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iResident: Virtual care on hospital medicine teaching services during a pandemic
At the start of each shift on his clinical service with rotating internal medicine residents, Benji Mathews, MD, SFHM, now adds a few components to his usual preparation. First, visiting the Minnesota Department of Health and various organizational websites to review the latest COVID-19 updates and guidelines. Next comes checking to see where he needs to pick up the surgical mask and eye protection that he will need to wear through the day. Last, he evaluates which of his patients are in telemedicine-equipped rooms; this last change has fast become a crucial part of working with his resident learners during a pandemic.
During the COVID-19 pandemic, residents and residency programs find themselves in a unique situation. Balancing the educational needs of a training program with the safety of trainees is a challenging task, specifically when taking care of patients who are COVID-19 positive or patients under investigation (PUI). One increasingly available tool that can help protect trainees while continuing to prioritize patient care and medical education is the use of telemedicine for virtual rounding. For our internal medicine residents through the University of Minnesota Internal Medicine Residency program rotating at Regions Hospital in Saint Paul, Minn., we have used video visits to continue our mandate as both health care and education professionals.
Virtual care decision tree
Virtual care can mitigate exposure risk, minimize use of personal protective equipment (PPE), and improve communications with patients and their families. To guide our teaching teams on the optimal situations for telemedicine, we needed to select those patients who would be most appropriate for a virtual visit.
For example, patients with advanced dementia, or intubated in the intensive care unit, would have less utility from a real-time video encounter. Further, we implemented a simple decision tree (Figure 1). First, the team needs to decide whether the patient needs an immediate in-person assessment; for instance, for critically ill patients or those who need end-of-life care discussions, telemedicine would not be an appropriate modality. Next, the decision is made on whether a patient requires an in-person exam at that time. The idea of forgoing the in-person physical exam may run counterintuitive to the core training medical providers undergo, but in certain circumstances telemedicine can still provide the appropriate level of care a patient requires.
Virtual rounding with residents: Pros and cons
Through the course of this pandemic, there have many questions raised regarding how to handle inpatient teaching services: Should resident teams be assigned COVID-19 positives or PUIs? How do you optimize assessing and learning from patients’ conditions that require human touch? Should all members of the teaching team be donning PPE and entering the patient room?
Internal medicine residents in our hospital have been assigned COVID-19 positive and PUI patients. With proper PPE, and donning and doffing practices, residents may continue to learn from this important training opportunity while also optimizing care for patients supplemented by telemedicine. This pandemic has flattened the hierarchy; often residents are teaching their attendings much of the latest literature and best practices around COVID-19. Residents also benefit by joining the organization’s daily virtual interprofessional COVID-19 huddle where they partner with infectious disease, critical care, pharmacy, and other experts to collaborate in the care of these patients.
There have been counterarguments made for residents joining the front lines with COVID-19 patients. Some have conditions that limit them from seeing this subgroup of patients, such as their immune status or other issues. For these residents, we do not assign COVID-19–positive patients. However, they may continue to support in virtually updating COVID-19 patients and their families. A second argument has been the use of PPE. We have implemented telemedicine to limit the total number of exposures and have a protocol for the fewest number of providers possible to see any at-risk or confirmed COVID-19 patient. For example, a resident who sees a COVID-19 patient in person may also be simultaneously virtually supervised by the attending.
Webside manner
The physical exam is only one of several operational considerations when delivering virtual care, whether with a teaching or nonteaching service. One important aspect is the “webside manner” of the provider, the virtual analogue to bedside manner.
Inherent parts of in-person encounters, such as eye contact and allowing for patients to finish their sentences, have added nuances with virtual care. For instance, providers must adjust to looking into the web camera to make eye contact, even though the patient’s face may be on the screen below. Additionally, for patients who are hard of hearing or unfamiliar with video calling, providers must be cognizant of projecting well over an Internet connection and timing responses to avoid overlapping conversation.
Similarly, there are nuances to the virtual physical exam, some specific to care in the COVID-19 era. In our previous virtual care practice, a bedside facilitator assisted in using tools such a digital stethoscope. In contrast, our current practice aims to refine the observational skills of our learners in conjunction with chart review, vital signs, and actively incorporating the patient in the physical exam. This does not mean asking them to auscultate themselves, but is more toward allowing patients to participate in focused evaluations, such as assessing abdominal tenderness or working through range of motion. Remote guidance for virtual exams also extends itself to teaching teams; for example, in our practice, we have been able to conduct bedside ultrasound teaching with in-person team members and a virtual facilitator.
Maskless connections: ‘Face-to-face’ visits with patients
As many hospitalists have witnessed, COVID-19 is so isolating for patients and their families. Patients have limited visitors, and their care team members are aiming to minimize exposures. Those who are entering the rooms wear masks and face shields that limit connecting with patients in a truly “face-to-face” manner. Telemedicine provides a face-to-face encounter that arguably improves upon portions of the traditional in-person encounter during this pandemic, with providers wearing PPE. For medical learners, gaining the interpersonal skills essential for health care professionals has been skewed with pandemic-related limitations; telemedicine can provide a tool to adapt to this unique era and augment this important educational piece.
Limitations, equity, and technological considerations
Realistically, the virtual exam during COVID-19 does have its limitations. An important part of virtual care and teaching services is instilling the appropriate times for use of telemedicine. If a patient has a clinical change (such as increase in FiO2 requirements) or other clinical need, there should be no hesitation for learners to conduct in-person assessments with appropriate PPE.
Nonexam indications are just as important – for example, if a patient requires extensive goals of care counseling, we recommend this not be done virtually. Other indications may vary between organizations; in our practice, we suggest at least one in-person assessment on the initial and discharge hospital days. Regardless of the specific indications, a successful virtual inpatient teaching service must be predicated on outlining the appropriate uses of telemedicine.
In the United States, there are already health care disparities for people of color and non–English speakers. If there is not a careful consideration for these marginalized groups, their health disparities could be further exacerbated – not just around COVID-19, but also for other inpatient conditions where telemedicine is being used. Groups whose equity must be thoughtfully managed include those who do not speak English and those who do not have access to smartphones or the Internet. Our HealthPartners organization has implemented the integration of interpreters for virtual three-way connections with patients and their clinicians to help mitigate this for non–English speakers. Additionally, utilizing easy-to-use tablets and telemedicine-capable carts has helped patients overcome technology barriers.
Last, the members of the teaching team must know the essential technical aspects of the technology they are using. Robust information technology (IT) support is also needed, but no matter how simple the equipment may be, staff and trainees must know how to both operate it and handle basic troubleshooting (such as audio or video disconnections). This also dovetails with the important element of on-boarding other members of the care team. In our practice, nursing staff, chaplains, interpreters, and dietitians also use virtual care as part of their workflow. However, even if it is used only by the teaching team, orienting other care team members will limit technical problems such as equipment being turned off or moved out of position.
Prior to the COVID-19 pandemic, telemedicine adoption was limited because of lack of awareness, barriers in training, understanding, and narrow beliefs regarding the innovation. The COVID-19 pandemic has resulted in a remarkable increase in the provision of telemedicine services in the inpatient hospital medicine services. Importantly, it is, and should be, a developing part of the education and training for health care learners. This pandemic has underscored the need for providing telemedicine services that will likely long outlast this crisis, and to support our health care learners in being effective “iResidents” on our care teams.
Takeaways
- The future of graduate medical education involves virtual care.
The COVID-19 pandemic response has demonstrated that virtual care plays an instrumental part in patient care, and its effects will not dissipate when the pandemic is done. The curriculum for health care trainees should incorporate telemedicine competencies so that they may more effectively leverage this technology for improving care delivery.
- Selection of telemedicine patients must be stratified.
In order to obtain the highest utility for medical learners on telemedicine, there needs to be a clear decision process for which patients can be seen virtually. This involves both clinical criteria, such as avoiding virtual care for end-of-life discussions, and patient criteria, such as those who are hard of hearing.
- Virtual communication requires new communication skills.
Seeing patients via telemedicine mandates a different skill set than in-person communication. Learners must improve their “webside manner” in order to build the patient-provider relationship. Instilling these tools can pay dividends in settings where telemedicine has high yield, such as maskless communication during a pandemic.
- Health disparities could be further exacerbated by telemedicine and should not be overlooked.
Equity in access to health care applies to telemedicine as it does to many other elements. There are multiple groups that can suffer from disparities, such as patients who need interpreters, or those who have lower technological literacy and access to digital devices. Creating awareness of these pitfalls in virtual care can help medical learners recognize and support in creative solutions for these factors.
Dr. Mathews is chief, hospital medicine, at Regions Hospital, HealthPartners, St. Paul, Minn. Dr. Doshi is telemedicine director, hospital medicine, HealthPartners.
At the start of each shift on his clinical service with rotating internal medicine residents, Benji Mathews, MD, SFHM, now adds a few components to his usual preparation. First, visiting the Minnesota Department of Health and various organizational websites to review the latest COVID-19 updates and guidelines. Next comes checking to see where he needs to pick up the surgical mask and eye protection that he will need to wear through the day. Last, he evaluates which of his patients are in telemedicine-equipped rooms; this last change has fast become a crucial part of working with his resident learners during a pandemic.
During the COVID-19 pandemic, residents and residency programs find themselves in a unique situation. Balancing the educational needs of a training program with the safety of trainees is a challenging task, specifically when taking care of patients who are COVID-19 positive or patients under investigation (PUI). One increasingly available tool that can help protect trainees while continuing to prioritize patient care and medical education is the use of telemedicine for virtual rounding. For our internal medicine residents through the University of Minnesota Internal Medicine Residency program rotating at Regions Hospital in Saint Paul, Minn., we have used video visits to continue our mandate as both health care and education professionals.
Virtual care decision tree
Virtual care can mitigate exposure risk, minimize use of personal protective equipment (PPE), and improve communications with patients and their families. To guide our teaching teams on the optimal situations for telemedicine, we needed to select those patients who would be most appropriate for a virtual visit.
For example, patients with advanced dementia, or intubated in the intensive care unit, would have less utility from a real-time video encounter. Further, we implemented a simple decision tree (Figure 1). First, the team needs to decide whether the patient needs an immediate in-person assessment; for instance, for critically ill patients or those who need end-of-life care discussions, telemedicine would not be an appropriate modality. Next, the decision is made on whether a patient requires an in-person exam at that time. The idea of forgoing the in-person physical exam may run counterintuitive to the core training medical providers undergo, but in certain circumstances telemedicine can still provide the appropriate level of care a patient requires.
Virtual rounding with residents: Pros and cons
Through the course of this pandemic, there have many questions raised regarding how to handle inpatient teaching services: Should resident teams be assigned COVID-19 positives or PUIs? How do you optimize assessing and learning from patients’ conditions that require human touch? Should all members of the teaching team be donning PPE and entering the patient room?
Internal medicine residents in our hospital have been assigned COVID-19 positive and PUI patients. With proper PPE, and donning and doffing practices, residents may continue to learn from this important training opportunity while also optimizing care for patients supplemented by telemedicine. This pandemic has flattened the hierarchy; often residents are teaching their attendings much of the latest literature and best practices around COVID-19. Residents also benefit by joining the organization’s daily virtual interprofessional COVID-19 huddle where they partner with infectious disease, critical care, pharmacy, and other experts to collaborate in the care of these patients.
There have been counterarguments made for residents joining the front lines with COVID-19 patients. Some have conditions that limit them from seeing this subgroup of patients, such as their immune status or other issues. For these residents, we do not assign COVID-19–positive patients. However, they may continue to support in virtually updating COVID-19 patients and their families. A second argument has been the use of PPE. We have implemented telemedicine to limit the total number of exposures and have a protocol for the fewest number of providers possible to see any at-risk or confirmed COVID-19 patient. For example, a resident who sees a COVID-19 patient in person may also be simultaneously virtually supervised by the attending.
Webside manner
The physical exam is only one of several operational considerations when delivering virtual care, whether with a teaching or nonteaching service. One important aspect is the “webside manner” of the provider, the virtual analogue to bedside manner.
Inherent parts of in-person encounters, such as eye contact and allowing for patients to finish their sentences, have added nuances with virtual care. For instance, providers must adjust to looking into the web camera to make eye contact, even though the patient’s face may be on the screen below. Additionally, for patients who are hard of hearing or unfamiliar with video calling, providers must be cognizant of projecting well over an Internet connection and timing responses to avoid overlapping conversation.
Similarly, there are nuances to the virtual physical exam, some specific to care in the COVID-19 era. In our previous virtual care practice, a bedside facilitator assisted in using tools such a digital stethoscope. In contrast, our current practice aims to refine the observational skills of our learners in conjunction with chart review, vital signs, and actively incorporating the patient in the physical exam. This does not mean asking them to auscultate themselves, but is more toward allowing patients to participate in focused evaluations, such as assessing abdominal tenderness or working through range of motion. Remote guidance for virtual exams also extends itself to teaching teams; for example, in our practice, we have been able to conduct bedside ultrasound teaching with in-person team members and a virtual facilitator.
Maskless connections: ‘Face-to-face’ visits with patients
As many hospitalists have witnessed, COVID-19 is so isolating for patients and their families. Patients have limited visitors, and their care team members are aiming to minimize exposures. Those who are entering the rooms wear masks and face shields that limit connecting with patients in a truly “face-to-face” manner. Telemedicine provides a face-to-face encounter that arguably improves upon portions of the traditional in-person encounter during this pandemic, with providers wearing PPE. For medical learners, gaining the interpersonal skills essential for health care professionals has been skewed with pandemic-related limitations; telemedicine can provide a tool to adapt to this unique era and augment this important educational piece.
Limitations, equity, and technological considerations
Realistically, the virtual exam during COVID-19 does have its limitations. An important part of virtual care and teaching services is instilling the appropriate times for use of telemedicine. If a patient has a clinical change (such as increase in FiO2 requirements) or other clinical need, there should be no hesitation for learners to conduct in-person assessments with appropriate PPE.
Nonexam indications are just as important – for example, if a patient requires extensive goals of care counseling, we recommend this not be done virtually. Other indications may vary between organizations; in our practice, we suggest at least one in-person assessment on the initial and discharge hospital days. Regardless of the specific indications, a successful virtual inpatient teaching service must be predicated on outlining the appropriate uses of telemedicine.
In the United States, there are already health care disparities for people of color and non–English speakers. If there is not a careful consideration for these marginalized groups, their health disparities could be further exacerbated – not just around COVID-19, but also for other inpatient conditions where telemedicine is being used. Groups whose equity must be thoughtfully managed include those who do not speak English and those who do not have access to smartphones or the Internet. Our HealthPartners organization has implemented the integration of interpreters for virtual three-way connections with patients and their clinicians to help mitigate this for non–English speakers. Additionally, utilizing easy-to-use tablets and telemedicine-capable carts has helped patients overcome technology barriers.
Last, the members of the teaching team must know the essential technical aspects of the technology they are using. Robust information technology (IT) support is also needed, but no matter how simple the equipment may be, staff and trainees must know how to both operate it and handle basic troubleshooting (such as audio or video disconnections). This also dovetails with the important element of on-boarding other members of the care team. In our practice, nursing staff, chaplains, interpreters, and dietitians also use virtual care as part of their workflow. However, even if it is used only by the teaching team, orienting other care team members will limit technical problems such as equipment being turned off or moved out of position.
Prior to the COVID-19 pandemic, telemedicine adoption was limited because of lack of awareness, barriers in training, understanding, and narrow beliefs regarding the innovation. The COVID-19 pandemic has resulted in a remarkable increase in the provision of telemedicine services in the inpatient hospital medicine services. Importantly, it is, and should be, a developing part of the education and training for health care learners. This pandemic has underscored the need for providing telemedicine services that will likely long outlast this crisis, and to support our health care learners in being effective “iResidents” on our care teams.
Takeaways
- The future of graduate medical education involves virtual care.
The COVID-19 pandemic response has demonstrated that virtual care plays an instrumental part in patient care, and its effects will not dissipate when the pandemic is done. The curriculum for health care trainees should incorporate telemedicine competencies so that they may more effectively leverage this technology for improving care delivery.
- Selection of telemedicine patients must be stratified.
In order to obtain the highest utility for medical learners on telemedicine, there needs to be a clear decision process for which patients can be seen virtually. This involves both clinical criteria, such as avoiding virtual care for end-of-life discussions, and patient criteria, such as those who are hard of hearing.
- Virtual communication requires new communication skills.
Seeing patients via telemedicine mandates a different skill set than in-person communication. Learners must improve their “webside manner” in order to build the patient-provider relationship. Instilling these tools can pay dividends in settings where telemedicine has high yield, such as maskless communication during a pandemic.
- Health disparities could be further exacerbated by telemedicine and should not be overlooked.
Equity in access to health care applies to telemedicine as it does to many other elements. There are multiple groups that can suffer from disparities, such as patients who need interpreters, or those who have lower technological literacy and access to digital devices. Creating awareness of these pitfalls in virtual care can help medical learners recognize and support in creative solutions for these factors.
Dr. Mathews is chief, hospital medicine, at Regions Hospital, HealthPartners, St. Paul, Minn. Dr. Doshi is telemedicine director, hospital medicine, HealthPartners.
At the start of each shift on his clinical service with rotating internal medicine residents, Benji Mathews, MD, SFHM, now adds a few components to his usual preparation. First, visiting the Minnesota Department of Health and various organizational websites to review the latest COVID-19 updates and guidelines. Next comes checking to see where he needs to pick up the surgical mask and eye protection that he will need to wear through the day. Last, he evaluates which of his patients are in telemedicine-equipped rooms; this last change has fast become a crucial part of working with his resident learners during a pandemic.
During the COVID-19 pandemic, residents and residency programs find themselves in a unique situation. Balancing the educational needs of a training program with the safety of trainees is a challenging task, specifically when taking care of patients who are COVID-19 positive or patients under investigation (PUI). One increasingly available tool that can help protect trainees while continuing to prioritize patient care and medical education is the use of telemedicine for virtual rounding. For our internal medicine residents through the University of Minnesota Internal Medicine Residency program rotating at Regions Hospital in Saint Paul, Minn., we have used video visits to continue our mandate as both health care and education professionals.
Virtual care decision tree
Virtual care can mitigate exposure risk, minimize use of personal protective equipment (PPE), and improve communications with patients and their families. To guide our teaching teams on the optimal situations for telemedicine, we needed to select those patients who would be most appropriate for a virtual visit.
For example, patients with advanced dementia, or intubated in the intensive care unit, would have less utility from a real-time video encounter. Further, we implemented a simple decision tree (Figure 1). First, the team needs to decide whether the patient needs an immediate in-person assessment; for instance, for critically ill patients or those who need end-of-life care discussions, telemedicine would not be an appropriate modality. Next, the decision is made on whether a patient requires an in-person exam at that time. The idea of forgoing the in-person physical exam may run counterintuitive to the core training medical providers undergo, but in certain circumstances telemedicine can still provide the appropriate level of care a patient requires.
Virtual rounding with residents: Pros and cons
Through the course of this pandemic, there have many questions raised regarding how to handle inpatient teaching services: Should resident teams be assigned COVID-19 positives or PUIs? How do you optimize assessing and learning from patients’ conditions that require human touch? Should all members of the teaching team be donning PPE and entering the patient room?
