Federal Practitioner

Patients with psychotic disorders such as schizophrenia are more than twice as likely as those without a psychotic disorder to eventually develop dementia, new research suggests.

Results from a review and meta-analysis of almost 13 million total participants from nine countries showed that, across multiple different psychotic disorders, there was a 2.5-fold higher risk of developing dementia later in life compared with individuals who did not have a disorder. This was regardless of the age at which the patients first developed the mental illness.

Moreover, participants with a psychotic disorder tended to be younger than average when diagnosed with dementia. Two studies showed that those with psychotic disorders were more likely to be diagnosed with dementia as early as in their 60s.

“The findings add to a growing body of evidence linking psychiatric disorders with later cognitive decline and dementia,” senior investigator Jean Stafford, PhD, a research fellow at MRC Unit for Lifelong Health and Ageing, University College London, told this news organization.

Dr. Stafford noted that the results highlight the importance of being aware of and watchful for symptoms of cognitive decline in patients with psychotic disorders in mid- and late life.

“In addition, given that people with psychotic disorders are at higher risk of experiencing multiple health conditions, including dementia, managing overall physical and mental health in this group is crucial,” she said.

The findings were published online in Psychological Medicine.
 

Bringing the evidence together

There is increasing evidence that multiple psychiatric symptoms and diagnoses are associated with cognitive decline and dementia, with particularly strong evidence for late-life depression, Dr. Stafford said.

“However, the relationship between psychotic disorders and dementia is less well-established,” she added.

Last year, her team published a study showing a strong association between very late onset psychotic disorders, defined as first diagnosed after age 60 years, and increased risk for dementia in Swedish population register data.

“We also became aware of several other large studies on the topic published in the last few years and realized that an up-to-date systematic review and meta-analysis was needed to bring together the evidence, specifically focusing on longitudinal studies,” Dr. Stafford said.

The researchers searched four databases of prospective and retrospective longitudinal studies published through March 2022. Studies were required to focus on adults aged 18 years or older with a clinical diagnosis of a nonaffective psychotic disorder and a comparison group consisting of adults without a nonaffective psychotic disorder.

Of 9,496 papers, the investigators selected 11 published from 2003 to 2022 that met criteria for inclusion in their meta-analysis (12,997,101 participants), with follow-up periods ranging from 1.57 to 33 years.

The studies hailed from Denmark, Finland, Sweden, the United Kingdom, the United States, Australia, Taiwan, New Zealand, and Israel.

Random-effects meta-analyses were used to pool estimates across studies. The researchers assessed the risk of bias for each study. They also included two additional studies in the review, but not the meta-analysis, that focused specifically on late-onset acute and transient psychosis and late-onset delusional disorder.

The other studies focused on late-onset schizophrenia and/or very late onset schizophrenia-like psychoses, schizophrenia, psychotic disorders, and schizophrenia in older people.

Most studies investigated the incidence of all-cause dementia, although one study focused on the incidence of Alzheimer’s disease.
 

Potential mechanisms

The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.

Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.

Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I², 99.7%).

Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I², 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I², 98.9%; P < .001).

The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).

Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).

There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).

“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.

“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.

It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
 

Neuroimaging evidence lacking

Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”

Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.

Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.

However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.

Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.

There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.

The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.

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

Patients with psychotic disorders such as schizophrenia are more than twice as likely as those without a psychotic disorder to eventually develop dementia, new research suggests.

Results from a review and meta-analysis of almost 13 million total participants from nine countries showed that, across multiple different psychotic disorders, there was a 2.5-fold higher risk of developing dementia later in life compared with individuals who did not have a disorder. This was regardless of the age at which the patients first developed the mental illness.

Moreover, participants with a psychotic disorder tended to be younger than average when diagnosed with dementia. Two studies showed that those with psychotic disorders were more likely to be diagnosed with dementia as early as in their 60s.

“The findings add to a growing body of evidence linking psychiatric disorders with later cognitive decline and dementia,” senior investigator Jean Stafford, PhD, a research fellow at MRC Unit for Lifelong Health and Ageing, University College London, told this news organization.

Dr. Stafford noted that the results highlight the importance of being aware of and watchful for symptoms of cognitive decline in patients with psychotic disorders in mid- and late life.

“In addition, given that people with psychotic disorders are at higher risk of experiencing multiple health conditions, including dementia, managing overall physical and mental health in this group is crucial,” she said.

The findings were published online in Psychological Medicine.
 

Bringing the evidence together

There is increasing evidence that multiple psychiatric symptoms and diagnoses are associated with cognitive decline and dementia, with particularly strong evidence for late-life depression, Dr. Stafford said.

“However, the relationship between psychotic disorders and dementia is less well-established,” she added.

Last year, her team published a study showing a strong association between very late onset psychotic disorders, defined as first diagnosed after age 60 years, and increased risk for dementia in Swedish population register data.

“We also became aware of several other large studies on the topic published in the last few years and realized that an up-to-date systematic review and meta-analysis was needed to bring together the evidence, specifically focusing on longitudinal studies,” Dr. Stafford said.

The researchers searched four databases of prospective and retrospective longitudinal studies published through March 2022. Studies were required to focus on adults aged 18 years or older with a clinical diagnosis of a nonaffective psychotic disorder and a comparison group consisting of adults without a nonaffective psychotic disorder.

Of 9,496 papers, the investigators selected 11 published from 2003 to 2022 that met criteria for inclusion in their meta-analysis (12,997,101 participants), with follow-up periods ranging from 1.57 to 33 years.

The studies hailed from Denmark, Finland, Sweden, the United Kingdom, the United States, Australia, Taiwan, New Zealand, and Israel.

Random-effects meta-analyses were used to pool estimates across studies. The researchers assessed the risk of bias for each study. They also included two additional studies in the review, but not the meta-analysis, that focused specifically on late-onset acute and transient psychosis and late-onset delusional disorder.

The other studies focused on late-onset schizophrenia and/or very late onset schizophrenia-like psychoses, schizophrenia, psychotic disorders, and schizophrenia in older people.

Most studies investigated the incidence of all-cause dementia, although one study focused on the incidence of Alzheimer’s disease.
 

Potential mechanisms

The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.

Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.

Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I², 99.7%).

Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I², 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I², 98.9%; P < .001).

The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).

Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).

There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).

“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.

“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.

It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
 

Neuroimaging evidence lacking

Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”

Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.

Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.

However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.

Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.

There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.

The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.

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

Patients with psychotic disorders such as schizophrenia are more than twice as likely as those without a psychotic disorder to eventually develop dementia, new research suggests.

Results from a review and meta-analysis of almost 13 million total participants from nine countries showed that, across multiple different psychotic disorders, there was a 2.5-fold higher risk of developing dementia later in life compared with individuals who did not have a disorder. This was regardless of the age at which the patients first developed the mental illness.

Moreover, participants with a psychotic disorder tended to be younger than average when diagnosed with dementia. Two studies showed that those with psychotic disorders were more likely to be diagnosed with dementia as early as in their 60s.

“The findings add to a growing body of evidence linking psychiatric disorders with later cognitive decline and dementia,” senior investigator Jean Stafford, PhD, a research fellow at MRC Unit for Lifelong Health and Ageing, University College London, told this news organization.

Dr. Stafford noted that the results highlight the importance of being aware of and watchful for symptoms of cognitive decline in patients with psychotic disorders in mid- and late life.

“In addition, given that people with psychotic disorders are at higher risk of experiencing multiple health conditions, including dementia, managing overall physical and mental health in this group is crucial,” she said.

The findings were published online in Psychological Medicine.
 

Bringing the evidence together

There is increasing evidence that multiple psychiatric symptoms and diagnoses are associated with cognitive decline and dementia, with particularly strong evidence for late-life depression, Dr. Stafford said.

“However, the relationship between psychotic disorders and dementia is less well-established,” she added.

Last year, her team published a study showing a strong association between very late onset psychotic disorders, defined as first diagnosed after age 60 years, and increased risk for dementia in Swedish population register data.

“We also became aware of several other large studies on the topic published in the last few years and realized that an up-to-date systematic review and meta-analysis was needed to bring together the evidence, specifically focusing on longitudinal studies,” Dr. Stafford said.

The researchers searched four databases of prospective and retrospective longitudinal studies published through March 2022. Studies were required to focus on adults aged 18 years or older with a clinical diagnosis of a nonaffective psychotic disorder and a comparison group consisting of adults without a nonaffective psychotic disorder.

Of 9,496 papers, the investigators selected 11 published from 2003 to 2022 that met criteria for inclusion in their meta-analysis (12,997,101 participants), with follow-up periods ranging from 1.57 to 33 years.

The studies hailed from Denmark, Finland, Sweden, the United Kingdom, the United States, Australia, Taiwan, New Zealand, and Israel.

Random-effects meta-analyses were used to pool estimates across studies. The researchers assessed the risk of bias for each study. They also included two additional studies in the review, but not the meta-analysis, that focused specifically on late-onset acute and transient psychosis and late-onset delusional disorder.

The other studies focused on late-onset schizophrenia and/or very late onset schizophrenia-like psychoses, schizophrenia, psychotic disorders, and schizophrenia in older people.

Most studies investigated the incidence of all-cause dementia, although one study focused on the incidence of Alzheimer’s disease.
 

Potential mechanisms

The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.

Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.

Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I², 99.7%).

Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I², 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I², 98.9%; P < .001).

The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).

Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).

There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).

“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.

“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.

It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
 

Neuroimaging evidence lacking

Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”

Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.

Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.

However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.

Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.

There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.

The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.

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

Peter A. Lio, MD, is a big user of the “big guns” for his patients with atopic dermatitis – biologics, conventional immunosuppressants, and JAK inhibitors. But he also has a big menu of treatments – from oral hempseed oil and black tea compresses to probiotics and acupressure – that he encourages patients to try as they use the big guns, or as they attempt to wean off of them or avoid their use altogether.

During a presentation at the annual Integrative Dermatology Symposium, Dr. Lio said that he uses “5 pillars” to guide his integrative treatment plans: The skin barrier, the psyche, the microbiome, inflammation, and itch. “I try to flag approaches that predominantly address the categories that I think need the most help,” he said. “And I tell patients [which pillar or pillars] each treatment is addressing.”

PicturePartners/Getty Images

Most commonly, the greatest challenge with AD – and the “single biggest weakness of conventional Western medicine” – lies not with getting patients clear in the first place, but in keeping them clear safely, he said. “I don’t think that using immunosuppressive [medications] is okay for the long-term unless there is no other choice,” said Dr. Lio, who cofounded the Chicago Integrative Eczema Center about 6 years ago and is clinical assistant professor of dermatology and pediatrics at Northwestern University, Chicago. Oftentimes, he said, complementary approaches, including dietary changes, can also serve as supportive adjunctive therapy to biologics and JAK inhibitors.

He has three main criteria, or “filters,” for evaluating these treatments before recommending them to patients: At least some clinical evidence for efficacy (preferably randomized trials but not necessarily), safety, and practicality. The “only way we’re going to move things forward [for AD and other conditions] is to try out less tested treatments ... to open up to them,” Dr. Lio said in an interview after the meeting. And in doing so, he said, dermatologists “can connect with a lot of patients whom naysayers can’t connect with.”
 

An integrative menu

Dr. Lio individualizes plans, suggesting treatments after “listening to patients’ stories” and considering their age, history, symptoms and skin presentation, and other factors. He said he “goes little by little,” telling a patient, for instance, “I’d love for us to try adding a little hemp oil to your diet.”

If patients aren’t pleased with or are tired of treatments, he said in the interview, “we move on and try something else.”

At the meeting, he described some of the treatments on his menu and the supporting evidence for those treatments:

Oral hempseed oil. A randomized crossover study of 20 adult patients with AD found that daily consumption of 2 tablespoons of hempseed oil decreased skin dryness, itchiness, and use of topical medications compared with consumption of olive oil. “It was statistically significant and seemed clinically meaningful,” likely resulting from the high concentration of polyunsaturated fatty acids in the oil, Dr. Lio said.

Topical vitamin B12. In a phase 3 randomized controlled trial of topical B₁₂ applied twice a day for 8 weeks, patients experienced significant improvements in the extent and severity of AD compared with placebo. Another study in children with AD aged 6 months to 18 years found significant improvement in as early as 2 weeks of use. “It really does help, and is very gentle in babies,” Dr. Lio said.

Black tea compresses. “It’s absolutely my favorite kind of compress,” he said. “It was studied on the face and eyelids but I use it all over the body for adults and kids.” A German study of 22 patients with AD or contact facial dermatitis showed significant improvements in facial dermatitis within the first 3 days of treatment with application of black tea dressings plus an emollient cream, with significant reductions in four disease activity scores (the Facial Eczema Area and Severity Index, visual analog scale for pruritus, Investigator’s Global Assessment score, and Patient’s Self-Assessment Score) that continued through day 6.

Oolong tea. In a 2001 study, after 1 month of drinking oolong tea after each meal, 64% of patients with recalcitrant AD who continued with their regular treatment showed marked to moderate improvements in AD, with a beneficial effect first noticed after 1-2 weeks. At 6 months, 54% still had a good response to treatment. “It’s super cheap and accessible,” Dr. Lio said.

