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FDA expands oral JAK abrocitinib to adolescents with AD
Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.
It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.
The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.
Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.
The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.
Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.
Select JADE TEEN findings include the following:
- IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
- EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
- Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.
Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.
In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.
He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.
Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.
JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.
Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.
A version of this article first appeared on Medscape.com.
Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.
It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.
The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.
Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.
The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.
Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.
Select JADE TEEN findings include the following:
- IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
- EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
- Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.
Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.
In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.
He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.
Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.
JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.
Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.
A version of this article first appeared on Medscape.com.
Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.
It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.
The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.
Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.
The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.
Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.
Select JADE TEEN findings include the following:
- IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
- EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
- Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.
Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.
In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.
He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.
Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.
JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.
Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.
A version of this article first appeared on Medscape.com.
Mental health system failing kids leaving ED
Only 56% of children enrolled in Medicaid received any outpatient follow-up within 30 days after a mental health emergency department discharge, according to results of a large study released in Pediatrics.
Fewer than one-third (31.2%) had an outpatient visit within a week after a mental health ED discharge.
Researchers conducted a retrospective study of 28,551 children ages 6-17 years old who had mental health discharges from EDs from January 2018 to June 2019.
The researchers, led by Jennifer A. Hoffmann, MD, MS, with the division of emergency medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, Chicago, also analyzed the effect that having a timely follow-up had on whether the child was likely to return to the ED.
Follow-up within 30 days cuts risk of quick return to ED
They found that follow-up within 30 days was linked with a 26% decreased risk of return within 5 days of the initial ED discharge (hazard ratio, 0.74; 95% confidence interval, 0.63-0.91).
The researchers also found racial disparities in the data. The odds for getting follow-up outpatient care were lower for non-Hispanic Black children, for children with fee-for-service insurance, and for children with no previous mental health outpatient visits.
The numbers were particularly striking for Black children, who were 10% less likely to get outpatient follow-up than their White counterparts.
In addition, 27% of all children in this sample returned to the ED for mental health-related symptoms within 6 months, 20% spent more than 48 hours in the ED for their initial mental health visit, and children with 14 or more mental health outpatient visits had five times higher adjusted odds of follow-up within 7 days and 9.5 times higher adjusted odds of follow-up within 30 days, compared with children with no outpatient mental health visits in the previous year.
A ‘mental health system of care in crisis’
In an accompanying editorial, Hannah E. Karpman, MSW, PhD, with the department of pediatrics, University of Massachusetts, Worcester, and colleagues said those statistics help expose other signs of “a pediatric mental health system of care in crisis.”
If one in five children are spending more than 2 days in the ED for their initial mental health visit, they wrote, that signals the follow-up care they need is not readily available.
The 27% returning to the ED shows that, even if the children are getting outpatient services, that environment is failing them, they noted.
Additionally, 28% of children presented with more than four mental health diagnoses, “suggesting poor diagnostic specificity or perhaps inadequate diagnostic categories to characterize their needs.”
The authors called for interventions that link patients to outpatient care within 5 days of a mental health ED discharge.
The editorialists wrote: “We believe it is time for a “child mental health moonshot,” and call on the field and its funders to come together to launch the next wave of bold mental health research for the benefit of these children and their families who so desperately need our support.”
Things may even be worse in light of COVID
David Rettew, MD, a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland, said in an interview the numbers won’t surprise clinicians who support these children or the patients’ families.
He added that he wouldn’t be surprised if things are even worse now after this study’s data collection, “as COVID and other factors have driven more mental health professionals away from many of the people who need them the most.”
The study does present new evidence that quick access to care is particularly tough for young people who aren’t already established in care, he noted.
“As wait lists grow at outpatient clinics, we are seeing ever stronger need for centers willing and able to provide actual mental health assessment and treatment for people right ‘off the street,’” he said.
Dr. Rettew emphasized that, because mental health conditions rarely improve quickly, having a timely follow-up appointment is important, but won’t likely bring quick improvement.
He agreed with the editorialists’ argument and emphasized, “not only do we need to focus on more rapid care, but also more comprehensive and effective care.
“For an adolescent in crisis, achieving stability often involves more than a medication tweak and a supportive conversation,” Dr. Rettew said. “Rather, it can require an intensive multimodal approach that addresses things like family financial stressors, parental mental health and substance use concerns, school supports, and health promotion or lifestyle changes. What we desperately need are more teams that can quickly intervene on all these levels.”
Addressing problems before crisis is essential
Ideally, teams would address these issues before a crisis. That helps support the “moonshot” charge the editorialists suggest, which “would significantly disrupt the current way we value different components of our health care system,” Dr. Rettew said.
He highlighted a statistic that may get lost in the data: Nearly 40% of youth in enough danger to need an ED visit had no more than one health-related appointment of any kind in the previous year.
“To me, this speaks volumes about the need for earlier involvement before things escalate to the level of an emergency,” Dr. Rettew said.
The authors and editorialists declared no relevant financial relationships. Dr. Rettew is author of the book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.”
Only 56% of children enrolled in Medicaid received any outpatient follow-up within 30 days after a mental health emergency department discharge, according to results of a large study released in Pediatrics.
Fewer than one-third (31.2%) had an outpatient visit within a week after a mental health ED discharge.
Researchers conducted a retrospective study of 28,551 children ages 6-17 years old who had mental health discharges from EDs from January 2018 to June 2019.
The researchers, led by Jennifer A. Hoffmann, MD, MS, with the division of emergency medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, Chicago, also analyzed the effect that having a timely follow-up had on whether the child was likely to return to the ED.
Follow-up within 30 days cuts risk of quick return to ED
They found that follow-up within 30 days was linked with a 26% decreased risk of return within 5 days of the initial ED discharge (hazard ratio, 0.74; 95% confidence interval, 0.63-0.91).
The researchers also found racial disparities in the data. The odds for getting follow-up outpatient care were lower for non-Hispanic Black children, for children with fee-for-service insurance, and for children with no previous mental health outpatient visits.
The numbers were particularly striking for Black children, who were 10% less likely to get outpatient follow-up than their White counterparts.
In addition, 27% of all children in this sample returned to the ED for mental health-related symptoms within 6 months, 20% spent more than 48 hours in the ED for their initial mental health visit, and children with 14 or more mental health outpatient visits had five times higher adjusted odds of follow-up within 7 days and 9.5 times higher adjusted odds of follow-up within 30 days, compared with children with no outpatient mental health visits in the previous year.
A ‘mental health system of care in crisis’
In an accompanying editorial, Hannah E. Karpman, MSW, PhD, with the department of pediatrics, University of Massachusetts, Worcester, and colleagues said those statistics help expose other signs of “a pediatric mental health system of care in crisis.”
If one in five children are spending more than 2 days in the ED for their initial mental health visit, they wrote, that signals the follow-up care they need is not readily available.
The 27% returning to the ED shows that, even if the children are getting outpatient services, that environment is failing them, they noted.
Additionally, 28% of children presented with more than four mental health diagnoses, “suggesting poor diagnostic specificity or perhaps inadequate diagnostic categories to characterize their needs.”
The authors called for interventions that link patients to outpatient care within 5 days of a mental health ED discharge.
The editorialists wrote: “We believe it is time for a “child mental health moonshot,” and call on the field and its funders to come together to launch the next wave of bold mental health research for the benefit of these children and their families who so desperately need our support.”
Things may even be worse in light of COVID
David Rettew, MD, a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland, said in an interview the numbers won’t surprise clinicians who support these children or the patients’ families.
He added that he wouldn’t be surprised if things are even worse now after this study’s data collection, “as COVID and other factors have driven more mental health professionals away from many of the people who need them the most.”
The study does present new evidence that quick access to care is particularly tough for young people who aren’t already established in care, he noted.
“As wait lists grow at outpatient clinics, we are seeing ever stronger need for centers willing and able to provide actual mental health assessment and treatment for people right ‘off the street,’” he said.
Dr. Rettew emphasized that, because mental health conditions rarely improve quickly, having a timely follow-up appointment is important, but won’t likely bring quick improvement.
He agreed with the editorialists’ argument and emphasized, “not only do we need to focus on more rapid care, but also more comprehensive and effective care.
“For an adolescent in crisis, achieving stability often involves more than a medication tweak and a supportive conversation,” Dr. Rettew said. “Rather, it can require an intensive multimodal approach that addresses things like family financial stressors, parental mental health and substance use concerns, school supports, and health promotion or lifestyle changes. What we desperately need are more teams that can quickly intervene on all these levels.”
Addressing problems before crisis is essential
Ideally, teams would address these issues before a crisis. That helps support the “moonshot” charge the editorialists suggest, which “would significantly disrupt the current way we value different components of our health care system,” Dr. Rettew said.
He highlighted a statistic that may get lost in the data: Nearly 40% of youth in enough danger to need an ED visit had no more than one health-related appointment of any kind in the previous year.
“To me, this speaks volumes about the need for earlier involvement before things escalate to the level of an emergency,” Dr. Rettew said.
The authors and editorialists declared no relevant financial relationships. Dr. Rettew is author of the book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.”
Only 56% of children enrolled in Medicaid received any outpatient follow-up within 30 days after a mental health emergency department discharge, according to results of a large study released in Pediatrics.
Fewer than one-third (31.2%) had an outpatient visit within a week after a mental health ED discharge.
Researchers conducted a retrospective study of 28,551 children ages 6-17 years old who had mental health discharges from EDs from January 2018 to June 2019.
The researchers, led by Jennifer A. Hoffmann, MD, MS, with the division of emergency medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, Chicago, also analyzed the effect that having a timely follow-up had on whether the child was likely to return to the ED.
Follow-up within 30 days cuts risk of quick return to ED
They found that follow-up within 30 days was linked with a 26% decreased risk of return within 5 days of the initial ED discharge (hazard ratio, 0.74; 95% confidence interval, 0.63-0.91).
The researchers also found racial disparities in the data. The odds for getting follow-up outpatient care were lower for non-Hispanic Black children, for children with fee-for-service insurance, and for children with no previous mental health outpatient visits.
The numbers were particularly striking for Black children, who were 10% less likely to get outpatient follow-up than their White counterparts.
In addition, 27% of all children in this sample returned to the ED for mental health-related symptoms within 6 months, 20% spent more than 48 hours in the ED for their initial mental health visit, and children with 14 or more mental health outpatient visits had five times higher adjusted odds of follow-up within 7 days and 9.5 times higher adjusted odds of follow-up within 30 days, compared with children with no outpatient mental health visits in the previous year.
A ‘mental health system of care in crisis’
In an accompanying editorial, Hannah E. Karpman, MSW, PhD, with the department of pediatrics, University of Massachusetts, Worcester, and colleagues said those statistics help expose other signs of “a pediatric mental health system of care in crisis.”
If one in five children are spending more than 2 days in the ED for their initial mental health visit, they wrote, that signals the follow-up care they need is not readily available.
The 27% returning to the ED shows that, even if the children are getting outpatient services, that environment is failing them, they noted.
Additionally, 28% of children presented with more than four mental health diagnoses, “suggesting poor diagnostic specificity or perhaps inadequate diagnostic categories to characterize their needs.”
The authors called for interventions that link patients to outpatient care within 5 days of a mental health ED discharge.
The editorialists wrote: “We believe it is time for a “child mental health moonshot,” and call on the field and its funders to come together to launch the next wave of bold mental health research for the benefit of these children and their families who so desperately need our support.”
Things may even be worse in light of COVID
David Rettew, MD, a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland, said in an interview the numbers won’t surprise clinicians who support these children or the patients’ families.
He added that he wouldn’t be surprised if things are even worse now after this study’s data collection, “as COVID and other factors have driven more mental health professionals away from many of the people who need them the most.”
The study does present new evidence that quick access to care is particularly tough for young people who aren’t already established in care, he noted.
“As wait lists grow at outpatient clinics, we are seeing ever stronger need for centers willing and able to provide actual mental health assessment and treatment for people right ‘off the street,’” he said.
