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FDA approves autoinjector pen for Humira biosimilar, Cyltezo
The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.
Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.
“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.
Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.
“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.
Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.
“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”
A version of this article first appeared on Medscape.com.
Docs can help combat TikTok misinformation on rare psychiatric disorder
SAN FRANCISCO – , new research shows.
These findings, say investigators, underscore the need for mental health professionals to help counter the spread of false information by creating accurate content and posting it on the popular social media platform.
“Health care professionals need to make engaging content to post on social media platforms like YouTube and especially TikTok, to reach wider audiences and combat misinformation about DID,” study investigator Isreal Bladimir Munoz, a fourth-year medical student at University of Texas, Galveston, said in an interview.
The findings were presented at the annual meeting of the American Psychiatric Association.
Popularized by the media
A rare condition affecting less than 1% of the general population, DID involves two or more distinct personality states, along with changes in behavior and memory gaps.
The condition has been popularized in books and the media. Movies such as “Split,” “Psycho,” and “Fight Club” all feature characters with DID.
“These bring awareness about the condition, but also often sensationalize or stigmatize it and reinforce stereotypes,” said Mr. Munoz.
In recent years, social media has become an integral part of everyday life. An estimated 4.2 billion people actively frequent sites such as YouTube, TikTok, Twitter, and Meta.
Although social media allows for instant communication and the opportunity for self-expression, there are mounting concerns about the spread of misinformation and its potential impact on mental health and privacy, said Mr. Munoz.
To evaluate the quality and accuracy of information about DID on social media, investigators analyzed 60 YouTube and 97 TikTok videos on the condition.
To evaluate the reliability and the intent and reliability of videos, researchers used the modified DISCERN instrument and the Global Quality Scale, a five-point rating system.
Using these tools, the researchers determined whether the selected videos were useful, misleading, or neither. Mr. Munoz said videos were classified as useful if they contained accurate information about the condition and its pathogenesis, treatment, and management.
Researchers determined that for YouTube videos, 51.7% were useful, 6.6% were misleading, and 34.7% were neither. About 43.3% of these videos involved interviews, 21.7% were educational, 15% involved personal stories, 8.3% were films/TV programs, 5% were comedy skits, and 3.3% were another content type.
The highest quality YouTube videos were from educational organizations and health care professionals. The least accurate videos came from independent users and film/TV sources.
As for TikTok videos on DID, only 5.2% were useful, 10.3% were misleading, and 41.7% were neither.
The main sources for TikTok videos were independent organizations, whereas podcasts and film/TV were the least common sources.
The findings, said Mr. Munoz, underscore the need for medical professionals to develop high-quality content about DID and post it on TikTok to counter misinformation on social media.
Call to action
In a comment, Howard Y. Liu, MD, a child and adolescent psychiatrist and chair of the department of psychiatry, University of Nebraska, Omaha, described the study as “compelling.”
When it comes to public health messages, it’s important to know what social media people are using. Today’s parents are on Twitter and Facebook, whereas their children are more likely to be checking out YouTube and TikTok, said Dr. Liu, chair of the APA’s Council on Communications.
“TikTok is critical because that’s where all the youth eyeballs are,” he said.
The medical profession needs to engage with the platform to reach this next-generation audience and help stop the spread of misinformation about DID, said Dr. Liu. He noted that the APA is looking into undertaking such an initiative.
The study investigators report no relevant disclosures. Dr. Liu reports no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , new research shows.
These findings, say investigators, underscore the need for mental health professionals to help counter the spread of false information by creating accurate content and posting it on the popular social media platform.
“Health care professionals need to make engaging content to post on social media platforms like YouTube and especially TikTok, to reach wider audiences and combat misinformation about DID,” study investigator Isreal Bladimir Munoz, a fourth-year medical student at University of Texas, Galveston, said in an interview.
The findings were presented at the annual meeting of the American Psychiatric Association.
Popularized by the media
A rare condition affecting less than 1% of the general population, DID involves two or more distinct personality states, along with changes in behavior and memory gaps.
The condition has been popularized in books and the media. Movies such as “Split,” “Psycho,” and “Fight Club” all feature characters with DID.
“These bring awareness about the condition, but also often sensationalize or stigmatize it and reinforce stereotypes,” said Mr. Munoz.
In recent years, social media has become an integral part of everyday life. An estimated 4.2 billion people actively frequent sites such as YouTube, TikTok, Twitter, and Meta.
Although social media allows for instant communication and the opportunity for self-expression, there are mounting concerns about the spread of misinformation and its potential impact on mental health and privacy, said Mr. Munoz.
To evaluate the quality and accuracy of information about DID on social media, investigators analyzed 60 YouTube and 97 TikTok videos on the condition.
To evaluate the reliability and the intent and reliability of videos, researchers used the modified DISCERN instrument and the Global Quality Scale, a five-point rating system.
Using these tools, the researchers determined whether the selected videos were useful, misleading, or neither. Mr. Munoz said videos were classified as useful if they contained accurate information about the condition and its pathogenesis, treatment, and management.
Researchers determined that for YouTube videos, 51.7% were useful, 6.6% were misleading, and 34.7% were neither. About 43.3% of these videos involved interviews, 21.7% were educational, 15% involved personal stories, 8.3% were films/TV programs, 5% were comedy skits, and 3.3% were another content type.
The highest quality YouTube videos were from educational organizations and health care professionals. The least accurate videos came from independent users and film/TV sources.
As for TikTok videos on DID, only 5.2% were useful, 10.3% were misleading, and 41.7% were neither.
The main sources for TikTok videos were independent organizations, whereas podcasts and film/TV were the least common sources.
The findings, said Mr. Munoz, underscore the need for medical professionals to develop high-quality content about DID and post it on TikTok to counter misinformation on social media.
Call to action
In a comment, Howard Y. Liu, MD, a child and adolescent psychiatrist and chair of the department of psychiatry, University of Nebraska, Omaha, described the study as “compelling.”
When it comes to public health messages, it’s important to know what social media people are using. Today’s parents are on Twitter and Facebook, whereas their children are more likely to be checking out YouTube and TikTok, said Dr. Liu, chair of the APA’s Council on Communications.
“TikTok is critical because that’s where all the youth eyeballs are,” he said.
The medical profession needs to engage with the platform to reach this next-generation audience and help stop the spread of misinformation about DID, said Dr. Liu. He noted that the APA is looking into undertaking such an initiative.
The study investigators report no relevant disclosures. Dr. Liu reports no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , new research shows.
These findings, say investigators, underscore the need for mental health professionals to help counter the spread of false information by creating accurate content and posting it on the popular social media platform.
“Health care professionals need to make engaging content to post on social media platforms like YouTube and especially TikTok, to reach wider audiences and combat misinformation about DID,” study investigator Isreal Bladimir Munoz, a fourth-year medical student at University of Texas, Galveston, said in an interview.
The findings were presented at the annual meeting of the American Psychiatric Association.
Popularized by the media
A rare condition affecting less than 1% of the general population, DID involves two or more distinct personality states, along with changes in behavior and memory gaps.
The condition has been popularized in books and the media. Movies such as “Split,” “Psycho,” and “Fight Club” all feature characters with DID.
“These bring awareness about the condition, but also often sensationalize or stigmatize it and reinforce stereotypes,” said Mr. Munoz.
In recent years, social media has become an integral part of everyday life. An estimated 4.2 billion people actively frequent sites such as YouTube, TikTok, Twitter, and Meta.
Although social media allows for instant communication and the opportunity for self-expression, there are mounting concerns about the spread of misinformation and its potential impact on mental health and privacy, said Mr. Munoz.
To evaluate the quality and accuracy of information about DID on social media, investigators analyzed 60 YouTube and 97 TikTok videos on the condition.
To evaluate the reliability and the intent and reliability of videos, researchers used the modified DISCERN instrument and the Global Quality Scale, a five-point rating system.
Using these tools, the researchers determined whether the selected videos were useful, misleading, or neither. Mr. Munoz said videos were classified as useful if they contained accurate information about the condition and its pathogenesis, treatment, and management.
Researchers determined that for YouTube videos, 51.7% were useful, 6.6% were misleading, and 34.7% were neither. About 43.3% of these videos involved interviews, 21.7% were educational, 15% involved personal stories, 8.3% were films/TV programs, 5% were comedy skits, and 3.3% were another content type.
The highest quality YouTube videos were from educational organizations and health care professionals. The least accurate videos came from independent users and film/TV sources.
As for TikTok videos on DID, only 5.2% were useful, 10.3% were misleading, and 41.7% were neither.
The main sources for TikTok videos were independent organizations, whereas podcasts and film/TV were the least common sources.
The findings, said Mr. Munoz, underscore the need for medical professionals to develop high-quality content about DID and post it on TikTok to counter misinformation on social media.
Call to action
In a comment, Howard Y. Liu, MD, a child and adolescent psychiatrist and chair of the department of psychiatry, University of Nebraska, Omaha, described the study as “compelling.”
When it comes to public health messages, it’s important to know what social media people are using. Today’s parents are on Twitter and Facebook, whereas their children are more likely to be checking out YouTube and TikTok, said Dr. Liu, chair of the APA’s Council on Communications.
“TikTok is critical because that’s where all the youth eyeballs are,” he said.
The medical profession needs to engage with the platform to reach this next-generation audience and help stop the spread of misinformation about DID, said Dr. Liu. He noted that the APA is looking into undertaking such an initiative.
The study investigators report no relevant disclosures. Dr. Liu reports no relevant disclosures.
A version of this article first appeared on Medscape.com.
AT APA 2023
Counting electric sheep: Dreaming of AI in sleep medicine
“Artificial intelligence (AI) in healthcare refers to the use of machine learning (ML), deep learning, natural language processing, and computer vision to process and analyze large amounts of health care data.”
The preceding line is a direct quote from ChatGPT when prompted with the question “What is AI in health care?” (OpenAI, 2022). AI has rapidly infiltrated our lives. From using facial recognition software to unlock our cellphones to scrolling through targeted media suggested by streaming services, our daily existence is interwoven with algorithms. With the recent introduction of GPT-3 (the model that powers ChatGPT) in late 2022 and its even more capable successor, GPT-4, in March 2023, AI will continue to dominate our everyday environment in even more complex and meaningful ways.
For sleep medicine, the initial applications of AI in this field have been innovative and promising. (OSA) (Bandyopadhyay A, et al. Sleep Breath. 2023;27[1]:39). Pépin and colleagues (JAMA Netw Open. 2020;3[1]:e1919657) combined ML with mandibular movement to diagnose OSA with a reasonable agreement to polysomnography as a novel home-based alternative for diagnosis. AI has also been used to predict adherence to positive airway pressure (PAP) therapy in OSA (Scioscia G, et al. Inform Health Soc Care. 2022;47[3]:274) and as a digital intervention tool accessed via a smartphone app for people with insomnia (Philip P, et al, J Med Internet Res. 2020;22[12]:e24268). The data-rich field of sleep medicine is primed for further advancements through AI, albeit with a few hurdles and regulations to overcome before becoming mainstream.
Future promise
Sleep medicine is uniquely positioned to develop robust AI algorithms because of its vast data trove. Using AI, scientists can efficiently analyze the raw data from polysomnography, consumer sleep technology (CST), and nightly remote monitoring (from PAP devices) to substantially improve comprehension and management of sleep disorders.
AI can redefine OSA through analysis of the big data available, rather than solely relying on the apnea-hypopnea index. In addition, novel variables such as facial structure; snoring index; temperature trends; and sleep environment, position, and timing using a camera-based contactless technology may be incorporated to enhance the diagnostic accuracy for OSA or better describe sleep quality. AI algorithms can also be embedded into the electronic health record (EHR) to facilitate screening for sleep disorders using patient characteristics, thus accelerating the recognition and evaluation of possible sleep disorders.
New ways of collecting data may deliver deeper insights into sleep health, as well. CST such as wearables, nearables, and phone applications are improving with each iteration, resulting in more data about sleep for millions of people over thousands of nights.
AI can help achieve precision medicine by integrating multimodal data to establish endotypes and phenotypes of various sleep disorders. Delineating endotypes and phenotypes allows for personalized treatment recommendations, which may improve patient adherence and health outcomes.
Treatment personalization can also be achieved through AI by predicting compliance to various therapies and responses, as well as by discovering alternative forms of delivery to accomplish desired health outcomes. For example, to predict PAP compliance, we can record a patient encounter and use natural language processing to analyze their opinion of their treatment, extracting relevant keywords and combining such processing with other available data, such as environmental factors, sleep schedule, medical history, and other information extracted from the EHR. As another example, AI can determine the optimal time for cancer therapy by predicting a patient’s circadian timing (Hesse J, et al. Cancers (Basel). 2020;12[11]:3103). Circadian timing of drug delivery may be relevant in other specialties including cardiovascular disease, endocrine disorders, and psychiatric conditions due to its associations with sleep. Integration of the various “-omics” (eg, proteomics, genomics, and transcriptomics) with physiologic, behavioral, and environmental data can offer opportunities for drug discovery and possible prediction of sleep disorders and sleep-related morbidity. Although generative pretrained transformers are currently used to predict text (ie, ChatGPT), it is theoretically possible to also apply this technique to identify patients at risk for future sleep disorders from an earlier age.