Coconut oil. One of the greatest benefits of coconut oil is on the microbiome and the dysbiosis that can result from a disrupted, or “leaky,” skin barrier – especially overgrowth of Staphylococcus aureus, which “drives AD,” Dr. Lio said. In a study of adults with AD from the Philippines, topically applied coconut oil decreased S. aureus colonization by 95% when applied twice daily for 4 weeks, compared with a 50% decrease in an olive oil control group. Other research has shown coconut oil to be superior to mineral oil as a moisturizer, he said at the meeting.

Acupressure. After a pilot study conducted by Dr. Lio and colleagues showed greater decreases in itch (per the visual analogue scale) in adults with AD who applied an acupressure bead at the LI11 point (near the elbow) for 3 minutes three times a week for 4 weeks, than among those who did not use the acupressure tool, Dr. Lio began trying it with some of his patients. “Now I use it broadly,” he added in the interview. “Kids over 10 can figure out how to use it and teenagers love it [to relief itch]. Some don’t use the beads anymore, they just use their fingertips.”
 

Advice on diet, vitamin D, and probiotics

AD severity is “powerfully” correlated with IgE food allergy, but Dr. Lio said at the meeting that he currently takes a cautious approach toward strict elimination diets.

There is a growing school of thought among allergists, he said, that positive IgE tests without evidence of acute reactions may not indicate true allergy, but rather sensitivity – and may not warrant food eliminations. And as has been shown with peanuts, there can be a serious downside to elimination, as food avoidance can lead to serious allergy later on, he said.

“More and more people are thinking that if you can tolerate [a food], continue it,” he added in the interview. In the absence of clear reactions, the only way to really know if a food is making eczema worse is to do a double-blind, placebo-controlled food challenge test, he noted.

Patients often come to see him believing that food is the “root cause” of their eczema and feeling frustrated, even anxious, about strict dietary restrictions they’ve implemented. But for many of these patients, the right question “would be to ask, why is my eczema causing my food allergy?” he said at the meeting, referring to the epithelial barrier hypothesis, which posits that skin barrier dysfunction can lead to asthma, allergic rhinitis, and food allergy.

Dr. Lio often recommends the Autoimmune Protocol (AIP) diet, a “close cousin” of the paleo diet for patients with AD, as general guidance to be followed “holistically” and often without the strict eliminations it prescribes. Minimizing processed foods and dairy and grains, which “can be inflammatory in some people,” and focusing on whole, nutrient-rich foods – all in keeping with the AIP principles – should have positive effects on the microbiome, overall health, and likely AD as well, he said.

Across the board, Dr. Lio recommends vitamin D (at nationally recommended dosages) and probiotics. Vitamin D has been shown to significantly help a small percentage of patients with eczema, he said, so he advises patients that it’s worth a trial. “I tell patients that I don’t know how to pick that small group out, so let’s try for a few months and see,” he said. “Inevitably, a percentage of patients come back and say it makes a huge difference.”

Dr. Lio’s understanding and use of probiotics has been “dynamic” over the years. “The “best, most reliable evidence” that probiotics can improve AD symptoms comes with the use of multiple probiotic strains together, he said. Based on limited but growing literature, he ensures that recommended formulations for babies include Lactobacillus rhamnosus, and that formulations for adults include Lactobacillus salivarius.

Dr. Lio works closely with dietitians, hypnotherapists, and psychologists – and will occasionally refer interested patients with AD to a Chinese medicine practitioner who personalizes the use of herbal formulations.

He reported no relevant disclosures.

Peter A. Lio, MD, is a big user of the “big guns” for his patients with atopic dermatitis – biologics, conventional immunosuppressants, and JAK inhibitors. But he also has a big menu of treatments – from oral hempseed oil and black tea compresses to probiotics and acupressure – that he encourages patients to try as they use the big guns, or as they attempt to wean off of them or avoid their use altogether.

During a presentation at the annual Integrative Dermatology Symposium, Dr. Lio said that he uses “5 pillars” to guide his integrative treatment plans: The skin barrier, the psyche, the microbiome, inflammation, and itch. “I try to flag approaches that predominantly address the categories that I think need the most help,” he said. “And I tell patients [which pillar or pillars] each treatment is addressing.”

PicturePartners/Getty Images

Most commonly, the greatest challenge with AD – and the “single biggest weakness of conventional Western medicine” – lies not with getting patients clear in the first place, but in keeping them clear safely, he said. “I don’t think that using immunosuppressive [medications] is okay for the long-term unless there is no other choice,” said Dr. Lio, who cofounded the Chicago Integrative Eczema Center about 6 years ago and is clinical assistant professor of dermatology and pediatrics at Northwestern University, Chicago. Oftentimes, he said, complementary approaches, including dietary changes, can also serve as supportive adjunctive therapy to biologics and JAK inhibitors.

He has three main criteria, or “filters,” for evaluating these treatments before recommending them to patients: At least some clinical evidence for efficacy (preferably randomized trials but not necessarily), safety, and practicality. The “only way we’re going to move things forward [for AD and other conditions] is to try out less tested treatments ... to open up to them,” Dr. Lio said in an interview after the meeting. And in doing so, he said, dermatologists “can connect with a lot of patients whom naysayers can’t connect with.”
 

An integrative menu

Dr. Lio individualizes plans, suggesting treatments after “listening to patients’ stories” and considering their age, history, symptoms and skin presentation, and other factors. He said he “goes little by little,” telling a patient, for instance, “I’d love for us to try adding a little hemp oil to your diet.”

If patients aren’t pleased with or are tired of treatments, he said in the interview, “we move on and try something else.”

At the meeting, he described some of the treatments on his menu and the supporting evidence for those treatments:

Oral hempseed oil. A randomized crossover study of 20 adult patients with AD found that daily consumption of 2 tablespoons of hempseed oil decreased skin dryness, itchiness, and use of topical medications compared with consumption of olive oil. “It was statistically significant and seemed clinically meaningful,” likely resulting from the high concentration of polyunsaturated fatty acids in the oil, Dr. Lio said.

Topical vitamin B12. In a phase 3 randomized controlled trial of topical B₁₂ applied twice a day for 8 weeks, patients experienced significant improvements in the extent and severity of AD compared with placebo. Another study in children with AD aged 6 months to 18 years found significant improvement in as early as 2 weeks of use. “It really does help, and is very gentle in babies,” Dr. Lio said.

Black tea compresses. “It’s absolutely my favorite kind of compress,” he said. “It was studied on the face and eyelids but I use it all over the body for adults and kids.” A German study of 22 patients with AD or contact facial dermatitis showed significant improvements in facial dermatitis within the first 3 days of treatment with application of black tea dressings plus an emollient cream, with significant reductions in four disease activity scores (the Facial Eczema Area and Severity Index, visual analog scale for pruritus, Investigator’s Global Assessment score, and Patient’s Self-Assessment Score) that continued through day 6.

Oolong tea. In a 2001 study, after 1 month of drinking oolong tea after each meal, 64% of patients with recalcitrant AD who continued with their regular treatment showed marked to moderate improvements in AD, with a beneficial effect first noticed after 1-2 weeks. At 6 months, 54% still had a good response to treatment. “It’s super cheap and accessible,” Dr. Lio said.

Coconut oil. One of the greatest benefits of coconut oil is on the microbiome and the dysbiosis that can result from a disrupted, or “leaky,” skin barrier – especially overgrowth of Staphylococcus aureus, which “drives AD,” Dr. Lio said. In a study of adults with AD from the Philippines, topically applied coconut oil decreased S. aureus colonization by 95% when applied twice daily for 4 weeks, compared with a 50% decrease in an olive oil control group. Other research has shown coconut oil to be superior to mineral oil as a moisturizer, he said at the meeting.

Acupressure. After a pilot study conducted by Dr. Lio and colleagues showed greater decreases in itch (per the visual analogue scale) in adults with AD who applied an acupressure bead at the LI11 point (near the elbow) for 3 minutes three times a week for 4 weeks, than among those who did not use the acupressure tool, Dr. Lio began trying it with some of his patients. “Now I use it broadly,” he added in the interview. “Kids over 10 can figure out how to use it and teenagers love it [to relief itch]. Some don’t use the beads anymore, they just use their fingertips.”
 

Advice on diet, vitamin D, and probiotics

AD severity is “powerfully” correlated with IgE food allergy, but Dr. Lio said at the meeting that he currently takes a cautious approach toward strict elimination diets.

There is a growing school of thought among allergists, he said, that positive IgE tests without evidence of acute reactions may not indicate true allergy, but rather sensitivity – and may not warrant food eliminations. And as has been shown with peanuts, there can be a serious downside to elimination, as food avoidance can lead to serious allergy later on, he said.

“More and more people are thinking that if you can tolerate [a food], continue it,” he added in the interview. In the absence of clear reactions, the only way to really know if a food is making eczema worse is to do a double-blind, placebo-controlled food challenge test, he noted.

Patients often come to see him believing that food is the “root cause” of their eczema and feeling frustrated, even anxious, about strict dietary restrictions they’ve implemented. But for many of these patients, the right question “would be to ask, why is my eczema causing my food allergy?” he said at the meeting, referring to the epithelial barrier hypothesis, which posits that skin barrier dysfunction can lead to asthma, allergic rhinitis, and food allergy.

Dr. Lio often recommends the Autoimmune Protocol (AIP) diet, a “close cousin” of the paleo diet for patients with AD, as general guidance to be followed “holistically” and often without the strict eliminations it prescribes. Minimizing processed foods and dairy and grains, which “can be inflammatory in some people,” and focusing on whole, nutrient-rich foods – all in keeping with the AIP principles – should have positive effects on the microbiome, overall health, and likely AD as well, he said.

Across the board, Dr. Lio recommends vitamin D (at nationally recommended dosages) and probiotics. Vitamin D has been shown to significantly help a small percentage of patients with eczema, he said, so he advises patients that it’s worth a trial. “I tell patients that I don’t know how to pick that small group out, so let’s try for a few months and see,” he said. “Inevitably, a percentage of patients come back and say it makes a huge difference.”

Dr. Lio’s understanding and use of probiotics has been “dynamic” over the years. “The “best, most reliable evidence” that probiotics can improve AD symptoms comes with the use of multiple probiotic strains together, he said. Based on limited but growing literature, he ensures that recommended formulations for babies include Lactobacillus rhamnosus, and that formulations for adults include Lactobacillus salivarius.

Dr. Lio works closely with dietitians, hypnotherapists, and psychologists – and will occasionally refer interested patients with AD to a Chinese medicine practitioner who personalizes the use of herbal formulations.

He reported no relevant disclosures.

Peter A. Lio, MD, is a big user of the “big guns” for his patients with atopic dermatitis – biologics, conventional immunosuppressants, and JAK inhibitors. But he also has a big menu of treatments – from oral hempseed oil and black tea compresses to probiotics and acupressure – that he encourages patients to try as they use the big guns, or as they attempt to wean off of them or avoid their use altogether.

During a presentation at the annual Integrative Dermatology Symposium, Dr. Lio said that he uses “5 pillars” to guide his integrative treatment plans: The skin barrier, the psyche, the microbiome, inflammation, and itch. “I try to flag approaches that predominantly address the categories that I think need the most help,” he said. “And I tell patients [which pillar or pillars] each treatment is addressing.”

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Most commonly, the greatest challenge with AD – and the “single biggest weakness of conventional Western medicine” – lies not with getting patients clear in the first place, but in keeping them clear safely, he said. “I don’t think that using immunosuppressive [medications] is okay for the long-term unless there is no other choice,” said Dr. Lio, who cofounded the Chicago Integrative Eczema Center about 6 years ago and is clinical assistant professor of dermatology and pediatrics at Northwestern University, Chicago. Oftentimes, he said, complementary approaches, including dietary changes, can also serve as supportive adjunctive therapy to biologics and JAK inhibitors.

He has three main criteria, or “filters,” for evaluating these treatments before recommending them to patients: At least some clinical evidence for efficacy (preferably randomized trials but not necessarily), safety, and practicality. The “only way we’re going to move things forward [for AD and other conditions] is to try out less tested treatments ... to open up to them,” Dr. Lio said in an interview after the meeting. And in doing so, he said, dermatologists “can connect with a lot of patients whom naysayers can’t connect with.”
 

An integrative menu

Dr. Lio individualizes plans, suggesting treatments after “listening to patients’ stories” and considering their age, history, symptoms and skin presentation, and other factors. He said he “goes little by little,” telling a patient, for instance, “I’d love for us to try adding a little hemp oil to your diet.”

If patients aren’t pleased with or are tired of treatments, he said in the interview, “we move on and try something else.”

At the meeting, he described some of the treatments on his menu and the supporting evidence for those treatments:

Oral hempseed oil. A randomized crossover study of 20 adult patients with AD found that daily consumption of 2 tablespoons of hempseed oil decreased skin dryness, itchiness, and use of topical medications compared with consumption of olive oil. “It was statistically significant and seemed clinically meaningful,” likely resulting from the high concentration of polyunsaturated fatty acids in the oil, Dr. Lio said.