Internal medicine residents in our hospital have been assigned COVID-19 positive and PUI patients. With proper PPE, and donning and doffing practices, residents may continue to learn from this important training opportunity while also optimizing care for patients supplemented by telemedicine. This pandemic has flattened the hierarchy; often residents are teaching their attendings much of the latest literature and best practices around COVID-19. Residents also benefit by joining the organization’s daily virtual interprofessional COVID-19 huddle where they partner with infectious disease, critical care, pharmacy, and other experts to collaborate in the care of these patients.
There have been counterarguments made for residents joining the front lines with COVID-19 patients. Some have conditions that limit them from seeing this subgroup of patients, such as their immune status or other issues. For these residents, we do not assign COVID-19–positive patients. However, they may continue to support in virtually updating COVID-19 patients and their families. A second argument has been the use of PPE. We have implemented telemedicine to limit the total number of exposures and have a protocol for the fewest number of providers possible to see any at-risk or confirmed COVID-19 patient. For example, a resident who sees a COVID-19 patient in person may also be simultaneously virtually supervised by the attending.
Webside manner
The physical exam is only one of several operational considerations when delivering virtual care, whether with a teaching or nonteaching service. One important aspect is the “webside manner” of the provider, the virtual analogue to bedside manner.
Inherent parts of in-person encounters, such as eye contact and allowing for patients to finish their sentences, have added nuances with virtual care. For instance, providers must adjust to looking into the web camera to make eye contact, even though the patient’s face may be on the screen below. Additionally, for patients who are hard of hearing or unfamiliar with video calling, providers must be cognizant of projecting well over an Internet connection and timing responses to avoid overlapping conversation.
Similarly, there are nuances to the virtual physical exam, some specific to care in the COVID-19 era. In our previous virtual care practice, a bedside facilitator assisted in using tools such a digital stethoscope. In contrast, our current practice aims to refine the observational skills of our learners in conjunction with chart review, vital signs, and actively incorporating the patient in the physical exam. This does not mean asking them to auscultate themselves, but is more toward allowing patients to participate in focused evaluations, such as assessing abdominal tenderness or working through range of motion. Remote guidance for virtual exams also extends itself to teaching teams; for example, in our practice, we have been able to conduct bedside ultrasound teaching with in-person team members and a virtual facilitator.
Maskless connections: ‘Face-to-face’ visits with patients
As many hospitalists have witnessed, COVID-19 is so isolating for patients and their families. Patients have limited visitors, and their care team members are aiming to minimize exposures. Those who are entering the rooms wear masks and face shields that limit connecting with patients in a truly “face-to-face” manner. Telemedicine provides a face-to-face encounter that arguably improves upon portions of the traditional in-person encounter during this pandemic, with providers wearing PPE. For medical learners, gaining the interpersonal skills essential for health care professionals has been skewed with pandemic-related limitations; telemedicine can provide a tool to adapt to this unique era and augment this important educational piece.
Limitations, equity, and technological considerations
Realistically, the virtual exam during COVID-19 does have its limitations. An important part of virtual care and teaching services is instilling the appropriate times for use of telemedicine. If a patient has a clinical change (such as increase in FiO2 requirements) or other clinical need, there should be no hesitation for learners to conduct in-person assessments with appropriate PPE.
Nonexam indications are just as important – for example, if a patient requires extensive goals of care counseling, we recommend this not be done virtually. Other indications may vary between organizations; in our practice, we suggest at least one in-person assessment on the initial and discharge hospital days. Regardless of the specific indications, a successful virtual inpatient teaching service must be predicated on outlining the appropriate uses of telemedicine.
In the United States, there are already health care disparities for people of color and non–English speakers. If there is not a careful consideration for these marginalized groups, their health disparities could be further exacerbated – not just around COVID-19, but also for other inpatient conditions where telemedicine is being used. Groups whose equity must be thoughtfully managed include those who do not speak English and those who do not have access to smartphones or the Internet. Our HealthPartners organization has implemented the integration of interpreters for virtual three-way connections with patients and their clinicians to help mitigate this for non–English speakers. Additionally, utilizing easy-to-use tablets and telemedicine-capable carts has helped patients overcome technology barriers.
Last, the members of the teaching team must know the essential technical aspects of the technology they are using. Robust information technology (IT) support is also needed, but no matter how simple the equipment may be, staff and trainees must know how to both operate it and handle basic troubleshooting (such as audio or video disconnections). This also dovetails with the important element of on-boarding other members of the care team. In our practice, nursing staff, chaplains, interpreters, and dietitians also use virtual care as part of their workflow. However, even if it is used only by the teaching team, orienting other care team members will limit technical problems such as equipment being turned off or moved out of position.
Prior to the COVID-19 pandemic, telemedicine adoption was limited because of lack of awareness, barriers in training, understanding, and narrow beliefs regarding the innovation. The COVID-19 pandemic has resulted in a remarkable increase in the provision of telemedicine services in the inpatient hospital medicine services. Importantly, it is, and should be, a developing part of the education and training for health care learners. This pandemic has underscored the need for providing telemedicine services that will likely long outlast this crisis, and to support our health care learners in being effective “iResidents” on our care teams.
Takeaways
- The future of graduate medical education involves virtual care.
The COVID-19 pandemic response has demonstrated that virtual care plays an instrumental part in patient care, and its effects will not dissipate when the pandemic is done. The curriculum for health care trainees should incorporate telemedicine competencies so that they may more effectively leverage this technology for improving care delivery.
- Selection of telemedicine patients must be stratified.
In order to obtain the highest utility for medical learners on telemedicine, there needs to be a clear decision process for which patients can be seen virtually. This involves both clinical criteria, such as avoiding virtual care for end-of-life discussions, and patient criteria, such as those who are hard of hearing.
- Virtual communication requires new communication skills.
Seeing patients via telemedicine mandates a different skill set than in-person communication. Learners must improve their “webside manner” in order to build the patient-provider relationship. Instilling these tools can pay dividends in settings where telemedicine has high yield, such as maskless communication during a pandemic.
- Health disparities could be further exacerbated by telemedicine and should not be overlooked.
Equity in access to health care applies to telemedicine as it does to many other elements. There are multiple groups that can suffer from disparities, such as patients who need interpreters, or those who have lower technological literacy and access to digital devices. Creating awareness of these pitfalls in virtual care can help medical learners recognize and support in creative solutions for these factors.
Dr. Mathews is chief, hospital medicine, at Regions Hospital, HealthPartners, St. Paul, Minn. Dr. Doshi is telemedicine director, hospital medicine, HealthPartners.
Apremilast and Systemic Retinoid Combination Treatment for Moderate to Severe Palmoplantar Psoriasis
To the Editor:
Psoriasis is a chronic inflammatory papulosquamous skin disease affecting 2% to 3% of the population.1 Its pathogenesis is multifactorial, consisting of a disrupted skin barrier and dysregulated immune activation.2
A wide armamentarium of topical and systemic treatments targeting different aspects of the disease pathogenesis have been developed over the years.3,4 Psoriasis was once considered a skin disease exclusively, but accumulating evidence suggests that it is accompanied by a multitude of systemic inflammatory comorbidities.5 This insight supports the concept of systemic treatment for patients with moderate to severe psoriasis. As a chronic disease, psoriasis requires continuous therapy. The treatment approach should focus on achieving efficacy and minimizing side effects. These goals can be achieved by combination, rotational, and sequential treatment approaches.6 Many therapeutic combinations have proven effective, using beneficially different mechanisms of action (MOAs) and toxicity profiles.7 We present a patient with moderate to severe recalcitrant palmoplantar psoriasis who demonstrated improvement with combination therapy.
A 50-year-old man presented with palmoplantar psoriasis of 7 years’ duration. His medical history included mild hyperlipidemia treated with atorvastatin. Prior topical treatments including calcipotriene, betamethasone dipropionate, and tacrolimus ointment did not result in improvement. Persistent acral involvement required further intervention, and the excimer laser was added to the therapeutic regimen with a minor additive therapeutic value. Acitretin (25 mg/d) was initiated; however, the disease flared up soon after. Acitretin was discontinued, and the patient was treated with apremilast (30 mg twice daily) for 9 months with a slight improvement. Physical examination revealed erythematous, fissured, scaly plaques involving both the palms and soles. Acitretin (25 mg/d) was reintroduced to the therapeutic regimen, and the acitretin-apremilast combination was used for 2 months. With this regimen, the patient experienced 90% improvement (Figures 1 and 2).
Palmoplantar psoriasis is a debilitating dermatosis that is extremely challenging to treat and is unresponsive to many modalities.8 Increased understanding of psoriasis mechanisms paved the path for the development of highly targeted biologic therapies9 with fewer side effects than drugs such as cyclosporine that indiscriminately neutralize multiple components of the immune system. Although highly specific, these targeted approaches are not without side effects10 and lead to diverse therapeutic outcomes, particularly when prescribed for palmoplantar psoriasis.11,12
The small-molecule inhibitor of phosphodiesterase 4—apremilast—was approved for plaque psoriasis treatment in late 2014. Although not fully elucidated, its MOA involves interfering with intracellular signaling, leading to increased intracellular cyclic adenosine monophosphate levels in inflammatory cells and keratinocytes.13 Proximal interruption of the pathologic cascade leads to the reduction of multiple proinflammatory cytokines with a simultaneous increase in anti-inflammatory mediators.13 Its efficacy and safety in the treatment of psoriasis have been shown in phase 2 and 3 clinical trials.14,15 In contrast to traditional oral therapies for psoriasis (ie, methotrexate, cyclosporine, acitretin), no laboratory test monitoring is needed and the safety profile is notably better.16
Acitretin, the active metabolite of etretinate, modulates epidermal differentiation and has immunomodulating activities.17 It commonly is used for treating palmoplantar psoriasis.8 Until recently, it was the only nonimmunosuppressive systemic treatment for psoriasis, and its combination with other systemic treatments, particularly biologics, has been advocated.18 Prior reports showed remarkable disease improvement when combining acitretin with alefacept, etanercept, infliximab, adalimumab, and ustekinumab.19 The optimal combination should include modalities with different MOAs without overlapping toxicities.19 Apremilast and acitretin have different MOAs and side-effect profiles, but another theoretical advantage is that they both interfere with intracellular signaling on the transcription level rather than affecting extracellular targets.13
Our patient with moderate to severe recalcitrant palmoplantar psoriasis demonstrated approximately 90% improvement following apremilast and acitretin combination therapy. This treatment regimen should be considered in cases of persistent acral disease resistant to other therapeutic efforts.
- Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516.
- Nograles KE, Davidovici B, Krueger JG. New insights in the immunologic basis of psoriasis. Semin Cutan Med Surg. 2010;29:3-9.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-485.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 3. guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60:643-659.
- Ryan C, Kirby B. Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities. Dermatol Clin. 2015;33:41-44.
- Lebwohl M, Menter A, Koo J, et al. Combination therapy to treat moderate to severe psoriasis. J Am Acad Dermatol. 2004;50:416-430.
- Cather JC, Menter A. Combining traditional agents and biologics for the treatment of psoriasis. Semin Cutan Med Surg. 2005;24:37-45.
- Janagond AB, Kanwar AJ, Handa S. Efficacy and safety of systemic methotrexate vs. acitretin in psoriasis patients with significant palmoplantar involvement: a prospective, randomized study. J Eur Acad Dermatol Venereol. 2013;27:E384-E389.
- Campa M, Mansouri B, Warren R, et al. A review of biologic therapies targeting IL-23 and IL-17 for use in moderate-to-severe plaque psoriasis [published online December 29, 2015]. Dermatol Ther (Heidelb). 2015;6:1-12.
- Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.
- Jacobi A, Schuler G, Hertl M. Differential clinical response to alefacept in combination with methotrexate in two patients with refractory palmar psoriasis. Br J Dermatol. 2007;156:178-180.
- Meyer V, Goerge T, Luger TA, et al. Successful treatment of palmoplantar hyperkeratotic psoriasis with a combination of etanercept and alitretinoin. J Clin Aesthet Dermatol. 2011;4:45-46.
- Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583-1590.
- Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73:37-49.
- Paul C, Cather J, Gooderham M, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol. 2015;173:1387-1399.
- Zerilli T, Ocheretyaner E. Apremilast (Otezla): a new oral treatment for adults with psoriasis and psoriatic arthritis. P T. 2015;40:495-500.
- Pilkington T, Brogden RN. Acitretin—a review of its pharmacology and therapeutic use. Drugs. 1992;43:597-627.
- Lebwohl M. Combining the new biologic agents with our current psoriasis armamentarium. J Am Acad Dermatol. 2003;49:S118-S124.
- Heinecke GM, Luber AJ, Levitt JO, et al. Combination use of ustekinumab with other systemic therapies: a retrospective study in a tertiary referral center. J Drugs Dermatol. 2013;12:1098-1102.
To the Editor:
Psoriasis is a chronic inflammatory papulosquamous skin disease affecting 2% to 3% of the population.1 Its pathogenesis is multifactorial, consisting of a disrupted skin barrier and dysregulated immune activation.2
A wide armamentarium of topical and systemic treatments targeting different aspects of the disease pathogenesis have been developed over the years.3,4 Psoriasis was once considered a skin disease exclusively, but accumulating evidence suggests that it is accompanied by a multitude of systemic inflammatory comorbidities.5 This insight supports the concept of systemic treatment for patients with moderate to severe psoriasis. As a chronic disease, psoriasis requires continuous therapy. The treatment approach should focus on achieving efficacy and minimizing side effects. These goals can be achieved by combination, rotational, and sequential treatment approaches.6 Many therapeutic combinations have proven effective, using beneficially different mechanisms of action (MOAs) and toxicity profiles.7 We present a patient with moderate to severe recalcitrant palmoplantar psoriasis who demonstrated improvement with combination therapy.
A 50-year-old man presented with palmoplantar psoriasis of 7 years’ duration. His medical history included mild hyperlipidemia treated with atorvastatin. Prior topical treatments including calcipotriene, betamethasone dipropionate, and tacrolimus ointment did not result in improvement. Persistent acral involvement required further intervention, and the excimer laser was added to the therapeutic regimen with a minor additive therapeutic value. Acitretin (25 mg/d) was initiated; however, the disease flared up soon after. Acitretin was discontinued, and the patient was treated with apremilast (30 mg twice daily) for 9 months with a slight improvement. Physical examination revealed erythematous, fissured, scaly plaques involving both the palms and soles. Acitretin (25 mg/d) was reintroduced to the therapeutic regimen, and the acitretin-apremilast combination was used for 2 months. With this regimen, the patient experienced 90% improvement (Figures 1 and 2).
Palmoplantar psoriasis is a debilitating dermatosis that is extremely challenging to treat and is unresponsive to many modalities.8 Increased understanding of psoriasis mechanisms paved the path for the development of highly targeted biologic therapies9 with fewer side effects than drugs such as cyclosporine that indiscriminately neutralize multiple components of the immune system. Although highly specific, these targeted approaches are not without side effects10 and lead to diverse therapeutic outcomes, particularly when prescribed for palmoplantar psoriasis.11,12
The small-molecule inhibitor of phosphodiesterase 4—apremilast—was approved for plaque psoriasis treatment in late 2014. Although not fully elucidated, its MOA involves interfering with intracellular signaling, leading to increased intracellular cyclic adenosine monophosphate levels in inflammatory cells and keratinocytes.13 Proximal interruption of the pathologic cascade leads to the reduction of multiple proinflammatory cytokines with a simultaneous increase in anti-inflammatory mediators.13 Its efficacy and safety in the treatment of psoriasis have been shown in phase 2 and 3 clinical trials.14,15 In contrast to traditional oral therapies for psoriasis (ie, methotrexate, cyclosporine, acitretin), no laboratory test monitoring is needed and the safety profile is notably better.16
Acitretin, the active metabolite of etretinate, modulates epidermal differentiation and has immunomodulating activities.17 It commonly is used for treating palmoplantar psoriasis.8 Until recently, it was the only nonimmunosuppressive systemic treatment for psoriasis, and its combination with other systemic treatments, particularly biologics, has been advocated.18 Prior reports showed remarkable disease improvement when combining acitretin with alefacept, etanercept, infliximab, adalimumab, and ustekinumab.19 The optimal combination should include modalities with different MOAs without overlapping toxicities.19 Apremilast and acitretin have different MOAs and side-effect profiles, but another theoretical advantage is that they both interfere with intracellular signaling on the transcription level rather than affecting extracellular targets.13
Our patient with moderate to severe recalcitrant palmoplantar psoriasis demonstrated approximately 90% improvement following apremilast and acitretin combination therapy. This treatment regimen should be considered in cases of persistent acral disease resistant to other therapeutic efforts.
To the Editor:
Psoriasis is a chronic inflammatory papulosquamous skin disease affecting 2% to 3% of the population.1 Its pathogenesis is multifactorial, consisting of a disrupted skin barrier and dysregulated immune activation.2
A wide armamentarium of topical and systemic treatments targeting different aspects of the disease pathogenesis have been developed over the years.3,4 Psoriasis was once considered a skin disease exclusively, but accumulating evidence suggests that it is accompanied by a multitude of systemic inflammatory comorbidities.5 This insight supports the concept of systemic treatment for patients with moderate to severe psoriasis. As a chronic disease, psoriasis requires continuous therapy. The treatment approach should focus on achieving efficacy and minimizing side effects. These goals can be achieved by combination, rotational, and sequential treatment approaches.6 Many therapeutic combinations have proven effective, using beneficially different mechanisms of action (MOAs) and toxicity profiles.7 We present a patient with moderate to severe recalcitrant palmoplantar psoriasis who demonstrated improvement with combination therapy.
A 50-year-old man presented with palmoplantar psoriasis of 7 years’ duration. His medical history included mild hyperlipidemia treated with atorvastatin. Prior topical treatments including calcipotriene, betamethasone dipropionate, and tacrolimus ointment did not result in improvement. Persistent acral involvement required further intervention, and the excimer laser was added to the therapeutic regimen with a minor additive therapeutic value. Acitretin (25 mg/d) was initiated; however, the disease flared up soon after. Acitretin was discontinued, and the patient was treated with apremilast (30 mg twice daily) for 9 months with a slight improvement. Physical examination revealed erythematous, fissured, scaly plaques involving both the palms and soles. Acitretin (25 mg/d) was reintroduced to the therapeutic regimen, and the acitretin-apremilast combination was used for 2 months. With this regimen, the patient experienced 90% improvement (Figures 1 and 2).
Palmoplantar psoriasis is a debilitating dermatosis that is extremely challenging to treat and is unresponsive to many modalities.8 Increased understanding of psoriasis mechanisms paved the path for the development of highly targeted biologic therapies9 with fewer side effects than drugs such as cyclosporine that indiscriminately neutralize multiple components of the immune system. Although highly specific, these targeted approaches are not without side effects10 and lead to diverse therapeutic outcomes, particularly when prescribed for palmoplantar psoriasis.11,12
The small-molecule inhibitor of phosphodiesterase 4—apremilast—was approved for plaque psoriasis treatment in late 2014. Although not fully elucidated, its MOA involves interfering with intracellular signaling, leading to increased intracellular cyclic adenosine monophosphate levels in inflammatory cells and keratinocytes.13 Proximal interruption of the pathologic cascade leads to the reduction of multiple proinflammatory cytokines with a simultaneous increase in anti-inflammatory mediators.13 Its efficacy and safety in the treatment of psoriasis have been shown in phase 2 and 3 clinical trials.14,15 In contrast to traditional oral therapies for psoriasis (ie, methotrexate, cyclosporine, acitretin), no laboratory test monitoring is needed and the safety profile is notably better.16
Acitretin, the active metabolite of etretinate, modulates epidermal differentiation and has immunomodulating activities.17 It commonly is used for treating palmoplantar psoriasis.8 Until recently, it was the only nonimmunosuppressive systemic treatment for psoriasis, and its combination with other systemic treatments, particularly biologics, has been advocated.18 Prior reports showed remarkable disease improvement when combining acitretin with alefacept, etanercept, infliximab, adalimumab, and ustekinumab.19 The optimal combination should include modalities with different MOAs without overlapping toxicities.19 Apremilast and acitretin have different MOAs and side-effect profiles, but another theoretical advantage is that they both interfere with intracellular signaling on the transcription level rather than affecting extracellular targets.13
Our patient with moderate to severe recalcitrant palmoplantar psoriasis demonstrated approximately 90% improvement following apremilast and acitretin combination therapy. This treatment regimen should be considered in cases of persistent acral disease resistant to other therapeutic efforts.
- Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516.
- Nograles KE, Davidovici B, Krueger JG. New insights in the immunologic basis of psoriasis. Semin Cutan Med Surg. 2010;29:3-9.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-485.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 3. guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60:643-659.
- Ryan C, Kirby B. Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities. Dermatol Clin. 2015;33:41-44.
- Lebwohl M, Menter A, Koo J, et al. Combination therapy to treat moderate to severe psoriasis. J Am Acad Dermatol. 2004;50:416-430.
- Cather JC, Menter A. Combining traditional agents and biologics for the treatment of psoriasis. Semin Cutan Med Surg. 2005;24:37-45.
- Janagond AB, Kanwar AJ, Handa S. Efficacy and safety of systemic methotrexate vs. acitretin in psoriasis patients with significant palmoplantar involvement: a prospective, randomized study. J Eur Acad Dermatol Venereol. 2013;27:E384-E389.
- Campa M, Mansouri B, Warren R, et al. A review of biologic therapies targeting IL-23 and IL-17 for use in moderate-to-severe plaque psoriasis [published online December 29, 2015]. Dermatol Ther (Heidelb). 2015;6:1-12.
- Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.
- Jacobi A, Schuler G, Hertl M. Differential clinical response to alefacept in combination with methotrexate in two patients with refractory palmar psoriasis. Br J Dermatol. 2007;156:178-180.
- Meyer V, Goerge T, Luger TA, et al. Successful treatment of palmoplantar hyperkeratotic psoriasis with a combination of etanercept and alitretinoin. J Clin Aesthet Dermatol. 2011;4:45-46.
- Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583-1590.
- Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73:37-49.
- Paul C, Cather J, Gooderham M, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol. 2015;173:1387-1399.
- Zerilli T, Ocheretyaner E. Apremilast (Otezla): a new oral treatment for adults with psoriasis and psoriatic arthritis. P T. 2015;40:495-500.
- Pilkington T, Brogden RN. Acitretin—a review of its pharmacology and therapeutic use. Drugs. 1992;43:597-627.
- Lebwohl M. Combining the new biologic agents with our current psoriasis armamentarium. J Am Acad Dermatol. 2003;49:S118-S124.
- Heinecke GM, Luber AJ, Levitt JO, et al. Combination use of ustekinumab with other systemic therapies: a retrospective study in a tertiary referral center. J Drugs Dermatol. 2013;12:1098-1102.
- Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516.
- Nograles KE, Davidovici B, Krueger JG. New insights in the immunologic basis of psoriasis. Semin Cutan Med Surg. 2010;29:3-9.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-485.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 3. guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60:643-659.
- Ryan C, Kirby B. Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities. Dermatol Clin. 2015;33:41-44.
- Lebwohl M, Menter A, Koo J, et al. Combination therapy to treat moderate to severe psoriasis. J Am Acad Dermatol. 2004;50:416-430.
- Cather JC, Menter A. Combining traditional agents and biologics for the treatment of psoriasis. Semin Cutan Med Surg. 2005;24:37-45.
- Janagond AB, Kanwar AJ, Handa S. Efficacy and safety of systemic methotrexate vs. acitretin in psoriasis patients with significant palmoplantar involvement: a prospective, randomized study. J Eur Acad Dermatol Venereol. 2013;27:E384-E389.
- Campa M, Mansouri B, Warren R, et al. A review of biologic therapies targeting IL-23 and IL-17 for use in moderate-to-severe plaque psoriasis [published online December 29, 2015]. Dermatol Ther (Heidelb). 2015;6:1-12.
- Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.
- Jacobi A, Schuler G, Hertl M. Differential clinical response to alefacept in combination with methotrexate in two patients with refractory palmar psoriasis. Br J Dermatol. 2007;156:178-180.
- Meyer V, Goerge T, Luger TA, et al. Successful treatment of palmoplantar hyperkeratotic psoriasis with a combination of etanercept and alitretinoin. J Clin Aesthet Dermatol. 2011;4:45-46.
- Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583-1590.
- Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73:37-49.
- Paul C, Cather J, Gooderham M, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol. 2015;173:1387-1399.
- Zerilli T, Ocheretyaner E. Apremilast (Otezla): a new oral treatment for adults with psoriasis and psoriatic arthritis. P T. 2015;40:495-500.
- Pilkington T, Brogden RN. Acitretin—a review of its pharmacology and therapeutic use. Drugs. 1992;43:597-627.
- Lebwohl M. Combining the new biologic agents with our current psoriasis armamentarium. J Am Acad Dermatol. 2003;49:S118-S124.
- Heinecke GM, Luber AJ, Levitt JO, et al. Combination use of ustekinumab with other systemic therapies: a retrospective study in a tertiary referral center. J Drugs Dermatol. 2013;12:1098-1102.
Practice Points
- Palmoplantar psoriasis is challenging to treat and is unresponsive to many modalities.
- Combination, rotational, and sequential treatment approaches may minimize side effects and loss of efficacy as well as enhance treatment responses.
- Apremilast and acitretin combination therapy led to 90% skin improvement in a case of severe recalcitrant palmoplantar psoriasis.
Sintilimab scintillates in first-line nonsquamous NSCLC
The investigational anti-PD-1 antibody sintilimab (Tyvyt, Innovent Biologics and Eli Lilly) has shown that it improves the efficacy of platinum-based chemotherapy in the first-line treatment of patients with advanced nonsquamous non–small cell lung cancer (NSCLC) in a phase 3 trial dubbed ORIENT-11.
The study was presented at the World Congress on Lung Cancer 2020 Virtual Presidential Symposium, held virtually due to the COVID-19 pandemic, on August 8. It was also published simultaneously in the Journal of Thoracic Oncology.
Sintilimab is a fully human IgG4 monoclonal antibody that blocks the binding of programmed death (PD)-1 to PD-ligand 1 (PD-L1) or PD-L2 with high affinity, and has received market authorization in China for the treatment of Hodgkin lymphoma.
For ORIENT-11, almost 400 patients with advanced nonsquamous NSCLC were randomly assigned to sintilimab or placebo plus pemetrexed and platinum-based chemotherapy in a 2:1 ratio.
“The addition of sintilimab to pemetrexed and platinum significantly improved PFS [progression-free survival], compared to placebo,” reducing progression rates by 52%, noted lead investigator Li Zhang, MD, professor of medical oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Crucially, this benefit “was seen across key clinical subgroups,” he added.
He noted that the overall response rate “was also improved, with a durable response,” while the results, which are not yet mature, suggest the experimental arm was associated with an overall survival (OS) benefit.
Study discussant Misako Nagasaka, MD, a thoracic oncologist and clinical investigator at Karmanos Cancer Institute, Detroit, said that the PFS benefit seen in the study is “certainly encouraging.”
Adding a note of caution, she continued: “But we have seen studies with PFS improvement which did not translate into OS improvement.
“Longer follow-up would allow events to mature and we will ultimately see if there would be a significant OS benefit,” she said.
Dr. Nagasaka also pointed out that the greater benefit with sintilimab seen in patients with high PD-L1 begs the question as to what would be the preferred regimen in those with higher or lower expression.
And, she said, this is not just about what regimen to choose but “more importantly, why?”
“Perhaps you’d like to use something with the best response rate, perhaps you’re sticking to a single agent immunotherapy because the toxicity profile is more favorable, or perhaps you [are] convinced with a certain regimen because of the robust PFS and OS data,” she said.
“Whatever you chose, there was a reason for your choice,” she said, adding that the sintilimab combination would have to “fulfill those reasons for you to consider choosing this regimen.”
Study details
Dr. Zhang began his presentation by noting that previous phase 1b studies have shown that sintilimab plus pemetrexed and platinum-based chemotherapy has a “tolerable safety profile and promising efficacy” in previously untreated non-squamous NSCLC.
They therefore conducted ORIENT-11, a randomized, double-blind, phase 3 study involving 397 patients with untreated stage IIIB/C or IV nonsquamous NSCLC who had neither EGFR nor ALK gene alterations.
The patients were randomly assigned in a 2:1 fashion to sintilimab plus pemetrexed and platinum-based chemotherapy (n = 266) or placebo plus pemetrexed and chemo (n = 131) for four cycles, followed by sintilimab or placebo plus pemetrexed for up to 24 months.
Thirty-five patients in the placebo arm crossed over to sintilimab monotherapy, representing 31.3% of the intention-to-treat population.
At the data cutoff of Nov. 15, 2019, 198 events had occurred, at a median follow-up of 8.9 months.
The team found that median PFS was significantly higher with sintilimab than placebo combination therapy, at 8.9 months vs. 5.0 months, or a hazard ratio of 0.482 (P < .00001).
Dr. Zhang noted that the benefit with sintilimab plus pemetrexed and platinum-based chemotherapy was seen across all subgroups.
However, it was notable that the impact of adding sintilimab on PFS was greater in patients with a tumor proportion score (TPS) ≥50%.
The HR for progression vs. the placebo treatment arm was 0.310, with median PFS not reached, which decreased to 0.503 in patients with a TPS of 1%-49% and 0.664 among those with a TPS <1%.
The results also showed that there was a “nominally significant improvement” in overall survival with sintilimab versus placebo, at a HR of 0.609 (P = 0.01921).
The ORR was markedly different between the sintilimab and placebo groups, at 51.9% vs. 29.8%, with the duration of response not reached in the sintilimab arm compared with 5.5 months in the placebo arm.
The sintilimab arm included three (1.1%) complete responses, which was not observed with pemetrexed and platinum-based chemotherapy alone.
Finally, Dr. Zhang observed that the safety profiles of the sintilimab and placebo arms were similar, with comparable rates of any, grade 3-5, and serious adverse events largely driven by high rates of chemotherapy-related events.
While there were fewer adverse events that led to death with sintilimab, at 2.3% vs. 6.9% with placebo, there were, as expected, more immune-related adverse events, at 43.2% vs. 36.6%, respectively.
Comparison with pembrolizumab
In her discussion, Dr. Nagasaka said that the first question that came to mind when she saw the results was: “How does the ORIENT-11 data compare with KEYNOTE-189?”
For that study, pembrolizumab (Keytruda, Merck) was added to pemetrexed plus carboplatin chemotherapy and compared with standard of care alone in patients with untreated metastatic nonsquamous NSCLC.
As reported by Medscape Medical News, pembrolizumab was associated with a 48% reduced risk of disease progression, as well as improved overall survival.
Dr. Nagasaka said that ORIENT-11 “had patients that tended to be younger, there were more males, more with performance status 1, and those who had never smoked” than those in KEYNOTE-189.
“But most importantly, KEYNOTE-189 had a very small number of patients from East Asia, only 1% in the pembro arm and 2.9% in the placebo arm.”
In contrast, all the patients included in ORIENT-11 were from East Asia, making the study of “high importance.”
She added that, “while across-trial comparisons must be taken with caution, the medium PFS of ORIENT-11 ... appears comparable to those of KEYNOTE-189,” while the HR “appears identical.”
This is despite median follow-up time in ORIENT-11 of “only” 8.9 months vs. a median of 23.1 months in the updated KEYNOTE-189 data.
There are plans to register the sintilimab combination therapy in China for the treatment of nonsquamous NSCLC, where it will go up against pembrolizumab as well as, potentially, tislelizumab (BeiGene).
The study was sponsored by Innovent Biologics and Eli Lilly. Dr. Zhang disclosed research grants from Eli Lilly and Pfizer. Dr. Nagasaka disclosed serving on the advisory boards of AstraZeneca, Daiichi Sankyo, Takeda, Novartis, and EMD Serono; as a consultant for Caris Life Sciences; and receiving travel support from An Hearts Therapeutics.
This article first appeared on Medscape.com.
The investigational anti-PD-1 antibody sintilimab (Tyvyt, Innovent Biologics and Eli Lilly) has shown that it improves the efficacy of platinum-based chemotherapy in the first-line treatment of patients with advanced nonsquamous non–small cell lung cancer (NSCLC) in a phase 3 trial dubbed ORIENT-11.
The study was presented at the World Congress on Lung Cancer 2020 Virtual Presidential Symposium, held virtually due to the COVID-19 pandemic, on August 8. It was also published simultaneously in the Journal of Thoracic Oncology.
Sintilimab is a fully human IgG4 monoclonal antibody that blocks the binding of programmed death (PD)-1 to PD-ligand 1 (PD-L1) or PD-L2 with high affinity, and has received market authorization in China for the treatment of Hodgkin lymphoma.
For ORIENT-11, almost 400 patients with advanced nonsquamous NSCLC were randomly assigned to sintilimab or placebo plus pemetrexed and platinum-based chemotherapy in a 2:1 ratio.
“The addition of sintilimab to pemetrexed and platinum significantly improved PFS [progression-free survival], compared to placebo,” reducing progression rates by 52%, noted lead investigator Li Zhang, MD, professor of medical oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Crucially, this benefit “was seen across key clinical subgroups,” he added.
He noted that the overall response rate “was also improved, with a durable response,” while the results, which are not yet mature, suggest the experimental arm was associated with an overall survival (OS) benefit.
Study discussant Misako Nagasaka, MD, a thoracic oncologist and clinical investigator at Karmanos Cancer Institute, Detroit, said that the PFS benefit seen in the study is “certainly encouraging.”
Adding a note of caution, she continued: “But we have seen studies with PFS improvement which did not translate into OS improvement.
“Longer follow-up would allow events to mature and we will ultimately see if there would be a significant OS benefit,” she said.
Dr. Nagasaka also pointed out that the greater benefit with sintilimab seen in patients with high PD-L1 begs the question as to what would be the preferred regimen in those with higher or lower expression.
And, she said, this is not just about what regimen to choose but “more importantly, why?”
“Perhaps you’d like to use something with the best response rate, perhaps you’re sticking to a single agent immunotherapy because the toxicity profile is more favorable, or perhaps you [are] convinced with a certain regimen because of the robust PFS and OS data,” she said.
“Whatever you chose, there was a reason for your choice,” she said, adding that the sintilimab combination would have to “fulfill those reasons for you to consider choosing this regimen.”
Study details
Dr. Zhang began his presentation by noting that previous phase 1b studies have shown that sintilimab plus pemetrexed and platinum-based chemotherapy has a “tolerable safety profile and promising efficacy” in previously untreated non-squamous NSCLC.
They therefore conducted ORIENT-11, a randomized, double-blind, phase 3 study involving 397 patients with untreated stage IIIB/C or IV nonsquamous NSCLC who had neither EGFR nor ALK gene alterations.
The patients were randomly assigned in a 2:1 fashion to sintilimab plus pemetrexed and platinum-based chemotherapy (n = 266) or placebo plus pemetrexed and chemo (n = 131) for four cycles, followed by sintilimab or placebo plus pemetrexed for up to 24 months.
Thirty-five patients in the placebo arm crossed over to sintilimab monotherapy, representing 31.3% of the intention-to-treat population.
At the data cutoff of Nov. 15, 2019, 198 events had occurred, at a median follow-up of 8.9 months.
The team found that median PFS was significantly higher with sintilimab than placebo combination therapy, at 8.9 months vs. 5.0 months, or a hazard ratio of 0.482 (P < .00001).
Dr. Zhang noted that the benefit with sintilimab plus pemetrexed and platinum-based chemotherapy was seen across all subgroups.
However, it was notable that the impact of adding sintilimab on PFS was greater in patients with a tumor proportion score (TPS) ≥50%.
The HR for progression vs. the placebo treatment arm was 0.310, with median PFS not reached, which decreased to 0.503 in patients with a TPS of 1%-49% and 0.664 among those with a TPS <1%.
The results also showed that there was a “nominally significant improvement” in overall survival with sintilimab versus placebo, at a HR of 0.609 (P = 0.01921).
The ORR was markedly different between the sintilimab and placebo groups, at 51.9% vs. 29.8%, with the duration of response not reached in the sintilimab arm compared with 5.5 months in the placebo arm.
The sintilimab arm included three (1.1%) complete responses, which was not observed with pemetrexed and platinum-based chemotherapy alone.
Finally, Dr. Zhang observed that the safety profiles of the sintilimab and placebo arms were similar, with comparable rates of any, grade 3-5, and serious adverse events largely driven by high rates of chemotherapy-related events.
While there were fewer adverse events that led to death with sintilimab, at 2.3% vs. 6.9% with placebo, there were, as expected, more immune-related adverse events, at 43.2% vs. 36.6%, respectively.
Comparison with pembrolizumab
In her discussion, Dr. Nagasaka said that the first question that came to mind when she saw the results was: “How does the ORIENT-11 data compare with KEYNOTE-189?”
For that study, pembrolizumab (Keytruda, Merck) was added to pemetrexed plus carboplatin chemotherapy and compared with standard of care alone in patients with untreated metastatic nonsquamous NSCLC.
As reported by Medscape Medical News, pembrolizumab was associated with a 48% reduced risk of disease progression, as well as improved overall survival.
Dr. Nagasaka said that ORIENT-11 “had patients that tended to be younger, there were more males, more with performance status 1, and those who had never smoked” than those in KEYNOTE-189.
“But most importantly, KEYNOTE-189 had a very small number of patients from East Asia, only 1% in the pembro arm and 2.9% in the placebo arm.”
In contrast, all the patients included in ORIENT-11 were from East Asia, making the study of “high importance.”
She added that, “while across-trial comparisons must be taken with caution, the medium PFS of ORIENT-11 ... appears comparable to those of KEYNOTE-189,” while the HR “appears identical.”
This is despite median follow-up time in ORIENT-11 of “only” 8.9 months vs. a median of 23.1 months in the updated KEYNOTE-189 data.
There are plans to register the sintilimab combination therapy in China for the treatment of nonsquamous NSCLC, where it will go up against pembrolizumab as well as, potentially, tislelizumab (BeiGene).
The study was sponsored by Innovent Biologics and Eli Lilly. Dr. Zhang disclosed research grants from Eli Lilly and Pfizer. Dr. Nagasaka disclosed serving on the advisory boards of AstraZeneca, Daiichi Sankyo, Takeda, Novartis, and EMD Serono; as a consultant for Caris Life Sciences; and receiving travel support from An Hearts Therapeutics.
This article first appeared on Medscape.com.
The investigational anti-PD-1 antibody sintilimab (Tyvyt, Innovent Biologics and Eli Lilly) has shown that it improves the efficacy of platinum-based chemotherapy in the first-line treatment of patients with advanced nonsquamous non–small cell lung cancer (NSCLC) in a phase 3 trial dubbed ORIENT-11.
The study was presented at the World Congress on Lung Cancer 2020 Virtual Presidential Symposium, held virtually due to the COVID-19 pandemic, on August 8. It was also published simultaneously in the Journal of Thoracic Oncology.
Sintilimab is a fully human IgG4 monoclonal antibody that blocks the binding of programmed death (PD)-1 to PD-ligand 1 (PD-L1) or PD-L2 with high affinity, and has received market authorization in China for the treatment of Hodgkin lymphoma.
For ORIENT-11, almost 400 patients with advanced nonsquamous NSCLC were randomly assigned to sintilimab or placebo plus pemetrexed and platinum-based chemotherapy in a 2:1 ratio.
“The addition of sintilimab to pemetrexed and platinum significantly improved PFS [progression-free survival], compared to placebo,” reducing progression rates by 52%, noted lead investigator Li Zhang, MD, professor of medical oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Crucially, this benefit “was seen across key clinical subgroups,” he added.
He noted that the overall response rate “was also improved, with a durable response,” while the results, which are not yet mature, suggest the experimental arm was associated with an overall survival (OS) benefit.
Study discussant Misako Nagasaka, MD, a thoracic oncologist and clinical investigator at Karmanos Cancer Institute, Detroit, said that the PFS benefit seen in the study is “certainly encouraging.”
Adding a note of caution, she continued: “But we have seen studies with PFS improvement which did not translate into OS improvement.
“Longer follow-up would allow events to mature and we will ultimately see if there would be a significant OS benefit,” she said.
Dr. Nagasaka also pointed out that the greater benefit with sintilimab seen in patients with high PD-L1 begs the question as to what would be the preferred regimen in those with higher or lower expression.
And, she said, this is not just about what regimen to choose but “more importantly, why?”
“Perhaps you’d like to use something with the best response rate, perhaps you’re sticking to a single agent immunotherapy because the toxicity profile is more favorable, or perhaps you [are] convinced with a certain regimen because of the robust PFS and OS data,” she said.
“Whatever you chose, there was a reason for your choice,” she said, adding that the sintilimab combination would have to “fulfill those reasons for you to consider choosing this regimen.”
Study details
Dr. Zhang began his presentation by noting that previous phase 1b studies have shown that sintilimab plus pemetrexed and platinum-based chemotherapy has a “tolerable safety profile and promising efficacy” in previously untreated non-squamous NSCLC.
They therefore conducted ORIENT-11, a randomized, double-blind, phase 3 study involving 397 patients with untreated stage IIIB/C or IV nonsquamous NSCLC who had neither EGFR nor ALK gene alterations.
The patients were randomly assigned in a 2:1 fashion to sintilimab plus pemetrexed and platinum-based chemotherapy (n = 266) or placebo plus pemetrexed and chemo (n = 131) for four cycles, followed by sintilimab or placebo plus pemetrexed for up to 24 months.
Thirty-five patients in the placebo arm crossed over to sintilimab monotherapy, representing 31.3% of the intention-to-treat population.
At the data cutoff of Nov. 15, 2019, 198 events had occurred, at a median follow-up of 8.9 months.
The team found that median PFS was significantly higher with sintilimab than placebo combination therapy, at 8.9 months vs. 5.0 months, or a hazard ratio of 0.482 (P < .00001).
Dr. Zhang noted that the benefit with sintilimab plus pemetrexed and platinum-based chemotherapy was seen across all subgroups.
However, it was notable that the impact of adding sintilimab on PFS was greater in patients with a tumor proportion score (TPS) ≥50%.
The HR for progression vs. the placebo treatment arm was 0.310, with median PFS not reached, which decreased to 0.503 in patients with a TPS of 1%-49% and 0.664 among those with a TPS <1%.
The results also showed that there was a “nominally significant improvement” in overall survival with sintilimab versus placebo, at a HR of 0.609 (P = 0.01921).
The ORR was markedly different between the sintilimab and placebo groups, at 51.9% vs. 29.8%, with the duration of response not reached in the sintilimab arm compared with 5.5 months in the placebo arm.
The sintilimab arm included three (1.1%) complete responses, which was not observed with pemetrexed and platinum-based chemotherapy alone.
Finally, Dr. Zhang observed that the safety profiles of the sintilimab and placebo arms were similar, with comparable rates of any, grade 3-5, and serious adverse events largely driven by high rates of chemotherapy-related events.
While there were fewer adverse events that led to death with sintilimab, at 2.3% vs. 6.9% with placebo, there were, as expected, more immune-related adverse events, at 43.2% vs. 36.6%, respectively.
Comparison with pembrolizumab
In her discussion, Dr. Nagasaka said that the first question that came to mind when she saw the results was: “How does the ORIENT-11 data compare with KEYNOTE-189?”
For that study, pembrolizumab (Keytruda, Merck) was added to pemetrexed plus carboplatin chemotherapy and compared with standard of care alone in patients with untreated metastatic nonsquamous NSCLC.
As reported by Medscape Medical News, pembrolizumab was associated with a 48% reduced risk of disease progression, as well as improved overall survival.
Dr. Nagasaka said that ORIENT-11 “had patients that tended to be younger, there were more males, more with performance status 1, and those who had never smoked” than those in KEYNOTE-189.
“But most importantly, KEYNOTE-189 had a very small number of patients from East Asia, only 1% in the pembro arm and 2.9% in the placebo arm.”
In contrast, all the patients included in ORIENT-11 were from East Asia, making the study of “high importance.”
She added that, “while across-trial comparisons must be taken with caution, the medium PFS of ORIENT-11 ... appears comparable to those of KEYNOTE-189,” while the HR “appears identical.”
This is despite median follow-up time in ORIENT-11 of “only” 8.9 months vs. a median of 23.1 months in the updated KEYNOTE-189 data.
There are plans to register the sintilimab combination therapy in China for the treatment of nonsquamous NSCLC, where it will go up against pembrolizumab as well as, potentially, tislelizumab (BeiGene).
The study was sponsored by Innovent Biologics and Eli Lilly. Dr. Zhang disclosed research grants from Eli Lilly and Pfizer. Dr. Nagasaka disclosed serving on the advisory boards of AstraZeneca, Daiichi Sankyo, Takeda, Novartis, and EMD Serono; as a consultant for Caris Life Sciences; and receiving travel support from An Hearts Therapeutics.
This article first appeared on Medscape.com.
Chemo-free management of mesothelioma on horizon
Patients with untreated mesothelioma may be able to avoid chemotherapy, say researchers reporting new survival data with the immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy).
The two approaches were compared in more than 600 patients with treatment-naive mesothelioma in the phase 3 CheckMate 743 trial, which was supported by the manufacturer of both immunotherapies, Bristol-Myers Squibb.
The trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported Paul Baas, MD, PhD, Netherlands Cancer Institute, Amsterdam, The Netherlands,
The combined nivo+ipi immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive, vs 27% in the chemotherapy group.
“This is the first positive randomized trial of dual immunotherapy in the first-line treatment of patients with mesothelioma,” he said. He suggested that it should therefore “be considered as a new standard of care.”
The data were presented on August 8 in the presidential symposium of the World Congress on Lung Cancer 2020, which was held online because of the COVID-19 pandemic.
A key analysis for the study was by histologic subgroup. It is known that standard-of-care chemotherapy performs better in patients with epithelioid as opposed to nonepithelioid tumor subtypes.
Bass highlighted that the performance of nivo+ipi was “almost the same” in patients with epithelioid and nonepithelioid tumors, at a median overall survival of 18.7 months and 18.1 months, respectively.
In contrast, overall survival in the chemotherapy arm was markedly lower in patients with nonepithelioid tumors, at 8.8 months vs 16.5 months among those with epithelioid tumors.
This was reflected in the hazard ratios for overall survival vs nivo+ipi, at 0.46 and 0.86, respectively, the latter nonsignificantly different from combination immunotherapy.
For study discussant Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester, United Kingdom, the epithet of a “new standard of care” for nivo+ipi should be reserved for nonepithelioid disease.
In this setting, he described the overall survival improvement as “transformative,” considering the “marked chemo resistance” of nonepithelioid tumors, which is “almost certainly” associated with epithelial-to-mesenchymal transition (EMT).
In the future, he suggested, combinations of chemotherapy and immunotherapy involving all histologies or selective targeting of nonepithelioid mesothelioma “could further extend the benefit for patients.”
Improving survival in mesothelioma
“We have been trying to improve the overall survival of patients with mesothelioma now for many decades,” Bass commented. Platinum-based chemotherapy plus pemetrexed is a standard of care, although the 5-year survival rate «is still below 10%,” he noted.
Randomized trials of single-agent immune checkpoint inhibitor therapy in the second-line treatment of patients with mesothelioma have not shown any significant benefits.
However, nivolumab and ipilimumab have a “complementary mechanism of action,” and two previous reports have indicated that together, they have clinical activity in the second-line setting.
The team conducted CheckMate 743 to determine the efficacy of the combination in the first-line setting.
The study involved 605 patients with pleural mesothelioma who had received no prior systemic therapy and had good performance status.
They were randomly assigned in a 1:1 ratio to receive nivo+ipi for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin until disease progression or unacceptable toxicity occurred.
“Patients could have a subsequent therapy,” Bass noted; 44.0% of patients in the experimental arm received subsequent therapy, vs 44.1% of those in the chemotherapy arm.
Of the latter, 20% received an immune checkpoint inhibitor as subsequent therapy.
The minimum follow-up for overall survival was 22.1 months; the median follow-up was 29.7 months.
Nivo+ipi was associated with a significant improvement in overall survival vs standard-of-care chemotherapy, at a median overall survival of 18.1 months vs 14.1 months, with a hazard ratio of 0.74 (P = .0020).
The results indicated that overall survival was similar across key subgroups, which suggests that “no subgroup was harmed” by nivo+ipi, Bass said.
Stratification by PD-LI expression
Stratifying the patients by the absence or presence of programmed cell death–ligand-1 (PD-L1) expression, the team found that the performance of nivo+ipi was “the same” as that of chemotherapy, Bass said.
“But in cases where there is any expression of PD-L1, the experimental arm performs better,” at an overall survival 18.0 months vs 13.3 months for chemotherapy and a hazard ratio of 0.69, he said.
There was no difference between the two treatment arms in progression-free survival. Chemotherapy performed better in the first 6 months of treatment, after which the nivo+ipi arm had lower event rates.
Nivo+ipi was also associated with a greater duration of response, at a median of 11.0 months vs 6.7 months for standard-of-care chemotherapy.
Moreover, at 24 months, 32% of nivo+ipi patients were still experiencing a response, whereas 8% of those in the chemotherapy arm were.
Treatment-related adverse events rates were almost identical between the two treatment groups, although treatment with nivo+ipi was associated with more grade 3/4 serious treatment-related adverse events, at 15 vs six for chemotherapy.
Choosing immunotherapy vs. chemotherapy
In his discussion of the new study, Fennell compared the current results with those from two studies, INITIATE and MAPS2. “What’s very clear is the response rate is slightly higher,” as is the disease control rate, he said.
This, he explained, “is perhaps not surprising, given that these two previous trials were in the relapse setting.”
He pointed out, however, that the progression-free survival data from those previous trials were “not a million miles away” from results seen in CheckMate 743, “suggesting that this immunotherapy does have significant activity in the relapse setting.”
For Fennell, the “pivotal data” are in patients with nonepithelioid tumors, particularly inasmuch as chemotherapy performed “poorly” in this setting, whereas it performs “as expected” in epithelioid mesothelioma.
He believes that the driver for this is the poor prognosis associated with sarcomatoid biphasic disease, a subtype characterized by increased expression of vimentin and ZEB1, proteins both associated with EMT.
“What does this mean?” Fennell asked.
“If you have have enrichment of EMT, what you see is increased drug resistance, increased invasiveness, something we know well with sarcomatoid mesotheliomas in particular, and this drug-resistance phenotype may account for the drug resistance that we see in CheckMate 743 with chemotherapy.
“This does not appear, however, to impact in any way the efficacy of the immunotherapy,” he noted.
Fennell believes that, with regard to both efficacy and safety, the balance is “very much in favor” of nivo+ipi in epithelioid mesothelioma, although there is less to choose between immunotherapy and chemotherapy in the nonepithelioid setting.
Indeed, the choice is “possible tilting slightly towards chemotherapy” in patients with the nonepithelioid tumors, owing to the lower rates of grade 3/4 serious treatment-related adverse events in comparison with combination immunotherapy.
The study was supported by Bristol-Myers Squibb. Bass has served on the advisory boards of MSD, AstraZeneca, and Takeda. Fennell has received research support from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, MSD, and Roche; research funding from Astex Therapeutics, Bayer, and Boehringer Ingelheim; has served on the speaker bureau of AstraZeneca, Boehringer Ingelheim, and Roche; has acted as a consultant for Bayer and Lab 21; and has served on the advisory board of Atara Biotherapeutics, Boehringer Ingelheim, and Inventiva.
This article first appeared on Medscape.com.
Patients with untreated mesothelioma may be able to avoid chemotherapy, say researchers reporting new survival data with the immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy).
The two approaches were compared in more than 600 patients with treatment-naive mesothelioma in the phase 3 CheckMate 743 trial, which was supported by the manufacturer of both immunotherapies, Bristol-Myers Squibb.
The trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported Paul Baas, MD, PhD, Netherlands Cancer Institute, Amsterdam, The Netherlands,
The combined nivo+ipi immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive, vs 27% in the chemotherapy group.
“This is the first positive randomized trial of dual immunotherapy in the first-line treatment of patients with mesothelioma,” he said. He suggested that it should therefore “be considered as a new standard of care.”
The data were presented on August 8 in the presidential symposium of the World Congress on Lung Cancer 2020, which was held online because of the COVID-19 pandemic.
A key analysis for the study was by histologic subgroup. It is known that standard-of-care chemotherapy performs better in patients with epithelioid as opposed to nonepithelioid tumor subtypes.
Bass highlighted that the performance of nivo+ipi was “almost the same” in patients with epithelioid and nonepithelioid tumors, at a median overall survival of 18.7 months and 18.1 months, respectively.
In contrast, overall survival in the chemotherapy arm was markedly lower in patients with nonepithelioid tumors, at 8.8 months vs 16.5 months among those with epithelioid tumors.
This was reflected in the hazard ratios for overall survival vs nivo+ipi, at 0.46 and 0.86, respectively, the latter nonsignificantly different from combination immunotherapy.
For study discussant Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester, United Kingdom, the epithet of a “new standard of care” for nivo+ipi should be reserved for nonepithelioid disease.
In this setting, he described the overall survival improvement as “transformative,” considering the “marked chemo resistance” of nonepithelioid tumors, which is “almost certainly” associated with epithelial-to-mesenchymal transition (EMT).
In the future, he suggested, combinations of chemotherapy and immunotherapy involving all histologies or selective targeting of nonepithelioid mesothelioma “could further extend the benefit for patients.”
Improving survival in mesothelioma
“We have been trying to improve the overall survival of patients with mesothelioma now for many decades,” Bass commented. Platinum-based chemotherapy plus pemetrexed is a standard of care, although the 5-year survival rate «is still below 10%,” he noted.
Randomized trials of single-agent immune checkpoint inhibitor therapy in the second-line treatment of patients with mesothelioma have not shown any significant benefits.
However, nivolumab and ipilimumab have a “complementary mechanism of action,” and two previous reports have indicated that together, they have clinical activity in the second-line setting.
The team conducted CheckMate 743 to determine the efficacy of the combination in the first-line setting.
The study involved 605 patients with pleural mesothelioma who had received no prior systemic therapy and had good performance status.
They were randomly assigned in a 1:1 ratio to receive nivo+ipi for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin until disease progression or unacceptable toxicity occurred.
“Patients could have a subsequent therapy,” Bass noted; 44.0% of patients in the experimental arm received subsequent therapy, vs 44.1% of those in the chemotherapy arm.
Of the latter, 20% received an immune checkpoint inhibitor as subsequent therapy.
The minimum follow-up for overall survival was 22.1 months; the median follow-up was 29.7 months.
Nivo+ipi was associated with a significant improvement in overall survival vs standard-of-care chemotherapy, at a median overall survival of 18.1 months vs 14.1 months, with a hazard ratio of 0.74 (P = .0020).
The results indicated that overall survival was similar across key subgroups, which suggests that “no subgroup was harmed” by nivo+ipi, Bass said.
Stratification by PD-LI expression
Stratifying the patients by the absence or presence of programmed cell death–ligand-1 (PD-L1) expression, the team found that the performance of nivo+ipi was “the same” as that of chemotherapy, Bass said.
“But in cases where there is any expression of PD-L1, the experimental arm performs better,” at an overall survival 18.0 months vs 13.3 months for chemotherapy and a hazard ratio of 0.69, he said.
There was no difference between the two treatment arms in progression-free survival. Chemotherapy performed better in the first 6 months of treatment, after which the nivo+ipi arm had lower event rates.
Nivo+ipi was also associated with a greater duration of response, at a median of 11.0 months vs 6.7 months for standard-of-care chemotherapy.
Moreover, at 24 months, 32% of nivo+ipi patients were still experiencing a response, whereas 8% of those in the chemotherapy arm were.
Treatment-related adverse events rates were almost identical between the two treatment groups, although treatment with nivo+ipi was associated with more grade 3/4 serious treatment-related adverse events, at 15 vs six for chemotherapy.
Choosing immunotherapy vs. chemotherapy
In his discussion of the new study, Fennell compared the current results with those from two studies, INITIATE and MAPS2. “What’s very clear is the response rate is slightly higher,” as is the disease control rate, he said.
This, he explained, “is perhaps not surprising, given that these two previous trials were in the relapse setting.”
He pointed out, however, that the progression-free survival data from those previous trials were “not a million miles away” from results seen in CheckMate 743, “suggesting that this immunotherapy does have significant activity in the relapse setting.”
For Fennell, the “pivotal data” are in patients with nonepithelioid tumors, particularly inasmuch as chemotherapy performed “poorly” in this setting, whereas it performs “as expected” in epithelioid mesothelioma.
He believes that the driver for this is the poor prognosis associated with sarcomatoid biphasic disease, a subtype characterized by increased expression of vimentin and ZEB1, proteins both associated with EMT.
“What does this mean?” Fennell asked.
“If you have have enrichment of EMT, what you see is increased drug resistance, increased invasiveness, something we know well with sarcomatoid mesotheliomas in particular, and this drug-resistance phenotype may account for the drug resistance that we see in CheckMate 743 with chemotherapy.
“This does not appear, however, to impact in any way the efficacy of the immunotherapy,” he noted.
Fennell believes that, with regard to both efficacy and safety, the balance is “very much in favor” of nivo+ipi in epithelioid mesothelioma, although there is less to choose between immunotherapy and chemotherapy in the nonepithelioid setting.
Indeed, the choice is “possible tilting slightly towards chemotherapy” in patients with the nonepithelioid tumors, owing to the lower rates of grade 3/4 serious treatment-related adverse events in comparison with combination immunotherapy.
The study was supported by Bristol-Myers Squibb. Bass has served on the advisory boards of MSD, AstraZeneca, and Takeda. Fennell has received research support from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, MSD, and Roche; research funding from Astex Therapeutics, Bayer, and Boehringer Ingelheim; has served on the speaker bureau of AstraZeneca, Boehringer Ingelheim, and Roche; has acted as a consultant for Bayer and Lab 21; and has served on the advisory board of Atara Biotherapeutics, Boehringer Ingelheim, and Inventiva.
This article first appeared on Medscape.com.
Patients with untreated mesothelioma may be able to avoid chemotherapy, say researchers reporting new survival data with the immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy).
The two approaches were compared in more than 600 patients with treatment-naive mesothelioma in the phase 3 CheckMate 743 trial, which was supported by the manufacturer of both immunotherapies, Bristol-Myers Squibb.
The trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported Paul Baas, MD, PhD, Netherlands Cancer Institute, Amsterdam, The Netherlands,
The combined nivo+ipi immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive, vs 27% in the chemotherapy group.
“This is the first positive randomized trial of dual immunotherapy in the first-line treatment of patients with mesothelioma,” he said. He suggested that it should therefore “be considered as a new standard of care.”
The data were presented on August 8 in the presidential symposium of the World Congress on Lung Cancer 2020, which was held online because of the COVID-19 pandemic.
A key analysis for the study was by histologic subgroup. It is known that standard-of-care chemotherapy performs better in patients with epithelioid as opposed to nonepithelioid tumor subtypes.
Bass highlighted that the performance of nivo+ipi was “almost the same” in patients with epithelioid and nonepithelioid tumors, at a median overall survival of 18.7 months and 18.1 months, respectively.
In contrast, overall survival in the chemotherapy arm was markedly lower in patients with nonepithelioid tumors, at 8.8 months vs 16.5 months among those with epithelioid tumors.
This was reflected in the hazard ratios for overall survival vs nivo+ipi, at 0.46 and 0.86, respectively, the latter nonsignificantly different from combination immunotherapy.
For study discussant Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester, United Kingdom, the epithet of a “new standard of care” for nivo+ipi should be reserved for nonepithelioid disease.
In this setting, he described the overall survival improvement as “transformative,” considering the “marked chemo resistance” of nonepithelioid tumors, which is “almost certainly” associated with epithelial-to-mesenchymal transition (EMT).
In the future, he suggested, combinations of chemotherapy and immunotherapy involving all histologies or selective targeting of nonepithelioid mesothelioma “could further extend the benefit for patients.”
Improving survival in mesothelioma
“We have been trying to improve the overall survival of patients with mesothelioma now for many decades,” Bass commented. Platinum-based chemotherapy plus pemetrexed is a standard of care, although the 5-year survival rate «is still below 10%,” he noted.
Randomized trials of single-agent immune checkpoint inhibitor therapy in the second-line treatment of patients with mesothelioma have not shown any significant benefits.
However, nivolumab and ipilimumab have a “complementary mechanism of action,” and two previous reports have indicated that together, they have clinical activity in the second-line setting.
The team conducted CheckMate 743 to determine the efficacy of the combination in the first-line setting.
The study involved 605 patients with pleural mesothelioma who had received no prior systemic therapy and had good performance status.
They were randomly assigned in a 1:1 ratio to receive nivo+ipi for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin until disease progression or unacceptable toxicity occurred.
“Patients could have a subsequent therapy,” Bass noted; 44.0% of patients in the experimental arm received subsequent therapy, vs 44.1% of those in the chemotherapy arm.
Of the latter, 20% received an immune checkpoint inhibitor as subsequent therapy.
The minimum follow-up for overall survival was 22.1 months; the median follow-up was 29.7 months.
Nivo+ipi was associated with a significant improvement in overall survival vs standard-of-care chemotherapy, at a median overall survival of 18.1 months vs 14.1 months, with a hazard ratio of 0.74 (P = .0020).
The results indicated that overall survival was similar across key subgroups, which suggests that “no subgroup was harmed” by nivo+ipi, Bass said.
Stratification by PD-LI expression
Stratifying the patients by the absence or presence of programmed cell death–ligand-1 (PD-L1) expression, the team found that the performance of nivo+ipi was “the same” as that of chemotherapy, Bass said.
“But in cases where there is any expression of PD-L1, the experimental arm performs better,” at an overall survival 18.0 months vs 13.3 months for chemotherapy and a hazard ratio of 0.69, he said.
There was no difference between the two treatment arms in progression-free survival. Chemotherapy performed better in the first 6 months of treatment, after which the nivo+ipi arm had lower event rates.
Nivo+ipi was also associated with a greater duration of response, at a median of 11.0 months vs 6.7 months for standard-of-care chemotherapy.
Moreover, at 24 months, 32% of nivo+ipi patients were still experiencing a response, whereas 8% of those in the chemotherapy arm were.
Treatment-related adverse events rates were almost identical between the two treatment groups, although treatment with nivo+ipi was associated with more grade 3/4 serious treatment-related adverse events, at 15 vs six for chemotherapy.
Choosing immunotherapy vs. chemotherapy
In his discussion of the new study, Fennell compared the current results with those from two studies, INITIATE and MAPS2. “What’s very clear is the response rate is slightly higher,” as is the disease control rate, he said.
This, he explained, “is perhaps not surprising, given that these two previous trials were in the relapse setting.”
He pointed out, however, that the progression-free survival data from those previous trials were “not a million miles away” from results seen in CheckMate 743, “suggesting that this immunotherapy does have significant activity in the relapse setting.”
For Fennell, the “pivotal data” are in patients with nonepithelioid tumors, particularly inasmuch as chemotherapy performed “poorly” in this setting, whereas it performs “as expected” in epithelioid mesothelioma.
He believes that the driver for this is the poor prognosis associated with sarcomatoid biphasic disease, a subtype characterized by increased expression of vimentin and ZEB1, proteins both associated with EMT.
“What does this mean?” Fennell asked.
“If you have have enrichment of EMT, what you see is increased drug resistance, increased invasiveness, something we know well with sarcomatoid mesotheliomas in particular, and this drug-resistance phenotype may account for the drug resistance that we see in CheckMate 743 with chemotherapy.
“This does not appear, however, to impact in any way the efficacy of the immunotherapy,” he noted.
Fennell believes that, with regard to both efficacy and safety, the balance is “very much in favor” of nivo+ipi in epithelioid mesothelioma, although there is less to choose between immunotherapy and chemotherapy in the nonepithelioid setting.
Indeed, the choice is “possible tilting slightly towards chemotherapy” in patients with the nonepithelioid tumors, owing to the lower rates of grade 3/4 serious treatment-related adverse events in comparison with combination immunotherapy.
The study was supported by Bristol-Myers Squibb. Bass has served on the advisory boards of MSD, AstraZeneca, and Takeda. Fennell has received research support from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, MSD, and Roche; research funding from Astex Therapeutics, Bayer, and Boehringer Ingelheim; has served on the speaker bureau of AstraZeneca, Boehringer Ingelheim, and Roche; has acted as a consultant for Bayer and Lab 21; and has served on the advisory board of Atara Biotherapeutics, Boehringer Ingelheim, and Inventiva.
This article first appeared on Medscape.com.
Extensive Purpura and Necrosis of the Leg
The Diagnosis: Disseminated Mucormycosis
Histopathologic examination of a 6-mm punch biopsy of the edge of the lesion revealed numerous intravascular, broad, nonseptate hyphae in the deep vessels and perivascular dermis that stained bright red with periodic acid-Schiff (Figure). Acid-fast bacilli and Gram stains were negative. Tissue culture grew Rhizopus species. Given the patient's overall poor prognosis, her family decided to pursue hospice care following this diagnosis.
Mucormycosis (formerly zygomycosis) refers to infections from a variety of genera of fungi, most commonly Mucor and Rhizopus, that cause infections primarily in immunocompromised individuals.1 Mucormycosis infections are characterized by tissue necrosis that results from invasion of the vasculature and subsequent thrombosis. The typical presentation of cutaneous mucormycosis is a necrotic eschar accompanied by surrounding erythema and induration.2 Diagnosis is based on clinical suspicion, requiring additional testing with skin biopsy and tissue cultures for confirmation.
Cutaneous infection is the third most common presentation of mucormycosis, following rhinocerebral and pulmonary involvement.1 Although rhinocerebral and pulmonary infections normally are caused by inhalation of spores, cutaneous mucormycosis typically is caused by local inoculation, often following skin trauma.2 The skin is the most common location of iatrogenic mucormycosis, often from skin injury related to surgery, catheters, and adhesive tape.3 Most patients with cutaneous mucormycosis have underlying conditions such as hematologic malignancies, diabetes mellitus, or immunosuppression.1 However, outbreaks have occurred in immunocompetent patients following natural disasters.4 Cutaneous mucormycosis disseminates in 13% to 20% of cases in which mortality rates typically exceed 90%.1
Treatment consists of prompt surgical debridement and antifungal agents such as amphotericin B, posaconazole, and isavuconazonium sulfate.1 Our patient had multiple risk factors for infection, including hematopoietic stem cell transplantation, prolonged neutropenia, and treatment with eculizumab, a monoclonal antibody against C5 that blocks the terminal complement cascade. Eculizumab has been associated with increased risk for meningococcemia,5 but the association with mucormycosis is rare. We highlight the importance of recognizing and promptly diagnosing cutaneous mucormycosis given the difficulty of treating this disease and its poor prognosis.
Disseminated aspergillosis demonstrates septate rather than nonseptate hyphae on biopsy. Disseminated intravascular coagulation and purpura fulminans may be associated with thrombocytopenia but demonstrate thrombotic microangiopathy on biopsy. Pyoderma gangrenosum demonstrates neutrophilic infiltrate on biopsy.
- Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41:634-653.
- Petrikkos G, Skiada A, Lortholary O, et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012;54(suppl 1):S23-S34.
- Rammaert B, Lanternier F, Zahar JR, et al. Healthcare-associated mucormycosis. Clin Infect Dis. 2012;54(suppl 1):S44-S54.
- Neblett Fanfair R, Benedict K, Bos J, et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N Engl J Med. 2012;367:2214-2225.
- McNamara LA, Topaz N, Wang X, et al. High risk for invasive meningococcal disease among patients receiving eculizumab (Soliris) despite receipt of meningococcal vaccine. MMWR Morb Mortal Wkly Rep. 2017;66:734-737.
The Diagnosis: Disseminated Mucormycosis
Histopathologic examination of a 6-mm punch biopsy of the edge of the lesion revealed numerous intravascular, broad, nonseptate hyphae in the deep vessels and perivascular dermis that stained bright red with periodic acid-Schiff (Figure). Acid-fast bacilli and Gram stains were negative. Tissue culture grew Rhizopus species. Given the patient's overall poor prognosis, her family decided to pursue hospice care following this diagnosis.
Mucormycosis (formerly zygomycosis) refers to infections from a variety of genera of fungi, most commonly Mucor and Rhizopus, that cause infections primarily in immunocompromised individuals.1 Mucormycosis infections are characterized by tissue necrosis that results from invasion of the vasculature and subsequent thrombosis. The typical presentation of cutaneous mucormycosis is a necrotic eschar accompanied by surrounding erythema and induration.2 Diagnosis is based on clinical suspicion, requiring additional testing with skin biopsy and tissue cultures for confirmation.
Cutaneous infection is the third most common presentation of mucormycosis, following rhinocerebral and pulmonary involvement.1 Although rhinocerebral and pulmonary infections normally are caused by inhalation of spores, cutaneous mucormycosis typically is caused by local inoculation, often following skin trauma.2 The skin is the most common location of iatrogenic mucormycosis, often from skin injury related to surgery, catheters, and adhesive tape.3 Most patients with cutaneous mucormycosis have underlying conditions such as hematologic malignancies, diabetes mellitus, or immunosuppression.1 However, outbreaks have occurred in immunocompetent patients following natural disasters.4 Cutaneous mucormycosis disseminates in 13% to 20% of cases in which mortality rates typically exceed 90%.1
Treatment consists of prompt surgical debridement and antifungal agents such as amphotericin B, posaconazole, and isavuconazonium sulfate.1 Our patient had multiple risk factors for infection, including hematopoietic stem cell transplantation, prolonged neutropenia, and treatment with eculizumab, a monoclonal antibody against C5 that blocks the terminal complement cascade. Eculizumab has been associated with increased risk for meningococcemia,5 but the association with mucormycosis is rare. We highlight the importance of recognizing and promptly diagnosing cutaneous mucormycosis given the difficulty of treating this disease and its poor prognosis.
Disseminated aspergillosis demonstrates septate rather than nonseptate hyphae on biopsy. Disseminated intravascular coagulation and purpura fulminans may be associated with thrombocytopenia but demonstrate thrombotic microangiopathy on biopsy. Pyoderma gangrenosum demonstrates neutrophilic infiltrate on biopsy.
The Diagnosis: Disseminated Mucormycosis
Histopathologic examination of a 6-mm punch biopsy of the edge of the lesion revealed numerous intravascular, broad, nonseptate hyphae in the deep vessels and perivascular dermis that stained bright red with periodic acid-Schiff (Figure). Acid-fast bacilli and Gram stains were negative. Tissue culture grew Rhizopus species. Given the patient's overall poor prognosis, her family decided to pursue hospice care following this diagnosis.
Mucormycosis (formerly zygomycosis) refers to infections from a variety of genera of fungi, most commonly Mucor and Rhizopus, that cause infections primarily in immunocompromised individuals.1 Mucormycosis infections are characterized by tissue necrosis that results from invasion of the vasculature and subsequent thrombosis. The typical presentation of cutaneous mucormycosis is a necrotic eschar accompanied by surrounding erythema and induration.2 Diagnosis is based on clinical suspicion, requiring additional testing with skin biopsy and tissue cultures for confirmation.
Cutaneous infection is the third most common presentation of mucormycosis, following rhinocerebral and pulmonary involvement.1 Although rhinocerebral and pulmonary infections normally are caused by inhalation of spores, cutaneous mucormycosis typically is caused by local inoculation, often following skin trauma.2 The skin is the most common location of iatrogenic mucormycosis, often from skin injury related to surgery, catheters, and adhesive tape.3 Most patients with cutaneous mucormycosis have underlying conditions such as hematologic malignancies, diabetes mellitus, or immunosuppression.1 However, outbreaks have occurred in immunocompetent patients following natural disasters.4 Cutaneous mucormycosis disseminates in 13% to 20% of cases in which mortality rates typically exceed 90%.1
Treatment consists of prompt surgical debridement and antifungal agents such as amphotericin B, posaconazole, and isavuconazonium sulfate.1 Our patient had multiple risk factors for infection, including hematopoietic stem cell transplantation, prolonged neutropenia, and treatment with eculizumab, a monoclonal antibody against C5 that blocks the terminal complement cascade. Eculizumab has been associated with increased risk for meningococcemia,5 but the association with mucormycosis is rare. We highlight the importance of recognizing and promptly diagnosing cutaneous mucormycosis given the difficulty of treating this disease and its poor prognosis.
Disseminated aspergillosis demonstrates septate rather than nonseptate hyphae on biopsy. Disseminated intravascular coagulation and purpura fulminans may be associated with thrombocytopenia but demonstrate thrombotic microangiopathy on biopsy. Pyoderma gangrenosum demonstrates neutrophilic infiltrate on biopsy.
- Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41:634-653.
- Petrikkos G, Skiada A, Lortholary O, et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012;54(suppl 1):S23-S34.
- Rammaert B, Lanternier F, Zahar JR, et al. Healthcare-associated mucormycosis. Clin Infect Dis. 2012;54(suppl 1):S44-S54.
- Neblett Fanfair R, Benedict K, Bos J, et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N Engl J Med. 2012;367:2214-2225.
- McNamara LA, Topaz N, Wang X, et al. High risk for invasive meningococcal disease among patients receiving eculizumab (Soliris) despite receipt of meningococcal vaccine. MMWR Morb Mortal Wkly Rep. 2017;66:734-737.
- Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41:634-653.
- Petrikkos G, Skiada A, Lortholary O, et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012;54(suppl 1):S23-S34.
- Rammaert B, Lanternier F, Zahar JR, et al. Healthcare-associated mucormycosis. Clin Infect Dis. 2012;54(suppl 1):S44-S54.
- Neblett Fanfair R, Benedict K, Bos J, et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N Engl J Med. 2012;367:2214-2225.
- McNamara LA, Topaz N, Wang X, et al. High risk for invasive meningococcal disease among patients receiving eculizumab (Soliris) despite receipt of meningococcal vaccine. MMWR Morb Mortal Wkly Rep. 2017;66:734-737.
A 57-year-old woman presented with expanding purpura on the left leg of 2 weeks’ duration following a recent hematopoietic stem cell transplant for refractory diffuse large B-cell lymphoma. Prior to dermatologic consultation, the patient had been hospitalized for 2 months following the transplant due to Clostridium difficile colitis, Enterococcus faecium bacteremia, cardiac arrest, delayed engraftment with pancytopenia, and atypical hemolytic uremic syndrome with acute renal failure requiring hemodialysis and treatment with eculizumab. Her care team in the hospital initially noticed a small purpuric lesion on the posterior aspect of the left knee. The patient subsequently developed persistent fevers and expansion of the lesion, which prompted consultation of the dermatology service. Physical examination revealed a 22×10-cm, rectangular, indurated, purpuric plaque with central dusky, violaceous to black necrosis with superficial skin sloughing and peripheral dusky erythema extending from the inner thigh to the lower leg. The left distal leg felt cool, and both dorsalis pedis and posterior tibial pulses were absent. Laboratory test results revealed neutropenia and thrombocytopenia (white blood cell count, 0.2×103 /mm3 [reference range, 5–10×103 /mm3 ]; hematocrit, 23.2% [reference range, 41%–50%]; platelet count, 105×103 /µL [reference range, 150–350×103 /µL]). A punch biopsy was performed.
Chloroquine linked to serious psychiatric side effects
Chloroquine may be associated with serious psychiatric side effects, even in patients with no family or personal history of psychiatric disorders, a new review suggests.
In a letter to the editor published online July 28 in The Journal of Clinical Psychiatry, the authors summarize data from several studies published as far back as 1993 and as recently as May 2020.
“In addition to previously reported side effects, chloroquine could also induce psychiatric side effects which are polymorphic and can persist even after stopping the drug,” lead author Florence Gressier, MD, PhD, CESP, Inserm, department of psychiatry, Le Kremlin Bicêtre, France, said in an interview.
“In COVID-19 patients who may still be [undergoing treatment] with chloroquine, close psychiatric assessment and monitoring should be performed,” she said.
Heated controversy
Following findings of a small French study that suggested efficacy in lowering the viral load in patients with COVID-19, President Donald Trump expressed optimism regarding the role of hydroxychloroquine in treating COVID-19, calling it a “game changer”.
Other studies, however, have called into question both the efficacy and the safety of hydroxychloroquine in treating COVID-19. On June 15, the Food and Drug Administration revoked the emergency use authorization it had given in March to chloroquine and hydroxychloroquine for the treatment of COVID-19.
Nevertheless, hydroxychloroquine continues to be prescribed for COVID-19. For example, an article that appeared in Click2Houston on June 15 quoted the chief medical officer of Houston’s United Memorial Center as saying he plans to continue prescribing hydroxychloroquine for patients with COVID-19 until he finds a better alternative.
As discussed in a Medscape expert commentary, a group of physicians who held a “white coat summit” in front of the U.S. Supreme Court building promoted the use of hydroxychloroquine for the treatment of COVID-19. The video of their summit was retweeted by President Trump and garnered millions of views before it was taken down by Twitter, Facebook, and YouTube.
Sudden onset
For the new review, “we wanted to alert the public and practitioners on the potentially psychiatric risks induced by chloroquine, as it could be taken as self-medication or potentially still prescribed,” Dr. Gressier said.
“We think the format of the letter to the editor allows information to be provided in a concise and clear manner,” she added.
According to the FDA’s Adverse Event Reporting System database, 12% of reported adverse events (520 of 4,336) following the use of chloroquine that occurred between the fourth quarter of 2012 and the fourth quarter of 2019 were neuropsychiatric. These events included amnesia, delirium, hallucinations, depression, and loss of consciousness, the authors write.
The researchers acknowledged that the incidence of psychiatric adverse effects associated with the use of chloroquine is “unclear in the absence of high-quality, randomized placebo-controlled trials of its safety.” Nevertheless, they pointed out that there have been reports of insomnia and depression when the drug was used as prophylaxis against malaria .
Moreover, some case series or case reports describe symptoms such as depression, anxiety, agitation, violent outburst, suicidal ideation, and psychosis in patients who have been treated with chloroquine for malaria, lupus erythematosus, and rheumatoid arthritis .
“In contrast to many other psychoses, chloroquine psychosis may be more affective and include prominent visual hallucinations, symptoms of derealization, and disorders of thought, with preserved insight,” the authors wrote.
They noted that the frequency of symptoms does not appear to be connected to the cumulative dose or the duration of treatment, and the onset of psychosis or other adverse effects is usually “sudden.”
In addition, they warn that the drug’s psychiatric effects may go unnoticed, especially because COVID-19 itself has been associated with neuropsychiatric symptoms, making it hard to distinguish between symptoms caused by the illness and those caused by the drug.
Although the psychiatric symptoms typically occur early after treatment initiation, some “subtle” symptoms might persist after stopping the drug, possibly owing to its “extremely long” half-life, the authors stated.
Dr. Gressier noted that practicing clinicians should look up reports about self-medication with chloroquine “and warn their patients about the risk induced by chloroquine.”
Safe but ‘not benign’
Nilanjana Bose, MD, MBA, a rheumatologist at the Rheumatology Center of Houston, said she uses hydroxychloroquine “all the time” in clinical practice to treat patients with rheumatic conditions.
“I cannot comment on whether it [hydroxychloroquine or chloroquine] is a potential prophylactic or treatment for COVID-19, but I can say that, from a safety point of view, as a rheumatologist who uses hydroxychloroquine at a dose of 400 mg/day, I do not think we need to worry about serious [psychiatric] side effects,” Dr. Bose said in an interview.
Because clinicians are trying all types of possible treatments for COVID-19, “if this medication has possible efficacy, it is a great medicine from a rheumatologic perspective and is safe,” she added.
Nevertheless, the drug is “not benign, and regular side effects will be there, and of course, higher doses will cause more side effects,” said Dr. Bose, who was not involved in authoring the letter.
She counsels patients about potential psychiatric side effects of hydroxychloroquine because some of her patients have complained about irritability, worsening anxiety and depression, and difficulty sleeping.
Be wary
James “Jimmy” Potash, MD, MPH, Henry Phipps Professor of Psychiatry and Behavioral Sciences, Johns Hopkins Medicine, Baltimore, said in an interview that the “take-home message of this letter is that serious psychiatric effects, psychotic illness in particular,” can occur in individuals who take chloroquine and hydroxychloroquine.
In addition, “these are potentially very concerning side effects that psychiatrists should be aware of,” noted Dr. Potash, department director and psychiatrist-in-chief at Johns Hopkins.
He said that one of his patients who had been “completely psychiatrically healthy” took chloroquine prophylactically prior to traveling overseas. After she began taking the drug, she had an episode of mania that resolved once she discontinued the medication and received treatment for the mania.
“If you add potential psychiatric side effects to the other side effects that can result from these medications, that adds up to a pretty important reason to be wary of taking them, particularly for the indication of COVID-19, where the level of evidence that it helps in any way is still quite weak,” Dr. Potash said.
In an interview, Remington Nevin, MD, MPH, DrPH, executive director at the Quinism Foundation, White River Junction, Vt., a nonprofit organization that supports and promotes education and research on disorders caused by poisoning by quinoline drugs; and faculty associate in the department of mental health at Johns Hopkins Bloomberg School of Public Health, said that the authors of the letter “are to be commended for their efforts in raising awareness of the potentially lasting and disabling psychiatric effects of chloroquine and hydroxychloroquine, which, as with similar effects from other synthetic quinoline antimalarials, have occasionally been overlooked or misattributed to other conditions.”
He added: “I have proposed that the chronic neuropsychiatric effects of this class of drug are best considered not as side effects but as signs and symptoms of a disorder known as chronic quinoline encephalopathy caused by poisoning of the central nervous system.”
Dr. Gressier and the other letter authors, Dr. Bose, and Dr. Potash have reported no relevant financial relationships. Dr. Nevin has been retained as a consultant and expert witness in legal cases involving claims of adverse effects from quinoline antimalarial drugs.
A version of this article originally appeared on Medscape.com.
Chloroquine may be associated with serious psychiatric side effects, even in patients with no family or personal history of psychiatric disorders, a new review suggests.
In a letter to the editor published online July 28 in The Journal of Clinical Psychiatry, the authors summarize data from several studies published as far back as 1993 and as recently as May 2020.
“In addition to previously reported side effects, chloroquine could also induce psychiatric side effects which are polymorphic and can persist even after stopping the drug,” lead author Florence Gressier, MD, PhD, CESP, Inserm, department of psychiatry, Le Kremlin Bicêtre, France, said in an interview.
“In COVID-19 patients who may still be [undergoing treatment] with chloroquine, close psychiatric assessment and monitoring should be performed,” she said.
Heated controversy
Following findings of a small French study that suggested efficacy in lowering the viral load in patients with COVID-19, President Donald Trump expressed optimism regarding the role of hydroxychloroquine in treating COVID-19, calling it a “game changer”.
Other studies, however, have called into question both the efficacy and the safety of hydroxychloroquine in treating COVID-19. On June 15, the Food and Drug Administration revoked the emergency use authorization it had given in March to chloroquine and hydroxychloroquine for the treatment of COVID-19.
Nevertheless, hydroxychloroquine continues to be prescribed for COVID-19. For example, an article that appeared in Click2Houston on June 15 quoted the chief medical officer of Houston’s United Memorial Center as saying he plans to continue prescribing hydroxychloroquine for patients with COVID-19 until he finds a better alternative.
As discussed in a Medscape expert commentary, a group of physicians who held a “white coat summit” in front of the U.S. Supreme Court building promoted the use of hydroxychloroquine for the treatment of COVID-19. The video of their summit was retweeted by President Trump and garnered millions of views before it was taken down by Twitter, Facebook, and YouTube.
Sudden onset
For the new review, “we wanted to alert the public and practitioners on the potentially psychiatric risks induced by chloroquine, as it could be taken as self-medication or potentially still prescribed,” Dr. Gressier said.
“We think the format of the letter to the editor allows information to be provided in a concise and clear manner,” she added.
According to the FDA’s Adverse Event Reporting System database, 12% of reported adverse events (520 of 4,336) following the use of chloroquine that occurred between the fourth quarter of 2012 and the fourth quarter of 2019 were neuropsychiatric. These events included amnesia, delirium, hallucinations, depression, and loss of consciousness, the authors write.
The researchers acknowledged that the incidence of psychiatric adverse effects associated with the use of chloroquine is “unclear in the absence of high-quality, randomized placebo-controlled trials of its safety.” Nevertheless, they pointed out that there have been reports of insomnia and depression when the drug was used as prophylaxis against malaria .
Moreover, some case series or case reports describe symptoms such as depression, anxiety, agitation, violent outburst, suicidal ideation, and psychosis in patients who have been treated with chloroquine for malaria, lupus erythematosus, and rheumatoid arthritis .
“In contrast to many other psychoses, chloroquine psychosis may be more affective and include prominent visual hallucinations, symptoms of derealization, and disorders of thought, with preserved insight,” the authors wrote.
They noted that the frequency of symptoms does not appear to be connected to the cumulative dose or the duration of treatment, and the onset of psychosis or other adverse effects is usually “sudden.”
In addition, they warn that the drug’s psychiatric effects may go unnoticed, especially because COVID-19 itself has been associated with neuropsychiatric symptoms, making it hard to distinguish between symptoms caused by the illness and those caused by the drug.
Although the psychiatric symptoms typically occur early after treatment initiation, some “subtle” symptoms might persist after stopping the drug, possibly owing to its “extremely long” half-life, the authors stated.
Dr. Gressier noted that practicing clinicians should look up reports about self-medication with chloroquine “and warn their patients about the risk induced by chloroquine.”
Safe but ‘not benign’
Nilanjana Bose, MD, MBA, a rheumatologist at the Rheumatology Center of Houston, said she uses hydroxychloroquine “all the time” in clinical practice to treat patients with rheumatic conditions.
“I cannot comment on whether it [hydroxychloroquine or chloroquine] is a potential prophylactic or treatment for COVID-19, but I can say that, from a safety point of view, as a rheumatologist who uses hydroxychloroquine at a dose of 400 mg/day, I do not think we need to worry about serious [psychiatric] side effects,” Dr. Bose said in an interview.
Because clinicians are trying all types of possible treatments for COVID-19, “if this medication has possible efficacy, it is a great medicine from a rheumatologic perspective and is safe,” she added.
Nevertheless, the drug is “not benign, and regular side effects will be there, and of course, higher doses will cause more side effects,” said Dr. Bose, who was not involved in authoring the letter.
She counsels patients about potential psychiatric side effects of hydroxychloroquine because some of her patients have complained about irritability, worsening anxiety and depression, and difficulty sleeping.
Be wary
James “Jimmy” Potash, MD, MPH, Henry Phipps Professor of Psychiatry and Behavioral Sciences, Johns Hopkins Medicine, Baltimore, said in an interview that the “take-home message of this letter is that serious psychiatric effects, psychotic illness in particular,” can occur in individuals who take chloroquine and hydroxychloroquine.
In addition, “these are potentially very concerning side effects that psychiatrists should be aware of,” noted Dr. Potash, department director and psychiatrist-in-chief at Johns Hopkins.
He said that one of his patients who had been “completely psychiatrically healthy” took chloroquine prophylactically prior to traveling overseas. After she began taking the drug, she had an episode of mania that resolved once she discontinued the medication and received treatment for the mania.
“If you add potential psychiatric side effects to the other side effects that can result from these medications, that adds up to a pretty important reason to be wary of taking them, particularly for the indication of COVID-19, where the level of evidence that it helps in any way is still quite weak,” Dr. Potash said.
In an interview, Remington Nevin, MD, MPH, DrPH, executive director at the Quinism Foundation, White River Junction, Vt., a nonprofit organization that supports and promotes education and research on disorders caused by poisoning by quinoline drugs; and faculty associate in the department of mental health at Johns Hopkins Bloomberg School of Public Health, said that the authors of the letter “are to be commended for their efforts in raising awareness of the potentially lasting and disabling psychiatric effects of chloroquine and hydroxychloroquine, which, as with similar effects from other synthetic quinoline antimalarials, have occasionally been overlooked or misattributed to other conditions.”
He added: “I have proposed that the chronic neuropsychiatric effects of this class of drug are best considered not as side effects but as signs and symptoms of a disorder known as chronic quinoline encephalopathy caused by poisoning of the central nervous system.”
Dr. Gressier and the other letter authors, Dr. Bose, and Dr. Potash have reported no relevant financial relationships. Dr. Nevin has been retained as a consultant and expert witness in legal cases involving claims of adverse effects from quinoline antimalarial drugs.
A version of this article originally appeared on Medscape.com.
Chloroquine may be associated with serious psychiatric side effects, even in patients with no family or personal history of psychiatric disorders, a new review suggests.
In a letter to the editor published online July 28 in The Journal of Clinical Psychiatry, the authors summarize data from several studies published as far back as 1993 and as recently as May 2020.
“In addition to previously reported side effects, chloroquine could also induce psychiatric side effects which are polymorphic and can persist even after stopping the drug,” lead author Florence Gressier, MD, PhD, CESP, Inserm, department of psychiatry, Le Kremlin Bicêtre, France, said in an interview.
“In COVID-19 patients who may still be [undergoing treatment] with chloroquine, close psychiatric assessment and monitoring should be performed,” she said.
Heated controversy
Following findings of a small French study that suggested efficacy in lowering the viral load in patients with COVID-19, President Donald Trump expressed optimism regarding the role of hydroxychloroquine in treating COVID-19, calling it a “game changer”.
Other studies, however, have called into question both the efficacy and the safety of hydroxychloroquine in treating COVID-19. On June 15, the Food and Drug Administration revoked the emergency use authorization it had given in March to chloroquine and hydroxychloroquine for the treatment of COVID-19.
Nevertheless, hydroxychloroquine continues to be prescribed for COVID-19. For example, an article that appeared in Click2Houston on June 15 quoted the chief medical officer of Houston’s United Memorial Center as saying he plans to continue prescribing hydroxychloroquine for patients with COVID-19 until he finds a better alternative.
As discussed in a Medscape expert commentary, a group of physicians who held a “white coat summit” in front of the U.S. Supreme Court building promoted the use of hydroxychloroquine for the treatment of COVID-19. The video of their summit was retweeted by President Trump and garnered millions of views before it was taken down by Twitter, Facebook, and YouTube.
Sudden onset
For the new review, “we wanted to alert the public and practitioners on the potentially psychiatric risks induced by chloroquine, as it could be taken as self-medication or potentially still prescribed,” Dr. Gressier said.
“We think the format of the letter to the editor allows information to be provided in a concise and clear manner,” she added.
According to the FDA’s Adverse Event Reporting System database, 12% of reported adverse events (520 of 4,336) following the use of chloroquine that occurred between the fourth quarter of 2012 and the fourth quarter of 2019 were neuropsychiatric. These events included amnesia, delirium, hallucinations, depression, and loss of consciousness, the authors write.
The researchers acknowledged that the incidence of psychiatric adverse effects associated with the use of chloroquine is “unclear in the absence of high-quality, randomized placebo-controlled trials of its safety.” Nevertheless, they pointed out that there have been reports of insomnia and depression when the drug was used as prophylaxis against malaria .
Moreover, some case series or case reports describe symptoms such as depression, anxiety, agitation, violent outburst, suicidal ideation, and psychosis in patients who have been treated with chloroquine for malaria, lupus erythematosus, and rheumatoid arthritis .
“In contrast to many other psychoses, chloroquine psychosis may be more affective and include prominent visual hallucinations, symptoms of derealization, and disorders of thought, with preserved insight,” the authors wrote.
They noted that the frequency of symptoms does not appear to be connected to the cumulative dose or the duration of treatment, and the onset of psychosis or other adverse effects is usually “sudden.”
In addition, they warn that the drug’s psychiatric effects may go unnoticed, especially because COVID-19 itself has been associated with neuropsychiatric symptoms, making it hard to distinguish between symptoms caused by the illness and those caused by the drug.
Although the psychiatric symptoms typically occur early after treatment initiation, some “subtle” symptoms might persist after stopping the drug, possibly owing to its “extremely long” half-life, the authors stated.
Dr. Gressier noted that practicing clinicians should look up reports about self-medication with chloroquine “and warn their patients about the risk induced by chloroquine.”
Safe but ‘not benign’
Nilanjana Bose, MD, MBA, a rheumatologist at the Rheumatology Center of Houston, said she uses hydroxychloroquine “all the time” in clinical practice to treat patients with rheumatic conditions.
“I cannot comment on whether it [hydroxychloroquine or chloroquine] is a potential prophylactic or treatment for COVID-19, but I can say that, from a safety point of view, as a rheumatologist who uses hydroxychloroquine at a dose of 400 mg/day, I do not think we need to worry about serious [psychiatric] side effects,” Dr. Bose said in an interview.
Because clinicians are trying all types of possible treatments for COVID-19, “if this medication has possible efficacy, it is a great medicine from a rheumatologic perspective and is safe,” she added.
Nevertheless, the drug is “not benign, and regular side effects will be there, and of course, higher doses will cause more side effects,” said Dr. Bose, who was not involved in authoring the letter.
She counsels patients about potential psychiatric side effects of hydroxychloroquine because some of her patients have complained about irritability, worsening anxiety and depression, and difficulty sleeping.
Be wary
James “Jimmy” Potash, MD, MPH, Henry Phipps Professor of Psychiatry and Behavioral Sciences, Johns Hopkins Medicine, Baltimore, said in an interview that the “take-home message of this letter is that serious psychiatric effects, psychotic illness in particular,” can occur in individuals who take chloroquine and hydroxychloroquine.
In addition, “these are potentially very concerning side effects that psychiatrists should be aware of,” noted Dr. Potash, department director and psychiatrist-in-chief at Johns Hopkins.
He said that one of his patients who had been “completely psychiatrically healthy” took chloroquine prophylactically prior to traveling overseas. After she began taking the drug, she had an episode of mania that resolved once she discontinued the medication and received treatment for the mania.
“If you add potential psychiatric side effects to the other side effects that can result from these medications, that adds up to a pretty important reason to be wary of taking them, particularly for the indication of COVID-19, where the level of evidence that it helps in any way is still quite weak,” Dr. Potash said.
In an interview, Remington Nevin, MD, MPH, DrPH, executive director at the Quinism Foundation, White River Junction, Vt., a nonprofit organization that supports and promotes education and research on disorders caused by poisoning by quinoline drugs; and faculty associate in the department of mental health at Johns Hopkins Bloomberg School of Public Health, said that the authors of the letter “are to be commended for their efforts in raising awareness of the potentially lasting and disabling psychiatric effects of chloroquine and hydroxychloroquine, which, as with similar effects from other synthetic quinoline antimalarials, have occasionally been overlooked or misattributed to other conditions.”
He added: “I have proposed that the chronic neuropsychiatric effects of this class of drug are best considered not as side effects but as signs and symptoms of a disorder known as chronic quinoline encephalopathy caused by poisoning of the central nervous system.”
Dr. Gressier and the other letter authors, Dr. Bose, and Dr. Potash have reported no relevant financial relationships. Dr. Nevin has been retained as a consultant and expert witness in legal cases involving claims of adverse effects from quinoline antimalarial drugs.
A version of this article originally appeared on Medscape.com.
Botulinum toxin associated with antidepressant effects across indications, injection sites
, according to the study’s authors.
Their results show that the antidepressant effect of botulinum toxin “administered for various indications goes beyond the control of the intended disease states and does not depend on the location of the injection,” according to Tigran Makunts, PharmD, of the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, and coauthors.
Previous high-quality studies have found botulinum toxin treatment has been associated with antidepressant effects when administered to the glabellar region of the face, they noted. The study was published in Scientific Reports.
The researchers evaluated adverse events reported to the Food and Drug Administration’s current adverse event reporting system (FAERS) between September 2012 and December 2019, and the FDA’s previous adverse event reporting system between January 2004 and August 2012. Overall, they analyzed 174,243 reports, which were divided into eight treatment-related groups based on the indication for botulinum toxin: Cosmetic use (20,684 patients), migraine (4,180 patients), spasms and spasticity not involving facial muscles (2,335 patients), neurological and urinary bladder disorders (915 patients), torticollis (1,360 patients), hyperhidrosis (601 patients), blepharospasm (487 patients), and sialorrhea (157 patients). Each group was matched to controls from the FAERS database, who had different treatments for the same indications. (Reports in which patients were on an antidepressant or where depression was listed as an indication were not included).
In nearly all treatment groups, reports of depression and depression-related adverse events were significantly lower among those who received botulinum toxin, compared with controls: For those who received botulinum toxin injections in facial muscles for cosmetic uses, the reporting odds ratio was 0.46 (95% confidence interval, 0.27-0.78). Significant effects were also see in the following groups: those who received injections into facial and head muscles for migraine (ROR, 0.60; 95% CI, 0.48-0.74), injections into the upper and lower limbs for spasms and spasticity (ROR, 0.28; 95% CI, 0.18-0.42), injections into neck muscles for torticollis and neck pain (ROR, 0.30; 95% CI, 0.20-0.44), injections into eyelid muscles for blepharospasm (ROR, 0.13; 95% CI, 0.05-0.39), and injections into the axilla and palm for hyperhidrosis (ROR, 0.12; 95% CI, 0.04-0.33).
There were no cases of depression or depression-related adverse event reports among those treated with botulinum toxin for sialorrhea with injections into the parotid and submandibular glands, and there were decreased reports of depression among those who received detrusor muscle injections for neurological and urinary bladder disorders, but the results in both groups were not statistically significant, according to the researchers.
In an interview, Ruben Abagyan, PhD, study coauthor and professor at Skaggs School of Pharmacy and Pharmaceutical Sciences, said the study’s finding go “beyond breaking a positive feedback loop between depression and the ‘frown’ wrinkles in the glabellar region of the forehead.” The data showing efficacy with botulinum toxin injected in other areas of the body can help clinicians “expand their search for the most effective injection location and dose beyond the facial injections to improve the depression-related therapeutic outcomes.”
Another takeaway from the study, he noted, is that botulinum toxin can have effects beyond the local effect seen near an injection site. Administering botulinum toxin for spasms and spasticity, excessive sweating, migraine, urinary bladder disorders, blepharospasm, or excessive salivation/drooling could result in reduced depression and improved systemic neurological effects.
“Severe depression remains a very difficult condition to treat. The existing drugs have dangerous side effects, the onset of the therapeutic action is delayed by at least a month, and the adherence to the medication is suboptimal. Therefore, finding new ways to treat depression is critical,” Dr. Abagyan said. “Botulinum toxin opens up a new physiological mechanism to be tried to reduce depression.”
Michelle Magid, MD, MBA, of the department of psychiatry at the University of Texas at Austin, said in an interview that, although the study was retrospective, “physicians can feel confident that botulinum toxin treatment will not cause depression; it may very well lead to improved mood in some of their patients.” Dr. Magid was not an author of this study, but has studied botulinum toxin as a possible treatment of depression.
“Previous studies have shown that botulinum toxin injected into the forehead region can improve symptoms of depression. The studies were small and confined to treating the glabellar region only,” she added. “This is a large retrospective study showing that botulinum toxin injected into other regions, such as the neck, underarms, bladder, hands, arms, and legs, can also have an antidepressant effect.”
Dr. Magid agreed that the use of botulinum toxin as an antidepressant should be investigated further, and could be a tool for patients who do not respond well to traditional antidepressant medications.
In their paper, the authors offered several plausible mechanisms for the antidepressant effects of botulinum toxin, including transneuronal transport to the parts of the central nervous system that regulate mood and emotion, systemic distribution, distributed muscle stress memory, and efficacy in the primary indication treatment. Although the mechanism of action is not well understood, Dr. Magid noted it could be the removal of somatic symptoms that contribute to an improvement in mood.
“It is possible that alleviating the psychological distress associated with neck spasms, excessive sweating [and so on] can be causing the antidepressive effects,” she said. “However, it is also possible that depression is actualized by a series of somatic symptoms – body aches, insomnia, sweating, for example. By removing somatic symptoms, one may also remove the correlating mood dysregulation.”
The study “certainly raises a lot of questions,” particularly about the “apparent multiple mechanisms of action of BoNT that we don’t understand yet,” Mark Rubin, MD, a cosmetic dermatologist who practices in Beverly Hills, Calif., said in an interview. “I believe it lends great deal of credence to the use of [botulinum toxin] for depression and certainly validates the need for more robust clinical trials for that indication,” he added.
“I think what we all as clinicians need to take away from this paper is that there is a great deal we don’t understand about the global pharmacologic effects of [botulinum toxin] and equally important, that there are apparently other pharmacologic pathways we need to explore in the treatment of depression, said Dr. Rubin, of the department of dermatology at the University of California, San Diego, who was not an investigator in the study.
One author reported being a consultant for Allergan. Dr. Makunts and the other author report no relevant conflicts of interest; Dr. Magid reported being a consultant for Allergan and a speaker for Ipsen. Dr. Rubin had no related disclosures.
SOURCE: Makunts T et al. Sci Rep. 2020 Jul 30;10(1):12851. doi: 10.1038/s41598-020-69773-7.
, according to the study’s authors.
Their results show that the antidepressant effect of botulinum toxin “administered for various indications goes beyond the control of the intended disease states and does not depend on the location of the injection,” according to Tigran Makunts, PharmD, of the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, and coauthors.
Previous high-quality studies have found botulinum toxin treatment has been associated with antidepressant effects when administered to the glabellar region of the face, they noted. The study was published in Scientific Reports.
The researchers evaluated adverse events reported to the Food and Drug Administration’s current adverse event reporting system (FAERS) between September 2012 and December 2019, and the FDA’s previous adverse event reporting system between January 2004 and August 2012. Overall, they analyzed 174,243 reports, which were divided into eight treatment-related groups based on the indication for botulinum toxin: Cosmetic use (20,684 patients), migraine (4,180 patients), spasms and spasticity not involving facial muscles (2,335 patients), neurological and urinary bladder disorders (915 patients), torticollis (1,360 patients), hyperhidrosis (601 patients), blepharospasm (487 patients), and sialorrhea (157 patients). Each group was matched to controls from the FAERS database, who had different treatments for the same indications. (Reports in which patients were on an antidepressant or where depression was listed as an indication were not included).
In nearly all treatment groups, reports of depression and depression-related adverse events were significantly lower among those who received botulinum toxin, compared with controls: For those who received botulinum toxin injections in facial muscles for cosmetic uses, the reporting odds ratio was 0.46 (95% confidence interval, 0.27-0.78). Significant effects were also see in the following groups: those who received injections into facial and head muscles for migraine (ROR, 0.60; 95% CI, 0.48-0.74), injections into the upper and lower limbs for spasms and spasticity (ROR, 0.28; 95% CI, 0.18-0.42), injections into neck muscles for torticollis and neck pain (ROR, 0.30; 95% CI, 0.20-0.44), injections into eyelid muscles for blepharospasm (ROR, 0.13; 95% CI, 0.05-0.39), and injections into the axilla and palm for hyperhidrosis (ROR, 0.12; 95% CI, 0.04-0.33).
There were no cases of depression or depression-related adverse event reports among those treated with botulinum toxin for sialorrhea with injections into the parotid and submandibular glands, and there were decreased reports of depression among those who received detrusor muscle injections for neurological and urinary bladder disorders, but the results in both groups were not statistically significant, according to the researchers.
In an interview, Ruben Abagyan, PhD, study coauthor and professor at Skaggs School of Pharmacy and Pharmaceutical Sciences, said the study’s finding go “beyond breaking a positive feedback loop between depression and the ‘frown’ wrinkles in the glabellar region of the forehead.” The data showing efficacy with botulinum toxin injected in other areas of the body can help clinicians “expand their search for the most effective injection location and dose beyond the facial injections to improve the depression-related therapeutic outcomes.”
Another takeaway from the study, he noted, is that botulinum toxin can have effects beyond the local effect seen near an injection site. Administering botulinum toxin for spasms and spasticity, excessive sweating, migraine, urinary bladder disorders, blepharospasm, or excessive salivation/drooling could result in reduced depression and improved systemic neurological effects.
“Severe depression remains a very difficult condition to treat. The existing drugs have dangerous side effects, the onset of the therapeutic action is delayed by at least a month, and the adherence to the medication is suboptimal. Therefore, finding new ways to treat depression is critical,” Dr. Abagyan said. “Botulinum toxin opens up a new physiological mechanism to be tried to reduce depression.”
Michelle Magid, MD, MBA, of the department of psychiatry at the University of Texas at Austin, said in an interview that, although the study was retrospective, “physicians can feel confident that botulinum toxin treatment will not cause depression; it may very well lead to improved mood in some of their patients.” Dr. Magid was not an author of this study, but has studied botulinum toxin as a possible treatment of depression.
“Previous studies have shown that botulinum toxin injected into the forehead region can improve symptoms of depression. The studies were small and confined to treating the glabellar region only,” she added. “This is a large retrospective study showing that botulinum toxin injected into other regions, such as the neck, underarms, bladder, hands, arms, and legs, can also have an antidepressant effect.”
Dr. Magid agreed that the use of botulinum toxin as an antidepressant should be investigated further, and could be a tool for patients who do not respond well to traditional antidepressant medications.
In their paper, the authors offered several plausible mechanisms for the antidepressant effects of botulinum toxin, including transneuronal transport to the parts of the central nervous system that regulate mood and emotion, systemic distribution, distributed muscle stress memory, and efficacy in the primary indication treatment. Although the mechanism of action is not well understood, Dr. Magid noted it could be the removal of somatic symptoms that contribute to an improvement in mood.
“It is possible that alleviating the psychological distress associated with neck spasms, excessive sweating [and so on] can be causing the antidepressive effects,” she said. “However, it is also possible that depression is actualized by a series of somatic symptoms – body aches, insomnia, sweating, for example. By removing somatic symptoms, one may also remove the correlating mood dysregulation.”
The study “certainly raises a lot of questions,” particularly about the “apparent multiple mechanisms of action of BoNT that we don’t understand yet,” Mark Rubin, MD, a cosmetic dermatologist who practices in Beverly Hills, Calif., said in an interview. “I believe it lends great deal of credence to the use of [botulinum toxin] for depression and certainly validates the need for more robust clinical trials for that indication,” he added.
“I think what we all as clinicians need to take away from this paper is that there is a great deal we don’t understand about the global pharmacologic effects of [botulinum toxin] and equally important, that there are apparently other pharmacologic pathways we need to explore in the treatment of depression, said Dr. Rubin, of the department of dermatology at the University of California, San Diego, who was not an investigator in the study.
One author reported being a consultant for Allergan. Dr. Makunts and the other author report no relevant conflicts of interest; Dr. Magid reported being a consultant for Allergan and a speaker for Ipsen. Dr. Rubin had no related disclosures.
SOURCE: Makunts T et al. Sci Rep. 2020 Jul 30;10(1):12851. doi: 10.1038/s41598-020-69773-7.
, according to the study’s authors.
Their results show that the antidepressant effect of botulinum toxin “administered for various indications goes beyond the control of the intended disease states and does not depend on the location of the injection,” according to Tigran Makunts, PharmD, of the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, and coauthors.
Previous high-quality studies have found botulinum toxin treatment has been associated with antidepressant effects when administered to the glabellar region of the face, they noted. The study was published in Scientific Reports.
The researchers evaluated adverse events reported to the Food and Drug Administration’s current adverse event reporting system (FAERS) between September 2012 and December 2019, and the FDA’s previous adverse event reporting system between January 2004 and August 2012. Overall, they analyzed 174,243 reports, which were divided into eight treatment-related groups based on the indication for botulinum toxin: Cosmetic use (20,684 patients), migraine (4,180 patients), spasms and spasticity not involving facial muscles (2,335 patients), neurological and urinary bladder disorders (915 patients), torticollis (1,360 patients), hyperhidrosis (601 patients), blepharospasm (487 patients), and sialorrhea (157 patients). Each group was matched to controls from the FAERS database, who had different treatments for the same indications. (Reports in which patients were on an antidepressant or where depression was listed as an indication were not included).
In nearly all treatment groups, reports of depression and depression-related adverse events were significantly lower among those who received botulinum toxin, compared with controls: For those who received botulinum toxin injections in facial muscles for cosmetic uses, the reporting odds ratio was 0.46 (95% confidence interval, 0.27-0.78). Significant effects were also see in the following groups: those who received injections into facial and head muscles for migraine (ROR, 0.60; 95% CI, 0.48-0.74), injections into the upper and lower limbs for spasms and spasticity (ROR, 0.28; 95% CI, 0.18-0.42), injections into neck muscles for torticollis and neck pain (ROR, 0.30; 95% CI, 0.20-0.44), injections into eyelid muscles for blepharospasm (ROR, 0.13; 95% CI, 0.05-0.39), and injections into the axilla and palm for hyperhidrosis (ROR, 0.12; 95% CI, 0.04-0.33).
There were no cases of depression or depression-related adverse event reports among those treated with botulinum toxin for sialorrhea with injections into the parotid and submandibular glands, and there were decreased reports of depression among those who received detrusor muscle injections for neurological and urinary bladder disorders, but the results in both groups were not statistically significant, according to the researchers.
In an interview, Ruben Abagyan, PhD, study coauthor and professor at Skaggs School of Pharmacy and Pharmaceutical Sciences, said the study’s finding go “beyond breaking a positive feedback loop between depression and the ‘frown’ wrinkles in the glabellar region of the forehead.” The data showing efficacy with botulinum toxin injected in other areas of the body can help clinicians “expand their search for the most effective injection location and dose beyond the facial injections to improve the depression-related therapeutic outcomes.”
Another takeaway from the study, he noted, is that botulinum toxin can have effects beyond the local effect seen near an injection site. Administering botulinum toxin for spasms and spasticity, excessive sweating, migraine, urinary bladder disorders, blepharospasm, or excessive salivation/drooling could result in reduced depression and improved systemic neurological effects.
“Severe depression remains a very difficult condition to treat. The existing drugs have dangerous side effects, the onset of the therapeutic action is delayed by at least a month, and the adherence to the medication is suboptimal. Therefore, finding new ways to treat depression is critical,” Dr. Abagyan said. “Botulinum toxin opens up a new physiological mechanism to be tried to reduce depression.”
Michelle Magid, MD, MBA, of the department of psychiatry at the University of Texas at Austin, said in an interview that, although the study was retrospective, “physicians can feel confident that botulinum toxin treatment will not cause depression; it may very well lead to improved mood in some of their patients.” Dr. Magid was not an author of this study, but has studied botulinum toxin as a possible treatment of depression.
“Previous studies have shown that botulinum toxin injected into the forehead region can improve symptoms of depression. The studies were small and confined to treating the glabellar region only,” she added. “This is a large retrospective study showing that botulinum toxin injected into other regions, such as the neck, underarms, bladder, hands, arms, and legs, can also have an antidepressant effect.”
Dr. Magid agreed that the use of botulinum toxin as an antidepressant should be investigated further, and could be a tool for patients who do not respond well to traditional antidepressant medications.
In their paper, the authors offered several plausible mechanisms for the antidepressant effects of botulinum toxin, including transneuronal transport to the parts of the central nervous system that regulate mood and emotion, systemic distribution, distributed muscle stress memory, and efficacy in the primary indication treatment. Although the mechanism of action is not well understood, Dr. Magid noted it could be the removal of somatic symptoms that contribute to an improvement in mood.
“It is possible that alleviating the psychological distress associated with neck spasms, excessive sweating [and so on] can be causing the antidepressive effects,” she said. “However, it is also possible that depression is actualized by a series of somatic symptoms – body aches, insomnia, sweating, for example. By removing somatic symptoms, one may also remove the correlating mood dysregulation.”
The study “certainly raises a lot of questions,” particularly about the “apparent multiple mechanisms of action of BoNT that we don’t understand yet,” Mark Rubin, MD, a cosmetic dermatologist who practices in Beverly Hills, Calif., said in an interview. “I believe it lends great deal of credence to the use of [botulinum toxin] for depression and certainly validates the need for more robust clinical trials for that indication,” he added.
“I think what we all as clinicians need to take away from this paper is that there is a great deal we don’t understand about the global pharmacologic effects of [botulinum toxin] and equally important, that there are apparently other pharmacologic pathways we need to explore in the treatment of depression, said Dr. Rubin, of the department of dermatology at the University of California, San Diego, who was not an investigator in the study.
One author reported being a consultant for Allergan. Dr. Makunts and the other author report no relevant conflicts of interest; Dr. Magid reported being a consultant for Allergan and a speaker for Ipsen. Dr. Rubin had no related disclosures.
SOURCE: Makunts T et al. Sci Rep. 2020 Jul 30;10(1):12851. doi: 10.1038/s41598-020-69773-7.
FROM SCIENTIFIC REPORTS
Rapid cycle pediatric simulation exercises promise improved readiness
Focused repetition builds sustained skill
A methodical, constructive, goal-oriented rapid repetition of emergency response simulations has emerged as a dominant strategy for pediatric readiness in the hospital setting, according to a detailed description of one such program at the virtual Pediatric Hospital Medicine.
Rather than a single run-through followed by a lengthy debriefing, which has been a traditional approach, short simulations done rapidly and repeatedly until skills are mastered improve skill development, according to Jeanmarie Schied, MD, of the department of pediatrics, University of Chicago Medicine.
“This method utilizes repetitions to develop muscle memory much like an athlete who ‘practices, practices, practices’ until it becomes second nature,” Dr. Schied explained.
Dr. Schied credited this approach to Elizabeth Hunt, MD, PhD, director of the Johns Hopkins Medicine Simulation Center. The method created by Dr. Hunt is called Rapid Cycle Deliberate Practice (RCDP). At the University of Chicago, where the same principles are being applied, “we have had great success,” Dr. Schied said.
Deficiencies in the traditional approach prompted the change. It has been shown that when experienced residents who have performed multiple simulations are compared to new residents with limited experience or when those certified in Pediatric Advanced Life Support (PAL) are compared to those who are not, they “do not necessarily do better” in the metrics used in simulations to measure competence, according to Dr. Schied.
With the RDCP, learners get multiple chances to master skills.
“Everyone makes mistakes, and letting the participants know this ahead of time puts people at ease,” Dr. Schied said. “People want to know they will have a chance to rewind and do it right.”
In setting up an effective simulation program, the first step is a needs assessment. By first gauging the skill and experience level of those scheduled to participate, Dr. Schied said the program can be tailored to the audience.