Challenges to an AI renaissance
Despite making strides in numerous specialties such as radiology, ophthalmology, pathology, oncology, and dermatology, AI has not yet gained mainstream usage. Why isn’t AI as ubiquitous and heavily entrenched in health care as it is in other industries? According to the National Academy of Medicine’s AI in Healthcare: The Hope, The Hype, The Promise, The Peril, there are several realities to address before we fully embrace the AI revolution (Matheny M, et al. 2019).
First, AI algorithms should be trained on quality data that are representative of the population. Interoperability between health care systems and standardization across platforms is required to access large volumes of quality data. The current framework for data gathering is limited due to regulations, patient privacy concerns, and organizational preferences. The challenges to data acquisition and standardization of information will continue to snarl progress unless there are legislative remedies.
Furthermore, datasets should be diverse enough to avoid introducing bias into the AI algorithm. If the dataset is limited and health inequities (eg, societal bias and social determinants of health) are excluded from the training set, then the outcome will perpetuate further explicit and implicit biases.
The Food and Drug Administration (FDA) reviews and authorizes AI/ML-enabled devices. Its current regulatory structure treats AI as a static process and does not allow for exercise of its intrinsic ability to continuously learn from additional data, thereby preventing it from becoming more accurate and evolving with the population over time. A more flexible approach is needed.
Lastly, recent advanced AI algorithms including deep learning and neural network methodology function like a “black box.” The models are not explainable or transparent. Without clear comprehension of its methods, acceptance in clinical practice will be guarded and further risk of inherent biases may ensue.
A path forward
But these challenges, like any, can be overcome. Research in the area of differential privacy and the adoption of recent data-sharing standards (eg, HL7 FHIR) can facilitate access to training data (Saripalle R, et al. J Biomed Inform. 2019;94:103188). Regulators are also open to incorporating feedback from the AI research community and industry in favor of innovation in this frenetic domain. The FDA developed the AI/ML Software as a Medical Device Action Plan in response to stakeholder feedback for oversight (FDA, 2021). Specifically, the “Good Machine Learning Practice” will be developed to describe AI/ML best practices (eg, data management, training, interpretability, evaluation, and documentation) to guide product development and standardization.
Sleep medicine has significantly progressed over the last several decades. Rather than maintain the status quo, AI can help fill the existing knowledge gaps, augment clinical practice, and streamline operations by analyzing and processing data at a volume and efficiency beyond human capacity. Fallibility is inevitable in machines and humans; however, like humans, machines can improve with continued training and exposure.
We asked ChatGPT about the future of AI in sleep medicine. It states that AI could have a “significant impact” on sleep disorders diagnosis, treatment, prevention, and sleep tracking and monitoring. Only time will tell if its claims are accurate.
Dr. Tan is Clinical Associate Professor with the Division of Sleep Medicine at the Stanford University School of Medicine. Dr. Bhargava is Clinical Professor with the Division of Pediatric Pulmonary, Asthma, and Sleep Medicine at the Stanford University School of Medicine.
“Artificial intelligence (AI) in healthcare refers to the use of machine learning (ML), deep learning, natural language processing, and computer vision to process and analyze large amounts of health care data.”
The preceding line is a direct quote from ChatGPT when prompted with the question “What is AI in health care?” (OpenAI, 2022). AI has rapidly infiltrated our lives. From using facial recognition software to unlock our cellphones to scrolling through targeted media suggested by streaming services, our daily existence is interwoven with algorithms. With the recent introduction of GPT-3 (the model that powers ChatGPT) in late 2022 and its even more capable successor, GPT-4, in March 2023, AI will continue to dominate our everyday environment in even more complex and meaningful ways.
For sleep medicine, the initial applications of AI in this field have been innovative and promising. (OSA) (Bandyopadhyay A, et al. Sleep Breath. 2023;27[1]:39). Pépin and colleagues (JAMA Netw Open. 2020;3[1]:e1919657) combined ML with mandibular movement to diagnose OSA with a reasonable agreement to polysomnography as a novel home-based alternative for diagnosis. AI has also been used to predict adherence to positive airway pressure (PAP) therapy in OSA (Scioscia G, et al. Inform Health Soc Care. 2022;47[3]:274) and as a digital intervention tool accessed via a smartphone app for people with insomnia (Philip P, et al, J Med Internet Res. 2020;22[12]:e24268). The data-rich field of sleep medicine is primed for further advancements through AI, albeit with a few hurdles and regulations to overcome before becoming mainstream.
Future promise
Sleep medicine is uniquely positioned to develop robust AI algorithms because of its vast data trove. Using AI, scientists can efficiently analyze the raw data from polysomnography, consumer sleep technology (CST), and nightly remote monitoring (from PAP devices) to substantially improve comprehension and management of sleep disorders.
AI can redefine OSA through analysis of the big data available, rather than solely relying on the apnea-hypopnea index. In addition, novel variables such as facial structure; snoring index; temperature trends; and sleep environment, position, and timing using a camera-based contactless technology may be incorporated to enhance the diagnostic accuracy for OSA or better describe sleep quality. AI algorithms can also be embedded into the electronic health record (EHR) to facilitate screening for sleep disorders using patient characteristics, thus accelerating the recognition and evaluation of possible sleep disorders.
New ways of collecting data may deliver deeper insights into sleep health, as well. CST such as wearables, nearables, and phone applications are improving with each iteration, resulting in more data about sleep for millions of people over thousands of nights.
AI can help achieve precision medicine by integrating multimodal data to establish endotypes and phenotypes of various sleep disorders. Delineating endotypes and phenotypes allows for personalized treatment recommendations, which may improve patient adherence and health outcomes.
Treatment personalization can also be achieved through AI by predicting compliance to various therapies and responses, as well as by discovering alternative forms of delivery to accomplish desired health outcomes. For example, to predict PAP compliance, we can record a patient encounter and use natural language processing to analyze their opinion of their treatment, extracting relevant keywords and combining such processing with other available data, such as environmental factors, sleep schedule, medical history, and other information extracted from the EHR. As another example, AI can determine the optimal time for cancer therapy by predicting a patient’s circadian timing (Hesse J, et al. Cancers (Basel). 2020;12[11]:3103). Circadian timing of drug delivery may be relevant in other specialties including cardiovascular disease, endocrine disorders, and psychiatric conditions due to its associations with sleep. Integration of the various “-omics” (eg, proteomics, genomics, and transcriptomics) with physiologic, behavioral, and environmental data can offer opportunities for drug discovery and possible prediction of sleep disorders and sleep-related morbidity. Although generative pretrained transformers are currently used to predict text (ie, ChatGPT), it is theoretically possible to also apply this technique to identify patients at risk for future sleep disorders from an earlier age.
Challenges to an AI renaissance
Despite making strides in numerous specialties such as radiology, ophthalmology, pathology, oncology, and dermatology, AI has not yet gained mainstream usage. Why isn’t AI as ubiquitous and heavily entrenched in health care as it is in other industries? According to the National Academy of Medicine’s AI in Healthcare: The Hope, The Hype, The Promise, The Peril, there are several realities to address before we fully embrace the AI revolution (Matheny M, et al. 2019).
First, AI algorithms should be trained on quality data that are representative of the population. Interoperability between health care systems and standardization across platforms is required to access large volumes of quality data. The current framework for data gathering is limited due to regulations, patient privacy concerns, and organizational preferences. The challenges to data acquisition and standardization of information will continue to snarl progress unless there are legislative remedies.
Furthermore, datasets should be diverse enough to avoid introducing bias into the AI algorithm. If the dataset is limited and health inequities (eg, societal bias and social determinants of health) are excluded from the training set, then the outcome will perpetuate further explicit and implicit biases.
The Food and Drug Administration (FDA) reviews and authorizes AI/ML-enabled devices. Its current regulatory structure treats AI as a static process and does not allow for exercise of its intrinsic ability to continuously learn from additional data, thereby preventing it from becoming more accurate and evolving with the population over time. A more flexible approach is needed.
Lastly, recent advanced AI algorithms including deep learning and neural network methodology function like a “black box.” The models are not explainable or transparent. Without clear comprehension of its methods, acceptance in clinical practice will be guarded and further risk of inherent biases may ensue.
A path forward
But these challenges, like any, can be overcome. Research in the area of differential privacy and the adoption of recent data-sharing standards (eg, HL7 FHIR) can facilitate access to training data (Saripalle R, et al. J Biomed Inform. 2019;94:103188). Regulators are also open to incorporating feedback from the AI research community and industry in favor of innovation in this frenetic domain. The FDA developed the AI/ML Software as a Medical Device Action Plan in response to stakeholder feedback for oversight (FDA, 2021). Specifically, the “Good Machine Learning Practice” will be developed to describe AI/ML best practices (eg, data management, training, interpretability, evaluation, and documentation) to guide product development and standardization.
Sleep medicine has significantly progressed over the last several decades. Rather than maintain the status quo, AI can help fill the existing knowledge gaps, augment clinical practice, and streamline operations by analyzing and processing data at a volume and efficiency beyond human capacity. Fallibility is inevitable in machines and humans; however, like humans, machines can improve with continued training and exposure.
We asked ChatGPT about the future of AI in sleep medicine. It states that AI could have a “significant impact” on sleep disorders diagnosis, treatment, prevention, and sleep tracking and monitoring. Only time will tell if its claims are accurate.
Dr. Tan is Clinical Associate Professor with the Division of Sleep Medicine at the Stanford University School of Medicine. Dr. Bhargava is Clinical Professor with the Division of Pediatric Pulmonary, Asthma, and Sleep Medicine at the Stanford University School of Medicine.
“Artificial intelligence (AI) in healthcare refers to the use of machine learning (ML), deep learning, natural language processing, and computer vision to process and analyze large amounts of health care data.”
The preceding line is a direct quote from ChatGPT when prompted with the question “What is AI in health care?” (OpenAI, 2022). AI has rapidly infiltrated our lives. From using facial recognition software to unlock our cellphones to scrolling through targeted media suggested by streaming services, our daily existence is interwoven with algorithms. With the recent introduction of GPT-3 (the model that powers ChatGPT) in late 2022 and its even more capable successor, GPT-4, in March 2023, AI will continue to dominate our everyday environment in even more complex and meaningful ways.
For sleep medicine, the initial applications of AI in this field have been innovative and promising. (OSA) (Bandyopadhyay A, et al. Sleep Breath. 2023;27[1]:39). Pépin and colleagues (JAMA Netw Open. 2020;3[1]:e1919657) combined ML with mandibular movement to diagnose OSA with a reasonable agreement to polysomnography as a novel home-based alternative for diagnosis. AI has also been used to predict adherence to positive airway pressure (PAP) therapy in OSA (Scioscia G, et al. Inform Health Soc Care. 2022;47[3]:274) and as a digital intervention tool accessed via a smartphone app for people with insomnia (Philip P, et al, J Med Internet Res. 2020;22[12]:e24268). The data-rich field of sleep medicine is primed for further advancements through AI, albeit with a few hurdles and regulations to overcome before becoming mainstream.
Future promise
Sleep medicine is uniquely positioned to develop robust AI algorithms because of its vast data trove. Using AI, scientists can efficiently analyze the raw data from polysomnography, consumer sleep technology (CST), and nightly remote monitoring (from PAP devices) to substantially improve comprehension and management of sleep disorders.
AI can redefine OSA through analysis of the big data available, rather than solely relying on the apnea-hypopnea index. In addition, novel variables such as facial structure; snoring index; temperature trends; and sleep environment, position, and timing using a camera-based contactless technology may be incorporated to enhance the diagnostic accuracy for OSA or better describe sleep quality. AI algorithms can also be embedded into the electronic health record (EHR) to facilitate screening for sleep disorders using patient characteristics, thus accelerating the recognition and evaluation of possible sleep disorders.
New ways of collecting data may deliver deeper insights into sleep health, as well. CST such as wearables, nearables, and phone applications are improving with each iteration, resulting in more data about sleep for millions of people over thousands of nights.
AI can help achieve precision medicine by integrating multimodal data to establish endotypes and phenotypes of various sleep disorders. Delineating endotypes and phenotypes allows for personalized treatment recommendations, which may improve patient adherence and health outcomes.
Treatment personalization can also be achieved through AI by predicting compliance to various therapies and responses, as well as by discovering alternative forms of delivery to accomplish desired health outcomes. For example, to predict PAP compliance, we can record a patient encounter and use natural language processing to analyze their opinion of their treatment, extracting relevant keywords and combining such processing with other available data, such as environmental factors, sleep schedule, medical history, and other information extracted from the EHR. As another example, AI can determine the optimal time for cancer therapy by predicting a patient’s circadian timing (Hesse J, et al. Cancers (Basel). 2020;12[11]:3103). Circadian timing of drug delivery may be relevant in other specialties including cardiovascular disease, endocrine disorders, and psychiatric conditions due to its associations with sleep. Integration of the various “-omics” (eg, proteomics, genomics, and transcriptomics) with physiologic, behavioral, and environmental data can offer opportunities for drug discovery and possible prediction of sleep disorders and sleep-related morbidity. Although generative pretrained transformers are currently used to predict text (ie, ChatGPT), it is theoretically possible to also apply this technique to identify patients at risk for future sleep disorders from an earlier age.
