Autism can be detected in children almost from birth using an algorithm to review their health records, a study from Duke University, Durham, N.C., says.

“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.

Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.

“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”

USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.

The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.

“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”

Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.

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

Autism can be detected in children almost from birth using an algorithm to review their health records, a study from Duke University, Durham, N.C., says.

“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.

Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.

“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”

USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.

The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.

“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”

Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.

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

Autism can be detected in children almost from birth using an algorithm to review their health records, a study from Duke University, Durham, N.C., says.

“We can use the first 30 days of a child’s health care experience to say, ‘This child is really at risk,’ ” said David Mandell, DSc, a professor of psychiatry at the University of Pennsylvania, Philadelphia, in USA Today. He was not involved in the research.

Researchers analyzed electronic medical records of 45,000 children treated in the Duke University Health System as infants between 2006 and 2020. They created an algorithm that could predict which babies later developed autism. These babies were more likely to have been to an ophthalmologist or neurologist; had stomach or gastrointestinal issues; or received physical therapy.

“A huge number of factors across the infant’s entire health profile” went into the models, said study coauthor Matthew Engelhard, MD, an assistant professor of biostatistics and bioinformatics at Duke University. “Each one of those factors contributes incrementally.”

USA Today said the team “paid particular attention to how the model performed in groups of children who are often overlooked by traditional screening methods and, therefore, miss the advantages of early diagnosis, including girls, children of color, and children with combined diagnoses of autism and ADHD,” according to Dr. Engelhard.

The study could lead to the algorithm being used with other tools to diagnose and help children earlier, said study author Geraldine Dawson, PhD, who directs the Duke Center for Autism and Brain Development.

“We need to be thinking about autism as not only a behavioral health condition but also a condition that involves physical health,” she said. “This is one way to take advantage of that information: in doing a better job at early detection.”

Autism is a complicated condition that includes communication and behavior challenges involving a range of symptoms and skills. It can be minor or a disability that requires full-time care.

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

Among pediatric patients with psoriasis who began treatment with ustekinumab, etanercept, or methotrexate, the rate of serious infections at 6 months was low, with an incidence ranging between 14.9 and 25.6 per 1,000 person-years.

Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.

“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”

Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.

Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.

Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”

She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”

Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.

Among pediatric patients with psoriasis who began treatment with ustekinumab, etanercept, or methotrexate, the rate of serious infections at 6 months was low, with an incidence ranging between 14.9 and 25.6 per 1,000 person-years.

Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.

“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”

Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.

Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.

Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”

She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”

Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.

Among pediatric patients with psoriasis who began treatment with ustekinumab, etanercept, or methotrexate, the rate of serious infections at 6 months was low, with an incidence ranging between 14.9 and 25.6 per 1,000 person-years.

Those are key findings from what is believed to be the largest cohort study of its kind to estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.

“Clinical trials have demonstrated high efficacy of new immunomodulatory agents in treating children with psoriasis,” lead author Maria C. Schneeweiss, MD, of the division of pharmacoepidemiology in the departments of medicine and dermatology at Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote in the article, which was published online in JAMA Dermatology. “However, the risk of infections in clinical practice has not been fully characterized by comparing these medications against each other in pairwise comparisons.”

Drawing from two large U.S. insurance claims databases, the researchers identified 2,338 patients aged 17 years and younger who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. They stratified their analysis by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021), and their follow-up of patients started 1 day after initiating treatment and ended at 6 months.

Of the 2,338 patients, 1,368 (58%) were girls. From 2009 through 2021, 379 patients began treatment with ustekinumab, 779 patients began treatment with etanercept, and 1,180 patients began treatment with methotrexate. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1,000 person-years (3 events) for those who used ustekinumab, 25.6 per 1,000 person-years (9 events) for those who used etanercept, and 14.9 per 1,000 person-years (8 events) for those who used methotrexate. The adjusted rate of outpatient infections was 254.9 per 1,000 person-years (39 events) for those who used ustekinumab, 435.7 per 1,000 person-years (139 events) for those who used etanercept, and 433.6 per 1,000 person-years (209 events) for those who used methotrexate. Meanwhile, the adjusted rate ratio of outpatient infections was 0.58 for ustekinumab vs. etanercept, 0.66 for ustekinumab vs. methotrexate, and 0.95 for etanercept vs. methotrexate. The researchers found that ratios were similar during the off-label use era and after pediatric labeling.

Anna L. Grossberg, MD, director of pediatric dermatology at the Johns Hopkins Children’s Center, Baltimore, who was asked to comment on the work, told this news organization that the data on outpatient infections in ustekinumab users “demonstrated that they may have a decreased risk of infection compared to pediatric psoriasis patients treated with methotrexate or the TNF-alpha inhibitor etanercept. This is previously unreported and reflects my personal experience with this medication in my own pediatric psoriasis patients.” She added the study’s overall findings lend further support to the safety of biologic medications and nonbiologic systemic immunomodulatory treatments for management of psoriasis. “This study will help guide pediatric dermatologists in counseling patients and their families about these risks [of infection], and in general providing reassurance that these risks appear to be quite low,” Dr. Grossberg said. “In particular, ustekinumab, a newer biologic medication that was recently FDA-approved for children 6 years and older for pediatric psoriasis, was not associated with higher infection rates than the other agents analyzed in this study, and in fact appears to carry a reduced risk compared to both etanercept and methotrexate.”

She noted certain limitations of the study, including its reliance on insurance claims data, “which can be limiting because information on possible confounding variables may not be known,” she said. “For example, the authors point out that environmental and behavioral risk factors for serious infection could not be evaluated or adjusted for, nor could the severity of the patients’ psoriasis. Additionally, this study only reported on outpatient infections that resulted in an antibiotic or other medications being prescribed and filled. It therefore may have missed children who presented with certain viral infections (examples could include the common cold and uncomplicated ear infections), which often will not require a prescription medication. Furthermore, it would fail to capture those who may have been seen for an infection but failed to fill the intended prescription.”

Dr. Schneeweiss reported receiving grants from AbbVie and UCB to Brigham and Women’s Hospital unrelated to the topic of this study and outside the submitted work. The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Grossberg reported having no financial disclosures.

Bright light therapy significantly improved depressive symptoms in approximately half of adults with bipolar depression in a pilot study of 41 individuals.

Both depression and bipolar disorder are leading causes of disability worldwide, and data show that only 50%-60% of these patients respond to first-line antidepressants, wrote Alessandro Cuomo, MD, of the University of Siena Medical Center, Italy, and colleagues.

Bright light therapy (BLT) was originally introduced as a treatment for seasonal affective disorder, but its use has been expanded to treat nonseasonal depression and bipolar disorder, they said. However, the impact of BLT on depressive symptoms in bipolar depression in particular has not been examined, they noted.

In a study published in the Journal of Affective Disorders, the researchers identified 18 men and 23 women aged 18 years and older with bipolar depression based on DSM-5 criteria who had already been treated with antidepressants. The participants were randomized to antidepressants combined with BLT or antidepressants combined with red light exposure (controls). The participants were positioned at 30-80 cm from the 10,000-lux light source for 30 minutes daily. The mean age of the participants was 49.1 years.

The primary outcome was scores on the Montgomery-Åsberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and CGI-Severity of illness (CGI-S), Fatigue Severity Scale (FSS), and Quality of Life Scale (QOLS) after the 8 weeks of treatment.

After 4 weeks, MADRS scores and HAMD-17 scores were significantly lower in the treatment group, compared with the controls (20 and 18 vs. 27.5 and 24.9, respectively; P < .001). Quality of life scores increased in the treatment group, compared with controls, with median scores of 39 vs. 29.50, respectively.

After 8 weeks, the treatment group continued to show significant improvement, compared with the control group, with scores on the MADRS, HAMD-17, CGI-S, and QOLS of 14.0, 9.0, 1.0, and 62.0 vs. 16.0, 15.5, 2.0, and 40.0, respectively. No side effects were reported.

“From our findings, BLT [proved] particularly effective in bipolar patients without triggering any manic switch, as evidenced instead in some similar studies,” the researchers wrote in their discussion.

Although the mechanism of action for BLT remains unclear, the current study findings confirm the existing knowledge of BLT, they noted. The positive effect of BLT on quality of life “might be attributable to the ability of BLT to reduce the latency times of antidepressants and increase the production of serotonin and melatonin,” as shown in previous work, they said.

The study findings were limited by several factors including the small sample size, which prevents definitive conclusions about the effectiveness of BLT in combination with different antidepressants, and the heterogeneity of the antidepressant treatments, the researchers noted. Larger, prospective studies and randomized, controlled trials are needed, as are studies of special populations such as older adults or those with degenerative diseases, they said.

However, the results suggest BLT has value as a safe and effective treatment and a way to boost therapeutic response and reduce the impact of long-lasting therapies, they concluded.

The study received no outside funding. Dr. Cuomo disclosed serving as a consultant and/or a speaker for Angelini, Glaxo Smith Kline, Lundbeck, Janssen, Otsuka, Pfizer, and Recordati.

Bright light therapy significantly improved depressive symptoms in approximately half of adults with bipolar depression in a pilot study of 41 individuals.

Both depression and bipolar disorder are leading causes of disability worldwide, and data show that only 50%-60% of these patients respond to first-line antidepressants, wrote Alessandro Cuomo, MD, of the University of Siena Medical Center, Italy, and colleagues.

Bright light therapy (BLT) was originally introduced as a treatment for seasonal affective disorder, but its use has been expanded to treat nonseasonal depression and bipolar disorder, they said. However, the impact of BLT on depressive symptoms in bipolar depression in particular has not been examined, they noted.

In a study published in the Journal of Affective Disorders, the researchers identified 18 men and 23 women aged 18 years and older with bipolar depression based on DSM-5 criteria who had already been treated with antidepressants. The participants were randomized to antidepressants combined with BLT or antidepressants combined with red light exposure (controls). The participants were positioned at 30-80 cm from the 10,000-lux light source for 30 minutes daily. The mean age of the participants was 49.1 years.

The primary outcome was scores on the Montgomery-Åsberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and CGI-Severity of illness (CGI-S), Fatigue Severity Scale (FSS), and Quality of Life Scale (QOLS) after the 8 weeks of treatment.

After 4 weeks, MADRS scores and HAMD-17 scores were significantly lower in the treatment group, compared with the controls (20 and 18 vs. 27.5 and 24.9, respectively; P < .001). Quality of life scores increased in the treatment group, compared with controls, with median scores of 39 vs. 29.50, respectively.

After 8 weeks, the treatment group continued to show significant improvement, compared with the control group, with scores on the MADRS, HAMD-17, CGI-S, and QOLS of 14.0, 9.0, 1.0, and 62.0 vs. 16.0, 15.5, 2.0, and 40.0, respectively. No side effects were reported.

“From our findings, BLT [proved] particularly effective in bipolar patients without triggering any manic switch, as evidenced instead in some similar studies,” the researchers wrote in their discussion.

Although the mechanism of action for BLT remains unclear, the current study findings confirm the existing knowledge of BLT, they noted. The positive effect of BLT on quality of life “might be attributable to the ability of BLT to reduce the latency times of antidepressants and increase the production of serotonin and melatonin,” as shown in previous work, they said.

The study findings were limited by several factors including the small sample size, which prevents definitive conclusions about the effectiveness of BLT in combination with different antidepressants, and the heterogeneity of the antidepressant treatments, the researchers noted. Larger, prospective studies and randomized, controlled trials are needed, as are studies of special populations such as older adults or those with degenerative diseases, they said.