Dr. Rettew emphasized that, because mental health conditions rarely improve quickly, having a timely follow-up appointment is important, but won’t likely bring quick improvement.
He agreed with the editorialists’ argument and emphasized, “not only do we need to focus on more rapid care, but also more comprehensive and effective care.
“For an adolescent in crisis, achieving stability often involves more than a medication tweak and a supportive conversation,” Dr. Rettew said. “Rather, it can require an intensive multimodal approach that addresses things like family financial stressors, parental mental health and substance use concerns, school supports, and health promotion or lifestyle changes. What we desperately need are more teams that can quickly intervene on all these levels.”
Addressing problems before crisis is essential
Ideally, teams would address these issues before a crisis. That helps support the “moonshot” charge the editorialists suggest, which “would significantly disrupt the current way we value different components of our health care system,” Dr. Rettew said.
He highlighted a statistic that may get lost in the data: Nearly 40% of youth in enough danger to need an ED visit had no more than one health-related appointment of any kind in the previous year.
“To me, this speaks volumes about the need for earlier involvement before things escalate to the level of an emergency,” Dr. Rettew said.
The authors and editorialists declared no relevant financial relationships. Dr. Rettew is author of the book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.”
FROM PEDIATRICS
In adults with prediabetes, vitamin D cuts diabetes risk
Results of the analysis, led by Anastassios G. Pittas, MD, MS, with the division of endocrinology, diabetes, and metabolism at Tufts Medical Center, in Boston, were published online in Annals of Internal Medicine (2023 Feb 7. doi: 10.7326/M22-3018).
All three eligible trials included in the analysis were randomized, double blinded, and placebo controlled. The three eligible trials tested three oral formulations of Vitamin D: cholecalciferol, 20,000 IU (500 mcg) weekly; cholecalciferol, 4,000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, against placebos.
The authors of the new paper found that vitamin D reduced the risk for diabetes in people with prediabetes by a statistically significant 15% in adjusted analyses. The 3-year absolute risk reduction was 3.3%.
They found no difference in the rate ratios for adverse events (kidney stones, 1.17, 95% confidence interval, 0.69-1.99; hypercalcemia, 2.34; 95% CI, 0.83-6.66]; hypercalciuria, 1.65; 95% CI, 0.83-3.28]; death, 0.85; 95% CI, 0.31-2.36]) when study participants got vitamin D instead of placebo.
Differences from previous analyses
The relationship between vitamin D levels and risk for type 2 diabetes has been studied in previous trials and results have been mixed.
The authors note that two previous meta-analyses included trials “that had relatively short durations for assessment of diabetes risk (for example, ≤ 1 year), had high risk of bias (for example, open-label trials), or were not specifically designed and conducted for primary prevention of type 2 diabetes, potentially undermining the validity of the results.”
Each of the trials in this meta-analysis had a low risk of bias as determined by the Cochrane risk-of-bias tool, Dr. Pittas and colleagues said.
“The present study does not reach an opposite conclusion from the D2d study,” said Dr. Pittas, who coauthored that paper as well. “Rather, it confirms the results of the D2d study. In D2d and two other similar vitamin D and diabetes prevention trials (one in Norway and one in Japan), vitamin D reduced the rate of progression to diabetes in adults with prediabetes, but the observed differences were not statistically significant because the reported relative risk reductions (10%-13%) were smaller than each trial was powered to detect (25%-36%).”
“Individual participant data meta-analyses increase the statistical power to detect an effect. After combining data, we found that vitamin D reduced the risk of progression from prediabetes to diabetes by 15% and this result was statistically significant. So, the conclusion of the meta-analysis is essentially the same conclusion as in D2d and the other two trials. The difference is that the result is now statistically significant,” Dr. Pittas added.
Small reduction but large population
The authors acknowledged that the absolute risk reduction number is small, especially when compared with the risk reduction seen with intensive lifestyle changes (58%) and metformin (31%), as reported in an article published in the New England of Journal of Medicine (2002 Feb 7;346:393-403). But “extrapolating to the more than 374 million adults worldwide who have prediabetes suggests that inexpensive vitamin D supplementation could delay the development of diabetes in more than 10 million people,” they said.
As for how high vitamin D levels need to be, the authors write that their research indicates that the optimal level of vitamin D in the blood needed to reduce diabetes risk may be higher than an Institute of Medicine committee recommendation in 2011.
“The blood 25-hydroxy vitamin D level needed to optimally reduce diabetes risk may be near and possibly above the range of 125-150 nmol/L (50-60 ng/mL) that the 2011 Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D provided as the range corresponding to the tolerable upper intake level (UL) of 4,000 IU/d for vitamin D,” the authors of the new paper said.
Editorialists urge caution
In an accompanying editorial also published in the Annals of Internal Medicine, Malachi J. McKenna, MD, with the department of clinical chemistry, at St. Vincent’s University Hospital, and Mary A.T. Flynn, PhD, RD, with the Food Safety Authority of Ireland in Dublin, urge caution regarding vitamin D dosing.
They write that there are important distinctions between vitamin D supplements and vitamin D therapy, and the potential harms of high-dose vitamin D are still unclear.
“Vitamin D supplementation of 10 to 20 mcg (400 to 800 IU) daily can be applied safely at the population level to prevent skeletal and possibly nonskeletal disease. Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm,” they note.
Dr. Pittas said in an interview that there have been some studies with high-dose vitamin D (up to 500,000 IU a year in one study) that reported an increased fall risk in older adults who had high fall risk. “However, these findings are not generalizable to other populations that are younger and at low or average fall risk, such as the prediabetes population to which the results of this meta-analysis apply,” he noted.
“The benefit-to-risk ratio for vitamin D depends on the target population and medical condition,” Dr. Pittas said. “The editorial refers to the NAM (National Academy of Medicine) vitamin D guidelines for the general, healthy population to promote bone health. The guidelines should not be extrapolated to specific populations, for example [patients with] prediabetes,” where the vitamin D benefit-to-risk ratio would be different from that in the general population.
Dr. Pittas and colleagues caution that the people studied in this meta-analysis were at high risk for type 2 diabetes, so these results do not apply to the general healthy population. The results also should not be extrapolated to people at average risk for any type of diabetes, they add.
Several physicians either declined to comment or did not respond to requests for comment on this research.
Dr. Pittas reports the National Institutes of Health and the American Diabetes Association made payments to his institution to conduct Vitamin D-related research. He is an unpaid cochair of the Endocrine Society’s Evaluation, Treatment and Prevention of Vitamin D Deficiency Clinical Practice Guideline team.
Coauthor Dr. Jorde reports grants from Novo Nordisk Foundation, North Norwegian Regional Health Authorities, and the Research Council of Norway.
Dr. Dawson-Hughes reports she is on the DSMB for AgNovos Healthcare. AgNovos is developing a bone implant to reduce hip fracture risk and she gets a stipend from the company. She reports Helsinn Therapeutics provided anamorelin and matching placebo for an NIH-funded clinical trial.
Dr. Trikalinos was supported by the D2d study. He is a technical methodological consultant to Latham and Watkins, who is retained by Pacira Pharmaceuticals.
Dr. Angellotti has been employed by Takeda and owns stock in the company.
The editorialists report no relevant financial relationships.
Results of the analysis, led by Anastassios G. Pittas, MD, MS, with the division of endocrinology, diabetes, and metabolism at Tufts Medical Center, in Boston, were published online in Annals of Internal Medicine (2023 Feb 7. doi: 10.7326/M22-3018).
All three eligible trials included in the analysis were randomized, double blinded, and placebo controlled. The three eligible trials tested three oral formulations of Vitamin D: cholecalciferol, 20,000 IU (500 mcg) weekly; cholecalciferol, 4,000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, against placebos.
The authors of the new paper found that vitamin D reduced the risk for diabetes in people with prediabetes by a statistically significant 15% in adjusted analyses. The 3-year absolute risk reduction was 3.3%.
They found no difference in the rate ratios for adverse events (kidney stones, 1.17, 95% confidence interval, 0.69-1.99; hypercalcemia, 2.34; 95% CI, 0.83-6.66]; hypercalciuria, 1.65; 95% CI, 0.83-3.28]; death, 0.85; 95% CI, 0.31-2.36]) when study participants got vitamin D instead of placebo.
Differences from previous analyses
The relationship between vitamin D levels and risk for type 2 diabetes has been studied in previous trials and results have been mixed.
The authors note that two previous meta-analyses included trials “that had relatively short durations for assessment of diabetes risk (for example, ≤ 1 year), had high risk of bias (for example, open-label trials), or were not specifically designed and conducted for primary prevention of type 2 diabetes, potentially undermining the validity of the results.”
Each of the trials in this meta-analysis had a low risk of bias as determined by the Cochrane risk-of-bias tool, Dr. Pittas and colleagues said.
“The present study does not reach an opposite conclusion from the D2d study,” said Dr. Pittas, who coauthored that paper as well. “Rather, it confirms the results of the D2d study. In D2d and two other similar vitamin D and diabetes prevention trials (one in Norway and one in Japan), vitamin D reduced the rate of progression to diabetes in adults with prediabetes, but the observed differences were not statistically significant because the reported relative risk reductions (10%-13%) were smaller than each trial was powered to detect (25%-36%).”
“Individual participant data meta-analyses increase the statistical power to detect an effect. After combining data, we found that vitamin D reduced the risk of progression from prediabetes to diabetes by 15% and this result was statistically significant. So, the conclusion of the meta-analysis is essentially the same conclusion as in D2d and the other two trials. The difference is that the result is now statistically significant,” Dr. Pittas added.
Small reduction but large population
The authors acknowledged that the absolute risk reduction number is small, especially when compared with the risk reduction seen with intensive lifestyle changes (58%) and metformin (31%), as reported in an article published in the New England of Journal of Medicine (2002 Feb 7;346:393-403). But “extrapolating to the more than 374 million adults worldwide who have prediabetes suggests that inexpensive vitamin D supplementation could delay the development of diabetes in more than 10 million people,” they said.
As for how high vitamin D levels need to be, the authors write that their research indicates that the optimal level of vitamin D in the blood needed to reduce diabetes risk may be higher than an Institute of Medicine committee recommendation in 2011.
“The blood 25-hydroxy vitamin D level needed to optimally reduce diabetes risk may be near and possibly above the range of 125-150 nmol/L (50-60 ng/mL) that the 2011 Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D provided as the range corresponding to the tolerable upper intake level (UL) of 4,000 IU/d for vitamin D,” the authors of the new paper said.
Editorialists urge caution
In an accompanying editorial also published in the Annals of Internal Medicine, Malachi J. McKenna, MD, with the department of clinical chemistry, at St. Vincent’s University Hospital, and Mary A.T. Flynn, PhD, RD, with the Food Safety Authority of Ireland in Dublin, urge caution regarding vitamin D dosing.
They write that there are important distinctions between vitamin D supplements and vitamin D therapy, and the potential harms of high-dose vitamin D are still unclear.
“Vitamin D supplementation of 10 to 20 mcg (400 to 800 IU) daily can be applied safely at the population level to prevent skeletal and possibly nonskeletal disease. Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm,” they note.
Dr. Pittas said in an interview that there have been some studies with high-dose vitamin D (up to 500,000 IU a year in one study) that reported an increased fall risk in older adults who had high fall risk. “However, these findings are not generalizable to other populations that are younger and at low or average fall risk, such as the prediabetes population to which the results of this meta-analysis apply,” he noted.
“The benefit-to-risk ratio for vitamin D depends on the target population and medical condition,” Dr. Pittas said. “The editorial refers to the NAM (National Academy of Medicine) vitamin D guidelines for the general, healthy population to promote bone health. The guidelines should not be extrapolated to specific populations, for example [patients with] prediabetes,” where the vitamin D benefit-to-risk ratio would be different from that in the general population.
Dr. Pittas and colleagues caution that the people studied in this meta-analysis were at high risk for type 2 diabetes, so these results do not apply to the general healthy population. The results also should not be extrapolated to people at average risk for any type of diabetes, they add.
