User login
Don’t call them ‘private parts’
This transcript has been edited for clarity.
Today, I’d like to talk about private parts. You know: the genitals, down there.
I hate all of that. I really wish that we can get to a place where we can talk about genitals and sexual health the same way we do about high blood pressure and diabetes. In fact, when a new patient comes in and they get a new diagnosis of diabetes, you spend time explaining to them how their pancreas works. I don’t remember all the details because I’m a urologist. But you explain the details of diabetes, how it works, why therapy is important, and how it’s very important for quality of life.
I say to patients, “You have to know what parts you have in order to figure out how they drive, right?” We want them to drive better.
Let me give you an example. Many men come to see me with complaints of erectile dysfunction. They refuse to take sildenafil and tadalafil (Viagra and Cialis), saying, “Oh my gosh, those are magic pills. I won’t be a man if take them.” We all know that doesn’t make any sense. I explain to them how their penis works: “Your penis is a muscle. The muscle does two things. It contracts and it relaxes, just like your bicep. It’s just that your penis muscle is smooth muscle, which means it responds to fight or flight. It’s on the autonomic nervous system.”
I explain that if the muscle of the penis is relaxed, it fills with blood and expands. It gets big and hard, and it traps the blood. But when the muscles of the penis are contracted, when they are tight, it squeezes out all the blood, like squeezing out a sponge. So the important thing to do if you want to have good erections is to get the muscles to relax. Relaxed muscle increases erections. I get them to understand that sildenafil and tadalafil are phosphodiesterase 5 inhibitors: smooth-muscle relaxants. Instead of saying, “I need to take Viagra or Cialis because I’m broken,” it’s, “Oh hey honey, I need to take my muscle relaxants because my muscles aren’t working the way that they used to.”
In the future, I’ll go into what happens in erectile dysfunction. We’ll go into what can happen with erectile dysfunction and the many reasons why it happens. It’s getting them to understand that if we get the muscles to relax, you will have better erections. This is how the penis works. It’s why the medicine works. The patients will actually try the therapy and they’ll feel so much better about it. They’ll say, “Oh my gosh, this makes so much sense.” They work on their mental muscles to get the muscles of the penis to relax. Understanding anatomy and physiology helps them understand the treatments, which leads to better outcomes.
How about the female side? If a woman comes to see me reporting that she can’t have an orgasm, part of it is education and understanding the anatomy and physiology. The clitoris and the penis are exactly the same thing. The head of the clitoris and the head of the penis are the same. The clitoris has legs that go all the way down to the butt bone. So everyone is sitting on their genitals right now. The butt bones connect to the bottom of the clitoris or the bottom of the penis. They each have legs called crura. When you get patients to understand where their anatomy is and how it functions, they will then understand how to maximize their quality of life.
The clitoris has smooth muscle just like the penis. When that smooth muscle relaxes, it gorges with blood. When you stimulate it, it can lead to orgasm for most people. But, wait a minute. The clitoris is not inside the vagina. It’s outside. It’s behind the labia majora. If you follow the labia minora up, you get to the head of the clitoris. If patients understand that, they then will understand that penetration is not the way the majority of people orgasm.
I love pictures. I show everyone pictures in my office. They help patients to understand why vibration or outside stimulation on the vulva will allow orgasm to happen. And so instead of patients coming in saying, “I’m broken, I can’t orgasm from penetration,” or, “Dr. Rubin, I’m broken because I can’t get erections,” getting them to understand the anatomy and physiology helps them understand the treatment.
As we go forward, I’ll talk more about anatomy and physiology and how to increase the sexual health of our patients. For now though, please stop calling them private parts. Please use your understanding of anatomy and physiology to educate your patients to have better sexual health and higher quality of life. You may be the only clinician to ever do so, and it will make their life so much better.
Dr. Rubin is an assistant clinical professor, department of urology, at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Today, I’d like to talk about private parts. You know: the genitals, down there.
I hate all of that. I really wish that we can get to a place where we can talk about genitals and sexual health the same way we do about high blood pressure and diabetes. In fact, when a new patient comes in and they get a new diagnosis of diabetes, you spend time explaining to them how their pancreas works. I don’t remember all the details because I’m a urologist. But you explain the details of diabetes, how it works, why therapy is important, and how it’s very important for quality of life.
I say to patients, “You have to know what parts you have in order to figure out how they drive, right?” We want them to drive better.
Let me give you an example. Many men come to see me with complaints of erectile dysfunction. They refuse to take sildenafil and tadalafil (Viagra and Cialis), saying, “Oh my gosh, those are magic pills. I won’t be a man if take them.” We all know that doesn’t make any sense. I explain to them how their penis works: “Your penis is a muscle. The muscle does two things. It contracts and it relaxes, just like your bicep. It’s just that your penis muscle is smooth muscle, which means it responds to fight or flight. It’s on the autonomic nervous system.”
I explain that if the muscle of the penis is relaxed, it fills with blood and expands. It gets big and hard, and it traps the blood. But when the muscles of the penis are contracted, when they are tight, it squeezes out all the blood, like squeezing out a sponge. So the important thing to do if you want to have good erections is to get the muscles to relax. Relaxed muscle increases erections. I get them to understand that sildenafil and tadalafil are phosphodiesterase 5 inhibitors: smooth-muscle relaxants. Instead of saying, “I need to take Viagra or Cialis because I’m broken,” it’s, “Oh hey honey, I need to take my muscle relaxants because my muscles aren’t working the way that they used to.”
In the future, I’ll go into what happens in erectile dysfunction. We’ll go into what can happen with erectile dysfunction and the many reasons why it happens. It’s getting them to understand that if we get the muscles to relax, you will have better erections. This is how the penis works. It’s why the medicine works. The patients will actually try the therapy and they’ll feel so much better about it. They’ll say, “Oh my gosh, this makes so much sense.” They work on their mental muscles to get the muscles of the penis to relax. Understanding anatomy and physiology helps them understand the treatments, which leads to better outcomes.
How about the female side? If a woman comes to see me reporting that she can’t have an orgasm, part of it is education and understanding the anatomy and physiology. The clitoris and the penis are exactly the same thing. The head of the clitoris and the head of the penis are the same. The clitoris has legs that go all the way down to the butt bone. So everyone is sitting on their genitals right now. The butt bones connect to the bottom of the clitoris or the bottom of the penis. They each have legs called crura. When you get patients to understand where their anatomy is and how it functions, they will then understand how to maximize their quality of life.
The clitoris has smooth muscle just like the penis. When that smooth muscle relaxes, it gorges with blood. When you stimulate it, it can lead to orgasm for most people. But, wait a minute. The clitoris is not inside the vagina. It’s outside. It’s behind the labia majora. If you follow the labia minora up, you get to the head of the clitoris. If patients understand that, they then will understand that penetration is not the way the majority of people orgasm.
I love pictures. I show everyone pictures in my office. They help patients to understand why vibration or outside stimulation on the vulva will allow orgasm to happen. And so instead of patients coming in saying, “I’m broken, I can’t orgasm from penetration,” or, “Dr. Rubin, I’m broken because I can’t get erections,” getting them to understand the anatomy and physiology helps them understand the treatment.
As we go forward, I’ll talk more about anatomy and physiology and how to increase the sexual health of our patients. For now though, please stop calling them private parts. Please use your understanding of anatomy and physiology to educate your patients to have better sexual health and higher quality of life. You may be the only clinician to ever do so, and it will make their life so much better.
Dr. Rubin is an assistant clinical professor, department of urology, at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Today, I’d like to talk about private parts. You know: the genitals, down there.
I hate all of that. I really wish that we can get to a place where we can talk about genitals and sexual health the same way we do about high blood pressure and diabetes. In fact, when a new patient comes in and they get a new diagnosis of diabetes, you spend time explaining to them how their pancreas works. I don’t remember all the details because I’m a urologist. But you explain the details of diabetes, how it works, why therapy is important, and how it’s very important for quality of life.
I say to patients, “You have to know what parts you have in order to figure out how they drive, right?” We want them to drive better.
Let me give you an example. Many men come to see me with complaints of erectile dysfunction. They refuse to take sildenafil and tadalafil (Viagra and Cialis), saying, “Oh my gosh, those are magic pills. I won’t be a man if take them.” We all know that doesn’t make any sense. I explain to them how their penis works: “Your penis is a muscle. The muscle does two things. It contracts and it relaxes, just like your bicep. It’s just that your penis muscle is smooth muscle, which means it responds to fight or flight. It’s on the autonomic nervous system.”
I explain that if the muscle of the penis is relaxed, it fills with blood and expands. It gets big and hard, and it traps the blood. But when the muscles of the penis are contracted, when they are tight, it squeezes out all the blood, like squeezing out a sponge. So the important thing to do if you want to have good erections is to get the muscles to relax. Relaxed muscle increases erections. I get them to understand that sildenafil and tadalafil are phosphodiesterase 5 inhibitors: smooth-muscle relaxants. Instead of saying, “I need to take Viagra or Cialis because I’m broken,” it’s, “Oh hey honey, I need to take my muscle relaxants because my muscles aren’t working the way that they used to.”
In the future, I’ll go into what happens in erectile dysfunction. We’ll go into what can happen with erectile dysfunction and the many reasons why it happens. It’s getting them to understand that if we get the muscles to relax, you will have better erections. This is how the penis works. It’s why the medicine works. The patients will actually try the therapy and they’ll feel so much better about it. They’ll say, “Oh my gosh, this makes so much sense.” They work on their mental muscles to get the muscles of the penis to relax. Understanding anatomy and physiology helps them understand the treatments, which leads to better outcomes.
How about the female side? If a woman comes to see me reporting that she can’t have an orgasm, part of it is education and understanding the anatomy and physiology. The clitoris and the penis are exactly the same thing. The head of the clitoris and the head of the penis are the same. The clitoris has legs that go all the way down to the butt bone. So everyone is sitting on their genitals right now. The butt bones connect to the bottom of the clitoris or the bottom of the penis. They each have legs called crura. When you get patients to understand where their anatomy is and how it functions, they will then understand how to maximize their quality of life.
The clitoris has smooth muscle just like the penis. When that smooth muscle relaxes, it gorges with blood. When you stimulate it, it can lead to orgasm for most people. But, wait a minute. The clitoris is not inside the vagina. It’s outside. It’s behind the labia majora. If you follow the labia minora up, you get to the head of the clitoris. If patients understand that, they then will understand that penetration is not the way the majority of people orgasm.
I love pictures. I show everyone pictures in my office. They help patients to understand why vibration or outside stimulation on the vulva will allow orgasm to happen. And so instead of patients coming in saying, “I’m broken, I can’t orgasm from penetration,” or, “Dr. Rubin, I’m broken because I can’t get erections,” getting them to understand the anatomy and physiology helps them understand the treatment.
As we go forward, I’ll talk more about anatomy and physiology and how to increase the sexual health of our patients. For now though, please stop calling them private parts. Please use your understanding of anatomy and physiology to educate your patients to have better sexual health and higher quality of life. You may be the only clinician to ever do so, and it will make their life so much better.
Dr. Rubin is an assistant clinical professor, department of urology, at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.
A version of this article first appeared on Medscape.com.
Social media use may promote depression in pregnancy
Depressive symptoms among pregnant women have risen in recent years, but the potential impact of social media use on depression in pregnancy has not been well studied, wrote Lotte Muskens, a PhD candidate at Tilburg (the Netherlands) University and colleagues.
In a study published in the Journal of Affective Disorders, the researchers surveyed 697 pregnant women aged 19-42 years who were part of a larger longitudinal prospective study (the Brabant Study) in the Netherlands. The mean age of the participants was 31 years; 96% were employed, 99% had a partner, and 71% had a bachelor’s degree or higher. Depressive symptoms were assessed at 12, 20, and 28 weeks of pregnancy using the Dutch version of the 10-item Edinburgh Depression Scale (EDS).
The researchers categorized the participants into trajectories of depressive symptoms during pregnancy, with 489 identified as low stable (mean EDS scores 2.8-3.0), 183 as intermediate stable (mean EDS scores 8.4-8.8), and 25 as high stable (mean EDS scores 15.1-16.9).
Problematic SMU was identified using the six-item Bergen Social Media Addiction Scale (BSMAS) at 12 weeks of pregnancy; scores ranged from 6 to 30, with higher scores representing more problematic SMU.
The mean BSMAS scores were 9.0, 10.7, and 12.6 for the low-stable, intermediate-stable, and high-stable depression groups, respectively.
Data on social media use (SMU) were collected at 12 weeks of pregnancy. Social media was defined as common platforms including Facebook, Instagram, LinkedIn, Pinterest, Twitter, and YouTube.
SMU was defined in terms of intensity, measured by time and frequency. Time was measured by asking participants to list how many hours per day they used social media on a scale of 1 (no use of social media) to 9 (7 or more hours per day). Frequency was measured by asking how often participants visited the various social media platforms, on a scale of 1 (no use of social media) to 7 (five or more visits per day). Overall, the participants averaged 1.6 hours per day and 19.5 visits per week on SMU.
Increased time and frequency of SMU was significantly associated with increased odds of being in the high-stable group, compared with the low-stable group in an adjusted analysis (odds ratios, 1.51 and 1.05, respectively; P = .017 and P = .019, respectively).
In addition, problematic SMU (as defined by higher BSMAS scores) remained significantly associated with increased odds of belonging to the intermediate-stable or high-stable classes in an adjusted analysis (odds ratios, 1.17 and 1.31; P < .001 for both).
“While our results suggest that SMU can have negative consequences for pregnant women’s mental wellbeing, it is important to note that SMU during pregnancy may also be helpful for some pregnant women,” as many women, especially first-time mothers, find information and support through social media, the researchers wrote in their discussion.
The findings were limited by several factors, including the variation in group sizes for depressive symptoms, reliance on self-reports, and the collection of data during the COVID-19 pandemic, which may have affected the results, the researchers noted.
However, the results were strengthened by the large sample size and longitudinal design that allowed measurement of trajectories. More research is needed to determine causal relationships, but the data indicate an association between higher levels of depression during pregnancy and more intense and problematic SMU use, and health care providers should discuss SMU in addition to other risk factors for depression in pregnant women, the researchers concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Depressive symptoms among pregnant women have risen in recent years, but the potential impact of social media use on depression in pregnancy has not been well studied, wrote Lotte Muskens, a PhD candidate at Tilburg (the Netherlands) University and colleagues.
In a study published in the Journal of Affective Disorders, the researchers surveyed 697 pregnant women aged 19-42 years who were part of a larger longitudinal prospective study (the Brabant Study) in the Netherlands. The mean age of the participants was 31 years; 96% were employed, 99% had a partner, and 71% had a bachelor’s degree or higher. Depressive symptoms were assessed at 12, 20, and 28 weeks of pregnancy using the Dutch version of the 10-item Edinburgh Depression Scale (EDS).
The researchers categorized the participants into trajectories of depressive symptoms during pregnancy, with 489 identified as low stable (mean EDS scores 2.8-3.0), 183 as intermediate stable (mean EDS scores 8.4-8.8), and 25 as high stable (mean EDS scores 15.1-16.9).
Problematic SMU was identified using the six-item Bergen Social Media Addiction Scale (BSMAS) at 12 weeks of pregnancy; scores ranged from 6 to 30, with higher scores representing more problematic SMU.
The mean BSMAS scores were 9.0, 10.7, and 12.6 for the low-stable, intermediate-stable, and high-stable depression groups, respectively.
Data on social media use (SMU) were collected at 12 weeks of pregnancy. Social media was defined as common platforms including Facebook, Instagram, LinkedIn, Pinterest, Twitter, and YouTube.
