac disease remains challenging, but ongoing studies can provide the proper diagnostic criteria and identify the optimal management strategies, according to a new American Gastroenterological Association expert review published in Gastroenterology.

Celiac disease is present in about 1% of the U.S. population and can cause various symptoms, wrote Peter H. R. Green, MD, director of the Celiac Disease Center at Columbia University, New York, and colleagues. Adhering to a strict gluten-free diet can improve symptoms, normalize serum antibody levels, and reverse small bowel villous atrophy. However, persistent or recurrent symptoms and elevated celiac antibodies can persist in some patients after a year of trying a gluten-free diet, a condition called nonresponsive celiac disease. In some patients, this raises concern for refractory celiac disease, or RCD.

“RCD is believed to occur in only approximately 1% of patients with celiac disease, although this may be an overestimate, as data are obtained from referral centers,” the authors wrote.

RCD can be classified into two subtypes with different diagnostic criteria, prognoses, and therapy responses. The first, called RCD1, is characterized by villous atrophy but has intraepithelial lymphocytes similar to conventional celiac disease. The other, called RCD2, is characterized by aberrant clonal T-cell expansion in the intestinal tract and other organs, has a poorer prognosis than RCD1, and has a risk of developing ulcerative jejunoileitis or enteropathy-associated T-cell lymphoma.

The experts developed 10 clinical practice advice statements based on a review of the published literature and expert opinion.

First, in patients who have persistent or recurring symptoms, an initial celiac disease diagnosis should be confirmed through review of prior diagnostic testing, including serologies, endoscopies, and histologic findings. Celiac disease can overlap with other gastrointestinal conditions, and some pathologic findings aren’t specific to celiac disease. Results of serologic testing with tissue transglutaminase immunoglobulin A, deamidated gliadin peptide IgA and IgG, and endomysial antibodies should be reviewed or obtained if not previously performed.

Next, in those with confirmed but nonresponsive celiac disease, ongoing gluten ingestion should be excluded as a cause of symptoms with serologic testing, dietitian review, and potentially detection of immunogenic peptides in stool or urine samples. The authors noted that persistent gluten ingestion, whether intentional or inadvertent, accounts for 40%-50% of patients with nonresponsive celiac disease. In these cases, esophagogastroduodenoscopy and small bowel biopsies should be performed to look for persistent villous atrophy, which can also be caused by common variable immunodeficiency, autoimmune enteropathy, tropical sprue, and medication-induced enteropathy. Patients with villous atrophy due to other causes won’t respond to a gluten-free diet.

After excluding gluten, clinicians should perform a systematic evaluation for other potential causes of symptoms, including functional bowel disorders, lactose or fructose intolerance, microscopic colitis, pancreatic insufficiency, inflammatory bowel disease, and small intestinal bacterial growth. Irritable bowel syndrome, for instance, may contribute to persistent symptoms and respond to fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) restriction. RCD should be strongly considered in patients with persistent symptoms or signs of malabsorption after the exclusion of the other causes.

To distinguish between the two subtypes of RCD and exclude enteropathy-associated T-cell lymphoma, clinicians should use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies. RCD1 has a normal intraepithelial lymphocyte population, and RCD2 has an aberrant, clonal intraepithelial lymphocyte population. Consulting with a hematopathologist may be necessary to interpret these studies.

After RCD2 is diagnosed, complications such as enteropathy-associated T-cell lymphoma and ulcerative jejunoileitis should be excluded through small bowel imaging with capsule endoscopy and either computed tomography (CT) or magnetic resonance enterography. In general, the extent and severity of villous atrophy is greater in patients with RCD2, compared with RCD1.

In patients diagnosed with RCD, clinicians should complete a detailed nutritional assessment with investigation of micronutrient and macronutrient deficiencies. Check albumin as an independent prognostic factor. Then, try to correct deficiencies with oral supplements. Malnourished patients may need enteral support, and those with severe malnutrition due to malabsorption may need parenteral support.

So far, RCD management suggestions are based on small retrospective studies and expert opinion, with minimal prospective data and no Food and Drug Administration–approved therapies. The goals should be to improve symptoms and duodenal mucosal abnormalities, manage malnutrition, and prevent lymphoma. Glucocorticoids are considered first-line therapy, typically open-capsule budesonide given as 3 mg three times daily. Prednisone serves as an alternative with proven efficacy but a higher risk for adverse effects.

The optimal choice for second-line therapy is unknown, but the addition of an immunosuppressant agent to steroids appears to be effective in RCD1, including azathioprine, mercaptopurine, and tioguanine. The best treatment for RCD2 is unknown, though clinical response has been reported with steroids, and cladribine has been well tolerated in some patients.

Patients with RCD who don’t respond to steroids may benefit from referral to a center with expertise for management or evaluation for inclusion in clinical trials. Frequent medical visits are advised until the disease is well controlled, with regular follow-up after that. 

Ultimately, “patients with RCD benefit from evaluation and regular follow-up by a multidisciplinary team, including gastroenterologists and dietitians, to assess clinical and histologic response to therapy,” the authors wrote. “Identify local experts with expertise in celiac disease to assist with management.”

The authors reported no grant support or funding sources for this study. One author has received research report from Freenome, and another is on the celiac disease advisory board for Takeda. The remaining authors disclosed no conflicts.

The diagnosis and management of refractory celiac disease remains challenging, but ongoing studies can provide the proper diagnostic criteria and identify the optimal management strategies, according to a new American Gastroenterological Association expert review published in Gastroenterology.

Celiac disease is present in about 1% of the U.S. population and can cause various symptoms, wrote Peter H. R. Green, MD, director of the Celiac Disease Center at Columbia University, New York, and colleagues. Adhering to a strict gluten-free diet can improve symptoms, normalize serum antibody levels, and reverse small bowel villous atrophy. However, persistent or recurrent symptoms and elevated celiac antibodies can persist in some patients after a year of trying a gluten-free diet, a condition called nonresponsive celiac disease. In some patients, this raises concern for refractory celiac disease, or RCD.

“RCD is believed to occur in only approximately 1% of patients with celiac disease, although this may be an overestimate, as data are obtained from referral centers,” the authors wrote.

RCD can be classified into two subtypes with different diagnostic criteria, prognoses, and therapy responses. The first, called RCD1, is characterized by villous atrophy but has intraepithelial lymphocytes similar to conventional celiac disease. The other, called RCD2, is characterized by aberrant clonal T-cell expansion in the intestinal tract and other organs, has a poorer prognosis than RCD1, and has a risk of developing ulcerative jejunoileitis or enteropathy-associated T-cell lymphoma.

The experts developed 10 clinical practice advice statements based on a review of the published literature and expert opinion.

First, in patients who have persistent or recurring symptoms, an initial celiac disease diagnosis should be confirmed through review of prior diagnostic testing, including serologies, endoscopies, and histologic findings. Celiac disease can overlap with other gastrointestinal conditions, and some pathologic findings aren’t specific to celiac disease. Results of serologic testing with tissue transglutaminase immunoglobulin A, deamidated gliadin peptide IgA and IgG, and endomysial antibodies should be reviewed or obtained if not previously performed.

Next, in those with confirmed but nonresponsive celiac disease, ongoing gluten ingestion should be excluded as a cause of symptoms with serologic testing, dietitian review, and potentially detection of immunogenic peptides in stool or urine samples. The authors noted that persistent gluten ingestion, whether intentional or inadvertent, accounts for 40%-50% of patients with nonresponsive celiac disease. In these cases, esophagogastroduodenoscopy and small bowel biopsies should be performed to look for persistent villous atrophy, which can also be caused by common variable immunodeficiency, autoimmune enteropathy, tropical sprue, and medication-induced enteropathy. Patients with villous atrophy due to other causes won’t respond to a gluten-free diet.

After excluding gluten, clinicians should perform a systematic evaluation for other potential causes of symptoms, including functional bowel disorders, lactose or fructose intolerance, microscopic colitis, pancreatic insufficiency, inflammatory bowel disease, and small intestinal bacterial growth. Irritable bowel syndrome, for instance, may contribute to persistent symptoms and respond to fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) restriction. RCD should be strongly considered in patients with persistent symptoms or signs of malabsorption after the exclusion of the other causes.

To distinguish between the two subtypes of RCD and exclude enteropathy-associated T-cell lymphoma, clinicians should use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies. RCD1 has a normal intraepithelial lymphocyte population, and RCD2 has an aberrant, clonal intraepithelial lymphocyte population. Consulting with a hematopathologist may be necessary to interpret these studies.

After RCD2 is diagnosed, complications such as enteropathy-associated T-cell lymphoma and ulcerative jejunoileitis should be excluded through small bowel imaging with capsule endoscopy and either computed tomography (CT) or magnetic resonance enterography. In general, the extent and severity of villous atrophy is greater in patients with RCD2, compared with RCD1.

In patients diagnosed with RCD, clinicians should complete a detailed nutritional assessment with investigation of micronutrient and macronutrient deficiencies. Check albumin as an independent prognostic factor. Then, try to correct deficiencies with oral supplements. Malnourished patients may need enteral support, and those with severe malnutrition due to malabsorption may need parenteral support.

So far, RCD management suggestions are based on small retrospective studies and expert opinion, with minimal prospective data and no Food and Drug Administration–approved therapies. The goals should be to improve symptoms and duodenal mucosal abnormalities, manage malnutrition, and prevent lymphoma. Glucocorticoids are considered first-line therapy, typically open-capsule budesonide given as 3 mg three times daily. Prednisone serves as an alternative with proven efficacy but a higher risk for adverse effects.

The optimal choice for second-line therapy is unknown, but the addition of an immunosuppressant agent to steroids appears to be effective in RCD1, including azathioprine, mercaptopurine, and tioguanine. The best treatment for RCD2 is unknown, though clinical response has been reported with steroids, and cladribine has been well tolerated in some patients.