Topical vitamin B12. In a phase 3 randomized controlled trial of topical B₁₂ applied twice a day for 8 weeks, patients experienced significant improvements in the extent and severity of AD compared with placebo. Another study in children with AD aged 6 months to 18 years found significant improvement in as early as 2 weeks of use. “It really does help, and is very gentle in babies,” Dr. Lio said.

Black tea compresses. “It’s absolutely my favorite kind of compress,” he said. “It was studied on the face and eyelids but I use it all over the body for adults and kids.” A German study of 22 patients with AD or contact facial dermatitis showed significant improvements in facial dermatitis within the first 3 days of treatment with application of black tea dressings plus an emollient cream, with significant reductions in four disease activity scores (the Facial Eczema Area and Severity Index, visual analog scale for pruritus, Investigator’s Global Assessment score, and Patient’s Self-Assessment Score) that continued through day 6.

Oolong tea. In a 2001 study, after 1 month of drinking oolong tea after each meal, 64% of patients with recalcitrant AD who continued with their regular treatment showed marked to moderate improvements in AD, with a beneficial effect first noticed after 1-2 weeks. At 6 months, 54% still had a good response to treatment. “It’s super cheap and accessible,” Dr. Lio said.

Coconut oil. One of the greatest benefits of coconut oil is on the microbiome and the dysbiosis that can result from a disrupted, or “leaky,” skin barrier – especially overgrowth of Staphylococcus aureus, which “drives AD,” Dr. Lio said. In a study of adults with AD from the Philippines, topically applied coconut oil decreased S. aureus colonization by 95% when applied twice daily for 4 weeks, compared with a 50% decrease in an olive oil control group. Other research has shown coconut oil to be superior to mineral oil as a moisturizer, he said at the meeting.

Acupressure. After a pilot study conducted by Dr. Lio and colleagues showed greater decreases in itch (per the visual analogue scale) in adults with AD who applied an acupressure bead at the LI11 point (near the elbow) for 3 minutes three times a week for 4 weeks, than among those who did not use the acupressure tool, Dr. Lio began trying it with some of his patients. “Now I use it broadly,” he added in the interview. “Kids over 10 can figure out how to use it and teenagers love it [to relief itch]. Some don’t use the beads anymore, they just use their fingertips.”
 

Advice on diet, vitamin D, and probiotics

AD severity is “powerfully” correlated with IgE food allergy, but Dr. Lio said at the meeting that he currently takes a cautious approach toward strict elimination diets.

There is a growing school of thought among allergists, he said, that positive IgE tests without evidence of acute reactions may not indicate true allergy, but rather sensitivity – and may not warrant food eliminations. And as has been shown with peanuts, there can be a serious downside to elimination, as food avoidance can lead to serious allergy later on, he said.

“More and more people are thinking that if you can tolerate [a food], continue it,” he added in the interview. In the absence of clear reactions, the only way to really know if a food is making eczema worse is to do a double-blind, placebo-controlled food challenge test, he noted.

Patients often come to see him believing that food is the “root cause” of their eczema and feeling frustrated, even anxious, about strict dietary restrictions they’ve implemented. But for many of these patients, the right question “would be to ask, why is my eczema causing my food allergy?” he said at the meeting, referring to the epithelial barrier hypothesis, which posits that skin barrier dysfunction can lead to asthma, allergic rhinitis, and food allergy.

Dr. Lio often recommends the Autoimmune Protocol (AIP) diet, a “close cousin” of the paleo diet for patients with AD, as general guidance to be followed “holistically” and often without the strict eliminations it prescribes. Minimizing processed foods and dairy and grains, which “can be inflammatory in some people,” and focusing on whole, nutrient-rich foods – all in keeping with the AIP principles – should have positive effects on the microbiome, overall health, and likely AD as well, he said.

Across the board, Dr. Lio recommends vitamin D (at nationally recommended dosages) and probiotics. Vitamin D has been shown to significantly help a small percentage of patients with eczema, he said, so he advises patients that it’s worth a trial. “I tell patients that I don’t know how to pick that small group out, so let’s try for a few months and see,” he said. “Inevitably, a percentage of patients come back and say it makes a huge difference.”

Dr. Lio’s understanding and use of probiotics has been “dynamic” over the years. “The “best, most reliable evidence” that probiotics can improve AD symptoms comes with the use of multiple probiotic strains together, he said. Based on limited but growing literature, he ensures that recommended formulations for babies include Lactobacillus rhamnosus, and that formulations for adults include Lactobacillus salivarius.

Dr. Lio works closely with dietitians, hypnotherapists, and psychologists – and will occasionally refer interested patients with AD to a Chinese medicine practitioner who personalizes the use of herbal formulations.

He reported no relevant disclosures.

Among high-risk early breast cancer patients, delivery of a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from the phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from six to three weeks. They showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant during a presentation given by Frank Vicini, MD, FASTRO, GenesisCare, during the annual meeting of the American Society for Radiation Oncology.

“This is substantially more convenient. It’s cost effective both for the health care system and individual patients. Importantly, our patients come in for treatment every day and they’re taking time from work which means they have to arrange for childcare and transportation. So, this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

“One of the things that was surprising is that I think all of us were thinking this might be a more toxic regimen, but as Dr. Vicini showed, it was equally effective over time with minimal toxicity and cosmesis was stable over time, which is important. Importantly, it included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, including all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It represents an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice calls for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds 1 week to a 1.5 week–long treatment.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score (GCS) to assess outcomes from the perspective of both physicians and patients. 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation – compared to a sequential boost – results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient rated cosmesis, and no significant difference in physician rated cosmesis. The entire treatment was delivered in three weeks, even for high-risk patients. Just as critical, the use of target volume based radiation planning for [three-dimensional conformal or IMRT whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” Dr. Vincini said.

No conflicts of interest were disclosed for Dr. Horst or Dr. Vicini.

Among high-risk early breast cancer patients, delivery of a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from the phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from six to three weeks. They showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant during a presentation given by Frank Vicini, MD, FASTRO, GenesisCare, during the annual meeting of the American Society for Radiation Oncology.

“This is substantially more convenient. It’s cost effective both for the health care system and individual patients. Importantly, our patients come in for treatment every day and they’re taking time from work which means they have to arrange for childcare and transportation. So, this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

“One of the things that was surprising is that I think all of us were thinking this might be a more toxic regimen, but as Dr. Vicini showed, it was equally effective over time with minimal toxicity and cosmesis was stable over time, which is important. Importantly, it included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, including all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It represents an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice calls for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds 1 week to a 1.5 week–long treatment.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score (GCS) to assess outcomes from the perspective of both physicians and patients. 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation – compared to a sequential boost – results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient rated cosmesis, and no significant difference in physician rated cosmesis. The entire treatment was delivered in three weeks, even for high-risk patients. Just as critical, the use of target volume based radiation planning for [three-dimensional conformal or IMRT whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” Dr. Vincini said.

No conflicts of interest were disclosed for Dr. Horst or Dr. Vicini.

Among high-risk early breast cancer patients, delivery of a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from the phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from six to three weeks. They showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant during a presentation given by Frank Vicini, MD, FASTRO, GenesisCare, during the annual meeting of the American Society for Radiation Oncology.

“This is substantially more convenient. It’s cost effective both for the health care system and individual patients. Importantly, our patients come in for treatment every day and they’re taking time from work which means they have to arrange for childcare and transportation. So, this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

“One of the things that was surprising is that I think all of us were thinking this might be a more toxic regimen, but as Dr. Vicini showed, it was equally effective over time with minimal toxicity and cosmesis was stable over time, which is important. Importantly, it included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, including all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It represents an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice calls for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds 1 week to a 1.5 week–long treatment.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score (GCS) to assess outcomes from the perspective of both physicians and patients. 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation – compared to a sequential boost – results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient rated cosmesis, and no significant difference in physician rated cosmesis. The entire treatment was delivered in three weeks, even for high-risk patients. Just as critical, the use of target volume based radiation planning for [three-dimensional conformal or IMRT whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” Dr. Vincini said.

No conflicts of interest were disclosed for Dr. Horst or Dr. Vicini.

Among patients with advanced hepatocellular carcinoma (HCC), and especially those with macrovascular invasion, stereotactic body radiation therapy (SBRT) appears to grant a survival benefit when added to systemic therapy. That was the finding from a phase 3 clinical trial presented at the annual meeting of the American Society for Radiation Oncology.

For unresectable HCC or cases that cannot be treated with thermal ablation or regional therapy, the current standard of care is systemic therapy. When the study was conducted, the recommended therapy was the sorafenib, a tyrosine kinase inhibitor. But with the publication of the IMbrave 150 study in 2021, atezolizumab plus bevacizumab is now increasingly preferred by some oncologists.

In 2008, the SHARP study found that sorafenib improved median survival, but it provided less benefit for patients with macrovascular invasion. Various studies have addressed the question of whether radiation could improve survival among this patient population, but results have not been encouraging. Direct comparisons between sorafenib and radiotherapy in the SARAH and SIRveNIB studies showed no significant differences in outcomes.

To determine the efficacy of combined SBRT and sorafenib, researchers randomized 177 patients with locally advanced HCC to receive 400 mg sorafenib every 12 hours or SBRT of 27.5-50 Gy in five fractions, followed by 200 mg sorafenib every 12 hours for 4 weeks, then 400 mg sorafenib every 12 hours thereafter. The median age was 66 years, 85% of patients were male, 74% had macrovascular invasion. The study included patients with locally advanced tumors up to a 20-cm sum of diameters or up to a 20-cm conglomerate tumor, as well as those with metastases of 3 cm size or smaller.

After a median follow-up of 13.2 months, median overall survival was 15.8 months in the combination group, versus 12.3 months in sorafenib group (hazard ratio, 0.77; 1-sided P = .055). After a multivariable analysis, the combined treatment was associated with better overall survival (HR, 0.72; P = .042).

“This overall survival is greater than expected and impressive even in the era now of immunotherapy trials,” said Laura Dawson, MD, who presented the results of the study during a press conference at the meeting. Dr. Dawson is a professor of radiation oncology at University of Toronto and a radiation oncologist at Princess Margaret Hospital in Toronto.

Median progression-free survival was 9.2 months in the combined group versus 5.5 months in the sorafenib-only group (HR, 0.55; P = .0001). At 24 months, 17% of the combination group had 7% of the sorafenib group remained had not progressed. The median time to progression was 18.5 months in the combination group and 9.5 months in the sorafenib group (HR, 0.69; P = .034). The frequency of adverse events was similar in both groups. The study admitted patients with any level of vascular invasion, which contrasted with many earlier trials that excluded those with involvement of the main portal vein.

“I think this is really one of the most important studies that’s come out in many years in terms of practice changing outcomes. We’ve seen that with patients who have very high-risk HCC, especially patients who have portal vein or macrovascular vascular invasion, there’s been a significant improvement in overall survival for these patients, and this is a very difficult patient population. Adding SBRT in this group improved both the progression free survival and overall survival, so I think we’re really at a point where we can call this a standard of care for patients,” Karyn A. Goodman, MD, professor and vice chair of clinical research and radiation oncology at the Icahn School of Medicine at Mount Sinai, New York, said at the press conference.

A limitation of the study is that it closed early to accrual because of a change in the standard of care.

Dr. Goodman has served on advisory boards for Novartis, Philips Healthcare, and Genentech, and has consulted for RenovoRx and Syntactx. Dr. Dawson has received research grants from Merck and received patent/license fees or copyright compensation from RaySearch.

Among patients with advanced hepatocellular carcinoma (HCC), and especially those with macrovascular invasion, stereotactic body radiation therapy (SBRT) appears to grant a survival benefit when added to systemic therapy. That was the finding from a phase 3 clinical trial presented at the annual meeting of the American Society for Radiation Oncology.

For unresectable HCC or cases that cannot be treated with thermal ablation or regional therapy, the current standard of care is systemic therapy. When the study was conducted, the recommended therapy was the sorafenib, a tyrosine kinase inhibitor. But with the publication of the IMbrave 150 study in 2021, atezolizumab plus bevacizumab is now increasingly preferred by some oncologists.

In 2008, the SHARP study found that sorafenib improved median survival, but it provided less benefit for patients with macrovascular invasion. Various studies have addressed the question of whether radiation could improve survival among this patient population, but results have not been encouraging. Direct comparisons between sorafenib and radiotherapy in the SARAH and SIRveNIB studies showed no significant differences in outcomes.

To determine the efficacy of combined SBRT and sorafenib, researchers randomized 177 patients with locally advanced HCC to receive 400 mg sorafenib every 12 hours or SBRT of 27.5-50 Gy in five fractions, followed by 200 mg sorafenib every 12 hours for 4 weeks, then 400 mg sorafenib every 12 hours thereafter. The median age was 66 years, 85% of patients were male, 74% had macrovascular invasion. The study included patients with locally advanced tumors up to a 20-cm sum of diameters or up to a 20-cm conglomerate tumor, as well as those with metastases of 3 cm size or smaller.