SMU was defined in terms of intensity, measured by time and frequency. Time was measured by asking participants to list how many hours per day they used social media on a scale of 1 (no use of social media) to 9 (7 or more hours per day). Frequency was measured by asking how often participants visited the various social media platforms, on a scale of 1 (no use of social media) to 7 (five or more visits per day). Overall, the participants averaged 1.6 hours per day and 19.5 visits per week on SMU.
Increased time and frequency of SMU was significantly associated with increased odds of being in the high-stable group, compared with the low-stable group in an adjusted analysis (odds ratios, 1.51 and 1.05, respectively; P = .017 and P = .019, respectively).
In addition, problematic SMU (as defined by higher BSMAS scores) remained significantly associated with increased odds of belonging to the intermediate-stable or high-stable classes in an adjusted analysis (odds ratios, 1.17 and 1.31; P < .001 for both).
“While our results suggest that SMU can have negative consequences for pregnant women’s mental wellbeing, it is important to note that SMU during pregnancy may also be helpful for some pregnant women,” as many women, especially first-time mothers, find information and support through social media, the researchers wrote in their discussion.
The findings were limited by several factors, including the variation in group sizes for depressive symptoms, reliance on self-reports, and the collection of data during the COVID-19 pandemic, which may have affected the results, the researchers noted.
However, the results were strengthened by the large sample size and longitudinal design that allowed measurement of trajectories. More research is needed to determine causal relationships, but the data indicate an association between higher levels of depression during pregnancy and more intense and problematic SMU use, and health care providers should discuss SMU in addition to other risk factors for depression in pregnant women, the researchers concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Depressive symptoms among pregnant women have risen in recent years, but the potential impact of social media use on depression in pregnancy has not been well studied, wrote Lotte Muskens, a PhD candidate at Tilburg (the Netherlands) University and colleagues.
In a study published in the Journal of Affective Disorders, the researchers surveyed 697 pregnant women aged 19-42 years who were part of a larger longitudinal prospective study (the Brabant Study) in the Netherlands. The mean age of the participants was 31 years; 96% were employed, 99% had a partner, and 71% had a bachelor’s degree or higher. Depressive symptoms were assessed at 12, 20, and 28 weeks of pregnancy using the Dutch version of the 10-item Edinburgh Depression Scale (EDS).
The researchers categorized the participants into trajectories of depressive symptoms during pregnancy, with 489 identified as low stable (mean EDS scores 2.8-3.0), 183 as intermediate stable (mean EDS scores 8.4-8.8), and 25 as high stable (mean EDS scores 15.1-16.9).
Problematic SMU was identified using the six-item Bergen Social Media Addiction Scale (BSMAS) at 12 weeks of pregnancy; scores ranged from 6 to 30, with higher scores representing more problematic SMU.
The mean BSMAS scores were 9.0, 10.7, and 12.6 for the low-stable, intermediate-stable, and high-stable depression groups, respectively.
Data on social media use (SMU) were collected at 12 weeks of pregnancy. Social media was defined as common platforms including Facebook, Instagram, LinkedIn, Pinterest, Twitter, and YouTube.
SMU was defined in terms of intensity, measured by time and frequency. Time was measured by asking participants to list how many hours per day they used social media on a scale of 1 (no use of social media) to 9 (7 or more hours per day). Frequency was measured by asking how often participants visited the various social media platforms, on a scale of 1 (no use of social media) to 7 (five or more visits per day). Overall, the participants averaged 1.6 hours per day and 19.5 visits per week on SMU.
Increased time and frequency of SMU was significantly associated with increased odds of being in the high-stable group, compared with the low-stable group in an adjusted analysis (odds ratios, 1.51 and 1.05, respectively; P = .017 and P = .019, respectively).
In addition, problematic SMU (as defined by higher BSMAS scores) remained significantly associated with increased odds of belonging to the intermediate-stable or high-stable classes in an adjusted analysis (odds ratios, 1.17 and 1.31; P < .001 for both).
“While our results suggest that SMU can have negative consequences for pregnant women’s mental wellbeing, it is important to note that SMU during pregnancy may also be helpful for some pregnant women,” as many women, especially first-time mothers, find information and support through social media, the researchers wrote in their discussion.
The findings were limited by several factors, including the variation in group sizes for depressive symptoms, reliance on self-reports, and the collection of data during the COVID-19 pandemic, which may have affected the results, the researchers noted.
However, the results were strengthened by the large sample size and longitudinal design that allowed measurement of trajectories. More research is needed to determine causal relationships, but the data indicate an association between higher levels of depression during pregnancy and more intense and problematic SMU use, and health care providers should discuss SMU in addition to other risk factors for depression in pregnant women, the researchers concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
Osimertinib plus chemo ups PFS, toxicity in first line
(PFS), according to interim results from the FLAURA2 trial.
Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.
However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.
Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.
Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.
And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.
The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.
But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.
To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.
The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.
Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.
The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.
At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.
Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.
Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.
The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.
The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).
Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.
Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.
The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.
Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.
Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.
Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.
The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.
A version of this article first appeared on Medscape.com.
(PFS), according to interim results from the FLAURA2 trial.
Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.
However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.
Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.
Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.
And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.
The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.
But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.
To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.
The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.
Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.
The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.
At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.
Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.
Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.
The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.
The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).
Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.
Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.
The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.
Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.
Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.
Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.
The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.
A version of this article first appeared on Medscape.com.
(PFS), according to interim results from the FLAURA2 trial.
Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.
However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.
Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.
Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.
And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.
The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.
But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.
To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.
The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.
Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.
The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.
At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.
Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.
Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.
The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.
The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).
Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.
Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.
The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.
Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.
Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.
Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.
The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.
A version of this article first appeared on Medscape.com.
FROM WCLC 2023
Psychedelic experience and “oneiroid” state
David Nichols, PhD, a leading expert in the field of psychedelic research and the founding president of the Heffter Research Institute, often answers the question, “What is a psychedelic?” by saying, “The scientific definition I always use is that they are substances that produce changes in thought, mood, and affect, which only occur during dreaming or religious exaltation.”1,2 However, this definition does not account for the experiences of naturally occurring psychoses, such as those seen in schizophrenia.
The phenomenology of psychotic experiences between drug-induced and naturally occurring psychoses differs, and the use of psychedelics does not necessarily replicate or simulate the symptoms of schizophrenia. For example, drug induced hallucinations are often described as more intense and vivid, while those associated with schizophrenia are described as more persistent and distressing.3
An altered state of consciousness is a hallmark of a psychedelic trip, but not a characteristic of schizophrenia. Patients with schizophrenia who have used psychedelics typically report that their experiences under the influence of these drugs are distinct from their usual experiences with the condition. Additionally, according to many experts, the underlying neurobiological mechanisms are different, with psychedelics affecting serotonin receptors and schizophrenia thought to be linked more to dopamine dysregulation, among other factors.
However, there are some instances of naturally occurring psychoses that are difficult to distinguish from the experiences reported by those who take psychedelics. This article explores the similarities between psychedelic experiences induced by serotonergic psychedelics, 5-HT2A agonists, such as LSD, psilocybin, and mescaline, and a rare psychiatric disorder known as the “oneiroid state.”
Origins and definitions
The term “oneiroia” is derived from the Greek words for “sleep” and “similar,” referring to the dreamlike character of the condition. It is widely acknowledged that psychedelics can temporarily induce dreamlike states,4 but this article focuses specifically on the naturally occurring, endogenous dreamlike state.
Oneiroid state was first described by German psychiatrist Wilhelm Mayer-Gross in the early 20th century and was once well-known among European psychiatrists. Some classified it as a part of schizophrenia, others saw it as an unusual manifestation of affective disorder, and still others considered it an atypical psychosis. Nevertheless, this phenomenon has received limited attention in American psychiatric journals.
The key characteristic of this condition is a distinctive state of consciousness marked by vivid and florid hallucinations, and a succession of constantly shifting dreamlike or surrealistic visuals and imagery often similar to mystical or cosmic experiences. Self-awareness and orientation in time and place are often disturbed, and delusions are experienced within this altered state.5
To gain a better understanding of the oneiroid state, it may be helpful to turn to European or other schools of psychiatry with a history of studying this phenomenon, as American psychiatry has limited knowledge in this area.
As described in the “Handbook of Psychiatry” by Russian psychiatrist A.V. Snezhnevsky, published in 1983, oneiroid state, also known as oneiroid syndrome, is a dreamlike and imaginative state characterized by a bizarre combination of reality and vivid phantasmagoric imaginations.6 In this state, individuals are completely detached from their surroundings and experience a change in self-awareness, often displaying either a lack of movement or senseless excitement.
Patients often experience the oneiroid state as active participants, as if they are in a movie theater, not only watching the story, but also being part of it, reacting to it with either “external immobility” or senseless excitement, completely detached from their surroundings. This is similar to the portrayal of the emotions of the characters in Steven Spielberg’s film “Ready Player One.”
The entry in Dr. Snezhnevsky’s “Handbook” states: “Some patients in Oneiroid State experience travels to other worlds, such as interacting with inhabitants on Mars, collecting gems on the moon, exploring invisible cities, participating in conspiracies and insurrections, fighting with pirates, chasing The Flying Dutchman, wandering through ancient Rome, and even visiting heaven or hell. At times, the patient’s imagination reaches a state of mystical contemplation.”6
In contrast to delirium, which never impairs self-awareness, oneiroid state is marked by drastic changes in the sense of self. The memory of the subjective experience during the oneiroia is much more vivid and consistent than in delirium. Patients who have experienced the oneiroid state often have complete recall of their experience, as if they have just woken up from a dream.
It was commonly thought that oneiroid state was part of the group of functional psychoses, rather than organic psychoses, and was not considered to be a result of mind-altering psychedelics. It was not considered a manifestation of epilepsy either. Oneiroid state could last for weeks or even months, making it unlikely to be related to an epileptic seizure. Furthermore, EEG results did not show any seizurelike activity during the state.
An excellent case study on oneiroid state was published in Israel in 2000. The authors described two patients who experienced the oneiroid state for several days or even weeks.7 One of the patients reported that during the illness, he experienced himself aboard a spaceship as a cosmonaut, heading for a different universe. On another occasion, the patient perceived himself as a person living 2,000 years ago and being guilty of Christ’s death.
The second patient reported that everything around her appeared “like in the movies,” and she saw others as characters from comic strips. Both patients alternated between catatonic excitement and sluggishness and would sometimes come back to reality for a few minutes to respond to questions. Physical exams, laboratory tests, neurological tests, and a brain scan were all normal in both cases.
Conclusions
As mentioned earlier, oneiroid state is not widely discussed in American psychiatric journals and is now considered a rare condition globally, despite being a common occurrence in the past century. A diagnosis similar to oneiroid state, known as bouffée délirante, is still in use in some French-speaking countries, with a noticeable decline in frequency.2,8 The widespread acceptance of international classification systems such as the ICD-10, which does not recognize the diagnosis, is likely one of the reasons for this decline.
However, the decrease in the prevalence of the oneiroid state is not unique, as other forms of mental illness, such as the catatonic subtype of schizophrenia, are also becoming less prevalent. The cause of this decline is uncertain. Could changes in the way mental disorders affect 5HT2A receptors be a contributing factor?
In conclusion, as the field of psychedelic research experiences a resurgence, this little-known manifestation of mental illness, oneiroid state, may be worth reexamining.
With the expected approval and regulation of psilocybin and MDMA by the FDA, and classical psychedelics widely regarded as nonaddictive and safer than other recreational drugs, , rather than as a cause for concern.
Dr. Khetsuriani is a supervising psychiatrist at the Bronx Psychiatric Center in Bronx, N.Y., and has a private psychiatric practice located in Manhattan, N.Y.
References
1. Nichols DE. Keynote address, 39th Telluride Mushroom Festival, Aug. 15-18, 2019. https://www.youtube.com/watch?v=RlDCM5JQzRk.
2. Nichols DE. Psychedelics. Pharmacol Rev. 2016 Apr;68(2):264-355. doi: 10.1124/pr.115.011478.
3. Leptourgos P et al. Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison. Schizophr Bull. 2020 Dec 1;46(6):1396-1408. doi: 10.1093/schbul/sbaa117.
4. Kraehenmann R. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications. Curr Neuropharmacol. 2017;15(7):1032-42. doi: 10.2174/1573413713666170619092629.
5. Henri EY et al. “Acute Delusional Psychosis” in Hirsch SR and Shepherd M, eds. Themes and variations in European psychiatry: An anthology. Charlottesville: University Press of Virginia, 1974.
6. Snezhnevsky A, ed. Handbook of Psychiatry. Moscow: Meditsina, 1983.
7. Kaptsan A et al. Oneiroid syndrome: A concept of use for Western psychiatry. Isr J Psychiatry Relat Sci. 2000;37(4):278-85.
8. https://en.wikipedia.org/wiki/Bouff%C3%A9e_d%C3%A9lirante.
David Nichols, PhD, a leading expert in the field of psychedelic research and the founding president of the Heffter Research Institute, often answers the question, “What is a psychedelic?” by saying, “The scientific definition I always use is that they are substances that produce changes in thought, mood, and affect, which only occur during dreaming or religious exaltation.”1,2 However, this definition does not account for the experiences of naturally occurring psychoses, such as those seen in schizophrenia.
The phenomenology of psychotic experiences between drug-induced and naturally occurring psychoses differs, and the use of psychedelics does not necessarily replicate or simulate the symptoms of schizophrenia. For example, drug induced hallucinations are often described as more intense and vivid, while those associated with schizophrenia are described as more persistent and distressing.3
An altered state of consciousness is a hallmark of a psychedelic trip, but not a characteristic of schizophrenia. Patients with schizophrenia who have used psychedelics typically report that their experiences under the influence of these drugs are distinct from their usual experiences with the condition. Additionally, according to many experts, the underlying neurobiological mechanisms are different, with psychedelics affecting serotonin receptors and schizophrenia thought to be linked more to dopamine dysregulation, among other factors.
However, there are some instances of naturally occurring psychoses that are difficult to distinguish from the experiences reported by those who take psychedelics. This article explores the similarities between psychedelic experiences induced by serotonergic psychedelics, 5-HT2A agonists, such as LSD, psilocybin, and mescaline, and a rare psychiatric disorder known as the “oneiroid state.”
Origins and definitions
The term “oneiroia” is derived from the Greek words for “sleep” and “similar,” referring to the dreamlike character of the condition. It is widely acknowledged that psychedelics can temporarily induce dreamlike states,4 but this article focuses specifically on the naturally occurring, endogenous dreamlike state.
Oneiroid state was first described by German psychiatrist Wilhelm Mayer-Gross in the early 20th century and was once well-known among European psychiatrists. Some classified it as a part of schizophrenia, others saw it as an unusual manifestation of affective disorder, and still others considered it an atypical psychosis. Nevertheless, this phenomenon has received limited attention in American psychiatric journals.
The key characteristic of this condition is a distinctive state of consciousness marked by vivid and florid hallucinations, and a succession of constantly shifting dreamlike or surrealistic visuals and imagery often similar to mystical or cosmic experiences. Self-awareness and orientation in time and place are often disturbed, and delusions are experienced within this altered state.5
To gain a better understanding of the oneiroid state, it may be helpful to turn to European or other schools of psychiatry with a history of studying this phenomenon, as American psychiatry has limited knowledge in this area.
As described in the “Handbook of Psychiatry” by Russian psychiatrist A.V. Snezhnevsky, published in 1983, oneiroid state, also known as oneiroid syndrome, is a dreamlike and imaginative state characterized by a bizarre combination of reality and vivid phantasmagoric imaginations.6 In this state, individuals are completely detached from their surroundings and experience a change in self-awareness, often displaying either a lack of movement or senseless excitement.
Patients often experience the oneiroid state as active participants, as if they are in a movie theater, not only watching the story, but also being part of it, reacting to it with either “external immobility” or senseless excitement, completely detached from their surroundings. This is similar to the portrayal of the emotions of the characters in Steven Spielberg’s film “Ready Player One.”