Challenges to an AI renaissance
Despite making strides in numerous specialties such as radiology, ophthalmology, pathology, oncology, and dermatology, AI has not yet gained mainstream usage. Why isn’t AI as ubiquitous and heavily entrenched in health care as it is in other industries? According to the National Academy of Medicine’s AI in Healthcare: The Hope, The Hype, The Promise, The Peril, there are several realities to address before we fully embrace the AI revolution (Matheny M, et al. 2019).
First, AI algorithms should be trained on quality data that are representative of the population. Interoperability between health care systems and standardization across platforms is required to access large volumes of quality data. The current framework for data gathering is limited due to regulations, patient privacy concerns, and organizational preferences. The challenges to data acquisition and standardization of information will continue to snarl progress unless there are legislative remedies.
Furthermore, datasets should be diverse enough to avoid introducing bias into the AI algorithm. If the dataset is limited and health inequities (eg, societal bias and social determinants of health) are excluded from the training set, then the outcome will perpetuate further explicit and implicit biases.
The Food and Drug Administration (FDA) reviews and authorizes AI/ML-enabled devices. Its current regulatory structure treats AI as a static process and does not allow for exercise of its intrinsic ability to continuously learn from additional data, thereby preventing it from becoming more accurate and evolving with the population over time. A more flexible approach is needed.
Lastly, recent advanced AI algorithms including deep learning and neural network methodology function like a “black box.” The models are not explainable or transparent. Without clear comprehension of its methods, acceptance in clinical practice will be guarded and further risk of inherent biases may ensue.
A path forward
But these challenges, like any, can be overcome. Research in the area of differential privacy and the adoption of recent data-sharing standards (eg, HL7 FHIR) can facilitate access to training data (Saripalle R, et al. J Biomed Inform. 2019;94:103188). Regulators are also open to incorporating feedback from the AI research community and industry in favor of innovation in this frenetic domain. The FDA developed the AI/ML Software as a Medical Device Action Plan in response to stakeholder feedback for oversight (FDA, 2021). Specifically, the “Good Machine Learning Practice” will be developed to describe AI/ML best practices (eg, data management, training, interpretability, evaluation, and documentation) to guide product development and standardization.
Sleep medicine has significantly progressed over the last several decades. Rather than maintain the status quo, AI can help fill the existing knowledge gaps, augment clinical practice, and streamline operations by analyzing and processing data at a volume and efficiency beyond human capacity. Fallibility is inevitable in machines and humans; however, like humans, machines can improve with continued training and exposure.
We asked ChatGPT about the future of AI in sleep medicine. It states that AI could have a “significant impact” on sleep disorders diagnosis, treatment, prevention, and sleep tracking and monitoring. Only time will tell if its claims are accurate.
Dr. Tan is Clinical Associate Professor with the Division of Sleep Medicine at the Stanford University School of Medicine. Dr. Bhargava is Clinical Professor with the Division of Pediatric Pulmonary, Asthma, and Sleep Medicine at the Stanford University School of Medicine.
The family firearm often used in youth suicide
SAN FRANCISCO – , according to results of a novel “psychological autopsy study” of loved ones of youth who died by gun-related suicide.
Yet, families don’t always recognize the danger firearms pose to a young person with suicide risk factors, even when there is a young person in the house with a mental health condition, the data show.
Perhaps most importantly, many parents indicated that they would have removed firearms from the home if it had been suggested by their health care professionals.
The study was presented at the American Psychiatric Association annual meeting.
The message is very clear: Clinicians need to ask about guns and gun safety with patients and families, said study investigator Paul Nestadt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore.
“It’s never illegal to ask about gun access and it’s medically relevant. Just do it,” he said during a briefing with reporters.
Grim statistics
Suicide rates have been climbing in the United States for the majority of the past 20 years. Suicide is the second most common cause of death among youth.
Dr. Nestadt noted that overall about 8% of suicide attempts result in death, but when an attempt involves a firearm the percentage jumps astronomically to 90%.
Research has shown that for every 10% increase in household firearms in a given community there is a 27% increase in youth suicide deaths.
“In the world of public health and mental health, we think about having access to firearms as an important risk factor for completed suicide. But in the United States, guns have become an important part of how many Americans see themselves,” Dr. Nestadt told reporters.
Research has shown that half of gun owners say owning a gun is central to their identity and three quarters say it’s essential to their freedom, he noted.
To explore these attitudes further, Dr. Nestadt and colleagues did 11 “psychological autopsy interviews” with the loved ones of nine young people aged 17-21 who died by gun-related suicide. They interviewed six mothers, three fathers, one sibling, and one close friend.
Most of the families had some level of “familial engagement” with firearms, Dr. Nestadt reported.
In more than two-thirds of the families, the youth used a family-owned firearm to commit suicide.
Notably, more than three-quarters of the youth had received mental health care before taking their lives, with many receiving care in the weeks prior to their suicide; 44% had made a prior suicide attempt.
In many cases, parents shared that they had not considered their family-owned firearms to be sources of danger and indicated that had their clinicians expressed concern about the gun in the home, they may have acted to reduce the risk by removing it.
Several also shared that they would have considered using Maryland’s Extreme Risk Protective Order Law if it had existed at the time and they had been made aware of it.
Extreme risk protection order (ERPO) laws, or “red flag laws,” prohibit individuals at risk for harming themselves or others from purchasing or owning a firearm.
Dr. Nestadt said youth suicide interventions “must acknowledge culturally embedded roots of identity formation while rescripting firearms from expressions of family cohesion to instruments that may undermine that cohesion.”
‘Courageous study’
Dr. Nestadt noted that while this study was challenging on many fronts, it took no convincing to get these grieving families to participate.
“They wanted to talk to us, especially because they were hopeful that our work could help prevent future suicides, but also they wanted to talk about their loved ones,” he said.
“When you lose someone to cancer, people give you hugs and flowers. When you lose someone to suicide, people don’t discuss it. Suicide has a stigma to it.”
Briefing moderator Howard Liu, MD, MBA, chair of the department of psychiatry, University of Nebraska Medical Center, Omaha, praised the study team for a “courageous study that really required a tremendous amount of vulnerability from the research team and clearly from the survivors as well.”
This is an “important and timely public health discussion,” said Dr. Liu, chair of the APA Council on Communications.
“We’re all facing this challenge of how do we reduce suicide across all ages, from youth to adults as well. This is a really vital discussion and such an important clue about access and trying to reduce access in a moment of impulsivity,” he added.
The study had no commercial funding. Dr. Nestadt and Dr. Liu report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , according to results of a novel “psychological autopsy study” of loved ones of youth who died by gun-related suicide.
Yet, families don’t always recognize the danger firearms pose to a young person with suicide risk factors, even when there is a young person in the house with a mental health condition, the data show.
Perhaps most importantly, many parents indicated that they would have removed firearms from the home if it had been suggested by their health care professionals.
The study was presented at the American Psychiatric Association annual meeting.
The message is very clear: Clinicians need to ask about guns and gun safety with patients and families, said study investigator Paul Nestadt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore.
“It’s never illegal to ask about gun access and it’s medically relevant. Just do it,” he said during a briefing with reporters.
Grim statistics
Suicide rates have been climbing in the United States for the majority of the past 20 years. Suicide is the second most common cause of death among youth.
Dr. Nestadt noted that overall about 8% of suicide attempts result in death, but when an attempt involves a firearm the percentage jumps astronomically to 90%.
Research has shown that for every 10% increase in household firearms in a given community there is a 27% increase in youth suicide deaths.
“In the world of public health and mental health, we think about having access to firearms as an important risk factor for completed suicide. But in the United States, guns have become an important part of how many Americans see themselves,” Dr. Nestadt told reporters.
Research has shown that half of gun owners say owning a gun is central to their identity and three quarters say it’s essential to their freedom, he noted.
To explore these attitudes further, Dr. Nestadt and colleagues did 11 “psychological autopsy interviews” with the loved ones of nine young people aged 17-21 who died by gun-related suicide. They interviewed six mothers, three fathers, one sibling, and one close friend.
Most of the families had some level of “familial engagement” with firearms, Dr. Nestadt reported.
In more than two-thirds of the families, the youth used a family-owned firearm to commit suicide.
Notably, more than three-quarters of the youth had received mental health care before taking their lives, with many receiving care in the weeks prior to their suicide; 44% had made a prior suicide attempt.
In many cases, parents shared that they had not considered their family-owned firearms to be sources of danger and indicated that had their clinicians expressed concern about the gun in the home, they may have acted to reduce the risk by removing it.
Several also shared that they would have considered using Maryland’s Extreme Risk Protective Order Law if it had existed at the time and they had been made aware of it.
Extreme risk protection order (ERPO) laws, or “red flag laws,” prohibit individuals at risk for harming themselves or others from purchasing or owning a firearm.
Dr. Nestadt said youth suicide interventions “must acknowledge culturally embedded roots of identity formation while rescripting firearms from expressions of family cohesion to instruments that may undermine that cohesion.”
‘Courageous study’
Dr. Nestadt noted that while this study was challenging on many fronts, it took no convincing to get these grieving families to participate.
“They wanted to talk to us, especially because they were hopeful that our work could help prevent future suicides, but also they wanted to talk about their loved ones,” he said.
“When you lose someone to cancer, people give you hugs and flowers. When you lose someone to suicide, people don’t discuss it. Suicide has a stigma to it.”
Briefing moderator Howard Liu, MD, MBA, chair of the department of psychiatry, University of Nebraska Medical Center, Omaha, praised the study team for a “courageous study that really required a tremendous amount of vulnerability from the research team and clearly from the survivors as well.”
This is an “important and timely public health discussion,” said Dr. Liu, chair of the APA Council on Communications.
“We’re all facing this challenge of how do we reduce suicide across all ages, from youth to adults as well. This is a really vital discussion and such an important clue about access and trying to reduce access in a moment of impulsivity,” he added.
The study had no commercial funding. Dr. Nestadt and Dr. Liu report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , according to results of a novel “psychological autopsy study” of loved ones of youth who died by gun-related suicide.
Yet, families don’t always recognize the danger firearms pose to a young person with suicide risk factors, even when there is a young person in the house with a mental health condition, the data show.
Perhaps most importantly, many parents indicated that they would have removed firearms from the home if it had been suggested by their health care professionals.
The study was presented at the American Psychiatric Association annual meeting.
The message is very clear: Clinicians need to ask about guns and gun safety with patients and families, said study investigator Paul Nestadt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore.
“It’s never illegal to ask about gun access and it’s medically relevant. Just do it,” he said during a briefing with reporters.
Grim statistics
Suicide rates have been climbing in the United States for the majority of the past 20 years. Suicide is the second most common cause of death among youth.
Dr. Nestadt noted that overall about 8% of suicide attempts result in death, but when an attempt involves a firearm the percentage jumps astronomically to 90%.
Research has shown that for every 10% increase in household firearms in a given community there is a 27% increase in youth suicide deaths.
“In the world of public health and mental health, we think about having access to firearms as an important risk factor for completed suicide. But in the United States, guns have become an important part of how many Americans see themselves,” Dr. Nestadt told reporters.
Research has shown that half of gun owners say owning a gun is central to their identity and three quarters say it’s essential to their freedom, he noted.
To explore these attitudes further, Dr. Nestadt and colleagues did 11 “psychological autopsy interviews” with the loved ones of nine young people aged 17-21 who died by gun-related suicide. They interviewed six mothers, three fathers, one sibling, and one close friend.
Most of the families had some level of “familial engagement” with firearms, Dr. Nestadt reported.
In more than two-thirds of the families, the youth used a family-owned firearm to commit suicide.
Notably, more than three-quarters of the youth had received mental health care before taking their lives, with many receiving care in the weeks prior to their suicide; 44% had made a prior suicide attempt.
In many cases, parents shared that they had not considered their family-owned firearms to be sources of danger and indicated that had their clinicians expressed concern about the gun in the home, they may have acted to reduce the risk by removing it.
Several also shared that they would have considered using Maryland’s Extreme Risk Protective Order Law if it had existed at the time and they had been made aware of it.
Extreme risk protection order (ERPO) laws, or “red flag laws,” prohibit individuals at risk for harming themselves or others from purchasing or owning a firearm.
Dr. Nestadt said youth suicide interventions “must acknowledge culturally embedded roots of identity formation while rescripting firearms from expressions of family cohesion to instruments that may undermine that cohesion.”
‘Courageous study’
Dr. Nestadt noted that while this study was challenging on many fronts, it took no convincing to get these grieving families to participate.
“They wanted to talk to us, especially because they were hopeful that our work could help prevent future suicides, but also they wanted to talk about their loved ones,” he said.