After a median follow-up of 13.2 months, median overall survival was 15.8 months in the combination group, versus 12.3 months in sorafenib group (hazard ratio, 0.77; 1-sided P = .055). After a multivariable analysis, the combined treatment was associated with better overall survival (HR, 0.72; P = .042).

“This overall survival is greater than expected and impressive even in the era now of immunotherapy trials,” said Laura Dawson, MD, who presented the results of the study during a press conference at the meeting. Dr. Dawson is a professor of radiation oncology at University of Toronto and a radiation oncologist at Princess Margaret Hospital in Toronto.

Median progression-free survival was 9.2 months in the combined group versus 5.5 months in the sorafenib-only group (HR, 0.55; P = .0001). At 24 months, 17% of the combination group had 7% of the sorafenib group remained had not progressed. The median time to progression was 18.5 months in the combination group and 9.5 months in the sorafenib group (HR, 0.69; P = .034). The frequency of adverse events was similar in both groups. The study admitted patients with any level of vascular invasion, which contrasted with many earlier trials that excluded those with involvement of the main portal vein.

“I think this is really one of the most important studies that’s come out in many years in terms of practice changing outcomes. We’ve seen that with patients who have very high-risk HCC, especially patients who have portal vein or macrovascular vascular invasion, there’s been a significant improvement in overall survival for these patients, and this is a very difficult patient population. Adding SBRT in this group improved both the progression free survival and overall survival, so I think we’re really at a point where we can call this a standard of care for patients,” Karyn A. Goodman, MD, professor and vice chair of clinical research and radiation oncology at the Icahn School of Medicine at Mount Sinai, New York, said at the press conference.

A limitation of the study is that it closed early to accrual because of a change in the standard of care.

Dr. Goodman has served on advisory boards for Novartis, Philips Healthcare, and Genentech, and has consulted for RenovoRx and Syntactx. Dr. Dawson has received research grants from Merck and received patent/license fees or copyright compensation from RaySearch.

Among patients with advanced hepatocellular carcinoma (HCC), and especially those with macrovascular invasion, stereotactic body radiation therapy (SBRT) appears to grant a survival benefit when added to systemic therapy. That was the finding from a phase 3 clinical trial presented at the annual meeting of the American Society for Radiation Oncology.

For unresectable HCC or cases that cannot be treated with thermal ablation or regional therapy, the current standard of care is systemic therapy. When the study was conducted, the recommended therapy was the sorafenib, a tyrosine kinase inhibitor. But with the publication of the IMbrave 150 study in 2021, atezolizumab plus bevacizumab is now increasingly preferred by some oncologists.

In 2008, the SHARP study found that sorafenib improved median survival, but it provided less benefit for patients with macrovascular invasion. Various studies have addressed the question of whether radiation could improve survival among this patient population, but results have not been encouraging. Direct comparisons between sorafenib and radiotherapy in the SARAH and SIRveNIB studies showed no significant differences in outcomes.

To determine the efficacy of combined SBRT and sorafenib, researchers randomized 177 patients with locally advanced HCC to receive 400 mg sorafenib every 12 hours or SBRT of 27.5-50 Gy in five fractions, followed by 200 mg sorafenib every 12 hours for 4 weeks, then 400 mg sorafenib every 12 hours thereafter. The median age was 66 years, 85% of patients were male, 74% had macrovascular invasion. The study included patients with locally advanced tumors up to a 20-cm sum of diameters or up to a 20-cm conglomerate tumor, as well as those with metastases of 3 cm size or smaller.

After a median follow-up of 13.2 months, median overall survival was 15.8 months in the combination group, versus 12.3 months in sorafenib group (hazard ratio, 0.77; 1-sided P = .055). After a multivariable analysis, the combined treatment was associated with better overall survival (HR, 0.72; P = .042).

“This overall survival is greater than expected and impressive even in the era now of immunotherapy trials,” said Laura Dawson, MD, who presented the results of the study during a press conference at the meeting. Dr. Dawson is a professor of radiation oncology at University of Toronto and a radiation oncologist at Princess Margaret Hospital in Toronto.

Median progression-free survival was 9.2 months in the combined group versus 5.5 months in the sorafenib-only group (HR, 0.55; P = .0001). At 24 months, 17% of the combination group had 7% of the sorafenib group remained had not progressed. The median time to progression was 18.5 months in the combination group and 9.5 months in the sorafenib group (HR, 0.69; P = .034). The frequency of adverse events was similar in both groups. The study admitted patients with any level of vascular invasion, which contrasted with many earlier trials that excluded those with involvement of the main portal vein.

“I think this is really one of the most important studies that’s come out in many years in terms of practice changing outcomes. We’ve seen that with patients who have very high-risk HCC, especially patients who have portal vein or macrovascular vascular invasion, there’s been a significant improvement in overall survival for these patients, and this is a very difficult patient population. Adding SBRT in this group improved both the progression free survival and overall survival, so I think we’re really at a point where we can call this a standard of care for patients,” Karyn A. Goodman, MD, professor and vice chair of clinical research and radiation oncology at the Icahn School of Medicine at Mount Sinai, New York, said at the press conference.

A limitation of the study is that it closed early to accrual because of a change in the standard of care.

Dr. Goodman has served on advisory boards for Novartis, Philips Healthcare, and Genentech, and has consulted for RenovoRx and Syntactx. Dr. Dawson has received research grants from Merck and received patent/license fees or copyright compensation from RaySearch.

Rates of subarachnoid hemorrhage (SAH) are increasing, particularly in Black people, new research suggests.

Results of a new study based on hospital discharge data show Black people have disproportionately high rates of SAH versus other racial groups. Compared with White and Hispanic people, who had an average of 10 cases per 100,000, or Asian people, with 8 per 100,000 people, Black people had an average of 15 cases per 100,000 population.

Whereas case rates held steady for other racial groups in the study over a 10-year period, Black people were the only racial group for whom SAH incidence increased over time, at a rate of 1.8% per year.

“Root causes of the higher SAH incidence in Black [people] are complex and likely extend beyond simple differences in risk factor characteristics to other socioeconomic factors including level of education, poverty level, lack of insurance, access to quality care, and structural racism,” study investigator Fadar Oliver Otite, MD, assistant professor of neurology at SUNY Upstate Medical University, Syracuse, said in an interview.

“Addressing this racial disparity will require multidisciplinary factors targeted not just at subarachnoid hemorrhage risk factors but also at socioeconomic equity,” he added.

The study was published online in Neurology.
 

Uncontrolled hypertension

The average incidence of SAH for all participants was 11 cases per 100,000 people. Men had an average rate of 10 cases and women an average rate of 13 cases per 100,000.

As expected, incidence increased with age: For middle-aged men, the average was four cases per 100,000 people whereas for men 65 and older, the average was 22 cases.

Dr. Otite and his team combined U.S. Census data with two state hospitalization databases in New York and Florida and found that there were nearly 40,000 people hospitalized for SAH between 2007 and 2017. To find annual incidences of SAH per 100,000 population, they calculated the number of SAH cases and the total adult population for the year.

“Smoking and hypertension are two of the strongest risk factors for subarachnoid hemorrhage,” Dr. Otite said. “Hypertension is more prevalent in Black people in the United States, and Black patients with hypertension are more likely to have it uncontrolled.”
 

Racism, toxic stress

Anjail Sharieff, MD, associate professor of neurology at UT Health, Houston, said aside from a high rate of common SAH risk factors such as hypertension, Black Americans also face a barrage of inequities to health education and quality health care that contributes to higher SAH rates.

“The impact of toxic stress related to racism and discrimination experiences, and chronic stress related to poverty, can contribute to hypertension in Black people,” Dr. Sharieff said, adding that these factors contribute to stroke risk and are not usually accounted for in studies.

Dr. Sharieff said many of her first-time patients end up in her office due to a heart attack or stroke because they were previously uninsured and did not have access to primary care. “We need to begin leveraging trust with people in communities – meeting people where they are,” to educate them about hypertension and other health issues, she said.

A shining example of community engagement to reduce hypertension in Black communities was the Cedars-Sinai Barbershop Study, where 52 barbershops in Los Angeles implemented blood pressure checks and interventions among customers. A year later, the project was still working.

“Once we can identify the health problems in Black communities,” said Dr. Sharieff, “we can treat them.”

Dr. Otite and Dr. Sharieff report no relevant financial relationships.

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

Rates of subarachnoid hemorrhage (SAH) are increasing, particularly in Black people, new research suggests.

Results of a new study based on hospital discharge data show Black people have disproportionately high rates of SAH versus other racial groups. Compared with White and Hispanic people, who had an average of 10 cases per 100,000, or Asian people, with 8 per 100,000 people, Black people had an average of 15 cases per 100,000 population.

Whereas case rates held steady for other racial groups in the study over a 10-year period, Black people were the only racial group for whom SAH incidence increased over time, at a rate of 1.8% per year.

“Root causes of the higher SAH incidence in Black [people] are complex and likely extend beyond simple differences in risk factor characteristics to other socioeconomic factors including level of education, poverty level, lack of insurance, access to quality care, and structural racism,” study investigator Fadar Oliver Otite, MD, assistant professor of neurology at SUNY Upstate Medical University, Syracuse, said in an interview.

“Addressing this racial disparity will require multidisciplinary factors targeted not just at subarachnoid hemorrhage risk factors but also at socioeconomic equity,” he added.

The study was published online in Neurology.
 

Uncontrolled hypertension

The average incidence of SAH for all participants was 11 cases per 100,000 people. Men had an average rate of 10 cases and women an average rate of 13 cases per 100,000.

As expected, incidence increased with age: For middle-aged men, the average was four cases per 100,000 people whereas for men 65 and older, the average was 22 cases.

Dr. Otite and his team combined U.S. Census data with two state hospitalization databases in New York and Florida and found that there were nearly 40,000 people hospitalized for SAH between 2007 and 2017. To find annual incidences of SAH per 100,000 population, they calculated the number of SAH cases and the total adult population for the year.

“Smoking and hypertension are two of the strongest risk factors for subarachnoid hemorrhage,” Dr. Otite said. “Hypertension is more prevalent in Black people in the United States, and Black patients with hypertension are more likely to have it uncontrolled.”
 

Racism, toxic stress

Anjail Sharieff, MD, associate professor of neurology at UT Health, Houston, said aside from a high rate of common SAH risk factors such as hypertension, Black Americans also face a barrage of inequities to health education and quality health care that contributes to higher SAH rates.

“The impact of toxic stress related to racism and discrimination experiences, and chronic stress related to poverty, can contribute to hypertension in Black people,” Dr. Sharieff said, adding that these factors contribute to stroke risk and are not usually accounted for in studies.

Dr. Sharieff said many of her first-time patients end up in her office due to a heart attack or stroke because they were previously uninsured and did not have access to primary care. “We need to begin leveraging trust with people in communities – meeting people where they are,” to educate them about hypertension and other health issues, she said.

A shining example of community engagement to reduce hypertension in Black communities was the Cedars-Sinai Barbershop Study, where 52 barbershops in Los Angeles implemented blood pressure checks and interventions among customers. A year later, the project was still working.

“Once we can identify the health problems in Black communities,” said Dr. Sharieff, “we can treat them.”

Dr. Otite and Dr. Sharieff report no relevant financial relationships.

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

Rates of subarachnoid hemorrhage (SAH) are increasing, particularly in Black people, new research suggests.

Results of a new study based on hospital discharge data show Black people have disproportionately high rates of SAH versus other racial groups. Compared with White and Hispanic people, who had an average of 10 cases per 100,000, or Asian people, with 8 per 100,000 people, Black people had an average of 15 cases per 100,000 population.

Whereas case rates held steady for other racial groups in the study over a 10-year period, Black people were the only racial group for whom SAH incidence increased over time, at a rate of 1.8% per year.

“Root causes of the higher SAH incidence in Black [people] are complex and likely extend beyond simple differences in risk factor characteristics to other socioeconomic factors including level of education, poverty level, lack of insurance, access to quality care, and structural racism,” study investigator Fadar Oliver Otite, MD, assistant professor of neurology at SUNY Upstate Medical University, Syracuse, said in an interview.

“Addressing this racial disparity will require multidisciplinary factors targeted not just at subarachnoid hemorrhage risk factors but also at socioeconomic equity,” he added.

The study was published online in Neurology.
 

Uncontrolled hypertension

The average incidence of SAH for all participants was 11 cases per 100,000 people. Men had an average rate of 10 cases and women an average rate of 13 cases per 100,000.

As expected, incidence increased with age: For middle-aged men, the average was four cases per 100,000 people whereas for men 65 and older, the average was 22 cases.

Dr. Otite and his team combined U.S. Census data with two state hospitalization databases in New York and Florida and found that there were nearly 40,000 people hospitalized for SAH between 2007 and 2017. To find annual incidences of SAH per 100,000 population, they calculated the number of SAH cases and the total adult population for the year.

“Smoking and hypertension are two of the strongest risk factors for subarachnoid hemorrhage,” Dr. Otite said. “Hypertension is more prevalent in Black people in the United States, and Black patients with hypertension are more likely to have it uncontrolled.”
 

Racism, toxic stress

Anjail Sharieff, MD, associate professor of neurology at UT Health, Houston, said aside from a high rate of common SAH risk factors such as hypertension, Black Americans also face a barrage of inequities to health education and quality health care that contributes to higher SAH rates.