The entry in Dr. Snezhnevsky’s “Handbook” states: “Some patients in Oneiroid State experience travels to other worlds, such as interacting with inhabitants on Mars, collecting gems on the moon, exploring invisible cities, participating in conspiracies and insurrections, fighting with pirates, chasing The Flying Dutchman, wandering through ancient Rome, and even visiting heaven or hell. At times, the patient’s imagination reaches a state of mystical contemplation.”6
In contrast to delirium, which never impairs self-awareness, oneiroid state is marked by drastic changes in the sense of self. The memory of the subjective experience during the oneiroia is much more vivid and consistent than in delirium. Patients who have experienced the oneiroid state often have complete recall of their experience, as if they have just woken up from a dream.
It was commonly thought that oneiroid state was part of the group of functional psychoses, rather than organic psychoses, and was not considered to be a result of mind-altering psychedelics. It was not considered a manifestation of epilepsy either. Oneiroid state could last for weeks or even months, making it unlikely to be related to an epileptic seizure. Furthermore, EEG results did not show any seizurelike activity during the state.
An excellent case study on oneiroid state was published in Israel in 2000. The authors described two patients who experienced the oneiroid state for several days or even weeks.7 One of the patients reported that during the illness, he experienced himself aboard a spaceship as a cosmonaut, heading for a different universe. On another occasion, the patient perceived himself as a person living 2,000 years ago and being guilty of Christ’s death.
The second patient reported that everything around her appeared “like in the movies,” and she saw others as characters from comic strips. Both patients alternated between catatonic excitement and sluggishness and would sometimes come back to reality for a few minutes to respond to questions. Physical exams, laboratory tests, neurological tests, and a brain scan were all normal in both cases.
Conclusions
As mentioned earlier, oneiroid state is not widely discussed in American psychiatric journals and is now considered a rare condition globally, despite being a common occurrence in the past century. A diagnosis similar to oneiroid state, known as bouffée délirante, is still in use in some French-speaking countries, with a noticeable decline in frequency.2,8 The widespread acceptance of international classification systems such as the ICD-10, which does not recognize the diagnosis, is likely one of the reasons for this decline.
However, the decrease in the prevalence of the oneiroid state is not unique, as other forms of mental illness, such as the catatonic subtype of schizophrenia, are also becoming less prevalent. The cause of this decline is uncertain. Could changes in the way mental disorders affect 5HT2A receptors be a contributing factor?
In conclusion, as the field of psychedelic research experiences a resurgence, this little-known manifestation of mental illness, oneiroid state, may be worth reexamining.
With the expected approval and regulation of psilocybin and MDMA by the FDA, and classical psychedelics widely regarded as nonaddictive and safer than other recreational drugs, , rather than as a cause for concern.
Dr. Khetsuriani is a supervising psychiatrist at the Bronx Psychiatric Center in Bronx, N.Y., and has a private psychiatric practice located in Manhattan, N.Y.
References
1. Nichols DE. Keynote address, 39th Telluride Mushroom Festival, Aug. 15-18, 2019. https://www.youtube.com/watch?v=RlDCM5JQzRk.
2. Nichols DE. Psychedelics. Pharmacol Rev. 2016 Apr;68(2):264-355. doi: 10.1124/pr.115.011478.
3. Leptourgos P et al. Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison. Schizophr Bull. 2020 Dec 1;46(6):1396-1408. doi: 10.1093/schbul/sbaa117.
4. Kraehenmann R. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications. Curr Neuropharmacol. 2017;15(7):1032-42. doi: 10.2174/1573413713666170619092629.
5. Henri EY et al. “Acute Delusional Psychosis” in Hirsch SR and Shepherd M, eds. Themes and variations in European psychiatry: An anthology. Charlottesville: University Press of Virginia, 1974.
6. Snezhnevsky A, ed. Handbook of Psychiatry. Moscow: Meditsina, 1983.
7. Kaptsan A et al. Oneiroid syndrome: A concept of use for Western psychiatry. Isr J Psychiatry Relat Sci. 2000;37(4):278-85.
8. https://en.wikipedia.org/wiki/Bouff%C3%A9e_d%C3%A9lirante.
David Nichols, PhD, a leading expert in the field of psychedelic research and the founding president of the Heffter Research Institute, often answers the question, “What is a psychedelic?” by saying, “The scientific definition I always use is that they are substances that produce changes in thought, mood, and affect, which only occur during dreaming or religious exaltation.”1,2 However, this definition does not account for the experiences of naturally occurring psychoses, such as those seen in schizophrenia.
The phenomenology of psychotic experiences between drug-induced and naturally occurring psychoses differs, and the use of psychedelics does not necessarily replicate or simulate the symptoms of schizophrenia. For example, drug induced hallucinations are often described as more intense and vivid, while those associated with schizophrenia are described as more persistent and distressing.3
An altered state of consciousness is a hallmark of a psychedelic trip, but not a characteristic of schizophrenia. Patients with schizophrenia who have used psychedelics typically report that their experiences under the influence of these drugs are distinct from their usual experiences with the condition. Additionally, according to many experts, the underlying neurobiological mechanisms are different, with psychedelics affecting serotonin receptors and schizophrenia thought to be linked more to dopamine dysregulation, among other factors.
However, there are some instances of naturally occurring psychoses that are difficult to distinguish from the experiences reported by those who take psychedelics. This article explores the similarities between psychedelic experiences induced by serotonergic psychedelics, 5-HT2A agonists, such as LSD, psilocybin, and mescaline, and a rare psychiatric disorder known as the “oneiroid state.”
Origins and definitions
The term “oneiroia” is derived from the Greek words for “sleep” and “similar,” referring to the dreamlike character of the condition. It is widely acknowledged that psychedelics can temporarily induce dreamlike states,4 but this article focuses specifically on the naturally occurring, endogenous dreamlike state.
Oneiroid state was first described by German psychiatrist Wilhelm Mayer-Gross in the early 20th century and was once well-known among European psychiatrists. Some classified it as a part of schizophrenia, others saw it as an unusual manifestation of affective disorder, and still others considered it an atypical psychosis. Nevertheless, this phenomenon has received limited attention in American psychiatric journals.
The key characteristic of this condition is a distinctive state of consciousness marked by vivid and florid hallucinations, and a succession of constantly shifting dreamlike or surrealistic visuals and imagery often similar to mystical or cosmic experiences. Self-awareness and orientation in time and place are often disturbed, and delusions are experienced within this altered state.5
To gain a better understanding of the oneiroid state, it may be helpful to turn to European or other schools of psychiatry with a history of studying this phenomenon, as American psychiatry has limited knowledge in this area.
As described in the “Handbook of Psychiatry” by Russian psychiatrist A.V. Snezhnevsky, published in 1983, oneiroid state, also known as oneiroid syndrome, is a dreamlike and imaginative state characterized by a bizarre combination of reality and vivid phantasmagoric imaginations.6 In this state, individuals are completely detached from their surroundings and experience a change in self-awareness, often displaying either a lack of movement or senseless excitement.
Patients often experience the oneiroid state as active participants, as if they are in a movie theater, not only watching the story, but also being part of it, reacting to it with either “external immobility” or senseless excitement, completely detached from their surroundings. This is similar to the portrayal of the emotions of the characters in Steven Spielberg’s film “Ready Player One.”
The entry in Dr. Snezhnevsky’s “Handbook” states: “Some patients in Oneiroid State experience travels to other worlds, such as interacting with inhabitants on Mars, collecting gems on the moon, exploring invisible cities, participating in conspiracies and insurrections, fighting with pirates, chasing The Flying Dutchman, wandering through ancient Rome, and even visiting heaven or hell. At times, the patient’s imagination reaches a state of mystical contemplation.”6
In contrast to delirium, which never impairs self-awareness, oneiroid state is marked by drastic changes in the sense of self. The memory of the subjective experience during the oneiroia is much more vivid and consistent than in delirium. Patients who have experienced the oneiroid state often have complete recall of their experience, as if they have just woken up from a dream.
It was commonly thought that oneiroid state was part of the group of functional psychoses, rather than organic psychoses, and was not considered to be a result of mind-altering psychedelics. It was not considered a manifestation of epilepsy either. Oneiroid state could last for weeks or even months, making it unlikely to be related to an epileptic seizure. Furthermore, EEG results did not show any seizurelike activity during the state.
An excellent case study on oneiroid state was published in Israel in 2000. The authors described two patients who experienced the oneiroid state for several days or even weeks.7 One of the patients reported that during the illness, he experienced himself aboard a spaceship as a cosmonaut, heading for a different universe. On another occasion, the patient perceived himself as a person living 2,000 years ago and being guilty of Christ’s death.
The second patient reported that everything around her appeared “like in the movies,” and she saw others as characters from comic strips. Both patients alternated between catatonic excitement and sluggishness and would sometimes come back to reality for a few minutes to respond to questions. Physical exams, laboratory tests, neurological tests, and a brain scan were all normal in both cases.
Conclusions
As mentioned earlier, oneiroid state is not widely discussed in American psychiatric journals and is now considered a rare condition globally, despite being a common occurrence in the past century. A diagnosis similar to oneiroid state, known as bouffée délirante, is still in use in some French-speaking countries, with a noticeable decline in frequency.2,8 The widespread acceptance of international classification systems such as the ICD-10, which does not recognize the diagnosis, is likely one of the reasons for this decline.
However, the decrease in the prevalence of the oneiroid state is not unique, as other forms of mental illness, such as the catatonic subtype of schizophrenia, are also becoming less prevalent. The cause of this decline is uncertain. Could changes in the way mental disorders affect 5HT2A receptors be a contributing factor?
In conclusion, as the field of psychedelic research experiences a resurgence, this little-known manifestation of mental illness, oneiroid state, may be worth reexamining.
With the expected approval and regulation of psilocybin and MDMA by the FDA, and classical psychedelics widely regarded as nonaddictive and safer than other recreational drugs, , rather than as a cause for concern.
Dr. Khetsuriani is a supervising psychiatrist at the Bronx Psychiatric Center in Bronx, N.Y., and has a private psychiatric practice located in Manhattan, N.Y.
References
1. Nichols DE. Keynote address, 39th Telluride Mushroom Festival, Aug. 15-18, 2019. https://www.youtube.com/watch?v=RlDCM5JQzRk.
2. Nichols DE. Psychedelics. Pharmacol Rev. 2016 Apr;68(2):264-355. doi: 10.1124/pr.115.011478.
3. Leptourgos P et al. Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison. Schizophr Bull. 2020 Dec 1;46(6):1396-1408. doi: 10.1093/schbul/sbaa117.
4. Kraehenmann R. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications. Curr Neuropharmacol. 2017;15(7):1032-42. doi: 10.2174/1573413713666170619092629.
5. Henri EY et al. “Acute Delusional Psychosis” in Hirsch SR and Shepherd M, eds. Themes and variations in European psychiatry: An anthology. Charlottesville: University Press of Virginia, 1974.
6. Snezhnevsky A, ed. Handbook of Psychiatry. Moscow: Meditsina, 1983.
7. Kaptsan A et al. Oneiroid syndrome: A concept of use for Western psychiatry. Isr J Psychiatry Relat Sci. 2000;37(4):278-85.
8. https://en.wikipedia.org/wiki/Bouff%C3%A9e_d%C3%A9lirante.
Sleep apnea diagnosis: Awareness and tools
Obstructive sleep apnea (OSA) remains a significantly underdiagnosed condition, despite its high prevalence. Primary care physicians play a pivotal role in identifying patients afflicted by this condition. To effectively diagnose OSA in primary care, increasing awareness and enhancing communication are imperative. Fortunately, several straightforward diagnostic tools are readily available, and even more sophisticated ones, driven by artificial intelligence, are on the horizon.
Recognize the problem
At the annual congress of the European Respiratory Society, Cláudia Sofia De Almeida Vicente Ferreira, MD, a family physician from Coimbra, Portugal, and coordinator of the Respiratory Diseases Interest Group of the Portuguese Association of General and Family Medicine, highlighted the challenges of diagnosing OSA.
People do not come to the doctor and complain about it. Sometimes you catch it in the middle of other things,” she said in an interview.
Moreover, physicians’ busy schedules and limited appointment times often lead to a focus on the symptoms reported by patients, and insufficient attention is paid to the quality of sleep. This may be compounded by a tendency among medical professionals to underestimate the risks associated with OSA, as it is not directly linked to mortality, despite its clear connection to cardiovascular risks.
Identifying and recognizing risk factors can facilitate OSA suspicion during patient evaluations. These factors encompass both structural (for example, craniofacial and upper airway anomalies) and nonstructural elements (for example, smoking, alcohol use, or sedative consumption). While men are at higher risk, postmenopausal women who are not receiving hormone replacement therapy face similar risks. Certain medical conditions, such as hypothyroidism, acromegaly, amyloidosis, Cushing syndrome, and Down syndrome, have also been associated with OSA. A comprehensive physical examination can provide additional clues. Factors might include obesity, neck circumference, Mallampati score, and nasal and pharyngeal problems.
Inquire actively
Once the possibility of OSA is considered, the next step is to ask patients about their symptoms. Questionnaires are simple yet valuable tools for this purpose. The STOP questionnaire comprises four key questions:
- Do you SNORE loudly (louder than talking or loud enough to be heard through closed doors)?
- Do you often feel TIRED, fatigued, or sleepy during daytime?
- Has anyone OBSERVED you stop breathing during your sleep?
- Do you have or are you being treated for high blood PRESSURE?
The STOP-BANG questionnaire adds four clinical attributes: obesity (body mass index > 35 kg/m2), age (> 50 years), neck size (> 40 cm, or 16 inches), and sex.
Patients are classified as being at low, intermediate, or high risk for OSA.
The Epworth Sleepiness Scale, which is self-administered, is also useful: patients rate the likelihood of falling asleep in various daytime contexts. These questionnaires can be seamlessly integrated into routine patient appointments.
Comorbidities and occupation
Primary care physicians should carefully assess comorbidities, especially those linked to cardiovascular risk. Patients with resistant hypertension, pulmonary hypertension, and recurrent atrial fibrillation following cardioversion/ablation should be prioritized for diagnostic testing for OSA. Patients with other conditions, such as coronary artery disease or cerebrovascular disease, should also be referred to a sleep center if OSA is suspected on the basis of comprehensive sleep assessment. OSA has also been associated with type 2 diabetes, metabolic syndrome, and asthma.
Gaining access to sleep study services and subsequent therapy, such as continuous positive airway pressure (CPAP), can be challenging. Primary care physicians should prioritize patients on the basis of their risk levels. Occupation plays a significant role in this prioritization, as sleep fragmentation and daytime sleepiness can lead to workplace and vehicular accidents.
“You should include the occupation in the patient’s profile. What is he doing? Is he sitting at a desk, or is he working at height, driving, or operating machines? These workers are high-risk patients,” continued Dr. De Almeida Vicente Ferreira.
“I think that the family physician has a key role in the follow-up. Nobody else will look for CPAP compliance and will verify if CPAP is working or not. If the patient is not using it or if it is not effective, still there is someone paying for the machine (the national health care system or an insurance company). More importantly, if CPAP is not working, we are not improving our patient’s life in terms of reducing cardiovascular risk and ameliorating the quality of life.”
Is home testing a viable option?
Diagnosing OSA typically relies on overnight polysomnography in specialized sleep clinics, which is often associated with long waiting lists. Researchers are actively working on innovative sensors and digital solutions for home-based sleep testing, but according to Dr. De Almeida Vicente Ferreira, they are not yet ready for prime time: “Home-based studies with fewer evaluation parameters (such as pulse and oxygen levels) are not so secure or sensitive to establish a correct and complete diagnosis. Actually, the architecture of sleep is very complex. The test must be performed and read by a specialized team.”