Patients with RCD who don’t respond to steroids may benefit from referral to a center with expertise for management or evaluation for inclusion in clinical trials. Frequent medical visits are advised until the disease is well controlled, with regular follow-up after that. 

Ultimately, “patients with RCD benefit from evaluation and regular follow-up by a multidisciplinary team, including gastroenterologists and dietitians, to assess clinical and histologic response to therapy,” the authors wrote. “Identify local experts with expertise in celiac disease to assist with management.”

The authors reported no grant support or funding sources for this study. One author has received research report from Freenome, and another is on the celiac disease advisory board for Takeda. The remaining authors disclosed no conflicts.

The COVID-19 pandemic has been associated with the development of anorexia nervosa in Canadian children and adolescents, data suggest.

Preliminary results of the Canadian Paediatric Surveillance Program (CPSP) indicate that the pandemic has been a precipitating factor in the development of anorexia nervosa in almost half of children and adolescents studied. The pandemic also has precipitated hospitalizations for anorexia in more than one-third of cases.

“Data globally, and certainly our data here in Canada, have shown a real increase in health care utilization with the onset of the COVID-19 pandemic,” study author Debra Katzman, MD, professor of pediatrics at the Hospital for Sick Children in Toronto and the University of Toronto, said in an interview. “And when I talk about health care utilization, I’m talking about hospitalizations for eating disorders.”

The data were included in the 2021 results of the CPSP.
 

Focus on appearance

CPSP is a collaboration between the Public Health Agency of Canada and the Canadian Pediatric Society that consists of a network of 2,800 pediatricians and pediatric subspecialists across Canada. The latest results include surveillance studies on 14 diseases and conditions, with data collected during various periods.

From April 2020 to May 2021, researchers identified 1,800 COVID-19 cases in children and collected detailed information on 1,456 of them, including 405 cases hospitalized with pediatric inflammatory multisystem syndrome (PIMS). The median age of hospitalized cases was 3.2 years for SARS-CoV-2 infection and 5.4 years for PIMS.

Dr. Katzman and colleagues observed 118 first-time hospitalizations for anorexia nervosa between Sept. 1 and Dec. 31, 2021. More than 90% of reported cases were female, with 66% of verified cases in teens aged 14-17 years and the remainder in adolescents aged 11-13 years.

In 49% of cases, the reporting physician identified the COVID-19 pandemic as a precipitating factor in the development of anorexia nervosa. In 37% of cases, the reporting physician identified the pandemic as having precipitated the anorexia-related hospitalization.

Last year, a cross-sectional analysis of children in Canada reported that monthly hospitalizations for anorexia nervosa increased from 7.5 to 20 from March through November 2020. The monthly rate in the CPSP study was closer to 30 for first-time hospitalizations.

Dr. Katzman said that the findings about anorexia nervosa didn’t surprise her. “There was so much disruption and [so many] restrictions to young peoples’ daily routines – closures of schools and recreational activities – they lost regular connection with their peers, and they lost extracurricular and social activities,” she said. “That led to heightened anxiety and depression and really a lack of control.”

Adolescents and teens were also spending more time on social media than they were before the pandemic, she noted. “They were looking at themselves all the time, so they were getting preoccupied with their body image. There was a heightened focus on appearance, and I think that things like public-health mitigation strategies – things like hand washing, social distancing, mask wearing – may have impacted the psychological well-being of young people.”

The closure of outpatient facilities, long waiting lists to get into facilities that were opened, and “coronaphobia” about going to physicians’ offices and emergency departments compounded the problem, Dr. Katzman added.

The long-term effects of COVID and eating disorders in children are unknown, Dr. Katzman said. “This is sort of a wake-up call for the health care system that during times of stress or pandemics or crises, these kinds of things can happen, and we need to be prepared to provide the resources for vulnerable populations moving forward,” she said.
 

Heightened anxiety

Commenting on the data, Margaret Thew, APNP, director of the eating disorders program at Children’s Wisconsin in Milwaukee, said that isolation due to school closures and negative social media messages created the “perfect storm” for eating disorders in adolescents and teenagers because of higher rates of anxiety and depression. Ms. Thew was not involved in the research.

The storm is not over yet, she said. “What everyone needs to keep in mind is that we still have this very heightened state of anxiety and depression ... for adolescents, teenagers, and preteens alike,” Ms. Thew said in an interview, “and we know that many of them are not coping with their anxiety very well.”

In her experience, since the start of the pandemic, the average age of pediatric patients with eating disorders declined from 16 to 15 years, and the youngest age declined from 12 to 11 years.

Overall, the CPSP results show that children are affected by mental health issues at an earlier age than before the pandemic, said Ms. Thew. “Years ago, we wouldn’t have thought that an 8-year-old needed to be screened for some of these risk factors, but now we’re definitely getting more younger children who are struggling, and I think it’s taking too long for them to get the care they need because it’s being overlooked,” she said.

The report was funded by the Public Health Agency of Canada, Health Canada, Alberta Children’s Hospital Research Institute, Bethanys Hope Foundation, CHEO Research Institute, and Children’s Hospital Research Institute of Manitoba. Dr. Katzman and Ms. Thew have no relevant disclosures.

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

The COVID-19 pandemic has been associated with the development of anorexia nervosa in Canadian children and adolescents, data suggest.

Preliminary results of the Canadian Paediatric Surveillance Program (CPSP) indicate that the pandemic has been a precipitating factor in the development of anorexia nervosa in almost half of children and adolescents studied. The pandemic also has precipitated hospitalizations for anorexia in more than one-third of cases.

“Data globally, and certainly our data here in Canada, have shown a real increase in health care utilization with the onset of the COVID-19 pandemic,” study author Debra Katzman, MD, professor of pediatrics at the Hospital for Sick Children in Toronto and the University of Toronto, said in an interview. “And when I talk about health care utilization, I’m talking about hospitalizations for eating disorders.”

The data were included in the 2021 results of the CPSP.
 

Focus on appearance

CPSP is a collaboration between the Public Health Agency of Canada and the Canadian Pediatric Society that consists of a network of 2,800 pediatricians and pediatric subspecialists across Canada. The latest results include surveillance studies on 14 diseases and conditions, with data collected during various periods.

From April 2020 to May 2021, researchers identified 1,800 COVID-19 cases in children and collected detailed information on 1,456 of them, including 405 cases hospitalized with pediatric inflammatory multisystem syndrome (PIMS). The median age of hospitalized cases was 3.2 years for SARS-CoV-2 infection and 5.4 years for PIMS.

Dr. Katzman and colleagues observed 118 first-time hospitalizations for anorexia nervosa between Sept. 1 and Dec. 31, 2021. More than 90% of reported cases were female, with 66% of verified cases in teens aged 14-17 years and the remainder in adolescents aged 11-13 years.

In 49% of cases, the reporting physician identified the COVID-19 pandemic as a precipitating factor in the development of anorexia nervosa. In 37% of cases, the reporting physician identified the pandemic as having precipitated the anorexia-related hospitalization.

Last year, a cross-sectional analysis of children in Canada reported that monthly hospitalizations for anorexia nervosa increased from 7.5 to 20 from March through November 2020. The monthly rate in the CPSP study was closer to 30 for first-time hospitalizations.

Dr. Katzman said that the findings about anorexia nervosa didn’t surprise her. “There was so much disruption and [so many] restrictions to young peoples’ daily routines – closures of schools and recreational activities – they lost regular connection with their peers, and they lost extracurricular and social activities,” she said. “That led to heightened anxiety and depression and really a lack of control.”

Adolescents and teens were also spending more time on social media than they were before the pandemic, she noted. “They were looking at themselves all the time, so they were getting preoccupied with their body image. There was a heightened focus on appearance, and I think that things like public-health mitigation strategies – things like hand washing, social distancing, mask wearing – may have impacted the psychological well-being of young people.”

The closure of outpatient facilities, long waiting lists to get into facilities that were opened, and “coronaphobia” about going to physicians’ offices and emergency departments compounded the problem, Dr. Katzman added.

The long-term effects of COVID and eating disorders in children are unknown, Dr. Katzman said. “This is sort of a wake-up call for the health care system that during times of stress or pandemics or crises, these kinds of things can happen, and we need to be prepared to provide the resources for vulnerable populations moving forward,” she said.
 

Heightened anxiety

Commenting on the data, Margaret Thew, APNP, director of the eating disorders program at Children’s Wisconsin in Milwaukee, said that isolation due to school closures and negative social media messages created the “perfect storm” for eating disorders in adolescents and teenagers because of higher rates of anxiety and depression. Ms. Thew was not involved in the research.

The storm is not over yet, she said. “What everyone needs to keep in mind is that we still have this very heightened state of anxiety and depression ... for adolescents, teenagers, and preteens alike,” Ms. Thew said in an interview, “and we know that many of them are not coping with their anxiety very well.”

In her experience, since the start of the pandemic, the average age of pediatric patients with eating disorders declined from 16 to 15 years, and the youngest age declined from 12 to 11 years.

Overall, the CPSP results show that children are affected by mental health issues at an earlier age than before the pandemic, said Ms. Thew. “Years ago, we wouldn’t have thought that an 8-year-old needed to be screened for some of these risk factors, but now we’re definitely getting more younger children who are struggling, and I think it’s taking too long for them to get the care they need because it’s being overlooked,” she said.

The report was funded by the Public Health Agency of Canada, Health Canada, Alberta Children’s Hospital Research Institute, Bethanys Hope Foundation, CHEO Research Institute, and Children’s Hospital Research Institute of Manitoba. Dr. Katzman and Ms. Thew have no relevant disclosures.

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

The COVID-19 pandemic has been associated with the development of anorexia nervosa in Canadian children and adolescents, data suggest.

Preliminary results of the Canadian Paediatric Surveillance Program (CPSP) indicate that the pandemic has been a precipitating factor in the development of anorexia nervosa in almost half of children and adolescents studied. The pandemic also has precipitated hospitalizations for anorexia in more than one-third of cases.