However, the results suggest BLT has value as a safe and effective treatment and a way to boost therapeutic response and reduce the impact of long-lasting therapies, they concluded.

The study received no outside funding. Dr. Cuomo disclosed serving as a consultant and/or a speaker for Angelini, Glaxo Smith Kline, Lundbeck, Janssen, Otsuka, Pfizer, and Recordati.

Bright light therapy significantly improved depressive symptoms in approximately half of adults with bipolar depression in a pilot study of 41 individuals.

Both depression and bipolar disorder are leading causes of disability worldwide, and data show that only 50%-60% of these patients respond to first-line antidepressants, wrote Alessandro Cuomo, MD, of the University of Siena Medical Center, Italy, and colleagues.

Bright light therapy (BLT) was originally introduced as a treatment for seasonal affective disorder, but its use has been expanded to treat nonseasonal depression and bipolar disorder, they said. However, the impact of BLT on depressive symptoms in bipolar depression in particular has not been examined, they noted.

In a study published in the Journal of Affective Disorders, the researchers identified 18 men and 23 women aged 18 years and older with bipolar depression based on DSM-5 criteria who had already been treated with antidepressants. The participants were randomized to antidepressants combined with BLT or antidepressants combined with red light exposure (controls). The participants were positioned at 30-80 cm from the 10,000-lux light source for 30 minutes daily. The mean age of the participants was 49.1 years.

The primary outcome was scores on the Montgomery-Åsberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and CGI-Severity of illness (CGI-S), Fatigue Severity Scale (FSS), and Quality of Life Scale (QOLS) after the 8 weeks of treatment.

After 4 weeks, MADRS scores and HAMD-17 scores were significantly lower in the treatment group, compared with the controls (20 and 18 vs. 27.5 and 24.9, respectively; P < .001). Quality of life scores increased in the treatment group, compared with controls, with median scores of 39 vs. 29.50, respectively.

After 8 weeks, the treatment group continued to show significant improvement, compared with the control group, with scores on the MADRS, HAMD-17, CGI-S, and QOLS of 14.0, 9.0, 1.0, and 62.0 vs. 16.0, 15.5, 2.0, and 40.0, respectively. No side effects were reported.

“From our findings, BLT [proved] particularly effective in bipolar patients without triggering any manic switch, as evidenced instead in some similar studies,” the researchers wrote in their discussion.

Although the mechanism of action for BLT remains unclear, the current study findings confirm the existing knowledge of BLT, they noted. The positive effect of BLT on quality of life “might be attributable to the ability of BLT to reduce the latency times of antidepressants and increase the production of serotonin and melatonin,” as shown in previous work, they said.

The study findings were limited by several factors including the small sample size, which prevents definitive conclusions about the effectiveness of BLT in combination with different antidepressants, and the heterogeneity of the antidepressant treatments, the researchers noted. Larger, prospective studies and randomized, controlled trials are needed, as are studies of special populations such as older adults or those with degenerative diseases, they said.

However, the results suggest BLT has value as a safe and effective treatment and a way to boost therapeutic response and reduce the impact of long-lasting therapies, they concluded.

The study received no outside funding. Dr. Cuomo disclosed serving as a consultant and/or a speaker for Angelini, Glaxo Smith Kline, Lundbeck, Janssen, Otsuka, Pfizer, and Recordati.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• Following lumpectomy for early breast cancer, a 1-week schedule of partial breast radiation – 30 Gy delivered in 5 daily fractions – is safe, effective, and convenient for both patients and hospitals.

Why this matters

• According to numerous guidelines, partial breast irradiation after lumpectomy is a sound approach for early-stage breast cancer, but there is a lack of consensus about treatment schedules.
• The investigators suggest that 30 Gy in five daily fractions is a “valid option” for these patients in a field that lacks consensus.

Study design

• The team reviewed 381 women with early breast cancer treated with this approach (30 Gy in five daily fractions) at their center from 2013 to 2022.
• Half of patients had left-sided tumors, 94.5% had invasive ductal carcinomas, 96.6% had grade 1 or grade 2 disease, and tumors were luminal like in 99.2% of patients.
• Following lumpectomy, women underwent partial breast irradiation to the tumor bed plus 15 mm of isometric expansion beyond it.
• Follow-up was a median of 28 months.

Key results

• Seven patients (2%) had a local recurrence, of which two were in the treatment field.
• Three-year local control, disease-free survival, and overall survival were high (97.5%, 95.7%, and 96.9%, respectively).
• Nearly 90% of patients and 97% of physicians reported good or excellent cosmesis.
• Ten patients (2.9%) had grade 2 late toxicities, including edema, asthenia, and fibrosis; there were no grade 3 or higher adverse events.
• Five patients (1.5%) had late cardiac major events, four of whom were treated on the right breast; three patients (0.9%) had late pulmonary fibrosis.
• The safety and efficacy outcomes are in line with previous reports, including those that used different dosage and/or fractionation schedules.

Limitations

• The study was retrospective, with a relatively short follow-up.
• Quality of life was not assessed.
• There was no objective baseline measure of cosmesis against which to compare cosmetic results.

Disclosures

• There was no funding for the study, and the investigators didn’t have any conflicts of interest to report.

This is a summary of a preprint research study, “One-Week External Beam Partial Breast Irradiation: Survival and Toxicity Outcomes,” led by Riccardo Ray Colciago from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. The study has not been peer reviewed. The full text can be found at researchsquare.com.
 

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

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• Following lumpectomy for early breast cancer, a 1-week schedule of partial breast radiation – 30 Gy delivered in 5 daily fractions – is safe, effective, and convenient for both patients and hospitals.

Why this matters

• According to numerous guidelines, partial breast irradiation after lumpectomy is a sound approach for early-stage breast cancer, but there is a lack of consensus about treatment schedules.
• The investigators suggest that 30 Gy in five daily fractions is a “valid option” for these patients in a field that lacks consensus.

Study design

• The team reviewed 381 women with early breast cancer treated with this approach (30 Gy in five daily fractions) at their center from 2013 to 2022.
• Half of patients had left-sided tumors, 94.5% had invasive ductal carcinomas, 96.6% had grade 1 or grade 2 disease, and tumors were luminal like in 99.2% of patients.
• Following lumpectomy, women underwent partial breast irradiation to the tumor bed plus 15 mm of isometric expansion beyond it.
• Follow-up was a median of 28 months.

Key results

• Seven patients (2%) had a local recurrence, of which two were in the treatment field.
• Three-year local control, disease-free survival, and overall survival were high (97.5%, 95.7%, and 96.9%, respectively).
• Nearly 90% of patients and 97% of physicians reported good or excellent cosmesis.
• Ten patients (2.9%) had grade 2 late toxicities, including edema, asthenia, and fibrosis; there were no grade 3 or higher adverse events.
• Five patients (1.5%) had late cardiac major events, four of whom were treated on the right breast; three patients (0.9%) had late pulmonary fibrosis.
• The safety and efficacy outcomes are in line with previous reports, including those that used different dosage and/or fractionation schedules.

Limitations

• The study was retrospective, with a relatively short follow-up.
• Quality of life was not assessed.
• There was no objective baseline measure of cosmesis against which to compare cosmetic results.

Disclosures

• There was no funding for the study, and the investigators didn’t have any conflicts of interest to report.

This is a summary of a preprint research study, “One-Week External Beam Partial Breast Irradiation: Survival and Toxicity Outcomes,” led by Riccardo Ray Colciago from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. The study has not been peer reviewed. The full text can be found at researchsquare.com.
 

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

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• Following lumpectomy for early breast cancer, a 1-week schedule of partial breast radiation – 30 Gy delivered in 5 daily fractions – is safe, effective, and convenient for both patients and hospitals.

Why this matters

• According to numerous guidelines, partial breast irradiation after lumpectomy is a sound approach for early-stage breast cancer, but there is a lack of consensus about treatment schedules.
• The investigators suggest that 30 Gy in five daily fractions is a “valid option” for these patients in a field that lacks consensus.

Study design

• The team reviewed 381 women with early breast cancer treated with this approach (30 Gy in five daily fractions) at their center from 2013 to 2022.
• Half of patients had left-sided tumors, 94.5% had invasive ductal carcinomas, 96.6% had grade 1 or grade 2 disease, and tumors were luminal like in 99.2% of patients.
• Following lumpectomy, women underwent partial breast irradiation to the tumor bed plus 15 mm of isometric expansion beyond it.
• Follow-up was a median of 28 months.

Key results

• Seven patients (2%) had a local recurrence, of which two were in the treatment field.
• Three-year local control, disease-free survival, and overall survival were high (97.5%, 95.7%, and 96.9%, respectively).
• Nearly 90% of patients and 97% of physicians reported good or excellent cosmesis.
• Ten patients (2.9%) had grade 2 late toxicities, including edema, asthenia, and fibrosis; there were no grade 3 or higher adverse events.
• Five patients (1.5%) had late cardiac major events, four of whom were treated on the right breast; three patients (0.9%) had late pulmonary fibrosis.
• The safety and efficacy outcomes are in line with previous reports, including those that used different dosage and/or fractionation schedules.

Limitations

• The study was retrospective, with a relatively short follow-up.
• Quality of life was not assessed.
• There was no objective baseline measure of cosmesis against which to compare cosmetic results.

Disclosures

• There was no funding for the study, and the investigators didn’t have any conflicts of interest to report.

This is a summary of a preprint research study, “One-Week External Beam Partial Breast Irradiation: Survival and Toxicity Outcomes,” led by Riccardo Ray Colciago from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. The study has not been peer reviewed. The full text can be found at researchsquare.com.
 

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

Ozempic and Wegovy are two prescription drugs that have transformed the management of type 2 diabetes and obesity. Both are a form of semaglutide; the Food and Drug Administration approved Ozempic for treating type 2 diabetes in 2017, followed by Wegovy in 2021 for weight loss in adults with obesity or those who are overweight and have least one weight-related health condition, such as hypertension or hypercholesterolemia. Ozempic is not approved for weight loss, but it has been prescribed off label for that purpose.

An effective treatment, participants with overweight or obesity in one study experienced almost a mean 15% drop in body weight with subcutaneous semaglutide administered once a week versus about 2% with placebo after 68 weeks.

In 2022, high demand and global supply constraints gave rise to shortages of both medications. The FDA reported a Wegovy shortage in March 2022, followed by an Ozempic shortage in August. Social media attention and increased off-label prescribing, with some patients purporting to have had significant improvements with weight loss and their quality of life, including having their clothing fit better and being able to bend over and tie their shoes, increased attention on these medications to the point that off-label prescribing of both drugs for weight loss resulted in some patients with type 2 diabetes unable to receive their medication on time. In late January 2023, NBC reported that Ozempic prescriptions had “tripled from 2021 to 2022,” based on data from the prescription drug discount company SingleCare.

Semaglutide is designed to mimic a hormone that signals to the brain when a person is full and promotes the release of insulin. In turn, the medications can result in lower blood glucose levels, appetite suppression, and reduced caloric intake. Injected once weekly, the medication, a glucagonlike peptide–1 receptor agonist, specifically, activates GLP-1 receptors in the brain, increasing insulin secretion, decreasing glucagon secretion, and delaying gastric emptying (acting as an incretin mimetic).
 