Still, according to Renaud Tamisier, MD, PhD, professor of clinical physiology at the Université Grenoble Alpes in La Tronche, France, simplified sleep testing could be very useful. “There are many patients that still are not diagnosed despite having severe sleep apnea, with symptoms and comorbidities. These patients usually are not aware of their disease but complain about changes in their quality of life with excessive tiredness and sleepiness. Also, they are not connected to the healthcare system, for different reasons, including no time for consulting a sleep physician and performing a polysomnography, health cost, negligence. Therefore, providing through primary care a simple diagnostic approach deserves efforts and research,” he said in an interview.
New technologies could enable diagnostic sleep tests to be conducted at home, with the added benefit of multiple-night recordings to overcome the challenges of night-to-night variability in the apnea-hypopnea index. These novel testing methods should be cost effective, easy to install, and user friendly. Dr. Tamisier continued: “The issue about sleep diagnosis is that up to now, there was no such devices available. Many physicians use type III sleep recording that are dedicated to highly trained sleep scorers, but they use automatic analysis which in many cases is unsuccessful. For a trained sleep physician, it is easy to see that the result is inaccurate. New devices are being built for automatic analysis using artificial intelligence algorithms. Because by design they are automatic, the rate of success is very high, and if used with the right purpose, they could be highly effective and quick.”
In conclusion, the diagnosis of sleep apnea in primary care is becoming more feasible with advancements in diagnostic tools and technology. However, it is crucial for primary care physicians to exercise caution in cases in which the clinical presentation is not straightforward or when OSA is associated with comorbidities. Care management and clear boundaries are vital to ensure effective treatment and improve patient outcomes.
Dr. De Almeida Vicente Ferreira and Dr. Tamisier disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Obstructive sleep apnea (OSA) remains a significantly underdiagnosed condition, despite its high prevalence. Primary care physicians play a pivotal role in identifying patients afflicted by this condition. To effectively diagnose OSA in primary care, increasing awareness and enhancing communication are imperative. Fortunately, several straightforward diagnostic tools are readily available, and even more sophisticated ones, driven by artificial intelligence, are on the horizon.
Recognize the problem
At the annual congress of the European Respiratory Society, Cláudia Sofia De Almeida Vicente Ferreira, MD, a family physician from Coimbra, Portugal, and coordinator of the Respiratory Diseases Interest Group of the Portuguese Association of General and Family Medicine, highlighted the challenges of diagnosing OSA.
People do not come to the doctor and complain about it. Sometimes you catch it in the middle of other things,” she said in an interview.
Moreover, physicians’ busy schedules and limited appointment times often lead to a focus on the symptoms reported by patients, and insufficient attention is paid to the quality of sleep. This may be compounded by a tendency among medical professionals to underestimate the risks associated with OSA, as it is not directly linked to mortality, despite its clear connection to cardiovascular risks.
Identifying and recognizing risk factors can facilitate OSA suspicion during patient evaluations. These factors encompass both structural (for example, craniofacial and upper airway anomalies) and nonstructural elements (for example, smoking, alcohol use, or sedative consumption). While men are at higher risk, postmenopausal women who are not receiving hormone replacement therapy face similar risks. Certain medical conditions, such as hypothyroidism, acromegaly, amyloidosis, Cushing syndrome, and Down syndrome, have also been associated with OSA. A comprehensive physical examination can provide additional clues. Factors might include obesity, neck circumference, Mallampati score, and nasal and pharyngeal problems.
Inquire actively
Once the possibility of OSA is considered, the next step is to ask patients about their symptoms. Questionnaires are simple yet valuable tools for this purpose. The STOP questionnaire comprises four key questions:
- Do you SNORE loudly (louder than talking or loud enough to be heard through closed doors)?
- Do you often feel TIRED, fatigued, or sleepy during daytime?
- Has anyone OBSERVED you stop breathing during your sleep?
- Do you have or are you being treated for high blood PRESSURE?
The STOP-BANG questionnaire adds four clinical attributes: obesity (body mass index > 35 kg/m2), age (> 50 years), neck size (> 40 cm, or 16 inches), and sex.
Patients are classified as being at low, intermediate, or high risk for OSA.
The Epworth Sleepiness Scale, which is self-administered, is also useful: patients rate the likelihood of falling asleep in various daytime contexts. These questionnaires can be seamlessly integrated into routine patient appointments.
Comorbidities and occupation
Primary care physicians should carefully assess comorbidities, especially those linked to cardiovascular risk. Patients with resistant hypertension, pulmonary hypertension, and recurrent atrial fibrillation following cardioversion/ablation should be prioritized for diagnostic testing for OSA. Patients with other conditions, such as coronary artery disease or cerebrovascular disease, should also be referred to a sleep center if OSA is suspected on the basis of comprehensive sleep assessment. OSA has also been associated with type 2 diabetes, metabolic syndrome, and asthma.
Gaining access to sleep study services and subsequent therapy, such as continuous positive airway pressure (CPAP), can be challenging. Primary care physicians should prioritize patients on the basis of their risk levels. Occupation plays a significant role in this prioritization, as sleep fragmentation and daytime sleepiness can lead to workplace and vehicular accidents.
“You should include the occupation in the patient’s profile. What is he doing? Is he sitting at a desk, or is he working at height, driving, or operating machines? These workers are high-risk patients,” continued Dr. De Almeida Vicente Ferreira.
“I think that the family physician has a key role in the follow-up. Nobody else will look for CPAP compliance and will verify if CPAP is working or not. If the patient is not using it or if it is not effective, still there is someone paying for the machine (the national health care system or an insurance company). More importantly, if CPAP is not working, we are not improving our patient’s life in terms of reducing cardiovascular risk and ameliorating the quality of life.”
Is home testing a viable option?
Diagnosing OSA typically relies on overnight polysomnography in specialized sleep clinics, which is often associated with long waiting lists. Researchers are actively working on innovative sensors and digital solutions for home-based sleep testing, but according to Dr. De Almeida Vicente Ferreira, they are not yet ready for prime time: “Home-based studies with fewer evaluation parameters (such as pulse and oxygen levels) are not so secure or sensitive to establish a correct and complete diagnosis. Actually, the architecture of sleep is very complex. The test must be performed and read by a specialized team.”
Still, according to Renaud Tamisier, MD, PhD, professor of clinical physiology at the Université Grenoble Alpes in La Tronche, France, simplified sleep testing could be very useful. “There are many patients that still are not diagnosed despite having severe sleep apnea, with symptoms and comorbidities. These patients usually are not aware of their disease but complain about changes in their quality of life with excessive tiredness and sleepiness. Also, they are not connected to the healthcare system, for different reasons, including no time for consulting a sleep physician and performing a polysomnography, health cost, negligence. Therefore, providing through primary care a simple diagnostic approach deserves efforts and research,” he said in an interview.
New technologies could enable diagnostic sleep tests to be conducted at home, with the added benefit of multiple-night recordings to overcome the challenges of night-to-night variability in the apnea-hypopnea index. These novel testing methods should be cost effective, easy to install, and user friendly. Dr. Tamisier continued: “The issue about sleep diagnosis is that up to now, there was no such devices available. Many physicians use type III sleep recording that are dedicated to highly trained sleep scorers, but they use automatic analysis which in many cases is unsuccessful. For a trained sleep physician, it is easy to see that the result is inaccurate. New devices are being built for automatic analysis using artificial intelligence algorithms. Because by design they are automatic, the rate of success is very high, and if used with the right purpose, they could be highly effective and quick.”
In conclusion, the diagnosis of sleep apnea in primary care is becoming more feasible with advancements in diagnostic tools and technology. However, it is crucial for primary care physicians to exercise caution in cases in which the clinical presentation is not straightforward or when OSA is associated with comorbidities. Care management and clear boundaries are vital to ensure effective treatment and improve patient outcomes.
Dr. De Almeida Vicente Ferreira and Dr. Tamisier disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Obstructive sleep apnea (OSA) remains a significantly underdiagnosed condition, despite its high prevalence. Primary care physicians play a pivotal role in identifying patients afflicted by this condition. To effectively diagnose OSA in primary care, increasing awareness and enhancing communication are imperative. Fortunately, several straightforward diagnostic tools are readily available, and even more sophisticated ones, driven by artificial intelligence, are on the horizon.
Recognize the problem
At the annual congress of the European Respiratory Society, Cláudia Sofia De Almeida Vicente Ferreira, MD, a family physician from Coimbra, Portugal, and coordinator of the Respiratory Diseases Interest Group of the Portuguese Association of General and Family Medicine, highlighted the challenges of diagnosing OSA.
People do not come to the doctor and complain about it. Sometimes you catch it in the middle of other things,” she said in an interview.
Moreover, physicians’ busy schedules and limited appointment times often lead to a focus on the symptoms reported by patients, and insufficient attention is paid to the quality of sleep. This may be compounded by a tendency among medical professionals to underestimate the risks associated with OSA, as it is not directly linked to mortality, despite its clear connection to cardiovascular risks.
Identifying and recognizing risk factors can facilitate OSA suspicion during patient evaluations. These factors encompass both structural (for example, craniofacial and upper airway anomalies) and nonstructural elements (for example, smoking, alcohol use, or sedative consumption). While men are at higher risk, postmenopausal women who are not receiving hormone replacement therapy face similar risks. Certain medical conditions, such as hypothyroidism, acromegaly, amyloidosis, Cushing syndrome, and Down syndrome, have also been associated with OSA. A comprehensive physical examination can provide additional clues. Factors might include obesity, neck circumference, Mallampati score, and nasal and pharyngeal problems.
Inquire actively
Once the possibility of OSA is considered, the next step is to ask patients about their symptoms. Questionnaires are simple yet valuable tools for this purpose. The STOP questionnaire comprises four key questions:
- Do you SNORE loudly (louder than talking or loud enough to be heard through closed doors)?
- Do you often feel TIRED, fatigued, or sleepy during daytime?
- Has anyone OBSERVED you stop breathing during your sleep?
- Do you have or are you being treated for high blood PRESSURE?
The STOP-BANG questionnaire adds four clinical attributes: obesity (body mass index > 35 kg/m2), age (> 50 years), neck size (> 40 cm, or 16 inches), and sex.
Patients are classified as being at low, intermediate, or high risk for OSA.
The Epworth Sleepiness Scale, which is self-administered, is also useful: patients rate the likelihood of falling asleep in various daytime contexts. These questionnaires can be seamlessly integrated into routine patient appointments.
Comorbidities and occupation
Primary care physicians should carefully assess comorbidities, especially those linked to cardiovascular risk. Patients with resistant hypertension, pulmonary hypertension, and recurrent atrial fibrillation following cardioversion/ablation should be prioritized for diagnostic testing for OSA. Patients with other conditions, such as coronary artery disease or cerebrovascular disease, should also be referred to a sleep center if OSA is suspected on the basis of comprehensive sleep assessment. OSA has also been associated with type 2 diabetes, metabolic syndrome, and asthma.
Gaining access to sleep study services and subsequent therapy, such as continuous positive airway pressure (CPAP), can be challenging. Primary care physicians should prioritize patients on the basis of their risk levels. Occupation plays a significant role in this prioritization, as sleep fragmentation and daytime sleepiness can lead to workplace and vehicular accidents.
“You should include the occupation in the patient’s profile. What is he doing? Is he sitting at a desk, or is he working at height, driving, or operating machines? These workers are high-risk patients,” continued Dr. De Almeida Vicente Ferreira.
“I think that the family physician has a key role in the follow-up. Nobody else will look for CPAP compliance and will verify if CPAP is working or not. If the patient is not using it or if it is not effective, still there is someone paying for the machine (the national health care system or an insurance company). More importantly, if CPAP is not working, we are not improving our patient’s life in terms of reducing cardiovascular risk and ameliorating the quality of life.”
Is home testing a viable option?
Diagnosing OSA typically relies on overnight polysomnography in specialized sleep clinics, which is often associated with long waiting lists. Researchers are actively working on innovative sensors and digital solutions for home-based sleep testing, but according to Dr. De Almeida Vicente Ferreira, they are not yet ready for prime time: “Home-based studies with fewer evaluation parameters (such as pulse and oxygen levels) are not so secure or sensitive to establish a correct and complete diagnosis. Actually, the architecture of sleep is very complex. The test must be performed and read by a specialized team.”
Still, according to Renaud Tamisier, MD, PhD, professor of clinical physiology at the Université Grenoble Alpes in La Tronche, France, simplified sleep testing could be very useful. “There are many patients that still are not diagnosed despite having severe sleep apnea, with symptoms and comorbidities. These patients usually are not aware of their disease but complain about changes in their quality of life with excessive tiredness and sleepiness. Also, they are not connected to the healthcare system, for different reasons, including no time for consulting a sleep physician and performing a polysomnography, health cost, negligence. Therefore, providing through primary care a simple diagnostic approach deserves efforts and research,” he said in an interview.
New technologies could enable diagnostic sleep tests to be conducted at home, with the added benefit of multiple-night recordings to overcome the challenges of night-to-night variability in the apnea-hypopnea index. These novel testing methods should be cost effective, easy to install, and user friendly. Dr. Tamisier continued: “The issue about sleep diagnosis is that up to now, there was no such devices available. Many physicians use type III sleep recording that are dedicated to highly trained sleep scorers, but they use automatic analysis which in many cases is unsuccessful. For a trained sleep physician, it is easy to see that the result is inaccurate. New devices are being built for automatic analysis using artificial intelligence algorithms. Because by design they are automatic, the rate of success is very high, and if used with the right purpose, they could be highly effective and quick.”
In conclusion, the diagnosis of sleep apnea in primary care is becoming more feasible with advancements in diagnostic tools and technology. However, it is crucial for primary care physicians to exercise caution in cases in which the clinical presentation is not straightforward or when OSA is associated with comorbidities. Care management and clear boundaries are vital to ensure effective treatment and improve patient outcomes.
Dr. De Almeida Vicente Ferreira and Dr. Tamisier disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ERS 2023
Diagnosing progressive pulmonary fibrosis
MILAN – The European Respiratory Society Congress 2023 dedicated an entire session to the multifaceted challenges and ongoing debates surrounding progressive pulmonary fibrosis (PPF). Renowned medical professionals and experts congregated in Milan to explore the current landscape and future prospects of diagnosing PPF, with a particular focus on expediting the diagnostic process.
Anna Podolanczuk, MD, assistant professor of medicine at Weill Cornell Medicine, New York, dissected the diagnostic intricacies of PPF, addressing not only the existing challenges but also the opportunities to streamline diagnosis.
As the session’s cochair, Michael Kreuter, MD, director of the Lung Center at University Hospital, Mainz, Germany, emphasized the importance of patients’ voices in understanding and addressing diseases. Joining him as a cochair was Marlies S. Wijsenbeek, a pulmonary physician and the head of the Interstitial Lung Disease Centre at Erasmus University Medical Centre in Rotterdam, the Netherlands.
The session commenced with a powerful testament from Elisabeth Robertson, a PPF patient representative from the United Kingdom. Diagnosed with PPF in 2011, her journey to diagnosis was far from straightforward, and she spoke in a video about the frustrations she encountered due to the lack of accessible information. Ms. Robertson called for a clearer diagnostic pathway.
Timely diagnosis: Key to better outcomes
Dr. Podolanczuk underscored the significance of early diagnosis, citing Ms. Robertson’s personal experience as a poignant example. An early diagnosis not only alleviates patients’ uncertainties and anxieties about their future but also enables the utilization of available treatments, such as antifibrotic therapies, which can slow the decline in forced vital capacity (FVC) in patients with progressive fibrotic interstitial lung diseases.
Data gleaned from the INBUILD trial was presented, revealing that patients in the placebo group experienced a nearly 200 mL decline in lung function over 52 weeks. Dr. Podolanczuk stressed that initiating antifibrotic therapies sooner could lead to better outcomes, as baseline conditions are likely to worsen over time.