“Data globally, and certainly our data here in Canada, have shown a real increase in health care utilization with the onset of the COVID-19 pandemic,” study author Debra Katzman, MD, professor of pediatrics at the Hospital for Sick Children in Toronto and the University of Toronto, said in an interview. “And when I talk about health care utilization, I’m talking about hospitalizations for eating disorders.”

The data were included in the 2021 results of the CPSP.
 

Focus on appearance

CPSP is a collaboration between the Public Health Agency of Canada and the Canadian Pediatric Society that consists of a network of 2,800 pediatricians and pediatric subspecialists across Canada. The latest results include surveillance studies on 14 diseases and conditions, with data collected during various periods.

From April 2020 to May 2021, researchers identified 1,800 COVID-19 cases in children and collected detailed information on 1,456 of them, including 405 cases hospitalized with pediatric inflammatory multisystem syndrome (PIMS). The median age of hospitalized cases was 3.2 years for SARS-CoV-2 infection and 5.4 years for PIMS.

Dr. Katzman and colleagues observed 118 first-time hospitalizations for anorexia nervosa between Sept. 1 and Dec. 31, 2021. More than 90% of reported cases were female, with 66% of verified cases in teens aged 14-17 years and the remainder in adolescents aged 11-13 years.

In 49% of cases, the reporting physician identified the COVID-19 pandemic as a precipitating factor in the development of anorexia nervosa. In 37% of cases, the reporting physician identified the pandemic as having precipitated the anorexia-related hospitalization.

Last year, a cross-sectional analysis of children in Canada reported that monthly hospitalizations for anorexia nervosa increased from 7.5 to 20 from March through November 2020. The monthly rate in the CPSP study was closer to 30 for first-time hospitalizations.

Dr. Katzman said that the findings about anorexia nervosa didn’t surprise her. “There was so much disruption and [so many] restrictions to young peoples’ daily routines – closures of schools and recreational activities – they lost regular connection with their peers, and they lost extracurricular and social activities,” she said. “That led to heightened anxiety and depression and really a lack of control.”

Adolescents and teens were also spending more time on social media than they were before the pandemic, she noted. “They were looking at themselves all the time, so they were getting preoccupied with their body image. There was a heightened focus on appearance, and I think that things like public-health mitigation strategies – things like hand washing, social distancing, mask wearing – may have impacted the psychological well-being of young people.”

The closure of outpatient facilities, long waiting lists to get into facilities that were opened, and “coronaphobia” about going to physicians’ offices and emergency departments compounded the problem, Dr. Katzman added.

The long-term effects of COVID and eating disorders in children are unknown, Dr. Katzman said. “This is sort of a wake-up call for the health care system that during times of stress or pandemics or crises, these kinds of things can happen, and we need to be prepared to provide the resources for vulnerable populations moving forward,” she said.
 

Heightened anxiety

Commenting on the data, Margaret Thew, APNP, director of the eating disorders program at Children’s Wisconsin in Milwaukee, said that isolation due to school closures and negative social media messages created the “perfect storm” for eating disorders in adolescents and teenagers because of higher rates of anxiety and depression. Ms. Thew was not involved in the research.

The storm is not over yet, she said. “What everyone needs to keep in mind is that we still have this very heightened state of anxiety and depression ... for adolescents, teenagers, and preteens alike,” Ms. Thew said in an interview, “and we know that many of them are not coping with their anxiety very well.”

In her experience, since the start of the pandemic, the average age of pediatric patients with eating disorders declined from 16 to 15 years, and the youngest age declined from 12 to 11 years.

Overall, the CPSP results show that children are affected by mental health issues at an earlier age than before the pandemic, said Ms. Thew. “Years ago, we wouldn’t have thought that an 8-year-old needed to be screened for some of these risk factors, but now we’re definitely getting more younger children who are struggling, and I think it’s taking too long for them to get the care they need because it’s being overlooked,” she said.

The report was funded by the Public Health Agency of Canada, Health Canada, Alberta Children’s Hospital Research Institute, Bethanys Hope Foundation, CHEO Research Institute, and Children’s Hospital Research Institute of Manitoba. Dr. Katzman and Ms. Thew have no relevant disclosures.

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

This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.

It was 100 years ago when Leonard Thompson, age 13, received a reprieve from a death sentence. Young master Thompson had type 1 diabetes, a disease that was uniformly fatal within months of diagnosis. But he received a new treatment, insulin, from a canine pancreas. He would live 13 more years before dying at age 26 of pneumonia.

The history of type 1 diabetes since that time has been a battle on two fronts: First, the search for a cause of and cure for the disease; second, the effort to make the administration of insulin safer, more reliable, and easier.

The past 2 decades have seen a technological revolution in type 1 diabetes care, with continuous glucose monitors decreasing the need for painful finger sticks, and insulin pumps allowing for more precise titration of doses.

The dream, of course, has been to combine those two technologies, continuous glucose monitoring and insulin pumps, to create so-called closed-loop systems – basically an artificial pancreas – that would obviate the need for any intervention on the part of the patient, save the occasional refilling of an insulin reservoir.

We aren’t there yet, but we are closer than ever.

Closed-loop systems for insulin delivery, like the Tandem Control IQ system, are a marvel of technology, but they are not exactly hands-free. Users need to dial in settings for their insulin usage, count carbohydrates at meals, and inform the system that they are about to eat those meals to allow the algorithm to administer an appropriate insulin dose.

The perceived complexity of these systems may be responsible for why there are substantial disparities in the prescription of closed-loop systems. Kids of lower socioeconomic status are dramatically less likely to receive these advanced technologies. Providers may feel that patients with lower health literacy or social supports are not “ideal” for these technologies, even though they lead to demonstrably better outcomes.

That means that easier might be better. And a “bionic pancreas,” as reported in an article from The New England Journal of Medicine, is exactly that.

Broadly, it’s another closed-loop system. The bionic pancreas integrates with a continuous glucose monitor and administers insulin when needed. But the algorithm appears to be a bit smarter than what we have in existing devices. For example, patients do not need to provide any information about their usual insulin doses – just their body weight. They don’t need to count carbohydrates at meals – just to inform the device when they are eating, and whether the meal is the usual amount they eat, more, or less. The algorithm learns and adapts as it is used. Easy.

And in this randomized trial, easy does it.

A total of 219 participants were randomized in a 2:1 ratio to the bionic pancreas or usual diabetes care, though it was required that control participants use a continuous glucose monitor. Participants were as young as 6 years old and up to 79 years old; the majority were White and had a relatively high household income. The mean A1c was around 7.8% at baseline.

By the end of the study, the A1c was significantly improved in the bionic pancreas group, with a mean of 7.3% vs. 7.7% in the usual-care group.

This effect was most pronounced in those with a higher A1c at baseline.

People randomized to the bionic pancreas also spent more time in the target glucose range of 70-180 mg/dL.

All in all, the technology that makes it easy to manage your blood sugar, well, made it easy to manage your blood sugar.

But new technology is never without its hiccups. Those randomized to the bionic pancreas had a markedly higher rate of adverse events (244 events in 126 people compared with 10 events in 8 people in the usual-care group.)

This is actually a little misleading, though. The vast majority of these events were hyperglycemic episodes due to infusion set failures, which were reportable only in the bionic pancreas group. In other words, the patients in the control group who had an infusion set failure (assuming they were using an insulin pump at all) would have just called their regular doctor to get things sorted and not reported it to the study team.

Nevertheless, these adverse events – not serious, but common – highlight the fact that good software is not the only key to solving the closed-loop problem. We need good hardware too, hardware that can withstand the very active lives that children with type 1 diabetes deserve to live.

In short, the dream of a functional cure to type 1 diabetes, a true artificial pancreas, is closer than ever, but it’s still just a dream. With iterative advances like this, though, the reality may be here before you know it.

Dr. Wilson is associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. A version of this article first appeared on Medscape.com.

This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.

It was 100 years ago when Leonard Thompson, age 13, received a reprieve from a death sentence. Young master Thompson had type 1 diabetes, a disease that was uniformly fatal within months of diagnosis. But he received a new treatment, insulin, from a canine pancreas. He would live 13 more years before dying at age 26 of pneumonia.

The history of type 1 diabetes since that time has been a battle on two fronts: First, the search for a cause of and cure for the disease; second, the effort to make the administration of insulin safer, more reliable, and easier.

The past 2 decades have seen a technological revolution in type 1 diabetes care, with continuous glucose monitors decreasing the need for painful finger sticks, and insulin pumps allowing for more precise titration of doses.

The dream, of course, has been to combine those two technologies, continuous glucose monitoring and insulin pumps, to create so-called closed-loop systems – basically an artificial pancreas – that would obviate the need for any intervention on the part of the patient, save the occasional refilling of an insulin reservoir.

We aren’t there yet, but we are closer than ever.

Closed-loop systems for insulin delivery, like the Tandem Control IQ system, are a marvel of technology, but they are not exactly hands-free. Users need to dial in settings for their insulin usage, count carbohydrates at meals, and inform the system that they are about to eat those meals to allow the algorithm to administer an appropriate insulin dose.

The perceived complexity of these systems may be responsible for why there are substantial disparities in the prescription of closed-loop systems. Kids of lower socioeconomic status are dramatically less likely to receive these advanced technologies. Providers may feel that patients with lower health literacy or social supports are not “ideal” for these technologies, even though they lead to demonstrably better outcomes.

That means that easier might be better. And a “bionic pancreas,” as reported in an article from The New England Journal of Medicine, is exactly that.

Broadly, it’s another closed-loop system. The bionic pancreas integrates with a continuous glucose monitor and administers insulin when needed. But the algorithm appears to be a bit smarter than what we have in existing devices. For example, patients do not need to provide any information about their usual insulin doses – just their body weight. They don’t need to count carbohydrates at meals – just to inform the device when they are eating, and whether the meal is the usual amount they eat, more, or less. The algorithm learns and adapts as it is used. Easy.

And in this randomized trial, easy does it.