‘Ozempic face’

Common adverse events with semaglutide can include nausea, vomiting, diarrhea, abdominal pain, constipation, and injection-site reactions. Rare, but more severe adverse events may include thyroid C-cell tumor (in animal studies), medullary thyroid cancer risk, hypersensitivity reaction, anaphylaxis, acute renal injury, chronic renal failure exacerbation, pancreatitis, and cholelithiasis.

A less severe but noticeable side effect that has gained attention is facial wasting and aging, reportedly coined “Ozempic face” by a dermatologist interviewed for an article published in January in The New York Times.

As of Feb. 9, TikTok videos from individuals describing their personal experiences, health care professionals, and others with the tag #ozempicface had 4.8 million views.

Weight loss in the face is not specific to Ozempic or Wegovy, but may occur with any weight-loss treatment as fat loss affects the entire body, including the face. Theories as to why noticeable facial changes occur with these medications include: accelerated loss of facial pads that already tend to diminish or shift with normal aging, as well as the inability of skin elasticity to keep up with the loss of volume (fat), resulting in more prominent hanging skin and the appearance of “jowls.” Wan and colleagues have described the fat pad distribution in the face and the facial aging that occurs as a result of the loss and shifting of these fat pads over time.

In the same way that we use facial fillers to help treat and correct volume/fat loss associated with photoaging, facial fillers may be used to help restore volume where it’s been lost after weight loss. The sagging skin or loss of elasticity often associated with Ozempic-related weight loss or with rapid or noticeable weight loss in general, may or may not also require other interventions that include treatment with tissue tightening devices – such as radiofrequency energy, high-focused ultrasound energy, threads, and/or surgery – such as a face lift. The potential high cost of both off-label prescribing of these medications (especially without use of prescription health insurance) as well as treatment to correct any facial wasting has also received attention in news media and social media discussions of this topic.

Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at dermnews@mdedge.com. She has no relevant disclosures.

*Correction 1/28/23: An earlier version of this story misstated the approval date of Wegovy. It was in 2021.

Ozempic and Wegovy are two prescription drugs that have transformed the management of type 2 diabetes and obesity. Both are a form of semaglutide; the Food and Drug Administration approved Ozempic for treating type 2 diabetes in 2017, followed by Wegovy in 2021 for weight loss in adults with obesity or those who are overweight and have least one weight-related health condition, such as hypertension or hypercholesterolemia. Ozempic is not approved for weight loss, but it has been prescribed off label for that purpose.

An effective treatment, participants with overweight or obesity in one study experienced almost a mean 15% drop in body weight with subcutaneous semaglutide administered once a week versus about 2% with placebo after 68 weeks.

In 2022, high demand and global supply constraints gave rise to shortages of both medications. The FDA reported a Wegovy shortage in March 2022, followed by an Ozempic shortage in August. Social media attention and increased off-label prescribing, with some patients purporting to have had significant improvements with weight loss and their quality of life, including having their clothing fit better and being able to bend over and tie their shoes, increased attention on these medications to the point that off-label prescribing of both drugs for weight loss resulted in some patients with type 2 diabetes unable to receive their medication on time. In late January 2023, NBC reported that Ozempic prescriptions had “tripled from 2021 to 2022,” based on data from the prescription drug discount company SingleCare.

Semaglutide is designed to mimic a hormone that signals to the brain when a person is full and promotes the release of insulin. In turn, the medications can result in lower blood glucose levels, appetite suppression, and reduced caloric intake. Injected once weekly, the medication, a glucagonlike peptide–1 receptor agonist, specifically, activates GLP-1 receptors in the brain, increasing insulin secretion, decreasing glucagon secretion, and delaying gastric emptying (acting as an incretin mimetic).
 

‘Ozempic face’

Common adverse events with semaglutide can include nausea, vomiting, diarrhea, abdominal pain, constipation, and injection-site reactions. Rare, but more severe adverse events may include thyroid C-cell tumor (in animal studies), medullary thyroid cancer risk, hypersensitivity reaction, anaphylaxis, acute renal injury, chronic renal failure exacerbation, pancreatitis, and cholelithiasis.

A less severe but noticeable side effect that has gained attention is facial wasting and aging, reportedly coined “Ozempic face” by a dermatologist interviewed for an article published in January in The New York Times.

As of Feb. 9, TikTok videos from individuals describing their personal experiences, health care professionals, and others with the tag #ozempicface had 4.8 million views.

Weight loss in the face is not specific to Ozempic or Wegovy, but may occur with any weight-loss treatment as fat loss affects the entire body, including the face. Theories as to why noticeable facial changes occur with these medications include: accelerated loss of facial pads that already tend to diminish or shift with normal aging, as well as the inability of skin elasticity to keep up with the loss of volume (fat), resulting in more prominent hanging skin and the appearance of “jowls.” Wan and colleagues have described the fat pad distribution in the face and the facial aging that occurs as a result of the loss and shifting of these fat pads over time.

In the same way that we use facial fillers to help treat and correct volume/fat loss associated with photoaging, facial fillers may be used to help restore volume where it’s been lost after weight loss. The sagging skin or loss of elasticity often associated with Ozempic-related weight loss or with rapid or noticeable weight loss in general, may or may not also require other interventions that include treatment with tissue tightening devices – such as radiofrequency energy, high-focused ultrasound energy, threads, and/or surgery – such as a face lift. The potential high cost of both off-label prescribing of these medications (especially without use of prescription health insurance) as well as treatment to correct any facial wasting has also received attention in news media and social media discussions of this topic.

Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at dermnews@mdedge.com. She has no relevant disclosures.

*Correction 1/28/23: An earlier version of this story misstated the approval date of Wegovy. It was in 2021.

Ozempic and Wegovy are two prescription drugs that have transformed the management of type 2 diabetes and obesity. Both are a form of semaglutide; the Food and Drug Administration approved Ozempic for treating type 2 diabetes in 2017, followed by Wegovy in 2021 for weight loss in adults with obesity or those who are overweight and have least one weight-related health condition, such as hypertension or hypercholesterolemia. Ozempic is not approved for weight loss, but it has been prescribed off label for that purpose.

An effective treatment, participants with overweight or obesity in one study experienced almost a mean 15% drop in body weight with subcutaneous semaglutide administered once a week versus about 2% with placebo after 68 weeks.

In 2022, high demand and global supply constraints gave rise to shortages of both medications. The FDA reported a Wegovy shortage in March 2022, followed by an Ozempic shortage in August. Social media attention and increased off-label prescribing, with some patients purporting to have had significant improvements with weight loss and their quality of life, including having their clothing fit better and being able to bend over and tie their shoes, increased attention on these medications to the point that off-label prescribing of both drugs for weight loss resulted in some patients with type 2 diabetes unable to receive their medication on time. In late January 2023, NBC reported that Ozempic prescriptions had “tripled from 2021 to 2022,” based on data from the prescription drug discount company SingleCare.

Semaglutide is designed to mimic a hormone that signals to the brain when a person is full and promotes the release of insulin. In turn, the medications can result in lower blood glucose levels, appetite suppression, and reduced caloric intake. Injected once weekly, the medication, a glucagonlike peptide–1 receptor agonist, specifically, activates GLP-1 receptors in the brain, increasing insulin secretion, decreasing glucagon secretion, and delaying gastric emptying (acting as an incretin mimetic).
 

‘Ozempic face’

Common adverse events with semaglutide can include nausea, vomiting, diarrhea, abdominal pain, constipation, and injection-site reactions. Rare, but more severe adverse events may include thyroid C-cell tumor (in animal studies), medullary thyroid cancer risk, hypersensitivity reaction, anaphylaxis, acute renal injury, chronic renal failure exacerbation, pancreatitis, and cholelithiasis.

A less severe but noticeable side effect that has gained attention is facial wasting and aging, reportedly coined “Ozempic face” by a dermatologist interviewed for an article published in January in The New York Times.

As of Feb. 9, TikTok videos from individuals describing their personal experiences, health care professionals, and others with the tag #ozempicface had 4.8 million views.

Weight loss in the face is not specific to Ozempic or Wegovy, but may occur with any weight-loss treatment as fat loss affects the entire body, including the face. Theories as to why noticeable facial changes occur with these medications include: accelerated loss of facial pads that already tend to diminish or shift with normal aging, as well as the inability of skin elasticity to keep up with the loss of volume (fat), resulting in more prominent hanging skin and the appearance of “jowls.” Wan and colleagues have described the fat pad distribution in the face and the facial aging that occurs as a result of the loss and shifting of these fat pads over time.

In the same way that we use facial fillers to help treat and correct volume/fat loss associated with photoaging, facial fillers may be used to help restore volume where it’s been lost after weight loss. The sagging skin or loss of elasticity often associated with Ozempic-related weight loss or with rapid or noticeable weight loss in general, may or may not also require other interventions that include treatment with tissue tightening devices – such as radiofrequency energy, high-focused ultrasound energy, threads, and/or surgery – such as a face lift. The potential high cost of both off-label prescribing of these medications (especially without use of prescription health insurance) as well as treatment to correct any facial wasting has also received attention in news media and social media discussions of this topic.

Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at dermnews@mdedge.com. She has no relevant disclosures.

*Correction 1/28/23: An earlier version of this story misstated the approval date of Wegovy. It was in 2021.

A novel anti-inflammatory agent given to stroke patients receiving endovascular therapy significantly cut the mortality rate, reduced infarct size, and improved disability, preliminary results of a first-in-human study show.

The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.

Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Best doses

The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.

The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.

The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.

“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.

Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.

Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.

“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.

Those who were eligible also received tissue plasminogen activator.

The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
 

Lower mortality

At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).

The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”

The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).

About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.

A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).

This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
 

Clear shift in disability

“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.

He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.

“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”

These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”

Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.

Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”

The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”

The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
 

‘Very robust results’

In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”

“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.

He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.

“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”

However, he stressed the drug “is not ready for prime-time practice.”

“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.

The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.

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

A novel anti-inflammatory agent given to stroke patients receiving endovascular therapy significantly cut the mortality rate, reduced infarct size, and improved disability, preliminary results of a first-in-human study show.

The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.

Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Best doses

The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.

The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.

The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.

“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.

Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.

Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.

“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.

Those who were eligible also received tissue plasminogen activator.

The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
 

Lower mortality

At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).

The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”

The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).

About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.

A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).

This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
 

Clear shift in disability

“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.

He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.

“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”

These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”

Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.

Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”

The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”

The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
 

‘Very robust results’

In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”

“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.

He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.

“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”

However, he stressed the drug “is not ready for prime-time practice.”

“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.

The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.

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

A novel anti-inflammatory agent given to stroke patients receiving endovascular therapy significantly cut the mortality rate, reduced infarct size, and improved disability, preliminary results of a first-in-human study show.

The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.

Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Best doses

The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.

The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.

The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.

“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.

Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.

Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.

“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.

Those who were eligible also received tissue plasminogen activator.

The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
 

Lower mortality

At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).

The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”

The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).

About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.

A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).

This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
 

Clear shift in disability

“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.

He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.

“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”

These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”

Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.

Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”

The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”

The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
 

‘Very robust results’

In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”

“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.

He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.

“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”

However, he stressed the drug “is not ready for prime-time practice.”

“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.

The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.

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

When treating early-stage breast cancer, decisions made on age alone can miss the mark, say researchers reporting new data showing a sharp cut-off at age 70.

“In our study, one of the most significant variables in determining whether breast cancer patients who are close their 70th birthday are recommended standard-of-care radiation or de-escalated treatment is whether they show up a few months before or a few months after that 70th birthday,” commented study author Wesley J. Talcott, MD, of the department of therapeutic radiology at the Yale School of Medicine, New Haven, Conn.