“General practitioners can have a role in diagnosing and managing PPF. They are the frontline. We need to increase awareness, because they are generally not aware of this disease, and they usually think about COPD, asthma, or cardiovascular diseases whenever a patient presents with such symptoms,” Dr. Podolanczuk told this news organization.
Defining the challenge
The foundation of any diagnosis lies in a clear definition and established diagnostic criteria. During the session, it became apparent that different criteria could be employed for PPF diagnosis, leading to the identification of distinct patient populations.
In 2022, the Official ATS/ERS/JRS/ALAT Clinical Practice Guideline provided the first comprehensive definition of the PPF phenotype. According to this guideline, PPF is defined by the presence of at least two of three criteria: worsening symptoms, radiological progression, or physiologic progression defined as a ≥ 5% absolute decline in FVC or ≥ 10% absolute decline in diffusion lung CO (DLCO) within the past year in a patient with interstitial lung disease (ILD) and lung scarring other than idiopathic pulmonary fibrosis (IPF), with no alternative explanation.
“Definitions from the guidelines were based on the available trials at that moment. Registry data suggest that using different criteria will probably lead to the identification of different, but always progressive, populations,” Dr. Wijsenbeek commented to this news organization. “I think we should not worry too much about the details of the criteria and it is good that we have a multimodality assessment: We ask the patient, we look at the pictures, and we measure the lung function. Combining those data, you can have a robust indication of progression.”
The current landscape
Currently, PPF diagnosis hinges on a combination of CT scans, patient narratives, and, in some cases, histological examination. Dr. Wijsenbeek stressed the need to transition to novel diagnostic modalities, including tools that can be readily employed by GPs in their practices.
“GPs have to care about a lot of different diseases, and it makes it more complicated to be aware of conditions like PPF: Symptoms are in fact extremely unspecific” Dr. Kreuter told this news organization. “My suggestion to GPs is to pay attention to the so-called inspiratory crackles because they represent a very early and specific sign of lung fibrosis. This sound does not resemble any other sound that you can hear with your stethoscope: It is like the sound you make walking on fresh snow,” he added, recommending a referral to the pulmonologist in case of identification of inspiratory crackles.
Additionally, several biomarkers can contribute to early PPF diagnosis, including the identification of the usual interstitial pneumonia (UIP) pattern through biopsy or imaging. “We know that this pattern predicts poor outcomes regardless of ILD type,” Dr. Podolanczuk explained, underlining the possibility of using a molecular classifier to identify a UIP pattern on transbronchial lung biopsy. “This is an already existing technology used to identify a gene expression pattern that is strongly predictive of a UIP pattern,” she said.
Furthermore, blood biomarkers, such as high peripheral blood monocyte count and telomere length, hold promise for early PPF detection and prognosis assessment.
The road ahead
The diagnostic landscape for PPF is evolving rapidly, with various emerging biomarkers and tools showing promise. Proteomics, alongside home spirometry as a digital biomarker for frequent FVC monitoring, have demonstrated potential for identifying patients who may benefit from early treatment. A 2022 study defined a 12-proteomic biomarkers signature of progressive fibrosing ILD that can identify patients who may benefit from early treatment and is predictive of outcomes regardless of the underlying CT pattern.
The integration of artificial intelligence into the interpretation of CT and x-ray images represents another avenue of advancement in PPF diagnosis. Dr. Podolanczuk highlighted the role of AI and quantitative CTs in enhancing diagnostic accuracy. She also mentioned innovative imaging methods, such as hyperpolarized gas MRI and endobronchial optical coherence tomography (EB-OCT), which offer new insights into disease progression and treatment response.
Beyond imaging and AI, various research tools are entering the diagnostic arena, including real-time breath analysis for distinguishing between different respiratory conditions. These tools collectively promise to shorten the time from symptom presentation to PPF diagnosis, a vital step in improving patient outcomes. In the words of Dr. Podolanczuk, “How early is too early to identify these patients? Let me say that there’s no such thing as ‘too early’ in the diagnosis of PPF!”
Dr. Podolanczuk disclosed grant funding from NHLBI, ALA, and Three Lakes Foundation; consulting fees from Regeneron, Roche, Imvaria, Boehringer Ingelheim, Veracyte, United Therapeutics, and Eisai; and honoraria from NACE and EBSCO/DynaMed. Ms. Robertson disclosed having no conflict.
A version of this article first appeared on Medscape.com.
MILAN – The European Respiratory Society Congress 2023 dedicated an entire session to the multifaceted challenges and ongoing debates surrounding progressive pulmonary fibrosis (PPF). Renowned medical professionals and experts congregated in Milan to explore the current landscape and future prospects of diagnosing PPF, with a particular focus on expediting the diagnostic process.
Anna Podolanczuk, MD, assistant professor of medicine at Weill Cornell Medicine, New York, dissected the diagnostic intricacies of PPF, addressing not only the existing challenges but also the opportunities to streamline diagnosis.
As the session’s cochair, Michael Kreuter, MD, director of the Lung Center at University Hospital, Mainz, Germany, emphasized the importance of patients’ voices in understanding and addressing diseases. Joining him as a cochair was Marlies S. Wijsenbeek, a pulmonary physician and the head of the Interstitial Lung Disease Centre at Erasmus University Medical Centre in Rotterdam, the Netherlands.
The session commenced with a powerful testament from Elisabeth Robertson, a PPF patient representative from the United Kingdom. Diagnosed with PPF in 2011, her journey to diagnosis was far from straightforward, and she spoke in a video about the frustrations she encountered due to the lack of accessible information. Ms. Robertson called for a clearer diagnostic pathway.
Timely diagnosis: Key to better outcomes
Dr. Podolanczuk underscored the significance of early diagnosis, citing Ms. Robertson’s personal experience as a poignant example. An early diagnosis not only alleviates patients’ uncertainties and anxieties about their future but also enables the utilization of available treatments, such as antifibrotic therapies, which can slow the decline in forced vital capacity (FVC) in patients with progressive fibrotic interstitial lung diseases.
Data gleaned from the INBUILD trial was presented, revealing that patients in the placebo group experienced a nearly 200 mL decline in lung function over 52 weeks. Dr. Podolanczuk stressed that initiating antifibrotic therapies sooner could lead to better outcomes, as baseline conditions are likely to worsen over time.
“General practitioners can have a role in diagnosing and managing PPF. They are the frontline. We need to increase awareness, because they are generally not aware of this disease, and they usually think about COPD, asthma, or cardiovascular diseases whenever a patient presents with such symptoms,” Dr. Podolanczuk told this news organization.
Defining the challenge
The foundation of any diagnosis lies in a clear definition and established diagnostic criteria. During the session, it became apparent that different criteria could be employed for PPF diagnosis, leading to the identification of distinct patient populations.
In 2022, the Official ATS/ERS/JRS/ALAT Clinical Practice Guideline provided the first comprehensive definition of the PPF phenotype. According to this guideline, PPF is defined by the presence of at least two of three criteria: worsening symptoms, radiological progression, or physiologic progression defined as a ≥ 5% absolute decline in FVC or ≥ 10% absolute decline in diffusion lung CO (DLCO) within the past year in a patient with interstitial lung disease (ILD) and lung scarring other than idiopathic pulmonary fibrosis (IPF), with no alternative explanation.
“Definitions from the guidelines were based on the available trials at that moment. Registry data suggest that using different criteria will probably lead to the identification of different, but always progressive, populations,” Dr. Wijsenbeek commented to this news organization. “I think we should not worry too much about the details of the criteria and it is good that we have a multimodality assessment: We ask the patient, we look at the pictures, and we measure the lung function. Combining those data, you can have a robust indication of progression.”
The current landscape
Currently, PPF diagnosis hinges on a combination of CT scans, patient narratives, and, in some cases, histological examination. Dr. Wijsenbeek stressed the need to transition to novel diagnostic modalities, including tools that can be readily employed by GPs in their practices.
“GPs have to care about a lot of different diseases, and it makes it more complicated to be aware of conditions like PPF: Symptoms are in fact extremely unspecific” Dr. Kreuter told this news organization. “My suggestion to GPs is to pay attention to the so-called inspiratory crackles because they represent a very early and specific sign of lung fibrosis. This sound does not resemble any other sound that you can hear with your stethoscope: It is like the sound you make walking on fresh snow,” he added, recommending a referral to the pulmonologist in case of identification of inspiratory crackles.
Additionally, several biomarkers can contribute to early PPF diagnosis, including the identification of the usual interstitial pneumonia (UIP) pattern through biopsy or imaging. “We know that this pattern predicts poor outcomes regardless of ILD type,” Dr. Podolanczuk explained, underlining the possibility of using a molecular classifier to identify a UIP pattern on transbronchial lung biopsy. “This is an already existing technology used to identify a gene expression pattern that is strongly predictive of a UIP pattern,” she said.
Furthermore, blood biomarkers, such as high peripheral blood monocyte count and telomere length, hold promise for early PPF detection and prognosis assessment.
The road ahead
The diagnostic landscape for PPF is evolving rapidly, with various emerging biomarkers and tools showing promise. Proteomics, alongside home spirometry as a digital biomarker for frequent FVC monitoring, have demonstrated potential for identifying patients who may benefit from early treatment. A 2022 study defined a 12-proteomic biomarkers signature of progressive fibrosing ILD that can identify patients who may benefit from early treatment and is predictive of outcomes regardless of the underlying CT pattern.
The integration of artificial intelligence into the interpretation of CT and x-ray images represents another avenue of advancement in PPF diagnosis. Dr. Podolanczuk highlighted the role of AI and quantitative CTs in enhancing diagnostic accuracy. She also mentioned innovative imaging methods, such as hyperpolarized gas MRI and endobronchial optical coherence tomography (EB-OCT), which offer new insights into disease progression and treatment response.
Beyond imaging and AI, various research tools are entering the diagnostic arena, including real-time breath analysis for distinguishing between different respiratory conditions. These tools collectively promise to shorten the time from symptom presentation to PPF diagnosis, a vital step in improving patient outcomes. In the words of Dr. Podolanczuk, “How early is too early to identify these patients? Let me say that there’s no such thing as ‘too early’ in the diagnosis of PPF!”
Dr. Podolanczuk disclosed grant funding from NHLBI, ALA, and Three Lakes Foundation; consulting fees from Regeneron, Roche, Imvaria, Boehringer Ingelheim, Veracyte, United Therapeutics, and Eisai; and honoraria from NACE and EBSCO/DynaMed. Ms. Robertson disclosed having no conflict.
A version of this article first appeared on Medscape.com.
MILAN – The European Respiratory Society Congress 2023 dedicated an entire session to the multifaceted challenges and ongoing debates surrounding progressive pulmonary fibrosis (PPF). Renowned medical professionals and experts congregated in Milan to explore the current landscape and future prospects of diagnosing PPF, with a particular focus on expediting the diagnostic process.
Anna Podolanczuk, MD, assistant professor of medicine at Weill Cornell Medicine, New York, dissected the diagnostic intricacies of PPF, addressing not only the existing challenges but also the opportunities to streamline diagnosis.
As the session’s cochair, Michael Kreuter, MD, director of the Lung Center at University Hospital, Mainz, Germany, emphasized the importance of patients’ voices in understanding and addressing diseases. Joining him as a cochair was Marlies S. Wijsenbeek, a pulmonary physician and the head of the Interstitial Lung Disease Centre at Erasmus University Medical Centre in Rotterdam, the Netherlands.
The session commenced with a powerful testament from Elisabeth Robertson, a PPF patient representative from the United Kingdom. Diagnosed with PPF in 2011, her journey to diagnosis was far from straightforward, and she spoke in a video about the frustrations she encountered due to the lack of accessible information. Ms. Robertson called for a clearer diagnostic pathway.
Timely diagnosis: Key to better outcomes
Dr. Podolanczuk underscored the significance of early diagnosis, citing Ms. Robertson’s personal experience as a poignant example. An early diagnosis not only alleviates patients’ uncertainties and anxieties about their future but also enables the utilization of available treatments, such as antifibrotic therapies, which can slow the decline in forced vital capacity (FVC) in patients with progressive fibrotic interstitial lung diseases.
Data gleaned from the INBUILD trial was presented, revealing that patients in the placebo group experienced a nearly 200 mL decline in lung function over 52 weeks. Dr. Podolanczuk stressed that initiating antifibrotic therapies sooner could lead to better outcomes, as baseline conditions are likely to worsen over time.
“General practitioners can have a role in diagnosing and managing PPF. They are the frontline. We need to increase awareness, because they are generally not aware of this disease, and they usually think about COPD, asthma, or cardiovascular diseases whenever a patient presents with such symptoms,” Dr. Podolanczuk told this news organization.
Defining the challenge
The foundation of any diagnosis lies in a clear definition and established diagnostic criteria. During the session, it became apparent that different criteria could be employed for PPF diagnosis, leading to the identification of distinct patient populations.
In 2022, the Official ATS/ERS/JRS/ALAT Clinical Practice Guideline provided the first comprehensive definition of the PPF phenotype. According to this guideline, PPF is defined by the presence of at least two of three criteria: worsening symptoms, radiological progression, or physiologic progression defined as a ≥ 5% absolute decline in FVC or ≥ 10% absolute decline in diffusion lung CO (DLCO) within the past year in a patient with interstitial lung disease (ILD) and lung scarring other than idiopathic pulmonary fibrosis (IPF), with no alternative explanation.
“Definitions from the guidelines were based on the available trials at that moment. Registry data suggest that using different criteria will probably lead to the identification of different, but always progressive, populations,” Dr. Wijsenbeek commented to this news organization. “I think we should not worry too much about the details of the criteria and it is good that we have a multimodality assessment: We ask the patient, we look at the pictures, and we measure the lung function. Combining those data, you can have a robust indication of progression.”
The current landscape
Currently, PPF diagnosis hinges on a combination of CT scans, patient narratives, and, in some cases, histological examination. Dr. Wijsenbeek stressed the need to transition to novel diagnostic modalities, including tools that can be readily employed by GPs in their practices.
“GPs have to care about a lot of different diseases, and it makes it more complicated to be aware of conditions like PPF: Symptoms are in fact extremely unspecific” Dr. Kreuter told this news organization. “My suggestion to GPs is to pay attention to the so-called inspiratory crackles because they represent a very early and specific sign of lung fibrosis. This sound does not resemble any other sound that you can hear with your stethoscope: It is like the sound you make walking on fresh snow,” he added, recommending a referral to the pulmonologist in case of identification of inspiratory crackles.
Additionally, several biomarkers can contribute to early PPF diagnosis, including the identification of the usual interstitial pneumonia (UIP) pattern through biopsy or imaging. “We know that this pattern predicts poor outcomes regardless of ILD type,” Dr. Podolanczuk explained, underlining the possibility of using a molecular classifier to identify a UIP pattern on transbronchial lung biopsy. “This is an already existing technology used to identify a gene expression pattern that is strongly predictive of a UIP pattern,” she said.
Furthermore, blood biomarkers, such as high peripheral blood monocyte count and telomere length, hold promise for early PPF detection and prognosis assessment.
The road ahead
The diagnostic landscape for PPF is evolving rapidly, with various emerging biomarkers and tools showing promise. Proteomics, alongside home spirometry as a digital biomarker for frequent FVC monitoring, have demonstrated potential for identifying patients who may benefit from early treatment. A 2022 study defined a 12-proteomic biomarkers signature of progressive fibrosing ILD that can identify patients who may benefit from early treatment and is predictive of outcomes regardless of the underlying CT pattern.
The integration of artificial intelligence into the interpretation of CT and x-ray images represents another avenue of advancement in PPF diagnosis. Dr. Podolanczuk highlighted the role of AI and quantitative CTs in enhancing diagnostic accuracy. She also mentioned innovative imaging methods, such as hyperpolarized gas MRI and endobronchial optical coherence tomography (EB-OCT), which offer new insights into disease progression and treatment response.