“The impact of toxic stress related to racism and discrimination experiences, and chronic stress related to poverty, can contribute to hypertension in Black people,” Dr. Sharieff said, adding that these factors contribute to stroke risk and are not usually accounted for in studies.

Dr. Sharieff said many of her first-time patients end up in her office due to a heart attack or stroke because they were previously uninsured and did not have access to primary care. “We need to begin leveraging trust with people in communities – meeting people where they are,” to educate them about hypertension and other health issues, she said.

A shining example of community engagement to reduce hypertension in Black communities was the Cedars-Sinai Barbershop Study, where 52 barbershops in Los Angeles implemented blood pressure checks and interventions among customers. A year later, the project was still working.

“Once we can identify the health problems in Black communities,” said Dr. Sharieff, “we can treat them.”

Dr. Otite and Dr. Sharieff report no relevant financial relationships.

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

Listening to birdsong appears to have a positive and significant impact on mental health and mood, new research suggests.

Investigators found that people who listened to recordings of birds singing experienced a significant reduction in anxiety and paranoia. In contrast, the researchers also found that recordings of traffic noises, including car engines, sirens, and construction, increased depressive states.

“The results suggest that it may be worthwhile to investigate the targeted use of natural sounds such as birdsong in a clinical setting – for example, in hospital waiting rooms or in psychiatric settings,” study investigator Emil Stobbe, MSc, a predoctoral fellow at the Max Planck Institute for Human Development, Berlin, said in an interview.

“If someone is seeking an easily accessible intervention to lower distress, listening to an audio clip of birds singing might be a great option,” he added.

The study was published online in Scientific Reports.
 

Nature’s calming effect

The aim of the research was “to investigate how the physical environment impact brain and mental health,” Mr. Stobbe said.

Mr. Stobbe said that there is significantly more research examining visual properties of the physical environment but that the auditory domain is not as well researched, although, he added, that the beneficial effects of interactions with nature are “well studied.”

He noted that anxiety and paranoia can be experienced by many individuals even though they may be unaware that they are experiencing these states.

“We wanted to investigate if the beneficial effects of nature can also exert their impact on these states. In theory, birds can be representational for natural and vital environment, which, in turn, transfer the positive effects of nature on birdsong listeners,” he said.

A previous study compared nature versus city soundscape conditions and showed that the nature soundscape improved participants’ cognitive performance but did not improve mood. The present study added diversity to the soundscapes and focused not only on cognition and general mood but also on state paranoia, “which can be measured in a change-sensitive manner” and “has been shown to increase in response to traffic noise.”

The researchers hypothesized that birdsong would have a greater beneficial effect on mood and paranoia and on cognitive performance compared with traffic noise. They also investigated whether greater versus lower diversity of bird species or noise sources within the soundscapes “would be a relevant factor modulating the effects.”

The researchers recruited participants (n = 295) from a crowdsourcing platform. Participants’ mean age was late 20s (standard deviations ranged from 6.30 to 7.72), with a greater proportion of male versus female participants.

To be included, participants were required to have no history of mental illness, hearing difficulties, substance/drug intake, or suicidal thoughts/tendencies.

The outcomes of interest (mood, paranoia, cognitive performance) were measured before and after soundscape exposure and each soundscape had a low- versus high-diversity version. This resulted in several analyses that compared two types of sounds (birdsongs vs. traffic noise) x two levels of diversity (low vs. high diversity) and two time points (pre- vs. post exposure).

The exposure to sounds lasted for 6 minutes, after which they were asked to report (on a 0-100 visual scale) how diverse/monotone, beautiful, and pleasant they perceived the soundscape to be.
 

Reduction in depressive symptoms

Participants were divided into four groups: low-diversity traffic noise soundscape (n = 83), high-diversity traffic noise soundscape (n = 60), low-diversity birdsong soundscape (n = 63), and high-diversity birdsong soundscape (n = 80)

In addition to listening to the sounds, participants completed questionnaires measuring mood (depression and anxiety) and paranoia as well as a test of digit span cognitive performance (both the forward and the backward versions).

The type, diversity, and type x diversity all revealed significant effect sizes (F[3, 276] = 78.6; P < .001; eta-squared = 0.461; F[3, 276] = 3.16; P = .025; eta-squared = 0.033; and F[3, 276] = 2.66; P = .028, respectively), “suggesting that all of these factors, as well as their interaction, had a significant impact on the perception of soundscapes (that is, ratings on monotony/diversity, beauty, and pleasantness).”

A post hoc examination showed that depressive symptoms significantly increased within the low- and high-diversity urban soundscapes but decreased significantly in the high-diversity birdsong soundscapes (T[1, 60] = –2.57; P = .012; d = –0.29).

For anxiety, the post hoc within-group analyses found no effects within low- and high-diversity traffic noise conditions (T[1, 82] = –1.37; P = .174; d = –0.15 and T[1, 68] = 0.49; P = .629; d = 0.06, respectively). By contrast, there were significant declines in both birdsong conditions (low diversity: T[1, 62] = –6.13; P < .001; d = –0.77; high diversity: T[1, 60] = –6.32; P < .001; d =  –0.70).

Similarly, there were no changes in participants with paranoia when they listened to either low- or high-diversity traffic noises (T[1, 82] = –0.55; P = .583; d = –0.06 and T[1, 68] = 0.67; P = .507; d = 0.08, respectively). On the other hand, both birdsong conditions yielded reductions in paranoia (low diversity: T[1, 62] = –5.90; P < .001; d = –0.74; high diversity: T[1, 60] =  –4.11; P < .001; d = –0.46).

None of the soundscapes had any effect on cognition.

“In theory, birds can be representational for natural and vital environments which, in turn, transfer the positive effects of nature on birdsong listeners,” said Mr. Stobbe.

“Taken together, the findings of the current study provide another facet of why interactions with nature can be beneficial for our mental health, and it is highly important to preserve nature,” he added.

Mr. Stobbe said that future research should focus on investigating mixed soundscapes including examining whether the presence of natural sounds in urban settings lower stressors such as traffic noise.
 

An understudied area

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness called the study “interesting but limited.”

Dr. Duckworth, who was not involved in the research said that the “benefits of nature are understudied” and agreed with the investigators that it is potentially important to study the use of birdsongs in psychiatric facilities. “Future studies could also correlate the role of birdsong with the mental health benefits/aspects of ‘being in nature,’ which has been found to have some effect.”

Open Access funding was enabled and organized by Projekt DEAL. The authors and Dr. Duckworth declared no competing interests.

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

Listening to birdsong appears to have a positive and significant impact on mental health and mood, new research suggests.

Investigators found that people who listened to recordings of birds singing experienced a significant reduction in anxiety and paranoia. In contrast, the researchers also found that recordings of traffic noises, including car engines, sirens, and construction, increased depressive states.

“The results suggest that it may be worthwhile to investigate the targeted use of natural sounds such as birdsong in a clinical setting – for example, in hospital waiting rooms or in psychiatric settings,” study investigator Emil Stobbe, MSc, a predoctoral fellow at the Max Planck Institute for Human Development, Berlin, said in an interview.

“If someone is seeking an easily accessible intervention to lower distress, listening to an audio clip of birds singing might be a great option,” he added.

The study was published online in Scientific Reports.
 

Nature’s calming effect

The aim of the research was “to investigate how the physical environment impact brain and mental health,” Mr. Stobbe said.

Mr. Stobbe said that there is significantly more research examining visual properties of the physical environment but that the auditory domain is not as well researched, although, he added, that the beneficial effects of interactions with nature are “well studied.”

He noted that anxiety and paranoia can be experienced by many individuals even though they may be unaware that they are experiencing these states.

“We wanted to investigate if the beneficial effects of nature can also exert their impact on these states. In theory, birds can be representational for natural and vital environment, which, in turn, transfer the positive effects of nature on birdsong listeners,” he said.

A previous study compared nature versus city soundscape conditions and showed that the nature soundscape improved participants’ cognitive performance but did not improve mood. The present study added diversity to the soundscapes and focused not only on cognition and general mood but also on state paranoia, “which can be measured in a change-sensitive manner” and “has been shown to increase in response to traffic noise.”

The researchers hypothesized that birdsong would have a greater beneficial effect on mood and paranoia and on cognitive performance compared with traffic noise. They also investigated whether greater versus lower diversity of bird species or noise sources within the soundscapes “would be a relevant factor modulating the effects.”

The researchers recruited participants (n = 295) from a crowdsourcing platform. Participants’ mean age was late 20s (standard deviations ranged from 6.30 to 7.72), with a greater proportion of male versus female participants.

To be included, participants were required to have no history of mental illness, hearing difficulties, substance/drug intake, or suicidal thoughts/tendencies.

The outcomes of interest (mood, paranoia, cognitive performance) were measured before and after soundscape exposure and each soundscape had a low- versus high-diversity version. This resulted in several analyses that compared two types of sounds (birdsongs vs. traffic noise) x two levels of diversity (low vs. high diversity) and two time points (pre- vs. post exposure).

The exposure to sounds lasted for 6 minutes, after which they were asked to report (on a 0-100 visual scale) how diverse/monotone, beautiful, and pleasant they perceived the soundscape to be.
 

Reduction in depressive symptoms

Participants were divided into four groups: low-diversity traffic noise soundscape (n = 83), high-diversity traffic noise soundscape (n = 60), low-diversity birdsong soundscape (n = 63), and high-diversity birdsong soundscape (n = 80)

In addition to listening to the sounds, participants completed questionnaires measuring mood (depression and anxiety) and paranoia as well as a test of digit span cognitive performance (both the forward and the backward versions).

The type, diversity, and type x diversity all revealed significant effect sizes (F[3, 276] = 78.6; P < .001; eta-squared = 0.461; F[3, 276] = 3.16; P = .025; eta-squared = 0.033; and F[3, 276] = 2.66; P = .028, respectively), “suggesting that all of these factors, as well as their interaction, had a significant impact on the perception of soundscapes (that is, ratings on monotony/diversity, beauty, and pleasantness).”

A post hoc examination showed that depressive symptoms significantly increased within the low- and high-diversity urban soundscapes but decreased significantly in the high-diversity birdsong soundscapes (T[1, 60] = –2.57; P = .012; d = –0.29).

For anxiety, the post hoc within-group analyses found no effects within low- and high-diversity traffic noise conditions (T[1, 82] = –1.37; P = .174; d = –0.15 and T[1, 68] = 0.49; P = .629; d = 0.06, respectively). By contrast, there were significant declines in both birdsong conditions (low diversity: T[1, 62] = –6.13; P < .001; d = –0.77; high diversity: T[1, 60] = –6.32; P < .001; d =  –0.70).

Similarly, there were no changes in participants with paranoia when they listened to either low- or high-diversity traffic noises (T[1, 82] = –0.55; P = .583; d = –0.06 and T[1, 68] = 0.67; P = .507; d = 0.08, respectively). On the other hand, both birdsong conditions yielded reductions in paranoia (low diversity: T[1, 62] = –5.90; P < .001; d = –0.74; high diversity: T[1, 60] =  –4.11; P < .001; d = –0.46).

None of the soundscapes had any effect on cognition.

“In theory, birds can be representational for natural and vital environments which, in turn, transfer the positive effects of nature on birdsong listeners,” said Mr. Stobbe.

“Taken together, the findings of the current study provide another facet of why interactions with nature can be beneficial for our mental health, and it is highly important to preserve nature,” he added.

Mr. Stobbe said that future research should focus on investigating mixed soundscapes including examining whether the presence of natural sounds in urban settings lower stressors such as traffic noise.
 

An understudied area

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness called the study “interesting but limited.”

Dr. Duckworth, who was not involved in the research said that the “benefits of nature are understudied” and agreed with the investigators that it is potentially important to study the use of birdsongs in psychiatric facilities. “Future studies could also correlate the role of birdsong with the mental health benefits/aspects of ‘being in nature,’ which has been found to have some effect.”

Open Access funding was enabled and organized by Projekt DEAL. The authors and Dr. Duckworth declared no competing interests.

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

Listening to birdsong appears to have a positive and significant impact on mental health and mood, new research suggests.

Investigators found that people who listened to recordings of birds singing experienced a significant reduction in anxiety and paranoia. In contrast, the researchers also found that recordings of traffic noises, including car engines, sirens, and construction, increased depressive states.

“The results suggest that it may be worthwhile to investigate the targeted use of natural sounds such as birdsong in a clinical setting – for example, in hospital waiting rooms or in psychiatric settings,” study investigator Emil Stobbe, MSc, a predoctoral fellow at the Max Planck Institute for Human Development, Berlin, said in an interview.

“If someone is seeking an easily accessible intervention to lower distress, listening to an audio clip of birds singing might be a great option,” he added.

The study was published online in Scientific Reports.
 

Nature’s calming effect

The aim of the research was “to investigate how the physical environment impact brain and mental health,” Mr. Stobbe said.

Mr. Stobbe said that there is significantly more research examining visual properties of the physical environment but that the auditory domain is not as well researched, although, he added, that the beneficial effects of interactions with nature are “well studied.”

