User login
The promise of endoscopy simulation–based training and gaps as targets for innovation
SAN FRANCISCO – The growing sophistication of simulation technology has the potential to improve training and assessment of skills in gastrointestinal endoscopy, but there are gaps between the promise and evidence, according to an overview of this form of training at the 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.
For endoscopy, the term simulator encompasses a broad expanse of tools that can range from a simple physical model with holes used to practice endoscope navigation skills to a complex virtual world that challenges technical skills as well as decision-making processes. In 2012, the American Society of Gastrointestinal Endoscopy (ASGE) issued a statement encouraging endoscopy simulation-based training in the context of other strategies to gain skills, but Catharine Walsh, MD, MEd, PhD, of the University of Toronto, warned of the current limits as well as the advantages of simulation training.
“There are many companies making simulators of varying price and complexity. For early skill acquisition, more expensive devices may not necessarily be better,” Dr. Walsh said. She highlighted that “one’s choice of simulator should be based on the educational goals as opposed to technology, as the effectiveness of simulation depends highly on a close match between the training goals and the simulation tool.” A longstanding issue in the field of simulation relates to cost and access. Simulation will not have widespread impact unless it is accessible. “There is a need for future development of inexpensive, portable simulators targeting specific skills to help facilitate uptake of simulation across endoscopy units and training programs,” said Dr. Walsh. Other strategies to increase uptake include specific learning modules designed to complement simulators.
Although simulators are increasingly being used during training to help endoscopists develop basic endoscopic skills, Dr. Walsh focused on the gap in development of simulator devices targeting practicing endoscopists and research examining their use for training new skills within practice, preventing skills decay, and remediating performance deficits. She explained that “currently, there is a lack of evidence that simulation adoption by practicing endoscopists leads to better patient outcomes. This remains a priority area for simulation education, research, and development.” It also remains to be seen how cost-effective simulators are compared with other reaching modalities, she said.
“The potential is certainly there, but it is essential to develop simulators targeting training for low-volume, higher stakes therapeutic techniques, emerging procedures, and techniques and advanced endoscopic procedures, and perform well-controlled studies to demonstrate their effectiveness in practice,” Dr. Walsh said. “Embedding assessments within emerging simulation technology is key as it permits identification of skills requiring further practice and can form the basis of virtual coaching employing endoscopic simulation to improve skills and outcomes.”
Simulators offer the very important advantage of giving the physician the chance to acquire skills before participating in a clinical case and allowing errors to occur in a risk-free environment, suggesting that this type of training will only grow. For example, Dr. Walsh described emerging simulation-based team training that allows endoscopy teams to practice both technical skills as well as nontechnical skills, such as communication and decision making, which may be particularly important in the event of a crisis. Gamification is also being pursued as a potential adjunct strategy to help improve engagement and skill acquisition.
Current simulators are limited in their ability to train and assess cognitive and nontechnical skills. Development of simulation-based cognitive training tools for key areas such as lesion recognition, classification, and management decision-making skills is also a promising area to pursue. Such education could be delivered via portable electronic devices and incorporate assessment and feedback to facilitate skills acquisition.
“There remains a substantial gap between the promise of many types of simulation training and objective evidence that these are helping endoscopists gain skills,” Dr. Walsh said. This in no way diminishes the enormous promise of new simulation technology to be an effective and safe approach for clinicians to learn and maintain performance of endoscopic skills, but Dr. Walsh focused on the need for the development of new simulation technologies and controlled studies that will render these approaches evidence based.
SAN FRANCISCO – The growing sophistication of simulation technology has the potential to improve training and assessment of skills in gastrointestinal endoscopy, but there are gaps between the promise and evidence, according to an overview of this form of training at the 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.
For endoscopy, the term simulator encompasses a broad expanse of tools that can range from a simple physical model with holes used to practice endoscope navigation skills to a complex virtual world that challenges technical skills as well as decision-making processes. In 2012, the American Society of Gastrointestinal Endoscopy (ASGE) issued a statement encouraging endoscopy simulation-based training in the context of other strategies to gain skills, but Catharine Walsh, MD, MEd, PhD, of the University of Toronto, warned of the current limits as well as the advantages of simulation training.
“There are many companies making simulators of varying price and complexity. For early skill acquisition, more expensive devices may not necessarily be better,” Dr. Walsh said. She highlighted that “one’s choice of simulator should be based on the educational goals as opposed to technology, as the effectiveness of simulation depends highly on a close match between the training goals and the simulation tool.” A longstanding issue in the field of simulation relates to cost and access. Simulation will not have widespread impact unless it is accessible. “There is a need for future development of inexpensive, portable simulators targeting specific skills to help facilitate uptake of simulation across endoscopy units and training programs,” said Dr. Walsh. Other strategies to increase uptake include specific learning modules designed to complement simulators.
Although simulators are increasingly being used during training to help endoscopists develop basic endoscopic skills, Dr. Walsh focused on the gap in development of simulator devices targeting practicing endoscopists and research examining their use for training new skills within practice, preventing skills decay, and remediating performance deficits. She explained that “currently, there is a lack of evidence that simulation adoption by practicing endoscopists leads to better patient outcomes. This remains a priority area for simulation education, research, and development.” It also remains to be seen how cost-effective simulators are compared with other reaching modalities, she said.
“The potential is certainly there, but it is essential to develop simulators targeting training for low-volume, higher stakes therapeutic techniques, emerging procedures, and techniques and advanced endoscopic procedures, and perform well-controlled studies to demonstrate their effectiveness in practice,” Dr. Walsh said. “Embedding assessments within emerging simulation technology is key as it permits identification of skills requiring further practice and can form the basis of virtual coaching employing endoscopic simulation to improve skills and outcomes.”
Simulators offer the very important advantage of giving the physician the chance to acquire skills before participating in a clinical case and allowing errors to occur in a risk-free environment, suggesting that this type of training will only grow. For example, Dr. Walsh described emerging simulation-based team training that allows endoscopy teams to practice both technical skills as well as nontechnical skills, such as communication and decision making, which may be particularly important in the event of a crisis. Gamification is also being pursued as a potential adjunct strategy to help improve engagement and skill acquisition.
Current simulators are limited in their ability to train and assess cognitive and nontechnical skills. Development of simulation-based cognitive training tools for key areas such as lesion recognition, classification, and management decision-making skills is also a promising area to pursue. Such education could be delivered via portable electronic devices and incorporate assessment and feedback to facilitate skills acquisition.
“There remains a substantial gap between the promise of many types of simulation training and objective evidence that these are helping endoscopists gain skills,” Dr. Walsh said. This in no way diminishes the enormous promise of new simulation technology to be an effective and safe approach for clinicians to learn and maintain performance of endoscopic skills, but Dr. Walsh focused on the need for the development of new simulation technologies and controlled studies that will render these approaches evidence based.
SAN FRANCISCO – The growing sophistication of simulation technology has the potential to improve training and assessment of skills in gastrointestinal endoscopy, but there are gaps between the promise and evidence, according to an overview of this form of training at the 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.
For endoscopy, the term simulator encompasses a broad expanse of tools that can range from a simple physical model with holes used to practice endoscope navigation skills to a complex virtual world that challenges technical skills as well as decision-making processes. In 2012, the American Society of Gastrointestinal Endoscopy (ASGE) issued a statement encouraging endoscopy simulation-based training in the context of other strategies to gain skills, but Catharine Walsh, MD, MEd, PhD, of the University of Toronto, warned of the current limits as well as the advantages of simulation training.
“There are many companies making simulators of varying price and complexity. For early skill acquisition, more expensive devices may not necessarily be better,” Dr. Walsh said. She highlighted that “one’s choice of simulator should be based on the educational goals as opposed to technology, as the effectiveness of simulation depends highly on a close match between the training goals and the simulation tool.” A longstanding issue in the field of simulation relates to cost and access. Simulation will not have widespread impact unless it is accessible. “There is a need for future development of inexpensive, portable simulators targeting specific skills to help facilitate uptake of simulation across endoscopy units and training programs,” said Dr. Walsh. Other strategies to increase uptake include specific learning modules designed to complement simulators.
Although simulators are increasingly being used during training to help endoscopists develop basic endoscopic skills, Dr. Walsh focused on the gap in development of simulator devices targeting practicing endoscopists and research examining their use for training new skills within practice, preventing skills decay, and remediating performance deficits. She explained that “currently, there is a lack of evidence that simulation adoption by practicing endoscopists leads to better patient outcomes. This remains a priority area for simulation education, research, and development.” It also remains to be seen how cost-effective simulators are compared with other reaching modalities, she said.
“The potential is certainly there, but it is essential to develop simulators targeting training for low-volume, higher stakes therapeutic techniques, emerging procedures, and techniques and advanced endoscopic procedures, and perform well-controlled studies to demonstrate their effectiveness in practice,” Dr. Walsh said. “Embedding assessments within emerging simulation technology is key as it permits identification of skills requiring further practice and can form the basis of virtual coaching employing endoscopic simulation to improve skills and outcomes.”
Simulators offer the very important advantage of giving the physician the chance to acquire skills before participating in a clinical case and allowing errors to occur in a risk-free environment, suggesting that this type of training will only grow. For example, Dr. Walsh described emerging simulation-based team training that allows endoscopy teams to practice both technical skills as well as nontechnical skills, such as communication and decision making, which may be particularly important in the event of a crisis. Gamification is also being pursued as a potential adjunct strategy to help improve engagement and skill acquisition.
Current simulators are limited in their ability to train and assess cognitive and nontechnical skills. Development of simulation-based cognitive training tools for key areas such as lesion recognition, classification, and management decision-making skills is also a promising area to pursue. Such education could be delivered via portable electronic devices and incorporate assessment and feedback to facilitate skills acquisition.
“There remains a substantial gap between the promise of many types of simulation training and objective evidence that these are helping endoscopists gain skills,” Dr. Walsh said. This in no way diminishes the enormous promise of new simulation technology to be an effective and safe approach for clinicians to learn and maintain performance of endoscopic skills, but Dr. Walsh focused on the need for the development of new simulation technologies and controlled studies that will render these approaches evidence based.
REPORTING FROM 2019 AGA TECH SUMMIT
Virtual reality emerges as a therapeutic tool in gastroenterology
SAN FRANCISCO – The body of evidence to support virtual reality (VR) as a therapeutic modality will increasingly involve the GI tract, according to evidence summarized at the 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. Evolving from its early use in acute or chronic pain, where its function was to simply divert attention from symptoms, VR computer-generated environments are now being applied to alter patient perceptions and behavior that may involve changes in brain function, according to Brennan Spiegel, MD, AGAF, director of Health Services Research for Cedars-Sinai Medical Center, Los Angeles.
“The field of gastroenterology is a particularly promising area for treatment based on VR because of the well-established brain-gut interaction,” Dr. Spiegel explained. He said this tool has now been shown repeatedly to change how patients experience their symptoms in a variety of clinical contexts.