Beyond imaging and AI, various research tools are entering the diagnostic arena, including real-time breath analysis for distinguishing between different respiratory conditions. These tools collectively promise to shorten the time from symptom presentation to PPF diagnosis, a vital step in improving patient outcomes. In the words of Dr. Podolanczuk, “How early is too early to identify these patients? Let me say that there’s no such thing as ‘too early’ in the diagnosis of PPF!”
Dr. Podolanczuk disclosed grant funding from NHLBI, ALA, and Three Lakes Foundation; consulting fees from Regeneron, Roche, Imvaria, Boehringer Ingelheim, Veracyte, United Therapeutics, and Eisai; and honoraria from NACE and EBSCO/DynaMed. Ms. Robertson disclosed having no conflict.
A version of this article first appeared on Medscape.com.
AT ERS 2023
Anxiety (part 2): Treatment
This month we are following up on our previous piece on anxiety disorders. We wrote about how these disorders are common, amenable to treatment, and often curable, but are often missed as many children suffer silently or their symptoms are mistaken for signs of other problems. We reviewed the screening instruments that can help you to catch these “quiet” illnesses. Now, we are going to offer some detail about the effective treatments for the most common anxiety disorders and how to approach getting treatment started when a screen has turned up positive. If you are interested in a deeper dive, the American Academy of Child and Adolescent Psychiatry has detailed practice parameters for the disorders discussed below.
Anxiety disorders in young children
Separation anxiety disorder, specific phobia, generalized anxiety disorder, and social phobia are the anxiety disorders that most commonly affect the youngest children. Separation anxiety disorder is the most common childhood anxiety disorder and has an average age of onset of 6 years, whereas specific phobia peaks between 5 and 8 years of age, generalized anxiety disorder peaks at 8 years old and social phobia (or social anxiety disorder) has a peak age of onset of 13 years. The first-line treatment for each disorder is cognitive-behavioral therapy (CBT), and specifically a variant called exposure and response prevention. This treatment essentially helps patients to “learn” to have a different response, not anxiety, to the triggering thought or stimulus. CBT can be very effective, curative even, but these disorders can be difficult to treat when a child’s level of anxiety exceeds their ability to engage in treatment. In these cases, treatment can be facilitated by the addition of an SSRI, which is recommended by the American Academy of Child and Adolescent Psychiatry as a second-line treatment in children aged 6-18 years. Given the anxious child’s sensitivity to some side effects (such as GI distress) starting at a low dose and titrating up slowly is the recommendation, and effective dose ranges are higher than for the treatment of mood disorders. Without treatment, these disorders may become learned over years and predict complicating anxiety, mood, and substance use disorders in adolescence and adulthood. Any treatment can be helped by the addition of parent guidance, in which parents learn how to be emotionally supportive to their anxious children without accommodating to their demands or asking them to avoid of the source of anxiety.
Obsessive-compulsive disorder
Mild obsessive-compulsive disorder (OCD) describes what many of us do, like double-checking we have locked our door or put our work into our briefcase. OCD as a diagnosis with substantial dysfunction has a peak onset at age 10 and again at the age of 21. Over 50% of childhood-onset OCD will have a comorbid anxiety, attention, eating, or tic disorder. Without treatment, OCD is likely to become chronic, and the symptoms (intrusive thoughts, obsessive rumination, and compulsive behaviors) interfere with social and academic function. The behavioral accommodations and avoidance of distress that mark untreated OCD interfere with the healthy development of normal stress management skills that are a critical part of early and later adolescence. First-line treatment is CBT (with exposure and response prevention) with a therapist experienced in the treatment of OCD. A detailed symptom inventory (the Children’s Yale-Brown Obsessive Compulsive Scale) is relatively simple to complete, will confirm a suspected OCD diagnosis, and will create a valuable baseline by which treatment efficacy can be assessed. For those children with moderate to severe OCD, addition of an SSRI to augment and facilitate CBT therapy is recommended. Sertraline, fluvoxamine, fluoxetine, and paroxetine have all been studied and demonstrated efficacy. Clomipramine has well-established efficacy, but its more serious side effects and poorer tolerability make SSRIs the first choice. As with other anxiety disorders, starting at very low doses and titrating upward gradually is recommended. The efficacy of medication treatments is lower in those patients who have other psychiatric illnesses occurring with OCD. Again, parent guidance can be invaluable in supporting the child and improving family well-being.
PTSD
Studies have suggested that between 15% and 45% of children and adolescents in the United States experience a traumatic event, but of those children less than 15% of girls and 6% of boys will develop PTSD in the months that follow. It is important to consider other mood and anxiety disorders in assessing youth with a trauma history who present with symptoms of anxiety and impaired function more than 1 month after the traumatic event. With a history of a traumatic event, it can be helpful to use a specific screening instrument for PTSD, such as the Child PTSD Symptoms Scale or the UCLA PTSD Reaction Index. The symptoms of other disorders (including ADHD) can mimic PTSD, and these disorders may be comorbid with mood, substance use, and eating disorders. Treatment is trauma-focused CBT, with careful use of medications to manage specific symptoms (such as nightmares). Evidence has shown that inclusion of parents in the CBT treatment results in greater reduction in both mood and behavioral symptoms than treating the children alone.
Special cases: School refusal
School refusal affects between 2% and 5% of children, and it is critical to address it promptly or else it can become entrenched and much more difficult to treat. It peaks at 6 and again at 14 years old and often comes to the attention of the pediatrician as children complain of somatic concerns that prove to have no clear cause. It is important to screen for trauma, mood, and anxiety disorders so that you might make reasonable treatment recommendations. But the critical intervention is a behavioral plan that supports the child’s prompt return to school. This requires communication with school personnel and parents to create a plan for the child’s return to school (using natural rewards like friends and trusted teachers) and staying at school (with detailed contingency planning). Parents may need help finding ways to “demagnetize” home and “remagnetize” school, such as turning off the Internet at home and not allowing a child to play sports or with friends when not attending school. Psychotherapy will be helpful for an underlying anxiety or mood disorder, and medications may also be helpful, but education and support for parents to understand how to manage the distress avoidance and rewards of school refusal are generally the critical components of an effective response to this serious problem.
Special cases: Adolescents with new anxiety symptoms
Most childhood anxiety disorders occur before puberty, but anxiety is a common symptom of mood and substance use disorders in teenagers, and often the symptom that drives help-seeking. It is important to screen teens who present with anxiety for underlying mood or substance use disorders. For example, panic disorder is relatively common in young adults, while in teenagers, panic attacks are a frequent symptom of depression or of withdrawal from regular cannabis use. If anxiety has been present and untreated since childhood, adolescents may present with complex comorbid mood and anxiety disorders and struggle with distress tolerance, social difficulties, and perfectionism. Anxiety itself is a very regular developmental feature of adolescence as this is a time of navigating peer relationships, identity, gradual separation from family, and transition to college or work. Every teen would likely benefit from advice about their sleep, exercise, use of any substances, and screen time habits.
For all of your patients with anxiety (and their parents), recognize that anxiety about being liked, making a varsity team, competing for college entrance, and becoming a young adult is expected: uncomfortable, but part of life. It’s adaptive. It helps people to stay safe, get their homework done, and avoid accidents. When people have high levels of anxiety, they can learn to identify their feelings, distinguish between facts and feelings, and learn to manage the anxiety adaptively. If anxiety causes dysfunction in major areas (school, family, friends, activities, and mood), prompt attention is required.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
This month we are following up on our previous piece on anxiety disorders. We wrote about how these disorders are common, amenable to treatment, and often curable, but are often missed as many children suffer silently or their symptoms are mistaken for signs of other problems. We reviewed the screening instruments that can help you to catch these “quiet” illnesses. Now, we are going to offer some detail about the effective treatments for the most common anxiety disorders and how to approach getting treatment started when a screen has turned up positive. If you are interested in a deeper dive, the American Academy of Child and Adolescent Psychiatry has detailed practice parameters for the disorders discussed below.
Anxiety disorders in young children
Separation anxiety disorder, specific phobia, generalized anxiety disorder, and social phobia are the anxiety disorders that most commonly affect the youngest children. Separation anxiety disorder is the most common childhood anxiety disorder and has an average age of onset of 6 years, whereas specific phobia peaks between 5 and 8 years of age, generalized anxiety disorder peaks at 8 years old and social phobia (or social anxiety disorder) has a peak age of onset of 13 years. The first-line treatment for each disorder is cognitive-behavioral therapy (CBT), and specifically a variant called exposure and response prevention. This treatment essentially helps patients to “learn” to have a different response, not anxiety, to the triggering thought or stimulus. CBT can be very effective, curative even, but these disorders can be difficult to treat when a child’s level of anxiety exceeds their ability to engage in treatment. In these cases, treatment can be facilitated by the addition of an SSRI, which is recommended by the American Academy of Child and Adolescent Psychiatry as a second-line treatment in children aged 6-18 years. Given the anxious child’s sensitivity to some side effects (such as GI distress) starting at a low dose and titrating up slowly is the recommendation, and effective dose ranges are higher than for the treatment of mood disorders. Without treatment, these disorders may become learned over years and predict complicating anxiety, mood, and substance use disorders in adolescence and adulthood. Any treatment can be helped by the addition of parent guidance, in which parents learn how to be emotionally supportive to their anxious children without accommodating to their demands or asking them to avoid of the source of anxiety.
Obsessive-compulsive disorder
Mild obsessive-compulsive disorder (OCD) describes what many of us do, like double-checking we have locked our door or put our work into our briefcase. OCD as a diagnosis with substantial dysfunction has a peak onset at age 10 and again at the age of 21. Over 50% of childhood-onset OCD will have a comorbid anxiety, attention, eating, or tic disorder. Without treatment, OCD is likely to become chronic, and the symptoms (intrusive thoughts, obsessive rumination, and compulsive behaviors) interfere with social and academic function. The behavioral accommodations and avoidance of distress that mark untreated OCD interfere with the healthy development of normal stress management skills that are a critical part of early and later adolescence. First-line treatment is CBT (with exposure and response prevention) with a therapist experienced in the treatment of OCD. A detailed symptom inventory (the Children’s Yale-Brown Obsessive Compulsive Scale) is relatively simple to complete, will confirm a suspected OCD diagnosis, and will create a valuable baseline by which treatment efficacy can be assessed. For those children with moderate to severe OCD, addition of an SSRI to augment and facilitate CBT therapy is recommended. Sertraline, fluvoxamine, fluoxetine, and paroxetine have all been studied and demonstrated efficacy. Clomipramine has well-established efficacy, but its more serious side effects and poorer tolerability make SSRIs the first choice. As with other anxiety disorders, starting at very low doses and titrating upward gradually is recommended. The efficacy of medication treatments is lower in those patients who have other psychiatric illnesses occurring with OCD. Again, parent guidance can be invaluable in supporting the child and improving family well-being.
PTSD
Studies have suggested that between 15% and 45% of children and adolescents in the United States experience a traumatic event, but of those children less than 15% of girls and 6% of boys will develop PTSD in the months that follow. It is important to consider other mood and anxiety disorders in assessing youth with a trauma history who present with symptoms of anxiety and impaired function more than 1 month after the traumatic event. With a history of a traumatic event, it can be helpful to use a specific screening instrument for PTSD, such as the Child PTSD Symptoms Scale or the UCLA PTSD Reaction Index. The symptoms of other disorders (including ADHD) can mimic PTSD, and these disorders may be comorbid with mood, substance use, and eating disorders. Treatment is trauma-focused CBT, with careful use of medications to manage specific symptoms (such as nightmares). Evidence has shown that inclusion of parents in the CBT treatment results in greater reduction in both mood and behavioral symptoms than treating the children alone.
Special cases: School refusal
School refusal affects between 2% and 5% of children, and it is critical to address it promptly or else it can become entrenched and much more difficult to treat. It peaks at 6 and again at 14 years old and often comes to the attention of the pediatrician as children complain of somatic concerns that prove to have no clear cause. It is important to screen for trauma, mood, and anxiety disorders so that you might make reasonable treatment recommendations. But the critical intervention is a behavioral plan that supports the child’s prompt return to school. This requires communication with school personnel and parents to create a plan for the child’s return to school (using natural rewards like friends and trusted teachers) and staying at school (with detailed contingency planning). Parents may need help finding ways to “demagnetize” home and “remagnetize” school, such as turning off the Internet at home and not allowing a child to play sports or with friends when not attending school. Psychotherapy will be helpful for an underlying anxiety or mood disorder, and medications may also be helpful, but education and support for parents to understand how to manage the distress avoidance and rewards of school refusal are generally the critical components of an effective response to this serious problem.
Special cases: Adolescents with new anxiety symptoms
Most childhood anxiety disorders occur before puberty, but anxiety is a common symptom of mood and substance use disorders in teenagers, and often the symptom that drives help-seeking. It is important to screen teens who present with anxiety for underlying mood or substance use disorders. For example, panic disorder is relatively common in young adults, while in teenagers, panic attacks are a frequent symptom of depression or of withdrawal from regular cannabis use. If anxiety has been present and untreated since childhood, adolescents may present with complex comorbid mood and anxiety disorders and struggle with distress tolerance, social difficulties, and perfectionism. Anxiety itself is a very regular developmental feature of adolescence as this is a time of navigating peer relationships, identity, gradual separation from family, and transition to college or work. Every teen would likely benefit from advice about their sleep, exercise, use of any substances, and screen time habits.
For all of your patients with anxiety (and their parents), recognize that anxiety about being liked, making a varsity team, competing for college entrance, and becoming a young adult is expected: uncomfortable, but part of life. It’s adaptive. It helps people to stay safe, get their homework done, and avoid accidents. When people have high levels of anxiety, they can learn to identify their feelings, distinguish between facts and feelings, and learn to manage the anxiety adaptively. If anxiety causes dysfunction in major areas (school, family, friends, activities, and mood), prompt attention is required.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
This month we are following up on our previous piece on anxiety disorders. We wrote about how these disorders are common, amenable to treatment, and often curable, but are often missed as many children suffer silently or their symptoms are mistaken for signs of other problems. We reviewed the screening instruments that can help you to catch these “quiet” illnesses. Now, we are going to offer some detail about the effective treatments for the most common anxiety disorders and how to approach getting treatment started when a screen has turned up positive. If you are interested in a deeper dive, the American Academy of Child and Adolescent Psychiatry has detailed practice parameters for the disorders discussed below.
Anxiety disorders in young children
Separation anxiety disorder, specific phobia, generalized anxiety disorder, and social phobia are the anxiety disorders that most commonly affect the youngest children. Separation anxiety disorder is the most common childhood anxiety disorder and has an average age of onset of 6 years, whereas specific phobia peaks between 5 and 8 years of age, generalized anxiety disorder peaks at 8 years old and social phobia (or social anxiety disorder) has a peak age of onset of 13 years. The first-line treatment for each disorder is cognitive-behavioral therapy (CBT), and specifically a variant called exposure and response prevention. This treatment essentially helps patients to “learn” to have a different response, not anxiety, to the triggering thought or stimulus. CBT can be very effective, curative even, but these disorders can be difficult to treat when a child’s level of anxiety exceeds their ability to engage in treatment. In these cases, treatment can be facilitated by the addition of an SSRI, which is recommended by the American Academy of Child and Adolescent Psychiatry as a second-line treatment in children aged 6-18 years. Given the anxious child’s sensitivity to some side effects (such as GI distress) starting at a low dose and titrating up slowly is the recommendation, and effective dose ranges are higher than for the treatment of mood disorders. Without treatment, these disorders may become learned over years and predict complicating anxiety, mood, and substance use disorders in adolescence and adulthood. Any treatment can be helped by the addition of parent guidance, in which parents learn how to be emotionally supportive to their anxious children without accommodating to their demands or asking them to avoid of the source of anxiety.