Several physicians either declined to comment or did not respond to requests for comment on this research.
Dr. Pittas reports the National Institutes of Health and the American Diabetes Association made payments to his institution to conduct Vitamin D-related research. He is an unpaid cochair of the Endocrine Society’s Evaluation, Treatment and Prevention of Vitamin D Deficiency Clinical Practice Guideline team.
Coauthor Dr. Jorde reports grants from Novo Nordisk Foundation, North Norwegian Regional Health Authorities, and the Research Council of Norway.
Dr. Dawson-Hughes reports she is on the DSMB for AgNovos Healthcare. AgNovos is developing a bone implant to reduce hip fracture risk and she gets a stipend from the company. She reports Helsinn Therapeutics provided anamorelin and matching placebo for an NIH-funded clinical trial.
Dr. Trikalinos was supported by the D2d study. He is a technical methodological consultant to Latham and Watkins, who is retained by Pacira Pharmaceuticals.
Dr. Angellotti has been employed by Takeda and owns stock in the company.
The editorialists report no relevant financial relationships.
Results of the analysis, led by Anastassios G. Pittas, MD, MS, with the division of endocrinology, diabetes, and metabolism at Tufts Medical Center, in Boston, were published online in Annals of Internal Medicine (2023 Feb 7. doi: 10.7326/M22-3018).
All three eligible trials included in the analysis were randomized, double blinded, and placebo controlled. The three eligible trials tested three oral formulations of Vitamin D: cholecalciferol, 20,000 IU (500 mcg) weekly; cholecalciferol, 4,000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, against placebos.
The authors of the new paper found that vitamin D reduced the risk for diabetes in people with prediabetes by a statistically significant 15% in adjusted analyses. The 3-year absolute risk reduction was 3.3%.
They found no difference in the rate ratios for adverse events (kidney stones, 1.17, 95% confidence interval, 0.69-1.99; hypercalcemia, 2.34; 95% CI, 0.83-6.66]; hypercalciuria, 1.65; 95% CI, 0.83-3.28]; death, 0.85; 95% CI, 0.31-2.36]) when study participants got vitamin D instead of placebo.
Differences from previous analyses
The relationship between vitamin D levels and risk for type 2 diabetes has been studied in previous trials and results have been mixed.
The authors note that two previous meta-analyses included trials “that had relatively short durations for assessment of diabetes risk (for example, ≤ 1 year), had high risk of bias (for example, open-label trials), or were not specifically designed and conducted for primary prevention of type 2 diabetes, potentially undermining the validity of the results.”
Each of the trials in this meta-analysis had a low risk of bias as determined by the Cochrane risk-of-bias tool, Dr. Pittas and colleagues said.
“The present study does not reach an opposite conclusion from the D2d study,” said Dr. Pittas, who coauthored that paper as well. “Rather, it confirms the results of the D2d study. In D2d and two other similar vitamin D and diabetes prevention trials (one in Norway and one in Japan), vitamin D reduced the rate of progression to diabetes in adults with prediabetes, but the observed differences were not statistically significant because the reported relative risk reductions (10%-13%) were smaller than each trial was powered to detect (25%-36%).”
“Individual participant data meta-analyses increase the statistical power to detect an effect. After combining data, we found that vitamin D reduced the risk of progression from prediabetes to diabetes by 15% and this result was statistically significant. So, the conclusion of the meta-analysis is essentially the same conclusion as in D2d and the other two trials. The difference is that the result is now statistically significant,” Dr. Pittas added.
Small reduction but large population
The authors acknowledged that the absolute risk reduction number is small, especially when compared with the risk reduction seen with intensive lifestyle changes (58%) and metformin (31%), as reported in an article published in the New England of Journal of Medicine (2002 Feb 7;346:393-403). But “extrapolating to the more than 374 million adults worldwide who have prediabetes suggests that inexpensive vitamin D supplementation could delay the development of diabetes in more than 10 million people,” they said.
As for how high vitamin D levels need to be, the authors write that their research indicates that the optimal level of vitamin D in the blood needed to reduce diabetes risk may be higher than an Institute of Medicine committee recommendation in 2011.
“The blood 25-hydroxy vitamin D level needed to optimally reduce diabetes risk may be near and possibly above the range of 125-150 nmol/L (50-60 ng/mL) that the 2011 Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D provided as the range corresponding to the tolerable upper intake level (UL) of 4,000 IU/d for vitamin D,” the authors of the new paper said.
Editorialists urge caution
In an accompanying editorial also published in the Annals of Internal Medicine, Malachi J. McKenna, MD, with the department of clinical chemistry, at St. Vincent’s University Hospital, and Mary A.T. Flynn, PhD, RD, with the Food Safety Authority of Ireland in Dublin, urge caution regarding vitamin D dosing.
They write that there are important distinctions between vitamin D supplements and vitamin D therapy, and the potential harms of high-dose vitamin D are still unclear.
“Vitamin D supplementation of 10 to 20 mcg (400 to 800 IU) daily can be applied safely at the population level to prevent skeletal and possibly nonskeletal disease. Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm,” they note.
Dr. Pittas said in an interview that there have been some studies with high-dose vitamin D (up to 500,000 IU a year in one study) that reported an increased fall risk in older adults who had high fall risk. “However, these findings are not generalizable to other populations that are younger and at low or average fall risk, such as the prediabetes population to which the results of this meta-analysis apply,” he noted.
“The benefit-to-risk ratio for vitamin D depends on the target population and medical condition,” Dr. Pittas said. “The editorial refers to the NAM (National Academy of Medicine) vitamin D guidelines for the general, healthy population to promote bone health. The guidelines should not be extrapolated to specific populations, for example [patients with] prediabetes,” where the vitamin D benefit-to-risk ratio would be different from that in the general population.
Dr. Pittas and colleagues caution that the people studied in this meta-analysis were at high risk for type 2 diabetes, so these results do not apply to the general healthy population. The results also should not be extrapolated to people at average risk for any type of diabetes, they add.
Several physicians either declined to comment or did not respond to requests for comment on this research.
Dr. Pittas reports the National Institutes of Health and the American Diabetes Association made payments to his institution to conduct Vitamin D-related research. He is an unpaid cochair of the Endocrine Society’s Evaluation, Treatment and Prevention of Vitamin D Deficiency Clinical Practice Guideline team.
Coauthor Dr. Jorde reports grants from Novo Nordisk Foundation, North Norwegian Regional Health Authorities, and the Research Council of Norway.
Dr. Dawson-Hughes reports she is on the DSMB for AgNovos Healthcare. AgNovos is developing a bone implant to reduce hip fracture risk and she gets a stipend from the company. She reports Helsinn Therapeutics provided anamorelin and matching placebo for an NIH-funded clinical trial.
Dr. Trikalinos was supported by the D2d study. He is a technical methodological consultant to Latham and Watkins, who is retained by Pacira Pharmaceuticals.
Dr. Angellotti has been employed by Takeda and owns stock in the company.
The editorialists report no relevant financial relationships.
FROM ANNALS OF INTERNAL MEDICINE
Pandemic pregnancy-linked deaths up 35% from 2019
Pregnancy-associated deaths, including drug-related deaths and homicide, were up 35% in 2020, compared with prepandemic 2019, new research indicates.
The data also show a 7.1% decrease in pregnancy-related suicides in 2020 from 2019.
The study, led by Claire E. Margerison, PhD, with the department of epidemiology and biostatistics at Michigan State University, East Lansing, included 4,528 pregnancy-associated deaths. The rate of deaths per 100,000 live births from April to December 2020 was 66.9 (95% confidence interval, 63.9-70.1). The comparative rate from April to December 2019 was 49.6. Researchers looked at that time period because the pandemic started in March 2020.
The findings were published online in JAMA Open Network.
Drug-related deaths up 55.3%
During the study period, drug deaths increased 55.3% and deaths from homicide increased 41.2%. Deaths from obstetric and other causes (mainly vehicle crashes) increased 28.4% and 56.7%, respectively, according to Dr. Margerison's group.
“Although pregnancy-associated deaths increased over time, increases from 2019 to 2020 were substantially larger than increases from 2018 to 2019,” the authors wrote.
The findings align with deaths in the general population in that time frame, they added.
Another study – this one looking at all-cause and cause-specific mortality from 2019 to 2020 in recently pregnant women, also published in JAMA Network Open, found significant racial and ethnic disparities in rates and cause of death.
According to the study, “Compared with non-Hispanic White women, mortality rates were three- to fivefold higher among American Indian or Alaska Native women for every cause, including suicide. Likewise, these findings suggest that non-Hispanic Black women experienced significantly higher mortality rates across causes, with the highest rates for homicide.”
Dr. Margerison and colleagues did not try to answer what caused the increases but pointed to the fentanyl epidemic, the murder of George Floyd, and COVID-19–related economic strain as potential stressors. They also suggest fewer screenings during the pandemic may have played a role.
Prevention opportunities missed
“Although pregnancy is considered an opportunity for screening and prevention related to physical, mental, and behavioral health, our data suggest that such opportunities were missed for hundreds of pregnant people during the pandemic,” the authors wrote.
Researchers analyzed cross-sectional U.S. death certificates from Jan. 1, 2018, to Dec. 31, 2020, for female U.S. residents ages 15-44 years. They then obtained the count for live births for the same population and time frame from the Centers for Disease Control and Prevention WONDER database.
They were able to identify pregnancy-associated deaths as the 2003 Revised Death Certificate contains a standardized pregnancy checkbox that asks whether the person was pregnant at the time of death, within 42 days of death, or within 43 days to 1 year of death.
Researchers also included deaths with ICD-10 codes linked with death from obstetric causes.
Deaths from overdose, suicide, and homicide are making up large and growing proportions of all deaths during pregnancy and in the first year postpartum, the authors report.
Dr. Margerison and coauthors, in research published in 2022, reported that these causes account for more than one-fifth of all pregnancy-related deaths. They also reported that drug-related deaths and homicides in this population have increased over the past 10 years.
“Substantial racial and ethnic inequities in these deaths exist,” they wrote in that paper.
The authors concluded in the current research: “Our study findings suggest that there is a need for prevention and intervention efforts, including harm-reduction strategies, tailored to pregnant and postpartum women, particularly during times of population stress and decreased utilization of preventive care, such as a pandemic.”
Dr. Margerison and coauthors reported receiving grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the study. One coauthor received personal fees from the World Health Organization and Population Reference Bureau outside the submitted work. One coauthor reported receiving grant support from the National Institutes of Mental Health during the study.
*This story was updated on 2/1.
Pregnancy-associated deaths, including drug-related deaths and homicide, were up 35% in 2020, compared with prepandemic 2019, new research indicates.
The data also show a 7.1% decrease in pregnancy-related suicides in 2020 from 2019.
The study, led by Claire E. Margerison, PhD, with the department of epidemiology and biostatistics at Michigan State University, East Lansing, included 4,528 pregnancy-associated deaths. The rate of deaths per 100,000 live births from April to December 2020 was 66.9 (95% confidence interval, 63.9-70.1). The comparative rate from April to December 2019 was 49.6. Researchers looked at that time period because the pandemic started in March 2020.
The findings were published online in JAMA Open Network.
Drug-related deaths up 55.3%
During the study period, drug deaths increased 55.3% and deaths from homicide increased 41.2%. Deaths from obstetric and other causes (mainly vehicle crashes) increased 28.4% and 56.7%, respectively, according to Dr. Margerison's group.
“Although pregnancy-associated deaths increased over time, increases from 2019 to 2020 were substantially larger than increases from 2018 to 2019,” the authors wrote.
The findings align with deaths in the general population in that time frame, they added.
Another study – this one looking at all-cause and cause-specific mortality from 2019 to 2020 in recently pregnant women, also published in JAMA Network Open, found significant racial and ethnic disparities in rates and cause of death.
According to the study, “Compared with non-Hispanic White women, mortality rates were three- to fivefold higher among American Indian or Alaska Native women for every cause, including suicide. Likewise, these findings suggest that non-Hispanic Black women experienced significantly higher mortality rates across causes, with the highest rates for homicide.”