A total of 219 participants were randomized in a 2:1 ratio to the bionic pancreas or usual diabetes care, though it was required that control participants use a continuous glucose monitor. Participants were as young as 6 years old and up to 79 years old; the majority were White and had a relatively high household income. The mean A1c was around 7.8% at baseline.

By the end of the study, the A1c was significantly improved in the bionic pancreas group, with a mean of 7.3% vs. 7.7% in the usual-care group.

This effect was most pronounced in those with a higher A1c at baseline.

People randomized to the bionic pancreas also spent more time in the target glucose range of 70-180 mg/dL.

All in all, the technology that makes it easy to manage your blood sugar, well, made it easy to manage your blood sugar.

But new technology is never without its hiccups. Those randomized to the bionic pancreas had a markedly higher rate of adverse events (244 events in 126 people compared with 10 events in 8 people in the usual-care group.)

This is actually a little misleading, though. The vast majority of these events were hyperglycemic episodes due to infusion set failures, which were reportable only in the bionic pancreas group. In other words, the patients in the control group who had an infusion set failure (assuming they were using an insulin pump at all) would have just called their regular doctor to get things sorted and not reported it to the study team.

Nevertheless, these adverse events – not serious, but common – highlight the fact that good software is not the only key to solving the closed-loop problem. We need good hardware too, hardware that can withstand the very active lives that children with type 1 diabetes deserve to live.

In short, the dream of a functional cure to type 1 diabetes, a true artificial pancreas, is closer than ever, but it’s still just a dream. With iterative advances like this, though, the reality may be here before you know it.

Dr. Wilson is associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. A version of this article first appeared on Medscape.com.

This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.

It was 100 years ago when Leonard Thompson, age 13, received a reprieve from a death sentence. Young master Thompson had type 1 diabetes, a disease that was uniformly fatal within months of diagnosis. But he received a new treatment, insulin, from a canine pancreas. He would live 13 more years before dying at age 26 of pneumonia.

The history of type 1 diabetes since that time has been a battle on two fronts: First, the search for a cause of and cure for the disease; second, the effort to make the administration of insulin safer, more reliable, and easier.

The past 2 decades have seen a technological revolution in type 1 diabetes care, with continuous glucose monitors decreasing the need for painful finger sticks, and insulin pumps allowing for more precise titration of doses.

The dream, of course, has been to combine those two technologies, continuous glucose monitoring and insulin pumps, to create so-called closed-loop systems – basically an artificial pancreas – that would obviate the need for any intervention on the part of the patient, save the occasional refilling of an insulin reservoir.

We aren’t there yet, but we are closer than ever.

Closed-loop systems for insulin delivery, like the Tandem Control IQ system, are a marvel of technology, but they are not exactly hands-free. Users need to dial in settings for their insulin usage, count carbohydrates at meals, and inform the system that they are about to eat those meals to allow the algorithm to administer an appropriate insulin dose.

The perceived complexity of these systems may be responsible for why there are substantial disparities in the prescription of closed-loop systems. Kids of lower socioeconomic status are dramatically less likely to receive these advanced technologies. Providers may feel that patients with lower health literacy or social supports are not “ideal” for these technologies, even though they lead to demonstrably better outcomes.

That means that easier might be better. And a “bionic pancreas,” as reported in an article from The New England Journal of Medicine, is exactly that.

Broadly, it’s another closed-loop system. The bionic pancreas integrates with a continuous glucose monitor and administers insulin when needed. But the algorithm appears to be a bit smarter than what we have in existing devices. For example, patients do not need to provide any information about their usual insulin doses – just their body weight. They don’t need to count carbohydrates at meals – just to inform the device when they are eating, and whether the meal is the usual amount they eat, more, or less. The algorithm learns and adapts as it is used. Easy.

And in this randomized trial, easy does it.

A total of 219 participants were randomized in a 2:1 ratio to the bionic pancreas or usual diabetes care, though it was required that control participants use a continuous glucose monitor. Participants were as young as 6 years old and up to 79 years old; the majority were White and had a relatively high household income. The mean A1c was around 7.8% at baseline.

By the end of the study, the A1c was significantly improved in the bionic pancreas group, with a mean of 7.3% vs. 7.7% in the usual-care group.

This effect was most pronounced in those with a higher A1c at baseline.

People randomized to the bionic pancreas also spent more time in the target glucose range of 70-180 mg/dL.

All in all, the technology that makes it easy to manage your blood sugar, well, made it easy to manage your blood sugar.

But new technology is never without its hiccups. Those randomized to the bionic pancreas had a markedly higher rate of adverse events (244 events in 126 people compared with 10 events in 8 people in the usual-care group.)

This is actually a little misleading, though. The vast majority of these events were hyperglycemic episodes due to infusion set failures, which were reportable only in the bionic pancreas group. In other words, the patients in the control group who had an infusion set failure (assuming they were using an insulin pump at all) would have just called their regular doctor to get things sorted and not reported it to the study team.

Nevertheless, these adverse events – not serious, but common – highlight the fact that good software is not the only key to solving the closed-loop problem. We need good hardware too, hardware that can withstand the very active lives that children with type 1 diabetes deserve to live.

In short, the dream of a functional cure to type 1 diabetes, a true artificial pancreas, is closer than ever, but it’s still just a dream. With iterative advances like this, though, the reality may be here before you know it.

Dr. Wilson is associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. A version of this article first appeared on Medscape.com.

Developmental language disorder (DLD) is characterized by receptive or expressive language difficulties or both. Children with the neurodevelopmental condition “struggle to comprehend and use their native language for no obvious reason,” said the authors of a new study. This leads to problems with grammar, vocabulary, and holding conversations, and in turn an increased risk of “difficulties when learning to read, underachieving academically, being unemployed, and facing social and mental health challenges.”

The condition is common and estimated to affect 7% of children – approximately two in every classroom – but is “underrecognized” said the authors.

Saloni Krishnan, PhD, reader at Royal Holloway, University of London, who led the study as a research fellow at the University of Oxford, England, explained: “DLD is a relatively unknown and understudied condition, unlike better known neurodevelopmental conditions such as ADHD, dyslexia, or autism.”

It is suspected that children with DLD may have differences in areas of the brain involved with learning habits and rules. “Although we know that DLD does not result from gross neural lesions, we still do not have a clear picture of how brain anatomy differs in children with DLD,” the authors highlighted.
 

Language learning difficulties linked to brain differences

For their study, published in eLife, researchers used an MRI technique called multiparameter mapping (MPM) to investigate microstructural neural differences in children with DLD. The technique measures the properties of brain tissue and is particularly useful for measuring the amounts of myelin.

“Understanding the neural basis of DLD is particularly challenging given the developmental nature of the disorder, as well as the lack of animal models for understanding language,” explained the authors. However, they pointed out that MPM allows an “unparalleled in vivo method” to investigate microstructural neural changes in children with DLD.

Kate Watkins, PhD, professor of cognitive neuroscience at the University of Oxford and senior author, said: “This type of scan tells us more about the makeup or composition of the brain tissue in different areas.”

As part of the Oxford Brain Organisation in Language Development (OxBOLD) study, the researchers recruited and tested 175 children between the ages of 10 and 15 years. Subsequently, 56 children with typical language development and 33 children with DLD were scanned using MPM.

The researchers compared the two groups and found that children with DLD have less myelin in parts of the brain responsible for speaking, listening, and learning rules and habits.

Specifically, maps of magnetization transfer saturation (MTsat) – which index myelin – in children with DLD showed reductions in MTsat values in the caudate nucleus bilaterally, and in the left ventral sensorimotor cortex and Heschl’s gyrus.

“Our findings using this protocol suggest that the caudate nucleus, as well as regions in the wider speech and language network, show alterations in myelin in children with DLD,” explained the authors.

“Given myelin’s role in enabling fast and reliable communication in the brain, reduced myelin content may explain why children with DLD struggle with speech and language processing,” they highlighted.
 

Significant advance in DLD understanding

The study findings established changes in striatal and cortical myelin as a “neural basis for DLD,” explained the journal editor, who highlighted that this was a “significant advance” in the understanding of DLD. “These brain differences may explain the poorer language outcomes in this group,” the authors said.

The findings “strongly point” to a role for the striatum in the development of DLD, and this role is likely to be in the “learning of habits and sequences,” the authors said.

They pointed out, however, that myelin patterns can change over development, and that myelination can be observed after successful training. “It is important to assess whether these differences in myelin persist over development in DLD, and if they can be targeted through training using behavioral interventions,” they emphasized.

Professor Watkins commented: “The findings might help us understand the pathways involved at a biological level and ultimately allow us to explain why children with DLD have problems with language learning.”

A spokesperson for the RADLD (Raising Awareness of Developmental Language Disorder) organization, commented: “Developmental language disorder has long been understood to have a neurological basis; however, these differences in the brain development have received limited attention in research.” It added that utilizing new technology helps to better understand the “potential neurological differences” experienced by people with DLD.

More studies are needed to determine if these brain differences cause language problems and how or if experiencing language difficulties could cause these changes in the brain, explained the authors. They hoped that further research may help scientists find new treatments that target these brain differences.

Funding was provided by UK Research and Innovation, Wellcome Trust. The authors declared no competing interests.

A version of this article first appeared on MedscapeUK.

Developmental language disorder (DLD) is characterized by receptive or expressive language difficulties or both. Children with the neurodevelopmental condition “struggle to comprehend and use their native language for no obvious reason,” said the authors of a new study. This leads to problems with grammar, vocabulary, and holding conversations, and in turn an increased risk of “difficulties when learning to read, underachieving academically, being unemployed, and facing social and mental health challenges.”

The condition is common and estimated to affect 7% of children – approximately two in every classroom – but is “underrecognized” said the authors.

Saloni Krishnan, PhD, reader at Royal Holloway, University of London, who led the study as a research fellow at the University of Oxford, England, explained: “DLD is a relatively unknown and understudied condition, unlike better known neurodevelopmental conditions such as ADHD, dyslexia, or autism.”