Obsessive-compulsive disorder
Mild obsessive-compulsive disorder (OCD) describes what many of us do, like double-checking we have locked our door or put our work into our briefcase. OCD as a diagnosis with substantial dysfunction has a peak onset at age 10 and again at the age of 21. Over 50% of childhood-onset OCD will have a comorbid anxiety, attention, eating, or tic disorder. Without treatment, OCD is likely to become chronic, and the symptoms (intrusive thoughts, obsessive rumination, and compulsive behaviors) interfere with social and academic function. The behavioral accommodations and avoidance of distress that mark untreated OCD interfere with the healthy development of normal stress management skills that are a critical part of early and later adolescence. First-line treatment is CBT (with exposure and response prevention) with a therapist experienced in the treatment of OCD. A detailed symptom inventory (the Children’s Yale-Brown Obsessive Compulsive Scale) is relatively simple to complete, will confirm a suspected OCD diagnosis, and will create a valuable baseline by which treatment efficacy can be assessed. For those children with moderate to severe OCD, addition of an SSRI to augment and facilitate CBT therapy is recommended. Sertraline, fluvoxamine, fluoxetine, and paroxetine have all been studied and demonstrated efficacy. Clomipramine has well-established efficacy, but its more serious side effects and poorer tolerability make SSRIs the first choice. As with other anxiety disorders, starting at very low doses and titrating upward gradually is recommended. The efficacy of medication treatments is lower in those patients who have other psychiatric illnesses occurring with OCD. Again, parent guidance can be invaluable in supporting the child and improving family well-being.
PTSD
Studies have suggested that between 15% and 45% of children and adolescents in the United States experience a traumatic event, but of those children less than 15% of girls and 6% of boys will develop PTSD in the months that follow. It is important to consider other mood and anxiety disorders in assessing youth with a trauma history who present with symptoms of anxiety and impaired function more than 1 month after the traumatic event. With a history of a traumatic event, it can be helpful to use a specific screening instrument for PTSD, such as the Child PTSD Symptoms Scale or the UCLA PTSD Reaction Index. The symptoms of other disorders (including ADHD) can mimic PTSD, and these disorders may be comorbid with mood, substance use, and eating disorders. Treatment is trauma-focused CBT, with careful use of medications to manage specific symptoms (such as nightmares). Evidence has shown that inclusion of parents in the CBT treatment results in greater reduction in both mood and behavioral symptoms than treating the children alone.
Special cases: School refusal
School refusal affects between 2% and 5% of children, and it is critical to address it promptly or else it can become entrenched and much more difficult to treat. It peaks at 6 and again at 14 years old and often comes to the attention of the pediatrician as children complain of somatic concerns that prove to have no clear cause. It is important to screen for trauma, mood, and anxiety disorders so that you might make reasonable treatment recommendations. But the critical intervention is a behavioral plan that supports the child’s prompt return to school. This requires communication with school personnel and parents to create a plan for the child’s return to school (using natural rewards like friends and trusted teachers) and staying at school (with detailed contingency planning). Parents may need help finding ways to “demagnetize” home and “remagnetize” school, such as turning off the Internet at home and not allowing a child to play sports or with friends when not attending school. Psychotherapy will be helpful for an underlying anxiety or mood disorder, and medications may also be helpful, but education and support for parents to understand how to manage the distress avoidance and rewards of school refusal are generally the critical components of an effective response to this serious problem.
Special cases: Adolescents with new anxiety symptoms
Most childhood anxiety disorders occur before puberty, but anxiety is a common symptom of mood and substance use disorders in teenagers, and often the symptom that drives help-seeking. It is important to screen teens who present with anxiety for underlying mood or substance use disorders. For example, panic disorder is relatively common in young adults, while in teenagers, panic attacks are a frequent symptom of depression or of withdrawal from regular cannabis use. If anxiety has been present and untreated since childhood, adolescents may present with complex comorbid mood and anxiety disorders and struggle with distress tolerance, social difficulties, and perfectionism. Anxiety itself is a very regular developmental feature of adolescence as this is a time of navigating peer relationships, identity, gradual separation from family, and transition to college or work. Every teen would likely benefit from advice about their sleep, exercise, use of any substances, and screen time habits.
For all of your patients with anxiety (and their parents), recognize that anxiety about being liked, making a varsity team, competing for college entrance, and becoming a young adult is expected: uncomfortable, but part of life. It’s adaptive. It helps people to stay safe, get their homework done, and avoid accidents. When people have high levels of anxiety, they can learn to identify their feelings, distinguish between facts and feelings, and learn to manage the anxiety adaptively. If anxiety causes dysfunction in major areas (school, family, friends, activities, and mood), prompt attention is required.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
SGLT2 inhibitors: No benefit or harm in hospitalized COVID-19
A new meta-analysis has shown that SGLT2 inhibitors do not lead to lower 28-day all-cause mortality, compared with usual care or placebo, in patients hospitalized with COVID-19.
However, no major safety issues were identified with the use of SGLT2 inhibitors in these acutely ill patients, the researchers report.
“While these findings do not support the use of SGLT2-inhibitors as standard of care for patients hospitalized with COVID-19, I think the most important take home message here is that the use of these medications appears to be safe even in really acutely ill hospitalized patients,” lead investigator of the meta-analysis, Mikhail Kosiborod, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., concluded.
He said this was important because the list of indications for SGLT2 inhibitors is rapidly growing.
“These medications are being used in more and more patients. And we know that when we discontinue medications in the hospital they frequently don’t get restarted, which can lead to real risks if SGLT2 inhibitors are stopped in patients with heart failure, chronic kidney disease, or diabetes. So, ,” he added.
The new meta-analysis was presented at the recent annual congress of the European Society of Cardiology, held in Amsterdam.
Discussant of the presentation at the ESC Hotline session, Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital, Boston, agreed with Dr. Kosiborod’s interpretation.
“Until today we have had very limited information on the safety of SGLT2-inhibitors in acute illness, as the pivotal trials which established the use of these drugs in diabetes and chronic kidney disease largely excluded patients who were hospitalized,” Dr. Vaduganathan said.
“While the overall results of this meta-analysis are neutral and SGLT2 inhibitors will not be added as drugs to be used in the primary care of patients with COVID-19, it certainly sends a strong message of safety in acutely ill patients,” he added.
Dr. Vaduganathan explained that from the beginning of the COVID-19 pandemic, there was great interest in repurposing established therapies for alternative indications for their use in the management of COVID-19.
“Conditions that strongly predispose to adverse COVID outcomes strongly overlap with established indications for SGLT2-inhibitors. So many wondered whether these drugs may be an ideal treatment candidate for the management of COVID-19. However, there have been many safety concerns about the use of SGLT2-inhibitors in this acute setting, with worries that they may induce hemodynamic changes such an excessive lowering of blood pressure, or metabolic changes such as ketoacidosis in acutely ill patients,” he noted.
The initial DARE-19 study investigating SGLT2-inhibitors in COVID-19, with 1,250 participants, found a 20% reduction in the primary outcome of organ dysfunction or death, but this did not reach statistical significance, and no safety issues were seen. This “intriguing” result led to two further larger trials – the ACTIV-4a and RECOVERY trials, Dr. Vaduganathan reported.
“Those early signals of benefit seen in DARE-19 were largely not substantiated in the ACTIV-4A and RECOVERY trials, or in this new meta-analysis, and now we have this much larger body of evidence and more stable estimates about the efficacy of these drugs in acutely ill COVID-19 patients,” he said.
“But the story that we will all take forward is one of safety. This set of trials was arguably conducted in some of the sickest patients we’ve seen who have been exposed to SGLT2-inhibitors, and they strongly affirm that these agents can be safely continued in the setting of acute illness, with very low rates of ketoacidosis and kidney injury, and there was no prolongation of hospital stay,” he commented.
In his presentation, Dr. Kosiborod explained that treatments targeting COVID-19 pathobiology such as dysregulated immune responses, endothelial damage, microvascular thrombosis, and inflammation have been shown to improve the key outcomes in this patient group.
SGLT2 inhibitors, which modulate similar pathobiology, provide cardiovascular protection and prevent the progression of kidney disease in patients at risk for these events, including those with type 2 diabetes, heart failure, and kidney disease, and may also lead to organ protection in a setting of acute illness such as COVID-19, he noted. However, the role of SGLT2 inhibitors in patients hospitalized with COVID-19 remains uncertain.
To address the need for more definitive efficacy data, the World Health Organization Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group conducted a prospective meta-analysis using data from the three randomized controlled trials, DARE-19, RECOVERY, and ACTIV-4a, evaluating SGLT2 inhibitors in patients hospitalized with COVID-19.
Overall, these trials randomized 6,096 participants: 3,025 to SGLT2 inhibitors and 3,071 to usual care or placebo. The average age of participants ranged between 62 and 73 years across the trials, 39% were women, and 25% had type 2 diabetes.
By 28 days after randomization, all-cause mortality, the primary endpoint, had occurred in 11.6% of the SGLT2-inhibitor patients, compared with 12.4% of those randomized to usual care or placebo, giving an odds ratio of 0.93 (95% confidence interval, 0.79-1.08; P = .33) for SGLT2 inhibitors, with consistency across trials.
Data on in-hospital and 90-day all-cause mortality were only available for two out of three trials (DARE-19 and ACTIV-4a), but the results were similar to the primary endpoint showing nonsignificant trends toward a possible benefit in the SGLT2-inhibitor group.
The results were also similar for the secondary outcomes of progression to acute kidney injury or requirement for dialysis or death, and progression to invasive mechanical ventilation, extracorporeal membrane oxygenation, or death, both assessed at 28 days.
The primary safety outcome of ketoacidosis by 28 days was observed in seven and two patients allocated to SGLT2 inhibitors and usual care or placebo, respectively, and overall, the incidence of reported serious adverse events was balanced between treatment groups.
The RECOVERY trial was supported by grants to the University of Oxford from UK Research and Innovation, the National Institute for Health and Care Research, and Wellcome. The ACTIV-4a platform was sponsored by the National Heart, Lung, and Blood Institute. DARE-19 was an investigator-initiated collaborative trial supported by AstraZeneca. Dr. Kosiborod reported numerous conflicts of interest.
A version of this article first appeared on Medscape.com.
A new meta-analysis has shown that SGLT2 inhibitors do not lead to lower 28-day all-cause mortality, compared with usual care or placebo, in patients hospitalized with COVID-19.
However, no major safety issues were identified with the use of SGLT2 inhibitors in these acutely ill patients, the researchers report.
“While these findings do not support the use of SGLT2-inhibitors as standard of care for patients hospitalized with COVID-19, I think the most important take home message here is that the use of these medications appears to be safe even in really acutely ill hospitalized patients,” lead investigator of the meta-analysis, Mikhail Kosiborod, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., concluded.
He said this was important because the list of indications for SGLT2 inhibitors is rapidly growing.
“These medications are being used in more and more patients. And we know that when we discontinue medications in the hospital they frequently don’t get restarted, which can lead to real risks if SGLT2 inhibitors are stopped in patients with heart failure, chronic kidney disease, or diabetes. So, ,” he added.
The new meta-analysis was presented at the recent annual congress of the European Society of Cardiology, held in Amsterdam.
Discussant of the presentation at the ESC Hotline session, Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital, Boston, agreed with Dr. Kosiborod’s interpretation.
“Until today we have had very limited information on the safety of SGLT2-inhibitors in acute illness, as the pivotal trials which established the use of these drugs in diabetes and chronic kidney disease largely excluded patients who were hospitalized,” Dr. Vaduganathan said.
“While the overall results of this meta-analysis are neutral and SGLT2 inhibitors will not be added as drugs to be used in the primary care of patients with COVID-19, it certainly sends a strong message of safety in acutely ill patients,” he added.
Dr. Vaduganathan explained that from the beginning of the COVID-19 pandemic, there was great interest in repurposing established therapies for alternative indications for their use in the management of COVID-19.
“Conditions that strongly predispose to adverse COVID outcomes strongly overlap with established indications for SGLT2-inhibitors. So many wondered whether these drugs may be an ideal treatment candidate for the management of COVID-19. However, there have been many safety concerns about the use of SGLT2-inhibitors in this acute setting, with worries that they may induce hemodynamic changes such an excessive lowering of blood pressure, or metabolic changes such as ketoacidosis in acutely ill patients,” he noted.
The initial DARE-19 study investigating SGLT2-inhibitors in COVID-19, with 1,250 participants, found a 20% reduction in the primary outcome of organ dysfunction or death, but this did not reach statistical significance, and no safety issues were seen. This “intriguing” result led to two further larger trials – the ACTIV-4a and RECOVERY trials, Dr. Vaduganathan reported.
“Those early signals of benefit seen in DARE-19 were largely not substantiated in the ACTIV-4A and RECOVERY trials, or in this new meta-analysis, and now we have this much larger body of evidence and more stable estimates about the efficacy of these drugs in acutely ill COVID-19 patients,” he said.
“But the story that we will all take forward is one of safety. This set of trials was arguably conducted in some of the sickest patients we’ve seen who have been exposed to SGLT2-inhibitors, and they strongly affirm that these agents can be safely continued in the setting of acute illness, with very low rates of ketoacidosis and kidney injury, and there was no prolongation of hospital stay,” he commented.
In his presentation, Dr. Kosiborod explained that treatments targeting COVID-19 pathobiology such as dysregulated immune responses, endothelial damage, microvascular thrombosis, and inflammation have been shown to improve the key outcomes in this patient group.
SGLT2 inhibitors, which modulate similar pathobiology, provide cardiovascular protection and prevent the progression of kidney disease in patients at risk for these events, including those with type 2 diabetes, heart failure, and kidney disease, and may also lead to organ protection in a setting of acute illness such as COVID-19, he noted. However, the role of SGLT2 inhibitors in patients hospitalized with COVID-19 remains uncertain.
To address the need for more definitive efficacy data, the World Health Organization Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group conducted a prospective meta-analysis using data from the three randomized controlled trials, DARE-19, RECOVERY, and ACTIV-4a, evaluating SGLT2 inhibitors in patients hospitalized with COVID-19.
Overall, these trials randomized 6,096 participants: 3,025 to SGLT2 inhibitors and 3,071 to usual care or placebo. The average age of participants ranged between 62 and 73 years across the trials, 39% were women, and 25% had type 2 diabetes.
By 28 days after randomization, all-cause mortality, the primary endpoint, had occurred in 11.6% of the SGLT2-inhibitor patients, compared with 12.4% of those randomized to usual care or placebo, giving an odds ratio of 0.93 (95% confidence interval, 0.79-1.08; P = .33) for SGLT2 inhibitors, with consistency across trials.
Data on in-hospital and 90-day all-cause mortality were only available for two out of three trials (DARE-19 and ACTIV-4a), but the results were similar to the primary endpoint showing nonsignificant trends toward a possible benefit in the SGLT2-inhibitor group.
The results were also similar for the secondary outcomes of progression to acute kidney injury or requirement for dialysis or death, and progression to invasive mechanical ventilation, extracorporeal membrane oxygenation, or death, both assessed at 28 days.
The primary safety outcome of ketoacidosis by 28 days was observed in seven and two patients allocated to SGLT2 inhibitors and usual care or placebo, respectively, and overall, the incidence of reported serious adverse events was balanced between treatment groups.
The RECOVERY trial was supported by grants to the University of Oxford from UK Research and Innovation, the National Institute for Health and Care Research, and Wellcome. The ACTIV-4a platform was sponsored by the National Heart, Lung, and Blood Institute. DARE-19 was an investigator-initiated collaborative trial supported by AstraZeneca. Dr. Kosiborod reported numerous conflicts of interest.
A version of this article first appeared on Medscape.com.
A new meta-analysis has shown that SGLT2 inhibitors do not lead to lower 28-day all-cause mortality, compared with usual care or placebo, in patients hospitalized with COVID-19.