“When you lose someone to cancer, people give you hugs and flowers. When you lose someone to suicide, people don’t discuss it. Suicide has a stigma to it.”
Briefing moderator Howard Liu, MD, MBA, chair of the department of psychiatry, University of Nebraska Medical Center, Omaha, praised the study team for a “courageous study that really required a tremendous amount of vulnerability from the research team and clearly from the survivors as well.”
This is an “important and timely public health discussion,” said Dr. Liu, chair of the APA Council on Communications.
“We’re all facing this challenge of how do we reduce suicide across all ages, from youth to adults as well. This is a really vital discussion and such an important clue about access and trying to reduce access in a moment of impulsivity,” he added.
The study had no commercial funding. Dr. Nestadt and Dr. Liu report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT APA 2023
Beta-blocker gel shows promise for diabetic foot ulcers
say Indian researchers.
Esmolol is a short-acting beta-adrenergic receptor blocker that is currently approved by the Food and Drug Administration for cardiac indications such as short-term use for supraventricular tachycardia.
As a gel, esmolol hydrochloride is administered topically to stimulate wound healing via mechanisms such as the migration of keratinocytes, fibroblasts, and endothelial cells into wound tissue.
The current trial enrolled patients with type 1 or 2 diabetes, finding that, among 140 assessed, target ulcer closure within 12 weeks was more than twice as likely in those assigned esmolol gel plus standard of care than those given standard of care alone.
The impact of adding esmolol gel to standard of care was even greater in patients with a body mass index (BMI) over 25 kg/m2 and in those who weighed more than 80 kg (176 lb).
“The use of esmolol in the treatment of diabetic foot ulcers in addition to standard of care may be an important addition to the endeavor of healing diabetic foot ulcers,” wrote Ashu Rastogi, MD, DM, department of endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, and colleagues, in their article recently published in JAMA Network Open.
Dr. Rastogi first presented the findings at the 2022 annual meeting of the European Association for the Study of Diabetes. The results were well received, with one clinician describing them as “astounding.”
However, Andrew Boulton, MD, PhD, said in an interview that, although the final published data are “interesting,” they “need further confirmation” because “there are one or two unusual features” about the study. Dr. Boulton is a professor of medicine, division of diabetes, endocrinology & gastroenterology, at the University of Manchester (England).
He highlighted that the study was of “basically neuropathic ulcers, many of which were plantar and should be able to heal without any specific additional therapy.”
In addition, the inclusion criteria state that the ulcers could be below the malleoli or 5 cm above them, which Dr. Boulton explained is “very unusual and would therefore include some atypical and not truly diabetic ‘foot’ ulcers.”
And Frances Game, MBBCh, department of diabetes and endocrinology, University Hospitals of Derby (England) and Burton NHS Foundation Trust, added that there are questions about the study methodology.
She said in an interview that although it is a “fascinating study,” the main comparison group did not receive vehicle, or placebo, gel in addition to standard of care. “How were they blinded [to treatment]?”
The “biggest problem” with the study, however, is that the primary outcome was reported as a per-protocol endpoint, not as a standard intention-to-treat analysis, which allowed the researchers to exclude patients whose ulcers increased in size by over 30% on two consecutive visits.
“That kind of makes [esmolol gel] look better than it is because they’ve taken out the ones who got worse,” Dr. Game noted. However, the findings, while not conclusive, do warrant further study of esmolol gel.
The authors noted that diabetic foot ulcers are a severe complication of diabetes, with a prevalence of 1.3%-12.0% across various countries, And the complication contributes to patient morbidity and mortality, with a 5-year mortality that is substantially higher than that of many cancers.
Moreover, “even with the best therapy,” such as advanced moist wound therapy, bioengineered tissue or skin substitutes, peptides, growth factors, electric stimulation, and negative-pressure wound therapy, just 30% of wounds linked to diabetes heal and recurrence is as high as 70%.
Against this backdrop, topical esmolol 14% gel was shown in a phase 1/2 study to be associated with ulcer area reduction and earlier wound closure versus standard of care plus a control vehicle gel.
The current phase 3, randomized, controlled trial involved individuals aged 18-75 years with type 1 or type 2 diabetes and noninfected diabetic foot ulcers classified as grade 1A and 1C on the University of Texas Wound Classification System, which had been open for at least 6 weeks and had an area of 2-25 cm2.
Patients from 27 tertiary care centers across India were enrolled in 2018-2020. They were randomized in a 3:3:1 ratio to one of three groups: esmolol 14% gel plus standard of care, standard of care only, or vehicle plus standard of care.
The study lasted 25 weeks and included a 1-week screening phase, during which all patients received standard of care, a 12-week treatment phase, and a 12-week follow-up phase. The latter included a closure confirmation period of 4 weeks and an observation period of 8 weeks.
Patients were assessed once a week during the treatment phase, and then at weeks 14, 16, 20, and 24.
In all, 176 patients were enrolled. Participants were a mean age of 56.4 years and 69.3% were men. Average hemoglobin A1c was 8.6%. Mean diabetic foot ulcer area was 4.7 cm2 and the average ulcer duration was 49.8 weeks.
The primary outcome was the proportion of patients who achieved target ulcer closure during the 12-week treatment phase and was assessed in 140 patients.
Overall, 60.3% of patients treated with esmolol gel plus standard of care achieved target ulcer closure versus 41.7% of those in the standard of care alone group (odds ratio, 2.13; P = .03).
The secondary outcome was the proportion of patients with target ulcer closure by the study end and was assessed in 120 patients.
In total, 77.2% of patients in the esmolol gel plus standard of care group met the secondary endpoint, compared with 55.6% of those receiving standard of care alone (OR, 1.72; P = .01).
Further analysis suggested the benefit seen with esmolol gel plus standard of care was greater in patients with a weight greater than 80 kg versus standard of care alone (OR, 4.04; P = .04), and in those with a BMI greater than 25 (OR, 2.72; P = .03).
Treatment-emergent adverse events were reported by 33 (18.8%) participants, with 12 events deemed serious. “However, none of the serious adverse events were considered as drug-related by the investigators,” concluded the researchers.
The study was partly funded by NovaLead Pharma and the Biotechnology Industry Research Assistance Council, New Delhi, set up by the Department of Biotechnology, Government of India. Dr. Rastogi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
say Indian researchers.
Esmolol is a short-acting beta-adrenergic receptor blocker that is currently approved by the Food and Drug Administration for cardiac indications such as short-term use for supraventricular tachycardia.
As a gel, esmolol hydrochloride is administered topically to stimulate wound healing via mechanisms such as the migration of keratinocytes, fibroblasts, and endothelial cells into wound tissue.
The current trial enrolled patients with type 1 or 2 diabetes, finding that, among 140 assessed, target ulcer closure within 12 weeks was more than twice as likely in those assigned esmolol gel plus standard of care than those given standard of care alone.
The impact of adding esmolol gel to standard of care was even greater in patients with a body mass index (BMI) over 25 kg/m2 and in those who weighed more than 80 kg (176 lb).
“The use of esmolol in the treatment of diabetic foot ulcers in addition to standard of care may be an important addition to the endeavor of healing diabetic foot ulcers,” wrote Ashu Rastogi, MD, DM, department of endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, and colleagues, in their article recently published in JAMA Network Open.
Dr. Rastogi first presented the findings at the 2022 annual meeting of the European Association for the Study of Diabetes. The results were well received, with one clinician describing them as “astounding.”
However, Andrew Boulton, MD, PhD, said in an interview that, although the final published data are “interesting,” they “need further confirmation” because “there are one or two unusual features” about the study. Dr. Boulton is a professor of medicine, division of diabetes, endocrinology & gastroenterology, at the University of Manchester (England).
He highlighted that the study was of “basically neuropathic ulcers, many of which were plantar and should be able to heal without any specific additional therapy.”
In addition, the inclusion criteria state that the ulcers could be below the malleoli or 5 cm above them, which Dr. Boulton explained is “very unusual and would therefore include some atypical and not truly diabetic ‘foot’ ulcers.”
And Frances Game, MBBCh, department of diabetes and endocrinology, University Hospitals of Derby (England) and Burton NHS Foundation Trust, added that there are questions about the study methodology.
She said in an interview that although it is a “fascinating study,” the main comparison group did not receive vehicle, or placebo, gel in addition to standard of care. “How were they blinded [to treatment]?”
The “biggest problem” with the study, however, is that the primary outcome was reported as a per-protocol endpoint, not as a standard intention-to-treat analysis, which allowed the researchers to exclude patients whose ulcers increased in size by over 30% on two consecutive visits.
“That kind of makes [esmolol gel] look better than it is because they’ve taken out the ones who got worse,” Dr. Game noted. However, the findings, while not conclusive, do warrant further study of esmolol gel.
The authors noted that diabetic foot ulcers are a severe complication of diabetes, with a prevalence of 1.3%-12.0% across various countries, And the complication contributes to patient morbidity and mortality, with a 5-year mortality that is substantially higher than that of many cancers.
Moreover, “even with the best therapy,” such as advanced moist wound therapy, bioengineered tissue or skin substitutes, peptides, growth factors, electric stimulation, and negative-pressure wound therapy, just 30% of wounds linked to diabetes heal and recurrence is as high as 70%.
Against this backdrop, topical esmolol 14% gel was shown in a phase 1/2 study to be associated with ulcer area reduction and earlier wound closure versus standard of care plus a control vehicle gel.
The current phase 3, randomized, controlled trial involved individuals aged 18-75 years with type 1 or type 2 diabetes and noninfected diabetic foot ulcers classified as grade 1A and 1C on the University of Texas Wound Classification System, which had been open for at least 6 weeks and had an area of 2-25 cm2.
Patients from 27 tertiary care centers across India were enrolled in 2018-2020. They were randomized in a 3:3:1 ratio to one of three groups: esmolol 14% gel plus standard of care, standard of care only, or vehicle plus standard of care.
The study lasted 25 weeks and included a 1-week screening phase, during which all patients received standard of care, a 12-week treatment phase, and a 12-week follow-up phase. The latter included a closure confirmation period of 4 weeks and an observation period of 8 weeks.
Patients were assessed once a week during the treatment phase, and then at weeks 14, 16, 20, and 24.
In all, 176 patients were enrolled. Participants were a mean age of 56.4 years and 69.3% were men. Average hemoglobin A1c was 8.6%. Mean diabetic foot ulcer area was 4.7 cm2 and the average ulcer duration was 49.8 weeks.
The primary outcome was the proportion of patients who achieved target ulcer closure during the 12-week treatment phase and was assessed in 140 patients.
Overall, 60.3% of patients treated with esmolol gel plus standard of care achieved target ulcer closure versus 41.7% of those in the standard of care alone group (odds ratio, 2.13; P = .03).
The secondary outcome was the proportion of patients with target ulcer closure by the study end and was assessed in 120 patients.
In total, 77.2% of patients in the esmolol gel plus standard of care group met the secondary endpoint, compared with 55.6% of those receiving standard of care alone (OR, 1.72; P = .01).
Further analysis suggested the benefit seen with esmolol gel plus standard of care was greater in patients with a weight greater than 80 kg versus standard of care alone (OR, 4.04; P = .04), and in those with a BMI greater than 25 (OR, 2.72; P = .03).
Treatment-emergent adverse events were reported by 33 (18.8%) participants, with 12 events deemed serious. “However, none of the serious adverse events were considered as drug-related by the investigators,” concluded the researchers.
The study was partly funded by NovaLead Pharma and the Biotechnology Industry Research Assistance Council, New Delhi, set up by the Department of Biotechnology, Government of India. Dr. Rastogi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
say Indian researchers.
Esmolol is a short-acting beta-adrenergic receptor blocker that is currently approved by the Food and Drug Administration for cardiac indications such as short-term use for supraventricular tachycardia.
As a gel, esmolol hydrochloride is administered topically to stimulate wound healing via mechanisms such as the migration of keratinocytes, fibroblasts, and endothelial cells into wound tissue.
The current trial enrolled patients with type 1 or 2 diabetes, finding that, among 140 assessed, target ulcer closure within 12 weeks was more than twice as likely in those assigned esmolol gel plus standard of care than those given standard of care alone.
The impact of adding esmolol gel to standard of care was even greater in patients with a body mass index (BMI) over 25 kg/m2 and in those who weighed more than 80 kg (176 lb).
“The use of esmolol in the treatment of diabetic foot ulcers in addition to standard of care may be an important addition to the endeavor of healing diabetic foot ulcers,” wrote Ashu Rastogi, MD, DM, department of endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, and colleagues, in their article recently published in JAMA Network Open.
Dr. Rastogi first presented the findings at the 2022 annual meeting of the European Association for the Study of Diabetes. The results were well received, with one clinician describing them as “astounding.”
However, Andrew Boulton, MD, PhD, said in an interview that, although the final published data are “interesting,” they “need further confirmation” because “there are one or two unusual features” about the study. Dr. Boulton is a professor of medicine, division of diabetes, endocrinology & gastroenterology, at the University of Manchester (England).