He noted that anxiety and paranoia can be experienced by many individuals even though they may be unaware that they are experiencing these states.

“We wanted to investigate if the beneficial effects of nature can also exert their impact on these states. In theory, birds can be representational for natural and vital environment, which, in turn, transfer the positive effects of nature on birdsong listeners,” he said.

A previous study compared nature versus city soundscape conditions and showed that the nature soundscape improved participants’ cognitive performance but did not improve mood. The present study added diversity to the soundscapes and focused not only on cognition and general mood but also on state paranoia, “which can be measured in a change-sensitive manner” and “has been shown to increase in response to traffic noise.”

The researchers hypothesized that birdsong would have a greater beneficial effect on mood and paranoia and on cognitive performance compared with traffic noise. They also investigated whether greater versus lower diversity of bird species or noise sources within the soundscapes “would be a relevant factor modulating the effects.”

The researchers recruited participants (n = 295) from a crowdsourcing platform. Participants’ mean age was late 20s (standard deviations ranged from 6.30 to 7.72), with a greater proportion of male versus female participants.

To be included, participants were required to have no history of mental illness, hearing difficulties, substance/drug intake, or suicidal thoughts/tendencies.

The outcomes of interest (mood, paranoia, cognitive performance) were measured before and after soundscape exposure and each soundscape had a low- versus high-diversity version. This resulted in several analyses that compared two types of sounds (birdsongs vs. traffic noise) x two levels of diversity (low vs. high diversity) and two time points (pre- vs. post exposure).

The exposure to sounds lasted for 6 minutes, after which they were asked to report (on a 0-100 visual scale) how diverse/monotone, beautiful, and pleasant they perceived the soundscape to be.
 

Reduction in depressive symptoms

Participants were divided into four groups: low-diversity traffic noise soundscape (n = 83), high-diversity traffic noise soundscape (n = 60), low-diversity birdsong soundscape (n = 63), and high-diversity birdsong soundscape (n = 80)

In addition to listening to the sounds, participants completed questionnaires measuring mood (depression and anxiety) and paranoia as well as a test of digit span cognitive performance (both the forward and the backward versions).

The type, diversity, and type x diversity all revealed significant effect sizes (F[3, 276] = 78.6; P < .001; eta-squared = 0.461; F[3, 276] = 3.16; P = .025; eta-squared = 0.033; and F[3, 276] = 2.66; P = .028, respectively), “suggesting that all of these factors, as well as their interaction, had a significant impact on the perception of soundscapes (that is, ratings on monotony/diversity, beauty, and pleasantness).”

A post hoc examination showed that depressive symptoms significantly increased within the low- and high-diversity urban soundscapes but decreased significantly in the high-diversity birdsong soundscapes (T[1, 60] = –2.57; P = .012; d = –0.29).

For anxiety, the post hoc within-group analyses found no effects within low- and high-diversity traffic noise conditions (T[1, 82] = –1.37; P = .174; d = –0.15 and T[1, 68] = 0.49; P = .629; d = 0.06, respectively). By contrast, there were significant declines in both birdsong conditions (low diversity: T[1, 62] = –6.13; P < .001; d = –0.77; high diversity: T[1, 60] = –6.32; P < .001; d =  –0.70).

Similarly, there were no changes in participants with paranoia when they listened to either low- or high-diversity traffic noises (T[1, 82] = –0.55; P = .583; d = –0.06 and T[1, 68] = 0.67; P = .507; d = 0.08, respectively). On the other hand, both birdsong conditions yielded reductions in paranoia (low diversity: T[1, 62] = –5.90; P < .001; d = –0.74; high diversity: T[1, 60] =  –4.11; P < .001; d = –0.46).

None of the soundscapes had any effect on cognition.

“In theory, birds can be representational for natural and vital environments which, in turn, transfer the positive effects of nature on birdsong listeners,” said Mr. Stobbe.

“Taken together, the findings of the current study provide another facet of why interactions with nature can be beneficial for our mental health, and it is highly important to preserve nature,” he added.

Mr. Stobbe said that future research should focus on investigating mixed soundscapes including examining whether the presence of natural sounds in urban settings lower stressors such as traffic noise.
 

An understudied area

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness called the study “interesting but limited.”

Dr. Duckworth, who was not involved in the research said that the “benefits of nature are understudied” and agreed with the investigators that it is potentially important to study the use of birdsongs in psychiatric facilities. “Future studies could also correlate the role of birdsong with the mental health benefits/aspects of ‘being in nature,’ which has been found to have some effect.”

Open Access funding was enabled and organized by Projekt DEAL. The authors and Dr. Duckworth declared no competing interests.

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

One in 5. It almost seems unimaginable that this is the real number of people who are struggling with long COVID, especially considering how many people in the United States have had COVID-19 at this point (more than 96 million). Yet I continue to hear of people who are struggling, and we continue to see a flood of people in the long COVID clinic. It isn’t over, and long COVID is the new pandemic.

Even more unimaginable at this time is that it’s happening to me. I’ve experienced not only the disabling effects of long COVID, but I’ve also seen, firsthand, the frustration of navigating diagnosis and treatment. It’s given me a taste of what millions of other patients are going through.
 

Vaxxed, masked, and (too) relaxed

I caught COVID-19 (probably Omicron BA.5) that presented as sniffles, making me think it was probably just allergies. However, my resting heart rate was up on my Garmin watch, so of course I got tested and was positive.

With my symptoms virtually nonexistent, it seemed, at the time, merely an inconvenience, because I was forced to isolate away from family and friends, who all stayed negative.

But 2 weeks later, I began to have urticaria – hives – after physical exertion. Did that mean my mast cells were angry? There’s some evidence these immune cells become overactivated in some patients with COVID. Next, I began to experience lightheadedness and the rapid heartbeat of tachycardia. The tachycardia was especially bad any time I physically exerted myself, including on a walk. Imagine me – a lover of all bargain shopping – cutting short a trip to the outlet mall on a particularly bad day when my heart rate was 140 after taking just a few steps. This was orthostatic intolerance.

Then came the severe worsening of my migraines – which are often vestibular, making me nauseated and dizzy on top of the throbbing.

I was of course familiar with these symptoms, as professor and chair of the department of rehabilitation medicine at the Joe R. and Teresa Lozano Long School of Medicine at University of Texas Health Science Center, San Antonio. I developed a post-COVID recovery clinic to help patients.

So I knew about postexertional malaise (PEM) and postexertional symptom exacerbation (PESE), but I was now experiencing these distressing symptoms firsthand.

Clinicians really need to look for this cardinal sign of long COVID as well as evidence of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). ME/CFS is marked by exacerbation of fatigue or symptoms after an activity that could previously be done without these aftereffects. In my case, as an All-American Masters miler with several marathons under my belt, running 5 miles is a walk in the park. But now, I pay for those 5 miles for the rest of the day on the couch or with palpitations, dizziness, and fatigue the following day. Busy clinic day full of procedures? I would have to be sitting by the end of it. Bed by 9 PM was not always early enough.
 

Becoming a statistic

Here I am, one of the leading experts in the country on caring for people with long COVID, featured in the national news and having testified in front of Congress, and now I am part of that lived experience. Me – a healthy athlete, with no comorbidities, a normal BMI, vaccinated and boosted, and after an almost asymptomatic bout of COVID-19, a victim to long COVID.

You just never know how your body is going to react. Neuroinflammation occurred in studies with mice with mild respiratory COVID and could be happening to me. I did not want a chronic immune-mediated vasculopathy.

So, I did what any other hyperaware physician-researcher would do. I enrolled in the RECOVER trial – a study my own institution is taking part in and one that I recommend to my own patients.

I also decided that I need to access care and not just ignore my symptoms or try to treat them myself.

That’s when things got difficult. There was a wait of at least a month to see my primary care provider – but I was able to use my privileged position as a physician to get in sooner.

My provider said that she had limited knowledge of long COVID, and she hesitated to order some of the tests and treatments that I recommended because they were not yet considered standard of care. I can understand the hesitation. It is engrained in medical education to follow evidence based on the highest-quality research studies. We are slowly learning more about long COVID, but acknowledging the learning curve offers little to patients who need help now.

This has made me realize that we cannot wait on an evidence-based approach – which can take decades to develop – while people are suffering. And it’s important that everyone on the front line learn about some of the manifestations and disease management of long COVID.

I left this first physician visit feeling more defeated than anything and decided to try to push through. That, I quickly realized, was not the right thing to do.

So again, after a couple of significant crashes and days of severe migraines, I phoned a friend: Ratna Bhavaraju-Sanka, MD, the amazing neurologist who treats patients with long COVID alongside me. She squeezed me in on a non-clinic day. Again, I had the privilege to see a specialist most people wait half a year to see. I was diagnosed with both autonomic dysfunction and intractable migraine.

She ordered some intravenous fluids and IV magnesium that would probably help both. But then another obstacle arose. My institution’s infusion center is focused on patients with cancer, and I was unable to schedule treatments there.

Luckily, I knew about the concierge mobile IV hydration therapy companies that come to your house – mostly offering a hangover treatment service. And I am thankful that I had the health literacy and financial ability to pay for some fluids at home.

On another particularly bad day, I phoned other friends – higher-ups at the hospital – who expedited a slot at the hospital infusion center and approval for the IV magnesium.

Thanks to my access, knowledge, and other privileges, I got fairly quick if imperfect care, enrolled in a research trial, and received medications. I knew to pace myself. The vast majority of others with long COVID lack these advantages.
 

The patient with long COVID

Things I have learned that others can learn, too:

• Acknowledge and recognize that long COVID is a disease that is affecting 1 in 5 Americans who catch COVID. Many look completely “normal on the outside.” Please listen to your patients.
• Autonomic dysfunction is a common manifestation of long COVID. A 10-minute stand test goes a long way in diagnosing this condition, from the American Academy of Physical Medicine and Rehabilitation. It is not just anxiety.
• “That’s only in research” is dismissive and harmful. Think outside the box. Follow guidelines. Consider encouraging patients to sign up for trials.
• Screen for PEM/PESE and teach your patients to pace themselves, because pushing through it or doing graded exercises will be harmful.
• We need to train more physicians to treat postacute sequelae of SARS-CoV-2 infection () and other postinfectious conditions, such as ME/CFS.

If long COVID is hard for physicians to understand and deal with, imagine how difficult it is for patients with no expertise in this area.

It is exponentially harder for those with fewer resources, time, and health literacy. My lived experience with long COVID has shown me that being a patient is never easy. You put your body and fate into the hands of trusted professionals and expect validation and assistance, not gaslighting or gatekeeping.

Along with millions of others, I am tired of waiting.

Dr. Gutierrez is Professor and Distinguished Chair, department of rehabilitation medicine, University of Texas Health Science Center at San Antonio. She reported receiving honoraria for lecturing on long COVID and receiving a research grant from Co-PI for the NIH RECOVER trial.

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

One in 5. It almost seems unimaginable that this is the real number of people who are struggling with long COVID, especially considering how many people in the United States have had COVID-19 at this point (more than 96 million). Yet I continue to hear of people who are struggling, and we continue to see a flood of people in the long COVID clinic. It isn’t over, and long COVID is the new pandemic.

Even more unimaginable at this time is that it’s happening to me. I’ve experienced not only the disabling effects of long COVID, but I’ve also seen, firsthand, the frustration of navigating diagnosis and treatment. It’s given me a taste of what millions of other patients are going through.
 

Vaxxed, masked, and (too) relaxed

I caught COVID-19 (probably Omicron BA.5) that presented as sniffles, making me think it was probably just allergies. However, my resting heart rate was up on my Garmin watch, so of course I got tested and was positive.

With my symptoms virtually nonexistent, it seemed, at the time, merely an inconvenience, because I was forced to isolate away from family and friends, who all stayed negative.

But 2 weeks later, I began to have urticaria – hives – after physical exertion. Did that mean my mast cells were angry? There’s some evidence these immune cells become overactivated in some patients with COVID. Next, I began to experience lightheadedness and the rapid heartbeat of tachycardia. The tachycardia was especially bad any time I physically exerted myself, including on a walk. Imagine me – a lover of all bargain shopping – cutting short a trip to the outlet mall on a particularly bad day when my heart rate was 140 after taking just a few steps. This was orthostatic intolerance.

Then came the severe worsening of my migraines – which are often vestibular, making me nauseated and dizzy on top of the throbbing.

I was of course familiar with these symptoms, as professor and chair of the department of rehabilitation medicine at the Joe R. and Teresa Lozano Long School of Medicine at University of Texas Health Science Center, San Antonio. I developed a post-COVID recovery clinic to help patients.

So I knew about postexertional malaise (PEM) and postexertional symptom exacerbation (PESE), but I was now experiencing these distressing symptoms firsthand.

Clinicians really need to look for this cardinal sign of long COVID as well as evidence of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). ME/CFS is marked by exacerbation of fatigue or symptoms after an activity that could previously be done without these aftereffects. In my case, as an All-American Masters miler with several marathons under my belt, running 5 miles is a walk in the park. But now, I pay for those 5 miles for the rest of the day on the couch or with palpitations, dizziness, and fatigue the following day. Busy clinic day full of procedures? I would have to be sitting by the end of it. Bed by 9 PM was not always early enough.
 