Dr. Margerison and colleagues did not try to answer what caused the increases but pointed to the fentanyl epidemic, the murder of George Floyd, and COVID-19–related economic strain as potential stressors. They also suggest fewer screenings during the pandemic may have played a role.
Prevention opportunities missed
“Although pregnancy is considered an opportunity for screening and prevention related to physical, mental, and behavioral health, our data suggest that such opportunities were missed for hundreds of pregnant people during the pandemic,” the authors wrote.
Researchers analyzed cross-sectional U.S. death certificates from Jan. 1, 2018, to Dec. 31, 2020, for female U.S. residents ages 15-44 years. They then obtained the count for live births for the same population and time frame from the Centers for Disease Control and Prevention WONDER database.
They were able to identify pregnancy-associated deaths as the 2003 Revised Death Certificate contains a standardized pregnancy checkbox that asks whether the person was pregnant at the time of death, within 42 days of death, or within 43 days to 1 year of death.
Researchers also included deaths with ICD-10 codes linked with death from obstetric causes.
Deaths from overdose, suicide, and homicide are making up large and growing proportions of all deaths during pregnancy and in the first year postpartum, the authors report.
Dr. Margerison and coauthors, in research published in 2022, reported that these causes account for more than one-fifth of all pregnancy-related deaths. They also reported that drug-related deaths and homicides in this population have increased over the past 10 years.
“Substantial racial and ethnic inequities in these deaths exist,” they wrote in that paper.
The authors concluded in the current research: “Our study findings suggest that there is a need for prevention and intervention efforts, including harm-reduction strategies, tailored to pregnant and postpartum women, particularly during times of population stress and decreased utilization of preventive care, such as a pandemic.”
Dr. Margerison and coauthors reported receiving grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the study. One coauthor received personal fees from the World Health Organization and Population Reference Bureau outside the submitted work. One coauthor reported receiving grant support from the National Institutes of Mental Health during the study.
*This story was updated on 2/1.
Pregnancy-associated deaths, including drug-related deaths and homicide, were up 35% in 2020, compared with prepandemic 2019, new research indicates.
The data also show a 7.1% decrease in pregnancy-related suicides in 2020 from 2019.
The study, led by Claire E. Margerison, PhD, with the department of epidemiology and biostatistics at Michigan State University, East Lansing, included 4,528 pregnancy-associated deaths. The rate of deaths per 100,000 live births from April to December 2020 was 66.9 (95% confidence interval, 63.9-70.1). The comparative rate from April to December 2019 was 49.6. Researchers looked at that time period because the pandemic started in March 2020.
The findings were published online in JAMA Open Network.
Drug-related deaths up 55.3%
During the study period, drug deaths increased 55.3% and deaths from homicide increased 41.2%. Deaths from obstetric and other causes (mainly vehicle crashes) increased 28.4% and 56.7%, respectively, according to Dr. Margerison's group.
“Although pregnancy-associated deaths increased over time, increases from 2019 to 2020 were substantially larger than increases from 2018 to 2019,” the authors wrote.
The findings align with deaths in the general population in that time frame, they added.
Another study – this one looking at all-cause and cause-specific mortality from 2019 to 2020 in recently pregnant women, also published in JAMA Network Open, found significant racial and ethnic disparities in rates and cause of death.
According to the study, “Compared with non-Hispanic White women, mortality rates were three- to fivefold higher among American Indian or Alaska Native women for every cause, including suicide. Likewise, these findings suggest that non-Hispanic Black women experienced significantly higher mortality rates across causes, with the highest rates for homicide.”
Dr. Margerison and colleagues did not try to answer what caused the increases but pointed to the fentanyl epidemic, the murder of George Floyd, and COVID-19–related economic strain as potential stressors. They also suggest fewer screenings during the pandemic may have played a role.
Prevention opportunities missed
“Although pregnancy is considered an opportunity for screening and prevention related to physical, mental, and behavioral health, our data suggest that such opportunities were missed for hundreds of pregnant people during the pandemic,” the authors wrote.
Researchers analyzed cross-sectional U.S. death certificates from Jan. 1, 2018, to Dec. 31, 2020, for female U.S. residents ages 15-44 years. They then obtained the count for live births for the same population and time frame from the Centers for Disease Control and Prevention WONDER database.
They were able to identify pregnancy-associated deaths as the 2003 Revised Death Certificate contains a standardized pregnancy checkbox that asks whether the person was pregnant at the time of death, within 42 days of death, or within 43 days to 1 year of death.
Researchers also included deaths with ICD-10 codes linked with death from obstetric causes.
Deaths from overdose, suicide, and homicide are making up large and growing proportions of all deaths during pregnancy and in the first year postpartum, the authors report.
Dr. Margerison and coauthors, in research published in 2022, reported that these causes account for more than one-fifth of all pregnancy-related deaths. They also reported that drug-related deaths and homicides in this population have increased over the past 10 years.
“Substantial racial and ethnic inequities in these deaths exist,” they wrote in that paper.
The authors concluded in the current research: “Our study findings suggest that there is a need for prevention and intervention efforts, including harm-reduction strategies, tailored to pregnant and postpartum women, particularly during times of population stress and decreased utilization of preventive care, such as a pandemic.”
Dr. Margerison and coauthors reported receiving grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the study. One coauthor received personal fees from the World Health Organization and Population Reference Bureau outside the submitted work. One coauthor reported receiving grant support from the National Institutes of Mental Health during the study.
*This story was updated on 2/1.
FROM JAMA NETWORK OPEN
Pediatricians, specialists largely agree on ASD diagnoses
General pediatricians and a multidisciplinary team of specialists agreed most of the time on which children should be diagnosed with autism spectrum disorder (ASD), data from a new study suggest.
But when it came to ruling out ASD, the agreement rate was much lower.
The study by Melanie Penner, MSc, MD, with the Autism Research Centre at Bloorview Research Institute, Toronto, and colleagues found that 89% of the time when a physician determined a child had ASD, the multidisciplinary team agreed. But when a pediatrician thought a child did not have ASD, the multidisciplinary team agreed only 60% of the time. The study was published in JAMA Network Open.
Multidisciplinary team model can’t keep up with demand
The findings are important as many guidelines recommend multidisciplinary teams (MDTs) for all ASD diagnostic assessment. However, the resources for this model can’t meet the demand of children needing a diagnosis and can lead to long waits for ASD therapies.
In Canada, the researchers note, the average wait time from referral to receipt of ASD diagnosis has been reported as 7 months and “has likely lengthened since the COVID-19 pandemic.”
Jennifer Gerdts, PhD, an attending psychologist at the Seattle Children’s Autism Center, said in an interview that the wait there for diagnosis in children older than 4 is “multiple years,” a length of time that’s common across the United States. Meanwhile, in many states families can’t access services without a diagnosis.
Expanding capacity with diagnoses by general pediatricians may improve access, but the diagnostic accuracy is critical.
Dr. Gerdts, who was not part of the study, said this research is “hugely important in the work that is under way to build community capacity for diagnostic evaluation.”
She said this study shows that not all diagnoses need the resources of a multiple-disciplinary team and that “pediatricians can do it, too, and they can do it pretty accurately.” Dr. Gerdts evaluates children for autism and helps train pediatricians to make diagnoses.
Pediatricians, specialist team completed blinded assessments
The 17 pediatricians in the study and the specialist team independently completed blinded assessment and each recorded a decision on whether the child had ASD. The prospective diagnostic study was conducted in a specialist assessment center in Toronto and in general pediatrician practices in Ontario from June 2016 to March 2020.
Children were younger than 5.5 years, did not have an ASD diagnosis and were referred because there was a development concern. The pediatricians referred 106 children (75% boys; average age, 3.5 years). More than half (57%) of the participating children were from minority racial and ethnic groups.
The children were randomly assigned to two groups: One included children who had their MDT visits before their pediatrician assessment and the other group included those who had their MDT visits after their pediatrician assessment.
The MDT diagnosed more than two-thirds of the children (68%) with ASD.
Sensitivity and specificity of the pediatrician assessments, compared with that of the specialist team, were 0.75 (95% confidence interval, 0.67-0.83) and 0.79 (95% CI, 0.62-0.91), respectively.
A look at pediatricians’ accuracy
Pediatricians reported the decisions they would have made had the child not been in the study.
- In 69% of the true-positive cases, pediatricians would have given an ASD diagnosis.
- In 44% of true-negative cases, they would have told the family the child did not have autism; in 30% of those case, they would give alternative diagnoses (most commonly ADHD and language delay).
- The pediatrician would have diagnosed ASD in only one of the seven false-positive cases and would refer those patients to a subspecialist 71% of the time.
- In false-negative cases, the pediatrician would incorrectly tell the family the child does not have autism 44% of the time.
Regarding the false-negative cases, the authors wrote, “more caution is needed for pediatricians when definitively ruling out ASD, which might result in diagnostic delays.”
Confidence is key
Physician confidence was also correlated with accuracy.
The authors wrote: “Among true-positive cases (MDT and pediatrician agree the child has ASD), the pediatrician was certain or very certain 80% of the time (43 cases) and the MDT was certain or very certain 96% of the time (52 cases). As such, if pediatricians conferred ASD diagnoses when feeling certain or very certain, they would make 46 correct diagnoses and 2 incorrect diagnoses.”
The high accuracy of diagnosis when physicians are confident suggests “listening to that sense of certainty is important,” Dr. Gerdts said. Conversely, these numbers show when a physician is uncertain about diagnosing ASD, they should listen to that instinct, too, and refer.
The results of the study support having general pediatricians diagnose and move forward with their patients when the signs of ASD are more definitive, saving the less-certain cases for the more resource-intensive teams to diagnose. Many states are moving toward that “tiered” system, Dr. Gerdts said.
“For many, and in fact most children, general pediatricians are pretty accurate when making an autism diagnosis,” she said.
“Let’s get [general pediatricians] confident in recognizing when this is outside their skill and ability level,” she said. “If you’re not sure, it is better to refer them on than to misdiagnose them.”
The important missing piece she said is how to support them “so they don’t feel pressure to make that call,” Dr. Gerdts said.
This project was funded by a grant from the Bloorview Research Institute, a grant from the Canadian Institutes of Health Research and a grant from the Canadian Institutes of Health. Three coauthors consult for and receive grants from several pharmaceutical companies and other organizations. Dr. Gerdts declared no relevant financial relationships.
General pediatricians and a multidisciplinary team of specialists agreed most of the time on which children should be diagnosed with autism spectrum disorder (ASD), data from a new study suggest.
But when it came to ruling out ASD, the agreement rate was much lower.
The study by Melanie Penner, MSc, MD, with the Autism Research Centre at Bloorview Research Institute, Toronto, and colleagues found that 89% of the time when a physician determined a child had ASD, the multidisciplinary team agreed. But when a pediatrician thought a child did not have ASD, the multidisciplinary team agreed only 60% of the time. The study was published in JAMA Network Open.
Multidisciplinary team model can’t keep up with demand
The findings are important as many guidelines recommend multidisciplinary teams (MDTs) for all ASD diagnostic assessment. However, the resources for this model can’t meet the demand of children needing a diagnosis and can lead to long waits for ASD therapies.
In Canada, the researchers note, the average wait time from referral to receipt of ASD diagnosis has been reported as 7 months and “has likely lengthened since the COVID-19 pandemic.”
Jennifer Gerdts, PhD, an attending psychologist at the Seattle Children’s Autism Center, said in an interview that the wait there for diagnosis in children older than 4 is “multiple years,” a length of time that’s common across the United States. Meanwhile, in many states families can’t access services without a diagnosis.
Expanding capacity with diagnoses by general pediatricians may improve access, but the diagnostic accuracy is critical.
Dr. Gerdts, who was not part of the study, said this research is “hugely important in the work that is under way to build community capacity for diagnostic evaluation.”