The results show a trend in which radiation therapy is 50% less likely to be prescribed for patients age 70 and older with early-stage breast cancer, even when controlling for population size, patient demographics, and disease specific variables.

This suggests that oncologists are weighing the variable of age too heavily when deciding on adjuvant treatments, the authors suggest.

“In certain circumstances, breast cancer oncology providers are treating age like a binary categorical variable when selecting patients for treatments or diagnostic procedures, rather than the continuous variable that it is,” Dr. Talcott commented.

The study was published online in the International Journal of Radiation Oncology: Biology, Physics.

Approached for comment, Casey Chollet-Lipscomb, MD, radiation oncologist with Tennessee Oncology, Nashville, who was not associated with the study, agreed with its main finding.

“The study helps emphasize the importance of individualized care,” she said. “Increasing age is the most common risk factor for breast cancer, but breast cancer is an incredibly diverse disease. While you can observe trends based on age, every patient is unique, and they can’t be lumped into one bucket and prescribed treatment based on a strict age cutoff.”

The retrospective study included two cohorts of women identified in the National Cancer Data Base (2004-2017) all of whom underwent lumpectomy for early-stage breast cancer. All patients had “strong indications” for adjuvant treatment.

Patients in cohort 1 (n = 160,990) included women with estrogen-receptor negative cancer, tumor size greater than 3 cm, who were determined to be “appropriate” for radiation therapy.

Patients in cohort 2 (n = 394,946) had hormone-receptor positive cancer, tumor size greater than 5 mm, and were considered to be “appropriate” candidates for endocrine therapy.

Multivariable analysis was performed to control for comorbidity burden (measured by the Charlson-Deyo Comorbidity Index), race and ethnicity, insurance status, academic versus non-academic treatment center, median annual income of a patient’s area of residence, distance from the site of treatment, and pathology variables including number of lymph nodes sampled, histologic grade, and genomic risk score.

In cohort 1, radiation was recommended for 90%-92% of patients between the ages of 50-69; this dropped to 81% for those aged 70.

After MVA, it was determined that age difference was an independent predictor for adjuvant radiation recommendation only at age 70 versus 69 (odds ratio, 0.47; 95% confidence interval 0.39-0.57, P < .001).

For cohort 2, year-over-year age difference predicted endocrine therapy recommendation only at the juncture between age 70 versus 69 (OR, 0.86, 95% CI 0.74-0.99, P = .001).

“Our results don’t say that we should be increasing the amount of treatment for patients over the age [of] 70 or decreasing that patient treatment for patients younger than age 70. What we believe is that we need to be assessing physiologic age of our patients when treating patients,” Dr. Talcott said.

“We would do this by looking at not just how many years a patient has been on this Earth but also what their current health status is, how many good quality-of-life years they might have after treatment or without it, and what the patient wants in terms of burden of treatment. This is a much more valuable way to approach the allocation of treatments than using age alone,” he added.

Both Dr. Talcott and Dr. Chollet-Lipscomb agreed that a limitation of the study was a lack of data on how physicians decided on a specific treatment in each individual case, but they agree that even without this information the results were “significant.”

Dr. Chollet-Lipscomb also highlighted the factors other than age she would use to determine the best adjuvant treatment for a patient with early stage breast cancer, including the individual features of the tumor, how aggressive it looks under the microscope, what the receptor status is, and a patient’s overall performance status and comorbidities.

Dr. Talcott and Dr. Chollet-Lipscomb report no relevant financial relationships. The authors had no acknowledgement of research support for this study.

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

When treating early-stage breast cancer, decisions made on age alone can miss the mark, say researchers reporting new data showing a sharp cut-off at age 70.

“In our study, one of the most significant variables in determining whether breast cancer patients who are close their 70th birthday are recommended standard-of-care radiation or de-escalated treatment is whether they show up a few months before or a few months after that 70th birthday,” commented study author Wesley J. Talcott, MD, of the department of therapeutic radiology at the Yale School of Medicine, New Haven, Conn.

The results show a trend in which radiation therapy is 50% less likely to be prescribed for patients age 70 and older with early-stage breast cancer, even when controlling for population size, patient demographics, and disease specific variables.

This suggests that oncologists are weighing the variable of age too heavily when deciding on adjuvant treatments, the authors suggest.

“In certain circumstances, breast cancer oncology providers are treating age like a binary categorical variable when selecting patients for treatments or diagnostic procedures, rather than the continuous variable that it is,” Dr. Talcott commented.

The study was published online in the International Journal of Radiation Oncology: Biology, Physics.

Approached for comment, Casey Chollet-Lipscomb, MD, radiation oncologist with Tennessee Oncology, Nashville, who was not associated with the study, agreed with its main finding.

“The study helps emphasize the importance of individualized care,” she said. “Increasing age is the most common risk factor for breast cancer, but breast cancer is an incredibly diverse disease. While you can observe trends based on age, every patient is unique, and they can’t be lumped into one bucket and prescribed treatment based on a strict age cutoff.”

The retrospective study included two cohorts of women identified in the National Cancer Data Base (2004-2017) all of whom underwent lumpectomy for early-stage breast cancer. All patients had “strong indications” for adjuvant treatment.

Patients in cohort 1 (n = 160,990) included women with estrogen-receptor negative cancer, tumor size greater than 3 cm, who were determined to be “appropriate” for radiation therapy.

Patients in cohort 2 (n = 394,946) had hormone-receptor positive cancer, tumor size greater than 5 mm, and were considered to be “appropriate” candidates for endocrine therapy.

Multivariable analysis was performed to control for comorbidity burden (measured by the Charlson-Deyo Comorbidity Index), race and ethnicity, insurance status, academic versus non-academic treatment center, median annual income of a patient’s area of residence, distance from the site of treatment, and pathology variables including number of lymph nodes sampled, histologic grade, and genomic risk score.

In cohort 1, radiation was recommended for 90%-92% of patients between the ages of 50-69; this dropped to 81% for those aged 70.

After MVA, it was determined that age difference was an independent predictor for adjuvant radiation recommendation only at age 70 versus 69 (odds ratio, 0.47; 95% confidence interval 0.39-0.57, P < .001).

For cohort 2, year-over-year age difference predicted endocrine therapy recommendation only at the juncture between age 70 versus 69 (OR, 0.86, 95% CI 0.74-0.99, P = .001).

“Our results don’t say that we should be increasing the amount of treatment for patients over the age [of] 70 or decreasing that patient treatment for patients younger than age 70. What we believe is that we need to be assessing physiologic age of our patients when treating patients,” Dr. Talcott said.

“We would do this by looking at not just how many years a patient has been on this Earth but also what their current health status is, how many good quality-of-life years they might have after treatment or without it, and what the patient wants in terms of burden of treatment. This is a much more valuable way to approach the allocation of treatments than using age alone,” he added.

Both Dr. Talcott and Dr. Chollet-Lipscomb agreed that a limitation of the study was a lack of data on how physicians decided on a specific treatment in each individual case, but they agree that even without this information the results were “significant.”

Dr. Chollet-Lipscomb also highlighted the factors other than age she would use to determine the best adjuvant treatment for a patient with early stage breast cancer, including the individual features of the tumor, how aggressive it looks under the microscope, what the receptor status is, and a patient’s overall performance status and comorbidities.

Dr. Talcott and Dr. Chollet-Lipscomb report no relevant financial relationships. The authors had no acknowledgement of research support for this study.

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

When treating early-stage breast cancer, decisions made on age alone can miss the mark, say researchers reporting new data showing a sharp cut-off at age 70.

“In our study, one of the most significant variables in determining whether breast cancer patients who are close their 70th birthday are recommended standard-of-care radiation or de-escalated treatment is whether they show up a few months before or a few months after that 70th birthday,” commented study author Wesley J. Talcott, MD, of the department of therapeutic radiology at the Yale School of Medicine, New Haven, Conn.

The results show a trend in which radiation therapy is 50% less likely to be prescribed for patients age 70 and older with early-stage breast cancer, even when controlling for population size, patient demographics, and disease specific variables.

This suggests that oncologists are weighing the variable of age too heavily when deciding on adjuvant treatments, the authors suggest.

“In certain circumstances, breast cancer oncology providers are treating age like a binary categorical variable when selecting patients for treatments or diagnostic procedures, rather than the continuous variable that it is,” Dr. Talcott commented.

The study was published online in the International Journal of Radiation Oncology: Biology, Physics.

Approached for comment, Casey Chollet-Lipscomb, MD, radiation oncologist with Tennessee Oncology, Nashville, who was not associated with the study, agreed with its main finding.

“The study helps emphasize the importance of individualized care,” she said. “Increasing age is the most common risk factor for breast cancer, but breast cancer is an incredibly diverse disease. While you can observe trends based on age, every patient is unique, and they can’t be lumped into one bucket and prescribed treatment based on a strict age cutoff.”

The retrospective study included two cohorts of women identified in the National Cancer Data Base (2004-2017) all of whom underwent lumpectomy for early-stage breast cancer. All patients had “strong indications” for adjuvant treatment.

Patients in cohort 1 (n = 160,990) included women with estrogen-receptor negative cancer, tumor size greater than 3 cm, who were determined to be “appropriate” for radiation therapy.

Patients in cohort 2 (n = 394,946) had hormone-receptor positive cancer, tumor size greater than 5 mm, and were considered to be “appropriate” candidates for endocrine therapy.

Multivariable analysis was performed to control for comorbidity burden (measured by the Charlson-Deyo Comorbidity Index), race and ethnicity, insurance status, academic versus non-academic treatment center, median annual income of a patient’s area of residence, distance from the site of treatment, and pathology variables including number of lymph nodes sampled, histologic grade, and genomic risk score.

In cohort 1, radiation was recommended for 90%-92% of patients between the ages of 50-69; this dropped to 81% for those aged 70.

After MVA, it was determined that age difference was an independent predictor for adjuvant radiation recommendation only at age 70 versus 69 (odds ratio, 0.47; 95% confidence interval 0.39-0.57, P < .001).

For cohort 2, year-over-year age difference predicted endocrine therapy recommendation only at the juncture between age 70 versus 69 (OR, 0.86, 95% CI 0.74-0.99, P = .001).

“Our results don’t say that we should be increasing the amount of treatment for patients over the age [of] 70 or decreasing that patient treatment for patients younger than age 70. What we believe is that we need to be assessing physiologic age of our patients when treating patients,” Dr. Talcott said.

“We would do this by looking at not just how many years a patient has been on this Earth but also what their current health status is, how many good quality-of-life years they might have after treatment or without it, and what the patient wants in terms of burden of treatment. This is a much more valuable way to approach the allocation of treatments than using age alone,” he added.

Both Dr. Talcott and Dr. Chollet-Lipscomb agreed that a limitation of the study was a lack of data on how physicians decided on a specific treatment in each individual case, but they agree that even without this information the results were “significant.”

Dr. Chollet-Lipscomb also highlighted the factors other than age she would use to determine the best adjuvant treatment for a patient with early stage breast cancer, including the individual features of the tumor, how aggressive it looks under the microscope, what the receptor status is, and a patient’s overall performance status and comorbidities.

Dr. Talcott and Dr. Chollet-Lipscomb report no relevant financial relationships. The authors had no acknowledgement of research support for this study.