Becoming a statistic

Here I am, one of the leading experts in the country on caring for people with long COVID, featured in the national news and having testified in front of Congress, and now I am part of that lived experience. Me – a healthy athlete, with no comorbidities, a normal BMI, vaccinated and boosted, and after an almost asymptomatic bout of COVID-19, a victim to long COVID.

You just never know how your body is going to react. Neuroinflammation occurred in studies with mice with mild respiratory COVID and could be happening to me. I did not want a chronic immune-mediated vasculopathy.

So, I did what any other hyperaware physician-researcher would do. I enrolled in the RECOVER trial – a study my own institution is taking part in and one that I recommend to my own patients.

I also decided that I need to access care and not just ignore my symptoms or try to treat them myself.

That’s when things got difficult. There was a wait of at least a month to see my primary care provider – but I was able to use my privileged position as a physician to get in sooner.

My provider said that she had limited knowledge of long COVID, and she hesitated to order some of the tests and treatments that I recommended because they were not yet considered standard of care. I can understand the hesitation. It is engrained in medical education to follow evidence based on the highest-quality research studies. We are slowly learning more about long COVID, but acknowledging the learning curve offers little to patients who need help now.

This has made me realize that we cannot wait on an evidence-based approach – which can take decades to develop – while people are suffering. And it’s important that everyone on the front line learn about some of the manifestations and disease management of long COVID.

I left this first physician visit feeling more defeated than anything and decided to try to push through. That, I quickly realized, was not the right thing to do.

So again, after a couple of significant crashes and days of severe migraines, I phoned a friend: Ratna Bhavaraju-Sanka, MD, the amazing neurologist who treats patients with long COVID alongside me. She squeezed me in on a non-clinic day. Again, I had the privilege to see a specialist most people wait half a year to see. I was diagnosed with both autonomic dysfunction and intractable migraine.

She ordered some intravenous fluids and IV magnesium that would probably help both. But then another obstacle arose. My institution’s infusion center is focused on patients with cancer, and I was unable to schedule treatments there.

Luckily, I knew about the concierge mobile IV hydration therapy companies that come to your house – mostly offering a hangover treatment service. And I am thankful that I had the health literacy and financial ability to pay for some fluids at home.

On another particularly bad day, I phoned other friends – higher-ups at the hospital – who expedited a slot at the hospital infusion center and approval for the IV magnesium.

Thanks to my access, knowledge, and other privileges, I got fairly quick if imperfect care, enrolled in a research trial, and received medications. I knew to pace myself. The vast majority of others with long COVID lack these advantages.
 

The patient with long COVID

Things I have learned that others can learn, too:

• Acknowledge and recognize that long COVID is a disease that is affecting 1 in 5 Americans who catch COVID. Many look completely “normal on the outside.” Please listen to your patients.
• Autonomic dysfunction is a common manifestation of long COVID. A 10-minute stand test goes a long way in diagnosing this condition, from the American Academy of Physical Medicine and Rehabilitation. It is not just anxiety.
• “That’s only in research” is dismissive and harmful. Think outside the box. Follow guidelines. Consider encouraging patients to sign up for trials.
• Screen for PEM/PESE and teach your patients to pace themselves, because pushing through it or doing graded exercises will be harmful.
• We need to train more physicians to treat postacute sequelae of SARS-CoV-2 infection () and other postinfectious conditions, such as ME/CFS.

If long COVID is hard for physicians to understand and deal with, imagine how difficult it is for patients with no expertise in this area.

It is exponentially harder for those with fewer resources, time, and health literacy. My lived experience with long COVID has shown me that being a patient is never easy. You put your body and fate into the hands of trusted professionals and expect validation and assistance, not gaslighting or gatekeeping.

Along with millions of others, I am tired of waiting.

Dr. Gutierrez is Professor and Distinguished Chair, department of rehabilitation medicine, University of Texas Health Science Center at San Antonio. She reported receiving honoraria for lecturing on long COVID and receiving a research grant from Co-PI for the NIH RECOVER trial.

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

One in 5. It almost seems unimaginable that this is the real number of people who are struggling with long COVID, especially considering how many people in the United States have had COVID-19 at this point (more than 96 million). Yet I continue to hear of people who are struggling, and we continue to see a flood of people in the long COVID clinic. It isn’t over, and long COVID is the new pandemic.

Even more unimaginable at this time is that it’s happening to me. I’ve experienced not only the disabling effects of long COVID, but I’ve also seen, firsthand, the frustration of navigating diagnosis and treatment. It’s given me a taste of what millions of other patients are going through.
 

Vaxxed, masked, and (too) relaxed

I caught COVID-19 (probably Omicron BA.5) that presented as sniffles, making me think it was probably just allergies. However, my resting heart rate was up on my Garmin watch, so of course I got tested and was positive.

With my symptoms virtually nonexistent, it seemed, at the time, merely an inconvenience, because I was forced to isolate away from family and friends, who all stayed negative.

But 2 weeks later, I began to have urticaria – hives – after physical exertion. Did that mean my mast cells were angry? There’s some evidence these immune cells become overactivated in some patients with COVID. Next, I began to experience lightheadedness and the rapid heartbeat of tachycardia. The tachycardia was especially bad any time I physically exerted myself, including on a walk. Imagine me – a lover of all bargain shopping – cutting short a trip to the outlet mall on a particularly bad day when my heart rate was 140 after taking just a few steps. This was orthostatic intolerance.

Then came the severe worsening of my migraines – which are often vestibular, making me nauseated and dizzy on top of the throbbing.

I was of course familiar with these symptoms, as professor and chair of the department of rehabilitation medicine at the Joe R. and Teresa Lozano Long School of Medicine at University of Texas Health Science Center, San Antonio. I developed a post-COVID recovery clinic to help patients.

So I knew about postexertional malaise (PEM) and postexertional symptom exacerbation (PESE), but I was now experiencing these distressing symptoms firsthand.

Clinicians really need to look for this cardinal sign of long COVID as well as evidence of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). ME/CFS is marked by exacerbation of fatigue or symptoms after an activity that could previously be done without these aftereffects. In my case, as an All-American Masters miler with several marathons under my belt, running 5 miles is a walk in the park. But now, I pay for those 5 miles for the rest of the day on the couch or with palpitations, dizziness, and fatigue the following day. Busy clinic day full of procedures? I would have to be sitting by the end of it. Bed by 9 PM was not always early enough.
 

Becoming a statistic

Here I am, one of the leading experts in the country on caring for people with long COVID, featured in the national news and having testified in front of Congress, and now I am part of that lived experience. Me – a healthy athlete, with no comorbidities, a normal BMI, vaccinated and boosted, and after an almost asymptomatic bout of COVID-19, a victim to long COVID.

You just never know how your body is going to react. Neuroinflammation occurred in studies with mice with mild respiratory COVID and could be happening to me. I did not want a chronic immune-mediated vasculopathy.

So, I did what any other hyperaware physician-researcher would do. I enrolled in the RECOVER trial – a study my own institution is taking part in and one that I recommend to my own patients.

I also decided that I need to access care and not just ignore my symptoms or try to treat them myself.

That’s when things got difficult. There was a wait of at least a month to see my primary care provider – but I was able to use my privileged position as a physician to get in sooner.

My provider said that she had limited knowledge of long COVID, and she hesitated to order some of the tests and treatments that I recommended because they were not yet considered standard of care. I can understand the hesitation. It is engrained in medical education to follow evidence based on the highest-quality research studies. We are slowly learning more about long COVID, but acknowledging the learning curve offers little to patients who need help now.

This has made me realize that we cannot wait on an evidence-based approach – which can take decades to develop – while people are suffering. And it’s important that everyone on the front line learn about some of the manifestations and disease management of long COVID.

I left this first physician visit feeling more defeated than anything and decided to try to push through. That, I quickly realized, was not the right thing to do.

So again, after a couple of significant crashes and days of severe migraines, I phoned a friend: Ratna Bhavaraju-Sanka, MD, the amazing neurologist who treats patients with long COVID alongside me. She squeezed me in on a non-clinic day. Again, I had the privilege to see a specialist most people wait half a year to see. I was diagnosed with both autonomic dysfunction and intractable migraine.

She ordered some intravenous fluids and IV magnesium that would probably help both. But then another obstacle arose. My institution’s infusion center is focused on patients with cancer, and I was unable to schedule treatments there.

Luckily, I knew about the concierge mobile IV hydration therapy companies that come to your house – mostly offering a hangover treatment service. And I am thankful that I had the health literacy and financial ability to pay for some fluids at home.

On another particularly bad day, I phoned other friends – higher-ups at the hospital – who expedited a slot at the hospital infusion center and approval for the IV magnesium.

Thanks to my access, knowledge, and other privileges, I got fairly quick if imperfect care, enrolled in a research trial, and received medications. I knew to pace myself. The vast majority of others with long COVID lack these advantages.
 

The patient with long COVID

Things I have learned that others can learn, too:

• Acknowledge and recognize that long COVID is a disease that is affecting 1 in 5 Americans who catch COVID. Many look completely “normal on the outside.” Please listen to your patients.
• Autonomic dysfunction is a common manifestation of long COVID. A 10-minute stand test goes a long way in diagnosing this condition, from the American Academy of Physical Medicine and Rehabilitation. It is not just anxiety.
• “That’s only in research” is dismissive and harmful. Think outside the box. Follow guidelines. Consider encouraging patients to sign up for trials.
• Screen for PEM/PESE and teach your patients to pace themselves, because pushing through it or doing graded exercises will be harmful.
• We need to train more physicians to treat postacute sequelae of SARS-CoV-2 infection () and other postinfectious conditions, such as ME/CFS.

If long COVID is hard for physicians to understand and deal with, imagine how difficult it is for patients with no expertise in this area.

It is exponentially harder for those with fewer resources, time, and health literacy. My lived experience with long COVID has shown me that being a patient is never easy. You put your body and fate into the hands of trusted professionals and expect validation and assistance, not gaslighting or gatekeeping.

Along with millions of others, I am tired of waiting.

Dr. Gutierrez is Professor and Distinguished Chair, department of rehabilitation medicine, University of Texas Health Science Center at San Antonio. She reported receiving honoraria for lecturing on long COVID and receiving a research grant from Co-PI for the NIH RECOVER trial.

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

CHARLOTTE, N.C. – RBX2660 could be a new option for people who experience recurrent, debilitating Clostridioides difficile infections.

Following a standard course of antibiotics, a one-time treatment with RBX2660 was successful for three quarters of participants at 8 weeks, according to a new study. It also prevented additional bouts, with 84% of these initial responders remaining free of C. difficile infection at 6 months.

The ongoing phase 3, open-label PUNCH CD3-OLS study expands on clinical trial experience by treating more “real-world” patients. People who might have been excluded from previous research because of comorbidities, such as irritable bowel syndrome, inflammatory bowel disease, and immunosuppression, were included.

The study also placed no limit on the number of previous rounds of C. difficile infections.

“Even when you expand the patient population to make it more generalizable, we’re still seeing both a high cure rate and a high success rate,” Sahil Khanna, MBBS, a gastroenterologist and hepatologist at the Mayo Clinic in Rochester, Minn., said in an interview.

“We also are not seeing any kind of safety signals that can be attributed to this particular product,” he said.

Dr. Khanna presented the findings during the annual meeting of the American College of Gastroenterology, which were also published simultaneously in the journal Drugs. The research by Dr. Khanna and associates received an ACG Outstanding Research Award in the colon category.
 

Study design and results

RBX2660 (Rebyota) is a microbiota-based live biotherapeutic in development from Ferring Pharmaceuticals. The treatment contains human stool collected from prescreened, qualified donors and is prepared according to good manufacturing standards.

After standard-of-care antibiotics and a 72-hour washout period, participants received a single 150-mL dose rectally by enema. RBX2660 is administered by a health care professional.

The median age of study participants was 63 years, with 45% aged 65 years or older, and 70% were women. Overall, 37% of participants had Crohn’s disease and 4% had ulcerative colitis.

At the time of screening, about half of participants had a history of one or two infections with C. difficile, and the remaining half reported three or more episodes.

Of the 402 participants whose outcomes could be analyzed, 75% reported treatment success, meaning no further C. difficile infections at 8 weeks. This was consistent with the 75% of 60 participants free of C. difficile in the interim analysis reported in 2021. Efficacy results were based on a modified intent-to-treat analysis.

Of the 300 participants who responded to RBX2660 at 8 weeks, 262 were followed up to 6 months, with 84% of these reporting no C. difficile recurrence.

“If you succeeded to 8 weeks, there was a high likelihood that you would succeed up to 6 months,” Dr. Khanna said.

For the subset of participants with inflammatory bowel disease, Dr. Khanna noted that the success rates were in the 80% range, which is higher than what is seen in clinic fecal microbiota transplantation programs.
 

Adverse events

Of the participants, 63% reported treatment-emergent adverse events. Most events were mild to moderate in severity, the researchers reported, with diarrhea and abdominal pain being the most common.