He highlighted that the study was of “basically neuropathic ulcers, many of which were plantar and should be able to heal without any specific additional therapy.”
In addition, the inclusion criteria state that the ulcers could be below the malleoli or 5 cm above them, which Dr. Boulton explained is “very unusual and would therefore include some atypical and not truly diabetic ‘foot’ ulcers.”
And Frances Game, MBBCh, department of diabetes and endocrinology, University Hospitals of Derby (England) and Burton NHS Foundation Trust, added that there are questions about the study methodology.
She said in an interview that although it is a “fascinating study,” the main comparison group did not receive vehicle, or placebo, gel in addition to standard of care. “How were they blinded [to treatment]?”
The “biggest problem” with the study, however, is that the primary outcome was reported as a per-protocol endpoint, not as a standard intention-to-treat analysis, which allowed the researchers to exclude patients whose ulcers increased in size by over 30% on two consecutive visits.
“That kind of makes [esmolol gel] look better than it is because they’ve taken out the ones who got worse,” Dr. Game noted. However, the findings, while not conclusive, do warrant further study of esmolol gel.
The authors noted that diabetic foot ulcers are a severe complication of diabetes, with a prevalence of 1.3%-12.0% across various countries, And the complication contributes to patient morbidity and mortality, with a 5-year mortality that is substantially higher than that of many cancers.
Moreover, “even with the best therapy,” such as advanced moist wound therapy, bioengineered tissue or skin substitutes, peptides, growth factors, electric stimulation, and negative-pressure wound therapy, just 30% of wounds linked to diabetes heal and recurrence is as high as 70%.
Against this backdrop, topical esmolol 14% gel was shown in a phase 1/2 study to be associated with ulcer area reduction and earlier wound closure versus standard of care plus a control vehicle gel.
The current phase 3, randomized, controlled trial involved individuals aged 18-75 years with type 1 or type 2 diabetes and noninfected diabetic foot ulcers classified as grade 1A and 1C on the University of Texas Wound Classification System, which had been open for at least 6 weeks and had an area of 2-25 cm2.
Patients from 27 tertiary care centers across India were enrolled in 2018-2020. They were randomized in a 3:3:1 ratio to one of three groups: esmolol 14% gel plus standard of care, standard of care only, or vehicle plus standard of care.
The study lasted 25 weeks and included a 1-week screening phase, during which all patients received standard of care, a 12-week treatment phase, and a 12-week follow-up phase. The latter included a closure confirmation period of 4 weeks and an observation period of 8 weeks.
Patients were assessed once a week during the treatment phase, and then at weeks 14, 16, 20, and 24.
In all, 176 patients were enrolled. Participants were a mean age of 56.4 years and 69.3% were men. Average hemoglobin A1c was 8.6%. Mean diabetic foot ulcer area was 4.7 cm2 and the average ulcer duration was 49.8 weeks.
The primary outcome was the proportion of patients who achieved target ulcer closure during the 12-week treatment phase and was assessed in 140 patients.
Overall, 60.3% of patients treated with esmolol gel plus standard of care achieved target ulcer closure versus 41.7% of those in the standard of care alone group (odds ratio, 2.13; P = .03).
The secondary outcome was the proportion of patients with target ulcer closure by the study end and was assessed in 120 patients.
In total, 77.2% of patients in the esmolol gel plus standard of care group met the secondary endpoint, compared with 55.6% of those receiving standard of care alone (OR, 1.72; P = .01).
Further analysis suggested the benefit seen with esmolol gel plus standard of care was greater in patients with a weight greater than 80 kg versus standard of care alone (OR, 4.04; P = .04), and in those with a BMI greater than 25 (OR, 2.72; P = .03).
Treatment-emergent adverse events were reported by 33 (18.8%) participants, with 12 events deemed serious. “However, none of the serious adverse events were considered as drug-related by the investigators,” concluded the researchers.
The study was partly funded by NovaLead Pharma and the Biotechnology Industry Research Assistance Council, New Delhi, set up by the Department of Biotechnology, Government of India. Dr. Rastogi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Black patients most likely to be restrained in EDs, Latino patients least likely
SAN FRANCISCO – .
In contrast, Hispanic/Latino patients were less likely to be restrained than both Black and White patients, researchers reported in a poster presented at the annual meeting of the American Psychiatric Association. The study authors also found that clinicians rarely turned to restraints, using them in just 2,712 of 882,390 ED visits (0.3%) over a 7-year period.
The study doesn’t examine why the disparities exist. But lead author Erika Chang-Sing, a medical student at Yale University, New Haven, Conn., said in an interview that it’s clear that racial bias is the cause of the differences in restraint rates among White, Black, and Hispanics/Latino patients. “We think that there are multiple contributing factors to the higher rates of restraint for Black patients brought to the hospital by police, and all of them are rooted in systemic racism,” she said, adding that “the lower odds of restraint in the Hispanic or Latino group are also rooted in systemic racism and inequity.”
According to Ms. Chang-Sing, researchers launched the study to gain insight into the use of the restraints in the Southeast and to see what’s happening in light of the recent publicizing of killings of Black people by police. Being taken to the hospital by police “might contribute both to the individual patient’s behavior and the health care provider’s assessment of risk in determining whether or not to apply restraints,” she said.
Other research has linked ethnicity to higher rates of restraint use. For example, a 2021 study of 32,054 cases of patients under mandatory psychiatric hold in 11 Massachusetts emergency rooms found that Black (adjusted odds ratio, 1.22) and Hispanic (aOR, 1.45) patients were more likely to be restrained than White patients.
For the new study, researchers retrospectively tracked 885,102 emergency room visits at three North Carolina emergency departments from 2015 to 2022, including 9,130 who were brought in by police and 2,712 who were physically restrained because of the perceived risk of violence. “Providers use restraints, or straps, to secure the patient’s wrists and ankles to the bed,” Ms. Chang-Sing said.
Among all patients, 52.5% were Black, but 66% of those who were restrained were Black. The numbers for White patients were 35.7% and 23.9%, respectively, and 5.7% and 3.2% for Hispanics/Latino patients. Black patients were less likely than White patients to get a psychiatric primary emergency department diagnosis (aOR, 0.67), but those in that category were more likely than their White counterparts to be restrained (aOR, 1.36).
The higher risk of restraint use in Black patients overall disappeared when researchers adjusted their statistics to account for the effects of sex, age, and type of insurance (aOR, 0.86). Ms. Chang-Sing said the study team is reanalyzing the data since they think insurance may not be a confounder.
Why might Hispanic/Latino ethnicity be protective against restraint use? “This may be due to language barriers, fear of law enforcement, and avoidance of the hospital in the first place,” Ms. Chang-Sing said.
Emergency physician Wendy Macias-Konstantopoulos, MD, MPH, MBA, of Harvard Medical School and Massachusetts General Hospital, both in Boston, coauthored the 2021 study on police restraints. In an interview, she said the new findings add to previous research by providing data about the role played by the police who bring patients to the ED. She added that there is no evidence that certain populations simply need more restraints.
What can be done to reduce disparities in restraint use? Mental health teams can make a difference by responding to mental health emergencies, Ms. Chang-Sing said. “These providers can be instrumental in communicating to patients that the intention is to care for them, not to punish them.”
Another strategy is to increase the number of clinics and crisis response centers, she said. Hospital-based crisis response teams can also be helpful, she said. “Because these teams are focused only on behavioral emergencies, they can be more thoughtful in avoiding the use of restraints.”
No study funding was reported. The study authors and Dr. Macias-Konstantopoulos have no disclosures.
SAN FRANCISCO – .
In contrast, Hispanic/Latino patients were less likely to be restrained than both Black and White patients, researchers reported in a poster presented at the annual meeting of the American Psychiatric Association. The study authors also found that clinicians rarely turned to restraints, using them in just 2,712 of 882,390 ED visits (0.3%) over a 7-year period.
The study doesn’t examine why the disparities exist. But lead author Erika Chang-Sing, a medical student at Yale University, New Haven, Conn., said in an interview that it’s clear that racial bias is the cause of the differences in restraint rates among White, Black, and Hispanics/Latino patients. “We think that there are multiple contributing factors to the higher rates of restraint for Black patients brought to the hospital by police, and all of them are rooted in systemic racism,” she said, adding that “the lower odds of restraint in the Hispanic or Latino group are also rooted in systemic racism and inequity.”
According to Ms. Chang-Sing, researchers launched the study to gain insight into the use of the restraints in the Southeast and to see what’s happening in light of the recent publicizing of killings of Black people by police. Being taken to the hospital by police “might contribute both to the individual patient’s behavior and the health care provider’s assessment of risk in determining whether or not to apply restraints,” she said.
Other research has linked ethnicity to higher rates of restraint use. For example, a 2021 study of 32,054 cases of patients under mandatory psychiatric hold in 11 Massachusetts emergency rooms found that Black (adjusted odds ratio, 1.22) and Hispanic (aOR, 1.45) patients were more likely to be restrained than White patients.
For the new study, researchers retrospectively tracked 885,102 emergency room visits at three North Carolina emergency departments from 2015 to 2022, including 9,130 who were brought in by police and 2,712 who were physically restrained because of the perceived risk of violence. “Providers use restraints, or straps, to secure the patient’s wrists and ankles to the bed,” Ms. Chang-Sing said.
Among all patients, 52.5% were Black, but 66% of those who were restrained were Black. The numbers for White patients were 35.7% and 23.9%, respectively, and 5.7% and 3.2% for Hispanics/Latino patients. Black patients were less likely than White patients to get a psychiatric primary emergency department diagnosis (aOR, 0.67), but those in that category were more likely than their White counterparts to be restrained (aOR, 1.36).
The higher risk of restraint use in Black patients overall disappeared when researchers adjusted their statistics to account for the effects of sex, age, and type of insurance (aOR, 0.86). Ms. Chang-Sing said the study team is reanalyzing the data since they think insurance may not be a confounder.
Why might Hispanic/Latino ethnicity be protective against restraint use? “This may be due to language barriers, fear of law enforcement, and avoidance of the hospital in the first place,” Ms. Chang-Sing said.
Emergency physician Wendy Macias-Konstantopoulos, MD, MPH, MBA, of Harvard Medical School and Massachusetts General Hospital, both in Boston, coauthored the 2021 study on police restraints. In an interview, she said the new findings add to previous research by providing data about the role played by the police who bring patients to the ED. She added that there is no evidence that certain populations simply need more restraints.
What can be done to reduce disparities in restraint use? Mental health teams can make a difference by responding to mental health emergencies, Ms. Chang-Sing said. “These providers can be instrumental in communicating to patients that the intention is to care for them, not to punish them.”
Another strategy is to increase the number of clinics and crisis response centers, she said. Hospital-based crisis response teams can also be helpful, she said. “Because these teams are focused only on behavioral emergencies, they can be more thoughtful in avoiding the use of restraints.”
No study funding was reported. The study authors and Dr. Macias-Konstantopoulos have no disclosures.
SAN FRANCISCO – .
In contrast, Hispanic/Latino patients were less likely to be restrained than both Black and White patients, researchers reported in a poster presented at the annual meeting of the American Psychiatric Association. The study authors also found that clinicians rarely turned to restraints, using them in just 2,712 of 882,390 ED visits (0.3%) over a 7-year period.
The study doesn’t examine why the disparities exist. But lead author Erika Chang-Sing, a medical student at Yale University, New Haven, Conn., said in an interview that it’s clear that racial bias is the cause of the differences in restraint rates among White, Black, and Hispanics/Latino patients. “We think that there are multiple contributing factors to the higher rates of restraint for Black patients brought to the hospital by police, and all of them are rooted in systemic racism,” she said, adding that “the lower odds of restraint in the Hispanic or Latino group are also rooted in systemic racism and inequity.”
According to Ms. Chang-Sing, researchers launched the study to gain insight into the use of the restraints in the Southeast and to see what’s happening in light of the recent publicizing of killings of Black people by police. Being taken to the hospital by police “might contribute both to the individual patient’s behavior and the health care provider’s assessment of risk in determining whether or not to apply restraints,” she said.
Other research has linked ethnicity to higher rates of restraint use. For example, a 2021 study of 32,054 cases of patients under mandatory psychiatric hold in 11 Massachusetts emergency rooms found that Black (adjusted odds ratio, 1.22) and Hispanic (aOR, 1.45) patients were more likely to be restrained than White patients.
For the new study, researchers retrospectively tracked 885,102 emergency room visits at three North Carolina emergency departments from 2015 to 2022, including 9,130 who were brought in by police and 2,712 who were physically restrained because of the perceived risk of violence. “Providers use restraints, or straps, to secure the patient’s wrists and ankles to the bed,” Ms. Chang-Sing said.
Among all patients, 52.5% were Black, but 66% of those who were restrained were Black. The numbers for White patients were 35.7% and 23.9%, respectively, and 5.7% and 3.2% for Hispanics/Latino patients. Black patients were less likely than White patients to get a psychiatric primary emergency department diagnosis (aOR, 0.67), but those in that category were more likely than their White counterparts to be restrained (aOR, 1.36).