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

On Oct. 5, 2022, at 10:24 a.m., Chris Nowinski, PhD, cofounder of the Boston-based Concussion Legacy Foundation (CLF), was in his home office when the email came through. For the first time, the National Institutes of Health (NIH) acknowledged there was a causal link between repeated blows to the head and chronic traumatic encephalopathy (CTE).

“I pounded my desk, shouted YES! and went to find my wife so I could pick her up and give her a big hug,” he recalled. “It was the culmination of 15 years of research and hard work.”

Robert Cantu, MD, who has been studying head trauma for 50+ years and has published more than 500 papers about it, compares the announcement to the 1964 Surgeon General’s report that linked cigarette smoking with lung cancer and heart disease. With the NIH and the Centers of Disease Control and Prevention (CDC) now in agreement about the risks of participating in impact sports and activities, he said, “We’ve reached a tipping point that should finally prompt deniers such as the NHL, NCAA, FIFA, World Rugby, the International Olympic Committee, and other [sports organizations] to remove all unnecessary head trauma from their sports.”

“A lot of the credit for this must go to Chris,” added Dr. Cantu, medical director and director of clinical research at the Cantu Concussion Center at Emerson Hospital in Concord, Mass. “Clinicians like myself can reach only so many people by writing papers and giving speeches at medical conferences. For this to happen, the message needed to get out to parents, athletes, and society in general. And Chris was the vehicle for doing that.”

Dr. Nowinski didn’t set out to be the messenger. He played football at Harvard in the late 1990s, making second-team All-Ivy as a defensive tackle his senior year. In 2000, he enrolled in Killer Kowalski’s Wrestling Institute and eventually joined Vince McMahon’s World Wrestling Entertainment (WWE).

There he played the role of 295-pound villain “Chris Harvard,” an intellectual snob who dressed in crimson tights and insulted the crowd’s IQ. “Roses are red. Violets are blue. The reason I’m talking so slowly is because no one in [insert name of town he was appearing in] has passed grade 2!”

“I’d often apply my education during a match,” he wrote in his book, “Head Games: Football’s Concussion Crisis.“ In a match in Bridgeport, Conn., I assaulted [my opponent] with a human skeleton, ripped off the skull, got down on bended knee, and began reciting Hamlet. Those were good times.”

Those good times ended abruptly, however, during a match with Bubba Ray Dudley at the Hartford Civic Center in Connecticut in 2003. Even though pro wrestling matches are rehearsed, and the blows aren’t real, accidents happen. Mr. Dudley mistakenly kicked Dr. Nowinski in the jaw with enough force to put him on his back and make the whole ring shake.

“Holy shit, kid! You okay?” asked the referee. Before a foggy Dr. Nowinski could reply, 300-pound Mr. Dudley crashed down on him, hooked his leg, and the ref began counting, “One! Two! …” Dr. Nowinski instinctively kicked out but had forgotten the rest of the script. He managed to finish the match and stagger backstage.

His coherence and awareness gradually returned, but a “throbbing headache” persisted. A locker room doctor said he might have a concussion and recommended he wait to see how he felt before wrestling in Albany, N.Y., the next evening.

The following day the headache had subsided, but he still felt “a little strange.” Nonetheless, he told the doctor he was fine and strutted out to again battle Bubba Ray, this time in a match where he eventually got thrown through a ringside table and suffered the Dudley Death Drop. Afterward, “I crawled backstage and laid down. The headache was much, much worse.”
 

An event and a process

Dr. Nowinski continued to insist he was “fine” and wrestled a few more matches in the following days before finally acknowledging something was wrong. He’d had his bell rung numerous times in football, but this was different. Even more worrisome, none of the doctors he consulted could give him any definitive answers. He finally found his way to Emerson Hospital, where Dr. Cantu was the chief of neurosurgery. 

“I remember that day vividly,” said Dr. Cantu. “Chris was this big, strapping, handsome guy – a hell of an athlete whose star was rising. He didn’t realize that he’d suffered a series of concussions and that trying to push through them was the worst thing he could be doing.”

Concussions and their effects were misunderstood by many athletes, coaches, and even physicians back then. It was assumed that the quarter inch of bone surrounding the adult brain provided adequate protection from common sports impacts and that any aftereffects were temporary. A common treatment was smelling salts and a pat on the back as the athlete returned to action.

However, the brain floats inside the skull in a bath of cerebral fluid. Any significant impact causes it to slosh violently from side to side, damaging tissue, synapses, and cells resulting in inflammation that can manifest as confusion and brain fog.

“A concussion is actually not defined by a physical injury,” explained Dr. Nowinski, “but by a loss of brain function that is induced by trauma. Concussion is not just an event, but also a process.” It’s almost as if the person has suffered a small seizure.

Fortunately, most concussion symptoms resolve within 2 weeks, but in some cases, especially if there’s been additional head trauma, they can persist, causing anxiety, depression, anger, and/or sleep disorders. Known as postconcussion syndrome (PCS), this is what Dr. Nowinski was unknowingly suffering from when he consulted Dr. Cantu.

In fact, one night it an Indianapolis hotel, weeks after his initial concussion, he awoke to find himself on the floor and the room in shambles. His girlfriend was yelling his name and shaking him. She told him he’d been having a nightmare and had suddenly started screaming and tearing up the room. “I didn’t remember any of it,” he said.

Dr. Cantu eventually advised Dr. Nowinski against ever returning to the ring or any activity with the risk for head injury. Research shows that sustaining a single significant concussion increases the risk of subsequent more-severe brain injuries.

“My diagnosis could have sent Chris off the deep end because he could no longer do what he wanted to do with this life,” said Dr. Cantu. “But instead, he used it as a tool to find meaning for his life.”

Dr. Nowinski decided to use his experience as a teaching opportunity, not just for other athletes but also for sports organizations and the medical community.

His book, which focused on the NFL’s “tobacco-industry-like refusal to acknowledge the depths of the problem,” was published in 2006. A year later, Dr. Nowinski partnered with Dr. Cantu to found the Sports Legacy Institute, which eventually became the Concussion Legacy Foundation (CLF).


 

Cold calling for brain donations

Robert Stern, PhD, is another highly respected authority in the study of neurodegenerative disease. In 2007, he was directing the clinical core of Boston University’s Alzheimer’s Disease Center. After giving a lecture to a group of financial planners and elder-law attorneys one morning, he got a request for a private meeting from a fellow named Chris Nowinski.

“I’d never heard of him, but I agreed,” recalled Dr. Stern, a professor of neurology, neurosurgery, anatomy, and neurobiology at Boston University. “A few days later, this larger-than-life guy walked into our conference room at the BU School of Medicine, exuding a great deal of passion, intellect, and determination. He told me his story and then started talking about the long-term consequences of concussions in sports.”

Dr. Stern had seen patients with dementia pugilistica, the old-school term for CTE. These were mostly boxers with cognitive and behavioral impairment. “But I had not heard about football players,” he said. “I hadn’t put the two together. And as I was listening to Chris, I realized if what he was saying was true then it was not only a potentially huge public health issue, but it was also a potentially huge scientific issue in the field of neurodegenerative disease.” 

Dr. Nowinski introduced Dr. Stern to Dr. Cantu, and together with Ann McKee, MD, professor of neurology and pathology at BU, they cofounded the Center for the Study of Traumatic Encephalopathy (CSTE) in 2008. It was the first center of its kind devoted to the study of CTE in the world.

One of Dr. Nowinski’s first jobs at the CSTE was soliciting and procuring brain donations. Since CTE is generally a progressive condition that can take decades to manifest, autopsy was the only way to detect it.

The brains of two former Pittsburgh Steelers, Mike Webster and Terry Long, had been examined after their untimely deaths. After immunostaining, investigators found both former NFL players had “protein misfolds” characteristic of CTE.

This finding drew a lot of public and scientific attention, given that Mr. Long died by suicide and Mr. Webster was homeless when he died of a heart attack. But more scientific evidence was needed to prove a causal link between the head trauma and CTE.

Dr. Nowinski scoured obituaries looking for potential brains to study. When he found one, he would cold call the family and try to convince them to donate it to science. The first brain he secured for the center belonged to John Grimsley, a former NFL linebacker who in 2008 died at age 45 of an accidental gunshot wound. Often, Dr. Nowinski would even be the courier, traveling to pick up the brain after it had been harvested.

Over the next 10 years, Dr. Nowinski and his research team secured 500 brain donations. The research that resulted was staggering. In the beginning only 45 cases of CTE had been identified in the world, but in the first 111 NFL players who were autopsied, 110 had the disorder.

Of the first 53 college football players autopsied, 48 had CTE. Although Dr. Nowinski’s initial focus was football, evidence of CTE was soon detected among athletes in boxing, hockey, soccer, and rugby, as well as in combat veterans. However, the National Football League and other governing sports bodies initially denied any connection between sport-related head trauma and CTE.
 

Cumulative damage

In 2017, after 7 years of study, Dr. Nowinski earned a PhD in neurology. As the scientific evidence continued to accumulate, two shifts occurred that Dr. Stern said represent Dr. Nowinski’s greatest contributions. First, concussion is now widely recognized as an acute brain injury with symptoms that need to be immediately diagnosed and addressed.

“This is a completely different story from where things were just 10 years ago,” said Dr. Stern, “and Chris played a central role, if not the central role, in raising awareness about that.”

All 50 states and the District of Columbia now have laws regarding sports-related concussion. And there are brain banks in Australia, Canada, New Zealand, Brazil, and the United Kingdom studying CTE. More than 2,500 athletes in a variety of sports, including NASCAR’s Dale Earnhardt Jr. and NFL hall of famer Nick Buoniconti, have publicly pledged to donate their brains to science after their deaths.

Second, said Dr. Stern, we now know that although concussions can contribute to CTE, they are not the sole cause. It’s repetitive subconcussive trauma, without symptoms of concussion, that do the most damage.

“These happen during every practice and in every game,” said Dr. Stern. In fact, it’s estimated that pro football players suffer thousands of subconcussive incidents over the course of their careers. So, a player doesn’t have to see stars or lose consciousness to suffer brain damage; small impacts can accumulate over time.

Understanding this point is crucial for making youth sports safer. “Chris has played a critical role in raising awareness here, too,” said Dr. Stern. “Allowing our kids to get hit in the head over and over can put them at greater risk for later problems, plus it just doesn’t make common sense.”

“The biggest misconception surrounding head trauma in sports,” said Dr. Nowinski, “is the belief among players, coaches, and even the medical and scientific communities that if you get hit in the head and don’t have any symptoms then you’re okay and there hasn’t been any damage. That couldn’t be further from the truth. We now know that people are suffering serious brain injuries due to the accumulated effect of subconcussive impacts, and we need to get the word out about that.”

A major initiative from the Concussion Legacy Foundation called “Stop Hitting Kids in the Head” has the goal of convincing every sport to eliminate repetitive head impacts in players under age 14 – the time when the skull and brain are still developing and most vulnerable – by 2026. In fact, Dr. Nowinski wrote that “there could be a lot of kids who are misdiagnosed and medicated for various behavioral or emotional problems that may actually be head injury–related.”

Starting in 2009, the NFL adopted a series of rule changes designed to better protect its players against repeated head trauma. Among them is a ban on spearing or leading with the helmet, penalties for hitting defenseless players, and more stringent return-to-play guidelines, including concussion protocols.