“When you look at the treatment-emergent adverse events, it’s important to put them into context in terms of this patient population,” Dr. Khanna said. “This recurrent population has developed underlying gastrointestinal symptoms like abdominal pain, diarrhea, nausea, vomiting, and weight loss.”

Some of these adverse events persist beyond resolution of the C. difficile infection, and the adverse-event profile with RBX2660 is consistent with what is seen following fecal microbiota transplantation, he added.

The serious adverse events “were very, very few,” Dr. Khanna said.

Overall, 11% of participants reported a serious adverse event. The majority were related to the C. difficile infection or an underlying comorbidity, he noted.
 

“Excruciating for patients to deal with”

Traditionally, there could be “some hesitation on the patient’s part [to undergo therapy] just because it’s delivered rectally,” session comoderator Lisa Malter, MD, said in an interview.

However, C. difficile can be “excruciating for patients to deal with,” said Dr. Malter, a gastroenterologist and professor of medicine at New York University Langone Health. They “may be more than willing to take [this agent] because it gets them feeling better.”

“This is a positive adjunct to our current therapies for C. diff in terms of trying to knock it out once a standard course of antibiotics has been administered,” she added.

Currently, people with recurrent C. difficile seek fecal microbiota material from a biobank or from a close friend or loved one.

But Dr. Malter noted that asking someone you know to donate fecal matter for transplantation requires several steps. Donors are screened to make sure they are free of gastrointestinal illness, are not taking any contraindicated medications, and do not have active infection.

Fecal microbiota samples from a biobank are more standardized, but there have been intermittent shutdowns and availability has been limited during the pandemic, she said.

Dr. Malter added that one unanswered question is how much of the colon is covered by therapy delivery via enema compared with colonoscope delivery during fecal microbiota transplantation.

“If it’s delivered colonoscopically, you get the entire colon. In contrast with an enema, you really only hit the left side of the colon,” she said.
 

FDA advisory committee nod

On Sept. 26, the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee reviewed evidence for RBX2660. The committee voted 13 to 4 that data were adequate to support the effectiveness of RBX2660 to reduce the recurrence of C. difficile infection in adults following antibiotic treatment for recurrent infections.

Members also voted 12 to 4, with one abstention, that the data were adequate to support the product’s safety.

The FDA often follows its advisory committee recommendations but is not required to do so.

“The hope would be that this would get through the usual FDA pipeline of an approval in the near future,” Dr. Khanna said.

The study was funded by Ferring Pharmaceuticals. Dr. Khanna reported receiving grant and research funding from Ferring. Dr. Malter reported no relevant financial relationships.

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

CHARLOTTE, N.C. – RBX2660 could be a new option for people who experience recurrent, debilitating Clostridioides difficile infections.

Following a standard course of antibiotics, a one-time treatment with RBX2660 was successful for three quarters of participants at 8 weeks, according to a new study. It also prevented additional bouts, with 84% of these initial responders remaining free of C. difficile infection at 6 months.

The ongoing phase 3, open-label PUNCH CD3-OLS study expands on clinical trial experience by treating more “real-world” patients. People who might have been excluded from previous research because of comorbidities, such as irritable bowel syndrome, inflammatory bowel disease, and immunosuppression, were included.

The study also placed no limit on the number of previous rounds of C. difficile infections.

“Even when you expand the patient population to make it more generalizable, we’re still seeing both a high cure rate and a high success rate,” Sahil Khanna, MBBS, a gastroenterologist and hepatologist at the Mayo Clinic in Rochester, Minn., said in an interview.

“We also are not seeing any kind of safety signals that can be attributed to this particular product,” he said.

Dr. Khanna presented the findings during the annual meeting of the American College of Gastroenterology, which were also published simultaneously in the journal Drugs. The research by Dr. Khanna and associates received an ACG Outstanding Research Award in the colon category.
 

Study design and results

RBX2660 (Rebyota) is a microbiota-based live biotherapeutic in development from Ferring Pharmaceuticals. The treatment contains human stool collected from prescreened, qualified donors and is prepared according to good manufacturing standards.

After standard-of-care antibiotics and a 72-hour washout period, participants received a single 150-mL dose rectally by enema. RBX2660 is administered by a health care professional.

The median age of study participants was 63 years, with 45% aged 65 years or older, and 70% were women. Overall, 37% of participants had Crohn’s disease and 4% had ulcerative colitis.

At the time of screening, about half of participants had a history of one or two infections with C. difficile, and the remaining half reported three or more episodes.

Of the 402 participants whose outcomes could be analyzed, 75% reported treatment success, meaning no further C. difficile infections at 8 weeks. This was consistent with the 75% of 60 participants free of C. difficile in the interim analysis reported in 2021. Efficacy results were based on a modified intent-to-treat analysis.

Of the 300 participants who responded to RBX2660 at 8 weeks, 262 were followed up to 6 months, with 84% of these reporting no C. difficile recurrence.

“If you succeeded to 8 weeks, there was a high likelihood that you would succeed up to 6 months,” Dr. Khanna said.

For the subset of participants with inflammatory bowel disease, Dr. Khanna noted that the success rates were in the 80% range, which is higher than what is seen in clinic fecal microbiota transplantation programs.
 

Adverse events

Of the participants, 63% reported treatment-emergent adverse events. Most events were mild to moderate in severity, the researchers reported, with diarrhea and abdominal pain being the most common.

“When you look at the treatment-emergent adverse events, it’s important to put them into context in terms of this patient population,” Dr. Khanna said. “This recurrent population has developed underlying gastrointestinal symptoms like abdominal pain, diarrhea, nausea, vomiting, and weight loss.”

Some of these adverse events persist beyond resolution of the C. difficile infection, and the adverse-event profile with RBX2660 is consistent with what is seen following fecal microbiota transplantation, he added.

The serious adverse events “were very, very few,” Dr. Khanna said.

Overall, 11% of participants reported a serious adverse event. The majority were related to the C. difficile infection or an underlying comorbidity, he noted.
 

“Excruciating for patients to deal with”

Traditionally, there could be “some hesitation on the patient’s part [to undergo therapy] just because it’s delivered rectally,” session comoderator Lisa Malter, MD, said in an interview.

However, C. difficile can be “excruciating for patients to deal with,” said Dr. Malter, a gastroenterologist and professor of medicine at New York University Langone Health. They “may be more than willing to take [this agent] because it gets them feeling better.”

“This is a positive adjunct to our current therapies for C. diff in terms of trying to knock it out once a standard course of antibiotics has been administered,” she added.

Currently, people with recurrent C. difficile seek fecal microbiota material from a biobank or from a close friend or loved one.

But Dr. Malter noted that asking someone you know to donate fecal matter for transplantation requires several steps. Donors are screened to make sure they are free of gastrointestinal illness, are not taking any contraindicated medications, and do not have active infection.

Fecal microbiota samples from a biobank are more standardized, but there have been intermittent shutdowns and availability has been limited during the pandemic, she said.

Dr. Malter added that one unanswered question is how much of the colon is covered by therapy delivery via enema compared with colonoscope delivery during fecal microbiota transplantation.

“If it’s delivered colonoscopically, you get the entire colon. In contrast with an enema, you really only hit the left side of the colon,” she said.
 

FDA advisory committee nod

On Sept. 26, the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee reviewed evidence for RBX2660. The committee voted 13 to 4 that data were adequate to support the effectiveness of RBX2660 to reduce the recurrence of C. difficile infection in adults following antibiotic treatment for recurrent infections.

Members also voted 12 to 4, with one abstention, that the data were adequate to support the product’s safety.

The FDA often follows its advisory committee recommendations but is not required to do so.

“The hope would be that this would get through the usual FDA pipeline of an approval in the near future,” Dr. Khanna said.

The study was funded by Ferring Pharmaceuticals. Dr. Khanna reported receiving grant and research funding from Ferring. Dr. Malter reported no relevant financial relationships.

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

CHARLOTTE, N.C. – RBX2660 could be a new option for people who experience recurrent, debilitating Clostridioides difficile infections.

Following a standard course of antibiotics, a one-time treatment with RBX2660 was successful for three quarters of participants at 8 weeks, according to a new study. It also prevented additional bouts, with 84% of these initial responders remaining free of C. difficile infection at 6 months.

The ongoing phase 3, open-label PUNCH CD3-OLS study expands on clinical trial experience by treating more “real-world” patients. People who might have been excluded from previous research because of comorbidities, such as irritable bowel syndrome, inflammatory bowel disease, and immunosuppression, were included.

The study also placed no limit on the number of previous rounds of C. difficile infections.

“Even when you expand the patient population to make it more generalizable, we’re still seeing both a high cure rate and a high success rate,” Sahil Khanna, MBBS, a gastroenterologist and hepatologist at the Mayo Clinic in Rochester, Minn., said in an interview.

“We also are not seeing any kind of safety signals that can be attributed to this particular product,” he said.

Dr. Khanna presented the findings during the annual meeting of the American College of Gastroenterology, which were also published simultaneously in the journal Drugs. The research by Dr. Khanna and associates received an ACG Outstanding Research Award in the colon category.
 

Study design and results

RBX2660 (Rebyota) is a microbiota-based live biotherapeutic in development from Ferring Pharmaceuticals. The treatment contains human stool collected from prescreened, qualified donors and is prepared according to good manufacturing standards.

After standard-of-care antibiotics and a 72-hour washout period, participants received a single 150-mL dose rectally by enema. RBX2660 is administered by a health care professional.

The median age of study participants was 63 years, with 45% aged 65 years or older, and 70% were women. Overall, 37% of participants had Crohn’s disease and 4% had ulcerative colitis.

At the time of screening, about half of participants had a history of one or two infections with C. difficile, and the remaining half reported three or more episodes.

Of the 402 participants whose outcomes could be analyzed, 75% reported treatment success, meaning no further C. difficile infections at 8 weeks. This was consistent with the 75% of 60 participants free of C. difficile in the interim analysis reported in 2021. Efficacy results were based on a modified intent-to-treat analysis.

Of the 300 participants who responded to RBX2660 at 8 weeks, 262 were followed up to 6 months, with 84% of these reporting no C. difficile recurrence.

“If you succeeded to 8 weeks, there was a high likelihood that you would succeed up to 6 months,” Dr. Khanna said.

For the subset of participants with inflammatory bowel disease, Dr. Khanna noted that the success rates were in the 80% range, which is higher than what is seen in clinic fecal microbiota transplantation programs.
 

Adverse events

Of the participants, 63% reported treatment-emergent adverse events. Most events were mild to moderate in severity, the researchers reported, with diarrhea and abdominal pain being the most common.

“When you look at the treatment-emergent adverse events, it’s important to put them into context in terms of this patient population,” Dr. Khanna said. “This recurrent population has developed underlying gastrointestinal symptoms like abdominal pain, diarrhea, nausea, vomiting, and weight loss.”

Some of these adverse events persist beyond resolution of the C. difficile infection, and the adverse-event profile with RBX2660 is consistent with what is seen following fecal microbiota transplantation, he added.

The serious adverse events “were very, very few,” Dr. Khanna said.

Overall, 11% of participants reported a serious adverse event. The majority were related to the C. difficile infection or an underlying comorbidity, he noted.
 

“Excruciating for patients to deal with”

Traditionally, there could be “some hesitation on the patient’s part [to undergo therapy] just because it’s delivered rectally,” session comoderator Lisa Malter, MD, said in an interview.

However, C. difficile can be “excruciating for patients to deal with,” said Dr. Malter, a gastroenterologist and professor of medicine at New York University Langone Health. They “may be more than willing to take [this agent] because it gets them feeling better.”

“This is a positive adjunct to our current therapies for C. diff in terms of trying to knock it out once a standard course of antibiotics has been administered,” she added.

Currently, people with recurrent C. difficile seek fecal microbiota material from a biobank or from a close friend or loved one.

But Dr. Malter noted that asking someone you know to donate fecal matter for transplantation requires several steps. Donors are screened to make sure they are free of gastrointestinal illness, are not taking any contraindicated medications, and do not have active infection.

Fecal microbiota samples from a biobank are more standardized, but there have been intermittent shutdowns and availability has been limited during the pandemic, she said.

Dr. Malter added that one unanswered question is how much of the colon is covered by therapy delivery via enema compared with colonoscope delivery during fecal microbiota transplantation.

“If it’s delivered colonoscopically, you get the entire colon. In contrast with an enema, you really only hit the left side of the colon,” she said.
 

FDA advisory committee nod

On Sept. 26, the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee reviewed evidence for RBX2660. The committee voted 13 to 4 that data were adequate to support the effectiveness of RBX2660 to reduce the recurrence of C. difficile infection in adults following antibiotic treatment for recurrent infections.

Members also voted 12 to 4, with one abstention, that the data were adequate to support the product’s safety.

The FDA often follows its advisory committee recommendations but is not required to do so.

“The hope would be that this would get through the usual FDA pipeline of an approval in the near future,” Dr. Khanna said.

The study was funded by Ferring Pharmaceuticals. Dr. Khanna reported receiving grant and research funding from Ferring. Dr. Malter reported no relevant financial relationships.

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