The field is not entirely new. Already by 2017, 11 randomized controlled trials of VR for therapeutic purposes were identified in a systematic review (Innov Clin Neurosci 2017;14:14-21). These trials, dating back to 2010, have explored this technology in depression, cognitive and motor rehabilitation, and eating disorders. Most showed significant benefit. In eating disorders, for example, response at one year was 44% in those receiving VR as an adjunct to cognitive behavioral therapy versus 10% in the controls.
“VR may not just alter perception. In studies being conducted with functional MRI imaging, changes in brain function similar to those observed in patients taking opioids have been observed,” said Dr. Spiegel, outlining objective evidence that VR has physiological effects.
VR already has an established role as a training tool for physicians in GI and other areas of medicine, but Dr. Spiegel focused on the evidence of its applications in treatment. Earlier this year, an expert panel in which he participated published a methodology for VR clinical trials to help move the field forward by defining how to establish evidence of benefit (JMIR Mental Health 2019;6:e11973). With a growing body of data suggesting VR has measurable clinical benefits, the field is poised to grow quickly.
In gastroenterology specifically, Dr. Spiegel envisions applications in functional diseases, such as irritable bowel syndrome (IBS), in which there is already strong evidence of a mind-gut component to symptom flares. He said, “VR can help patients to engage with their body differently, changing how they react to symptoms and leading to better coping mechanisms.”
In one example, Dr. Spiegel displayed a video depicting a woman with severe pain due to liver ascites testifying to substantial pain relief after a VR experience that included images that took her far from the hospital room in which she was sitting at the time. He reported that gastrointestinal pain relief is so consistent with VR that failure to respond prompts him to reevaluate patients for missed organic pathology.
Implementation of VR as a therapeutic tool is not without obstacles. For example, patients susceptible to motion sickness can react poorly to the three-dimensional environment created by VR, according to Dr. Spiegel. Many patients have expressed reluctance to try VR for any one of a number of reasons, including skepticism. However, there are many potential advantages. In the management of pain, for example, VR circumvents a long list of adverse events related to opioids or other analgesics.
This technology is only being used in a few centers, but there is enough evidence of clinical benefit that Dr. Siegel expects it to be more broadly adopted as indications expand. With more controlled trials being performed to measure and establish benefits, he envisions an evidence-based VR pharmacy that will allow clinicians to prescribe specific VR software suitable not only for the target condition but matched to patient preferences for VR environments.
“We have good evidence that VR is a powerful tool to manage mood disorders and pain perception. Although there is so far a fairly limited about of research specific to GI conditions, this is coming,” Dr. Spiegel said.
SAN FRANCISCO – The body of evidence to support virtual reality (VR) as a therapeutic modality will increasingly involve the GI tract, according to evidence summarized at the 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. Evolving from its early use in acute or chronic pain, where its function was to simply divert attention from symptoms, VR computer-generated environments are now being applied to alter patient perceptions and behavior that may involve changes in brain function, according to Brennan Spiegel, MD, AGAF, director of Health Services Research for Cedars-Sinai Medical Center, Los Angeles.
“The field of gastroenterology is a particularly promising area for treatment based on VR because of the well-established brain-gut interaction,” Dr. Spiegel explained. He said this tool has now been shown repeatedly to change how patients experience their symptoms in a variety of clinical contexts.
The field is not entirely new. Already by 2017, 11 randomized controlled trials of VR for therapeutic purposes were identified in a systematic review (Innov Clin Neurosci 2017;14:14-21). These trials, dating back to 2010, have explored this technology in depression, cognitive and motor rehabilitation, and eating disorders. Most showed significant benefit. In eating disorders, for example, response at one year was 44% in those receiving VR as an adjunct to cognitive behavioral therapy versus 10% in the controls.
“VR may not just alter perception. In studies being conducted with functional MRI imaging, changes in brain function similar to those observed in patients taking opioids have been observed,” said Dr. Spiegel, outlining objective evidence that VR has physiological effects.
VR already has an established role as a training tool for physicians in GI and other areas of medicine, but Dr. Spiegel focused on the evidence of its applications in treatment. Earlier this year, an expert panel in which he participated published a methodology for VR clinical trials to help move the field forward by defining how to establish evidence of benefit (JMIR Mental Health 2019;6:e11973). With a growing body of data suggesting VR has measurable clinical benefits, the field is poised to grow quickly.
In gastroenterology specifically, Dr. Spiegel envisions applications in functional diseases, such as irritable bowel syndrome (IBS), in which there is already strong evidence of a mind-gut component to symptom flares. He said, “VR can help patients to engage with their body differently, changing how they react to symptoms and leading to better coping mechanisms.”
In one example, Dr. Spiegel displayed a video depicting a woman with severe pain due to liver ascites testifying to substantial pain relief after a VR experience that included images that took her far from the hospital room in which she was sitting at the time. He reported that gastrointestinal pain relief is so consistent with VR that failure to respond prompts him to reevaluate patients for missed organic pathology.
Implementation of VR as a therapeutic tool is not without obstacles. For example, patients susceptible to motion sickness can react poorly to the three-dimensional environment created by VR, according to Dr. Spiegel. Many patients have expressed reluctance to try VR for any one of a number of reasons, including skepticism. However, there are many potential advantages. In the management of pain, for example, VR circumvents a long list of adverse events related to opioids or other analgesics.
This technology is only being used in a few centers, but there is enough evidence of clinical benefit that Dr. Siegel expects it to be more broadly adopted as indications expand. With more controlled trials being performed to measure and establish benefits, he envisions an evidence-based VR pharmacy that will allow clinicians to prescribe specific VR software suitable not only for the target condition but matched to patient preferences for VR environments.
“We have good evidence that VR is a powerful tool to manage mood disorders and pain perception. Although there is so far a fairly limited about of research specific to GI conditions, this is coming,” Dr. Spiegel said.
SAN FRANCISCO – The body of evidence to support virtual reality (VR) as a therapeutic modality will increasingly involve the GI tract, according to evidence summarized at the 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. Evolving from its early use in acute or chronic pain, where its function was to simply divert attention from symptoms, VR computer-generated environments are now being applied to alter patient perceptions and behavior that may involve changes in brain function, according to Brennan Spiegel, MD, AGAF, director of Health Services Research for Cedars-Sinai Medical Center, Los Angeles.
“The field of gastroenterology is a particularly promising area for treatment based on VR because of the well-established brain-gut interaction,” Dr. Spiegel explained. He said this tool has now been shown repeatedly to change how patients experience their symptoms in a variety of clinical contexts.
The field is not entirely new. Already by 2017, 11 randomized controlled trials of VR for therapeutic purposes were identified in a systematic review (Innov Clin Neurosci 2017;14:14-21). These trials, dating back to 2010, have explored this technology in depression, cognitive and motor rehabilitation, and eating disorders. Most showed significant benefit. In eating disorders, for example, response at one year was 44% in those receiving VR as an adjunct to cognitive behavioral therapy versus 10% in the controls.
“VR may not just alter perception. In studies being conducted with functional MRI imaging, changes in brain function similar to those observed in patients taking opioids have been observed,” said Dr. Spiegel, outlining objective evidence that VR has physiological effects.
VR already has an established role as a training tool for physicians in GI and other areas of medicine, but Dr. Spiegel focused on the evidence of its applications in treatment. Earlier this year, an expert panel in which he participated published a methodology for VR clinical trials to help move the field forward by defining how to establish evidence of benefit (JMIR Mental Health 2019;6:e11973). With a growing body of data suggesting VR has measurable clinical benefits, the field is poised to grow quickly.
In gastroenterology specifically, Dr. Spiegel envisions applications in functional diseases, such as irritable bowel syndrome (IBS), in which there is already strong evidence of a mind-gut component to symptom flares. He said, “VR can help patients to engage with their body differently, changing how they react to symptoms and leading to better coping mechanisms.”
In one example, Dr. Spiegel displayed a video depicting a woman with severe pain due to liver ascites testifying to substantial pain relief after a VR experience that included images that took her far from the hospital room in which she was sitting at the time. He reported that gastrointestinal pain relief is so consistent with VR that failure to respond prompts him to reevaluate patients for missed organic pathology.
Implementation of VR as a therapeutic tool is not without obstacles. For example, patients susceptible to motion sickness can react poorly to the three-dimensional environment created by VR, according to Dr. Spiegel. Many patients have expressed reluctance to try VR for any one of a number of reasons, including skepticism. However, there are many potential advantages. In the management of pain, for example, VR circumvents a long list of adverse events related to opioids or other analgesics.
This technology is only being used in a few centers, but there is enough evidence of clinical benefit that Dr. Siegel expects it to be more broadly adopted as indications expand. With more controlled trials being performed to measure and establish benefits, he envisions an evidence-based VR pharmacy that will allow clinicians to prescribe specific VR software suitable not only for the target condition but matched to patient preferences for VR environments.
“We have good evidence that VR is a powerful tool to manage mood disorders and pain perception. Although there is so far a fairly limited about of research specific to GI conditions, this is coming,” Dr. Spiegel said.
EXPERT ANALYSIS FROM 2019 AGA TECH SUMMIT
AI boosts gastroendoscopy, supports clinicians
SAN FRANCISCO – Artificial intelligence (AI) can improve video recording and physician support during colonoscopy procedures, and the data being collected could eventually pave the way to AI systems powerful enough to detect polyps on their own.
AI has been touted as a means to reduce costs and improve patient outcomes, but there’s another benefit that is sometimes overlooked – physician satisfaction. Examining colonoscopy after colonoscopy can get a little overwhelming. “There’s only so much the human eye can see, and when you’re doing multiple colonoscopies a day, there’s a possibility that you’re just seeing too much. [AI] could help lessen the burden in making those diagnoses,” said Kurt Heine in an interview.
Mr. Heine is vice president of the endoscopy division at Olympus America. He joined other speakers at a panel on artificial intelligence at the 2019 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.
Physicians are under an increasing burden with the aging population and recommendations from the American Cancer Society that colonoscopies should begin at age 45. “We need a more efficient way to perform colonoscopies. Ideally AI would aid in the adenoma detection rate and perhaps someday in diagnosis. We’re trying to build a support tool to assist in that procedure,” said Heine.
That point was echoed by Matt Schwartz, CEO of Virgo, which specializes in video recording of colonoscopies. In an effort to ease physician burden, it is automating some simple tasks, like starting and stopping video recording during a procedure. That’s a time-consuming process, and “it’s the sort of task that AI is really good at, so it’s a natural fit to get our first foray of AI on the market,” said Mr. Schwartz in an interview. Virgo currently provides a small, Apple TV–sized box that connects directly to an existing endoscopy system that independently records procedures.
The system uploads captured video into the cloud, and automatically creates highlights for easy viewing. That feature is available now. In the future, Virgo hopes to offer advanced analysis of withdrawal time, cecal intubation rate, and other features. “We want to provide video analytics that can help doctors and physician groups make informed decisions on how to improve quality,” said Mr. Schwartz.
Developing AI poses distinct challenges, and can be costly and time-consuming, said Jason Tucker-Schwartz, PhD, director of marketing for NinePoint Medical. During the session, he outlined the development of the AI component of the company’s NvisionVLE Imaging System, which is the only Food and Drug Administration–approved AI product for upper GI imaging. It reveals layers inside the esophageal tissue wall with high resolution, where 90% of cancers begin.