The higher risk of restraint use in Black patients overall disappeared when researchers adjusted their statistics to account for the effects of sex, age, and type of insurance (aOR, 0.86). Ms. Chang-Sing said the study team is reanalyzing the data since they think insurance may not be a confounder.
Why might Hispanic/Latino ethnicity be protective against restraint use? “This may be due to language barriers, fear of law enforcement, and avoidance of the hospital in the first place,” Ms. Chang-Sing said.
Emergency physician Wendy Macias-Konstantopoulos, MD, MPH, MBA, of Harvard Medical School and Massachusetts General Hospital, both in Boston, coauthored the 2021 study on police restraints. In an interview, she said the new findings add to previous research by providing data about the role played by the police who bring patients to the ED. She added that there is no evidence that certain populations simply need more restraints.
What can be done to reduce disparities in restraint use? Mental health teams can make a difference by responding to mental health emergencies, Ms. Chang-Sing said. “These providers can be instrumental in communicating to patients that the intention is to care for them, not to punish them.”
Another strategy is to increase the number of clinics and crisis response centers, she said. Hospital-based crisis response teams can also be helpful, she said. “Because these teams are focused only on behavioral emergencies, they can be more thoughtful in avoiding the use of restraints.”
No study funding was reported. The study authors and Dr. Macias-Konstantopoulos have no disclosures.
AT APA 2023
FDA approves new indication for avapritinib
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
We can reduce suicide with enforced treatment and eyesight supervision
The old man was restrained at the last moment from jumping off the hospital’s fifth floor atrium parapet. He was suffering from terminal cancer and had been racked with chronic, severe pain for months.
The consult recognized symptoms of depression arising from his continuous physical suffering, advising that a male aide be dispatched to sit with the man and that he be put on a regimen of 10 mg of methadone twice a day to alleviate the pain. The following day the man was calm; he no longer wanted to kill himself. He expressed a strong desire to go home, return to gardening, and to play with his grandchildren.
Most of the 47,000 suicides that occur in the United States every year are preventable.1 Our national policy on this front has been nothing short of an abject failure. The government implemented a system with limited effect on completed suicides – a telephone hotline. This hotline is not called by the most common suicide victims: male, old, and quiet.2
The consequences of this national policy disaster have been profound, resulting in the biggest loss of productive years of life for any fatal condition.3 The grief experienced by the families of those who commit suicide is far greater than normal bereavement: The cause of death of their loved ones was not an unfortunate accident or a disease, it was an intentional act, and families take it personally.
One of the greatest achievements of psychiatry during the 20th century was the lowering of suicide rates in prisons by 70% with no treatment, no additional staffing, and no additional expenditures of funds. Today if inmates threaten suicide, they are immediately placed under eyesight supervision by guards. The federal pamphlet that describes this protocol was published in 1995 and is freely available online.4
Half of all suicide attempts are made by individuals who are legally drunk.5 Watch them for 6 hours and then ask them if they want to kill themselves and the response will almost invariably be “Of course not,” with the risk of further attempts dissipating in step with their blood alcohol level. The best resources to provide this kind of intervention are responsible adult family members, at no cost to the government. Indeed, in many cases family supervision is superior to that provided by a locked psychiatric ward with three staff members chasing after 20 agitated people all night long. The one-on-one attention that a family member can provide is free as well as far more personal and insightful, and more sincerely caring.
Guarantees in the field of medicine are rare. But, one such guarantee is that after their mood has improved, 100% of people will be thankful that they did not hurt themselves.6 This means that successful treatment will prevent 100% of all suicides.7 Not all treatments are successful, but 95% can be.8 At autopsy, few successful suicide victims have psychiatric medications in their system.9 The urge to kill oneself might best be characterized as a temporary chemical alteration of the brain causing delusional thoughts, including the ultimate delusion that life is not worth living.10 This alteration suppresses the strongest, most fundamental urge of all, namely, the survival instinct.
We must overturn the catastrophic decision of the U.S. Supreme Court that requires the showing of a dangerous act and the holding of a trial employing at least three lawyers for involuntary commitment to be authorized. Rather, involuntary treatment is justified by medical necessity as determined by two licensed professionals with no conflicts of interest. It can be outpatient.
The Supreme Court’s decision in O’Connor v. Donaldson in 1975 remedied an illusory wrong, addressing an act of blatant malpractice, not policy inequity.11 The superintendent of the state facility in that case was not even a doctor. He kept O’Connor prisoner for more than a decade, perhaps to keep a bed filled. Over the past half-century, this one decision has resulted in 1 million preventable suicides12 and half a million senseless murders by paranoid individuals, including many rampage shootings.13
More than two-thirds of homeless individuals suffer from an untreated mental condition.14 The vast majority of them will refuse all offers of treatment because they also have anosognosia, a brain-based disorder causing denial of illness.15 By referring to these individuals as “homeless,” we are also lowering real estate values for a square block around where they happen to be camped out. That cost has never been calculated, but it is another real consequence of this devastating Supreme Court decision.16
Detractors and mental health rights activists may argue that individual rights cannot be infringed. In that case, those same detractors and mental health rights activists must take responsibility for the thousands of lives and billions of dollars in economic damage caused by their refusal to allow an effective solution to the suicide epidemic to be implemented. Enforced outpatient treatment by the U.S. Air Force dropped its suicide rate by 60%. As an unintended benefit, the murder rate dropped by 50%.17
It is high time we did so.
Dr. Behar is a psychiatrist in Lower Merion, Pa. He graduated from Hahnemann Medical College, Philadelphia, in 1975, and has had postgraduate training at SUNY Stony Brook, University of Iowa, the National Institute of Mental Health, and Columbia University. His practice focuses on difficult, treatment-resistant cases.
References
1. U.S. Centers for Disease Control and Prevention. Suicide Prevention. 2020.
2. Luoma JB et al. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002 Jun 1. doi: 10.1176/appi.ajp.159.6.909.
3. World Health Organization. Suicide. 2021 Jun 17.
4. National Institute of Corrections. Correctional suicide prevention: Policies and procedures. 1995.
5. Hufford MR. Alcohol and suicidal behavior. Clin Psychol Rev. 2001 Jul;21(5):797-811.
6. Stanley B and Brown GK. Safety planning intervention: A brief intervention to mitigate suicide risk. Cogn Behav Pract. 2012 May;19(2):256-64.
7. Ibid.
8. Brown GK and Jager-Hyman S. Evidence-based psychotherapies for suicide prevention: Future directions. Am J Prev Med. 2014 Sep;47(3 Suppl 2):S186-94.
9. Isometsä ET. Psychological autopsy studies – A review. Eur Psychiatry. 2001 Nov;16(7):379-85.
10. Van Orden KA et al. The interpersonal theory of suicide. Psychol Rev. 2010 Apr; 117(2):575-600.
11. O’Connor v. Donaldson, 422 U.S. 563 (1975).
12. Calculated based on annual suicide statistics from the CDC and the time elapsed since the Supreme Court decision in O’Connor v. Donaldson.
13. Metzl JM and MacLeish KT. Mental illness, mass shootings, and the politics of American firearms. Am J Public Health. 2015 Feb;105(2):240-9.
14. Fazel S et al. The prevalence of mental disorders among the homeless in western countries: Systematic review and meta-regression analysis. PLoS Med. 2008 Dec 2;5(12):e225.
15. Amador XF and David AS. (eds.) Insight and psychosis: Awareness of illness in schizophrenia and related disorders (2nd ed.). Oxford Univ Press. 2004.
16. Calculated based on the potential impact of homelessness on property values and the relationship between untreated mental illness and homelessness.
17. Armed Forces Health Surveillance Branch. Surveillance snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998-2015. Medical Surveillance Monthly Report. 2016 Apr;23(4):19.
The old man was restrained at the last moment from jumping off the hospital’s fifth floor atrium parapet. He was suffering from terminal cancer and had been racked with chronic, severe pain for months.
The consult recognized symptoms of depression arising from his continuous physical suffering, advising that a male aide be dispatched to sit with the man and that he be put on a regimen of 10 mg of methadone twice a day to alleviate the pain. The following day the man was calm; he no longer wanted to kill himself. He expressed a strong desire to go home, return to gardening, and to play with his grandchildren.
Most of the 47,000 suicides that occur in the United States every year are preventable.1 Our national policy on this front has been nothing short of an abject failure. The government implemented a system with limited effect on completed suicides – a telephone hotline. This hotline is not called by the most common suicide victims: male, old, and quiet.2
The consequences of this national policy disaster have been profound, resulting in the biggest loss of productive years of life for any fatal condition.3 The grief experienced by the families of those who commit suicide is far greater than normal bereavement: The cause of death of their loved ones was not an unfortunate accident or a disease, it was an intentional act, and families take it personally.
One of the greatest achievements of psychiatry during the 20th century was the lowering of suicide rates in prisons by 70% with no treatment, no additional staffing, and no additional expenditures of funds. Today if inmates threaten suicide, they are immediately placed under eyesight supervision by guards. The federal pamphlet that describes this protocol was published in 1995 and is freely available online.4
Half of all suicide attempts are made by individuals who are legally drunk.5 Watch them for 6 hours and then ask them if they want to kill themselves and the response will almost invariably be “Of course not,” with the risk of further attempts dissipating in step with their blood alcohol level. The best resources to provide this kind of intervention are responsible adult family members, at no cost to the government. Indeed, in many cases family supervision is superior to that provided by a locked psychiatric ward with three staff members chasing after 20 agitated people all night long. The one-on-one attention that a family member can provide is free as well as far more personal and insightful, and more sincerely caring.
Guarantees in the field of medicine are rare. But, one such guarantee is that after their mood has improved, 100% of people will be thankful that they did not hurt themselves.6 This means that successful treatment will prevent 100% of all suicides.7 Not all treatments are successful, but 95% can be.8 At autopsy, few successful suicide victims have psychiatric medications in their system.9 The urge to kill oneself might best be characterized as a temporary chemical alteration of the brain causing delusional thoughts, including the ultimate delusion that life is not worth living.10 This alteration suppresses the strongest, most fundamental urge of all, namely, the survival instinct.
We must overturn the catastrophic decision of the U.S. Supreme Court that requires the showing of a dangerous act and the holding of a trial employing at least three lawyers for involuntary commitment to be authorized. Rather, involuntary treatment is justified by medical necessity as determined by two licensed professionals with no conflicts of interest. It can be outpatient.
The Supreme Court’s decision in O’Connor v. Donaldson in 1975 remedied an illusory wrong, addressing an act of blatant malpractice, not policy inequity.11 The superintendent of the state facility in that case was not even a doctor. He kept O’Connor prisoner for more than a decade, perhaps to keep a bed filled. Over the past half-century, this one decision has resulted in 1 million preventable suicides12 and half a million senseless murders by paranoid individuals, including many rampage shootings.13
More than two-thirds of homeless individuals suffer from an untreated mental condition.14 The vast majority of them will refuse all offers of treatment because they also have anosognosia, a brain-based disorder causing denial of illness.15 By referring to these individuals as “homeless,” we are also lowering real estate values for a square block around where they happen to be camped out. That cost has never been calculated, but it is another real consequence of this devastating Supreme Court decision.16
Detractors and mental health rights activists may argue that individual rights cannot be infringed. In that case, those same detractors and mental health rights activists must take responsibility for the thousands of lives and billions of dollars in economic damage caused by their refusal to allow an effective solution to the suicide epidemic to be implemented. Enforced outpatient treatment by the U.S. Air Force dropped its suicide rate by 60%. As an unintended benefit, the murder rate dropped by 50%.17
It is high time we did so.
Dr. Behar is a psychiatrist in Lower Merion, Pa. He graduated from Hahnemann Medical College, Philadelphia, in 1975, and has had postgraduate training at SUNY Stony Brook, University of Iowa, the National Institute of Mental Health, and Columbia University. His practice focuses on difficult, treatment-resistant cases.
References
1. U.S. Centers for Disease Control and Prevention. Suicide Prevention. 2020.
2. Luoma JB et al. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002 Jun 1. doi: 10.1176/appi.ajp.159.6.909.
3. World Health Organization. Suicide. 2021 Jun 17.
4. National Institute of Corrections. Correctional suicide prevention: Policies and procedures. 1995.
5. Hufford MR. Alcohol and suicidal behavior. Clin Psychol Rev. 2001 Jul;21(5):797-811.
6. Stanley B and Brown GK. Safety planning intervention: A brief intervention to mitigate suicide risk. Cogn Behav Pract. 2012 May;19(2):256-64.
7. Ibid.
8. Brown GK and Jager-Hyman S. Evidence-based psychotherapies for suicide prevention: Future directions. Am J Prev Med. 2014 Sep;47(3 Suppl 2):S186-94.