She said this study shows that not all diagnoses need the resources of a multiple-disciplinary team and that “pediatricians can do it, too, and they can do it pretty accurately.” Dr. Gerdts evaluates children for autism and helps train pediatricians to make diagnoses.
Pediatricians, specialist team completed blinded assessments
The 17 pediatricians in the study and the specialist team independently completed blinded assessment and each recorded a decision on whether the child had ASD. The prospective diagnostic study was conducted in a specialist assessment center in Toronto and in general pediatrician practices in Ontario from June 2016 to March 2020.
Children were younger than 5.5 years, did not have an ASD diagnosis and were referred because there was a development concern. The pediatricians referred 106 children (75% boys; average age, 3.5 years). More than half (57%) of the participating children were from minority racial and ethnic groups.
The children were randomly assigned to two groups: One included children who had their MDT visits before their pediatrician assessment and the other group included those who had their MDT visits after their pediatrician assessment.
The MDT diagnosed more than two-thirds of the children (68%) with ASD.
Sensitivity and specificity of the pediatrician assessments, compared with that of the specialist team, were 0.75 (95% confidence interval, 0.67-0.83) and 0.79 (95% CI, 0.62-0.91), respectively.
A look at pediatricians’ accuracy
Pediatricians reported the decisions they would have made had the child not been in the study.
- In 69% of the true-positive cases, pediatricians would have given an ASD diagnosis.
- In 44% of true-negative cases, they would have told the family the child did not have autism; in 30% of those case, they would give alternative diagnoses (most commonly ADHD and language delay).
- The pediatrician would have diagnosed ASD in only one of the seven false-positive cases and would refer those patients to a subspecialist 71% of the time.
- In false-negative cases, the pediatrician would incorrectly tell the family the child does not have autism 44% of the time.
Regarding the false-negative cases, the authors wrote, “more caution is needed for pediatricians when definitively ruling out ASD, which might result in diagnostic delays.”
Confidence is key
Physician confidence was also correlated with accuracy.
The authors wrote: “Among true-positive cases (MDT and pediatrician agree the child has ASD), the pediatrician was certain or very certain 80% of the time (43 cases) and the MDT was certain or very certain 96% of the time (52 cases). As such, if pediatricians conferred ASD diagnoses when feeling certain or very certain, they would make 46 correct diagnoses and 2 incorrect diagnoses.”
The high accuracy of diagnosis when physicians are confident suggests “listening to that sense of certainty is important,” Dr. Gerdts said. Conversely, these numbers show when a physician is uncertain about diagnosing ASD, they should listen to that instinct, too, and refer.
The results of the study support having general pediatricians diagnose and move forward with their patients when the signs of ASD are more definitive, saving the less-certain cases for the more resource-intensive teams to diagnose. Many states are moving toward that “tiered” system, Dr. Gerdts said.
“For many, and in fact most children, general pediatricians are pretty accurate when making an autism diagnosis,” she said.
“Let’s get [general pediatricians] confident in recognizing when this is outside their skill and ability level,” she said. “If you’re not sure, it is better to refer them on than to misdiagnose them.”
The important missing piece she said is how to support them “so they don’t feel pressure to make that call,” Dr. Gerdts said.
This project was funded by a grant from the Bloorview Research Institute, a grant from the Canadian Institutes of Health Research and a grant from the Canadian Institutes of Health. Three coauthors consult for and receive grants from several pharmaceutical companies and other organizations. Dr. Gerdts declared no relevant financial relationships.
General pediatricians and a multidisciplinary team of specialists agreed most of the time on which children should be diagnosed with autism spectrum disorder (ASD), data from a new study suggest.
But when it came to ruling out ASD, the agreement rate was much lower.
The study by Melanie Penner, MSc, MD, with the Autism Research Centre at Bloorview Research Institute, Toronto, and colleagues found that 89% of the time when a physician determined a child had ASD, the multidisciplinary team agreed. But when a pediatrician thought a child did not have ASD, the multidisciplinary team agreed only 60% of the time. The study was published in JAMA Network Open.
Multidisciplinary team model can’t keep up with demand
The findings are important as many guidelines recommend multidisciplinary teams (MDTs) for all ASD diagnostic assessment. However, the resources for this model can’t meet the demand of children needing a diagnosis and can lead to long waits for ASD therapies.
In Canada, the researchers note, the average wait time from referral to receipt of ASD diagnosis has been reported as 7 months and “has likely lengthened since the COVID-19 pandemic.”
Jennifer Gerdts, PhD, an attending psychologist at the Seattle Children’s Autism Center, said in an interview that the wait there for diagnosis in children older than 4 is “multiple years,” a length of time that’s common across the United States. Meanwhile, in many states families can’t access services without a diagnosis.
Expanding capacity with diagnoses by general pediatricians may improve access, but the diagnostic accuracy is critical.
Dr. Gerdts, who was not part of the study, said this research is “hugely important in the work that is under way to build community capacity for diagnostic evaluation.”
She said this study shows that not all diagnoses need the resources of a multiple-disciplinary team and that “pediatricians can do it, too, and they can do it pretty accurately.” Dr. Gerdts evaluates children for autism and helps train pediatricians to make diagnoses.
Pediatricians, specialist team completed blinded assessments
The 17 pediatricians in the study and the specialist team independently completed blinded assessment and each recorded a decision on whether the child had ASD. The prospective diagnostic study was conducted in a specialist assessment center in Toronto and in general pediatrician practices in Ontario from June 2016 to March 2020.
Children were younger than 5.5 years, did not have an ASD diagnosis and were referred because there was a development concern. The pediatricians referred 106 children (75% boys; average age, 3.5 years). More than half (57%) of the participating children were from minority racial and ethnic groups.
The children were randomly assigned to two groups: One included children who had their MDT visits before their pediatrician assessment and the other group included those who had their MDT visits after their pediatrician assessment.
The MDT diagnosed more than two-thirds of the children (68%) with ASD.
Sensitivity and specificity of the pediatrician assessments, compared with that of the specialist team, were 0.75 (95% confidence interval, 0.67-0.83) and 0.79 (95% CI, 0.62-0.91), respectively.
A look at pediatricians’ accuracy
Pediatricians reported the decisions they would have made had the child not been in the study.
- In 69% of the true-positive cases, pediatricians would have given an ASD diagnosis.
- In 44% of true-negative cases, they would have told the family the child did not have autism; in 30% of those case, they would give alternative diagnoses (most commonly ADHD and language delay).
- The pediatrician would have diagnosed ASD in only one of the seven false-positive cases and would refer those patients to a subspecialist 71% of the time.
- In false-negative cases, the pediatrician would incorrectly tell the family the child does not have autism 44% of the time.
Regarding the false-negative cases, the authors wrote, “more caution is needed for pediatricians when definitively ruling out ASD, which might result in diagnostic delays.”
Confidence is key
Physician confidence was also correlated with accuracy.
The authors wrote: “Among true-positive cases (MDT and pediatrician agree the child has ASD), the pediatrician was certain or very certain 80% of the time (43 cases) and the MDT was certain or very certain 96% of the time (52 cases). As such, if pediatricians conferred ASD diagnoses when feeling certain or very certain, they would make 46 correct diagnoses and 2 incorrect diagnoses.”
The high accuracy of diagnosis when physicians are confident suggests “listening to that sense of certainty is important,” Dr. Gerdts said. Conversely, these numbers show when a physician is uncertain about diagnosing ASD, they should listen to that instinct, too, and refer.
The results of the study support having general pediatricians diagnose and move forward with their patients when the signs of ASD are more definitive, saving the less-certain cases for the more resource-intensive teams to diagnose. Many states are moving toward that “tiered” system, Dr. Gerdts said.
“For many, and in fact most children, general pediatricians are pretty accurate when making an autism diagnosis,” she said.
“Let’s get [general pediatricians] confident in recognizing when this is outside their skill and ability level,” she said. “If you’re not sure, it is better to refer them on than to misdiagnose them.”
The important missing piece she said is how to support them “so they don’t feel pressure to make that call,” Dr. Gerdts said.
This project was funded by a grant from the Bloorview Research Institute, a grant from the Canadian Institutes of Health Research and a grant from the Canadian Institutes of Health. Three coauthors consult for and receive grants from several pharmaceutical companies and other organizations. Dr. Gerdts declared no relevant financial relationships.
FROM JAMA NETWORK OPEN
Outdoor play may mitigate screen time’s risk to brain development
Watching a screen more than an hour a day as a toddler is directly linked with poorer communication and daily living skills at age 4, but outdoor play may lessen some of the effects, new research suggests.
The results point to outdoor play as a potential targeted intervention to counter suboptimal brain development in young children who are watching screens at increasingly younger ages.
The findings were published online in JAMA Pediatrics.
The researchers first investigated whether higher screen time (more than 1 hour a day on a device or watching television) at age 2 years is associated with neurodevelopmental outcomes at age 4.
They found the 885 children in the sample from the Japanese Hamamatsu Birth Cohort Study for Mothers and Children who had more screen time had lower scores on communication and daily living skills than children who watched less than an hour a day.
Scores were based on the Vineland Adaptive Behavior Scale according to parent responses to questions. The children included were born between December 2007 and March 2012 and were followed from 18 months to 4 years.
After finding the connection between screen time and lower scores, the researchers investigated whether outdoor play (at least 30 minutes a day) introduced at a 2 years and 8 months made a difference. They considered 6 or 7 days per week frequent outdoor play.
Outdoor play mitigated poorer daily living scores
The researchers found that the outdoor play intervention mitigated 18% of the association between high screen time and lower daily living scores but did not mitigate the lower communication scores.
They also found that more screen time at age 2 was significantly linked with infrequent outdoor play at age 32 months (odds ratio, 2.03; 95% confidence interval, 1.48-2.76).
The associations were consistent after taking into account factors including a child’s sex, parental education, and any autism spectrum disorder symptoms at age 18 months.
The authors noted that neurodevelopment concerns with screen use are particularly troubling as the age for use is getting younger.
A recent meta-analysis found that 75% of children younger than 2 use or watch screens, even though guidelines recommend against any screen time before 2.
In addition, the “COVID-19 pandemic led to children having more screen time, less outdoor play, and less physical activity, putting them at potentially greater risk for neurodevelopmental problems,” the authors noted.
“What is concerning is that data show screen time has not decreased after seclusion measures were lifted,” they added.
Proven benefits for outdoor play
Jennifer Cross, MD,* assistant professor and section chief for developmental pediatrics at Weill Cornell Medicine, New York, who was not part of the study, said the mitigation properties of outdoor play were something she hadn’t seen before but the concept makes sense.
“The overwhelming evidence is that screen time is not helpful for young children under the age of 2,” she said.
Outdoor play, on the other hand, has proven benefits.
“Physical activity has been shown to be good for physical and mental health so there’s no reason to believe it wouldn’t be good for 2-and-a-half-year olds,” Dr. Cross said. “It’s also good for developmental health. You want them to be engaged in imaginative play and be interactive.”
“[Outdoor play] gets them away from screens and gives them an opportunity to experience another environment and work on their motor skills and motor planning,” she added. “Exercise will change, briefly, the way our brains process information.”
Dr. Cross added that a lot of motor skills are involved in daily living skills, such as feeding, dressing, and toileting.
Screen time is increasing
The authors acknowledged that screen time may be underestimated by parents. They also noted that they did not have access to what children were watching on the screens.
“This should have been collected because the effect of high screen time differs depending on the type of program,” the authors wrote.
They added that children born in the 2020s may have been exposed to more screen time than the children reared in the early 2010s in this study.
Dr. Cross said screen use in the 2020s may be higher than estimated here and higher in certain populations globally, so it’s not easy to tell if the intervention in this study would have the same mitigating effect on a real-world population.
However, she said, the effect of outdoor play is always going to be helpful for brain development and there’s no downside.
“Exercise is just as important for little kids as it is for grown-ups,” she said.
The authors reported no relevant financial disclosures. Dr. Cross reported no relevant financial disclosures.
*Dr. Jennifer Cross is the correct name, not Dr. Jennifer Frost. The correction was made on Jan. 27, 2023.
Watching a screen more than an hour a day as a toddler is directly linked with poorer communication and daily living skills at age 4, but outdoor play may lessen some of the effects, new research suggests.
The results point to outdoor play as a potential targeted intervention to counter suboptimal brain development in young children who are watching screens at increasingly younger ages.
The findings were published online in JAMA Pediatrics.
The researchers first investigated whether higher screen time (more than 1 hour a day on a device or watching television) at age 2 years is associated with neurodevelopmental outcomes at age 4.
They found the 885 children in the sample from the Japanese Hamamatsu Birth Cohort Study for Mothers and Children who had more screen time had lower scores on communication and daily living skills than children who watched less than an hour a day.
Scores were based on the Vineland Adaptive Behavior Scale according to parent responses to questions. The children included were born between December 2007 and March 2012 and were followed from 18 months to 4 years.
After finding the connection between screen time and lower scores, the researchers investigated whether outdoor play (at least 30 minutes a day) introduced at a 2 years and 8 months made a difference. They considered 6 or 7 days per week frequent outdoor play.
Outdoor play mitigated poorer daily living scores
The researchers found that the outdoor play intervention mitigated 18% of the association between high screen time and lower daily living scores but did not mitigate the lower communication scores.
They also found that more screen time at age 2 was significantly linked with infrequent outdoor play at age 32 months (odds ratio, 2.03; 95% confidence interval, 1.48-2.76).
The associations were consistent after taking into account factors including a child’s sex, parental education, and any autism spectrum disorder symptoms at age 18 months.
The authors noted that neurodevelopment concerns with screen use are particularly troubling as the age for use is getting younger.
A recent meta-analysis found that 75% of children younger than 2 use or watch screens, even though guidelines recommend against any screen time before 2.
In addition, the “COVID-19 pandemic led to children having more screen time, less outdoor play, and less physical activity, putting them at potentially greater risk for neurodevelopmental problems,” the authors noted.
“What is concerning is that data show screen time has not decreased after seclusion measures were lifted,” they added.
Proven benefits for outdoor play
Jennifer Cross, MD,* assistant professor and section chief for developmental pediatrics at Weill Cornell Medicine, New York, who was not part of the study, said the mitigation properties of outdoor play were something she hadn’t seen before but the concept makes sense.
“The overwhelming evidence is that screen time is not helpful for young children under the age of 2,” she said.
Outdoor play, on the other hand, has proven benefits.
“Physical activity has been shown to be good for physical and mental health so there’s no reason to believe it wouldn’t be good for 2-and-a-half-year olds,” Dr. Cross said. “It’s also good for developmental health. You want them to be engaged in imaginative play and be interactive.”
“[Outdoor play] gets them away from screens and gives them an opportunity to experience another environment and work on their motor skills and motor planning,” she added. “Exercise will change, briefly, the way our brains process information.”
Dr. Cross added that a lot of motor skills are involved in daily living skills, such as feeding, dressing, and toileting.
Screen time is increasing
The authors acknowledged that screen time may be underestimated by parents. They also noted that they did not have access to what children were watching on the screens.
“This should have been collected because the effect of high screen time differs depending on the type of program,” the authors wrote.
They added that children born in the 2020s may have been exposed to more screen time than the children reared in the early 2010s in this study.
Dr. Cross said screen use in the 2020s may be higher than estimated here and higher in certain populations globally, so it’s not easy to tell if the intervention in this study would have the same mitigating effect on a real-world population.
However, she said, the effect of outdoor play is always going to be helpful for brain development and there’s no downside.
“Exercise is just as important for little kids as it is for grown-ups,” she said.
The authors reported no relevant financial disclosures. Dr. Cross reported no relevant financial disclosures.
*Dr. Jennifer Cross is the correct name, not Dr. Jennifer Frost. The correction was made on Jan. 27, 2023.
Watching a screen more than an hour a day as a toddler is directly linked with poorer communication and daily living skills at age 4, but outdoor play may lessen some of the effects, new research suggests.
The results point to outdoor play as a potential targeted intervention to counter suboptimal brain development in young children who are watching screens at increasingly younger ages.
The findings were published online in JAMA Pediatrics.
The researchers first investigated whether higher screen time (more than 1 hour a day on a device or watching television) at age 2 years is associated with neurodevelopmental outcomes at age 4.
They found the 885 children in the sample from the Japanese Hamamatsu Birth Cohort Study for Mothers and Children who had more screen time had lower scores on communication and daily living skills than children who watched less than an hour a day.
Scores were based on the Vineland Adaptive Behavior Scale according to parent responses to questions. The children included were born between December 2007 and March 2012 and were followed from 18 months to 4 years.
After finding the connection between screen time and lower scores, the researchers investigated whether outdoor play (at least 30 minutes a day) introduced at a 2 years and 8 months made a difference. They considered 6 or 7 days per week frequent outdoor play.
Outdoor play mitigated poorer daily living scores
The researchers found that the outdoor play intervention mitigated 18% of the association between high screen time and lower daily living scores but did not mitigate the lower communication scores.
They also found that more screen time at age 2 was significantly linked with infrequent outdoor play at age 32 months (odds ratio, 2.03; 95% confidence interval, 1.48-2.76).
The associations were consistent after taking into account factors including a child’s sex, parental education, and any autism spectrum disorder symptoms at age 18 months.
The authors noted that neurodevelopment concerns with screen use are particularly troubling as the age for use is getting younger.
A recent meta-analysis found that 75% of children younger than 2 use or watch screens, even though guidelines recommend against any screen time before 2.
In addition, the “COVID-19 pandemic led to children having more screen time, less outdoor play, and less physical activity, putting them at potentially greater risk for neurodevelopmental problems,” the authors noted.
“What is concerning is that data show screen time has not decreased after seclusion measures were lifted,” they added.
Proven benefits for outdoor play
Jennifer Cross, MD,* assistant professor and section chief for developmental pediatrics at Weill Cornell Medicine, New York, who was not part of the study, said the mitigation properties of outdoor play were something she hadn’t seen before but the concept makes sense.
“The overwhelming evidence is that screen time is not helpful for young children under the age of 2,” she said.
Outdoor play, on the other hand, has proven benefits.
“Physical activity has been shown to be good for physical and mental health so there’s no reason to believe it wouldn’t be good for 2-and-a-half-year olds,” Dr. Cross said. “It’s also good for developmental health. You want them to be engaged in imaginative play and be interactive.”
“[Outdoor play] gets them away from screens and gives them an opportunity to experience another environment and work on their motor skills and motor planning,” she added. “Exercise will change, briefly, the way our brains process information.”
Dr. Cross added that a lot of motor skills are involved in daily living skills, such as feeding, dressing, and toileting.
Screen time is increasing
The authors acknowledged that screen time may be underestimated by parents. They also noted that they did not have access to what children were watching on the screens.
“This should have been collected because the effect of high screen time differs depending on the type of program,” the authors wrote.
They added that children born in the 2020s may have been exposed to more screen time than the children reared in the early 2010s in this study.
Dr. Cross said screen use in the 2020s may be higher than estimated here and higher in certain populations globally, so it’s not easy to tell if the intervention in this study would have the same mitigating effect on a real-world population.
However, she said, the effect of outdoor play is always going to be helpful for brain development and there’s no downside.
“Exercise is just as important for little kids as it is for grown-ups,” she said.
The authors reported no relevant financial disclosures. Dr. Cross reported no relevant financial disclosures.
*Dr. Jennifer Cross is the correct name, not Dr. Jennifer Frost. The correction was made on Jan. 27, 2023.
FROM JAMA PEDIATRICS
Ecopipam reduces Tourette’s tics without common side effects in phase 2 trial
Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.
Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.
Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.
First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.
The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.
They were randomly assigned 1:1 to ecopipam or placebo.
Significant reduction in tic severity
Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.
The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).
Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.
One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.
“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
Headaches, insomnia among side effects
Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.
The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).
A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.
Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.
Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.
Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.
“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.
The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.
Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.
Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.
Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.
First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.
The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.
They were randomly assigned 1:1 to ecopipam or placebo.
Significant reduction in tic severity
Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.
The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).
Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.
One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.
“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
Headaches, insomnia among side effects
Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.
The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).
A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.
Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.
Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.
Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.
“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.
The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.
Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.
Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.
Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.
First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.
The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.
They were randomly assigned 1:1 to ecopipam or placebo.
Significant reduction in tic severity
Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.
The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).
Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.
One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.
“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
Headaches, insomnia among side effects
Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.
The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).
A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.
Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.
Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.
Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.
“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.
The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.
FROM PEDIATRICS
What to know about newly approved Alzheimer’s drug
, offering hope where there has been little for patients and their families affected by the devastating disease.
More than 6 million people in the United States live with Alzheimer’s.
It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.
But many are wary. As explained in an editorial in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”
Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.
So what should patients and their families make of this news? Here we answer some of the top questions surrounding the drug.
What does the FDA action mean?
The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease.
The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.
With the FDA approval in hand, doctors can now prescribe the medication.
Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move, ramping up manufacturing – and eventually nationwide distribution and implementation – will take some time.
“Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”
The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.
Potential benefit?
Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.
Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase 3 study in our field of a disease-modifying drug where the clinical efficacy was very clear.”
Concerns about side effects
The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared with about 11% in the placebo group.
Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths.
Dr. Fillit notes that the first two people who died were on blood thinners when they received lecanemab.
“There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.
The third death is a little different, Dr. Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.
“We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.
Dr. Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”
The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
How much will it cost?
Eisai says that lecanemab will cost $26,500 a year.
In a draft report released in December, the Institute for Clinical and Economic Review said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.
An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.
Will Medicare cover it?
The Centers for Medicare & Medicaid Services, which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.
That means people would have to pay thousands out of pocket at first to get it.
The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial.
On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.
CMS says in a statement issued after the announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”
“If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.
Who benefits most from this drug?
Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.
Who makes lecanemab?
Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.
What’s the Alzheimer’s Association’s view?
The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results.
It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”
“We are energized at the progress we are seeing in the research pipeline. The science is telling us that although antiamyloid treatments are not a cure – they are not going to be the end of treating Alzheimer’s – they are certainly the beginning,” Dr. Edelmayer says.
Are there alternatives?
The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market.
Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.
A version of this article first appeared on WebMD.com.
, offering hope where there has been little for patients and their families affected by the devastating disease.
More than 6 million people in the United States live with Alzheimer’s.
It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.
But many are wary. As explained in an editorial in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”
Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.
So what should patients and their families make of this news? Here we answer some of the top questions surrounding the drug.
What does the FDA action mean?
The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease.
The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.
With the FDA approval in hand, doctors can now prescribe the medication.
Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move, ramping up manufacturing – and eventually nationwide distribution and implementation – will take some time.
“Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”
The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.
Potential benefit?
Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.
Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase 3 study in our field of a disease-modifying drug where the clinical efficacy was very clear.”
Concerns about side effects
The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared with about 11% in the placebo group.
Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths.
Dr. Fillit notes that the first two people who died were on blood thinners when they received lecanemab.
“There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.
The third death is a little different, Dr. Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.
“We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.
Dr. Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”
The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
How much will it cost?
Eisai says that lecanemab will cost $26,500 a year.
In a draft report released in December, the Institute for Clinical and Economic Review said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.
An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.
Will Medicare cover it?
The Centers for Medicare & Medicaid Services, which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.
That means people would have to pay thousands out of pocket at first to get it.
The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial.
On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.
CMS says in a statement issued after the announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”
“If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.
Who benefits most from this drug?
Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.
Who makes lecanemab?
Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.
What’s the Alzheimer’s Association’s view?
The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results.
It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”
“We are energized at the progress we are seeing in the research pipeline. The science is telling us that although antiamyloid treatments are not a cure – they are not going to be the end of treating Alzheimer’s – they are certainly the beginning,” Dr. Edelmayer says.
Are there alternatives?
The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market.
Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.
A version of this article first appeared on WebMD.com.
, offering hope where there has been little for patients and their families affected by the devastating disease.
More than 6 million people in the United States live with Alzheimer’s.
It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.
But many are wary. As explained in an editorial in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”
Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.
So what should patients and their families make of this news? Here we answer some of the top questions surrounding the drug.
What does the FDA action mean?
The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease.
The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.
With the FDA approval in hand, doctors can now prescribe the medication.
Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move, ramping up manufacturing – and eventually nationwide distribution and implementation – will take some time.
“Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”
The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.
Potential benefit?
Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.
Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase 3 study in our field of a disease-modifying drug where the clinical efficacy was very clear.”
Concerns about side effects
The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared with about 11% in the placebo group.
Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths.
Dr. Fillit notes that the first two people who died were on blood thinners when they received lecanemab.
“There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.
The third death is a little different, Dr. Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.
“We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.
Dr. Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”
The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
How much will it cost?
Eisai says that lecanemab will cost $26,500 a year.
In a draft report released in December, the Institute for Clinical and Economic Review said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.
An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.
Will Medicare cover it?
The Centers for Medicare & Medicaid Services, which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.
That means people would have to pay thousands out of pocket at first to get it.
The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial.
On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.
CMS says in a statement issued after the announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”
“If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.
Who benefits most from this drug?
Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.
Who makes lecanemab?
Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.
What’s the Alzheimer’s Association’s view?
The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results.
It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”
“We are energized at the progress we are seeing in the research pipeline. The science is telling us that although antiamyloid treatments are not a cure – they are not going to be the end of treating Alzheimer’s – they are certainly the beginning,” Dr. Edelmayer says.
Are there alternatives?
The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market.
Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.
A version of this article first appeared on WebMD.com.
Advanced Primary Care program boosts COVID-19 results
The better outcomes were seen in higher vaccination rates and fewer infections, hospitalizations, and deaths from the disease, according to study authors, led by Emily Gruber, MBA, MPH, with the Maryland Primary Care Program, Maryland Department of Health in Baltimore.
The results were published online in JAMA Network Open.
The study population was divided into MDPCP participants (n = 208,146) and a matched cohort (n = 37,203) of beneficiaries not attributed to MDPCP practices but who met eligibility criteria for study participation from Jan. 1, 2020, through Dec. 31, 2021.
More vaccinations, more antibody treatments
Researchers broke down the comparisons of better outcomes: 84.47% of MDPCP beneficiaries were fully vaccinated vs. 77.93% of nonparticipating beneficiaries (P less than .001). COVID-19–positive program beneficiaries also received monoclonal antibody treatment more often (8.45% vs. 6.11%; P less than .001).
Plus, program participants received more care via telehealth (62.95% vs. 54.53%; P less than .001) compared with those not participating.
Regarding secondary outcomes, MDPCP beneficiaries had lower rates of COVID cases (6.55% vs. 7.09%; P less than .001), lower rates of COVID-19 hospitalizations (1.81% vs. 2.06%; P = .001), and lower rates of death due to COVID-19 (0.56% vs. 0.77%; P less than .001).
Program components
Enrollment in the MDPCP is voluntary, and primary care practices can apply each year to be part of the program.
The model integrates primary care and public health in the pandemic response. It was created by the Maryland Department of Health (MDH) and the Centers for Medicare & Medicaid Services (CMS).
It expands the role of primary care to include services such as expanded care management, integrated behavioral health, data-driven care, and screenings and referrals to address social needs.
Coauthor Howard Haft, MD, MMM, with the Maryland Department of Public Health, said in an interview that among the most important factors in the program’s success were giving providers vaccines to distribute and then giving providers data on how many patients are vaccinated, and who’s not vaccinated but at high risk, and how those rates compare to other practices.
As to whether this could be a widespread model, Dr. Haft said, “It’s highly replicable.”
“Every state in the nation overall has all of these resources. It’s a matter of having the operational and political will to put those resources together. Almost every state has the technological ability to use their health information exchange to help tie pieces together.”
Vaccines and testing made available to providers
Making ample vaccines and testing available to providers in their offices helped patients get those services in a place they trust, Dr. Haft said.
The model also included a payment system for providers that included a significant amount of non–visit-based payments when many locations were closed in the height of the pandemic.
“That helped financially,” as did providing free telehealth platforms to practices with training on how to use them, Dr. Haft said.
‘Innovative and important’
Renu Tipirneni, MD, an assistant professor of internal medicine at the University of Michigan and at the Institute for Healthcare Policy and Innovation in Ann Arbor, said Maryland is out front putting into practice what practices nationwide aspire to do – coordinating physical and mental health and social needs and integrating primary and public health. Dr. Tipirneni, who was not involved with the study, said she was impressed the researchers were able to show statistically significant improvement with COVID-19 outcomes in the first 2 years.
“In terms of health outcomes, we often have to wait longer to see good outcomes,” she said. “It’s a really innovative and important model.”
She said states can learn from each other and this model is an example.
Integrating primary care and public health and addressing social needs may be the biggest challenges for states, she said, as those realms typically have been siloed.
“But they may be the key components to achieving these outcomes,” she said.
Take-home message
The most important benefit of the program is that data suggest it saves lives, according to Dr. Haft. While the actual difference between COVID deaths in the program and nonprogram groups was small, multiplying that savings across the nation shows substantial potential benefit, he explained.
“At a time when we were losing lives at an unconscionable rate, we were able to make a difference in saving lives,” Dr. Haft said.
Authors report no relevant financial disclosures.
The study received financial support from the Maryland Department of Health.
Dr. Tiperneni is helping evaluate Michigan’s Medicaid contract.
The better outcomes were seen in higher vaccination rates and fewer infections, hospitalizations, and deaths from the disease, according to study authors, led by Emily Gruber, MBA, MPH, with the Maryland Primary Care Program, Maryland Department of Health in Baltimore.
The results were published online in JAMA Network Open.
The study population was divided into MDPCP participants (n = 208,146) and a matched cohort (n = 37,203) of beneficiaries not attributed to MDPCP practices but who met eligibility criteria for study participation from Jan. 1, 2020, through Dec. 31, 2021.
More vaccinations, more antibody treatments
Researchers broke down the comparisons of better outcomes: 84.47% of MDPCP beneficiaries were fully vaccinated vs. 77.93% of nonparticipating beneficiaries (P less than .001). COVID-19–positive program beneficiaries also received monoclonal antibody treatment more often (8.45% vs. 6.11%; P less than .001).
Plus, program participants received more care via telehealth (62.95% vs. 54.53%; P less than .001) compared with those not participating.
Regarding secondary outcomes, MDPCP beneficiaries had lower rates of COVID cases (6.55% vs. 7.09%; P less than .001), lower rates of COVID-19 hospitalizations (1.81% vs. 2.06%; P = .001), and lower rates of death due to COVID-19 (0.56% vs. 0.77%; P less than .001).
Program components
Enrollment in the MDPCP is voluntary, and primary care practices can apply each year to be part of the program.
The model integrates primary care and public health in the pandemic response. It was created by the Maryland Department of Health (MDH) and the Centers for Medicare & Medicaid Services (CMS).
It expands the role of primary care to include services such as expanded care management, integrated behavioral health, data-driven care, and screenings and referrals to address social needs.
Coauthor Howard Haft, MD, MMM, with the Maryland Department of Public Health, said in an interview that among the most important factors in the program’s success were giving providers vaccines to distribute and then giving providers data on how many patients are vaccinated, and who’s not vaccinated but at high risk, and how those rates compare to other practices.
As to whether this could be a widespread model, Dr. Haft said, “It’s highly replicable.”
“Every state in the nation overall has all of these resources. It’s a matter of having the operational and political will to put those resources together. Almost every state has the technological ability to use their health information exchange to help tie pieces together.”
Vaccines and testing made available to providers
Making ample vaccines and testing available to providers in their offices helped patients get those services in a place they trust, Dr. Haft said.
The model also included a payment system for providers that included a significant amount of non–visit-based payments when many locations were closed in the height of the pandemic.
“That helped financially,” as did providing free telehealth platforms to practices with training on how to use them, Dr. Haft said.
‘Innovative and important’
Renu Tipirneni, MD, an assistant professor of internal medicine at the University of Michigan and at the Institute for Healthcare Policy and Innovation in Ann Arbor, said Maryland is out front putting into practice what practices nationwide aspire to do – coordinating physical and mental health and social needs and integrating primary and public health. Dr. Tipirneni, who was not involved with the study, said she was impressed the researchers were able to show statistically significant improvement with COVID-19 outcomes in the first 2 years.
“In terms of health outcomes, we often have to wait longer to see good outcomes,” she said. “It’s a really innovative and important model.”
She said states can learn from each other and this model is an example.
Integrating primary care and public health and addressing social needs may be the biggest challenges for states, she said, as those realms typically have been siloed.
“But they may be the key components to achieving these outcomes,” she said.
Take-home message
The most important benefit of the program is that data suggest it saves lives, according to Dr. Haft. While the actual difference between COVID deaths in the program and nonprogram groups was small, multiplying that savings across the nation shows substantial potential benefit, he explained.
“At a time when we were losing lives at an unconscionable rate, we were able to make a difference in saving lives,” Dr. Haft said.
Authors report no relevant financial disclosures.
The study received financial support from the Maryland Department of Health.
Dr. Tiperneni is helping evaluate Michigan’s Medicaid contract.
The better outcomes were seen in higher vaccination rates and fewer infections, hospitalizations, and deaths from the disease, according to study authors, led by Emily Gruber, MBA, MPH, with the Maryland Primary Care Program, Maryland Department of Health in Baltimore.
The results were published online in JAMA Network Open.
The study population was divided into MDPCP participants (n = 208,146) and a matched cohort (n = 37,203) of beneficiaries not attributed to MDPCP practices but who met eligibility criteria for study participation from Jan. 1, 2020, through Dec. 31, 2021.
More vaccinations, more antibody treatments
Researchers broke down the comparisons of better outcomes: 84.47% of MDPCP beneficiaries were fully vaccinated vs. 77.93% of nonparticipating beneficiaries (P less than .001). COVID-19–positive program beneficiaries also received monoclonal antibody treatment more often (8.45% vs. 6.11%; P less than .001).
Plus, program participants received more care via telehealth (62.95% vs. 54.53%; P less than .001) compared with those not participating.
Regarding secondary outcomes, MDPCP beneficiaries had lower rates of COVID cases (6.55% vs. 7.09%; P less than .001), lower rates of COVID-19 hospitalizations (1.81% vs. 2.06%; P = .001), and lower rates of death due to COVID-19 (0.56% vs. 0.77%; P less than .001).
Program components
Enrollment in the MDPCP is voluntary, and primary care practices can apply each year to be part of the program.
The model integrates primary care and public health in the pandemic response. It was created by the Maryland Department of Health (MDH) and the Centers for Medicare & Medicaid Services (CMS).
It expands the role of primary care to include services such as expanded care management, integrated behavioral health, data-driven care, and screenings and referrals to address social needs.
Coauthor Howard Haft, MD, MMM, with the Maryland Department of Public Health, said in an interview that among the most important factors in the program’s success were giving providers vaccines to distribute and then giving providers data on how many patients are vaccinated, and who’s not vaccinated but at high risk, and how those rates compare to other practices.
As to whether this could be a widespread model, Dr. Haft said, “It’s highly replicable.”
“Every state in the nation overall has all of these resources. It’s a matter of having the operational and political will to put those resources together. Almost every state has the technological ability to use their health information exchange to help tie pieces together.”
Vaccines and testing made available to providers
Making ample vaccines and testing available to providers in their offices helped patients get those services in a place they trust, Dr. Haft said.
The model also included a payment system for providers that included a significant amount of non–visit-based payments when many locations were closed in the height of the pandemic.
“That helped financially,” as did providing free telehealth platforms to practices with training on how to use them, Dr. Haft said.
‘Innovative and important’
Renu Tipirneni, MD, an assistant professor of internal medicine at the University of Michigan and at the Institute for Healthcare Policy and Innovation in Ann Arbor, said Maryland is out front putting into practice what practices nationwide aspire to do – coordinating physical and mental health and social needs and integrating primary and public health. Dr. Tipirneni, who was not involved with the study, said she was impressed the researchers were able to show statistically significant improvement with COVID-19 outcomes in the first 2 years.
“In terms of health outcomes, we often have to wait longer to see good outcomes,” she said. “It’s a really innovative and important model.”
She said states can learn from each other and this model is an example.
Integrating primary care and public health and addressing social needs may be the biggest challenges for states, she said, as those realms typically have been siloed.
“But they may be the key components to achieving these outcomes,” she said.
Take-home message
The most important benefit of the program is that data suggest it saves lives, according to Dr. Haft. While the actual difference between COVID deaths in the program and nonprogram groups was small, multiplying that savings across the nation shows substantial potential benefit, he explained.
“At a time when we were losing lives at an unconscionable rate, we were able to make a difference in saving lives,” Dr. Haft said.
Authors report no relevant financial disclosures.
The study received financial support from the Maryland Department of Health.
Dr. Tiperneni is helping evaluate Michigan’s Medicaid contract.
FROM JAMA NETWORK OPEN
Compulsively checking social media linked with altered brain patterns in teens
Teens who compulsively checked social media networks showed different development patterns in parts of the brain that involve reward and punishment than did those who didn’t check their platforms as often, new research suggests.
Results were published online in JAMA Pediatrics.
Researchers, led by Maria T. Maza, of the department of psychology and neuroscience at University of North Carolina at Chapel Hill, included 169 6th- and 7th-grade students recruited from three public middle schools in rural North Carolina in a 3-year longitudinal cohort.
Participants reported how frequently they checked Facebook, Instagram, and Snapchat. Answers were grouped into eight score groups depending on their per-day check times: less than 1; 1; 2-3; 4-5; 6-10; 11-15; 16-20; or more than 20 times. Those groups were then broken into three categories: low (nonhabitual); moderate; and high (habitual).
Imaging shows reactions
Researchers used functional magnetic resonance imaging (fMRI) to see how different areas of the brain react when participants looked at a series of indicators, such as happy and angry faces, which mimic social media rewards, punishments, or neutral feedback.
The research team focused on adolescents, for whom social media participation and neural sensitivity to social feedback from peers are high.
They found that participants who frequently checked social media showed distinct brain patterns when anticipating social feedback compared with those who had moderate or low use, “suggesting that habitual social media checking early in adolescence is associated with divergent brain development over time.”
The affected regions of the brain included the networks that respond to motivation and cognitive control.
However, the study was not able to determine whether the differences are a good or bad thing.
“While for some individuals with habitual checking behaviors, an initial hyposensitivity to potential social rewards and punishments followed by hypersensitivity may contribute to checking behaviors on social media becoming compulsive and problematic, for others, this change in sensitivity may reflect an adaptive behavior that allows them to better navigate their increasingly digital environment,” the authors wrote.
Chicken-and-egg questions
David Rettew, MD, a child and adolescent psychiatrist at the Oregon Health & Science University in Portland, who was not part of this research, said in an interview that it’s not clear from this study which came first – different brain development in the teens prior to this study that caused compulsive checking, or checking behaviors that caused different brain development. The authors acknowledge this is a limitation of the study.
“Hopefully, someday researchers will look at some of these brain activation patterns before kids have been exposed to social media to help us sort some of these questions out,” Dr. Rettew said.
“It wasn’t as though the groups looked the same at baseline and then diverged as they used more and more social media,” Dr. Rettew said. “It looked like there were some baseline differences that could be traced back maybe years before the study even started.”
People hear “divergent brain development” associated with social media and naturally get alarmed, he acknowledged.
“I get that, but the study isn’t really equipped to tell us what should be happening in the brain and what changes may have implications for other parts of an adolescent’s life,” Dr. Rettew said, “In the end, what we have is an association between heavy social media use and certain brain activation patterns which is cool to see and measure.”
He agrees with the authors, however, that overuse of social media is concerning and studying its effects is important.
Seventy-eight percent of early adolescents check every hour
According to the paper, 78% of 13- to 17-year-olds report checking their devices at least every hour and 46% check “almost constantly.”
“Regardless of which brain regions light up when looking at various emoji responses to their Instagram post, I think it is valid already to have some concerns about youth who can’t stay off their phone for more than 10 minutes,” Dr. Rettew said. “Technology is here to stay, but how we can learn to use it rather than have it use us is probably the more pressing question at this point.”
One coauthor reports grants from the National Institute on Drug Abuse (NIDA) during the conduct of the study and grants from NIDA and the National Science Foundation outside the submitted work; a coauthor reports grants from the Winston Family Foundation; and a coauthor reports a grant from NIDA and funds from the Winston Family Foundation – both during the conduct of the study. No other disclosures were reported. Dr. Rettew is author of the book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.”
Teens who compulsively checked social media networks showed different development patterns in parts of the brain that involve reward and punishment than did those who didn’t check their platforms as often, new research suggests.
Results were published online in JAMA Pediatrics.
Researchers, led by Maria T. Maza, of the department of psychology and neuroscience at University of North Carolina at Chapel Hill, included 169 6th- and 7th-grade students recruited from three public middle schools in rural North Carolina in a 3-year longitudinal cohort.
Participants reported how frequently they checked Facebook, Instagram, and Snapchat. Answers were grouped into eight score groups depending on their per-day check times: less than 1; 1; 2-3; 4-5; 6-10; 11-15; 16-20; or more than 20 times. Those groups were then broken into three categories: low (nonhabitual); moderate; and high (habitual).
Imaging shows reactions
Researchers used functional magnetic resonance imaging (fMRI) to see how different areas of the brain react when participants looked at a series of indicators, such as happy and angry faces, which mimic social media rewards, punishments, or neutral feedback.
The research team focused on adolescents, for whom social media participation and neural sensitivity to social feedback from peers are high.
They found that participants who frequently checked social media showed distinct brain patterns when anticipating social feedback compared with those who had moderate or low use, “suggesting that habitual social media checking early in adolescence is associated with divergent brain development over time.”
The affected regions of the brain included the networks that respond to motivation and cognitive control.
However, the study was not able to determine whether the differences are a good or bad thing.
“While for some individuals with habitual checking behaviors, an initial hyposensitivity to potential social rewards and punishments followed by hypersensitivity may contribute to checking behaviors on social media becoming compulsive and problematic, for others, this change in sensitivity may reflect an adaptive behavior that allows them to better navigate their increasingly digital environment,” the authors wrote.
Chicken-and-egg questions
David Rettew, MD, a child and adolescent psychiatrist at the Oregon Health & Science University in Portland, who was not part of this research, said in an interview that it’s not clear from this study which came first – different brain development in the teens prior to this study that caused compulsive checking, or checking behaviors that caused different brain development. The authors acknowledge this is a limitation of the study.
“Hopefully, someday researchers will look at some of these brain activation patterns before kids have been exposed to social media to help us sort some of these questions out,” Dr. Rettew said.
“It wasn’t as though the groups looked the same at baseline and then diverged as they used more and more social media,” Dr. Rettew said. “It looked like there were some baseline differences that could be traced back maybe years before the study even started.”
People hear “divergent brain development” associated with social media and naturally get alarmed, he acknowledged.
“I get that, but the study isn’t really equipped to tell us what should be happening in the brain and what changes may have implications for other parts of an adolescent’s life,” Dr. Rettew said, “In the end, what we have is an association between heavy social media use and certain brain activation patterns which is cool to see and measure.”
He agrees with the authors, however, that overuse of social media is concerning and studying its effects is important.
Seventy-eight percent of early adolescents check every hour
According to the paper, 78% of 13- to 17-year-olds report checking their devices at least every hour and 46% check “almost constantly.”
“Regardless of which brain regions light up when looking at various emoji responses to their Instagram post, I think it is valid already to have some concerns about youth who can’t stay off their phone for more than 10 minutes,” Dr. Rettew said. “Technology is here to stay, but how we can learn to use it rather than have it use us is probably the more pressing question at this point.”
One coauthor reports grants from the National Institute on Drug Abuse (NIDA) during the conduct of the study and grants from NIDA and the National Science Foundation outside the submitted work; a coauthor reports grants from the Winston Family Foundation; and a coauthor reports a grant from NIDA and funds from the Winston Family Foundation – both during the conduct of the study. No other disclosures were reported. Dr. Rettew is author of the book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.”
Teens who compulsively checked social media networks showed different development patterns in parts of the brain that involve reward and punishment than did those who didn’t check their platforms as often, new research suggests.
Results were published online in JAMA Pediatrics.
Researchers, led by Maria T. Maza, of the department of psychology and neuroscience at University of North Carolina at Chapel Hill, included 169 6th- and 7th-grade students recruited from three public middle schools in rural North Carolina in a 3-year longitudinal cohort.
Participants reported how frequently they checked Facebook, Instagram, and Snapchat. Answers were grouped into eight score groups depending on their per-day check times: less than 1; 1; 2-3; 4-5; 6-10; 11-15; 16-20; or more than 20 times. Those groups were then broken into three categories: low (nonhabitual); moderate; and high (habitual).
Imaging shows reactions
Researchers used functional magnetic resonance imaging (fMRI) to see how different areas of the brain react when participants looked at a series of indicators, such as happy and angry faces, which mimic social media rewards, punishments, or neutral feedback.
The research team focused on adolescents, for whom social media participation and neural sensitivity to social feedback from peers are high.
They found that participants who frequently checked social media showed distinct brain patterns when anticipating social feedback compared with those who had moderate or low use, “suggesting that habitual social media checking early in adolescence is associated with divergent brain development over time.”
The affected regions of the brain included the networks that respond to motivation and cognitive control.
However, the study was not able to determine whether the differences are a good or bad thing.
“While for some individuals with habitual checking behaviors, an initial hyposensitivity to potential social rewards and punishments followed by hypersensitivity may contribute to checking behaviors on social media becoming compulsive and problematic, for others, this change in sensitivity may reflect an adaptive behavior that allows them to better navigate their increasingly digital environment,” the authors wrote.
Chicken-and-egg questions
David Rettew, MD, a child and adolescent psychiatrist at the Oregon Health & Science University in Portland, who was not part of this research, said in an interview that it’s not clear from this study which came first – different brain development in the teens prior to this study that caused compulsive checking, or checking behaviors that caused different brain development. The authors acknowledge this is a limitation of the study.
“Hopefully, someday researchers will look at some of these brain activation patterns before kids have been exposed to social media to help us sort some of these questions out,” Dr. Rettew said.
“It wasn’t as though the groups looked the same at baseline and then diverged as they used more and more social media,” Dr. Rettew said. “It looked like there were some baseline differences that could be traced back maybe years before the study even started.”
People hear “divergent brain development” associated with social media and naturally get alarmed, he acknowledged.
“I get that, but the study isn’t really equipped to tell us what should be happening in the brain and what changes may have implications for other parts of an adolescent’s life,” Dr. Rettew said, “In the end, what we have is an association between heavy social media use and certain brain activation patterns which is cool to see and measure.”
He agrees with the authors, however, that overuse of social media is concerning and studying its effects is important.
Seventy-eight percent of early adolescents check every hour
According to the paper, 78% of 13- to 17-year-olds report checking their devices at least every hour and 46% check “almost constantly.”
“Regardless of which brain regions light up when looking at various emoji responses to their Instagram post, I think it is valid already to have some concerns about youth who can’t stay off their phone for more than 10 minutes,” Dr. Rettew said. “Technology is here to stay, but how we can learn to use it rather than have it use us is probably the more pressing question at this point.”
One coauthor reports grants from the National Institute on Drug Abuse (NIDA) during the conduct of the study and grants from NIDA and the National Science Foundation outside the submitted work; a coauthor reports grants from the Winston Family Foundation; and a coauthor reports a grant from NIDA and funds from the Winston Family Foundation – both during the conduct of the study. No other disclosures were reported. Dr. Rettew is author of the book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.”
FROM JAMA PEDIATRICS