However, no major safety issues were identified with the use of SGLT2 inhibitors in these acutely ill patients, the researchers report.
“While these findings do not support the use of SGLT2-inhibitors as standard of care for patients hospitalized with COVID-19, I think the most important take home message here is that the use of these medications appears to be safe even in really acutely ill hospitalized patients,” lead investigator of the meta-analysis, Mikhail Kosiborod, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., concluded.
He said this was important because the list of indications for SGLT2 inhibitors is rapidly growing.
“These medications are being used in more and more patients. And we know that when we discontinue medications in the hospital they frequently don’t get restarted, which can lead to real risks if SGLT2 inhibitors are stopped in patients with heart failure, chronic kidney disease, or diabetes. So, ,” he added.
The new meta-analysis was presented at the recent annual congress of the European Society of Cardiology, held in Amsterdam.
Discussant of the presentation at the ESC Hotline session, Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital, Boston, agreed with Dr. Kosiborod’s interpretation.
“Until today we have had very limited information on the safety of SGLT2-inhibitors in acute illness, as the pivotal trials which established the use of these drugs in diabetes and chronic kidney disease largely excluded patients who were hospitalized,” Dr. Vaduganathan said.
“While the overall results of this meta-analysis are neutral and SGLT2 inhibitors will not be added as drugs to be used in the primary care of patients with COVID-19, it certainly sends a strong message of safety in acutely ill patients,” he added.
Dr. Vaduganathan explained that from the beginning of the COVID-19 pandemic, there was great interest in repurposing established therapies for alternative indications for their use in the management of COVID-19.
“Conditions that strongly predispose to adverse COVID outcomes strongly overlap with established indications for SGLT2-inhibitors. So many wondered whether these drugs may be an ideal treatment candidate for the management of COVID-19. However, there have been many safety concerns about the use of SGLT2-inhibitors in this acute setting, with worries that they may induce hemodynamic changes such an excessive lowering of blood pressure, or metabolic changes such as ketoacidosis in acutely ill patients,” he noted.
The initial DARE-19 study investigating SGLT2-inhibitors in COVID-19, with 1,250 participants, found a 20% reduction in the primary outcome of organ dysfunction or death, but this did not reach statistical significance, and no safety issues were seen. This “intriguing” result led to two further larger trials – the ACTIV-4a and RECOVERY trials, Dr. Vaduganathan reported.
“Those early signals of benefit seen in DARE-19 were largely not substantiated in the ACTIV-4A and RECOVERY trials, or in this new meta-analysis, and now we have this much larger body of evidence and more stable estimates about the efficacy of these drugs in acutely ill COVID-19 patients,” he said.
“But the story that we will all take forward is one of safety. This set of trials was arguably conducted in some of the sickest patients we’ve seen who have been exposed to SGLT2-inhibitors, and they strongly affirm that these agents can be safely continued in the setting of acute illness, with very low rates of ketoacidosis and kidney injury, and there was no prolongation of hospital stay,” he commented.
In his presentation, Dr. Kosiborod explained that treatments targeting COVID-19 pathobiology such as dysregulated immune responses, endothelial damage, microvascular thrombosis, and inflammation have been shown to improve the key outcomes in this patient group.
SGLT2 inhibitors, which modulate similar pathobiology, provide cardiovascular protection and prevent the progression of kidney disease in patients at risk for these events, including those with type 2 diabetes, heart failure, and kidney disease, and may also lead to organ protection in a setting of acute illness such as COVID-19, he noted. However, the role of SGLT2 inhibitors in patients hospitalized with COVID-19 remains uncertain.
To address the need for more definitive efficacy data, the World Health Organization Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group conducted a prospective meta-analysis using data from the three randomized controlled trials, DARE-19, RECOVERY, and ACTIV-4a, evaluating SGLT2 inhibitors in patients hospitalized with COVID-19.
Overall, these trials randomized 6,096 participants: 3,025 to SGLT2 inhibitors and 3,071 to usual care or placebo. The average age of participants ranged between 62 and 73 years across the trials, 39% were women, and 25% had type 2 diabetes.
By 28 days after randomization, all-cause mortality, the primary endpoint, had occurred in 11.6% of the SGLT2-inhibitor patients, compared with 12.4% of those randomized to usual care or placebo, giving an odds ratio of 0.93 (95% confidence interval, 0.79-1.08; P = .33) for SGLT2 inhibitors, with consistency across trials.
Data on in-hospital and 90-day all-cause mortality were only available for two out of three trials (DARE-19 and ACTIV-4a), but the results were similar to the primary endpoint showing nonsignificant trends toward a possible benefit in the SGLT2-inhibitor group.
The results were also similar for the secondary outcomes of progression to acute kidney injury or requirement for dialysis or death, and progression to invasive mechanical ventilation, extracorporeal membrane oxygenation, or death, both assessed at 28 days.
The primary safety outcome of ketoacidosis by 28 days was observed in seven and two patients allocated to SGLT2 inhibitors and usual care or placebo, respectively, and overall, the incidence of reported serious adverse events was balanced between treatment groups.
The RECOVERY trial was supported by grants to the University of Oxford from UK Research and Innovation, the National Institute for Health and Care Research, and Wellcome. The ACTIV-4a platform was sponsored by the National Heart, Lung, and Blood Institute. DARE-19 was an investigator-initiated collaborative trial supported by AstraZeneca. Dr. Kosiborod reported numerous conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2023
Atypical antipsychotics no safer than haloperidol for postoperative delirium: Study
Dae Hyun Kim, MD, ScD, associate professor of medicine at Harvard Medical School, in Boston, who is the lead author of the study, said the findings were especially relevant, as the use of atypical antipsychotics, such as quetiapine, olanzapine, and risperidone, has increased while use of haloperidol has fallen.
A separate but related study led by Dr. Kim, which was recently published in the Journal of the American Geriatrics Society, showed that between 2008 and 2018, use of haloperidol and benzodiazepines in community hospitals and academic medical centers decreased while use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine rose (P < .01).
“Clinicians should not think atypical antipsychotics are the safer option to haloperidol,” Dr. Kim said. “We should focus on reducing prescriptions.”
Postoperative delirium
Postoperative delirium is the among the most common complications of surgery in older adults, affecting between 15% and 50% of those patients who undergo major operations. Postoperative delirium is associated with longer hospital stays, poor functional recovery, institutionalization, dementia, and death.
According to research from Harvard Medical School, postoperative delirium is linked to a 40% faster rate of cognitive decline among patients who develop the condition, compared with those who do not experience the complication.
While older patients often feel tired or a bit off after surgery, marked changes in mental function, such as confusion, disorientation, agitation, aggression, hallucinations, or persistent sleepiness, could indicate postoperative delirium.
“Antipsychotic medications are most commonly used off label for managing those symptoms of delirium,” Dr. Kim said. “What we’ve done is look at the comparative safety of two other drugs.”
Results
In the retrospective cohort study, researchers analyzed data from 17,115 patients aged 65 years and older who were without psychiatric disorders and who received oral antipsychotics after major surgery requiring general anesthesia.
“These results don’t apply to people in emergent situations where there is severe behavior that threatens their safety and others,” Dr. Kim noted.
There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%), olanzapine (2.8%; relative risk, 0.74; 95% confidence interval, 0.42-1.27), quetiapine (2.6%; RR, 0.70; 95% CI, 0.47-1.04), or risperidone (3.3%; RR, 0.90; CI, 0.53-1.41).
The study also found statistically insignificant differences in the risk for nonfatal clinical events. Those risks ranged from 2% to 2.6% for a cardiac arrhythmia, from 4.2% to 4.6% for pneumonia, and from 0.6% to 1.2% for strokes or transient ischemic attacks.
Esther Oh, MD, PhD, an associate professor at Johns Hopkins University, Baltimore, said that caring for patients who experience acute changes in mental status or behaviors during hospitalization can be difficult.
“Although there is a lot of evidence in the literature that nonpharmacological methods to address these problems are effective, staff shortages of recent years have made it even more difficult for the care team to institute these methods,” Dr. Oh said in an interview.
Prevention
Dr. Oh and Dr. Kim agreed that nonpharmacologic strategies, such as ensuring good nutrition and hydration, daily walking, cognitive-stimulating activities, and good sleep hygiene, are effective and safe in preventing postoperative delirium.
“These are common sense interventions, but they require a lot of staffing and training,” Dr. Kim said. “It’s a resource-intensive intervention that requires really changing the way hospital staff interacts with older patients in the hospital.”
Second-generation antipsychotic medications often are thought to be safer than haloperidol in terms of side effects, Dr. Oh said, but the new findings challenge that assumption.
“Based on the findings from this study and on prior studies of antipsychotic use for older adults, use of all antipsychotics, both first and second generation, should be reviewed carefully to ensure they are being administered at the lowest effective dose for the shortest duration possible,” she said.
The study was supported by the National Institute on Aging of the National Institutes of Health. Dr. Kim and Dr. Oh disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Dae Hyun Kim, MD, ScD, associate professor of medicine at Harvard Medical School, in Boston, who is the lead author of the study, said the findings were especially relevant, as the use of atypical antipsychotics, such as quetiapine, olanzapine, and risperidone, has increased while use of haloperidol has fallen.
A separate but related study led by Dr. Kim, which was recently published in the Journal of the American Geriatrics Society, showed that between 2008 and 2018, use of haloperidol and benzodiazepines in community hospitals and academic medical centers decreased while use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine rose (P < .01).
“Clinicians should not think atypical antipsychotics are the safer option to haloperidol,” Dr. Kim said. “We should focus on reducing prescriptions.”
Postoperative delirium
Postoperative delirium is the among the most common complications of surgery in older adults, affecting between 15% and 50% of those patients who undergo major operations. Postoperative delirium is associated with longer hospital stays, poor functional recovery, institutionalization, dementia, and death.
According to research from Harvard Medical School, postoperative delirium is linked to a 40% faster rate of cognitive decline among patients who develop the condition, compared with those who do not experience the complication.
While older patients often feel tired or a bit off after surgery, marked changes in mental function, such as confusion, disorientation, agitation, aggression, hallucinations, or persistent sleepiness, could indicate postoperative delirium.
“Antipsychotic medications are most commonly used off label for managing those symptoms of delirium,” Dr. Kim said. “What we’ve done is look at the comparative safety of two other drugs.”
Results
In the retrospective cohort study, researchers analyzed data from 17,115 patients aged 65 years and older who were without psychiatric disorders and who received oral antipsychotics after major surgery requiring general anesthesia.
“These results don’t apply to people in emergent situations where there is severe behavior that threatens their safety and others,” Dr. Kim noted.
There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%), olanzapine (2.8%; relative risk, 0.74; 95% confidence interval, 0.42-1.27), quetiapine (2.6%; RR, 0.70; 95% CI, 0.47-1.04), or risperidone (3.3%; RR, 0.90; CI, 0.53-1.41).
The study also found statistically insignificant differences in the risk for nonfatal clinical events. Those risks ranged from 2% to 2.6% for a cardiac arrhythmia, from 4.2% to 4.6% for pneumonia, and from 0.6% to 1.2% for strokes or transient ischemic attacks.
Esther Oh, MD, PhD, an associate professor at Johns Hopkins University, Baltimore, said that caring for patients who experience acute changes in mental status or behaviors during hospitalization can be difficult.
“Although there is a lot of evidence in the literature that nonpharmacological methods to address these problems are effective, staff shortages of recent years have made it even more difficult for the care team to institute these methods,” Dr. Oh said in an interview.
Prevention
Dr. Oh and Dr. Kim agreed that nonpharmacologic strategies, such as ensuring good nutrition and hydration, daily walking, cognitive-stimulating activities, and good sleep hygiene, are effective and safe in preventing postoperative delirium.
“These are common sense interventions, but they require a lot of staffing and training,” Dr. Kim said. “It’s a resource-intensive intervention that requires really changing the way hospital staff interacts with older patients in the hospital.”
Second-generation antipsychotic medications often are thought to be safer than haloperidol in terms of side effects, Dr. Oh said, but the new findings challenge that assumption.
“Based on the findings from this study and on prior studies of antipsychotic use for older adults, use of all antipsychotics, both first and second generation, should be reviewed carefully to ensure they are being administered at the lowest effective dose for the shortest duration possible,” she said.
The study was supported by the National Institute on Aging of the National Institutes of Health. Dr. Kim and Dr. Oh disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Dae Hyun Kim, MD, ScD, associate professor of medicine at Harvard Medical School, in Boston, who is the lead author of the study, said the findings were especially relevant, as the use of atypical antipsychotics, such as quetiapine, olanzapine, and risperidone, has increased while use of haloperidol has fallen.
A separate but related study led by Dr. Kim, which was recently published in the Journal of the American Geriatrics Society, showed that between 2008 and 2018, use of haloperidol and benzodiazepines in community hospitals and academic medical centers decreased while use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine rose (P < .01).
“Clinicians should not think atypical antipsychotics are the safer option to haloperidol,” Dr. Kim said. “We should focus on reducing prescriptions.”
Postoperative delirium
Postoperative delirium is the among the most common complications of surgery in older adults, affecting between 15% and 50% of those patients who undergo major operations. Postoperative delirium is associated with longer hospital stays, poor functional recovery, institutionalization, dementia, and death.
According to research from Harvard Medical School, postoperative delirium is linked to a 40% faster rate of cognitive decline among patients who develop the condition, compared with those who do not experience the complication.
While older patients often feel tired or a bit off after surgery, marked changes in mental function, such as confusion, disorientation, agitation, aggression, hallucinations, or persistent sleepiness, could indicate postoperative delirium.
“Antipsychotic medications are most commonly used off label for managing those symptoms of delirium,” Dr. Kim said. “What we’ve done is look at the comparative safety of two other drugs.”
Results
In the retrospective cohort study, researchers analyzed data from 17,115 patients aged 65 years and older who were without psychiatric disorders and who received oral antipsychotics after major surgery requiring general anesthesia.
“These results don’t apply to people in emergent situations where there is severe behavior that threatens their safety and others,” Dr. Kim noted.
There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%), olanzapine (2.8%; relative risk, 0.74; 95% confidence interval, 0.42-1.27), quetiapine (2.6%; RR, 0.70; 95% CI, 0.47-1.04), or risperidone (3.3%; RR, 0.90; CI, 0.53-1.41).
The study also found statistically insignificant differences in the risk for nonfatal clinical events. Those risks ranged from 2% to 2.6% for a cardiac arrhythmia, from 4.2% to 4.6% for pneumonia, and from 0.6% to 1.2% for strokes or transient ischemic attacks.
Esther Oh, MD, PhD, an associate professor at Johns Hopkins University, Baltimore, said that caring for patients who experience acute changes in mental status or behaviors during hospitalization can be difficult.
“Although there is a lot of evidence in the literature that nonpharmacological methods to address these problems are effective, staff shortages of recent years have made it even more difficult for the care team to institute these methods,” Dr. Oh said in an interview.
Prevention
Dr. Oh and Dr. Kim agreed that nonpharmacologic strategies, such as ensuring good nutrition and hydration, daily walking, cognitive-stimulating activities, and good sleep hygiene, are effective and safe in preventing postoperative delirium.
“These are common sense interventions, but they require a lot of staffing and training,” Dr. Kim said. “It’s a resource-intensive intervention that requires really changing the way hospital staff interacts with older patients in the hospital.”
Second-generation antipsychotic medications often are thought to be safer than haloperidol in terms of side effects, Dr. Oh said, but the new findings challenge that assumption.
“Based on the findings from this study and on prior studies of antipsychotic use for older adults, use of all antipsychotics, both first and second generation, should be reviewed carefully to ensure they are being administered at the lowest effective dose for the shortest duration possible,” she said.
The study was supported by the National Institute on Aging of the National Institutes of Health. Dr. Kim and Dr. Oh disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE