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Hospitalists play key role in advance care planning
Advance care planning (ACP) is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences for future medical care, according to Meredith A. MacMartin, MD, director of inpatient palliative care at the Dartmouth-Hitchcock Medical Center in Lebanon, N.H.
ACP “is really about planning for care in advance,” and in many ways, the inpatient setting is uniquely suited to this process, Dr. MacMartin said in a presentation at SHM Converge 2021, the annual conference of the Society of Hospital Medicine. “The key part is the advance part. You want conversations to happen before the care is actually needed,” she said.
Dr. MacMartin emphasized the importance of distinguishing between ACP and advance directives (ADs). ACP is a process, whereas ADs are documentation, “ideally of the content of advance care planning discussions,” she explained. ACP involves discussion about what is important to the patients, their goals, what information is helpful for them, and whether their current care is aligned with their goals, Dr. MacMartin said. ADs might involve a designated power of attorney for health care, a living will, and, in some states, specific clinician-signed orders regarding resuscitation or transport to hospital.
ACP is “more than whether a patient wants CPR [cardiopulmonary resuscitation] or not,” said Dr. MacMartin. ACP matters because it helps ensure that the care a patient receives aligns with the patient’s wishes and values, she said. ACP increases the likelihood that patients will die in their preferred locations, it allows them to discuss their wishes and prepare for decline, and it relieves family members of the burden of decision making, she said. From a hospital perspective, data show that use of an ACP can decrease intensive care unit (ICU) utilization and overall health care costs. “Often, when people are given the opportunity to express their wishes, they get less unnecessary care,” Dr. MacMartin noted.
Although ACP often takes place in an outpatient setting, hospitalists are in a unique position to conduct some ACP conversations with their patients, Dr. MacMartin said. “Hospitalists are available” and are physically present at least once a day, so there is a pragmatic advantage. Also, some data suggest that patients may feel more comfortable having ACP conversations with a hospitalist than with a primary care provider with whom they have a long-standing relationship, Dr. MacMartin added.
Another important advantage of ACP in the hospital setting is that, “as hospitalists, you are the expert on inpatient illness; you know what sick looks like, and you have a unique perspective on prognostication that may be harder to recreate in the outpatient setting,” Dr. MacMartin said.
Barriers to ACP include patient identification, logistics, attitudes
Settings in which ACP is appropriate include those in which a patient is undergoing “sentinel hospitalization,” meaning that the patient is at a transition point in the disease course. Examples are a patient newly diagnosed with metastatic solid cancer, a patient with progressive chronic kidney disease who is considering hemodialysis, or a patient who receives treatment in the ICU for longer than 7 days, Dr. MacMartin said.
Guidelines for identifying patients who might benefit from ACP include the use of the “surprise question” (“would you be surprised if this patient dies in the next year?”) as well as functional status assessments using tools such as the Australia-modified Karnofsky Performance Status or the Eastern Cooperative Oncology Group score, said Dr. MacMartin. Some studies suggest that any hospitalized patient older than 65 years should have an ACP discussion, she added.
Time pressure remains a significant barrier to ACP conversations. Some strategies to overcome this problem include enlisting help from other specialists, particularly social workers, Dr. MacMartin said. Social workers report a higher comfort level for talking to patients about death than any other medical specialty; “this is something they want to be doing,” she said. Also, the possibility of reimbursement may act as a buffer to create more time to have ACP conversations with patients, she noted.
Addressing clinicians’ discomfort with ACP conversations can be “a tougher nut to crack,” Dr. MacMartin acknowledged. Clinicians report that they don’t want to cause their patients distress, and some report that having conversations about end-of-life care is distressing for them as well. Some of these barriers can be overcome with skills training, including use of a prepared guideline or framework to help increase the comfort level for both clinicians and patients, said Dr. MacMartin.
A look ahead: Training strategies and COVID-19 impact
“For hospitalists interested in developing their ACP skills, I highly recommend two resources,” Dr. MacMartin said in an interview. “The Serious Illness Conversation Guide, from Ariadne Labs, is an excellent tool for any clinician to guide discussion about a patient’s goals and values,” she said.
“For clinicians wanting to build or improve their communication, including advance care planning discussions but also topics like responding to patient’s emotions, VitalTalk training offers a deeper dive into core communications skills,” she added.
“If your hospital has a palliative care team, they may also have more local resources available to you. To learn more about billing for ACP discussions, I recommend starting with your institutional billing and coding group, as these practices vary some between practices, and they will be able to provide the best guidance for clinicians. These are new codes that aren’t yet being very widely used so it’s a chance to innovate,” Dr. MacMartin noted.
“The hospital setting is an opportunity for patients to reflect on their health, both present and in the future, with a physician who has expertise in acute illness and prognostication and who is available for discussion on a daily basis during the hospitalization,” Dr. MacMartin emphasized.
As for whether the COVID-19 pandemic has affected ACP in the inpatient setting, the data are limited, but more information is forthcoming, Dr. MacMartin said. “In my personal experience and in talking to colleagues elsewhere, the pandemic has highlighted the need for ACP in some ways, as we have tried to ensure that people who wouldn’t want things like intensive care are identified early,” she said. “I hope that some of the workflows developed to identify patients who should get ACP in the hospital stay in practice and are strengthened over time,” she added.
Dr. MacMartin has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Advance care planning (ACP) is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences for future medical care, according to Meredith A. MacMartin, MD, director of inpatient palliative care at the Dartmouth-Hitchcock Medical Center in Lebanon, N.H.
ACP “is really about planning for care in advance,” and in many ways, the inpatient setting is uniquely suited to this process, Dr. MacMartin said in a presentation at SHM Converge 2021, the annual conference of the Society of Hospital Medicine. “The key part is the advance part. You want conversations to happen before the care is actually needed,” she said.
Dr. MacMartin emphasized the importance of distinguishing between ACP and advance directives (ADs). ACP is a process, whereas ADs are documentation, “ideally of the content of advance care planning discussions,” she explained. ACP involves discussion about what is important to the patients, their goals, what information is helpful for them, and whether their current care is aligned with their goals, Dr. MacMartin said. ADs might involve a designated power of attorney for health care, a living will, and, in some states, specific clinician-signed orders regarding resuscitation or transport to hospital.
ACP is “more than whether a patient wants CPR [cardiopulmonary resuscitation] or not,” said Dr. MacMartin. ACP matters because it helps ensure that the care a patient receives aligns with the patient’s wishes and values, she said. ACP increases the likelihood that patients will die in their preferred locations, it allows them to discuss their wishes and prepare for decline, and it relieves family members of the burden of decision making, she said. From a hospital perspective, data show that use of an ACP can decrease intensive care unit (ICU) utilization and overall health care costs. “Often, when people are given the opportunity to express their wishes, they get less unnecessary care,” Dr. MacMartin noted.
Although ACP often takes place in an outpatient setting, hospitalists are in a unique position to conduct some ACP conversations with their patients, Dr. MacMartin said. “Hospitalists are available” and are physically present at least once a day, so there is a pragmatic advantage. Also, some data suggest that patients may feel more comfortable having ACP conversations with a hospitalist than with a primary care provider with whom they have a long-standing relationship, Dr. MacMartin added.
Another important advantage of ACP in the hospital setting is that, “as hospitalists, you are the expert on inpatient illness; you know what sick looks like, and you have a unique perspective on prognostication that may be harder to recreate in the outpatient setting,” Dr. MacMartin said.
Barriers to ACP include patient identification, logistics, attitudes
Settings in which ACP is appropriate include those in which a patient is undergoing “sentinel hospitalization,” meaning that the patient is at a transition point in the disease course. Examples are a patient newly diagnosed with metastatic solid cancer, a patient with progressive chronic kidney disease who is considering hemodialysis, or a patient who receives treatment in the ICU for longer than 7 days, Dr. MacMartin said.
Guidelines for identifying patients who might benefit from ACP include the use of the “surprise question” (“would you be surprised if this patient dies in the next year?”) as well as functional status assessments using tools such as the Australia-modified Karnofsky Performance Status or the Eastern Cooperative Oncology Group score, said Dr. MacMartin. Some studies suggest that any hospitalized patient older than 65 years should have an ACP discussion, she added.
Time pressure remains a significant barrier to ACP conversations. Some strategies to overcome this problem include enlisting help from other specialists, particularly social workers, Dr. MacMartin said. Social workers report a higher comfort level for talking to patients about death than any other medical specialty; “this is something they want to be doing,” she said. Also, the possibility of reimbursement may act as a buffer to create more time to have ACP conversations with patients, she noted.
Addressing clinicians’ discomfort with ACP conversations can be “a tougher nut to crack,” Dr. MacMartin acknowledged. Clinicians report that they don’t want to cause their patients distress, and some report that having conversations about end-of-life care is distressing for them as well. Some of these barriers can be overcome with skills training, including use of a prepared guideline or framework to help increase the comfort level for both clinicians and patients, said Dr. MacMartin.
A look ahead: Training strategies and COVID-19 impact
“For hospitalists interested in developing their ACP skills, I highly recommend two resources,” Dr. MacMartin said in an interview. “The Serious Illness Conversation Guide, from Ariadne Labs, is an excellent tool for any clinician to guide discussion about a patient’s goals and values,” she said.
“For clinicians wanting to build or improve their communication, including advance care planning discussions but also topics like responding to patient’s emotions, VitalTalk training offers a deeper dive into core communications skills,” she added.
“If your hospital has a palliative care team, they may also have more local resources available to you. To learn more about billing for ACP discussions, I recommend starting with your institutional billing and coding group, as these practices vary some between practices, and they will be able to provide the best guidance for clinicians. These are new codes that aren’t yet being very widely used so it’s a chance to innovate,” Dr. MacMartin noted.
“The hospital setting is an opportunity for patients to reflect on their health, both present and in the future, with a physician who has expertise in acute illness and prognostication and who is available for discussion on a daily basis during the hospitalization,” Dr. MacMartin emphasized.
As for whether the COVID-19 pandemic has affected ACP in the inpatient setting, the data are limited, but more information is forthcoming, Dr. MacMartin said. “In my personal experience and in talking to colleagues elsewhere, the pandemic has highlighted the need for ACP in some ways, as we have tried to ensure that people who wouldn’t want things like intensive care are identified early,” she said. “I hope that some of the workflows developed to identify patients who should get ACP in the hospital stay in practice and are strengthened over time,” she added.
Dr. MacMartin has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Advance care planning (ACP) is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences for future medical care, according to Meredith A. MacMartin, MD, director of inpatient palliative care at the Dartmouth-Hitchcock Medical Center in Lebanon, N.H.
ACP “is really about planning for care in advance,” and in many ways, the inpatient setting is uniquely suited to this process, Dr. MacMartin said in a presentation at SHM Converge 2021, the annual conference of the Society of Hospital Medicine. “The key part is the advance part. You want conversations to happen before the care is actually needed,” she said.
Dr. MacMartin emphasized the importance of distinguishing between ACP and advance directives (ADs). ACP is a process, whereas ADs are documentation, “ideally of the content of advance care planning discussions,” she explained. ACP involves discussion about what is important to the patients, their goals, what information is helpful for them, and whether their current care is aligned with their goals, Dr. MacMartin said. ADs might involve a designated power of attorney for health care, a living will, and, in some states, specific clinician-signed orders regarding resuscitation or transport to hospital.
ACP is “more than whether a patient wants CPR [cardiopulmonary resuscitation] or not,” said Dr. MacMartin. ACP matters because it helps ensure that the care a patient receives aligns with the patient’s wishes and values, she said. ACP increases the likelihood that patients will die in their preferred locations, it allows them to discuss their wishes and prepare for decline, and it relieves family members of the burden of decision making, she said. From a hospital perspective, data show that use of an ACP can decrease intensive care unit (ICU) utilization and overall health care costs. “Often, when people are given the opportunity to express their wishes, they get less unnecessary care,” Dr. MacMartin noted.
Although ACP often takes place in an outpatient setting, hospitalists are in a unique position to conduct some ACP conversations with their patients, Dr. MacMartin said. “Hospitalists are available” and are physically present at least once a day, so there is a pragmatic advantage. Also, some data suggest that patients may feel more comfortable having ACP conversations with a hospitalist than with a primary care provider with whom they have a long-standing relationship, Dr. MacMartin added.
Another important advantage of ACP in the hospital setting is that, “as hospitalists, you are the expert on inpatient illness; you know what sick looks like, and you have a unique perspective on prognostication that may be harder to recreate in the outpatient setting,” Dr. MacMartin said.
Barriers to ACP include patient identification, logistics, attitudes
Settings in which ACP is appropriate include those in which a patient is undergoing “sentinel hospitalization,” meaning that the patient is at a transition point in the disease course. Examples are a patient newly diagnosed with metastatic solid cancer, a patient with progressive chronic kidney disease who is considering hemodialysis, or a patient who receives treatment in the ICU for longer than 7 days, Dr. MacMartin said.
Guidelines for identifying patients who might benefit from ACP include the use of the “surprise question” (“would you be surprised if this patient dies in the next year?”) as well as functional status assessments using tools such as the Australia-modified Karnofsky Performance Status or the Eastern Cooperative Oncology Group score, said Dr. MacMartin. Some studies suggest that any hospitalized patient older than 65 years should have an ACP discussion, she added.
Time pressure remains a significant barrier to ACP conversations. Some strategies to overcome this problem include enlisting help from other specialists, particularly social workers, Dr. MacMartin said. Social workers report a higher comfort level for talking to patients about death than any other medical specialty; “this is something they want to be doing,” she said. Also, the possibility of reimbursement may act as a buffer to create more time to have ACP conversations with patients, she noted.
Addressing clinicians’ discomfort with ACP conversations can be “a tougher nut to crack,” Dr. MacMartin acknowledged. Clinicians report that they don’t want to cause their patients distress, and some report that having conversations about end-of-life care is distressing for them as well. Some of these barriers can be overcome with skills training, including use of a prepared guideline or framework to help increase the comfort level for both clinicians and patients, said Dr. MacMartin.
A look ahead: Training strategies and COVID-19 impact
“For hospitalists interested in developing their ACP skills, I highly recommend two resources,” Dr. MacMartin said in an interview. “The Serious Illness Conversation Guide, from Ariadne Labs, is an excellent tool for any clinician to guide discussion about a patient’s goals and values,” she said.
“For clinicians wanting to build or improve their communication, including advance care planning discussions but also topics like responding to patient’s emotions, VitalTalk training offers a deeper dive into core communications skills,” she added.
“If your hospital has a palliative care team, they may also have more local resources available to you. To learn more about billing for ACP discussions, I recommend starting with your institutional billing and coding group, as these practices vary some between practices, and they will be able to provide the best guidance for clinicians. These are new codes that aren’t yet being very widely used so it’s a chance to innovate,” Dr. MacMartin noted.
“The hospital setting is an opportunity for patients to reflect on their health, both present and in the future, with a physician who has expertise in acute illness and prognostication and who is available for discussion on a daily basis during the hospitalization,” Dr. MacMartin emphasized.
As for whether the COVID-19 pandemic has affected ACP in the inpatient setting, the data are limited, but more information is forthcoming, Dr. MacMartin said. “In my personal experience and in talking to colleagues elsewhere, the pandemic has highlighted the need for ACP in some ways, as we have tried to ensure that people who wouldn’t want things like intensive care are identified early,” she said. “I hope that some of the workflows developed to identify patients who should get ACP in the hospital stay in practice and are strengthened over time,” she added.
Dr. MacMartin has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SHM CONVERGE 2021
CDC: New botulism guidelines focus on mass casualty events
Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose.
The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.
In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”
While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.
Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
Diagnosis
Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.
Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).
Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.
Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.
With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.
Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”
It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.
Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
Treatment
Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.
Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.
While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.
Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.
Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.
A version of this article first appeared on Medscape.com.
Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose.
The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.
In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”
While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.
Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
Diagnosis
Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.
Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).
Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.
Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.
With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.
Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”
It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.
Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
Treatment
Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.
Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.
While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.
Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.
Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.
A version of this article first appeared on Medscape.com.
Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose.
The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.
In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”
While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.
Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
Diagnosis
Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.
Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).
Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.
Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.
With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.
Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”
It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.
Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
Treatment
Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.
Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.
While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.
Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.
Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.
A version of this article first appeared on Medscape.com.
Subclinical myocarditis found in some athletes post COVID
Myocarditis is present in a small percentage of competitive athletes after COVID-19 infection, even in those without symptoms, new research suggests.
In a cohort study of 1,597 competitive collegiate athletes undergoing comprehensive cardiovascular testing in the United States, the prevalence of clinical myocarditis based on a symptom-based screening strategy was only 0.31%.
But screening with cardiac MRI increased the prevalence of clinical and subclinical myocarditis by a factor of 7.4, to 2.3%, the authors reported.
The findings are published online May 27, 2021, in JAMA Cardiology.
“It was the largest study to evaluate college athletes who have had COVID with extensive cardiac testing, including MRI, and this gave us a very objective look at the cardiac findings, as they were not purely based upon a subjective evaluation of symptoms,” lead investigator Curt J. Daniels, MD, professor at Ohio State University Wexner Medical Center, Columbus, said in an interview.
“Unfortunately, our study showed that athletes can be asymptomatic, or at least not report symptoms. This is a very subjective feature, and we don’t know if they don’t report symptoms because they didn’t want to get tested. That is why we took a very objective approach,” Dr. Daniels said.
The finding that more than half of the asymptomatic athletes had myocarditis, or as the investigators called it, “subclinical myocarditis,” was a surprise, he acknowledged.
“More than half of the athletes found to have myocarditis reported no symptoms, and yes, that was a surprise, because prior to this study, the protocols that had been published stated that you had to have symptoms to even enter into the protocol for cardiac MRI. But, as our ... paper shows, if we had followed that protocol, we only would have found about 5 cases of myocarditis, as opposed to the total of 37 we found with cardiac MRI,” Dr. Daniels said.
In October 2020, the American College of Cardiology’s Sports and Exercise Council recommended that cardiac MRI be limited to athletes who exhibited symptoms as part of their guide to ensuring a safe return to play.
As reported by this news organization the council recommended a tiered approach to screening based on the presence of symptoms, followed by electrocardiography, injury biomarkers, and echocardiography. Any abnormalities detected were to be further characterized by the selective use of cardiac MRI.
At the time, there were relatively few data to support the recommendations, and all stakeholders called for larger datasets to better drive informed recommendations in the future.
In the current study, Dr. Daniels and associates conducted comprehensive cardiac screening – including ECG, troponin testing, echocardiography, and cardiac MRI – of 1,597 college athlete survivors of COVID-19.
The athletes were part of the Big Ten athletic conference, which consists of 13 major American universities.
Cardiac MRI revealed that 37 (2.3%) of these athletes demonstrated diagnostic criteria for COVID-19 myocarditis; of these, 20 had no cardiovascular symptoms and had normal ECGs, echocardiography, and troponin test results.
“These patients would not have been identified without CMR imaging. If we were going according to the older protocol, we would not have made this discovery. Cardiac MRI is the most sensitive and specific test for myocardial inflammation, there is no argument about that,” Dr. Daniels said.
The catch is, cardiac MRI is expensive and often difficult to access, especially in remote, rural, or other underserviced areas.
“You can’t get an MRI for every person who has had COVID, it’s just not feasible,” Dr. Daniels said. “We are not advocating that everybody get an MRI. But we do hope that our study creates awareness among clinicians and athletes themselves that if you’ve had COVID, even if you’re asymptomatic, there may be some heart changes. So be aware when you start to exercise again, if you have any symptoms, pause and seek medical care.”
Kudos to the sports cardiology community
In an accompanying editorial, James E. Udelson, MD, Ethan J. Rowin, MD, and Barry J. Maron, MD, from the CardioVascular Center at Tufts Medical Center, Boston, applauded the sports cardiology community for its diligence in acquiring and publishing data about the post–COVID-19 prevalence of cardiac abnormalities in competitive athletes.
“It is a real tribute to the sports cardiology community. There has been an amazing growth of information, and they not only gathered this information, they analyzed and published it, starting out with a study of 29 or 30 athletes, and now thousands,” Dr. Udelson said in an interview.
At the start of the pandemic, it appeared that 15%-20% of athletes had myocarditis, and athletic conferences were discussing canceling sports events.
However, with greater numbers comes a more accurate picture of the extent of the problem.
“Once you get thousands of subjects in these studies, you can hone in on what the real number is, so now we understand that if you screen everybody with a cardiac MRI, 1%, 2%, or 3% will have some evidence of what looks like myocarditis,” he said.
Dr. Udelson agreed that doing cardiac imaging in everyone is not feasible.
“This study looked at a very large number of people who all had an MRI, but that doesn’t mean everyone should have them. If you just do an echo, an EKG, and a troponin test, and if everything is normal, which is kind of what current recommendations are, this paper tells us that we are going to miss one or two people out of a hundred, and that might be okay,” he said. “So, if you are at a huge university that has a large medical center and you want to screen all your athletes with MRI, great. But if you’re at a high school in a remote area, you know that the alternative, not having an MRI, isn’t so bad, either.”
A version of this article first appeared on Medscape.com.
Myocarditis is present in a small percentage of competitive athletes after COVID-19 infection, even in those without symptoms, new research suggests.
In a cohort study of 1,597 competitive collegiate athletes undergoing comprehensive cardiovascular testing in the United States, the prevalence of clinical myocarditis based on a symptom-based screening strategy was only 0.31%.
But screening with cardiac MRI increased the prevalence of clinical and subclinical myocarditis by a factor of 7.4, to 2.3%, the authors reported.
The findings are published online May 27, 2021, in JAMA Cardiology.
“It was the largest study to evaluate college athletes who have had COVID with extensive cardiac testing, including MRI, and this gave us a very objective look at the cardiac findings, as they were not purely based upon a subjective evaluation of symptoms,” lead investigator Curt J. Daniels, MD, professor at Ohio State University Wexner Medical Center, Columbus, said in an interview.
“Unfortunately, our study showed that athletes can be asymptomatic, or at least not report symptoms. This is a very subjective feature, and we don’t know if they don’t report symptoms because they didn’t want to get tested. That is why we took a very objective approach,” Dr. Daniels said.
The finding that more than half of the asymptomatic athletes had myocarditis, or as the investigators called it, “subclinical myocarditis,” was a surprise, he acknowledged.
“More than half of the athletes found to have myocarditis reported no symptoms, and yes, that was a surprise, because prior to this study, the protocols that had been published stated that you had to have symptoms to even enter into the protocol for cardiac MRI. But, as our ... paper shows, if we had followed that protocol, we only would have found about 5 cases of myocarditis, as opposed to the total of 37 we found with cardiac MRI,” Dr. Daniels said.
In October 2020, the American College of Cardiology’s Sports and Exercise Council recommended that cardiac MRI be limited to athletes who exhibited symptoms as part of their guide to ensuring a safe return to play.
As reported by this news organization the council recommended a tiered approach to screening based on the presence of symptoms, followed by electrocardiography, injury biomarkers, and echocardiography. Any abnormalities detected were to be further characterized by the selective use of cardiac MRI.
At the time, there were relatively few data to support the recommendations, and all stakeholders called for larger datasets to better drive informed recommendations in the future.
In the current study, Dr. Daniels and associates conducted comprehensive cardiac screening – including ECG, troponin testing, echocardiography, and cardiac MRI – of 1,597 college athlete survivors of COVID-19.
The athletes were part of the Big Ten athletic conference, which consists of 13 major American universities.
Cardiac MRI revealed that 37 (2.3%) of these athletes demonstrated diagnostic criteria for COVID-19 myocarditis; of these, 20 had no cardiovascular symptoms and had normal ECGs, echocardiography, and troponin test results.
“These patients would not have been identified without CMR imaging. If we were going according to the older protocol, we would not have made this discovery. Cardiac MRI is the most sensitive and specific test for myocardial inflammation, there is no argument about that,” Dr. Daniels said.
The catch is, cardiac MRI is expensive and often difficult to access, especially in remote, rural, or other underserviced areas.
“You can’t get an MRI for every person who has had COVID, it’s just not feasible,” Dr. Daniels said. “We are not advocating that everybody get an MRI. But we do hope that our study creates awareness among clinicians and athletes themselves that if you’ve had COVID, even if you’re asymptomatic, there may be some heart changes. So be aware when you start to exercise again, if you have any symptoms, pause and seek medical care.”
Kudos to the sports cardiology community
In an accompanying editorial, James E. Udelson, MD, Ethan J. Rowin, MD, and Barry J. Maron, MD, from the CardioVascular Center at Tufts Medical Center, Boston, applauded the sports cardiology community for its diligence in acquiring and publishing data about the post–COVID-19 prevalence of cardiac abnormalities in competitive athletes.
“It is a real tribute to the sports cardiology community. There has been an amazing growth of information, and they not only gathered this information, they analyzed and published it, starting out with a study of 29 or 30 athletes, and now thousands,” Dr. Udelson said in an interview.
At the start of the pandemic, it appeared that 15%-20% of athletes had myocarditis, and athletic conferences were discussing canceling sports events.
However, with greater numbers comes a more accurate picture of the extent of the problem.
“Once you get thousands of subjects in these studies, you can hone in on what the real number is, so now we understand that if you screen everybody with a cardiac MRI, 1%, 2%, or 3% will have some evidence of what looks like myocarditis,” he said.
Dr. Udelson agreed that doing cardiac imaging in everyone is not feasible.
“This study looked at a very large number of people who all had an MRI, but that doesn’t mean everyone should have them. If you just do an echo, an EKG, and a troponin test, and if everything is normal, which is kind of what current recommendations are, this paper tells us that we are going to miss one or two people out of a hundred, and that might be okay,” he said. “So, if you are at a huge university that has a large medical center and you want to screen all your athletes with MRI, great. But if you’re at a high school in a remote area, you know that the alternative, not having an MRI, isn’t so bad, either.”
A version of this article first appeared on Medscape.com.
Myocarditis is present in a small percentage of competitive athletes after COVID-19 infection, even in those without symptoms, new research suggests.
In a cohort study of 1,597 competitive collegiate athletes undergoing comprehensive cardiovascular testing in the United States, the prevalence of clinical myocarditis based on a symptom-based screening strategy was only 0.31%.
But screening with cardiac MRI increased the prevalence of clinical and subclinical myocarditis by a factor of 7.4, to 2.3%, the authors reported.
The findings are published online May 27, 2021, in JAMA Cardiology.
“It was the largest study to evaluate college athletes who have had COVID with extensive cardiac testing, including MRI, and this gave us a very objective look at the cardiac findings, as they were not purely based upon a subjective evaluation of symptoms,” lead investigator Curt J. Daniels, MD, professor at Ohio State University Wexner Medical Center, Columbus, said in an interview.
“Unfortunately, our study showed that athletes can be asymptomatic, or at least not report symptoms. This is a very subjective feature, and we don’t know if they don’t report symptoms because they didn’t want to get tested. That is why we took a very objective approach,” Dr. Daniels said.
The finding that more than half of the asymptomatic athletes had myocarditis, or as the investigators called it, “subclinical myocarditis,” was a surprise, he acknowledged.
“More than half of the athletes found to have myocarditis reported no symptoms, and yes, that was a surprise, because prior to this study, the protocols that had been published stated that you had to have symptoms to even enter into the protocol for cardiac MRI. But, as our ... paper shows, if we had followed that protocol, we only would have found about 5 cases of myocarditis, as opposed to the total of 37 we found with cardiac MRI,” Dr. Daniels said.
In October 2020, the American College of Cardiology’s Sports and Exercise Council recommended that cardiac MRI be limited to athletes who exhibited symptoms as part of their guide to ensuring a safe return to play.
As reported by this news organization the council recommended a tiered approach to screening based on the presence of symptoms, followed by electrocardiography, injury biomarkers, and echocardiography. Any abnormalities detected were to be further characterized by the selective use of cardiac MRI.
At the time, there were relatively few data to support the recommendations, and all stakeholders called for larger datasets to better drive informed recommendations in the future.
In the current study, Dr. Daniels and associates conducted comprehensive cardiac screening – including ECG, troponin testing, echocardiography, and cardiac MRI – of 1,597 college athlete survivors of COVID-19.
The athletes were part of the Big Ten athletic conference, which consists of 13 major American universities.
Cardiac MRI revealed that 37 (2.3%) of these athletes demonstrated diagnostic criteria for COVID-19 myocarditis; of these, 20 had no cardiovascular symptoms and had normal ECGs, echocardiography, and troponin test results.
“These patients would not have been identified without CMR imaging. If we were going according to the older protocol, we would not have made this discovery. Cardiac MRI is the most sensitive and specific test for myocardial inflammation, there is no argument about that,” Dr. Daniels said.
The catch is, cardiac MRI is expensive and often difficult to access, especially in remote, rural, or other underserviced areas.
“You can’t get an MRI for every person who has had COVID, it’s just not feasible,” Dr. Daniels said. “We are not advocating that everybody get an MRI. But we do hope that our study creates awareness among clinicians and athletes themselves that if you’ve had COVID, even if you’re asymptomatic, there may be some heart changes. So be aware when you start to exercise again, if you have any symptoms, pause and seek medical care.”
Kudos to the sports cardiology community
In an accompanying editorial, James E. Udelson, MD, Ethan J. Rowin, MD, and Barry J. Maron, MD, from the CardioVascular Center at Tufts Medical Center, Boston, applauded the sports cardiology community for its diligence in acquiring and publishing data about the post–COVID-19 prevalence of cardiac abnormalities in competitive athletes.
“It is a real tribute to the sports cardiology community. There has been an amazing growth of information, and they not only gathered this information, they analyzed and published it, starting out with a study of 29 or 30 athletes, and now thousands,” Dr. Udelson said in an interview.
At the start of the pandemic, it appeared that 15%-20% of athletes had myocarditis, and athletic conferences were discussing canceling sports events.
However, with greater numbers comes a more accurate picture of the extent of the problem.
“Once you get thousands of subjects in these studies, you can hone in on what the real number is, so now we understand that if you screen everybody with a cardiac MRI, 1%, 2%, or 3% will have some evidence of what looks like myocarditis,” he said.
Dr. Udelson agreed that doing cardiac imaging in everyone is not feasible.
“This study looked at a very large number of people who all had an MRI, but that doesn’t mean everyone should have them. If you just do an echo, an EKG, and a troponin test, and if everything is normal, which is kind of what current recommendations are, this paper tells us that we are going to miss one or two people out of a hundred, and that might be okay,” he said. “So, if you are at a huge university that has a large medical center and you want to screen all your athletes with MRI, great. But if you’re at a high school in a remote area, you know that the alternative, not having an MRI, isn’t so bad, either.”
A version of this article first appeared on Medscape.com.
High-flow nasal cannula improves dyspnea in palliative care patients with respiratory failure
Background: For patients receiving palliative care who develop respiratory distress, conventional oxygen therapy may not adequately relieve symptoms of dyspnea, and noninvasive ventilation may not promote comfort. Few randomized controlled trials have investigated the use of high-flow nasal cannula (HFNC) for treatment of palliative care patients who present to the hospital with respiratory distress.
Study design: Randomized crossover study.
Setting: Emergency department of a single institution.
Synopsis: Forty-eight palliative care patients who presented to the ED with acute dyspnea were enrolled and randomized to receive HFNC for 1 hour, followed by conventional oxygen therapy for 1 hour, or vice versa. The authors found that patients using HFNC reported significantly less dyspnea on a breathlessness severity scale, compared with patients using conventional oxygen therapy. Additionally, patients using HFNC had significantly lower respiratory rates, and HFNC use was associated with significantly lower need for morphine in a 1-hour period. The study was limited because of its single institution and small sample size, and therefore the results may not be generalizable to other patient populations.
Bottom line: Treatment with a high-flow nasal cannula may improve symptoms of acute dysp-nea in palliative patients when compared with conventional oxygen therapy.
Citation: Ruangsomboon O et al. High-flow nasal cannula versus conventional oxygen therapy in relieving dyspnea in emergency palliative patients with do-not-intubate status: A randomized crossover study. Ann Emerg Med. 2019 Dec 18. doi: 10.1016/j.annemergmed.2019.09.009.
Dr. Halford is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.
Background: For patients receiving palliative care who develop respiratory distress, conventional oxygen therapy may not adequately relieve symptoms of dyspnea, and noninvasive ventilation may not promote comfort. Few randomized controlled trials have investigated the use of high-flow nasal cannula (HFNC) for treatment of palliative care patients who present to the hospital with respiratory distress.
Study design: Randomized crossover study.
Setting: Emergency department of a single institution.
Synopsis: Forty-eight palliative care patients who presented to the ED with acute dyspnea were enrolled and randomized to receive HFNC for 1 hour, followed by conventional oxygen therapy for 1 hour, or vice versa. The authors found that patients using HFNC reported significantly less dyspnea on a breathlessness severity scale, compared with patients using conventional oxygen therapy. Additionally, patients using HFNC had significantly lower respiratory rates, and HFNC use was associated with significantly lower need for morphine in a 1-hour period. The study was limited because of its single institution and small sample size, and therefore the results may not be generalizable to other patient populations.
Bottom line: Treatment with a high-flow nasal cannula may improve symptoms of acute dysp-nea in palliative patients when compared with conventional oxygen therapy.
Citation: Ruangsomboon O et al. High-flow nasal cannula versus conventional oxygen therapy in relieving dyspnea in emergency palliative patients with do-not-intubate status: A randomized crossover study. Ann Emerg Med. 2019 Dec 18. doi: 10.1016/j.annemergmed.2019.09.009.
Dr. Halford is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.
Background: For patients receiving palliative care who develop respiratory distress, conventional oxygen therapy may not adequately relieve symptoms of dyspnea, and noninvasive ventilation may not promote comfort. Few randomized controlled trials have investigated the use of high-flow nasal cannula (HFNC) for treatment of palliative care patients who present to the hospital with respiratory distress.
Study design: Randomized crossover study.
Setting: Emergency department of a single institution.
Synopsis: Forty-eight palliative care patients who presented to the ED with acute dyspnea were enrolled and randomized to receive HFNC for 1 hour, followed by conventional oxygen therapy for 1 hour, or vice versa. The authors found that patients using HFNC reported significantly less dyspnea on a breathlessness severity scale, compared with patients using conventional oxygen therapy. Additionally, patients using HFNC had significantly lower respiratory rates, and HFNC use was associated with significantly lower need for morphine in a 1-hour period. The study was limited because of its single institution and small sample size, and therefore the results may not be generalizable to other patient populations.
Bottom line: Treatment with a high-flow nasal cannula may improve symptoms of acute dysp-nea in palliative patients when compared with conventional oxygen therapy.
Citation: Ruangsomboon O et al. High-flow nasal cannula versus conventional oxygen therapy in relieving dyspnea in emergency palliative patients with do-not-intubate status: A randomized crossover study. Ann Emerg Med. 2019 Dec 18. doi: 10.1016/j.annemergmed.2019.09.009.
Dr. Halford is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.
Avoiding excess oxygen in mechanically ventilated patients ‘seems sensible’
The respiratory therapists at Mount Sinai Beth Israel, New York, know when Lina Miyakawa, MD, starts a week in the ICU, because she turns down the fraction of inspired oxygen (FiO2) levels if patients tolerate it.
“Hyperoxia in mechanical ventilation is a topic that’s near and dear to my heart,” Dr. Miyakawa, a pulmonary and critical care medicine specialist at Mount Sinai Beth Israel, said during SHM Converge, the annual conference of the Society of Hospital Medicine. “You can always find ‘wean down FiO2’ in my consult notes.”
While it is believed that humans have built up evolutionary defenses against hypoxia but not against hyperoxia, medical literature on the topic of hyperoxia with supplemental oxygen is fairly young. “In medical school we were taught to give oxygen for anybody with chest pain and concern about acute coronary syndrome,” she said. “This was until recent data suggested harm from liberal oxygen use.”
In a single-center trial of 434 critical care patients with an ICU length of stay of 72 hours or longer, Italian researchers examined the effects of a conservative protocol for oxygen therapy versus conventional therapy on ICU mortality (JAMA. 2016;316[15]:1583-9). The trial was stopped because the patients who were assigned to receive conservative therapy had a significantly lower mortality than the ones who received usual care (P = .01). “The study was not perfect, and the premature stoppage likely exaggerated the effect size,” said Dr. Miyakawa, who was not affiliated with the trial. “However, subsequent retrospective studies continue to support a benefit with conservative oxygen use, especially in different groups of patients. One of note is hyperoxia following cardiac arrest. There’s something called a two-hit model that speaks to worsening ischemia with reperfusion injury after the initial hypoxic event from the cardiac arrest itself” (See Intensive Care Med. 2015;41:534-6).
In a multicenter cohort study that drew from the Project IMPACT critical care database of ICUs at 120 U.S. hospitals between 2001 and 2005, researchers led by J. Hope Kilgannon, MD, tested the hypothesis that post-resuscitation hyperoxia is associated with increased in-hospital mortality (JAMA. 2010;303[21]:2165-71). The study population consisted of 6,326 patients who were divided into three groups: the hypoxic group (a PaO2 of less than 60 mm Hg); the normoxic group (a PaO2 of 60-299 mm Hg), and the hyperoxic group (a PaO2 of over 300 mm Hg). The mortality for the hyperoxic group was 63%, the hypoxic group at 57%, and the normoxic group at 45%.
More recently, the ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group evaluated conservative versus liberal approaches in providing oxygen to 965 patients who were mechanically ventilated between 2015 and 2018 at 21 ICUs (N Eng J Med. 2020;382:989-98). Of the 965 patients, 484 were randomly assigned to the conservative oxygen group (defined as an SpO2 of 97% or lower) and 481 were assigned to the usual oxygen group (defined as having no specific measures limiting FiO2 or the SpO2). The primary outcome was the number of ventilator-free days from randomization until day 28, while the secondary outcome was mortality at 180 days. The researchers also performed a subgroup analysis of patients at risk for hypoxic-ischemic encephalopathy.
No significant differences were observed in the number of ventilator days between the two group (a median of 21 days in the conservative oxygen group versus 22 days in the usual oxygen group, respectively; P = .80) nor in mortality at 180 days (35.7% vs. 34.5%). However, in the subgroup analysis, patients with hypoxic-ischemic encephalopathy were noted to have more ventilator-free days (21 vs. 0 days), improved 180-day mortality (43% vs. 59%), and less functional impairment (55% vs. 68%) in the conservative-oxygen group.
“The results of this study suggest that conservative oxygen therapy has no additional advantage over standard oxygen therapy, but there may be benefits in those vulnerable to hyperoxia, which warrants further investigation,” Dr. Miyakawa said. “There are a few points to note on this topic. First, many of the previous studies had more liberal oxygen strategies than the ones used in this study, which could be the reason why we are seeing these results. In addition, O2 titration relies on imperfect approximations. PaO2 cannot be measured continuously; we really depend on the SpO2 on a minute-by-minute basis. Critically ill patients can also undergo episodes of hypoperfusion and shock state minute-by-minute. That’s when they’re at risk for hypoxemia. This would not be captured continuously with just O2 saturations.”
Dr. Miyakawa also highlighted the Liberal Oxygenation versus Conservative Oxygenation in Acute Respiratory Distress Syndrome trial (LOCO2) a prospective, multicenter, randomized, open-label trial involving patients with ARDS. It was carried out at 13 ICUs in France between June 2016 and September 2018 in an effort determine whether conservative oxygenation would reduce mortality at 28 days compared with the usual liberal-oxygen strategy (N Eng J Med. 2020;382:999-1008). The researchers detected a signal of increased mortality in the conservative oxygen group (34% vs. 27%), which led to a premature stoppage of the trial. “I’d like to postulate that the higher incidence of proning in the liberal oxygenation group compared to the conservative oxygen group (51% to 34%) may be the reason for the difference in mortality,” said Dr. Miyakawa, who was not affiliated with LOCO2. “This is supported from the 2013 PROSEVA Study Group, which reported that prone positioning in ARDS significantly decreases 28- and 90-day mortality” (see N Engl J Med. 2013; 368:2159-68).
She said that future trials on this topic “will have to address how a particular [oxygenation] target is both set and achieved in each group of patients, particularly those with specific organ injuries. In the meantime, in my opinion, avoiding excess oxygen seems sensible.”
Dr. Miyakawa reported having no financial disclosures.
The respiratory therapists at Mount Sinai Beth Israel, New York, know when Lina Miyakawa, MD, starts a week in the ICU, because she turns down the fraction of inspired oxygen (FiO2) levels if patients tolerate it.
“Hyperoxia in mechanical ventilation is a topic that’s near and dear to my heart,” Dr. Miyakawa, a pulmonary and critical care medicine specialist at Mount Sinai Beth Israel, said during SHM Converge, the annual conference of the Society of Hospital Medicine. “You can always find ‘wean down FiO2’ in my consult notes.”
While it is believed that humans have built up evolutionary defenses against hypoxia but not against hyperoxia, medical literature on the topic of hyperoxia with supplemental oxygen is fairly young. “In medical school we were taught to give oxygen for anybody with chest pain and concern about acute coronary syndrome,” she said. “This was until recent data suggested harm from liberal oxygen use.”
In a single-center trial of 434 critical care patients with an ICU length of stay of 72 hours or longer, Italian researchers examined the effects of a conservative protocol for oxygen therapy versus conventional therapy on ICU mortality (JAMA. 2016;316[15]:1583-9). The trial was stopped because the patients who were assigned to receive conservative therapy had a significantly lower mortality than the ones who received usual care (P = .01). “The study was not perfect, and the premature stoppage likely exaggerated the effect size,” said Dr. Miyakawa, who was not affiliated with the trial. “However, subsequent retrospective studies continue to support a benefit with conservative oxygen use, especially in different groups of patients. One of note is hyperoxia following cardiac arrest. There’s something called a two-hit model that speaks to worsening ischemia with reperfusion injury after the initial hypoxic event from the cardiac arrest itself” (See Intensive Care Med. 2015;41:534-6).
In a multicenter cohort study that drew from the Project IMPACT critical care database of ICUs at 120 U.S. hospitals between 2001 and 2005, researchers led by J. Hope Kilgannon, MD, tested the hypothesis that post-resuscitation hyperoxia is associated with increased in-hospital mortality (JAMA. 2010;303[21]:2165-71). The study population consisted of 6,326 patients who were divided into three groups: the hypoxic group (a PaO2 of less than 60 mm Hg); the normoxic group (a PaO2 of 60-299 mm Hg), and the hyperoxic group (a PaO2 of over 300 mm Hg). The mortality for the hyperoxic group was 63%, the hypoxic group at 57%, and the normoxic group at 45%.
More recently, the ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group evaluated conservative versus liberal approaches in providing oxygen to 965 patients who were mechanically ventilated between 2015 and 2018 at 21 ICUs (N Eng J Med. 2020;382:989-98). Of the 965 patients, 484 were randomly assigned to the conservative oxygen group (defined as an SpO2 of 97% or lower) and 481 were assigned to the usual oxygen group (defined as having no specific measures limiting FiO2 or the SpO2). The primary outcome was the number of ventilator-free days from randomization until day 28, while the secondary outcome was mortality at 180 days. The researchers also performed a subgroup analysis of patients at risk for hypoxic-ischemic encephalopathy.
No significant differences were observed in the number of ventilator days between the two group (a median of 21 days in the conservative oxygen group versus 22 days in the usual oxygen group, respectively; P = .80) nor in mortality at 180 days (35.7% vs. 34.5%). However, in the subgroup analysis, patients with hypoxic-ischemic encephalopathy were noted to have more ventilator-free days (21 vs. 0 days), improved 180-day mortality (43% vs. 59%), and less functional impairment (55% vs. 68%) in the conservative-oxygen group.
“The results of this study suggest that conservative oxygen therapy has no additional advantage over standard oxygen therapy, but there may be benefits in those vulnerable to hyperoxia, which warrants further investigation,” Dr. Miyakawa said. “There are a few points to note on this topic. First, many of the previous studies had more liberal oxygen strategies than the ones used in this study, which could be the reason why we are seeing these results. In addition, O2 titration relies on imperfect approximations. PaO2 cannot be measured continuously; we really depend on the SpO2 on a minute-by-minute basis. Critically ill patients can also undergo episodes of hypoperfusion and shock state minute-by-minute. That’s when they’re at risk for hypoxemia. This would not be captured continuously with just O2 saturations.”
Dr. Miyakawa also highlighted the Liberal Oxygenation versus Conservative Oxygenation in Acute Respiratory Distress Syndrome trial (LOCO2) a prospective, multicenter, randomized, open-label trial involving patients with ARDS. It was carried out at 13 ICUs in France between June 2016 and September 2018 in an effort determine whether conservative oxygenation would reduce mortality at 28 days compared with the usual liberal-oxygen strategy (N Eng J Med. 2020;382:999-1008). The researchers detected a signal of increased mortality in the conservative oxygen group (34% vs. 27%), which led to a premature stoppage of the trial. “I’d like to postulate that the higher incidence of proning in the liberal oxygenation group compared to the conservative oxygen group (51% to 34%) may be the reason for the difference in mortality,” said Dr. Miyakawa, who was not affiliated with LOCO2. “This is supported from the 2013 PROSEVA Study Group, which reported that prone positioning in ARDS significantly decreases 28- and 90-day mortality” (see N Engl J Med. 2013; 368:2159-68).
She said that future trials on this topic “will have to address how a particular [oxygenation] target is both set and achieved in each group of patients, particularly those with specific organ injuries. In the meantime, in my opinion, avoiding excess oxygen seems sensible.”
Dr. Miyakawa reported having no financial disclosures.
The respiratory therapists at Mount Sinai Beth Israel, New York, know when Lina Miyakawa, MD, starts a week in the ICU, because she turns down the fraction of inspired oxygen (FiO2) levels if patients tolerate it.
“Hyperoxia in mechanical ventilation is a topic that’s near and dear to my heart,” Dr. Miyakawa, a pulmonary and critical care medicine specialist at Mount Sinai Beth Israel, said during SHM Converge, the annual conference of the Society of Hospital Medicine. “You can always find ‘wean down FiO2’ in my consult notes.”
While it is believed that humans have built up evolutionary defenses against hypoxia but not against hyperoxia, medical literature on the topic of hyperoxia with supplemental oxygen is fairly young. “In medical school we were taught to give oxygen for anybody with chest pain and concern about acute coronary syndrome,” she said. “This was until recent data suggested harm from liberal oxygen use.”
In a single-center trial of 434 critical care patients with an ICU length of stay of 72 hours or longer, Italian researchers examined the effects of a conservative protocol for oxygen therapy versus conventional therapy on ICU mortality (JAMA. 2016;316[15]:1583-9). The trial was stopped because the patients who were assigned to receive conservative therapy had a significantly lower mortality than the ones who received usual care (P = .01). “The study was not perfect, and the premature stoppage likely exaggerated the effect size,” said Dr. Miyakawa, who was not affiliated with the trial. “However, subsequent retrospective studies continue to support a benefit with conservative oxygen use, especially in different groups of patients. One of note is hyperoxia following cardiac arrest. There’s something called a two-hit model that speaks to worsening ischemia with reperfusion injury after the initial hypoxic event from the cardiac arrest itself” (See Intensive Care Med. 2015;41:534-6).
In a multicenter cohort study that drew from the Project IMPACT critical care database of ICUs at 120 U.S. hospitals between 2001 and 2005, researchers led by J. Hope Kilgannon, MD, tested the hypothesis that post-resuscitation hyperoxia is associated with increased in-hospital mortality (JAMA. 2010;303[21]:2165-71). The study population consisted of 6,326 patients who were divided into three groups: the hypoxic group (a PaO2 of less than 60 mm Hg); the normoxic group (a PaO2 of 60-299 mm Hg), and the hyperoxic group (a PaO2 of over 300 mm Hg). The mortality for the hyperoxic group was 63%, the hypoxic group at 57%, and the normoxic group at 45%.
More recently, the ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group evaluated conservative versus liberal approaches in providing oxygen to 965 patients who were mechanically ventilated between 2015 and 2018 at 21 ICUs (N Eng J Med. 2020;382:989-98). Of the 965 patients, 484 were randomly assigned to the conservative oxygen group (defined as an SpO2 of 97% or lower) and 481 were assigned to the usual oxygen group (defined as having no specific measures limiting FiO2 or the SpO2). The primary outcome was the number of ventilator-free days from randomization until day 28, while the secondary outcome was mortality at 180 days. The researchers also performed a subgroup analysis of patients at risk for hypoxic-ischemic encephalopathy.
No significant differences were observed in the number of ventilator days between the two group (a median of 21 days in the conservative oxygen group versus 22 days in the usual oxygen group, respectively; P = .80) nor in mortality at 180 days (35.7% vs. 34.5%). However, in the subgroup analysis, patients with hypoxic-ischemic encephalopathy were noted to have more ventilator-free days (21 vs. 0 days), improved 180-day mortality (43% vs. 59%), and less functional impairment (55% vs. 68%) in the conservative-oxygen group.
“The results of this study suggest that conservative oxygen therapy has no additional advantage over standard oxygen therapy, but there may be benefits in those vulnerable to hyperoxia, which warrants further investigation,” Dr. Miyakawa said. “There are a few points to note on this topic. First, many of the previous studies had more liberal oxygen strategies than the ones used in this study, which could be the reason why we are seeing these results. In addition, O2 titration relies on imperfect approximations. PaO2 cannot be measured continuously; we really depend on the SpO2 on a minute-by-minute basis. Critically ill patients can also undergo episodes of hypoperfusion and shock state minute-by-minute. That’s when they’re at risk for hypoxemia. This would not be captured continuously with just O2 saturations.”
Dr. Miyakawa also highlighted the Liberal Oxygenation versus Conservative Oxygenation in Acute Respiratory Distress Syndrome trial (LOCO2) a prospective, multicenter, randomized, open-label trial involving patients with ARDS. It was carried out at 13 ICUs in France between June 2016 and September 2018 in an effort determine whether conservative oxygenation would reduce mortality at 28 days compared with the usual liberal-oxygen strategy (N Eng J Med. 2020;382:999-1008). The researchers detected a signal of increased mortality in the conservative oxygen group (34% vs. 27%), which led to a premature stoppage of the trial. “I’d like to postulate that the higher incidence of proning in the liberal oxygenation group compared to the conservative oxygen group (51% to 34%) may be the reason for the difference in mortality,” said Dr. Miyakawa, who was not affiliated with LOCO2. “This is supported from the 2013 PROSEVA Study Group, which reported that prone positioning in ARDS significantly decreases 28- and 90-day mortality” (see N Engl J Med. 2013; 368:2159-68).
She said that future trials on this topic “will have to address how a particular [oxygenation] target is both set and achieved in each group of patients, particularly those with specific organ injuries. In the meantime, in my opinion, avoiding excess oxygen seems sensible.”
Dr. Miyakawa reported having no financial disclosures.
FROM SHM CONVERGE 2021
Single subcutaneous shot offers fast, potent platelet inhibition in STEMI
A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.
Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.
The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.
The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.
Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.
“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.
RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.
In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.
The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.
The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).
The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.
“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”
The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.
Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”
The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.
“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.
Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.
CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.
A version of this article first appeared on Medscape.com.
A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.
Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.
The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.
The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.
Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.
“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.
RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.
In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.
The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.
The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).
The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.
“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”
The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.
Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”
The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.
“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.
Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.
CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.
A version of this article first appeared on Medscape.com.
A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.
Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.
The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.
The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.
Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.
“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.
RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.
In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.
The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.
The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).
The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.
“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”
The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.
Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”
The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.
“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.
Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.
CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.
A version of this article first appeared on Medscape.com.
Significant reduction of alcohol intake reduced AFib burden and recurrence
Background: Prior observational studies have suggested that a dose-dependent effect may exist between alcohol intake and incident AFib, recurrence after ablation, and cardiac structural changes.
Study design: Prospective, open-label, multicenter, randomized clinical trial, with an intention-to-treat analysis.
Setting: Six tertiary care hospitals in Australia.
Synopsis: Study authors enrolled 140 patients with symptomatic paroxysmal or persistent AFib and regular alcohol consumption of 10 or more standard drinks per week. Participants were randomized to alcohol abstinence or usual alcohol intake. They underwent comprehensive rhythm monitoring and alcohol intake assessment for 6 months with in-person visits and oral/electronic communication. Over the 6-month period, patients in the abstinence group reduced their mean drinks per week from approximately 17 to 2, with 61% achieving complete abstinence. Patients in the abstinence group had a significantly longer period before recurrence of AFib when compared with the control group. Furthermore, the AFib burden over 6 months was significantly lower in the abstinence group, compared with the control group (0.5% vs. 1.2%).
Bottom line: For patients with symptomatic paroxysmal or persistent atrial fibrillation and regular alcohol consumption, reducing alcohol intake may significantly lower AFib burden and increase the time-to-recurrence of AFib at 6 months.
Citation: Voskoboinik A et al. Alcohol abstinence in drinkers with atrial fibrillation. N Engl J Med 2020 Jan 2;382:20-8.
Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.
Background: Prior observational studies have suggested that a dose-dependent effect may exist between alcohol intake and incident AFib, recurrence after ablation, and cardiac structural changes.
Study design: Prospective, open-label, multicenter, randomized clinical trial, with an intention-to-treat analysis.
Setting: Six tertiary care hospitals in Australia.
Synopsis: Study authors enrolled 140 patients with symptomatic paroxysmal or persistent AFib and regular alcohol consumption of 10 or more standard drinks per week. Participants were randomized to alcohol abstinence or usual alcohol intake. They underwent comprehensive rhythm monitoring and alcohol intake assessment for 6 months with in-person visits and oral/electronic communication. Over the 6-month period, patients in the abstinence group reduced their mean drinks per week from approximately 17 to 2, with 61% achieving complete abstinence. Patients in the abstinence group had a significantly longer period before recurrence of AFib when compared with the control group. Furthermore, the AFib burden over 6 months was significantly lower in the abstinence group, compared with the control group (0.5% vs. 1.2%).
Bottom line: For patients with symptomatic paroxysmal or persistent atrial fibrillation and regular alcohol consumption, reducing alcohol intake may significantly lower AFib burden and increase the time-to-recurrence of AFib at 6 months.
Citation: Voskoboinik A et al. Alcohol abstinence in drinkers with atrial fibrillation. N Engl J Med 2020 Jan 2;382:20-8.
Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.
Background: Prior observational studies have suggested that a dose-dependent effect may exist between alcohol intake and incident AFib, recurrence after ablation, and cardiac structural changes.
Study design: Prospective, open-label, multicenter, randomized clinical trial, with an intention-to-treat analysis.
Setting: Six tertiary care hospitals in Australia.
Synopsis: Study authors enrolled 140 patients with symptomatic paroxysmal or persistent AFib and regular alcohol consumption of 10 or more standard drinks per week. Participants were randomized to alcohol abstinence or usual alcohol intake. They underwent comprehensive rhythm monitoring and alcohol intake assessment for 6 months with in-person visits and oral/electronic communication. Over the 6-month period, patients in the abstinence group reduced their mean drinks per week from approximately 17 to 2, with 61% achieving complete abstinence. Patients in the abstinence group had a significantly longer period before recurrence of AFib when compared with the control group. Furthermore, the AFib burden over 6 months was significantly lower in the abstinence group, compared with the control group (0.5% vs. 1.2%).
Bottom line: For patients with symptomatic paroxysmal or persistent atrial fibrillation and regular alcohol consumption, reducing alcohol intake may significantly lower AFib burden and increase the time-to-recurrence of AFib at 6 months.
Citation: Voskoboinik A et al. Alcohol abstinence in drinkers with atrial fibrillation. N Engl J Med 2020 Jan 2;382:20-8.
Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.
Hospitalists innovate in ICU management
With intensive care units stretched to their limits – and beyond – during the COVID-19 pandemic, hospitalists became more central than ever in orchestrating the response.
At SHM Converge, the annual conference of the Society of Hospital Medicine, two hospitalists shared how their teams helped to develop new critical care units and strategies for best managing and allocating care to COVID patients in the ICU.
“The pandemic has been a selective pressure on us as a specialty,” said Jason Stein, MD, SFHM, a full-time clinical hospitalist at Roper Hospital, a 332-bed facility in Charleston, S.C.
Dr. Stein explained how hospitalists at Roper helped create the Progressive Care Unit – a negative-pressure unit with 12 high-flow oxygen beds overseen by a hospital medicine team, with the help of a respiratory therapist, pharmacist, and nurses. Patients in this unit had escalating acuity – quickly increasing oxygen needs – or deescalating acuity, such as ICU transfers, Dr. Stein said. Cardiac catheterization space was converted for the unit, which was intended to preserve beds in the hospital ICU for patients needing mechanical ventilation or vasoactive medication.
Interdisciplinary rounds – to assess oxygen and inflammatory marker trends, and run through a COVID care checklist – took place every day at 10 a.m.
“Consistency was the key,” Dr. Stein said.
At Weill Cornell Medical Center in New York, hospitalists helped build the COVID Recovery Unit, which was dedicated to the care of patients coming out of the ICU, said Vishwas Anand Singh, MD, MS, FHM, cochief of hospital medicine at New York Presbyterian–Lower Manhattan Hospital.
“The pandemic created an unprecedented need for critical care, and post-ICU care,” Dr. Singh said. “After extubation, patients remain very complicated and they have unique needs.”
The 30-bed COVID Recovery Unit – converted from a behavioral health unit – was designed to meet those needs. It was staffed by one lead hospitalist, 3 hospitalist physicians, 3 advanced practitioners, about 12 nurses and a neurologist, psychiatrist, and neuropsychologist.
The idea was to integrate medical care with careful attention to rehab and neuropsychological needs, Dr. Singh said. To be in the unit, patients had to be medically stable but with ongoing medical and rehabilitation needs and able to tolerate about half an hour of physical or occupational therapy each day.
The space was set up so that patients could interact with each other as well as staff, and this ability to share their experiences of trauma and recovery “led to an improved sense of psychological well-being and to healing,” according to Dr. Singh. Group therapy and meditation were also held several times a week.
“All this together, we thought we were really meeting the need for a lot of these patients from medical to psychosocial,” he said.
New York Presbyterian––Lower Manhattan Hospital also established a program called ICU Outreach to give hospitalists a “bird’s eye view” of the ICU in order to help move patients from unit to unit for optimized care. One hospitalist acted as a bridge between the ICU, the floors, and the emergency room.
The hospitalist on duty touched based with the ICU each day at 10 a.m., assessed the available beds, compiled a list of patients being discharged, met with all of the hospitalists and individual teams in inpatient and emergency services, and compiled a list of “watchers” – the sickest patients who needed help being managed.
The broad perspective was important, Dr. Singh said.
“We quickly found that each individual team or provider only knew the patients they were caring for, and the ICU Outreach person knew the whole big picture and could put the pieces together,” he said. “They could answer who was next in line for a bed, who benefited from a goals of care discussion, who could be managed on the floor with assistance. And this bridge, having this person fill this role, allowed the intensivists to focus on the patients they had in the unit.”
Palliative care and patient flow
Dr. Singh also described how hospitalists played an important role in palliative care for COVID patients. The hospital medicine team offered hospitalist palliative care services, which included COVIDtalk, a course on communicating about end of life, which helped to expand the pool of palliative care providers. Those trained were taught that these difficult conversations had to be honest and clear, with the goals of care addressed very early in the admission, should a patient decompensate soon after arrival.
A palliative “rapid response team” included a virtual hospitalist, a palliative care nurse practitioner, and a virtual psychiatrist – a team available 24 hours a day to have longer conversations so that clinicians could better tend to their patients when the in-person palliative care service was stretched thin, or at off hours like the middle of the night.
These innovations not only helped serve patients and families better, but also gave hospitalists training and experience in palliative care.
At Roper Hospital, Dr. Stein explained how hospitalists helped improve management of COVID patient flow. Depending on the time of day and the staffing on duty, there could be considerable confusion about where patients should go after the ED, or the COVID progressive unit, or the floor.
Hospitalists helped develop hospitalwide algorithms for escalating and deescalating acuity, Dr. Stein said, providing a “shared mental model for where a patient should go.”
“There are many ways hospitalists can and did rise to meet the unique demands of COVID,” Dr. Singh said, “whether it was innovating a new unit or service or work flow or leading a multidisciplinary team to extend or support other services that may have been strained.”
With intensive care units stretched to their limits – and beyond – during the COVID-19 pandemic, hospitalists became more central than ever in orchestrating the response.
At SHM Converge, the annual conference of the Society of Hospital Medicine, two hospitalists shared how their teams helped to develop new critical care units and strategies for best managing and allocating care to COVID patients in the ICU.
“The pandemic has been a selective pressure on us as a specialty,” said Jason Stein, MD, SFHM, a full-time clinical hospitalist at Roper Hospital, a 332-bed facility in Charleston, S.C.
Dr. Stein explained how hospitalists at Roper helped create the Progressive Care Unit – a negative-pressure unit with 12 high-flow oxygen beds overseen by a hospital medicine team, with the help of a respiratory therapist, pharmacist, and nurses. Patients in this unit had escalating acuity – quickly increasing oxygen needs – or deescalating acuity, such as ICU transfers, Dr. Stein said. Cardiac catheterization space was converted for the unit, which was intended to preserve beds in the hospital ICU for patients needing mechanical ventilation or vasoactive medication.
Interdisciplinary rounds – to assess oxygen and inflammatory marker trends, and run through a COVID care checklist – took place every day at 10 a.m.
“Consistency was the key,” Dr. Stein said.
At Weill Cornell Medical Center in New York, hospitalists helped build the COVID Recovery Unit, which was dedicated to the care of patients coming out of the ICU, said Vishwas Anand Singh, MD, MS, FHM, cochief of hospital medicine at New York Presbyterian–Lower Manhattan Hospital.
“The pandemic created an unprecedented need for critical care, and post-ICU care,” Dr. Singh said. “After extubation, patients remain very complicated and they have unique needs.”
The 30-bed COVID Recovery Unit – converted from a behavioral health unit – was designed to meet those needs. It was staffed by one lead hospitalist, 3 hospitalist physicians, 3 advanced practitioners, about 12 nurses and a neurologist, psychiatrist, and neuropsychologist.
The idea was to integrate medical care with careful attention to rehab and neuropsychological needs, Dr. Singh said. To be in the unit, patients had to be medically stable but with ongoing medical and rehabilitation needs and able to tolerate about half an hour of physical or occupational therapy each day.
The space was set up so that patients could interact with each other as well as staff, and this ability to share their experiences of trauma and recovery “led to an improved sense of psychological well-being and to healing,” according to Dr. Singh. Group therapy and meditation were also held several times a week.
“All this together, we thought we were really meeting the need for a lot of these patients from medical to psychosocial,” he said.
New York Presbyterian––Lower Manhattan Hospital also established a program called ICU Outreach to give hospitalists a “bird’s eye view” of the ICU in order to help move patients from unit to unit for optimized care. One hospitalist acted as a bridge between the ICU, the floors, and the emergency room.
The hospitalist on duty touched based with the ICU each day at 10 a.m., assessed the available beds, compiled a list of patients being discharged, met with all of the hospitalists and individual teams in inpatient and emergency services, and compiled a list of “watchers” – the sickest patients who needed help being managed.
The broad perspective was important, Dr. Singh said.
“We quickly found that each individual team or provider only knew the patients they were caring for, and the ICU Outreach person knew the whole big picture and could put the pieces together,” he said. “They could answer who was next in line for a bed, who benefited from a goals of care discussion, who could be managed on the floor with assistance. And this bridge, having this person fill this role, allowed the intensivists to focus on the patients they had in the unit.”
Palliative care and patient flow
Dr. Singh also described how hospitalists played an important role in palliative care for COVID patients. The hospital medicine team offered hospitalist palliative care services, which included COVIDtalk, a course on communicating about end of life, which helped to expand the pool of palliative care providers. Those trained were taught that these difficult conversations had to be honest and clear, with the goals of care addressed very early in the admission, should a patient decompensate soon after arrival.
A palliative “rapid response team” included a virtual hospitalist, a palliative care nurse practitioner, and a virtual psychiatrist – a team available 24 hours a day to have longer conversations so that clinicians could better tend to their patients when the in-person palliative care service was stretched thin, or at off hours like the middle of the night.
These innovations not only helped serve patients and families better, but also gave hospitalists training and experience in palliative care.
At Roper Hospital, Dr. Stein explained how hospitalists helped improve management of COVID patient flow. Depending on the time of day and the staffing on duty, there could be considerable confusion about where patients should go after the ED, or the COVID progressive unit, or the floor.
Hospitalists helped develop hospitalwide algorithms for escalating and deescalating acuity, Dr. Stein said, providing a “shared mental model for where a patient should go.”
“There are many ways hospitalists can and did rise to meet the unique demands of COVID,” Dr. Singh said, “whether it was innovating a new unit or service or work flow or leading a multidisciplinary team to extend or support other services that may have been strained.”
With intensive care units stretched to their limits – and beyond – during the COVID-19 pandemic, hospitalists became more central than ever in orchestrating the response.
At SHM Converge, the annual conference of the Society of Hospital Medicine, two hospitalists shared how their teams helped to develop new critical care units and strategies for best managing and allocating care to COVID patients in the ICU.
“The pandemic has been a selective pressure on us as a specialty,” said Jason Stein, MD, SFHM, a full-time clinical hospitalist at Roper Hospital, a 332-bed facility in Charleston, S.C.
Dr. Stein explained how hospitalists at Roper helped create the Progressive Care Unit – a negative-pressure unit with 12 high-flow oxygen beds overseen by a hospital medicine team, with the help of a respiratory therapist, pharmacist, and nurses. Patients in this unit had escalating acuity – quickly increasing oxygen needs – or deescalating acuity, such as ICU transfers, Dr. Stein said. Cardiac catheterization space was converted for the unit, which was intended to preserve beds in the hospital ICU for patients needing mechanical ventilation or vasoactive medication.
Interdisciplinary rounds – to assess oxygen and inflammatory marker trends, and run through a COVID care checklist – took place every day at 10 a.m.
“Consistency was the key,” Dr. Stein said.
At Weill Cornell Medical Center in New York, hospitalists helped build the COVID Recovery Unit, which was dedicated to the care of patients coming out of the ICU, said Vishwas Anand Singh, MD, MS, FHM, cochief of hospital medicine at New York Presbyterian–Lower Manhattan Hospital.
“The pandemic created an unprecedented need for critical care, and post-ICU care,” Dr. Singh said. “After extubation, patients remain very complicated and they have unique needs.”
The 30-bed COVID Recovery Unit – converted from a behavioral health unit – was designed to meet those needs. It was staffed by one lead hospitalist, 3 hospitalist physicians, 3 advanced practitioners, about 12 nurses and a neurologist, psychiatrist, and neuropsychologist.
The idea was to integrate medical care with careful attention to rehab and neuropsychological needs, Dr. Singh said. To be in the unit, patients had to be medically stable but with ongoing medical and rehabilitation needs and able to tolerate about half an hour of physical or occupational therapy each day.
The space was set up so that patients could interact with each other as well as staff, and this ability to share their experiences of trauma and recovery “led to an improved sense of psychological well-being and to healing,” according to Dr. Singh. Group therapy and meditation were also held several times a week.
“All this together, we thought we were really meeting the need for a lot of these patients from medical to psychosocial,” he said.
New York Presbyterian––Lower Manhattan Hospital also established a program called ICU Outreach to give hospitalists a “bird’s eye view” of the ICU in order to help move patients from unit to unit for optimized care. One hospitalist acted as a bridge between the ICU, the floors, and the emergency room.
The hospitalist on duty touched based with the ICU each day at 10 a.m., assessed the available beds, compiled a list of patients being discharged, met with all of the hospitalists and individual teams in inpatient and emergency services, and compiled a list of “watchers” – the sickest patients who needed help being managed.
The broad perspective was important, Dr. Singh said.
“We quickly found that each individual team or provider only knew the patients they were caring for, and the ICU Outreach person knew the whole big picture and could put the pieces together,” he said. “They could answer who was next in line for a bed, who benefited from a goals of care discussion, who could be managed on the floor with assistance. And this bridge, having this person fill this role, allowed the intensivists to focus on the patients they had in the unit.”
Palliative care and patient flow
Dr. Singh also described how hospitalists played an important role in palliative care for COVID patients. The hospital medicine team offered hospitalist palliative care services, which included COVIDtalk, a course on communicating about end of life, which helped to expand the pool of palliative care providers. Those trained were taught that these difficult conversations had to be honest and clear, with the goals of care addressed very early in the admission, should a patient decompensate soon after arrival.
A palliative “rapid response team” included a virtual hospitalist, a palliative care nurse practitioner, and a virtual psychiatrist – a team available 24 hours a day to have longer conversations so that clinicians could better tend to their patients when the in-person palliative care service was stretched thin, or at off hours like the middle of the night.
These innovations not only helped serve patients and families better, but also gave hospitalists training and experience in palliative care.
At Roper Hospital, Dr. Stein explained how hospitalists helped improve management of COVID patient flow. Depending on the time of day and the staffing on duty, there could be considerable confusion about where patients should go after the ED, or the COVID progressive unit, or the floor.
Hospitalists helped develop hospitalwide algorithms for escalating and deescalating acuity, Dr. Stein said, providing a “shared mental model for where a patient should go.”
“There are many ways hospitalists can and did rise to meet the unique demands of COVID,” Dr. Singh said, “whether it was innovating a new unit or service or work flow or leading a multidisciplinary team to extend or support other services that may have been strained.”
FROM SHM CONVERGE 2021
Hospital admissions of nursing home patients declined after ACA quality initiatives
Background: Following the ACA’s implementation, several measures were introduced to reduce unnecessary admissions of long-term nursing home residents to hospitals. These measures included an initiative to enhance a nursing home’s on-site capability to handle target populations; the accountable care organization payment model; and the Hospital Readmissions Reduction Program.
Study design: Cross-sectional study using the claims-based nationwide Minimum Data Set during 2011-2016.
Setting: Federally licensed nursing homes in the United States.
Synopsis: The authors examined the number of transfers between federally funded nursing homes and the hospital settings (EDs, observation, or inpatient hospitalizations) for greater than 460,000 long term–stay patients with advanced dementia, advanced heart failure, and/or advanced chronic obstructive pulmonary disease (COPD). A risk-adjusted model showed that, during 2011-2016, there were significant decreases in transfers rates for potentially avoidable conditions, measured as the mean number of transfers per person-year alive, for patients with advanced dementia (2.4 vs. 1.6), heart failure (8.5 vs. 6.7), and COPD (7.8 vs 5.5). Most of this decrease was linked to reductions in acute hospitalizations. Notably, hospice enrollment remained low throughout this time period, despite a high 1-year mortality.
Bottom line: During the 2011-2016 period, transfer rates for patients with advanced dementia, heart failure, and/or COPD from nursing homes to the hospital setting decreased.
Citation: McCarthy EP et al. Hospital transfer rates among U.S. nursing home residents with advanced illness before and after initiatives to reduce hospitalizations. JAMA Intern Med. 2019 Dec 30. doi: 10.1001/jamainternmed.2019.6130.
Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.
Background: Following the ACA’s implementation, several measures were introduced to reduce unnecessary admissions of long-term nursing home residents to hospitals. These measures included an initiative to enhance a nursing home’s on-site capability to handle target populations; the accountable care organization payment model; and the Hospital Readmissions Reduction Program.
Study design: Cross-sectional study using the claims-based nationwide Minimum Data Set during 2011-2016.
Setting: Federally licensed nursing homes in the United States.
Synopsis: The authors examined the number of transfers between federally funded nursing homes and the hospital settings (EDs, observation, or inpatient hospitalizations) for greater than 460,000 long term–stay patients with advanced dementia, advanced heart failure, and/or advanced chronic obstructive pulmonary disease (COPD). A risk-adjusted model showed that, during 2011-2016, there were significant decreases in transfers rates for potentially avoidable conditions, measured as the mean number of transfers per person-year alive, for patients with advanced dementia (2.4 vs. 1.6), heart failure (8.5 vs. 6.7), and COPD (7.8 vs 5.5). Most of this decrease was linked to reductions in acute hospitalizations. Notably, hospice enrollment remained low throughout this time period, despite a high 1-year mortality.
Bottom line: During the 2011-2016 period, transfer rates for patients with advanced dementia, heart failure, and/or COPD from nursing homes to the hospital setting decreased.
Citation: McCarthy EP et al. Hospital transfer rates among U.S. nursing home residents with advanced illness before and after initiatives to reduce hospitalizations. JAMA Intern Med. 2019 Dec 30. doi: 10.1001/jamainternmed.2019.6130.
Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.
Background: Following the ACA’s implementation, several measures were introduced to reduce unnecessary admissions of long-term nursing home residents to hospitals. These measures included an initiative to enhance a nursing home’s on-site capability to handle target populations; the accountable care organization payment model; and the Hospital Readmissions Reduction Program.
Study design: Cross-sectional study using the claims-based nationwide Minimum Data Set during 2011-2016.
Setting: Federally licensed nursing homes in the United States.
Synopsis: The authors examined the number of transfers between federally funded nursing homes and the hospital settings (EDs, observation, or inpatient hospitalizations) for greater than 460,000 long term–stay patients with advanced dementia, advanced heart failure, and/or advanced chronic obstructive pulmonary disease (COPD). A risk-adjusted model showed that, during 2011-2016, there were significant decreases in transfers rates for potentially avoidable conditions, measured as the mean number of transfers per person-year alive, for patients with advanced dementia (2.4 vs. 1.6), heart failure (8.5 vs. 6.7), and COPD (7.8 vs 5.5). Most of this decrease was linked to reductions in acute hospitalizations. Notably, hospice enrollment remained low throughout this time period, despite a high 1-year mortality.
Bottom line: During the 2011-2016 period, transfer rates for patients with advanced dementia, heart failure, and/or COPD from nursing homes to the hospital setting decreased.
Citation: McCarthy EP et al. Hospital transfer rates among U.S. nursing home residents with advanced illness before and after initiatives to reduce hospitalizations. JAMA Intern Med. 2019 Dec 30. doi: 10.1001/jamainternmed.2019.6130.
Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.
Microbiome therapeutic offers durable protection against C. difficile recurrence
SER-109, an oral microbiome therapeutic, safely protects against Clostridioides difficile recurrence for up to 24 weeks, according to a recent phase 3 trial. Three days of treatment with purified Firmicutes spores reduced risk of recurrence by 54%, suggesting a sustained, clinically meaningful response, according to a multicenter study presented at this year’s Digestive Disease Week® (DDW).
“Antibiotics targeted against C. difficile bacteria are necessary but insufficient to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome,” the investigators reported at the meeting.
“The manufacturing processes for SER-109 are designed to inactivate potential pathogens, while enriching for beneficial Firmicutes spores, which play a central role in inhibiting the cycle of C. difficile,” said Louis Y. Korman, MD, a gastroenterologist in Washington, who was lead author.
Extended data from ECOSPOR-III
The ECOSPOR-III trial involved 182 patients with at least three episodes of C. difficile infection in the previous 12 months. Patients underwent 10-21 days of antibiotic therapy with fidaxomicin or vancomycin to resolve symptoms before they were then randomized in a 1:1 ratio to receive either SER-109 (four capsules daily for 3 days) or placebo, with stratification by specific antibiotic and patient age (threshold of 65 years).
The primary objectives were safety and efficacy at 8 weeks. These results, which were previously reported at ACG 2020, showed a 68% relative risk reduction in the SER-109 group, and favorable safety data. The findings presented at DDW added to those earlier ones by providing safety and efficacy data extending to week 24. At this time point, patients treated with SER-109 had a 54% relative risk reduction in C. difficile recurrence. Recurrence rates were 21.3% and 47.3% for the treatment and placebo groups, respectively (P less than .001).
Patients 65 years and older benefited the most from SER-109 therapy, based on a relative risk reduction of 56% (P less than .001), versus a 49% relative risk reduction (lacking statistical significance) for patients younger than 65 years (P = .093). The specific antibiotic therapy patients received also appeared to impact outcomes. Patients treated with fidaxomicin had a 73% relative risk reduction (P = .009), compared with 48% for vancomycin (P = .006). Safety profiles were similar between study arms.
“By enriching for Firmicutes spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent C. difficile infection,” the investigators concluded, noting that “an open-label study for patients with recurrent C. difficile infection is currently enrolling.”
Microbiome restoration therapies
According to Sahil Khanna, MBBS, professor of medicine at Mayo Clinic, Rochester, Minn., these findings “advance the field” because they show a sustained response. “We know that microbiome restoration therapies help restore colonization resistance,” Dr. Khanna said in an interview, noting that they offer benefits comparable to fecal microbiota transplantation (FMT) without the downsides.
“The trouble with FMT is that it’s heterogenous – everybody does it differently … and also it’s an invasive procedure,” Dr. Khanna said. He noted that FMT may transmit infectious agents between donors and patients, which isn’t an issue with purified products such as SER-109.
Several other standardized microbiota restoration products are under development, Dr. Khanna said, including an enema form (RBX2660) in phase 3 testing, and two other capsules (CP101 and VE303) in phase 2 trials. “The hope would be that one or more of these products would be approved for clinical use in the near future and would probably replace the vast majority of FMT [procedures] that we do clinically,” Dr. Khanna said. “That’s where the field is headed.”
The investigators reported no conflicts of interest. Dr. Khanna disclosed research support from Finch, Rebiotix/Ferring, Vedanta, and Seres.
SER-109, an oral microbiome therapeutic, safely protects against Clostridioides difficile recurrence for up to 24 weeks, according to a recent phase 3 trial. Three days of treatment with purified Firmicutes spores reduced risk of recurrence by 54%, suggesting a sustained, clinically meaningful response, according to a multicenter study presented at this year’s Digestive Disease Week® (DDW).
“Antibiotics targeted against C. difficile bacteria are necessary but insufficient to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome,” the investigators reported at the meeting.
“The manufacturing processes for SER-109 are designed to inactivate potential pathogens, while enriching for beneficial Firmicutes spores, which play a central role in inhibiting the cycle of C. difficile,” said Louis Y. Korman, MD, a gastroenterologist in Washington, who was lead author.
Extended data from ECOSPOR-III
The ECOSPOR-III trial involved 182 patients with at least three episodes of C. difficile infection in the previous 12 months. Patients underwent 10-21 days of antibiotic therapy with fidaxomicin or vancomycin to resolve symptoms before they were then randomized in a 1:1 ratio to receive either SER-109 (four capsules daily for 3 days) or placebo, with stratification by specific antibiotic and patient age (threshold of 65 years).
The primary objectives were safety and efficacy at 8 weeks. These results, which were previously reported at ACG 2020, showed a 68% relative risk reduction in the SER-109 group, and favorable safety data. The findings presented at DDW added to those earlier ones by providing safety and efficacy data extending to week 24. At this time point, patients treated with SER-109 had a 54% relative risk reduction in C. difficile recurrence. Recurrence rates were 21.3% and 47.3% for the treatment and placebo groups, respectively (P less than .001).
Patients 65 years and older benefited the most from SER-109 therapy, based on a relative risk reduction of 56% (P less than .001), versus a 49% relative risk reduction (lacking statistical significance) for patients younger than 65 years (P = .093). The specific antibiotic therapy patients received also appeared to impact outcomes. Patients treated with fidaxomicin had a 73% relative risk reduction (P = .009), compared with 48% for vancomycin (P = .006). Safety profiles were similar between study arms.
“By enriching for Firmicutes spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent C. difficile infection,” the investigators concluded, noting that “an open-label study for patients with recurrent C. difficile infection is currently enrolling.”
Microbiome restoration therapies
According to Sahil Khanna, MBBS, professor of medicine at Mayo Clinic, Rochester, Minn., these findings “advance the field” because they show a sustained response. “We know that microbiome restoration therapies help restore colonization resistance,” Dr. Khanna said in an interview, noting that they offer benefits comparable to fecal microbiota transplantation (FMT) without the downsides.
“The trouble with FMT is that it’s heterogenous – everybody does it differently … and also it’s an invasive procedure,” Dr. Khanna said. He noted that FMT may transmit infectious agents between donors and patients, which isn’t an issue with purified products such as SER-109.
Several other standardized microbiota restoration products are under development, Dr. Khanna said, including an enema form (RBX2660) in phase 3 testing, and two other capsules (CP101 and VE303) in phase 2 trials. “The hope would be that one or more of these products would be approved for clinical use in the near future and would probably replace the vast majority of FMT [procedures] that we do clinically,” Dr. Khanna said. “That’s where the field is headed.”
The investigators reported no conflicts of interest. Dr. Khanna disclosed research support from Finch, Rebiotix/Ferring, Vedanta, and Seres.
SER-109, an oral microbiome therapeutic, safely protects against Clostridioides difficile recurrence for up to 24 weeks, according to a recent phase 3 trial. Three days of treatment with purified Firmicutes spores reduced risk of recurrence by 54%, suggesting a sustained, clinically meaningful response, according to a multicenter study presented at this year’s Digestive Disease Week® (DDW).
“Antibiotics targeted against C. difficile bacteria are necessary but insufficient to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome,” the investigators reported at the meeting.
“The manufacturing processes for SER-109 are designed to inactivate potential pathogens, while enriching for beneficial Firmicutes spores, which play a central role in inhibiting the cycle of C. difficile,” said Louis Y. Korman, MD, a gastroenterologist in Washington, who was lead author.
Extended data from ECOSPOR-III
The ECOSPOR-III trial involved 182 patients with at least three episodes of C. difficile infection in the previous 12 months. Patients underwent 10-21 days of antibiotic therapy with fidaxomicin or vancomycin to resolve symptoms before they were then randomized in a 1:1 ratio to receive either SER-109 (four capsules daily for 3 days) or placebo, with stratification by specific antibiotic and patient age (threshold of 65 years).
The primary objectives were safety and efficacy at 8 weeks. These results, which were previously reported at ACG 2020, showed a 68% relative risk reduction in the SER-109 group, and favorable safety data. The findings presented at DDW added to those earlier ones by providing safety and efficacy data extending to week 24. At this time point, patients treated with SER-109 had a 54% relative risk reduction in C. difficile recurrence. Recurrence rates were 21.3% and 47.3% for the treatment and placebo groups, respectively (P less than .001).
Patients 65 years and older benefited the most from SER-109 therapy, based on a relative risk reduction of 56% (P less than .001), versus a 49% relative risk reduction (lacking statistical significance) for patients younger than 65 years (P = .093). The specific antibiotic therapy patients received also appeared to impact outcomes. Patients treated with fidaxomicin had a 73% relative risk reduction (P = .009), compared with 48% for vancomycin (P = .006). Safety profiles were similar between study arms.
“By enriching for Firmicutes spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent C. difficile infection,” the investigators concluded, noting that “an open-label study for patients with recurrent C. difficile infection is currently enrolling.”
Microbiome restoration therapies
According to Sahil Khanna, MBBS, professor of medicine at Mayo Clinic, Rochester, Minn., these findings “advance the field” because they show a sustained response. “We know that microbiome restoration therapies help restore colonization resistance,” Dr. Khanna said in an interview, noting that they offer benefits comparable to fecal microbiota transplantation (FMT) without the downsides.
“The trouble with FMT is that it’s heterogenous – everybody does it differently … and also it’s an invasive procedure,” Dr. Khanna said. He noted that FMT may transmit infectious agents between donors and patients, which isn’t an issue with purified products such as SER-109.
Several other standardized microbiota restoration products are under development, Dr. Khanna said, including an enema form (RBX2660) in phase 3 testing, and two other capsules (CP101 and VE303) in phase 2 trials. “The hope would be that one or more of these products would be approved for clinical use in the near future and would probably replace the vast majority of FMT [procedures] that we do clinically,” Dr. Khanna said. “That’s where the field is headed.”
The investigators reported no conflicts of interest. Dr. Khanna disclosed research support from Finch, Rebiotix/Ferring, Vedanta, and Seres.
FROM DDW 2021