It is suspected that children with DLD may have differences in areas of the brain involved with learning habits and rules. “Although we know that DLD does not result from gross neural lesions, we still do not have a clear picture of how brain anatomy differs in children with DLD,” the authors highlighted.
 

Language learning difficulties linked to brain differences

For their study, published in eLife, researchers used an MRI technique called multiparameter mapping (MPM) to investigate microstructural neural differences in children with DLD. The technique measures the properties of brain tissue and is particularly useful for measuring the amounts of myelin.

“Understanding the neural basis of DLD is particularly challenging given the developmental nature of the disorder, as well as the lack of animal models for understanding language,” explained the authors. However, they pointed out that MPM allows an “unparalleled in vivo method” to investigate microstructural neural changes in children with DLD.

Kate Watkins, PhD, professor of cognitive neuroscience at the University of Oxford and senior author, said: “This type of scan tells us more about the makeup or composition of the brain tissue in different areas.”

As part of the Oxford Brain Organisation in Language Development (OxBOLD) study, the researchers recruited and tested 175 children between the ages of 10 and 15 years. Subsequently, 56 children with typical language development and 33 children with DLD were scanned using MPM.

The researchers compared the two groups and found that children with DLD have less myelin in parts of the brain responsible for speaking, listening, and learning rules and habits.

Specifically, maps of magnetization transfer saturation (MTsat) – which index myelin – in children with DLD showed reductions in MTsat values in the caudate nucleus bilaterally, and in the left ventral sensorimotor cortex and Heschl’s gyrus.

“Our findings using this protocol suggest that the caudate nucleus, as well as regions in the wider speech and language network, show alterations in myelin in children with DLD,” explained the authors.

“Given myelin’s role in enabling fast and reliable communication in the brain, reduced myelin content may explain why children with DLD struggle with speech and language processing,” they highlighted.
 

Significant advance in DLD understanding

The study findings established changes in striatal and cortical myelin as a “neural basis for DLD,” explained the journal editor, who highlighted that this was a “significant advance” in the understanding of DLD. “These brain differences may explain the poorer language outcomes in this group,” the authors said.

The findings “strongly point” to a role for the striatum in the development of DLD, and this role is likely to be in the “learning of habits and sequences,” the authors said.

They pointed out, however, that myelin patterns can change over development, and that myelination can be observed after successful training. “It is important to assess whether these differences in myelin persist over development in DLD, and if they can be targeted through training using behavioral interventions,” they emphasized.

Professor Watkins commented: “The findings might help us understand the pathways involved at a biological level and ultimately allow us to explain why children with DLD have problems with language learning.”

A spokesperson for the RADLD (Raising Awareness of Developmental Language Disorder) organization, commented: “Developmental language disorder has long been understood to have a neurological basis; however, these differences in the brain development have received limited attention in research.” It added that utilizing new technology helps to better understand the “potential neurological differences” experienced by people with DLD.

More studies are needed to determine if these brain differences cause language problems and how or if experiencing language difficulties could cause these changes in the brain, explained the authors. They hoped that further research may help scientists find new treatments that target these brain differences.

Funding was provided by UK Research and Innovation, Wellcome Trust. The authors declared no competing interests.

A version of this article first appeared on MedscapeUK.

Developmental language disorder (DLD) is characterized by receptive or expressive language difficulties or both. Children with the neurodevelopmental condition “struggle to comprehend and use their native language for no obvious reason,” said the authors of a new study. This leads to problems with grammar, vocabulary, and holding conversations, and in turn an increased risk of “difficulties when learning to read, underachieving academically, being unemployed, and facing social and mental health challenges.”

The condition is common and estimated to affect 7% of children – approximately two in every classroom – but is “underrecognized” said the authors.

Saloni Krishnan, PhD, reader at Royal Holloway, University of London, who led the study as a research fellow at the University of Oxford, England, explained: “DLD is a relatively unknown and understudied condition, unlike better known neurodevelopmental conditions such as ADHD, dyslexia, or autism.”

It is suspected that children with DLD may have differences in areas of the brain involved with learning habits and rules. “Although we know that DLD does not result from gross neural lesions, we still do not have a clear picture of how brain anatomy differs in children with DLD,” the authors highlighted.
 

Language learning difficulties linked to brain differences

For their study, published in eLife, researchers used an MRI technique called multiparameter mapping (MPM) to investigate microstructural neural differences in children with DLD. The technique measures the properties of brain tissue and is particularly useful for measuring the amounts of myelin.

“Understanding the neural basis of DLD is particularly challenging given the developmental nature of the disorder, as well as the lack of animal models for understanding language,” explained the authors. However, they pointed out that MPM allows an “unparalleled in vivo method” to investigate microstructural neural changes in children with DLD.

Kate Watkins, PhD, professor of cognitive neuroscience at the University of Oxford and senior author, said: “This type of scan tells us more about the makeup or composition of the brain tissue in different areas.”

As part of the Oxford Brain Organisation in Language Development (OxBOLD) study, the researchers recruited and tested 175 children between the ages of 10 and 15 years. Subsequently, 56 children with typical language development and 33 children with DLD were scanned using MPM.

The researchers compared the two groups and found that children with DLD have less myelin in parts of the brain responsible for speaking, listening, and learning rules and habits.

Specifically, maps of magnetization transfer saturation (MTsat) – which index myelin – in children with DLD showed reductions in MTsat values in the caudate nucleus bilaterally, and in the left ventral sensorimotor cortex and Heschl’s gyrus.

“Our findings using this protocol suggest that the caudate nucleus, as well as regions in the wider speech and language network, show alterations in myelin in children with DLD,” explained the authors.

“Given myelin’s role in enabling fast and reliable communication in the brain, reduced myelin content may explain why children with DLD struggle with speech and language processing,” they highlighted.
 

Significant advance in DLD understanding

The study findings established changes in striatal and cortical myelin as a “neural basis for DLD,” explained the journal editor, who highlighted that this was a “significant advance” in the understanding of DLD. “These brain differences may explain the poorer language outcomes in this group,” the authors said.

The findings “strongly point” to a role for the striatum in the development of DLD, and this role is likely to be in the “learning of habits and sequences,” the authors said.

They pointed out, however, that myelin patterns can change over development, and that myelination can be observed after successful training. “It is important to assess whether these differences in myelin persist over development in DLD, and if they can be targeted through training using behavioral interventions,” they emphasized.

Professor Watkins commented: “The findings might help us understand the pathways involved at a biological level and ultimately allow us to explain why children with DLD have problems with language learning.”

A spokesperson for the RADLD (Raising Awareness of Developmental Language Disorder) organization, commented: “Developmental language disorder has long been understood to have a neurological basis; however, these differences in the brain development have received limited attention in research.” It added that utilizing new technology helps to better understand the “potential neurological differences” experienced by people with DLD.

More studies are needed to determine if these brain differences cause language problems and how or if experiencing language difficulties could cause these changes in the brain, explained the authors. They hoped that further research may help scientists find new treatments that target these brain differences.

Funding was provided by UK Research and Innovation, Wellcome Trust. The authors declared no competing interests.

A version of this article first appeared on MedscapeUK.

People at increased risk for syphilis – including asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at high risk for the disease – should be screened for it, according to a reaffirmation by the United States Preventive Services Task Force of its 2016 recommendation of syphilis screening for people at increased risk for infection.

“Using a reaffirmation process, the USPSTF concludes with high certainty that there is a substantial net benefit of screening for syphilis infection in nonpregnant persons who are at increased risk for infection,” the authors, led by Carol M. Mangione, MD, MSPH, of the University of California, Los Angeles, wrote in JAMA.

Reported cases in the United States of primary and secondary syphilis – a sexually transmitted infection caused by the bacterium Treponema pallidum that can damage the brain, nerves, eyes, and cardiovascular system if left untreated – increased from a low of 2.1 cases per 100,000 people in 2000 and 2001 to 11.9 cases per 100,000 in 2019, the authors reported. In 2019, men accounted for 83% of all primary and secondary syphilis cases, and men who have sex with men (MSM) accounted for 57% of all primary and secondary syphilis cases in men. Screening and follow-up treatment can cure syphilis and prevent complications.

To help them evaluate the effectiveness and safety of screening, the USPSTF authors reviewed the literature and visually displayed key questions and linkages to interventions and outcomes, Michelle L. Henninger, PhD, Sarah I. Bean, MPH, and Jennifer S. Lin, MD, MCR, of the Kaiser Permanente Evidence-based Practice Center in Portland, Ore., noted in a related evidence report of the post-2016 recommendation data.

Reaffirming its 2016 recommendation, the USPSTF now advises clinicians to:

Assess risk:

• Clinicians should know how common syphilis is in their community and assess their patient’s individual risk.
• Risk for syphilis is higher in MSM, people with HIV infection or other STIs, and those who use illicit drugs or have a history of incarceration, sex work, or military service.

Screen and confirm by testing:

• Traditional screening algorithm: Start with a nontreponemal test such as Venereal Disease Research Laborator or rapid plasma reagin. If positive, confirm result with a treponemal antibody detection test, such as T. pallidum particle agglutination.
• Reverse sequence algorithm: Screen with an initial automated treponemal test such as enzyme-linked or chemiluminescence immunoassay. If positive, confirm result with a nontreponemal test.

Consider screening interval:

• Evidence on optimal screening intervals is limited for the general population, but MSM and people with HIV may benefit from screening yearly or every 3-6 months if they remain at high risk.

The authors acknowledged that primary and secondary syphilis rates are higher in Blacks, Hispanics, Native Americans/Alaska Native, and Native Hawaiians/Pacific Islanders, and that the disparities are primarily driven by social determinants of health including differences in income, education, and access to coverage and care.

They added that differences in sexual networks also play a role in disparities and that sexually active people in communities with higher STI rates may be more likely to become infected.
 

More testing, treatment, and research are needed

Four experts welcomed the reaffirmation.

“It is important and necessary that the task force has chosen to reaffirm their syphilis screening recommendations, given the continued increase in sexually transmitted infections in the U.S. since the 2016 published recommendations,” Judith A. O’Donnell, MD, director of the department of infection prevention and control at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

“Awareness of the ongoing incidence, understanding of the importance of screening in interrupting transmission, and getting people diagnosed and treated before serious complications are key,” she added.

Heidi Gullettt, MD, MPH, associate director of the Center for Community Health Integration at Case Western Reserve University, Cleveland, said: “The reaffirmation document authors demonstrated a comprehensive review of high-quality studies and epidemiologic data.

“Primary care clinicians rely on USPSTF recommendations to help prioritize evidence-based prevention in practice, so this reaffirmation is a critical step to remind us of the importance of regularly assessing risk and screening with a readily available screening test in the office,” she added.

Testing during office visits is not easy, Dr. Gullettt said, because of competing priorities, stigma associated with STIs, and testing and treatment costs. 

“Under the Affordable Care Act, USPSTF screening recommendations are supposed to be covered without cost sharing by patients. This should be the case for syphilis screening,” Dr. Gullett pointed out. “Patients are often reluctant to do screening because of cost.”

Michael Anthony Moody, MD, director of the Collaborative Influenza Vaccine Innovation Center at Duke University, Durham, N.C., said that the true incidence and prevalence of syphilis is unknown.

“The more we test, the more accurate our data will be,” he said. “Syphilis can hide in plain sight, has symptoms that mimic many other diseases, and is usually not diagnosed. Reaffirming that testing for syphilis is important reminds providers that this is a key test for their patient’s health.”

Aniruddha Hazra, MD, medical director of the University of Chicago Medicine Sexual Wellness Clinic, noted that the United States is in a syphilis epidemic.

“Screening asymptomatic people at risk for syphilis is important, but without comprehensive education and training of primary care providers on how to address STIs and sexual health, these recommendations fall flat,” he said.

In an accompanying editorial, Susan Tuddenham, MD, MPH; and Khalil G. Ghanem, MD, PhD, of Johns Hopkins University, Baltimore, urged that funding to develop novel syphilis diagnostics be prioritized, “just as there has been for development of syphilis vaccines, which are still many years from becoming a reality.”

“Relying on emerging biomedical prevention interventions that hold promise, such as doxycycline postexposure prophylaxis, without concomitant robust screening strategies will not lead to syphilis control. Failure to modernize screening strategies for syphilis will also mean failure to control this infection,” they cautioned.

The authors of the recommendation statement and the evidence report, as well as Dr. O’Donnell, Dr. Gullettt, Dr. Moody, and Dr. Hazra, who were not involved in the study, reported no relevant financial relationships. Dr. Tuddenham reported financial relationships with the pharmaceutical and publishing industries. Dr. Ghanem reported financial relationships with the publishing industry. The research was federally funded.

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

People at increased risk for syphilis – including asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at high risk for the disease – should be screened for it, according to a reaffirmation by the United States Preventive Services Task Force of its 2016 recommendation of syphilis screening for people at increased risk for infection.

“Using a reaffirmation process, the USPSTF concludes with high certainty that there is a substantial net benefit of screening for syphilis infection in nonpregnant persons who are at increased risk for infection,” the authors, led by Carol M. Mangione, MD, MSPH, of the University of California, Los Angeles, wrote in JAMA.

Reported cases in the United States of primary and secondary syphilis – a sexually transmitted infection caused by the bacterium Treponema pallidum that can damage the brain, nerves, eyes, and cardiovascular system if left untreated – increased from a low of 2.1 cases per 100,000 people in 2000 and 2001 to 11.9 cases per 100,000 in 2019, the authors reported. In 2019, men accounted for 83% of all primary and secondary syphilis cases, and men who have sex with men (MSM) accounted for 57% of all primary and secondary syphilis cases in men. Screening and follow-up treatment can cure syphilis and prevent complications.

To help them evaluate the effectiveness and safety of screening, the USPSTF authors reviewed the literature and visually displayed key questions and linkages to interventions and outcomes, Michelle L. Henninger, PhD, Sarah I. Bean, MPH, and Jennifer S. Lin, MD, MCR, of the Kaiser Permanente Evidence-based Practice Center in Portland, Ore., noted in a related evidence report of the post-2016 recommendation data.

Reaffirming its 2016 recommendation, the USPSTF now advises clinicians to:

Assess risk:

• Clinicians should know how common syphilis is in their community and assess their patient’s individual risk.
• Risk for syphilis is higher in MSM, people with HIV infection or other STIs, and those who use illicit drugs or have a history of incarceration, sex work, or military service.

Screen and confirm by testing:

• Traditional screening algorithm: Start with a nontreponemal test such as Venereal Disease Research Laborator or rapid plasma reagin. If positive, confirm result with a treponemal antibody detection test, such as T. pallidum particle agglutination.
• Reverse sequence algorithm: Screen with an initial automated treponemal test such as enzyme-linked or chemiluminescence immunoassay. If positive, confirm result with a nontreponemal test.

Consider screening interval:

• Evidence on optimal screening intervals is limited for the general population, but MSM and people with HIV may benefit from screening yearly or every 3-6 months if they remain at high risk.

The authors acknowledged that primary and secondary syphilis rates are higher in Blacks, Hispanics, Native Americans/Alaska Native, and Native Hawaiians/Pacific Islanders, and that the disparities are primarily driven by social determinants of health including differences in income, education, and access to coverage and care.

They added that differences in sexual networks also play a role in disparities and that sexually active people in communities with higher STI rates may be more likely to become infected.
 

More testing, treatment, and research are needed

Four experts welcomed the reaffirmation.

“It is important and necessary that the task force has chosen to reaffirm their syphilis screening recommendations, given the continued increase in sexually transmitted infections in the U.S. since the 2016 published recommendations,” Judith A. O’Donnell, MD, director of the department of infection prevention and control at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

“Awareness of the ongoing incidence, understanding of the importance of screening in interrupting transmission, and getting people diagnosed and treated before serious complications are key,” she added.

Heidi Gullettt, MD, MPH, associate director of the Center for Community Health Integration at Case Western Reserve University, Cleveland, said: “The reaffirmation document authors demonstrated a comprehensive review of high-quality studies and epidemiologic data.

“Primary care clinicians rely on USPSTF recommendations to help prioritize evidence-based prevention in practice, so this reaffirmation is a critical step to remind us of the importance of regularly assessing risk and screening with a readily available screening test in the office,” she added.

Testing during office visits is not easy, Dr. Gullettt said, because of competing priorities, stigma associated with STIs, and testing and treatment costs. 

“Under the Affordable Care Act, USPSTF screening recommendations are supposed to be covered without cost sharing by patients. This should be the case for syphilis screening,” Dr. Gullett pointed out. “Patients are often reluctant to do screening because of cost.”

Michael Anthony Moody, MD, director of the Collaborative Influenza Vaccine Innovation Center at Duke University, Durham, N.C., said that the true incidence and prevalence of syphilis is unknown.

“The more we test, the more accurate our data will be,” he said. “Syphilis can hide in plain sight, has symptoms that mimic many other diseases, and is usually not diagnosed. Reaffirming that testing for syphilis is important reminds providers that this is a key test for their patient’s health.”

Aniruddha Hazra, MD, medical director of the University of Chicago Medicine Sexual Wellness Clinic, noted that the United States is in a syphilis epidemic.

“Screening asymptomatic people at risk for syphilis is important, but without comprehensive education and training of primary care providers on how to address STIs and sexual health, these recommendations fall flat,” he said.

In an accompanying editorial, Susan Tuddenham, MD, MPH; and Khalil G. Ghanem, MD, PhD, of Johns Hopkins University, Baltimore, urged that funding to develop novel syphilis diagnostics be prioritized, “just as there has been for development of syphilis vaccines, which are still many years from becoming a reality.”

“Relying on emerging biomedical prevention interventions that hold promise, such as doxycycline postexposure prophylaxis, without concomitant robust screening strategies will not lead to syphilis control. Failure to modernize screening strategies for syphilis will also mean failure to control this infection,” they cautioned.

The authors of the recommendation statement and the evidence report, as well as Dr. O’Donnell, Dr. Gullettt, Dr. Moody, and Dr. Hazra, who were not involved in the study, reported no relevant financial relationships. Dr. Tuddenham reported financial relationships with the pharmaceutical and publishing industries. Dr. Ghanem reported financial relationships with the publishing industry. The research was federally funded.

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

People at increased risk for syphilis – including asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at high risk for the disease – should be screened for it, according to a reaffirmation by the United States Preventive Services Task Force of its 2016 recommendation of syphilis screening for people at increased risk for infection.

“Using a reaffirmation process, the USPSTF concludes with high certainty that there is a substantial net benefit of screening for syphilis infection in nonpregnant persons who are at increased risk for infection,” the authors, led by Carol M. Mangione, MD, MSPH, of the University of California, Los Angeles, wrote in JAMA.

Reported cases in the United States of primary and secondary syphilis – a sexually transmitted infection caused by the bacterium Treponema pallidum that can damage the brain, nerves, eyes, and cardiovascular system if left untreated – increased from a low of 2.1 cases per 100,000 people in 2000 and 2001 to 11.9 cases per 100,000 in 2019, the authors reported. In 2019, men accounted for 83% of all primary and secondary syphilis cases, and men who have sex with men (MSM) accounted for 57% of all primary and secondary syphilis cases in men. Screening and follow-up treatment can cure syphilis and prevent complications.

To help them evaluate the effectiveness and safety of screening, the USPSTF authors reviewed the literature and visually displayed key questions and linkages to interventions and outcomes, Michelle L. Henninger, PhD, Sarah I. Bean, MPH, and Jennifer S. Lin, MD, MCR, of the Kaiser Permanente Evidence-based Practice Center in Portland, Ore., noted in a related evidence report of the post-2016 recommendation data.

Reaffirming its 2016 recommendation, the USPSTF now advises clinicians to:

Assess risk:

• Clinicians should know how common syphilis is in their community and assess their patient’s individual risk.
• Risk for syphilis is higher in MSM, people with HIV infection or other STIs, and those who use illicit drugs or have a history of incarceration, sex work, or military service.

Screen and confirm by testing:

• Traditional screening algorithm: Start with a nontreponemal test such as Venereal Disease Research Laborator or rapid plasma reagin. If positive, confirm result with a treponemal antibody detection test, such as T. pallidum particle agglutination.
• Reverse sequence algorithm: Screen with an initial automated treponemal test such as enzyme-linked or chemiluminescence immunoassay. If positive, confirm result with a nontreponemal test.

Consider screening interval:

• Evidence on optimal screening intervals is limited for the general population, but MSM and people with HIV may benefit from screening yearly or every 3-6 months if they remain at high risk.

The authors acknowledged that primary and secondary syphilis rates are higher in Blacks, Hispanics, Native Americans/Alaska Native, and Native Hawaiians/Pacific Islanders, and that the disparities are primarily driven by social determinants of health including differences in income, education, and access to coverage and care.

They added that differences in sexual networks also play a role in disparities and that sexually active people in communities with higher STI rates may be more likely to become infected.
 

More testing, treatment, and research are needed

Four experts welcomed the reaffirmation.

“It is important and necessary that the task force has chosen to reaffirm their syphilis screening recommendations, given the continued increase in sexually transmitted infections in the U.S. since the 2016 published recommendations,” Judith A. O’Donnell, MD, director of the department of infection prevention and control at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

“Awareness of the ongoing incidence, understanding of the importance of screening in interrupting transmission, and getting people diagnosed and treated before serious complications are key,” she added.

Heidi Gullettt, MD, MPH, associate director of the Center for Community Health Integration at Case Western Reserve University, Cleveland, said: “The reaffirmation document authors demonstrated a comprehensive review of high-quality studies and epidemiologic data.

“Primary care clinicians rely on USPSTF recommendations to help prioritize evidence-based prevention in practice, so this reaffirmation is a critical step to remind us of the importance of regularly assessing risk and screening with a readily available screening test in the office,” she added.

Testing during office visits is not easy, Dr. Gullettt said, because of competing priorities, stigma associated with STIs, and testing and treatment costs. 

“Under the Affordable Care Act, USPSTF screening recommendations are supposed to be covered without cost sharing by patients. This should be the case for syphilis screening,” Dr. Gullett pointed out. “Patients are often reluctant to do screening because of cost.”

Michael Anthony Moody, MD, director of the Collaborative Influenza Vaccine Innovation Center at Duke University, Durham, N.C., said that the true incidence and prevalence of syphilis is unknown.

“The more we test, the more accurate our data will be,” he said. “Syphilis can hide in plain sight, has symptoms that mimic many other diseases, and is usually not diagnosed. Reaffirming that testing for syphilis is important reminds providers that this is a key test for their patient’s health.”

Aniruddha Hazra, MD, medical director of the University of Chicago Medicine Sexual Wellness Clinic, noted that the United States is in a syphilis epidemic.

“Screening asymptomatic people at risk for syphilis is important, but without comprehensive education and training of primary care providers on how to address STIs and sexual health, these recommendations fall flat,” he said.

In an accompanying editorial, Susan Tuddenham, MD, MPH; and Khalil G. Ghanem, MD, PhD, of Johns Hopkins University, Baltimore, urged that funding to develop novel syphilis diagnostics be prioritized, “just as there has been for development of syphilis vaccines, which are still many years from becoming a reality.”

“Relying on emerging biomedical prevention interventions that hold promise, such as doxycycline postexposure prophylaxis, without concomitant robust screening strategies will not lead to syphilis control. Failure to modernize screening strategies for syphilis will also mean failure to control this infection,” they cautioned.

The authors of the recommendation statement and the evidence report, as well as Dr. O’Donnell, Dr. Gullettt, Dr. Moody, and Dr. Hazra, who were not involved in the study, reported no relevant financial relationships. Dr. Tuddenham reported financial relationships with the pharmaceutical and publishing industries. Dr. Ghanem reported financial relationships with the publishing industry. The research was federally funded.

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

Herpes to the rescue

Let’s face it: When people hear the word “herpes,” their first thoughts are not positive. But what if herpes could be a hero?

Scientists have found a way to make a strain of herpes that kills cancer because, hey, it’s 2022, and anything is possible. Trials have been going well and this seems like a safe and effective way to fight cancer.

Aunt_Spray/Thinkstock

Viruses may be one of our oldest enemies, but it’s also been said that the enemy of my enemy is my friend. So why not make herpes the enemy of cancer, thereby turning it into our friend? The genetically modified herpes virus is injected directly into tumors, where it destroys cancer cells from within. But wait, there’s more! The patient’s immune system also senses the virus and springs into action against it and the cancer in which it is residing.

During the phase 1 trial, three of the nine patients saw tumor reduction and the therapy proved safe as well. Future trials will be able to more specifically target various cancer types and make the treatment better. For once, we are rooting for you, herpes.
 

A breath of not-so-fresh air

There’s nothing quite like that first real warm day of spring. You can finally open the windows and clear out the old stuffy air that’s been hanging around all winter long. It’s a ritual that’s now backed up with some science in the form of a new study. Turns out that there’s actually a fair amount of smog in the average home. That’s right, smog’s not just for the big city anymore.

PxHere

As part of the HOMEChem project, a whole host of scientists gathered together under one roof in a typical suburban house and immediately started doing chores. Cooking, cleaning, the works. No, it wasn’t because they had trashed the place the night before. They had set up instrumentation all around the house to measure the chemical makeup of the air inside. A scientist’s idea of a wild party.

The results are perhaps not all that surprising, but interesting nonetheless. Your homemade smog certainly won’t kill you, but there’s both an increased amount and higher concentration of airborne toxins in indoor air, compared with outdoors. Benzene and formaldehyde were common, as were acrolein (a pulmonary toxicant emitted by lumber and burning fats) and isocyanic acid (which can react with proteins in the human body). The researchers noted that most of these chemicals can be removed with proper ventilation.

Although cleaning is certainly responsible for a fair share of the chemicals, cooking generally produced more toxic compounds, similar to what’s found in wildfire smoke. One of the researchers said this makes sense, since a wildfire can be considered an “extreme form of cooking.” Scientists may not know how to party, but their idea of a barbecue sounds … interesting. We’re looking forward to an upcoming study out of California: Can a 1-million acre wildfire adequately cook a ribeye steak?
 

We’re dying to try composting ... with humans, that is

We here at LOTME are not really fans of politicians, except as objects of ridicule. That is kind of fun. Whether we’re watching Fox News, listening to NPR, or reading Vladimir Putin’s fashion blog, one thing remains clear: If you want actual information, don’t ask a politician.

Recompose

There are, of course, always exceptions, and we just found one: California state representative Cristina Garcia. Rep. Garcia sponsored a bill just signed into law by Gov. Gavin Newsom that legalizes the practice of human composting, the reduction of remains by “placing bodies in individual vessels and fostering gentle transformation into a nutrient-dense soil.”

Since we’ve written about this sort of thing before – Washington was the first state to legalize the process back in 2019 – we’re more interested now in what Rep. Garcia told NBC News while describing her motivation: “I’ve always wanted to be a tree. The idea of having my family sitting under my shade one day – that brings a lot of joy.” How great is that? Tree-hugging is just not enough. Be the tree.

California is the fifth state to provide its residents with the human composting option, the other three being Colorado, Oregon, and Vermont. The process “typically involves putting a body into a steel vessel, then covering it with organic materials like straw, wood chips and alfalfa. Microbes break down the corpse and the plant matter, transforming the various components into nutrient-rich soil in roughly 30 days,” Smithsonian Magazine explained.

We just happen to have some good news for Rep. Garcia about that wanting-to-be-a-tree business. She’s already pretty close. For more on that, we go to our correspondent from beyond the grave, Carl Sagan, who shares a thought about trees. And no, we couldn’t just write out his quote here. You have to hear it in Dr. Sagan’s own voice.
 

That’ll be one pandemic with extra distress. Hold the goals

When the COVID-19 pandemic first hit it put a lot of stuff on hold for everyone. Couldn’t eat inside at your favorite restaurant, attend that long-awaited concert, or travel out of the country. Those were all pretty bad, but it was the disruption of pursuing long-term goals that seemed to have the most effect on people’s mental health.

xijian/Getty Images

Investigators from the University of Waterloo (Ont.) looked at how putting such goals on hold affected people’s mental well-being. The study’s 226 participants were asked about their “COVID-frozen” goals and the degree to which they were able to actively pursue each goal and how committed they were to achieving it.

What they found was that the participants’ COVID-frozen goals were associated with feelings of psychological distress, such as anxiety, depressive symptoms, stress, and lowered life satisfaction. It was only when participants were able to disengage from goal rumination that well-being was impacted positively.

“Goal rumination is compulsive and can aggravate worries and frustrations while also taking away mental resources from other goals,” Candice Hubley, lead author and a PhD candidate in psychology, said in a written statement. So in short, you’re only stressing yourself out more about something that is far off in the distance when you could be focusing more on short-term, tangible goals instead.

Now, no one is saying to give up on your goals. Just take them one at a time. You’ll have better life satisfaction and your COVID-frozen goals will thaw out before you know it.

Herpes to the rescue

Let’s face it: When people hear the word “herpes,” their first thoughts are not positive. But what if herpes could be a hero?

Scientists have found a way to make a strain of herpes that kills cancer because, hey, it’s 2022, and anything is possible. Trials have been going well and this seems like a safe and effective way to fight cancer.

Aunt_Spray/Thinkstock

Viruses may be one of our oldest enemies, but it’s also been said that the enemy of my enemy is my friend. So why not make herpes the enemy of cancer, thereby turning it into our friend? The genetically modified herpes virus is injected directly into tumors, where it destroys cancer cells from within. But wait, there’s more! The patient’s immune system also senses the virus and springs into action against it and the cancer in which it is residing.