9. Isometsä ET. Psychological autopsy studies – A review. Eur Psychiatry. 2001 Nov;16(7):379-85.
10. Van Orden KA et al. The interpersonal theory of suicide. Psychol Rev. 2010 Apr; 117(2):575-600.
11. O’Connor v. Donaldson, 422 U.S. 563 (1975).
12. Calculated based on annual suicide statistics from the CDC and the time elapsed since the Supreme Court decision in O’Connor v. Donaldson.
13. Metzl JM and MacLeish KT. Mental illness, mass shootings, and the politics of American firearms. Am J Public Health. 2015 Feb;105(2):240-9.
14. Fazel S et al. The prevalence of mental disorders among the homeless in western countries: Systematic review and meta-regression analysis. PLoS Med. 2008 Dec 2;5(12):e225.
15. Amador XF and David AS. (eds.) Insight and psychosis: Awareness of illness in schizophrenia and related disorders (2nd ed.). Oxford Univ Press. 2004.
16. Calculated based on the potential impact of homelessness on property values and the relationship between untreated mental illness and homelessness.
17. Armed Forces Health Surveillance Branch. Surveillance snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998-2015. Medical Surveillance Monthly Report. 2016 Apr;23(4):19.
The old man was restrained at the last moment from jumping off the hospital’s fifth floor atrium parapet. He was suffering from terminal cancer and had been racked with chronic, severe pain for months.
The consult recognized symptoms of depression arising from his continuous physical suffering, advising that a male aide be dispatched to sit with the man and that he be put on a regimen of 10 mg of methadone twice a day to alleviate the pain. The following day the man was calm; he no longer wanted to kill himself. He expressed a strong desire to go home, return to gardening, and to play with his grandchildren.
Most of the 47,000 suicides that occur in the United States every year are preventable.1 Our national policy on this front has been nothing short of an abject failure. The government implemented a system with limited effect on completed suicides – a telephone hotline. This hotline is not called by the most common suicide victims: male, old, and quiet.2
The consequences of this national policy disaster have been profound, resulting in the biggest loss of productive years of life for any fatal condition.3 The grief experienced by the families of those who commit suicide is far greater than normal bereavement: The cause of death of their loved ones was not an unfortunate accident or a disease, it was an intentional act, and families take it personally.
One of the greatest achievements of psychiatry during the 20th century was the lowering of suicide rates in prisons by 70% with no treatment, no additional staffing, and no additional expenditures of funds. Today if inmates threaten suicide, they are immediately placed under eyesight supervision by guards. The federal pamphlet that describes this protocol was published in 1995 and is freely available online.4
Half of all suicide attempts are made by individuals who are legally drunk.5 Watch them for 6 hours and then ask them if they want to kill themselves and the response will almost invariably be “Of course not,” with the risk of further attempts dissipating in step with their blood alcohol level. The best resources to provide this kind of intervention are responsible adult family members, at no cost to the government. Indeed, in many cases family supervision is superior to that provided by a locked psychiatric ward with three staff members chasing after 20 agitated people all night long. The one-on-one attention that a family member can provide is free as well as far more personal and insightful, and more sincerely caring.
Guarantees in the field of medicine are rare. But, one such guarantee is that after their mood has improved, 100% of people will be thankful that they did not hurt themselves.6 This means that successful treatment will prevent 100% of all suicides.7 Not all treatments are successful, but 95% can be.8 At autopsy, few successful suicide victims have psychiatric medications in their system.9 The urge to kill oneself might best be characterized as a temporary chemical alteration of the brain causing delusional thoughts, including the ultimate delusion that life is not worth living.10 This alteration suppresses the strongest, most fundamental urge of all, namely, the survival instinct.
We must overturn the catastrophic decision of the U.S. Supreme Court that requires the showing of a dangerous act and the holding of a trial employing at least three lawyers for involuntary commitment to be authorized. Rather, involuntary treatment is justified by medical necessity as determined by two licensed professionals with no conflicts of interest. It can be outpatient.
The Supreme Court’s decision in O’Connor v. Donaldson in 1975 remedied an illusory wrong, addressing an act of blatant malpractice, not policy inequity.11 The superintendent of the state facility in that case was not even a doctor. He kept O’Connor prisoner for more than a decade, perhaps to keep a bed filled. Over the past half-century, this one decision has resulted in 1 million preventable suicides12 and half a million senseless murders by paranoid individuals, including many rampage shootings.13
More than two-thirds of homeless individuals suffer from an untreated mental condition.14 The vast majority of them will refuse all offers of treatment because they also have anosognosia, a brain-based disorder causing denial of illness.15 By referring to these individuals as “homeless,” we are also lowering real estate values for a square block around where they happen to be camped out. That cost has never been calculated, but it is another real consequence of this devastating Supreme Court decision.16
Detractors and mental health rights activists may argue that individual rights cannot be infringed. In that case, those same detractors and mental health rights activists must take responsibility for the thousands of lives and billions of dollars in economic damage caused by their refusal to allow an effective solution to the suicide epidemic to be implemented. Enforced outpatient treatment by the U.S. Air Force dropped its suicide rate by 60%. As an unintended benefit, the murder rate dropped by 50%.17
It is high time we did so.
Dr. Behar is a psychiatrist in Lower Merion, Pa. He graduated from Hahnemann Medical College, Philadelphia, in 1975, and has had postgraduate training at SUNY Stony Brook, University of Iowa, the National Institute of Mental Health, and Columbia University. His practice focuses on difficult, treatment-resistant cases.
References
1. U.S. Centers for Disease Control and Prevention. Suicide Prevention. 2020.
2. Luoma JB et al. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002 Jun 1. doi: 10.1176/appi.ajp.159.6.909.
3. World Health Organization. Suicide. 2021 Jun 17.
4. National Institute of Corrections. Correctional suicide prevention: Policies and procedures. 1995.
5. Hufford MR. Alcohol and suicidal behavior. Clin Psychol Rev. 2001 Jul;21(5):797-811.
6. Stanley B and Brown GK. Safety planning intervention: A brief intervention to mitigate suicide risk. Cogn Behav Pract. 2012 May;19(2):256-64.
7. Ibid.
8. Brown GK and Jager-Hyman S. Evidence-based psychotherapies for suicide prevention: Future directions. Am J Prev Med. 2014 Sep;47(3 Suppl 2):S186-94.
9. Isometsä ET. Psychological autopsy studies – A review. Eur Psychiatry. 2001 Nov;16(7):379-85.
10. Van Orden KA et al. The interpersonal theory of suicide. Psychol Rev. 2010 Apr; 117(2):575-600.
11. O’Connor v. Donaldson, 422 U.S. 563 (1975).
12. Calculated based on annual suicide statistics from the CDC and the time elapsed since the Supreme Court decision in O’Connor v. Donaldson.
13. Metzl JM and MacLeish KT. Mental illness, mass shootings, and the politics of American firearms. Am J Public Health. 2015 Feb;105(2):240-9.
14. Fazel S et al. The prevalence of mental disorders among the homeless in western countries: Systematic review and meta-regression analysis. PLoS Med. 2008 Dec 2;5(12):e225.
15. Amador XF and David AS. (eds.) Insight and psychosis: Awareness of illness in schizophrenia and related disorders (2nd ed.). Oxford Univ Press. 2004.
16. Calculated based on the potential impact of homelessness on property values and the relationship between untreated mental illness and homelessness.
17. Armed Forces Health Surveillance Branch. Surveillance snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998-2015. Medical Surveillance Monthly Report. 2016 Apr;23(4):19.
Which interventions could lessen the burden of dementia?
Using a microsimulation algorithm that accounts for the effect on mortality, a team from Marseille, France, has shown that interventions targeting the three main vascular risk factors for dementia – hypertension, diabetes, and physical inactivity – could significantly reduce the burden of dementia by 2040.
Although these modeling results could appear too optimistic, since total disappearance of the risk factors was assumed, the authors say the results do show that targeted interventions for these factors could be effective in reducing the future burden of dementia.
Increasing prevalence
According to the World Alzheimer Report 2018, 50 million people around the world were living with dementia; a population roughly around the size of South Korea or Spain. That community is likely to rise to about 152 million people by 2050, which is similar to the size of Russia or Bangladesh, the result of an aging population.
Among modifiable risk factors, many studies support a deleterious effect of hypertension, diabetes, and physical inactivity on the risk of dementia. However, since the distribution of these risk factors could have a direct impact on mortality, reducing it should increase life expectancy and the number of cases of dementia.
The team, headed by Hélène Jacqmin-Gadda, PhD, research director at the University of Bordeaux (France), has developed a microsimulation model capable of predicting the burden of dementia while accounting for the impact on mortality. The team used this approach to assess the impact of interventions targeting these three main risk factors on the burden of dementia in France by 2040.
Removing risk factors
The researchers estimated the incidence of dementia for men and women using data from the 2020 PAQUID cohort, and these data were combined with the projections forecast by the French National Institute of Statistics and Economic Studies to account for mortality with and without dementia.
Without intervention, the prevalence rate of dementia in 2040 would be 9.6% among men and 14% among women older than 65 years.
These figures would decrease to 6.4% (−33%) and 10.4% (−26%), respectively, under the intervention scenario whereby the three modifiable vascular risk factors (hypertension, diabetes, and physical inactivity) would be removed simultaneously beginning in 2020. The prevalence rates are significantly reduced for men and women from age 75 years. In this scenario, life expectancy without dementia would increase by 3.4 years in men and 2.6 years in women, the result of men being more exposed to these three risk factors.
Other scenarios have estimated dementia prevalence with the disappearance of just one of these risk factors. For example, the disappearance of hypertension alone from 2020 could decrease dementia prevalence by 21% in men and 16% in women (because this risk factor is less common in women than in men) by 2040. This reduction would be associated with a decrease in the lifelong probability of dementia among men and women and a gain in life expectancy without dementia of 2 years in men and 1.4 years in women.
Among the three factors, hypertension has the largest impact on dementia burden in the French population, since this is, by far, the most prevalent (69% in men and 49% in women), while intervention targeting only diabetes or physical inactivity would lead to a reduction in dementia prevalence of only 4%-7%.
The authors reported no conflicts of interest.
This article was translated from Univadis France. A version appeared on Medscape.com.
Using a microsimulation algorithm that accounts for the effect on mortality, a team from Marseille, France, has shown that interventions targeting the three main vascular risk factors for dementia – hypertension, diabetes, and physical inactivity – could significantly reduce the burden of dementia by 2040.
Although these modeling results could appear too optimistic, since total disappearance of the risk factors was assumed, the authors say the results do show that targeted interventions for these factors could be effective in reducing the future burden of dementia.
Increasing prevalence
According to the World Alzheimer Report 2018, 50 million people around the world were living with dementia; a population roughly around the size of South Korea or Spain. That community is likely to rise to about 152 million people by 2050, which is similar to the size of Russia or Bangladesh, the result of an aging population.
Among modifiable risk factors, many studies support a deleterious effect of hypertension, diabetes, and physical inactivity on the risk of dementia. However, since the distribution of these risk factors could have a direct impact on mortality, reducing it should increase life expectancy and the number of cases of dementia.
The team, headed by Hélène Jacqmin-Gadda, PhD, research director at the University of Bordeaux (France), has developed a microsimulation model capable of predicting the burden of dementia while accounting for the impact on mortality. The team used this approach to assess the impact of interventions targeting these three main risk factors on the burden of dementia in France by 2040.
Removing risk factors
The researchers estimated the incidence of dementia for men and women using data from the 2020 PAQUID cohort, and these data were combined with the projections forecast by the French National Institute of Statistics and Economic Studies to account for mortality with and without dementia.
Without intervention, the prevalence rate of dementia in 2040 would be 9.6% among men and 14% among women older than 65 years.
These figures would decrease to 6.4% (−33%) and 10.4% (−26%), respectively, under the intervention scenario whereby the three modifiable vascular risk factors (hypertension, diabetes, and physical inactivity) would be removed simultaneously beginning in 2020. The prevalence rates are significantly reduced for men and women from age 75 years. In this scenario, life expectancy without dementia would increase by 3.4 years in men and 2.6 years in women, the result of men being more exposed to these three risk factors.
Other scenarios have estimated dementia prevalence with the disappearance of just one of these risk factors. For example, the disappearance of hypertension alone from 2020 could decrease dementia prevalence by 21% in men and 16% in women (because this risk factor is less common in women than in men) by 2040. This reduction would be associated with a decrease in the lifelong probability of dementia among men and women and a gain in life expectancy without dementia of 2 years in men and 1.4 years in women.
Among the three factors, hypertension has the largest impact on dementia burden in the French population, since this is, by far, the most prevalent (69% in men and 49% in women), while intervention targeting only diabetes or physical inactivity would lead to a reduction in dementia prevalence of only 4%-7%.
The authors reported no conflicts of interest.
This article was translated from Univadis France. A version appeared on Medscape.com.
Using a microsimulation algorithm that accounts for the effect on mortality, a team from Marseille, France, has shown that interventions targeting the three main vascular risk factors for dementia – hypertension, diabetes, and physical inactivity – could significantly reduce the burden of dementia by 2040.
Although these modeling results could appear too optimistic, since total disappearance of the risk factors was assumed, the authors say the results do show that targeted interventions for these factors could be effective in reducing the future burden of dementia.