“It’s a new type of data that gastroenterologists are not used to seeing,” said Dr. Tucker-Schwartz. But that has presented a challenge to physicians attempting to identify and process all that novel information.
That called for AI, but because NinePoint is a small company with limited resources, it needed to control development costs. To streamline matters, they developed a system that focuses on three features that are most useful in making esophageal diagnoses. “The AI algorithms find those features as a function of depth so we can flatten them and use them to create a roadmap that physicians can use to guide their [interpretation],” said Dr. Tucker-Schwartz.
The resulting system has garnered lots of positive feedback, according to Dr. Tucker-Schwartz. The experience highlights the need to incorporate physician input into product development. “You need to involve them in all the steps along the path to end with a product that meets not only their goals but your business goals as well,” he said.
The electric dream
The long-term goal for AI in colonoscopy is automated polyp detection, a so-called optical biopsy, but that vision lies well in the future, said Mr. Schwartz. The primary issue is that only still images are available as training sets, and these don’t capture the diversity of patients, endoscopy systems, and operators that will be required to create a robust, generalizable polyp detection system. Existing efforts have shown promise on training sets, but struggle in real-world tests. “AI is good at tricking you into thinking it’s a working system when it’s only looking at retrospective data,” said Mr. Schwartz.
Olympus signed an agreement last year with ai4gi, a commercial initiative applying deep learning to gastrointestinal cancer, to combine its AI systems with Olympus’ colonoscopy line, but Mr. Heine agreed that optical biopsies won’t appear any time soon: “We’re not ready right now to launch anything that’s making a diagnosis claim. It’s not about optical biopsies at this point. It’s about supporting the physician,” he said.
Along with improving video capture and quality-control efforts, Mr. Schwartz believes that Virgo’s systems can help solve the problem of limited training data. By capturing and storing video data from a wide range of procedures, it is generating a resource that could boost the field and may one day make optical biopsies a reality. “It becomes the training set to build the AI video systems of the future,” he said.
Mr. Heine is an employee of Olympus. Dr. Tucker-Schwartz is an employee of NinePoint Medical. Mr. Schwartz is an employee of Virgo.
SAN FRANCISCO – Artificial intelligence (AI) can improve video recording and physician support during colonoscopy procedures, and the data being collected could eventually pave the way to AI systems powerful enough to detect polyps on their own.
AI has been touted as a means to reduce costs and improve patient outcomes, but there’s another benefit that is sometimes overlooked – physician satisfaction. Examining colonoscopy after colonoscopy can get a little overwhelming. “There’s only so much the human eye can see, and when you’re doing multiple colonoscopies a day, there’s a possibility that you’re just seeing too much. [AI] could help lessen the burden in making those diagnoses,” said Kurt Heine in an interview.
Mr. Heine is vice president of the endoscopy division at Olympus America. He joined other speakers at a panel on artificial intelligence at the 2019 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.
Physicians are under an increasing burden with the aging population and recommendations from the American Cancer Society that colonoscopies should begin at age 45. “We need a more efficient way to perform colonoscopies. Ideally AI would aid in the adenoma detection rate and perhaps someday in diagnosis. We’re trying to build a support tool to assist in that procedure,” said Heine.
That point was echoed by Matt Schwartz, CEO of Virgo, which specializes in video recording of colonoscopies. In an effort to ease physician burden, it is automating some simple tasks, like starting and stopping video recording during a procedure. That’s a time-consuming process, and “it’s the sort of task that AI is really good at, so it’s a natural fit to get our first foray of AI on the market,” said Mr. Schwartz in an interview. Virgo currently provides a small, Apple TV–sized box that connects directly to an existing endoscopy system that independently records procedures.
The system uploads captured video into the cloud, and automatically creates highlights for easy viewing. That feature is available now. In the future, Virgo hopes to offer advanced analysis of withdrawal time, cecal intubation rate, and other features. “We want to provide video analytics that can help doctors and physician groups make informed decisions on how to improve quality,” said Mr. Schwartz.
Developing AI poses distinct challenges, and can be costly and time-consuming, said Jason Tucker-Schwartz, PhD, director of marketing for NinePoint Medical. During the session, he outlined the development of the AI component of the company’s NvisionVLE Imaging System, which is the only Food and Drug Administration–approved AI product for upper GI imaging. It reveals layers inside the esophageal tissue wall with high resolution, where 90% of cancers begin.
“It’s a new type of data that gastroenterologists are not used to seeing,” said Dr. Tucker-Schwartz. But that has presented a challenge to physicians attempting to identify and process all that novel information.
That called for AI, but because NinePoint is a small company with limited resources, it needed to control development costs. To streamline matters, they developed a system that focuses on three features that are most useful in making esophageal diagnoses. “The AI algorithms find those features as a function of depth so we can flatten them and use them to create a roadmap that physicians can use to guide their [interpretation],” said Dr. Tucker-Schwartz.
The resulting system has garnered lots of positive feedback, according to Dr. Tucker-Schwartz. The experience highlights the need to incorporate physician input into product development. “You need to involve them in all the steps along the path to end with a product that meets not only their goals but your business goals as well,” he said.
The electric dream
The long-term goal for AI in colonoscopy is automated polyp detection, a so-called optical biopsy, but that vision lies well in the future, said Mr. Schwartz. The primary issue is that only still images are available as training sets, and these don’t capture the diversity of patients, endoscopy systems, and operators that will be required to create a robust, generalizable polyp detection system. Existing efforts have shown promise on training sets, but struggle in real-world tests. “AI is good at tricking you into thinking it’s a working system when it’s only looking at retrospective data,” said Mr. Schwartz.
Olympus signed an agreement last year with ai4gi, a commercial initiative applying deep learning to gastrointestinal cancer, to combine its AI systems with Olympus’ colonoscopy line, but Mr. Heine agreed that optical biopsies won’t appear any time soon: “We’re not ready right now to launch anything that’s making a diagnosis claim. It’s not about optical biopsies at this point. It’s about supporting the physician,” he said.
Along with improving video capture and quality-control efforts, Mr. Schwartz believes that Virgo’s systems can help solve the problem of limited training data. By capturing and storing video data from a wide range of procedures, it is generating a resource that could boost the field and may one day make optical biopsies a reality. “It becomes the training set to build the AI video systems of the future,” he said.
Mr. Heine is an employee of Olympus. Dr. Tucker-Schwartz is an employee of NinePoint Medical. Mr. Schwartz is an employee of Virgo.
SAN FRANCISCO – Artificial intelligence (AI) can improve video recording and physician support during colonoscopy procedures, and the data being collected could eventually pave the way to AI systems powerful enough to detect polyps on their own.
AI has been touted as a means to reduce costs and improve patient outcomes, but there’s another benefit that is sometimes overlooked – physician satisfaction. Examining colonoscopy after colonoscopy can get a little overwhelming. “There’s only so much the human eye can see, and when you’re doing multiple colonoscopies a day, there’s a possibility that you’re just seeing too much. [AI] could help lessen the burden in making those diagnoses,” said Kurt Heine in an interview.
Mr. Heine is vice president of the endoscopy division at Olympus America. He joined other speakers at a panel on artificial intelligence at the 2019 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.
Physicians are under an increasing burden with the aging population and recommendations from the American Cancer Society that colonoscopies should begin at age 45. “We need a more efficient way to perform colonoscopies. Ideally AI would aid in the adenoma detection rate and perhaps someday in diagnosis. We’re trying to build a support tool to assist in that procedure,” said Heine.
That point was echoed by Matt Schwartz, CEO of Virgo, which specializes in video recording of colonoscopies. In an effort to ease physician burden, it is automating some simple tasks, like starting and stopping video recording during a procedure. That’s a time-consuming process, and “it’s the sort of task that AI is really good at, so it’s a natural fit to get our first foray of AI on the market,” said Mr. Schwartz in an interview. Virgo currently provides a small, Apple TV–sized box that connects directly to an existing endoscopy system that independently records procedures.
The system uploads captured video into the cloud, and automatically creates highlights for easy viewing. That feature is available now. In the future, Virgo hopes to offer advanced analysis of withdrawal time, cecal intubation rate, and other features. “We want to provide video analytics that can help doctors and physician groups make informed decisions on how to improve quality,” said Mr. Schwartz.
Developing AI poses distinct challenges, and can be costly and time-consuming, said Jason Tucker-Schwartz, PhD, director of marketing for NinePoint Medical. During the session, he outlined the development of the AI component of the company’s NvisionVLE Imaging System, which is the only Food and Drug Administration–approved AI product for upper GI imaging. It reveals layers inside the esophageal tissue wall with high resolution, where 90% of cancers begin.
“It’s a new type of data that gastroenterologists are not used to seeing,” said Dr. Tucker-Schwartz. But that has presented a challenge to physicians attempting to identify and process all that novel information.
That called for AI, but because NinePoint is a small company with limited resources, it needed to control development costs. To streamline matters, they developed a system that focuses on three features that are most useful in making esophageal diagnoses. “The AI algorithms find those features as a function of depth so we can flatten them and use them to create a roadmap that physicians can use to guide their [interpretation],” said Dr. Tucker-Schwartz.
The resulting system has garnered lots of positive feedback, according to Dr. Tucker-Schwartz. The experience highlights the need to incorporate physician input into product development. “You need to involve them in all the steps along the path to end with a product that meets not only their goals but your business goals as well,” he said.
The electric dream
The long-term goal for AI in colonoscopy is automated polyp detection, a so-called optical biopsy, but that vision lies well in the future, said Mr. Schwartz. The primary issue is that only still images are available as training sets, and these don’t capture the diversity of patients, endoscopy systems, and operators that will be required to create a robust, generalizable polyp detection system. Existing efforts have shown promise on training sets, but struggle in real-world tests. “AI is good at tricking you into thinking it’s a working system when it’s only looking at retrospective data,” said Mr. Schwartz.
Olympus signed an agreement last year with ai4gi, a commercial initiative applying deep learning to gastrointestinal cancer, to combine its AI systems with Olympus’ colonoscopy line, but Mr. Heine agreed that optical biopsies won’t appear any time soon: “We’re not ready right now to launch anything that’s making a diagnosis claim. It’s not about optical biopsies at this point. It’s about supporting the physician,” he said.
Along with improving video capture and quality-control efforts, Mr. Schwartz believes that Virgo’s systems can help solve the problem of limited training data. By capturing and storing video data from a wide range of procedures, it is generating a resource that could boost the field and may one day make optical biopsies a reality. “It becomes the training set to build the AI video systems of the future,” he said.
Mr. Heine is an employee of Olympus. Dr. Tucker-Schwartz is an employee of NinePoint Medical. Mr. Schwartz is an employee of Virgo.
REPORTING FROM THE 2019 AGA TECH SUMMIT
Interventional endoscopic ultrasonography is hitting its stride
SAN FRANCISCO – Interventional endoscopic ultrasonography (EUS) recently has brought transluminal stent placement to problems like walled off pancreatic necroses, Joo Ha Hwang, MD, PhD, professor of medicine at Stanford (Calif.) University, said in an interview at the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. He sees EUS taking over surgical territory beyond the usual biopsies in the gastrointestinal and biliary tracts and soon moving into tumor treatment in these areas. The field is “rapidly expanding,” he said, and the value of these minimally invasive procedures means that the field will soon need to train more interventional endoscopists.
SAN FRANCISCO – Interventional endoscopic ultrasonography (EUS) recently has brought transluminal stent placement to problems like walled off pancreatic necroses, Joo Ha Hwang, MD, PhD, professor of medicine at Stanford (Calif.) University, said in an interview at the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. He sees EUS taking over surgical territory beyond the usual biopsies in the gastrointestinal and biliary tracts and soon moving into tumor treatment in these areas. The field is “rapidly expanding,” he said, and the value of these minimally invasive procedures means that the field will soon need to train more interventional endoscopists.
SAN FRANCISCO – Interventional endoscopic ultrasonography (EUS) recently has brought transluminal stent placement to problems like walled off pancreatic necroses, Joo Ha Hwang, MD, PhD, professor of medicine at Stanford (Calif.) University, said in an interview at the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. He sees EUS taking over surgical territory beyond the usual biopsies in the gastrointestinal and biliary tracts and soon moving into tumor treatment in these areas. The field is “rapidly expanding,” he said, and the value of these minimally invasive procedures means that the field will soon need to train more interventional endoscopists.
REPORTING FROM 2019 AGA TECH SUMMIT
Dolutegravir passes late pregnancy test
SEATTLE – In HIV-positive pregnant women who had not previously been on antiretroviral therapy (ART), initiation of treatment with dolutegravir during the third trimester led to lower viral loads at delivery and reduced HIV transmission to offspring compared to treatment with efavirenz. The result comes from a study conducted in South Africa and Uganda. Both drugs were combined with two nucleoside reverse transcriptase inhibitors (NRTIs).
ART-naive women who start ART during the third trimester often do not achieve sufficient reduction of viral load, and the researchers believed that integrase inhibitors like dolutegravir may lead to greater success because they can lead to viral clearance faster than other classes of drugs, which aren’t powerful enough to get viral loads to undetectable levels by the time of delivery. In fact, women who start therapy in the third trimester are at a 600% higher risk of transmitting the virus to offspring, and infant mortality is doubled in the first year of life, according to Saye Khoo, MD, professor of molecular and clinical pharmacology at the University of Liverpool (England).
“Clearly the viral load and undetectable viral load at the time of delivery is the best proxy for the lowest risk of mother to child transmission,” Dr. Khoo said at the Conference on Retroviruses & Opportunistic Infections. “This study clearly showed that there were big differences between dolutegravir and efavirenz. Viral load was undetectable in 74% in the dolutegravir group compared to 43% in efavirenz, which was highly significant.”
In the open-label DolPHIN-2 study, 268 women were randomized after week 28 of their pregnancy (median, 31 weeks) to receive dolutegravir or efavirenz plus two NRTIs. The dolutegravir group was more likely to achieve viral load less than 50 copies/mL at delivery (74% vs. 43%; adjusted risk ratio, 1.66; 95% confidence interval, 1.32-2.09). The trend occurred across subanalyses that included baseline viral load, baseline CD4 count, and gestation at initiation. 93% of the women in the dolutegravir group had a viral load less than 1,000 copies/mL, compared with 83% in the efavirenz group (RR, 1.11; 95% CI, 1.00-1.23).
There were no differences between the two groups with respect to frequency of severe adverse events, organ class of severe adverse events, gestational age at delivery, births earlier than 34 weeks, or births earlier than 37 weeks.
Four stillbirths occurred in the dolutegravir arm, and none in the efavirenz group. “Each of these was examined in great detail, as you might imagine. There were clear explanations for the cause of death, and it was related to maternal infection in two cases and obstetric complications in the other two,” said Dr. Khoo. There were no observations of neural tube defects – a concern that has been raised in the use of dolutegravir at the time of conception.
“I think we did see clear differences in virologic response in the arms, and so that would argue that dolutegravir certainly could be considered in these high-risk scenarios,” said Dr. Khoo.
The study was funded by the University of Liverpool. Dr. Khoo reported consulting for and receiving research funding from ViiV.
SOURCE: Khoo S et al. CROI 2019, Abstract 40 LB.
SEATTLE – In HIV-positive pregnant women who had not previously been on antiretroviral therapy (ART), initiation of treatment with dolutegravir during the third trimester led to lower viral loads at delivery and reduced HIV transmission to offspring compared to treatment with efavirenz. The result comes from a study conducted in South Africa and Uganda. Both drugs were combined with two nucleoside reverse transcriptase inhibitors (NRTIs).
ART-naive women who start ART during the third trimester often do not achieve sufficient reduction of viral load, and the researchers believed that integrase inhibitors like dolutegravir may lead to greater success because they can lead to viral clearance faster than other classes of drugs, which aren’t powerful enough to get viral loads to undetectable levels by the time of delivery. In fact, women who start therapy in the third trimester are at a 600% higher risk of transmitting the virus to offspring, and infant mortality is doubled in the first year of life, according to Saye Khoo, MD, professor of molecular and clinical pharmacology at the University of Liverpool (England).
“Clearly the viral load and undetectable viral load at the time of delivery is the best proxy for the lowest risk of mother to child transmission,” Dr. Khoo said at the Conference on Retroviruses & Opportunistic Infections. “This study clearly showed that there were big differences between dolutegravir and efavirenz. Viral load was undetectable in 74% in the dolutegravir group compared to 43% in efavirenz, which was highly significant.”
In the open-label DolPHIN-2 study, 268 women were randomized after week 28 of their pregnancy (median, 31 weeks) to receive dolutegravir or efavirenz plus two NRTIs. The dolutegravir group was more likely to achieve viral load less than 50 copies/mL at delivery (74% vs. 43%; adjusted risk ratio, 1.66; 95% confidence interval, 1.32-2.09). The trend occurred across subanalyses that included baseline viral load, baseline CD4 count, and gestation at initiation. 93% of the women in the dolutegravir group had a viral load less than 1,000 copies/mL, compared with 83% in the efavirenz group (RR, 1.11; 95% CI, 1.00-1.23).
There were no differences between the two groups with respect to frequency of severe adverse events, organ class of severe adverse events, gestational age at delivery, births earlier than 34 weeks, or births earlier than 37 weeks.
Four stillbirths occurred in the dolutegravir arm, and none in the efavirenz group. “Each of these was examined in great detail, as you might imagine. There were clear explanations for the cause of death, and it was related to maternal infection in two cases and obstetric complications in the other two,” said Dr. Khoo. There were no observations of neural tube defects – a concern that has been raised in the use of dolutegravir at the time of conception.
“I think we did see clear differences in virologic response in the arms, and so that would argue that dolutegravir certainly could be considered in these high-risk scenarios,” said Dr. Khoo.
The study was funded by the University of Liverpool. Dr. Khoo reported consulting for and receiving research funding from ViiV.
SOURCE: Khoo S et al. CROI 2019, Abstract 40 LB.
SEATTLE – In HIV-positive pregnant women who had not previously been on antiretroviral therapy (ART), initiation of treatment with dolutegravir during the third trimester led to lower viral loads at delivery and reduced HIV transmission to offspring compared to treatment with efavirenz. The result comes from a study conducted in South Africa and Uganda. Both drugs were combined with two nucleoside reverse transcriptase inhibitors (NRTIs).
ART-naive women who start ART during the third trimester often do not achieve sufficient reduction of viral load, and the researchers believed that integrase inhibitors like dolutegravir may lead to greater success because they can lead to viral clearance faster than other classes of drugs, which aren’t powerful enough to get viral loads to undetectable levels by the time of delivery. In fact, women who start therapy in the third trimester are at a 600% higher risk of transmitting the virus to offspring, and infant mortality is doubled in the first year of life, according to Saye Khoo, MD, professor of molecular and clinical pharmacology at the University of Liverpool (England).
“Clearly the viral load and undetectable viral load at the time of delivery is the best proxy for the lowest risk of mother to child transmission,” Dr. Khoo said at the Conference on Retroviruses & Opportunistic Infections. “This study clearly showed that there were big differences between dolutegravir and efavirenz. Viral load was undetectable in 74% in the dolutegravir group compared to 43% in efavirenz, which was highly significant.”
In the open-label DolPHIN-2 study, 268 women were randomized after week 28 of their pregnancy (median, 31 weeks) to receive dolutegravir or efavirenz plus two NRTIs. The dolutegravir group was more likely to achieve viral load less than 50 copies/mL at delivery (74% vs. 43%; adjusted risk ratio, 1.66; 95% confidence interval, 1.32-2.09). The trend occurred across subanalyses that included baseline viral load, baseline CD4 count, and gestation at initiation. 93% of the women in the dolutegravir group had a viral load less than 1,000 copies/mL, compared with 83% in the efavirenz group (RR, 1.11; 95% CI, 1.00-1.23).
There were no differences between the two groups with respect to frequency of severe adverse events, organ class of severe adverse events, gestational age at delivery, births earlier than 34 weeks, or births earlier than 37 weeks.
Four stillbirths occurred in the dolutegravir arm, and none in the efavirenz group. “Each of these was examined in great detail, as you might imagine. There were clear explanations for the cause of death, and it was related to maternal infection in two cases and obstetric complications in the other two,” said Dr. Khoo. There were no observations of neural tube defects – a concern that has been raised in the use of dolutegravir at the time of conception.
“I think we did see clear differences in virologic response in the arms, and so that would argue that dolutegravir certainly could be considered in these high-risk scenarios,” said Dr. Khoo.
The study was funded by the University of Liverpool. Dr. Khoo reported consulting for and receiving research funding from ViiV.
SOURCE: Khoo S et al. CROI 2019, Abstract 40 LB.
REPORTING FROM CROI 2019
Should we defend the unrestrained availability of patented psychotropics?
Since the biological revolution in psychiatry, with the introduction of chlorpromazine in the 1950s,1 psychiatrists have been introduced to the economic questions inherent in the tension between funding psychotropic medications for the treatment of mental illness versus funding psychosocial interventions. Of course, our natural inclination is to advocate for all available treatments for our patients, but the economic realities of medical care – especially government-subsidized or regulated medical care – force us to weigh the relative advantages of these treatments and to promote our patients’ interests with a wise allocation of limited resources.
It has become common practice for the American Psychiatric Association to advocate for additional funds for both research into mental illness as well as treatment. The promotion of mental health parity and the demonization of prior authorizations are examples of our natural priorities in the debates over funding for medical care. A bias has played out in the national conversation about medical care in general regarding the right to said care, but economists understand that medical care is a limited resource and, as such, treating it as a “right,” per se, does not make sense: One has to make hard decisions about its allocation or simply leave it to the free market to make said decisions.