The NFL has also put more emphasis on flag football options for youngsters and, for the first time, showcased this alternative in the 2023 Pro Bowl. But Dr. Nowinski is pressuring the league to go further. “While acknowledging that the game causes CTE, the NFL still underwrites recruiting 5-year-olds to play tackle football,” he said. “In my opinion, that’s unethical, and it needs to be addressed.”
 

WWE one of the most responsive organizations

Dr. Nowinski said WWE has been one of the most responsive sports organizations for protecting athletes. A doctor is now ringside at every match as is an observer who knows the script, thereby allowing for instant medical intervention if something goes wrong. “Since everyone is trying to look like they have a concussion all the time, it takes a deep understanding of the business to recognize a real one,” he said.

But this hasn’t been the case with other sports. “I am eternally disappointed in the response of the professional sports industry to the knowledge of CTE and long-term concussion symptoms,” said Dr. Nowinski.

“For example, FIFA [international soccer’s governing body] still doesn’t allow doctors to evaluate [potentially concussed] players on the sidelines and put them back in the game with a free substitution [if they’re deemed okay]. Not giving players proper medical care for a brain injury is unethical,” he said. BU’s Center for the Study of Traumatic Encephalopathy diagnosed the first CTE case in soccer in 2012, and in 2015 Dr. Nowinski successfully lobbied U.S. Soccer to ban heading the ball before age 11.

“Unfortunately, many governing bodies have circled the wagons in denying their sport causes CTE,” he continued. “FIFA, World Rugby, the NHL, even the NCAA and International Olympic Committee refuse to acknowledge it and, therefore, aren’t taking any steps to prevent it. They see it as a threat to their business model. Hopefully, now that the NIH and CDC are aligned about the risks of head impact in sports, this will begin to change.”

Meanwhile, research is continuing. Scientists are getting closer to being able to diagnose CTE in living humans, with ongoing studies using PET scans, blood markers, and spinal fluid markers. In 2019, researchers identified tau proteins specific to CTE that they believe are distinct from those of Alzheimer’s and other neurodegenerative diseases. Next step would be developing a drug to slow the development of CTE once detected.

Nonetheless, athletes at all levels in impact sports still don’t fully appreciate the risks of repeated head trauma and especially subconcussive blows. “I talk to former NFL and college players every week,” said Dr. Stern. “Some tell me, ‘I love the sport, it gave me so much, and I would do it again, but I’m not letting my grandchildren play.’ But others say, ‘As long as they know the risks, they can make their own decision.’ “

Dr. Nowinski has a daughter who is 4 and a son who’s 2. Both play soccer but, thanks to dad, heading isn’t allowed in their age groups. If they continue playing sports, Dr. Nowinski said he’ll make sure they understand the risks and how to protect themselves. This is a conversation all parents should have with their kids at every level to make sure they play safe, he added.

Those in the medical community can also volunteer their time to explain head trauma to athletes, coaches, and school administrators to be sure they understand its seriousness and are doing everything to protect players.

As you watch this year’s Super Bowl, Dr. Nowinski and his team would like you to keep something in mind. Those young men on the field for your entertainment are receiving mild brain trauma repeatedly throughout the game.

Even if it’s not a huge hit that gets replayed and makes everyone gasp, even if no one gets ushered into the little sideline tent for a concussion screening, even if no one loses consciousness, brain damage is still occurring. Watch the heads of the players during every play and think about what’s going on inside their skulls regardless of how big and strong those helmets look.

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

On Oct. 5, 2022, at 10:24 a.m., Chris Nowinski, PhD, cofounder of the Boston-based Concussion Legacy Foundation (CLF), was in his home office when the email came through. For the first time, the National Institutes of Health (NIH) acknowledged there was a causal link between repeated blows to the head and chronic traumatic encephalopathy (CTE).

“I pounded my desk, shouted YES! and went to find my wife so I could pick her up and give her a big hug,” he recalled. “It was the culmination of 15 years of research and hard work.”

Robert Cantu, MD, who has been studying head trauma for 50+ years and has published more than 500 papers about it, compares the announcement to the 1964 Surgeon General’s report that linked cigarette smoking with lung cancer and heart disease. With the NIH and the Centers of Disease Control and Prevention (CDC) now in agreement about the risks of participating in impact sports and activities, he said, “We’ve reached a tipping point that should finally prompt deniers such as the NHL, NCAA, FIFA, World Rugby, the International Olympic Committee, and other [sports organizations] to remove all unnecessary head trauma from their sports.”

“A lot of the credit for this must go to Chris,” added Dr. Cantu, medical director and director of clinical research at the Cantu Concussion Center at Emerson Hospital in Concord, Mass. “Clinicians like myself can reach only so many people by writing papers and giving speeches at medical conferences. For this to happen, the message needed to get out to parents, athletes, and society in general. And Chris was the vehicle for doing that.”

Dr. Nowinski didn’t set out to be the messenger. He played football at Harvard in the late 1990s, making second-team All-Ivy as a defensive tackle his senior year. In 2000, he enrolled in Killer Kowalski’s Wrestling Institute and eventually joined Vince McMahon’s World Wrestling Entertainment (WWE).

There he played the role of 295-pound villain “Chris Harvard,” an intellectual snob who dressed in crimson tights and insulted the crowd’s IQ. “Roses are red. Violets are blue. The reason I’m talking so slowly is because no one in [insert name of town he was appearing in] has passed grade 2!”

“I’d often apply my education during a match,” he wrote in his book, “Head Games: Football’s Concussion Crisis.“ In a match in Bridgeport, Conn., I assaulted [my opponent] with a human skeleton, ripped off the skull, got down on bended knee, and began reciting Hamlet. Those were good times.”

Those good times ended abruptly, however, during a match with Bubba Ray Dudley at the Hartford Civic Center in Connecticut in 2003. Even though pro wrestling matches are rehearsed, and the blows aren’t real, accidents happen. Mr. Dudley mistakenly kicked Dr. Nowinski in the jaw with enough force to put him on his back and make the whole ring shake.

“Holy shit, kid! You okay?” asked the referee. Before a foggy Dr. Nowinski could reply, 300-pound Mr. Dudley crashed down on him, hooked his leg, and the ref began counting, “One! Two! …” Dr. Nowinski instinctively kicked out but had forgotten the rest of the script. He managed to finish the match and stagger backstage.

His coherence and awareness gradually returned, but a “throbbing headache” persisted. A locker room doctor said he might have a concussion and recommended he wait to see how he felt before wrestling in Albany, N.Y., the next evening.

The following day the headache had subsided, but he still felt “a little strange.” Nonetheless, he told the doctor he was fine and strutted out to again battle Bubba Ray, this time in a match where he eventually got thrown through a ringside table and suffered the Dudley Death Drop. Afterward, “I crawled backstage and laid down. The headache was much, much worse.”
 

An event and a process

Dr. Nowinski continued to insist he was “fine” and wrestled a few more matches in the following days before finally acknowledging something was wrong. He’d had his bell rung numerous times in football, but this was different. Even more worrisome, none of the doctors he consulted could give him any definitive answers. He finally found his way to Emerson Hospital, where Dr. Cantu was the chief of neurosurgery. 

“I remember that day vividly,” said Dr. Cantu. “Chris was this big, strapping, handsome guy – a hell of an athlete whose star was rising. He didn’t realize that he’d suffered a series of concussions and that trying to push through them was the worst thing he could be doing.”

Concussions and their effects were misunderstood by many athletes, coaches, and even physicians back then. It was assumed that the quarter inch of bone surrounding the adult brain provided adequate protection from common sports impacts and that any aftereffects were temporary. A common treatment was smelling salts and a pat on the back as the athlete returned to action.

However, the brain floats inside the skull in a bath of cerebral fluid. Any significant impact causes it to slosh violently from side to side, damaging tissue, synapses, and cells resulting in inflammation that can manifest as confusion and brain fog.

“A concussion is actually not defined by a physical injury,” explained Dr. Nowinski, “but by a loss of brain function that is induced by trauma. Concussion is not just an event, but also a process.” It’s almost as if the person has suffered a small seizure.

Fortunately, most concussion symptoms resolve within 2 weeks, but in some cases, especially if there’s been additional head trauma, they can persist, causing anxiety, depression, anger, and/or sleep disorders. Known as postconcussion syndrome (PCS), this is what Dr. Nowinski was unknowingly suffering from when he consulted Dr. Cantu.

In fact, one night it an Indianapolis hotel, weeks after his initial concussion, he awoke to find himself on the floor and the room in shambles. His girlfriend was yelling his name and shaking him. She told him he’d been having a nightmare and had suddenly started screaming and tearing up the room. “I didn’t remember any of it,” he said.

Dr. Cantu eventually advised Dr. Nowinski against ever returning to the ring or any activity with the risk for head injury. Research shows that sustaining a single significant concussion increases the risk of subsequent more-severe brain injuries.

“My diagnosis could have sent Chris off the deep end because he could no longer do what he wanted to do with this life,” said Dr. Cantu. “But instead, he used it as a tool to find meaning for his life.”

Dr. Nowinski decided to use his experience as a teaching opportunity, not just for other athletes but also for sports organizations and the medical community.

His book, which focused on the NFL’s “tobacco-industry-like refusal to acknowledge the depths of the problem,” was published in 2006. A year later, Dr. Nowinski partnered with Dr. Cantu to found the Sports Legacy Institute, which eventually became the Concussion Legacy Foundation (CLF).


 

Cold calling for brain donations

Robert Stern, PhD, is another highly respected authority in the study of neurodegenerative disease. In 2007, he was directing the clinical core of Boston University’s Alzheimer’s Disease Center. After giving a lecture to a group of financial planners and elder-law attorneys one morning, he got a request for a private meeting from a fellow named Chris Nowinski.

“I’d never heard of him, but I agreed,” recalled Dr. Stern, a professor of neurology, neurosurgery, anatomy, and neurobiology at Boston University. “A few days later, this larger-than-life guy walked into our conference room at the BU School of Medicine, exuding a great deal of passion, intellect, and determination. He told me his story and then started talking about the long-term consequences of concussions in sports.”

Dr. Stern had seen patients with dementia pugilistica, the old-school term for CTE. These were mostly boxers with cognitive and behavioral impairment. “But I had not heard about football players,” he said. “I hadn’t put the two together. And as I was listening to Chris, I realized if what he was saying was true then it was not only a potentially huge public health issue, but it was also a potentially huge scientific issue in the field of neurodegenerative disease.” 

Dr. Nowinski introduced Dr. Stern to Dr. Cantu, and together with Ann McKee, MD, professor of neurology and pathology at BU, they cofounded the Center for the Study of Traumatic Encephalopathy (CSTE) in 2008. It was the first center of its kind devoted to the study of CTE in the world.

One of Dr. Nowinski’s first jobs at the CSTE was soliciting and procuring brain donations. Since CTE is generally a progressive condition that can take decades to manifest, autopsy was the only way to detect it.

The brains of two former Pittsburgh Steelers, Mike Webster and Terry Long, had been examined after their untimely deaths. After immunostaining, investigators found both former NFL players had “protein misfolds” characteristic of CTE.

This finding drew a lot of public and scientific attention, given that Mr. Long died by suicide and Mr. Webster was homeless when he died of a heart attack. But more scientific evidence was needed to prove a causal link between the head trauma and CTE.

Dr. Nowinski scoured obituaries looking for potential brains to study. When he found one, he would cold call the family and try to convince them to donate it to science. The first brain he secured for the center belonged to John Grimsley, a former NFL linebacker who in 2008 died at age 45 of an accidental gunshot wound. Often, Dr. Nowinski would even be the courier, traveling to pick up the brain after it had been harvested.