Increasing prevalence
According to the World Alzheimer Report 2018, 50 million people around the world were living with dementia; a population roughly around the size of South Korea or Spain. That community is likely to rise to about 152 million people by 2050, which is similar to the size of Russia or Bangladesh, the result of an aging population.
Among modifiable risk factors, many studies support a deleterious effect of hypertension, diabetes, and physical inactivity on the risk of dementia. However, since the distribution of these risk factors could have a direct impact on mortality, reducing it should increase life expectancy and the number of cases of dementia.
The team, headed by Hélène Jacqmin-Gadda, PhD, research director at the University of Bordeaux (France), has developed a microsimulation model capable of predicting the burden of dementia while accounting for the impact on mortality. The team used this approach to assess the impact of interventions targeting these three main risk factors on the burden of dementia in France by 2040.
Removing risk factors
The researchers estimated the incidence of dementia for men and women using data from the 2020 PAQUID cohort, and these data were combined with the projections forecast by the French National Institute of Statistics and Economic Studies to account for mortality with and without dementia.
Without intervention, the prevalence rate of dementia in 2040 would be 9.6% among men and 14% among women older than 65 years.
These figures would decrease to 6.4% (−33%) and 10.4% (−26%), respectively, under the intervention scenario whereby the three modifiable vascular risk factors (hypertension, diabetes, and physical inactivity) would be removed simultaneously beginning in 2020. The prevalence rates are significantly reduced for men and women from age 75 years. In this scenario, life expectancy without dementia would increase by 3.4 years in men and 2.6 years in women, the result of men being more exposed to these three risk factors.
Other scenarios have estimated dementia prevalence with the disappearance of just one of these risk factors. For example, the disappearance of hypertension alone from 2020 could decrease dementia prevalence by 21% in men and 16% in women (because this risk factor is less common in women than in men) by 2040. This reduction would be associated with a decrease in the lifelong probability of dementia among men and women and a gain in life expectancy without dementia of 2 years in men and 1.4 years in women.
Among the three factors, hypertension has the largest impact on dementia burden in the French population, since this is, by far, the most prevalent (69% in men and 49% in women), while intervention targeting only diabetes or physical inactivity would lead to a reduction in dementia prevalence of only 4%-7%.
The authors reported no conflicts of interest.
This article was translated from Univadis France. A version appeared on Medscape.com.
FROM THE EUROPEAN JOURNAL OF EPIDEMIOLOGY
Scheduled bleeding may boost tolerability of hormone implants
BALTIMORE – The bleeding causes some women to have the device removed, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
In a randomized, double-blinded, placebo-controlled trial of 51 patients desiring the implants – which suppress ovulation by releasing progestin over a 3-year period – taking norethindrone acetate for 1 week every 4 weeks led to 80% of participants in the treatment group reporting satisfactory bleeding patterns with the etonogestrel implants in place.
Rates of early discontinuation have been variable, according to published literature, ranging from 13% to 21.1%, said Jordan Gray, MD, a fourth-year resident in ob.gyn. at Baylor Scott and White Medical Center, Temple, Tex., who helped conduct the new study. Reasons included bothersome bleeding. Dr. Gray and colleagues found that 24% of women in the placebo group requested removal of the implant, compared with 9% of those in the treatment group. Among these women, none requested removal for bothersome bleeding but rather for reasons such as wanting to get pregnant. One person requested removal because she did not like amenorrhea.
While the results of the study did not achieve statistical significance, owing to its size and noncompliance among some participants, it does indicate that norethindrone acetate may be helpful, Dr. Gray said.
During the study, participants in the treatment group (n = 22) received a monthly treatment regimen of 5 mg of oral norethindrone acetate daily for 7 days each month for the first 6 months after placement of an etonogestrel implant. The placebo group (n = 29) was given inert tablets prescribed in the same regimen. Both groups received products from a mail-order pharmacy.
Participants were women aged 18-48 years who desired an implant or those aged 14 years who had permission from a parent or guardian to receive the contraceptive. The study excluded people with known or suspected pregnancy, those less than 8 weeks’ post partum, those who experienced menarche less than 2 years ago, those with body mass index greater than 40, and those who received depot medroxyprogesterone acetate within the previous 12 weeks. Excessive bleeding was defined as bleeding or spotting on more than 7 consecutive days or a fifth episode of bleeding in 90 days.
Overall, 11 patients (38%) in the placebo group and 10 (45%) in the treatment arm withdrew from the study. Reasons included wanting to get pregnant, mood changes, or noncompliance with study parameters, which included not responding or returning bleeding diaries, Dr. Gray said.
A limitation of the study was that compliance was less than expected. In addition, there were challenges with rates of responses, Dr. Gray said. The study was conducted during the COVID-19 pandemic, when all in-person visits were transitioned to telehealth. Although the investigators offered payment to participants, not all returned text-message surveys. The researchers had intended to enroll 124 participants but curtailed the study early, owing to the limited number of participants.
Given that there is no standard approach to treating prolonged or excessive bleeding with etonogestrel implants, Dr. Gray said, “Our data suggests that this regimen is a simple and acceptable method to treat bothersome bleeding and that predictable bleeding may be more satisfactory than unpredictable bleeding.”
Veronica Maria Pimentel, MD, moderator of the session and a maternal-fetal medicine specialist and director of research for the ob.gyn. residency program at St. Francis Hospital, part of Trinity Health of New England in Hartford, Conn., praised the researchers for a well-designed study.
“However, unfortunately, they were not able to recruit the number of patients that they needed in order to achieve the power to show the difference [between treatment arms], so another study would have to be done to show if there is a difference,” Dr. Pimentel said.
Dr. Pimentel complimented Dr. Gray following her presentation, congratulating her for conducting a randomized, controlled trial: “That’s not easy, as you have shown, but it’s also a good try, so you can actually see how hard it is to obtain quality data from research.”
The study was supported in part by a research grant from the Investigator-Initiated Studies Program of Organon. Dr. Gray is a consultant for Johnson & Johnson. Dr. Pimentel has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BALTIMORE – The bleeding causes some women to have the device removed, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
In a randomized, double-blinded, placebo-controlled trial of 51 patients desiring the implants – which suppress ovulation by releasing progestin over a 3-year period – taking norethindrone acetate for 1 week every 4 weeks led to 80% of participants in the treatment group reporting satisfactory bleeding patterns with the etonogestrel implants in place.
Rates of early discontinuation have been variable, according to published literature, ranging from 13% to 21.1%, said Jordan Gray, MD, a fourth-year resident in ob.gyn. at Baylor Scott and White Medical Center, Temple, Tex., who helped conduct the new study. Reasons included bothersome bleeding. Dr. Gray and colleagues found that 24% of women in the placebo group requested removal of the implant, compared with 9% of those in the treatment group. Among these women, none requested removal for bothersome bleeding but rather for reasons such as wanting to get pregnant. One person requested removal because she did not like amenorrhea.
While the results of the study did not achieve statistical significance, owing to its size and noncompliance among some participants, it does indicate that norethindrone acetate may be helpful, Dr. Gray said.
During the study, participants in the treatment group (n = 22) received a monthly treatment regimen of 5 mg of oral norethindrone acetate daily for 7 days each month for the first 6 months after placement of an etonogestrel implant. The placebo group (n = 29) was given inert tablets prescribed in the same regimen. Both groups received products from a mail-order pharmacy.
Participants were women aged 18-48 years who desired an implant or those aged 14 years who had permission from a parent or guardian to receive the contraceptive. The study excluded people with known or suspected pregnancy, those less than 8 weeks’ post partum, those who experienced menarche less than 2 years ago, those with body mass index greater than 40, and those who received depot medroxyprogesterone acetate within the previous 12 weeks. Excessive bleeding was defined as bleeding or spotting on more than 7 consecutive days or a fifth episode of bleeding in 90 days.
Overall, 11 patients (38%) in the placebo group and 10 (45%) in the treatment arm withdrew from the study. Reasons included wanting to get pregnant, mood changes, or noncompliance with study parameters, which included not responding or returning bleeding diaries, Dr. Gray said.
A limitation of the study was that compliance was less than expected. In addition, there were challenges with rates of responses, Dr. Gray said. The study was conducted during the COVID-19 pandemic, when all in-person visits were transitioned to telehealth. Although the investigators offered payment to participants, not all returned text-message surveys. The researchers had intended to enroll 124 participants but curtailed the study early, owing to the limited number of participants.
Given that there is no standard approach to treating prolonged or excessive bleeding with etonogestrel implants, Dr. Gray said, “Our data suggests that this regimen is a simple and acceptable method to treat bothersome bleeding and that predictable bleeding may be more satisfactory than unpredictable bleeding.”
Veronica Maria Pimentel, MD, moderator of the session and a maternal-fetal medicine specialist and director of research for the ob.gyn. residency program at St. Francis Hospital, part of Trinity Health of New England in Hartford, Conn., praised the researchers for a well-designed study.
“However, unfortunately, they were not able to recruit the number of patients that they needed in order to achieve the power to show the difference [between treatment arms], so another study would have to be done to show if there is a difference,” Dr. Pimentel said.
Dr. Pimentel complimented Dr. Gray following her presentation, congratulating her for conducting a randomized, controlled trial: “That’s not easy, as you have shown, but it’s also a good try, so you can actually see how hard it is to obtain quality data from research.”
The study was supported in part by a research grant from the Investigator-Initiated Studies Program of Organon. Dr. Gray is a consultant for Johnson & Johnson. Dr. Pimentel has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BALTIMORE – The bleeding causes some women to have the device removed, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
In a randomized, double-blinded, placebo-controlled trial of 51 patients desiring the implants – which suppress ovulation by releasing progestin over a 3-year period – taking norethindrone acetate for 1 week every 4 weeks led to 80% of participants in the treatment group reporting satisfactory bleeding patterns with the etonogestrel implants in place.
Rates of early discontinuation have been variable, according to published literature, ranging from 13% to 21.1%, said Jordan Gray, MD, a fourth-year resident in ob.gyn. at Baylor Scott and White Medical Center, Temple, Tex., who helped conduct the new study. Reasons included bothersome bleeding. Dr. Gray and colleagues found that 24% of women in the placebo group requested removal of the implant, compared with 9% of those in the treatment group. Among these women, none requested removal for bothersome bleeding but rather for reasons such as wanting to get pregnant. One person requested removal because she did not like amenorrhea.
While the results of the study did not achieve statistical significance, owing to its size and noncompliance among some participants, it does indicate that norethindrone acetate may be helpful, Dr. Gray said.
During the study, participants in the treatment group (n = 22) received a monthly treatment regimen of 5 mg of oral norethindrone acetate daily for 7 days each month for the first 6 months after placement of an etonogestrel implant. The placebo group (n = 29) was given inert tablets prescribed in the same regimen. Both groups received products from a mail-order pharmacy.
Participants were women aged 18-48 years who desired an implant or those aged 14 years who had permission from a parent or guardian to receive the contraceptive. The study excluded people with known or suspected pregnancy, those less than 8 weeks’ post partum, those who experienced menarche less than 2 years ago, those with body mass index greater than 40, and those who received depot medroxyprogesterone acetate within the previous 12 weeks. Excessive bleeding was defined as bleeding or spotting on more than 7 consecutive days or a fifth episode of bleeding in 90 days.
Overall, 11 patients (38%) in the placebo group and 10 (45%) in the treatment arm withdrew from the study. Reasons included wanting to get pregnant, mood changes, or noncompliance with study parameters, which included not responding or returning bleeding diaries, Dr. Gray said.
A limitation of the study was that compliance was less than expected. In addition, there were challenges with rates of responses, Dr. Gray said. The study was conducted during the COVID-19 pandemic, when all in-person visits were transitioned to telehealth. Although the investigators offered payment to participants, not all returned text-message surveys. The researchers had intended to enroll 124 participants but curtailed the study early, owing to the limited number of participants.
Given that there is no standard approach to treating prolonged or excessive bleeding with etonogestrel implants, Dr. Gray said, “Our data suggests that this regimen is a simple and acceptable method to treat bothersome bleeding and that predictable bleeding may be more satisfactory than unpredictable bleeding.”
Veronica Maria Pimentel, MD, moderator of the session and a maternal-fetal medicine specialist and director of research for the ob.gyn. residency program at St. Francis Hospital, part of Trinity Health of New England in Hartford, Conn., praised the researchers for a well-designed study.
“However, unfortunately, they were not able to recruit the number of patients that they needed in order to achieve the power to show the difference [between treatment arms], so another study would have to be done to show if there is a difference,” Dr. Pimentel said.
Dr. Pimentel complimented Dr. Gray following her presentation, congratulating her for conducting a randomized, controlled trial: “That’s not easy, as you have shown, but it’s also a good try, so you can actually see how hard it is to obtain quality data from research.”
The study was supported in part by a research grant from the Investigator-Initiated Studies Program of Organon. Dr. Gray is a consultant for Johnson & Johnson. Dr. Pimentel has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACOG 2023