During the phase 1 trial, three of the nine patients saw tumor reduction and the therapy proved safe as well. Future trials will be able to more specifically target various cancer types and make the treatment better. For once, we are rooting for you, herpes.
 

A breath of not-so-fresh air

There’s nothing quite like that first real warm day of spring. You can finally open the windows and clear out the old stuffy air that’s been hanging around all winter long. It’s a ritual that’s now backed up with some science in the form of a new study. Turns out that there’s actually a fair amount of smog in the average home. That’s right, smog’s not just for the big city anymore.

PxHere

As part of the HOMEChem project, a whole host of scientists gathered together under one roof in a typical suburban house and immediately started doing chores. Cooking, cleaning, the works. No, it wasn’t because they had trashed the place the night before. They had set up instrumentation all around the house to measure the chemical makeup of the air inside. A scientist’s idea of a wild party.

The results are perhaps not all that surprising, but interesting nonetheless. Your homemade smog certainly won’t kill you, but there’s both an increased amount and higher concentration of airborne toxins in indoor air, compared with outdoors. Benzene and formaldehyde were common, as were acrolein (a pulmonary toxicant emitted by lumber and burning fats) and isocyanic acid (which can react with proteins in the human body). The researchers noted that most of these chemicals can be removed with proper ventilation.

Although cleaning is certainly responsible for a fair share of the chemicals, cooking generally produced more toxic compounds, similar to what’s found in wildfire smoke. One of the researchers said this makes sense, since a wildfire can be considered an “extreme form of cooking.” Scientists may not know how to party, but their idea of a barbecue sounds … interesting. We’re looking forward to an upcoming study out of California: Can a 1-million acre wildfire adequately cook a ribeye steak?
 

We’re dying to try composting ... with humans, that is

We here at LOTME are not really fans of politicians, except as objects of ridicule. That is kind of fun. Whether we’re watching Fox News, listening to NPR, or reading Vladimir Putin’s fashion blog, one thing remains clear: If you want actual information, don’t ask a politician.

Recompose

There are, of course, always exceptions, and we just found one: California state representative Cristina Garcia. Rep. Garcia sponsored a bill just signed into law by Gov. Gavin Newsom that legalizes the practice of human composting, the reduction of remains by “placing bodies in individual vessels and fostering gentle transformation into a nutrient-dense soil.”

Since we’ve written about this sort of thing before – Washington was the first state to legalize the process back in 2019 – we’re more interested now in what Rep. Garcia told NBC News while describing her motivation: “I’ve always wanted to be a tree. The idea of having my family sitting under my shade one day – that brings a lot of joy.” How great is that? Tree-hugging is just not enough. Be the tree.

California is the fifth state to provide its residents with the human composting option, the other three being Colorado, Oregon, and Vermont. The process “typically involves putting a body into a steel vessel, then covering it with organic materials like straw, wood chips and alfalfa. Microbes break down the corpse and the plant matter, transforming the various components into nutrient-rich soil in roughly 30 days,” Smithsonian Magazine explained.

We just happen to have some good news for Rep. Garcia about that wanting-to-be-a-tree business. She’s already pretty close. For more on that, we go to our correspondent from beyond the grave, Carl Sagan, who shares a thought about trees. And no, we couldn’t just write out his quote here. You have to hear it in Dr. Sagan’s own voice.
 

That’ll be one pandemic with extra distress. Hold the goals

When the COVID-19 pandemic first hit it put a lot of stuff on hold for everyone. Couldn’t eat inside at your favorite restaurant, attend that long-awaited concert, or travel out of the country. Those were all pretty bad, but it was the disruption of pursuing long-term goals that seemed to have the most effect on people’s mental health.

xijian/Getty Images

Investigators from the University of Waterloo (Ont.) looked at how putting such goals on hold affected people’s mental well-being. The study’s 226 participants were asked about their “COVID-frozen” goals and the degree to which they were able to actively pursue each goal and how committed they were to achieving it.

What they found was that the participants’ COVID-frozen goals were associated with feelings of psychological distress, such as anxiety, depressive symptoms, stress, and lowered life satisfaction. It was only when participants were able to disengage from goal rumination that well-being was impacted positively.

“Goal rumination is compulsive and can aggravate worries and frustrations while also taking away mental resources from other goals,” Candice Hubley, lead author and a PhD candidate in psychology, said in a written statement. So in short, you’re only stressing yourself out more about something that is far off in the distance when you could be focusing more on short-term, tangible goals instead.

Now, no one is saying to give up on your goals. Just take them one at a time. You’ll have better life satisfaction and your COVID-frozen goals will thaw out before you know it.

Herpes to the rescue

Let’s face it: When people hear the word “herpes,” their first thoughts are not positive. But what if herpes could be a hero?

Scientists have found a way to make a strain of herpes that kills cancer because, hey, it’s 2022, and anything is possible. Trials have been going well and this seems like a safe and effective way to fight cancer.

Aunt_Spray/Thinkstock

Viruses may be one of our oldest enemies, but it’s also been said that the enemy of my enemy is my friend. So why not make herpes the enemy of cancer, thereby turning it into our friend? The genetically modified herpes virus is injected directly into tumors, where it destroys cancer cells from within. But wait, there’s more! The patient’s immune system also senses the virus and springs into action against it and the cancer in which it is residing.

During the phase 1 trial, three of the nine patients saw tumor reduction and the therapy proved safe as well. Future trials will be able to more specifically target various cancer types and make the treatment better. For once, we are rooting for you, herpes.
 

A breath of not-so-fresh air

There’s nothing quite like that first real warm day of spring. You can finally open the windows and clear out the old stuffy air that’s been hanging around all winter long. It’s a ritual that’s now backed up with some science in the form of a new study. Turns out that there’s actually a fair amount of smog in the average home. That’s right, smog’s not just for the big city anymore.

PxHere

As part of the HOMEChem project, a whole host of scientists gathered together under one roof in a typical suburban house and immediately started doing chores. Cooking, cleaning, the works. No, it wasn’t because they had trashed the place the night before. They had set up instrumentation all around the house to measure the chemical makeup of the air inside. A scientist’s idea of a wild party.

The results are perhaps not all that surprising, but interesting nonetheless. Your homemade smog certainly won’t kill you, but there’s both an increased amount and higher concentration of airborne toxins in indoor air, compared with outdoors. Benzene and formaldehyde were common, as were acrolein (a pulmonary toxicant emitted by lumber and burning fats) and isocyanic acid (which can react with proteins in the human body). The researchers noted that most of these chemicals can be removed with proper ventilation.

Although cleaning is certainly responsible for a fair share of the chemicals, cooking generally produced more toxic compounds, similar to what’s found in wildfire smoke. One of the researchers said this makes sense, since a wildfire can be considered an “extreme form of cooking.” Scientists may not know how to party, but their idea of a barbecue sounds … interesting. We’re looking forward to an upcoming study out of California: Can a 1-million acre wildfire adequately cook a ribeye steak?
 

We’re dying to try composting ... with humans, that is

We here at LOTME are not really fans of politicians, except as objects of ridicule. That is kind of fun. Whether we’re watching Fox News, listening to NPR, or reading Vladimir Putin’s fashion blog, one thing remains clear: If you want actual information, don’t ask a politician.

Recompose

There are, of course, always exceptions, and we just found one: California state representative Cristina Garcia. Rep. Garcia sponsored a bill just signed into law by Gov. Gavin Newsom that legalizes the practice of human composting, the reduction of remains by “placing bodies in individual vessels and fostering gentle transformation into a nutrient-dense soil.”

Since we’ve written about this sort of thing before – Washington was the first state to legalize the process back in 2019 – we’re more interested now in what Rep. Garcia told NBC News while describing her motivation: “I’ve always wanted to be a tree. The idea of having my family sitting under my shade one day – that brings a lot of joy.” How great is that? Tree-hugging is just not enough. Be the tree.

California is the fifth state to provide its residents with the human composting option, the other three being Colorado, Oregon, and Vermont. The process “typically involves putting a body into a steel vessel, then covering it with organic materials like straw, wood chips and alfalfa. Microbes break down the corpse and the plant matter, transforming the various components into nutrient-rich soil in roughly 30 days,” Smithsonian Magazine explained.

We just happen to have some good news for Rep. Garcia about that wanting-to-be-a-tree business. She’s already pretty close. For more on that, we go to our correspondent from beyond the grave, Carl Sagan, who shares a thought about trees. And no, we couldn’t just write out his quote here. You have to hear it in Dr. Sagan’s own voice.
 

That’ll be one pandemic with extra distress. Hold the goals

When the COVID-19 pandemic first hit it put a lot of stuff on hold for everyone. Couldn’t eat inside at your favorite restaurant, attend that long-awaited concert, or travel out of the country. Those were all pretty bad, but it was the disruption of pursuing long-term goals that seemed to have the most effect on people’s mental health.

xijian/Getty Images

Investigators from the University of Waterloo (Ont.) looked at how putting such goals on hold affected people’s mental well-being. The study’s 226 participants were asked about their “COVID-frozen” goals and the degree to which they were able to actively pursue each goal and how committed they were to achieving it.

What they found was that the participants’ COVID-frozen goals were associated with feelings of psychological distress, such as anxiety, depressive symptoms, stress, and lowered life satisfaction. It was only when participants were able to disengage from goal rumination that well-being was impacted positively.

“Goal rumination is compulsive and can aggravate worries and frustrations while also taking away mental resources from other goals,” Candice Hubley, lead author and a PhD candidate in psychology, said in a written statement. So in short, you’re only stressing yourself out more about something that is far off in the distance when you could be focusing more on short-term, tangible goals instead.

Now, no one is saying to give up on your goals. Just take them one at a time. You’ll have better life satisfaction and your COVID-frozen goals will thaw out before you know it.