Over the next 10 years, Dr. Nowinski and his research team secured 500 brain donations. The research that resulted was staggering. In the beginning only 45 cases of CTE had been identified in the world, but in the first 111 NFL players who were autopsied, 110 had the disorder.

Of the first 53 college football players autopsied, 48 had CTE. Although Dr. Nowinski’s initial focus was football, evidence of CTE was soon detected among athletes in boxing, hockey, soccer, and rugby, as well as in combat veterans. However, the National Football League and other governing sports bodies initially denied any connection between sport-related head trauma and CTE.
 

Cumulative damage

In 2017, after 7 years of study, Dr. Nowinski earned a PhD in neurology. As the scientific evidence continued to accumulate, two shifts occurred that Dr. Stern said represent Dr. Nowinski’s greatest contributions. First, concussion is now widely recognized as an acute brain injury with symptoms that need to be immediately diagnosed and addressed.

“This is a completely different story from where things were just 10 years ago,” said Dr. Stern, “and Chris played a central role, if not the central role, in raising awareness about that.”

All 50 states and the District of Columbia now have laws regarding sports-related concussion. And there are brain banks in Australia, Canada, New Zealand, Brazil, and the United Kingdom studying CTE. More than 2,500 athletes in a variety of sports, including NASCAR’s Dale Earnhardt Jr. and NFL hall of famer Nick Buoniconti, have publicly pledged to donate their brains to science after their deaths.

Second, said Dr. Stern, we now know that although concussions can contribute to CTE, they are not the sole cause. It’s repetitive subconcussive trauma, without symptoms of concussion, that do the most damage.

“These happen during every practice and in every game,” said Dr. Stern. In fact, it’s estimated that pro football players suffer thousands of subconcussive incidents over the course of their careers. So, a player doesn’t have to see stars or lose consciousness to suffer brain damage; small impacts can accumulate over time.

Understanding this point is crucial for making youth sports safer. “Chris has played a critical role in raising awareness here, too,” said Dr. Stern. “Allowing our kids to get hit in the head over and over can put them at greater risk for later problems, plus it just doesn’t make common sense.”

“The biggest misconception surrounding head trauma in sports,” said Dr. Nowinski, “is the belief among players, coaches, and even the medical and scientific communities that if you get hit in the head and don’t have any symptoms then you’re okay and there hasn’t been any damage. That couldn’t be further from the truth. We now know that people are suffering serious brain injuries due to the accumulated effect of subconcussive impacts, and we need to get the word out about that.”

A major initiative from the Concussion Legacy Foundation called “Stop Hitting Kids in the Head” has the goal of convincing every sport to eliminate repetitive head impacts in players under age 14 – the time when the skull and brain are still developing and most vulnerable – by 2026. In fact, Dr. Nowinski wrote that “there could be a lot of kids who are misdiagnosed and medicated for various behavioral or emotional problems that may actually be head injury–related.”

Starting in 2009, the NFL adopted a series of rule changes designed to better protect its players against repeated head trauma. Among them is a ban on spearing or leading with the helmet, penalties for hitting defenseless players, and more stringent return-to-play guidelines, including concussion protocols.

The NFL has also put more emphasis on flag football options for youngsters and, for the first time, showcased this alternative in the 2023 Pro Bowl. But Dr. Nowinski is pressuring the league to go further. “While acknowledging that the game causes CTE, the NFL still underwrites recruiting 5-year-olds to play tackle football,” he said. “In my opinion, that’s unethical, and it needs to be addressed.”
 

WWE one of the most responsive organizations

Dr. Nowinski said WWE has been one of the most responsive sports organizations for protecting athletes. A doctor is now ringside at every match as is an observer who knows the script, thereby allowing for instant medical intervention if something goes wrong. “Since everyone is trying to look like they have a concussion all the time, it takes a deep understanding of the business to recognize a real one,” he said.

But this hasn’t been the case with other sports. “I am eternally disappointed in the response of the professional sports industry to the knowledge of CTE and long-term concussion symptoms,” said Dr. Nowinski.

“For example, FIFA [international soccer’s governing body] still doesn’t allow doctors to evaluate [potentially concussed] players on the sidelines and put them back in the game with a free substitution [if they’re deemed okay]. Not giving players proper medical care for a brain injury is unethical,” he said. BU’s Center for the Study of Traumatic Encephalopathy diagnosed the first CTE case in soccer in 2012, and in 2015 Dr. Nowinski successfully lobbied U.S. Soccer to ban heading the ball before age 11.

“Unfortunately, many governing bodies have circled the wagons in denying their sport causes CTE,” he continued. “FIFA, World Rugby, the NHL, even the NCAA and International Olympic Committee refuse to acknowledge it and, therefore, aren’t taking any steps to prevent it. They see it as a threat to their business model. Hopefully, now that the NIH and CDC are aligned about the risks of head impact in sports, this will begin to change.”

Meanwhile, research is continuing. Scientists are getting closer to being able to diagnose CTE in living humans, with ongoing studies using PET scans, blood markers, and spinal fluid markers. In 2019, researchers identified tau proteins specific to CTE that they believe are distinct from those of Alzheimer’s and other neurodegenerative diseases. Next step would be developing a drug to slow the development of CTE once detected.

Nonetheless, athletes at all levels in impact sports still don’t fully appreciate the risks of repeated head trauma and especially subconcussive blows. “I talk to former NFL and college players every week,” said Dr. Stern. “Some tell me, ‘I love the sport, it gave me so much, and I would do it again, but I’m not letting my grandchildren play.’ But others say, ‘As long as they know the risks, they can make their own decision.’ “

Dr. Nowinski has a daughter who is 4 and a son who’s 2. Both play soccer but, thanks to dad, heading isn’t allowed in their age groups. If they continue playing sports, Dr. Nowinski said he’ll make sure they understand the risks and how to protect themselves. This is a conversation all parents should have with their kids at every level to make sure they play safe, he added.

Those in the medical community can also volunteer their time to explain head trauma to athletes, coaches, and school administrators to be sure they understand its seriousness and are doing everything to protect players.

As you watch this year’s Super Bowl, Dr. Nowinski and his team would like you to keep something in mind. Those young men on the field for your entertainment are receiving mild brain trauma repeatedly throughout the game.

Even if it’s not a huge hit that gets replayed and makes everyone gasp, even if no one gets ushered into the little sideline tent for a concussion screening, even if no one loses consciousness, brain damage is still occurring. Watch the heads of the players during every play and think about what’s going on inside their skulls regardless of how big and strong those helmets look.

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

On Oct. 5, 2022, at 10:24 a.m., Chris Nowinski, PhD, cofounder of the Boston-based Concussion Legacy Foundation (CLF), was in his home office when the email came through. For the first time, the National Institutes of Health (NIH) acknowledged there was a causal link between repeated blows to the head and chronic traumatic encephalopathy (CTE).

“I pounded my desk, shouted YES! and went to find my wife so I could pick her up and give her a big hug,” he recalled. “It was the culmination of 15 years of research and hard work.”

Robert Cantu, MD, who has been studying head trauma for 50+ years and has published more than 500 papers about it, compares the announcement to the 1964 Surgeon General’s report that linked cigarette smoking with lung cancer and heart disease. With the NIH and the Centers of Disease Control and Prevention (CDC) now in agreement about the risks of participating in impact sports and activities, he said, “We’ve reached a tipping point that should finally prompt deniers such as the NHL, NCAA, FIFA, World Rugby, the International Olympic Committee, and other [sports organizations] to remove all unnecessary head trauma from their sports.”

“A lot of the credit for this must go to Chris,” added Dr. Cantu, medical director and director of clinical research at the Cantu Concussion Center at Emerson Hospital in Concord, Mass. “Clinicians like myself can reach only so many people by writing papers and giving speeches at medical conferences. For this to happen, the message needed to get out to parents, athletes, and society in general. And Chris was the vehicle for doing that.”

Dr. Nowinski didn’t set out to be the messenger. He played football at Harvard in the late 1990s, making second-team All-Ivy as a defensive tackle his senior year. In 2000, he enrolled in Killer Kowalski’s Wrestling Institute and eventually joined Vince McMahon’s World Wrestling Entertainment (WWE).

There he played the role of 295-pound villain “Chris Harvard,” an intellectual snob who dressed in crimson tights and insulted the crowd’s IQ. “Roses are red. Violets are blue. The reason I’m talking so slowly is because no one in [insert name of town he was appearing in] has passed grade 2!”

“I’d often apply my education during a match,” he wrote in his book, “Head Games: Football’s Concussion Crisis.“ In a match in Bridgeport, Conn., I assaulted [my opponent] with a human skeleton, ripped off the skull, got down on bended knee, and began reciting Hamlet. Those were good times.”

Those good times ended abruptly, however, during a match with Bubba Ray Dudley at the Hartford Civic Center in Connecticut in 2003. Even though pro wrestling matches are rehearsed, and the blows aren’t real, accidents happen. Mr. Dudley mistakenly kicked Dr. Nowinski in the jaw with enough force to put him on his back and make the whole ring shake.

“Holy shit, kid! You okay?” asked the referee. Before a foggy Dr. Nowinski could reply, 300-pound Mr. Dudley crashed down on him, hooked his leg, and the ref began counting, “One! Two! …” Dr. Nowinski instinctively kicked out but had forgotten the rest of the script. He managed to finish the match and stagger backstage.

His coherence and awareness gradually returned, but a “throbbing headache” persisted. A locker room doctor said he might have a concussion and recommended he wait to see how he felt before wrestling in Albany, N.Y., the next evening.

The following day the headache had subsided, but he still felt “a little strange.” Nonetheless, he told the doctor he was fine and strutted out to again battle Bubba Ray, this time in a match where he eventually got thrown through a ringside table and suffered the Dudley Death Drop. Afterward, “I crawled backstage and laid down. The headache was much, much worse.”
 

An event and a process

Dr. Nowinski continued to insist he was “fine” and wrestled a few more matches in the following days before finally acknowledging something was wrong. He’d had his bell rung numerous times in football, but this was different. Even more worrisome, none of the doctors he consulted could give him any definitive answers. He finally found his way to Emerson Hospital, where Dr. Cantu was the chief of neurosurgery. 

“I remember that day vividly,” said Dr. Cantu. “Chris was this big, strapping, handsome guy – a hell of an athlete whose star was rising. He didn’t realize that he’d suffered a series of concussions and that trying to push through them was the worst thing he could be doing.”

Concussions and their effects were misunderstood by many athletes, coaches, and even physicians back then. It was assumed that the quarter inch of bone surrounding the adult brain provided adequate protection from common sports impacts and that any aftereffects were temporary. A common treatment was smelling salts and a pat on the back as the athlete returned to action.

However, the brain floats inside the skull in a bath of cerebral fluid. Any significant impact causes it to slosh violently from side to side, damaging tissue, synapses, and cells resulting in inflammation that can manifest as confusion and brain fog.

“A concussion is actually not defined by a physical injury,” explained Dr. Nowinski, “but by a loss of brain function that is induced by trauma. Concussion is not just an event, but also a process.” It’s almost as if the person has suffered a small seizure.

Fortunately, most concussion symptoms resolve within 2 weeks, but in some cases, especially if there’s been additional head trauma, they can persist, causing anxiety, depression, anger, and/or sleep disorders. Known as postconcussion syndrome (PCS), this is what Dr. Nowinski was unknowingly suffering from when he consulted Dr. Cantu.

In fact, one night it an Indianapolis hotel, weeks after his initial concussion, he awoke to find himself on the floor and the room in shambles. His girlfriend was yelling his name and shaking him. She told him he’d been having a nightmare and had suddenly started screaming and tearing up the room. “I didn’t remember any of it,” he said.

Dr. Cantu eventually advised Dr. Nowinski against ever returning to the ring or any activity with the risk for head injury. Research shows that sustaining a single significant concussion increases the risk of subsequent more-severe brain injuries.

“My diagnosis could have sent Chris off the deep end because he could no longer do what he wanted to do with this life,” said Dr. Cantu. “But instead, he used it as a tool to find meaning for his life.”

Dr. Nowinski decided to use his experience as a teaching opportunity, not just for other athletes but also for sports organizations and the medical community.

His book, which focused on the NFL’s “tobacco-industry-like refusal to acknowledge the depths of the problem,” was published in 2006. A year later, Dr. Nowinski partnered with Dr. Cantu to found the Sports Legacy Institute, which eventually became the Concussion Legacy Foundation (CLF).


 

Cold calling for brain donations

Robert Stern, PhD, is another highly respected authority in the study of neurodegenerative disease. In 2007, he was directing the clinical core of Boston University’s Alzheimer’s Disease Center. After giving a lecture to a group of financial planners and elder-law attorneys one morning, he got a request for a private meeting from a fellow named Chris Nowinski.

“I’d never heard of him, but I agreed,” recalled Dr. Stern, a professor of neurology, neurosurgery, anatomy, and neurobiology at Boston University. “A few days later, this larger-than-life guy walked into our conference room at the BU School of Medicine, exuding a great deal of passion, intellect, and determination. He told me his story and then started talking about the long-term consequences of concussions in sports.”

Dr. Stern had seen patients with dementia pugilistica, the old-school term for CTE. These were mostly boxers with cognitive and behavioral impairment. “But I had not heard about football players,” he said. “I hadn’t put the two together. And as I was listening to Chris, I realized if what he was saying was true then it was not only a potentially huge public health issue, but it was also a potentially huge scientific issue in the field of neurodegenerative disease.” 

Dr. Nowinski introduced Dr. Stern to Dr. Cantu, and together with Ann McKee, MD, professor of neurology and pathology at BU, they cofounded the Center for the Study of Traumatic Encephalopathy (CSTE) in 2008. It was the first center of its kind devoted to the study of CTE in the world.

One of Dr. Nowinski’s first jobs at the CSTE was soliciting and procuring brain donations. Since CTE is generally a progressive condition that can take decades to manifest, autopsy was the only way to detect it.

The brains of two former Pittsburgh Steelers, Mike Webster and Terry Long, had been examined after their untimely deaths. After immunostaining, investigators found both former NFL players had “protein misfolds” characteristic of CTE.

This finding drew a lot of public and scientific attention, given that Mr. Long died by suicide and Mr. Webster was homeless when he died of a heart attack. But more scientific evidence was needed to prove a causal link between the head trauma and CTE.

Dr. Nowinski scoured obituaries looking for potential brains to study. When he found one, he would cold call the family and try to convince them to donate it to science. The first brain he secured for the center belonged to John Grimsley, a former NFL linebacker who in 2008 died at age 45 of an accidental gunshot wound. Often, Dr. Nowinski would even be the courier, traveling to pick up the brain after it had been harvested.

Over the next 10 years, Dr. Nowinski and his research team secured 500 brain donations. The research that resulted was staggering. In the beginning only 45 cases of CTE had been identified in the world, but in the first 111 NFL players who were autopsied, 110 had the disorder.

Of the first 53 college football players autopsied, 48 had CTE. Although Dr. Nowinski’s initial focus was football, evidence of CTE was soon detected among athletes in boxing, hockey, soccer, and rugby, as well as in combat veterans. However, the National Football League and other governing sports bodies initially denied any connection between sport-related head trauma and CTE.
 

Cumulative damage

In 2017, after 7 years of study, Dr. Nowinski earned a PhD in neurology. As the scientific evidence continued to accumulate, two shifts occurred that Dr. Stern said represent Dr. Nowinski’s greatest contributions. First, concussion is now widely recognized as an acute brain injury with symptoms that need to be immediately diagnosed and addressed.

“This is a completely different story from where things were just 10 years ago,” said Dr. Stern, “and Chris played a central role, if not the central role, in raising awareness about that.”

All 50 states and the District of Columbia now have laws regarding sports-related concussion. And there are brain banks in Australia, Canada, New Zealand, Brazil, and the United Kingdom studying CTE. More than 2,500 athletes in a variety of sports, including NASCAR’s Dale Earnhardt Jr. and NFL hall of famer Nick Buoniconti, have publicly pledged to donate their brains to science after their deaths.

Second, said Dr. Stern, we now know that although concussions can contribute to CTE, they are not the sole cause. It’s repetitive subconcussive trauma, without symptoms of concussion, that do the most damage.

“These happen during every practice and in every game,” said Dr. Stern. In fact, it’s estimated that pro football players suffer thousands of subconcussive incidents over the course of their careers. So, a player doesn’t have to see stars or lose consciousness to suffer brain damage; small impacts can accumulate over time.

Understanding this point is crucial for making youth sports safer. “Chris has played a critical role in raising awareness here, too,” said Dr. Stern. “Allowing our kids to get hit in the head over and over can put them at greater risk for later problems, plus it just doesn’t make common sense.”

“The biggest misconception surrounding head trauma in sports,” said Dr. Nowinski, “is the belief among players, coaches, and even the medical and scientific communities that if you get hit in the head and don’t have any symptoms then you’re okay and there hasn’t been any damage. That couldn’t be further from the truth. We now know that people are suffering serious brain injuries due to the accumulated effect of subconcussive impacts, and we need to get the word out about that.”

A major initiative from the Concussion Legacy Foundation called “Stop Hitting Kids in the Head” has the goal of convincing every sport to eliminate repetitive head impacts in players under age 14 – the time when the skull and brain are still developing and most vulnerable – by 2026. In fact, Dr. Nowinski wrote that “there could be a lot of kids who are misdiagnosed and medicated for various behavioral or emotional problems that may actually be head injury–related.”

Starting in 2009, the NFL adopted a series of rule changes designed to better protect its players against repeated head trauma. Among them is a ban on spearing or leading with the helmet, penalties for hitting defenseless players, and more stringent return-to-play guidelines, including concussion protocols.

The NFL has also put more emphasis on flag football options for youngsters and, for the first time, showcased this alternative in the 2023 Pro Bowl. But Dr. Nowinski is pressuring the league to go further. “While acknowledging that the game causes CTE, the NFL still underwrites recruiting 5-year-olds to play tackle football,” he said. “In my opinion, that’s unethical, and it needs to be addressed.”
 

WWE one of the most responsive organizations

Dr. Nowinski said WWE has been one of the most responsive sports organizations for protecting athletes. A doctor is now ringside at every match as is an observer who knows the script, thereby allowing for instant medical intervention if something goes wrong. “Since everyone is trying to look like they have a concussion all the time, it takes a deep understanding of the business to recognize a real one,” he said.

But this hasn’t been the case with other sports. “I am eternally disappointed in the response of the professional sports industry to the knowledge of CTE and long-term concussion symptoms,” said Dr. Nowinski.

“For example, FIFA [international soccer’s governing body] still doesn’t allow doctors to evaluate [potentially concussed] players on the sidelines and put them back in the game with a free substitution [if they’re deemed okay]. Not giving players proper medical care for a brain injury is unethical,” he said. BU’s Center for the Study of Traumatic Encephalopathy diagnosed the first CTE case in soccer in 2012, and in 2015 Dr. Nowinski successfully lobbied U.S. Soccer to ban heading the ball before age 11.

“Unfortunately, many governing bodies have circled the wagons in denying their sport causes CTE,” he continued. “FIFA, World Rugby, the NHL, even the NCAA and International Olympic Committee refuse to acknowledge it and, therefore, aren’t taking any steps to prevent it. They see it as a threat to their business model. Hopefully, now that the NIH and CDC are aligned about the risks of head impact in sports, this will begin to change.”

Meanwhile, research is continuing. Scientists are getting closer to being able to diagnose CTE in living humans, with ongoing studies using PET scans, blood markers, and spinal fluid markers. In 2019, researchers identified tau proteins specific to CTE that they believe are distinct from those of Alzheimer’s and other neurodegenerative diseases. Next step would be developing a drug to slow the development of CTE once detected.

Nonetheless, athletes at all levels in impact sports still don’t fully appreciate the risks of repeated head trauma and especially subconcussive blows. “I talk to former NFL and college players every week,” said Dr. Stern. “Some tell me, ‘I love the sport, it gave me so much, and I would do it again, but I’m not letting my grandchildren play.’ But others say, ‘As long as they know the risks, they can make their own decision.’ “

Dr. Nowinski has a daughter who is 4 and a son who’s 2. Both play soccer but, thanks to dad, heading isn’t allowed in their age groups. If they continue playing sports, Dr. Nowinski said he’ll make sure they understand the risks and how to protect themselves. This is a conversation all parents should have with their kids at every level to make sure they play safe, he added.

Those in the medical community can also volunteer their time to explain head trauma to athletes, coaches, and school administrators to be sure they understand its seriousness and are doing everything to protect players.

As you watch this year’s Super Bowl, Dr. Nowinski and his team would like you to keep something in mind. Those young men on the field for your entertainment are receiving mild brain trauma repeatedly throughout the game.

Even if it’s not a huge hit that gets replayed and makes everyone gasp, even if no one gets ushered into the little sideline tent for a concussion screening, even if no one loses consciousness, brain damage is still occurring. Watch the heads of the players during every play and think about what’s going on inside their skulls regardless of how big and strong those helmets look.

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

When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.

Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic. This past year brought some outstanding publications related to emergency medicine that are practice changers.

Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.

As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
 

Myocardial dysfunction after cardiac arrest: Tips and pitfalls

The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.

Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).

They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release

I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.

Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.

In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.

The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
 

Top myths of diagnosis and management of infectious diseases in hospital medicine

Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!

This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:

• “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
• “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
• “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
• “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
• “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.

The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
 

Guidelines for low-risk, recurrent abdominal pain in the emergency department

The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.

Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?

Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:

• Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.

Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
 

In summary

There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.

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

When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.

Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic. This past year brought some outstanding publications related to emergency medicine that are practice changers.

Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.

As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
 

Myocardial dysfunction after cardiac arrest: Tips and pitfalls

The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.

Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).

They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release

I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.

Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.

In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.

The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
 

Top myths of diagnosis and management of infectious diseases in hospital medicine

Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!

This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:

• “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
• “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
• “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
• “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
• “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.

The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
 

Guidelines for low-risk, recurrent abdominal pain in the emergency department

The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.

Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?

Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:

• Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.

Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
 

In summary

There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.

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

When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.

Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic. This past year brought some outstanding publications related to emergency medicine that are practice changers.

Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.

As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
 

Myocardial dysfunction after cardiac arrest: Tips and pitfalls

The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.

Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).

They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release

I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.

Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.

In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.

The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
 

Top myths of diagnosis and management of infectious diseases in hospital medicine

Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!

This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:

• “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
• “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
• “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
• “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
• “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.

The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
 

Guidelines for low-risk, recurrent abdominal pain in the emergency department

The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.

Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?

Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:

• Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.

Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
 

In summary

There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.

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

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.”