Recently, the government has proposed to eliminate certain psychotropic medications from their protected status within Medicare Part D. Those medications include all drugs labeled as antidepressants, antipsychotics, and anticonvulsants. As expected, the APA’s medical director has written a formal statement opposing the proposal. His statement includes warnings about suicides and overwhelmed emergency departments. He compared the mental health situation in the United States to a crisis. He described the availability of expensive and new psychotropics to be “lifesaving.”2
The goals of the APA and its leaders are honorable. We are inspired by the dedication that some psychiatrists have to advocate for us all as well as for our patients. However, we are concerned that unfounded claims are being made. We are even more troubled when those claims promote the interests of a fallible pharmaceutical industry, an industry that has opened up our field to extensive critical scrutiny over the past few years. We wonder whether a brief examination of the scientific evidence warrants the statements made by the APA.
After reviewing clinical textbooks and search engines, we were not able to find reliable and convincing evidence that newer psychotropics reduce emergency department stays or that lengths of stay in the hospital correlate with the use of newer agents. We have actually not even heard of that claim made before in any serious forum. Reviews of predictors of length of stay in psychiatric hospitals have typically included demographic factors, diagnostic factors, logistical factors such as time of day, and social factors, such as insurance status and homelessness.3,4 We found no review mentioning the use of patented drugs as a predictor of shorter stays.
At a larger level, The Food and Drug Administration approves psychiatric medications based on superiority to placebo and not superiority to existing – and usually much cheaper – medications. Our subscription to Epocrates informs us that a 1-month supply of once-a-day brand-name Abilify, Invega, or Latuda is more than $1,000.5 Alternatively, a 1-month supply of generic olanzapine, risperidone, or quetiapine is available for $4 at Walmart.6 As famously described in the CATIE trial7 of patients with schizophrenia, newer antipsychotics are not particularly better than older ones. In addition, a more recent meta-analysis8 did not find significant differences among antipsychotics’ efficacy.
A similar analysis can be made of antidepressants without addressing debates surrounding the effectiveness of antidepressants as a class and the value of psychological interventions over chemical ones. Reviews of the literature do not suggest that newer antidepressants are more effective than older ones. A recent meta-analysis of antidepressant efficacy did not find significant differences among antidepressants and, when looking at trends, amitriptyline, a much older antidepressant, was most effective.9
The most surprising part of the APA medical director’s statement was the claim of reduced suicidality. While lithium and clozapine have some evidence for reducing the risk of suicide, the evidence that antidepressants reduce suicide is equivocal. Quite the contrary, some evidence exists that antidepressants may increase the risk of suicide,10 and we are not aware of evidence suggesting that any newer agents can reduce suicide at any higher rate. One psychiatrist has even made a career out of testifying that antidepressants increase impulsivity and suicide.11
We are not politicians, and we trust the APA to have good intentions with a desire to help patients suffering from mental illness. We understand the need to advocate for any measure that provides additional resources for the treatment of mental illness. We have no doubt that a publicly funded and appropriately regulated mental health system is a wise goal from both an ethical as well as a societal perspective. The APA has an imperative to advocate for our patients with the goal to improve our society.
However, we are concerned when our field makes unfounded claims. Advocating that insurance companies and the government provide most psychotropics without prior authorization and without discrimination does not appear to be based on scientific evidence and has serious economic implications that are not being weighed in a transparent manner. Whatever funding levels the APA recommends for the treatment of mental illness, said treatments will remain a limited resource, and then it becomes a question not just of ethics but of economics. What combination of resources produce the most benefit for the most people in question? Would the increased cost of a newer psychotropic be better spent on a system with more elaborate psychosocial interventions? In making this argument, does one risk repeating the historical blunder made when, in the 1960s, long-term psychiatric hospitals were closed with the intention of replacing their costs with outpatient treatments that then never materialized?
A review of the literature does not support the claim that newer psychotropic agents are more effective from either a clinical or an economic perspective. Cost-saving measures are ethical and possibly beneficial if they permit a more justifiable allocation of resources.
Dr. Lehman is an associate professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He is also the course director for the UCSD third-year medical student psychiatry clerkship. Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019).
References
1. Ann Med Psychol (Paris). 1952 Jun;110(2 1):112-7.
2. https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2019.3b26.
3. Am J Emerg Med. 2016 Feb;34(2):133-9.
4. Eur Psychiatry. 2018 Feb;48:6-12.
5. https://online.epocrates.com/drugs. Retrieved March 3, 2019.
6. https://www.walmart.com/cp/$4-prescriptions/1078664. Retrieved March 27, 2019.
7. N Engl J Med. 2005 Sep 22;353(12):1209-23.
8. Am J Psychiatry. 2017. 174(10):927-42.
9. Lancet. 2018 Apr 7. 391(10128):P1357-66.
10. BMJ. 2009.339;b2880.
11. https://breggin.com/.
Since the biological revolution in psychiatry, with the introduction of chlorpromazine in the 1950s,1 psychiatrists have been introduced to the economic questions inherent in the tension between funding psychotropic medications for the treatment of mental illness versus funding psychosocial interventions. Of course, our natural inclination is to advocate for all available treatments for our patients, but the economic realities of medical care – especially government-subsidized or regulated medical care – force us to weigh the relative advantages of these treatments and to promote our patients’ interests with a wise allocation of limited resources.
It has become common practice for the American Psychiatric Association to advocate for additional funds for both research into mental illness as well as treatment. The promotion of mental health parity and the demonization of prior authorizations are examples of our natural priorities in the debates over funding for medical care. A bias has played out in the national conversation about medical care in general regarding the right to said care, but economists understand that medical care is a limited resource and, as such, treating it as a “right,” per se, does not make sense: One has to make hard decisions about its allocation or simply leave it to the free market to make said decisions.
Recently, the government has proposed to eliminate certain psychotropic medications from their protected status within Medicare Part D. Those medications include all drugs labeled as antidepressants, antipsychotics, and anticonvulsants. As expected, the APA’s medical director has written a formal statement opposing the proposal. His statement includes warnings about suicides and overwhelmed emergency departments. He compared the mental health situation in the United States to a crisis. He described the availability of expensive and new psychotropics to be “lifesaving.”2
The goals of the APA and its leaders are honorable. We are inspired by the dedication that some psychiatrists have to advocate for us all as well as for our patients. However, we are concerned that unfounded claims are being made. We are even more troubled when those claims promote the interests of a fallible pharmaceutical industry, an industry that has opened up our field to extensive critical scrutiny over the past few years. We wonder whether a brief examination of the scientific evidence warrants the statements made by the APA.
After reviewing clinical textbooks and search engines, we were not able to find reliable and convincing evidence that newer psychotropics reduce emergency department stays or that lengths of stay in the hospital correlate with the use of newer agents. We have actually not even heard of that claim made before in any serious forum. Reviews of predictors of length of stay in psychiatric hospitals have typically included demographic factors, diagnostic factors, logistical factors such as time of day, and social factors, such as insurance status and homelessness.3,4 We found no review mentioning the use of patented drugs as a predictor of shorter stays.
At a larger level, The Food and Drug Administration approves psychiatric medications based on superiority to placebo and not superiority to existing – and usually much cheaper – medications. Our subscription to Epocrates informs us that a 1-month supply of once-a-day brand-name Abilify, Invega, or Latuda is more than $1,000.5 Alternatively, a 1-month supply of generic olanzapine, risperidone, or quetiapine is available for $4 at Walmart.6 As famously described in the CATIE trial7 of patients with schizophrenia, newer antipsychotics are not particularly better than older ones. In addition, a more recent meta-analysis8 did not find significant differences among antipsychotics’ efficacy.
A similar analysis can be made of antidepressants without addressing debates surrounding the effectiveness of antidepressants as a class and the value of psychological interventions over chemical ones. Reviews of the literature do not suggest that newer antidepressants are more effective than older ones. A recent meta-analysis of antidepressant efficacy did not find significant differences among antidepressants and, when looking at trends, amitriptyline, a much older antidepressant, was most effective.9
The most surprising part of the APA medical director’s statement was the claim of reduced suicidality. While lithium and clozapine have some evidence for reducing the risk of suicide, the evidence that antidepressants reduce suicide is equivocal. Quite the contrary, some evidence exists that antidepressants may increase the risk of suicide,10 and we are not aware of evidence suggesting that any newer agents can reduce suicide at any higher rate. One psychiatrist has even made a career out of testifying that antidepressants increase impulsivity and suicide.11
We are not politicians, and we trust the APA to have good intentions with a desire to help patients suffering from mental illness. We understand the need to advocate for any measure that provides additional resources for the treatment of mental illness. We have no doubt that a publicly funded and appropriately regulated mental health system is a wise goal from both an ethical as well as a societal perspective. The APA has an imperative to advocate for our patients with the goal to improve our society.
However, we are concerned when our field makes unfounded claims. Advocating that insurance companies and the government provide most psychotropics without prior authorization and without discrimination does not appear to be based on scientific evidence and has serious economic implications that are not being weighed in a transparent manner. Whatever funding levels the APA recommends for the treatment of mental illness, said treatments will remain a limited resource, and then it becomes a question not just of ethics but of economics. What combination of resources produce the most benefit for the most people in question? Would the increased cost of a newer psychotropic be better spent on a system with more elaborate psychosocial interventions? In making this argument, does one risk repeating the historical blunder made when, in the 1960s, long-term psychiatric hospitals were closed with the intention of replacing their costs with outpatient treatments that then never materialized?
A review of the literature does not support the claim that newer psychotropic agents are more effective from either a clinical or an economic perspective. Cost-saving measures are ethical and possibly beneficial if they permit a more justifiable allocation of resources.
Dr. Lehman is an associate professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He is also the course director for the UCSD third-year medical student psychiatry clerkship. Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019).
References
1. Ann Med Psychol (Paris). 1952 Jun;110(2 1):112-7.
2. https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2019.3b26.
3. Am J Emerg Med. 2016 Feb;34(2):133-9.
4. Eur Psychiatry. 2018 Feb;48:6-12.
5. https://online.epocrates.com/drugs. Retrieved March 3, 2019.
6. https://www.walmart.com/cp/$4-prescriptions/1078664. Retrieved March 27, 2019.
7. N Engl J Med. 2005 Sep 22;353(12):1209-23.
8. Am J Psychiatry. 2017. 174(10):927-42.
9. Lancet. 2018 Apr 7. 391(10128):P1357-66.
10. BMJ. 2009.339;b2880.
11. https://breggin.com/.
Since the biological revolution in psychiatry, with the introduction of chlorpromazine in the 1950s,1 psychiatrists have been introduced to the economic questions inherent in the tension between funding psychotropic medications for the treatment of mental illness versus funding psychosocial interventions. Of course, our natural inclination is to advocate for all available treatments for our patients, but the economic realities of medical care – especially government-subsidized or regulated medical care – force us to weigh the relative advantages of these treatments and to promote our patients’ interests with a wise allocation of limited resources.
It has become common practice for the American Psychiatric Association to advocate for additional funds for both research into mental illness as well as treatment. The promotion of mental health parity and the demonization of prior authorizations are examples of our natural priorities in the debates over funding for medical care. A bias has played out in the national conversation about medical care in general regarding the right to said care, but economists understand that medical care is a limited resource and, as such, treating it as a “right,” per se, does not make sense: One has to make hard decisions about its allocation or simply leave it to the free market to make said decisions.
Recently, the government has proposed to eliminate certain psychotropic medications from their protected status within Medicare Part D. Those medications include all drugs labeled as antidepressants, antipsychotics, and anticonvulsants. As expected, the APA’s medical director has written a formal statement opposing the proposal. His statement includes warnings about suicides and overwhelmed emergency departments. He compared the mental health situation in the United States to a crisis. He described the availability of expensive and new psychotropics to be “lifesaving.”2
The goals of the APA and its leaders are honorable. We are inspired by the dedication that some psychiatrists have to advocate for us all as well as for our patients. However, we are concerned that unfounded claims are being made. We are even more troubled when those claims promote the interests of a fallible pharmaceutical industry, an industry that has opened up our field to extensive critical scrutiny over the past few years. We wonder whether a brief examination of the scientific evidence warrants the statements made by the APA.
After reviewing clinical textbooks and search engines, we were not able to find reliable and convincing evidence that newer psychotropics reduce emergency department stays or that lengths of stay in the hospital correlate with the use of newer agents. We have actually not even heard of that claim made before in any serious forum. Reviews of predictors of length of stay in psychiatric hospitals have typically included demographic factors, diagnostic factors, logistical factors such as time of day, and social factors, such as insurance status and homelessness.3,4 We found no review mentioning the use of patented drugs as a predictor of shorter stays.
At a larger level, The Food and Drug Administration approves psychiatric medications based on superiority to placebo and not superiority to existing – and usually much cheaper – medications. Our subscription to Epocrates informs us that a 1-month supply of once-a-day brand-name Abilify, Invega, or Latuda is more than $1,000.5 Alternatively, a 1-month supply of generic olanzapine, risperidone, or quetiapine is available for $4 at Walmart.6 As famously described in the CATIE trial7 of patients with schizophrenia, newer antipsychotics are not particularly better than older ones. In addition, a more recent meta-analysis8 did not find significant differences among antipsychotics’ efficacy.
A similar analysis can be made of antidepressants without addressing debates surrounding the effectiveness of antidepressants as a class and the value of psychological interventions over chemical ones. Reviews of the literature do not suggest that newer antidepressants are more effective than older ones. A recent meta-analysis of antidepressant efficacy did not find significant differences among antidepressants and, when looking at trends, amitriptyline, a much older antidepressant, was most effective.9
The most surprising part of the APA medical director’s statement was the claim of reduced suicidality. While lithium and clozapine have some evidence for reducing the risk of suicide, the evidence that antidepressants reduce suicide is equivocal. Quite the contrary, some evidence exists that antidepressants may increase the risk of suicide,10 and we are not aware of evidence suggesting that any newer agents can reduce suicide at any higher rate. One psychiatrist has even made a career out of testifying that antidepressants increase impulsivity and suicide.11
We are not politicians, and we trust the APA to have good intentions with a desire to help patients suffering from mental illness. We understand the need to advocate for any measure that provides additional resources for the treatment of mental illness. We have no doubt that a publicly funded and appropriately regulated mental health system is a wise goal from both an ethical as well as a societal perspective. The APA has an imperative to advocate for our patients with the goal to improve our society.
However, we are concerned when our field makes unfounded claims. Advocating that insurance companies and the government provide most psychotropics without prior authorization and without discrimination does not appear to be based on scientific evidence and has serious economic implications that are not being weighed in a transparent manner. Whatever funding levels the APA recommends for the treatment of mental illness, said treatments will remain a limited resource, and then it becomes a question not just of ethics but of economics. What combination of resources produce the most benefit for the most people in question? Would the increased cost of a newer psychotropic be better spent on a system with more elaborate psychosocial interventions? In making this argument, does one risk repeating the historical blunder made when, in the 1960s, long-term psychiatric hospitals were closed with the intention of replacing their costs with outpatient treatments that then never materialized?
A review of the literature does not support the claim that newer psychotropic agents are more effective from either a clinical or an economic perspective. Cost-saving measures are ethical and possibly beneficial if they permit a more justifiable allocation of resources.
Dr. Lehman is an associate professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He is also the course director for the UCSD third-year medical student psychiatry clerkship. Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019).
References
1. Ann Med Psychol (Paris). 1952 Jun;110(2 1):112-7.
2. https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2019.3b26.
3. Am J Emerg Med. 2016 Feb;34(2):133-9.
4. Eur Psychiatry. 2018 Feb;48:6-12.
5. https://online.epocrates.com/drugs. Retrieved March 3, 2019.
6. https://www.walmart.com/cp/$4-prescriptions/1078664. Retrieved March 27, 2019.
7. N Engl J Med. 2005 Sep 22;353(12):1209-23.
8. Am J Psychiatry. 2017. 174(10):927-42.
9. Lancet. 2018 Apr 7. 391(10128):P1357-66.
10. BMJ. 2009.339;b2880.
11. https://breggin.com/.
Anastrozole-fulvestrant in breast cancer and daily aspirin to prevent HCC
Welcome to the first edition of “How I will treat my next patient,” a regular column analyzing the practical clinical relevance of the latest literature. In this first column, I will take a look at two interesting studies – a combination hormonal treatment for metastatic ER-positive breast cancer and aspirin therapy for prevention of hepatocellular cancer.
Anastrozole plus fulvestrant
In a large SWOG trial for postmenopausal patients with stage IV, hormonally responsive breast cancer whose metastatic disease could be treated with frontline hormonal therapy, long-term survival analysis showed that the combination of anastrozole plus fulvestrant was superior to anastrozole alone, with essentially no increase in toxicity.
The study – “Overall Survival With Fulvestrant Plus Anastrozole in Metastatic Breast Cancer” – was published in the New England Journal of Medicine (2019;380:1226-34).
The overall survival difference was not only statistically and clinically significant, but impressively so among patients who had not received prior adjuvant hormonal therapy. That is despite the fact that 45% of patients who were assigned to initial treatment with anastrozole received single agent fulvestrant at first relapse.
What this means in practice
Because of the generally negative results of combined hormonal therapy in comparison with sequential use of the same agents and the potency of CDK4/6 inhibitors in combination with hormonal agents in the frontline setting, many oncologists have forgotten the initial publication of this regimen in 2012. In that study, the combination demonstrated improved progression-free survival over anastrozole alone, particularly in the subset of patients who presented with stage IV breast cancer as their initial presentation.
Although the benefits for CDK4/6 inhibitors as an addition to hormonal therapy are truly impressive, the practical aspects of utilizing the CDK4/6 inhibitors may be prohibitive for a small subset of our most vulnerable, medically underserved patients. Specifically, these are patients who are unable to return for frequent blood counts in the initial few months of therapy, patients with limited financial resources who cannot afford the out-of-pocket costs of an expensive oral medication and required laboratory testing, those with difficulty adhering to oral medication regimens, or those with constitutional neutropenia.
Not coincidentally, many of these patients are exactly the ones who present with stage IV disease as their initial manifestation of breast cancer. For such patients, the combination of anastrozole plus fulvestrant is an attractive alternative and may offer competitive survival benefits. This is not “yesterday’s therapy” in the era of CDK4/6 inhibitors, but rather represents a valuable option for treatment in at-risk populations.
When I see my next patient who presents with stage IV breast cancer, I will consider combined hormonal therapy among the various available treatment options.
Aspirin to prevent HCC
Investigators at Taichung (Taiwan) Veterans General Hospital recently analyzed 16 years of data from a cohort of more than 10,000 patients with chronic hepatitis B virus (HBV) infection and found statistically significantly fewer cases of hepatocellular cancer (HCC) in patients who took antiviral antinucleoside analogue therapy, statins, and aspirin.
The study – “Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B” – was published in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2018.8342).
Although there were more impressive reductions in relative risk of HCC among statin and antinucleoside analogue users, the authors highlighted that HCC developed in 5.20% of the approximately 2,100 chronic aspirin users and in 7.87% of nonusers – a 29% relative reduction in risk in this cohort study. Toxicity, including upper GI bleeding, was low.
What this means in practice
This is a hypothesis-generating analysis at best. Although the authors highlight possible mechanisms by which aspirin use could lead to reduction in HCC among patients with chronic inflammatory conditions affecting the liver, the study produces more questions than it answers (dose, chronicity of use, duration of protection, biomarkers for benefit).
Owing to the simplicity and low cost of the intervention, it may be worth studying prospectively in chronic HBV-infected patients and other populations at risk for HCC, but the intervention should not be adopted at this point based on an international cohort study.
The practicality of conducting such a large, complicated, prospective study of a widely available medication that has widely publicized additional health benefits is an open question.
When I see my next patient with a high risk for HCC, I won’t prescribe aspirin for chemoprevention.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.
Welcome to the first edition of “How I will treat my next patient,” a regular column analyzing the practical clinical relevance of the latest literature. In this first column, I will take a look at two interesting studies – a combination hormonal treatment for metastatic ER-positive breast cancer and aspirin therapy for prevention of hepatocellular cancer.
Anastrozole plus fulvestrant
In a large SWOG trial for postmenopausal patients with stage IV, hormonally responsive breast cancer whose metastatic disease could be treated with frontline hormonal therapy, long-term survival analysis showed that the combination of anastrozole plus fulvestrant was superior to anastrozole alone, with essentially no increase in toxicity.
The study – “Overall Survival With Fulvestrant Plus Anastrozole in Metastatic Breast Cancer” – was published in the New England Journal of Medicine (2019;380:1226-34).
The overall survival difference was not only statistically and clinically significant, but impressively so among patients who had not received prior adjuvant hormonal therapy. That is despite the fact that 45% of patients who were assigned to initial treatment with anastrozole received single agent fulvestrant at first relapse.
What this means in practice
Because of the generally negative results of combined hormonal therapy in comparison with sequential use of the same agents and the potency of CDK4/6 inhibitors in combination with hormonal agents in the frontline setting, many oncologists have forgotten the initial publication of this regimen in 2012. In that study, the combination demonstrated improved progression-free survival over anastrozole alone, particularly in the subset of patients who presented with stage IV breast cancer as their initial presentation.
Although the benefits for CDK4/6 inhibitors as an addition to hormonal therapy are truly impressive, the practical aspects of utilizing the CDK4/6 inhibitors may be prohibitive for a small subset of our most vulnerable, medically underserved patients. Specifically, these are patients who are unable to return for frequent blood counts in the initial few months of therapy, patients with limited financial resources who cannot afford the out-of-pocket costs of an expensive oral medication and required laboratory testing, those with difficulty adhering to oral medication regimens, or those with constitutional neutropenia.
Not coincidentally, many of these patients are exactly the ones who present with stage IV disease as their initial manifestation of breast cancer. For such patients, the combination of anastrozole plus fulvestrant is an attractive alternative and may offer competitive survival benefits. This is not “yesterday’s therapy” in the era of CDK4/6 inhibitors, but rather represents a valuable option for treatment in at-risk populations.
When I see my next patient who presents with stage IV breast cancer, I will consider combined hormonal therapy among the various available treatment options.
Aspirin to prevent HCC
Investigators at Taichung (Taiwan) Veterans General Hospital recently analyzed 16 years of data from a cohort of more than 10,000 patients with chronic hepatitis B virus (HBV) infection and found statistically significantly fewer cases of hepatocellular cancer (HCC) in patients who took antiviral antinucleoside analogue therapy, statins, and aspirin.
The study – “Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B” – was published in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2018.8342).
Although there were more impressive reductions in relative risk of HCC among statin and antinucleoside analogue users, the authors highlighted that HCC developed in 5.20% of the approximately 2,100 chronic aspirin users and in 7.87% of nonusers – a 29% relative reduction in risk in this cohort study. Toxicity, including upper GI bleeding, was low.
What this means in practice
This is a hypothesis-generating analysis at best. Although the authors highlight possible mechanisms by which aspirin use could lead to reduction in HCC among patients with chronic inflammatory conditions affecting the liver, the study produces more questions than it answers (dose, chronicity of use, duration of protection, biomarkers for benefit).
Owing to the simplicity and low cost of the intervention, it may be worth studying prospectively in chronic HBV-infected patients and other populations at risk for HCC, but the intervention should not be adopted at this point based on an international cohort study.
The practicality of conducting such a large, complicated, prospective study of a widely available medication that has widely publicized additional health benefits is an open question.
When I see my next patient with a high risk for HCC, I won’t prescribe aspirin for chemoprevention.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.
Welcome to the first edition of “How I will treat my next patient,” a regular column analyzing the practical clinical relevance of the latest literature. In this first column, I will take a look at two interesting studies – a combination hormonal treatment for metastatic ER-positive breast cancer and aspirin therapy for prevention of hepatocellular cancer.
Anastrozole plus fulvestrant
In a large SWOG trial for postmenopausal patients with stage IV, hormonally responsive breast cancer whose metastatic disease could be treated with frontline hormonal therapy, long-term survival analysis showed that the combination of anastrozole plus fulvestrant was superior to anastrozole alone, with essentially no increase in toxicity.
The study – “Overall Survival With Fulvestrant Plus Anastrozole in Metastatic Breast Cancer” – was published in the New England Journal of Medicine (2019;380:1226-34).
The overall survival difference was not only statistically and clinically significant, but impressively so among patients who had not received prior adjuvant hormonal therapy. That is despite the fact that 45% of patients who were assigned to initial treatment with anastrozole received single agent fulvestrant at first relapse.
What this means in practice
Because of the generally negative results of combined hormonal therapy in comparison with sequential use of the same agents and the potency of CDK4/6 inhibitors in combination with hormonal agents in the frontline setting, many oncologists have forgotten the initial publication of this regimen in 2012. In that study, the combination demonstrated improved progression-free survival over anastrozole alone, particularly in the subset of patients who presented with stage IV breast cancer as their initial presentation.
Although the benefits for CDK4/6 inhibitors as an addition to hormonal therapy are truly impressive, the practical aspects of utilizing the CDK4/6 inhibitors may be prohibitive for a small subset of our most vulnerable, medically underserved patients. Specifically, these are patients who are unable to return for frequent blood counts in the initial few months of therapy, patients with limited financial resources who cannot afford the out-of-pocket costs of an expensive oral medication and required laboratory testing, those with difficulty adhering to oral medication regimens, or those with constitutional neutropenia.
Not coincidentally, many of these patients are exactly the ones who present with stage IV disease as their initial manifestation of breast cancer. For such patients, the combination of anastrozole plus fulvestrant is an attractive alternative and may offer competitive survival benefits. This is not “yesterday’s therapy” in the era of CDK4/6 inhibitors, but rather represents a valuable option for treatment in at-risk populations.
When I see my next patient who presents with stage IV breast cancer, I will consider combined hormonal therapy among the various available treatment options.
Aspirin to prevent HCC
Investigators at Taichung (Taiwan) Veterans General Hospital recently analyzed 16 years of data from a cohort of more than 10,000 patients with chronic hepatitis B virus (HBV) infection and found statistically significantly fewer cases of hepatocellular cancer (HCC) in patients who took antiviral antinucleoside analogue therapy, statins, and aspirin.
The study – “Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B” – was published in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2018.8342).
Although there were more impressive reductions in relative risk of HCC among statin and antinucleoside analogue users, the authors highlighted that HCC developed in 5.20% of the approximately 2,100 chronic aspirin users and in 7.87% of nonusers – a 29% relative reduction in risk in this cohort study. Toxicity, including upper GI bleeding, was low.
What this means in practice
This is a hypothesis-generating analysis at best. Although the authors highlight possible mechanisms by which aspirin use could lead to reduction in HCC among patients with chronic inflammatory conditions affecting the liver, the study produces more questions than it answers (dose, chronicity of use, duration of protection, biomarkers for benefit).
Owing to the simplicity and low cost of the intervention, it may be worth studying prospectively in chronic HBV-infected patients and other populations at risk for HCC, but the intervention should not be adopted at this point based on an international cohort study.
The practicality of conducting such a large, complicated, prospective study of a widely available medication that has widely publicized additional health benefits is an open question.
When I see my next patient with a high risk for HCC, I won’t prescribe aspirin for chemoprevention.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.
Rivaroxaban versus heparin at preventing recurrent, cancer-related VTE
Clinical question: Is an oral direct factor Xa inhibitor an effective alternative to low-molecular-weight heparin (LMWH) in treating cancer related venous thromboembolism (VTE)?
Background: LMWH has been the standard of care for treatment in patients with VTE and cancer. A newer class of drug, the direct factor Xa inhibitors, have been shown to be noninferior to vitamin K antagonists (VKAs) in treatment of VTE in noncancer patients, but little is known about their use in patients with cancer.
Study Design: Randomized, open-label, multicenter pilot trial.
Setting: United Kingdom; patients were recruited through the Clinical Trials Unit at the University of Warwick, Coventry.
Synopsis: The authors randomly assigned 406 cancer patients with diagnosed VTE either to the LMWH group or to the oral direct factor Xa inhibitor group to evaluate the primary endpoint of VTE reoccurrence and secondary endpoints of major bleeding or clinically relevant but not major bleeding (CRNMB). Rivaroxaban was noninferior to dalteparin in preventing VTE reoccurrence, with a 6-month VTE reoccurrence rate for dalteparin of 11% (95% confidence interval, 7%-16%) and a reoccurrence rate of 6% for rivaroxaban (95% CI, 2%-9%). Rates of major bleeding events were similar, although patients with esophageal or gastroesophageal cancers tended to experience more major bleeds with rivaroxaban than with dalteparin (4 of 11 vs. 1 of 19). CRNMB was 4% for dalteparin and 13% for rivaroxaban (hazard ratio, 3.76; 95% CI, 1.64-8.69). Limitations include slow recruitment, high mortality rate, and the treatment length being only 6 months.
Bottom line: In this small study, rivaroxaban was equally effective at reducing the rate of reoccurrence of cancer related VTE at 6 months but had higher rates of CRNMB. Patients with GI cancers may be at higher risk for major GI bleeding with rivaroxaban.
Citation: Young AM et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: Results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10. 36(20):2017-23.
Dr. Marten is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.
Clinical question: Is an oral direct factor Xa inhibitor an effective alternative to low-molecular-weight heparin (LMWH) in treating cancer related venous thromboembolism (VTE)?
Background: LMWH has been the standard of care for treatment in patients with VTE and cancer. A newer class of drug, the direct factor Xa inhibitors, have been shown to be noninferior to vitamin K antagonists (VKAs) in treatment of VTE in noncancer patients, but little is known about their use in patients with cancer.
Study Design: Randomized, open-label, multicenter pilot trial.
Setting: United Kingdom; patients were recruited through the Clinical Trials Unit at the University of Warwick, Coventry.
Synopsis: The authors randomly assigned 406 cancer patients with diagnosed VTE either to the LMWH group or to the oral direct factor Xa inhibitor group to evaluate the primary endpoint of VTE reoccurrence and secondary endpoints of major bleeding or clinically relevant but not major bleeding (CRNMB). Rivaroxaban was noninferior to dalteparin in preventing VTE reoccurrence, with a 6-month VTE reoccurrence rate for dalteparin of 11% (95% confidence interval, 7%-16%) and a reoccurrence rate of 6% for rivaroxaban (95% CI, 2%-9%). Rates of major bleeding events were similar, although patients with esophageal or gastroesophageal cancers tended to experience more major bleeds with rivaroxaban than with dalteparin (4 of 11 vs. 1 of 19). CRNMB was 4% for dalteparin and 13% for rivaroxaban (hazard ratio, 3.76; 95% CI, 1.64-8.69). Limitations include slow recruitment, high mortality rate, and the treatment length being only 6 months.
Bottom line: In this small study, rivaroxaban was equally effective at reducing the rate of reoccurrence of cancer related VTE at 6 months but had higher rates of CRNMB. Patients with GI cancers may be at higher risk for major GI bleeding with rivaroxaban.
Citation: Young AM et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: Results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10. 36(20):2017-23.
Dr. Marten is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.
Clinical question: Is an oral direct factor Xa inhibitor an effective alternative to low-molecular-weight heparin (LMWH) in treating cancer related venous thromboembolism (VTE)?
Background: LMWH has been the standard of care for treatment in patients with VTE and cancer. A newer class of drug, the direct factor Xa inhibitors, have been shown to be noninferior to vitamin K antagonists (VKAs) in treatment of VTE in noncancer patients, but little is known about their use in patients with cancer.
Study Design: Randomized, open-label, multicenter pilot trial.
Setting: United Kingdom; patients were recruited through the Clinical Trials Unit at the University of Warwick, Coventry.
Synopsis: The authors randomly assigned 406 cancer patients with diagnosed VTE either to the LMWH group or to the oral direct factor Xa inhibitor group to evaluate the primary endpoint of VTE reoccurrence and secondary endpoints of major bleeding or clinically relevant but not major bleeding (CRNMB). Rivaroxaban was noninferior to dalteparin in preventing VTE reoccurrence, with a 6-month VTE reoccurrence rate for dalteparin of 11% (95% confidence interval, 7%-16%) and a reoccurrence rate of 6% for rivaroxaban (95% CI, 2%-9%). Rates of major bleeding events were similar, although patients with esophageal or gastroesophageal cancers tended to experience more major bleeds with rivaroxaban than with dalteparin (4 of 11 vs. 1 of 19). CRNMB was 4% for dalteparin and 13% for rivaroxaban (hazard ratio, 3.76; 95% CI, 1.64-8.69). Limitations include slow recruitment, high mortality rate, and the treatment length being only 6 months.
Bottom line: In this small study, rivaroxaban was equally effective at reducing the rate of reoccurrence of cancer related VTE at 6 months but had higher rates of CRNMB. Patients with GI cancers may be at higher risk for major GI bleeding with rivaroxaban.
Citation: Young AM et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: Results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10. 36(20):2017-23.
Dr. Marten is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.
Rate of objects ingested by young children increased over last two decades
– from an estimated 9 cases per 10,000 children to 18 cases per 10,000 (R2 = 0.90; P less than .001) – according to an analysis in Pediatrics.
The analysis was conducted by Danielle Orsagh-Yentis, MD, of Vanderbilt University, Nashville, Tenn., and her colleagues. They estimated that, during the study period, 759,074 children younger than 6 years of age were evaluated in U.S. EDs for suspected or confirmed foreign-body ingestions. These estimates were based on data for 29,893 actual cases taken from the National Electronic Injury Surveillance System (NEISS), which represents about 100 hospitals. Each case in this system is given a sample weight by the Consumer Product Safety Commission using a validated method, and the estimates are based on this weighting.
The analysis showed that children aged 1 year (21%) and boys (53%) were the most likely to ingest foreign bodies. Coins were the most frequently ingested objects, at 62%. Among cases which had the location noted (59%), most ingestions occurred in the home (97%).
The authors noted that, although batteries and magnets represented only 7% and 2% of all cases, respectively, “they can both enact considerable damage when ingested.” For example, despite being only the fourth mostly likely object to be ingested, batteries were the second mostly likely to be implicated among hospitalized patients.
The authors noted that the NEISS captures patients in the ED only; the total number of foreign-body ingestions, then, was likely underestimated. Despite this, the authors felt the long study period and large sample were strengths of their analysis.
Dr. Orsagh-Yentis and her associates disclosed no potential conflicts of interest.
SOURCE: Orsagh-Yentis D et al. Pediatrics. 2019 Apr 12. doi: 10.1542/peds.2018-1988.
– from an estimated 9 cases per 10,000 children to 18 cases per 10,000 (R2 = 0.90; P less than .001) – according to an analysis in Pediatrics.
The analysis was conducted by Danielle Orsagh-Yentis, MD, of Vanderbilt University, Nashville, Tenn., and her colleagues. They estimated that, during the study period, 759,074 children younger than 6 years of age were evaluated in U.S. EDs for suspected or confirmed foreign-body ingestions. These estimates were based on data for 29,893 actual cases taken from the National Electronic Injury Surveillance System (NEISS), which represents about 100 hospitals. Each case in this system is given a sample weight by the Consumer Product Safety Commission using a validated method, and the estimates are based on this weighting.
The analysis showed that children aged 1 year (21%) and boys (53%) were the most likely to ingest foreign bodies. Coins were the most frequently ingested objects, at 62%. Among cases which had the location noted (59%), most ingestions occurred in the home (97%).
The authors noted that, although batteries and magnets represented only 7% and 2% of all cases, respectively, “they can both enact considerable damage when ingested.” For example, despite being only the fourth mostly likely object to be ingested, batteries were the second mostly likely to be implicated among hospitalized patients.
The authors noted that the NEISS captures patients in the ED only; the total number of foreign-body ingestions, then, was likely underestimated. Despite this, the authors felt the long study period and large sample were strengths of their analysis.
Dr. Orsagh-Yentis and her associates disclosed no potential conflicts of interest.
SOURCE: Orsagh-Yentis D et al. Pediatrics. 2019 Apr 12. doi: 10.1542/peds.2018-1988.
– from an estimated 9 cases per 10,000 children to 18 cases per 10,000 (R2 = 0.90; P less than .001) – according to an analysis in Pediatrics.
The analysis was conducted by Danielle Orsagh-Yentis, MD, of Vanderbilt University, Nashville, Tenn., and her colleagues. They estimated that, during the study period, 759,074 children younger than 6 years of age were evaluated in U.S. EDs for suspected or confirmed foreign-body ingestions. These estimates were based on data for 29,893 actual cases taken from the National Electronic Injury Surveillance System (NEISS), which represents about 100 hospitals. Each case in this system is given a sample weight by the Consumer Product Safety Commission using a validated method, and the estimates are based on this weighting.
The analysis showed that children aged 1 year (21%) and boys (53%) were the most likely to ingest foreign bodies. Coins were the most frequently ingested objects, at 62%. Among cases which had the location noted (59%), most ingestions occurred in the home (97%).
The authors noted that, although batteries and magnets represented only 7% and 2% of all cases, respectively, “they can both enact considerable damage when ingested.” For example, despite being only the fourth mostly likely object to be ingested, batteries were the second mostly likely to be implicated among hospitalized patients.
The authors noted that the NEISS captures patients in the ED only; the total number of foreign-body ingestions, then, was likely underestimated. Despite this, the authors felt the long study period and large sample were strengths of their analysis.
Dr. Orsagh-Yentis and her associates disclosed no potential conflicts of interest.
SOURCE: Orsagh-Yentis D et al. Pediatrics. 2019 Apr 12. doi: 10.1542/peds.2018-1988.
FROM PEDIATRICS
Dr. Douglas Paauw: Consider rechallenging patients with penicillin allergy
PHILADELPHIA – As fluoroquinolone warnings stack up, internists seeking treatment alternatives should consider rechallenging patients with penicillin allergy or referring those patients for testing, said Douglas S. Paauw, MD, during a presentation.
This was one of the pieces of advice provided by Dr. Paauw, professor of medicine in the division of general internal medicine at the University of Washington, Seattle, at the annual meeting of the American College of Physicians.
“The FDA [Food and Drug Administration] has been just killing trees, sending us letters over the last 5-10 years, with fluoroquinolone warnings,” said Dr. Paauw, referencing previous warnings describing risks of tendon rupture, peripheral neuropathy, hypoglycemia, mental health side effects, and more.
“I think the buzz in 2019 is that we should not overreact to a history of penicillin allergy,” he said.
As many as 98% of patients who have reported penicillin allergy don’t have true allergy and can safely receive penicillin, he explained.
“If they don’t have an allergy, make sure you get it out of the electronic record,” Dr. Paauw also advised.
The latest warning on fluoroquinolones from the FDA, issued in Dec. 20, 2018, said that clinicians should avoid prescribing these antibiotics in patients who have, or are at risk of, aortic aneurysm. This comprises a very large proportion of patients in an internist’s practice, Dr. Paauw noted. The warning specifically singled out elderly patients as being in the at-risk population, along with patients who have peripheral atherosclerotic vascular diseases, hypertension, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome, he added.
Dr. Paauw further supported his suggestions by describing two relevant studies.
In one of those studies, which was published this year in an allergy and asthma journal, 20 subjects with a history of penicillin allergy agreed to direct oral amoxicillin rechallenge by an allergist, he said. None of those 20 patients were observed to have developed immediate or delayed hypersensitivity reactions, investigators reported. That study included a total of 50 adults with a penicillin allergy label, of whom 24 (48%) had the label removed from their medical records.
In another recent and reassuring study, penicillin allergy testing was conducted in 100 children with parent-reported penicillin allergy that was considered low risk based on reported symptoms, Dr. Paauw said. Of that group, all 100 children were found to be negative for true penicillin allergy.
Dr. Paauw had no relevant disclosures.
SOURCE: Paauw DS. Annual Meeting of the American College of Physicians, Presentation MTP 013.
PHILADELPHIA – As fluoroquinolone warnings stack up, internists seeking treatment alternatives should consider rechallenging patients with penicillin allergy or referring those patients for testing, said Douglas S. Paauw, MD, during a presentation.
This was one of the pieces of advice provided by Dr. Paauw, professor of medicine in the division of general internal medicine at the University of Washington, Seattle, at the annual meeting of the American College of Physicians.
“The FDA [Food and Drug Administration] has been just killing trees, sending us letters over the last 5-10 years, with fluoroquinolone warnings,” said Dr. Paauw, referencing previous warnings describing risks of tendon rupture, peripheral neuropathy, hypoglycemia, mental health side effects, and more.
“I think the buzz in 2019 is that we should not overreact to a history of penicillin allergy,” he said.
As many as 98% of patients who have reported penicillin allergy don’t have true allergy and can safely receive penicillin, he explained.
“If they don’t have an allergy, make sure you get it out of the electronic record,” Dr. Paauw also advised.
The latest warning on fluoroquinolones from the FDA, issued in Dec. 20, 2018, said that clinicians should avoid prescribing these antibiotics in patients who have, or are at risk of, aortic aneurysm. This comprises a very large proportion of patients in an internist’s practice, Dr. Paauw noted. The warning specifically singled out elderly patients as being in the at-risk population, along with patients who have peripheral atherosclerotic vascular diseases, hypertension, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome, he added.
Dr. Paauw further supported his suggestions by describing two relevant studies.
In one of those studies, which was published this year in an allergy and asthma journal, 20 subjects with a history of penicillin allergy agreed to direct oral amoxicillin rechallenge by an allergist, he said. None of those 20 patients were observed to have developed immediate or delayed hypersensitivity reactions, investigators reported. That study included a total of 50 adults with a penicillin allergy label, of whom 24 (48%) had the label removed from their medical records.
In another recent and reassuring study, penicillin allergy testing was conducted in 100 children with parent-reported penicillin allergy that was considered low risk based on reported symptoms, Dr. Paauw said. Of that group, all 100 children were found to be negative for true penicillin allergy.
Dr. Paauw had no relevant disclosures.
SOURCE: Paauw DS. Annual Meeting of the American College of Physicians, Presentation MTP 013.
PHILADELPHIA – As fluoroquinolone warnings stack up, internists seeking treatment alternatives should consider rechallenging patients with penicillin allergy or referring those patients for testing, said Douglas S. Paauw, MD, during a presentation.
This was one of the pieces of advice provided by Dr. Paauw, professor of medicine in the division of general internal medicine at the University of Washington, Seattle, at the annual meeting of the American College of Physicians.
“The FDA [Food and Drug Administration] has been just killing trees, sending us letters over the last 5-10 years, with fluoroquinolone warnings,” said Dr. Paauw, referencing previous warnings describing risks of tendon rupture, peripheral neuropathy, hypoglycemia, mental health side effects, and more.
“I think the buzz in 2019 is that we should not overreact to a history of penicillin allergy,” he said.
As many as 98% of patients who have reported penicillin allergy don’t have true allergy and can safely receive penicillin, he explained.
“If they don’t have an allergy, make sure you get it out of the electronic record,” Dr. Paauw also advised.
The latest warning on fluoroquinolones from the FDA, issued in Dec. 20, 2018, said that clinicians should avoid prescribing these antibiotics in patients who have, or are at risk of, aortic aneurysm. This comprises a very large proportion of patients in an internist’s practice, Dr. Paauw noted. The warning specifically singled out elderly patients as being in the at-risk population, along with patients who have peripheral atherosclerotic vascular diseases, hypertension, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome, he added.
Dr. Paauw further supported his suggestions by describing two relevant studies.
In one of those studies, which was published this year in an allergy and asthma journal, 20 subjects with a history of penicillin allergy agreed to direct oral amoxicillin rechallenge by an allergist, he said. None of those 20 patients were observed to have developed immediate or delayed hypersensitivity reactions, investigators reported. That study included a total of 50 adults with a penicillin allergy label, of whom 24 (48%) had the label removed from their medical records.
In another recent and reassuring study, penicillin allergy testing was conducted in 100 children with parent-reported penicillin allergy that was considered low risk based on reported symptoms, Dr. Paauw said. Of that group, all 100 children were found to be negative for true penicillin allergy.
Dr. Paauw had no relevant disclosures.
SOURCE: Paauw DS. Annual Meeting of the American College of Physicians, Presentation MTP 013.
REPORTING FROM INTERNAL MEDICINE 2019