The next step is formulating learning objectives. Dr. Schied recommended creating these objectives for the case overall and for each phase of the simulation as it progresses from basic clinical assessments through the specific interventions appropriate for the diagnosis.
Within these objectives there are additional goals. For example, the team should work to administer care within prespecified benchmarks, such as an elapsed time of 60 seconds or less for oxygenation or a time of 180 seconds or less for defibrillation, according to Dr. Schied.
Yet, Dr. Schied suggested that enforcing these goals on initial run-throughs might not be appropriate.
“Let the scenario run longer so you can see the deficits,” Dr. Schied said. If, for example, chest compression is not being done correctly, she recommended interrupting the process to provide immediate and direct feedback. In critiquing the performance, Dr. Schied advised against a critical or punitive tone.
“Inform the learners that they are in a safe environment,” she said. It is essential to identify errors so that they can be corrected on the next run of the practice simulation, but Dr. Schied advised instructors to “be nonjudgmental.” Praise is appropriate when warranted, but she also warned, “don’t sugarcoat” a substandard performance.
During the simulation, team leaders should employ action phrases, meaning that the problem and the action needed are expressed at the same time, according to Dr. Schied. Examples include, “the patient is not breathing, start bagging,” or “there is no pulse, start compression.”
“When the team gets used to these action-linked phrases, studies show that they react in a more timely fashion,” Dr. Schied explained at the event sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
In the study by Dr. Hunt that established the effectiveness of RDCP, 51 pediatric residents who had previously participated in a cardiopulmonary arrest simulation were retested again after being retrained with the RDCP methodology (Resuscitation 2014;85:945-51).
RDCP “was associated with improvement in performance of key measures of quality life support and progressive acquisition of resuscitation skills,” according to Dr. Hunt, who has published frequently on resuscitation training in pediatrics.
Prior to RDCP, traditional methods produced “little improvement” in resuscitation skills when measured over the course of pediatric residency, according to Dr. Hunt. After RDCP, third-year residents were shown to be “significantly more likely than first-years to defibrillate within 2 minutes,” she reported.
However, there are other strategies to improve retention of skills, according to Dr. Schied. For example, it is important to conduct simulations when the staff can focus. Specifically, Dr. Schied recommended conducting simulations immediately after a staff meeting or before a scheduled shift so that clinical responsibilities will not interfere or divert the learner’s attention. She also recommended conducting key simulations quarterly.
“Studies have shown that knowledge deterioration related to resuscitation begins about 4 months after the last simulation,” she said.
In addition to building the skills of individual participants, Dr. Schied emphasized the importance of also developing effective team dynamics and active communication. In the debriefing that should follow every simulation, she recommended encouraging a discussion of strengths and weaknesses of the team response.
Pediatric emergency simulation scenarios are readily available on multiple sites found on the Internet,” Dr. Schied said. She recommended documenting performance so the data are available for subsequent analysis.
Focused repetition builds sustained skill
Focused repetition builds sustained skill
A methodical, constructive, goal-oriented rapid repetition of emergency response simulations has emerged as a dominant strategy for pediatric readiness in the hospital setting, according to a detailed description of one such program at the virtual Pediatric Hospital Medicine.
Rather than a single run-through followed by a lengthy debriefing, which has been a traditional approach, short simulations done rapidly and repeatedly until skills are mastered improve skill development, according to Jeanmarie Schied, MD, of the department of pediatrics, University of Chicago Medicine.
“This method utilizes repetitions to develop muscle memory much like an athlete who ‘practices, practices, practices’ until it becomes second nature,” Dr. Schied explained.
Dr. Schied credited this approach to Elizabeth Hunt, MD, PhD, director of the Johns Hopkins Medicine Simulation Center. The method created by Dr. Hunt is called Rapid Cycle Deliberate Practice (RCDP). At the University of Chicago, where the same principles are being applied, “we have had great success,” Dr. Schied said.
Deficiencies in the traditional approach prompted the change. It has been shown that when experienced residents who have performed multiple simulations are compared to new residents with limited experience or when those certified in Pediatric Advanced Life Support (PAL) are compared to those who are not, they “do not necessarily do better” in the metrics used in simulations to measure competence, according to Dr. Schied.
With the RDCP, learners get multiple chances to master skills.
“Everyone makes mistakes, and letting the participants know this ahead of time puts people at ease,” Dr. Schied said. “People want to know they will have a chance to rewind and do it right.”
In setting up an effective simulation program, the first step is a needs assessment. By first gauging the skill and experience level of those scheduled to participate, Dr. Schied said the program can be tailored to the audience.
The next step is formulating learning objectives. Dr. Schied recommended creating these objectives for the case overall and for each phase of the simulation as it progresses from basic clinical assessments through the specific interventions appropriate for the diagnosis.
Within these objectives there are additional goals. For example, the team should work to administer care within prespecified benchmarks, such as an elapsed time of 60 seconds or less for oxygenation or a time of 180 seconds or less for defibrillation, according to Dr. Schied.
Yet, Dr. Schied suggested that enforcing these goals on initial run-throughs might not be appropriate.
“Let the scenario run longer so you can see the deficits,” Dr. Schied said. If, for example, chest compression is not being done correctly, she recommended interrupting the process to provide immediate and direct feedback. In critiquing the performance, Dr. Schied advised against a critical or punitive tone.
“Inform the learners that they are in a safe environment,” she said. It is essential to identify errors so that they can be corrected on the next run of the practice simulation, but Dr. Schied advised instructors to “be nonjudgmental.” Praise is appropriate when warranted, but she also warned, “don’t sugarcoat” a substandard performance.
During the simulation, team leaders should employ action phrases, meaning that the problem and the action needed are expressed at the same time, according to Dr. Schied. Examples include, “the patient is not breathing, start bagging,” or “there is no pulse, start compression.”
“When the team gets used to these action-linked phrases, studies show that they react in a more timely fashion,” Dr. Schied explained at the event sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
In the study by Dr. Hunt that established the effectiveness of RDCP, 51 pediatric residents who had previously participated in a cardiopulmonary arrest simulation were retested again after being retrained with the RDCP methodology (Resuscitation 2014;85:945-51).
RDCP “was associated with improvement in performance of key measures of quality life support and progressive acquisition of resuscitation skills,” according to Dr. Hunt, who has published frequently on resuscitation training in pediatrics.
Prior to RDCP, traditional methods produced “little improvement” in resuscitation skills when measured over the course of pediatric residency, according to Dr. Hunt. After RDCP, third-year residents were shown to be “significantly more likely than first-years to defibrillate within 2 minutes,” she reported.
However, there are other strategies to improve retention of skills, according to Dr. Schied. For example, it is important to conduct simulations when the staff can focus. Specifically, Dr. Schied recommended conducting simulations immediately after a staff meeting or before a scheduled shift so that clinical responsibilities will not interfere or divert the learner’s attention. She also recommended conducting key simulations quarterly.
“Studies have shown that knowledge deterioration related to resuscitation begins about 4 months after the last simulation,” she said.
In addition to building the skills of individual participants, Dr. Schied emphasized the importance of also developing effective team dynamics and active communication. In the debriefing that should follow every simulation, she recommended encouraging a discussion of strengths and weaknesses of the team response.
Pediatric emergency simulation scenarios are readily available on multiple sites found on the Internet,” Dr. Schied said. She recommended documenting performance so the data are available for subsequent analysis.
A methodical, constructive, goal-oriented rapid repetition of emergency response simulations has emerged as a dominant strategy for pediatric readiness in the hospital setting, according to a detailed description of one such program at the virtual Pediatric Hospital Medicine.
Rather than a single run-through followed by a lengthy debriefing, which has been a traditional approach, short simulations done rapidly and repeatedly until skills are mastered improve skill development, according to Jeanmarie Schied, MD, of the department of pediatrics, University of Chicago Medicine.
“This method utilizes repetitions to develop muscle memory much like an athlete who ‘practices, practices, practices’ until it becomes second nature,” Dr. Schied explained.
Dr. Schied credited this approach to Elizabeth Hunt, MD, PhD, director of the Johns Hopkins Medicine Simulation Center. The method created by Dr. Hunt is called Rapid Cycle Deliberate Practice (RCDP). At the University of Chicago, where the same principles are being applied, “we have had great success,” Dr. Schied said.
Deficiencies in the traditional approach prompted the change. It has been shown that when experienced residents who have performed multiple simulations are compared to new residents with limited experience or when those certified in Pediatric Advanced Life Support (PAL) are compared to those who are not, they “do not necessarily do better” in the metrics used in simulations to measure competence, according to Dr. Schied.
With the RDCP, learners get multiple chances to master skills.
“Everyone makes mistakes, and letting the participants know this ahead of time puts people at ease,” Dr. Schied said. “People want to know they will have a chance to rewind and do it right.”
In setting up an effective simulation program, the first step is a needs assessment. By first gauging the skill and experience level of those scheduled to participate, Dr. Schied said the program can be tailored to the audience.
The next step is formulating learning objectives. Dr. Schied recommended creating these objectives for the case overall and for each phase of the simulation as it progresses from basic clinical assessments through the specific interventions appropriate for the diagnosis.
Within these objectives there are additional goals. For example, the team should work to administer care within prespecified benchmarks, such as an elapsed time of 60 seconds or less for oxygenation or a time of 180 seconds or less for defibrillation, according to Dr. Schied.
Yet, Dr. Schied suggested that enforcing these goals on initial run-throughs might not be appropriate.
“Let the scenario run longer so you can see the deficits,” Dr. Schied said. If, for example, chest compression is not being done correctly, she recommended interrupting the process to provide immediate and direct feedback. In critiquing the performance, Dr. Schied advised against a critical or punitive tone.
“Inform the learners that they are in a safe environment,” she said. It is essential to identify errors so that they can be corrected on the next run of the practice simulation, but Dr. Schied advised instructors to “be nonjudgmental.” Praise is appropriate when warranted, but she also warned, “don’t sugarcoat” a substandard performance.
During the simulation, team leaders should employ action phrases, meaning that the problem and the action needed are expressed at the same time, according to Dr. Schied. Examples include, “the patient is not breathing, start bagging,” or “there is no pulse, start compression.”
“When the team gets used to these action-linked phrases, studies show that they react in a more timely fashion,” Dr. Schied explained at the event sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
In the study by Dr. Hunt that established the effectiveness of RDCP, 51 pediatric residents who had previously participated in a cardiopulmonary arrest simulation were retested again after being retrained with the RDCP methodology (Resuscitation 2014;85:945-51).
RDCP “was associated with improvement in performance of key measures of quality life support and progressive acquisition of resuscitation skills,” according to Dr. Hunt, who has published frequently on resuscitation training in pediatrics.
Prior to RDCP, traditional methods produced “little improvement” in resuscitation skills when measured over the course of pediatric residency, according to Dr. Hunt. After RDCP, third-year residents were shown to be “significantly more likely than first-years to defibrillate within 2 minutes,” she reported.
However, there are other strategies to improve retention of skills, according to Dr. Schied. For example, it is important to conduct simulations when the staff can focus. Specifically, Dr. Schied recommended conducting simulations immediately after a staff meeting or before a scheduled shift so that clinical responsibilities will not interfere or divert the learner’s attention. She also recommended conducting key simulations quarterly.
“Studies have shown that knowledge deterioration related to resuscitation begins about 4 months after the last simulation,” she said.
In addition to building the skills of individual participants, Dr. Schied emphasized the importance of also developing effective team dynamics and active communication. In the debriefing that should follow every simulation, she recommended encouraging a discussion of strengths and weaknesses of the team response.
Pediatric emergency simulation scenarios are readily available on multiple sites found on the Internet,” Dr. Schied said. She recommended documenting performance so the data are available for subsequent analysis.
FROM PHM20 VIRTUAL
Critical care readiness. Coding for telemedicine. Physical therapy teleconsultations. Physical therapy teleconsultations.
Preparation is key for disaster management. It includes identifying heath-care worker capability, surge capacity, disposable medical resources, and expert consultation availability.
Staff
In disaster, the hospital transitions to a mass casualty strategy, repurposing noncritical care staff to a tiered critical care model focusing on disaster triage and mass critical care. The goal is to provide care to minimize mortality.
Stuff
Critical care supplies improve survival and are implemented quickly and easily. Essential supplies include personal protective equipment, basic modes of mechanical ventilation, hemodynamic support, antimicrobial therapy or other disease-specific countermeasures, oxygen, and prophylactic treatments.
Structure
Disaster critical care can be delivered in noncritical care areas. Hospital policies should establish surge capacity strategies.
System
Providing quality lifesaving care to appropriately triaged patients by utilizing minimal qualifications for survival, predetermined ICU admission criteria, and dynamic protocols using the highest level of evidence available scalable to local resources.
Inappropriate triage results in suboptimal care and can lead to increased mortality.
Virtual critical care can augment critical care capacity and capability.
The implementation of mass critical care requires hospitals to rapidly increase its patient volume above its normal capacity. The essential four components are staff, stuff, space, and structure. Effective mass critical care requires a different mindset than critical care in day-to-day operations.
Patrick Moon, MD; and Alexis MacDonald, MD
(Drs. Reed and Tripp's Fellows)
Mary Jane Reed, MD, FCCP, and Michael Tripp, MD, FCCP
Steering Committee Members
Practice Operations
Over the years since telemedicine (TM) was developed in the 1960s, it has transformed into more mobile, compact, and interconnected forms. However, its widespread adoption has been limited by the regulatory, compensatory, and licensing status quo. The emergence of the COVID-19 pandemic and its necessity for physical distancing has brought TM into the limelight. With restrictions on TM use lifted by CMS, the scope of TM could extend from outpatient to inpatient care to emergency triaging and management of chronic medical conditions.
In February 2020, the comprehensive 2020 COVID-19 ICD 10 coding guidelines were released. To date, CMS has approved approximately 80 codes, which can be used with telehealth and non face-face-to-face (NFTF) encounters. They include telephone calls, online digital E/M services, interprofessional telephone/internet/electric health record consultations, digitally stored data services/remote physiologic monitoring, remote reporting of self-measure blood pressure, and remote physiologic monitoring treatment management services. Some of the key "rules of the game" are highlighted below.
- For telephone visits in the outpatient setting use the codes 99441 (5-10 minutes), 99442 (11-20 minutes), and 99443 (21-30 minutes).
- For interactive real-time audio and video telecommunication (RAVT) in the outpatient setting, use the codes normally used for outpatient E/M: 99201-99215.
- For using RAVT to perform an initial visit for an inpatient, use the codes that are normally used for inpatient E/M: 99221-99223.
- For using RAVT to perform a subsequent visit for an inpatient, use the codes that are normally used for subsequent hospital care service E/M: 99231-99233.
- Seeing a critically ill patient without being in the patient's room is allowed, as a physical exam is not required for either 99291 or 99292. Be sure to use 99292 for each 30 minutes beyond the initial 74 minutes and document the time spent on the patient.
The details of the coding/billing guidelines are intricate and full of nuances and for a better understanding on how to utilize TM both in an inpatient and outpatient setting, consider the following resources:
1. CHEST Experience presentation entitled "TELE MEDICINE/TELE HEALTH IN THE ERA OF PANDEMIC" at the CHEST Annual Meeting 2020.
1. Coding and Billing Guidelines by ATS:
https://www.thoracic.org/about/newsroom/newsletters/coding-and-billing/resources/2020/mostrecentcbqapril.pdf
2. Coding specific for management of COVID patients by the AMA:
https://www.ama-assn.org/system/files/2020-05/covid-19-coding-advice.pdf
Humayun Anjum, MD, FCCP
Vice-Chair, Practice Operations
Haala Rokadia, MD, FCCP
Practice Operations NetWork Steering Committee Member
Transplant
Physical therapy teleconsultations
The COVID 19 pandemic led the health-care community to rapidly adopt telecommunication tools allowing provision of care equivalent to in-person visits. Implementation of telemedicine visits demonstrated that providers can simultaneously distance and connect with patients to provide expert care.
The University of Pennsylvania lung transplant team adapted video communications to provide individualized physical therapy (PT) recommendations for lung transplantation candidates. The evaluation includes a systems review, musculoskeletal screen, submaximal aerobic capacity testing, and performance of the short physical performance battery test (SPPBT), a frequently used frailty evaluation tool focused on lower extremity function and balance. In the era of social distancing, telemedicine capabilities have made this crucial aspect of pretransplant evaluation possible.
In advance, patients are emailed a document outlining the telemedicine PT assessment, including the SPPBT. Patients receive videos of the SPPBT to ensure they understand the test and can prepare their home to safely perform the tasks. We are able to highlight the patient's functional capabilities and detail accurate assessments of their deficits. Our teleconsultations utilize BlueJeans for connectivity and typically last about 30 minutes. At this time, we are billing for these pretransplant visits but not for posttransplant PT follow-up.
Patient experiences with the PT teleconsultations have been overwhelmingly positive. Patients and their families appreciate the uninterrupted evaluation time and the individualized recommendations for improving their deficits. The providers can devote their full attention to the patient directly in front of them. Importantly, patients and providers report they have never felt a stronger connection than through these telemedicine encounters. Longitudinal telemedicine PT assessments will enable us to better monitor our patients throughout the lung transplantation process.
Joshua Diamond, MD
Steering Committee Member
Derek Zaleski, PT, DPT
Women's Lung Health
SARS-COV-2 and pregnancy
The SARS-COV-2 pandemic has brought on many fears and uncertainties with new information emerging daily, including the effect during pregnancy. At the time of this article,however, data pertaining to COVID-19 and pregnancy remain limited. Pregnant women do not seem to have a higher infection rate than the general population. In a correspondence where pregnant women admitted for delivery underwent universal screening in NY, 1.9% of women were symptomatic and tested positive, and 13.7% of the asymptomatic patients were found to be SARS-COV-2 positive.1 Furthermore, unlike H1NI, data suggest that pregnant women infected with SARS-COV-2 currently do not seem to have worse outcomes than the average person.2,3 As of now, there have not been any reports of maternal fetal vertical transmission from COVID-19 or any other coronavirus variants.4 Postpartum testing of infants has yielded a very small number of babies who have tested positive for virus, but this more likely represents transmission after birth. There are currently no specific FDA-approved medications for the treatment of moderate-severe infections with COVID-19 in pregnant women, although there are several clinical trials underway. Patients with moderate to severe symptoms should seek medical attention, while those with mild symptoms should continue with conservative therapies, as well as maintaining proper hygiene.5 Delivery methods and timing remain unchanged with cesarean delivery as currently indicated per established guidelines.5
Mariam Louis, MD
Steering Committee Member
Jorge Trabanco, MD
1. N Engl J Med. 2020 Apr 13;382:2163-4. April 13, 2020, DOI: 10.1056/NEJMc2009316
2. N Engl J Med. 2020 Jun 18; 382:e100. April 17, 2020 DOI: 10.1056/NEJMc2009226
3. Acta Obstet Gynecol Scand. 2020 Jul;99(7):823-829. 2020 Apr 7. doi: 10.1111/aogs.13867. [Epub ahead of print]
4. Arch Pathol Lab Med. 2020 Apr 27. doi: 10.5858/arpa.2020-0211-SA. [Epub ahead of print]
5. ACOG practice advisory, Novel Coronavirus 2019 (COVID-19) April 23, 2020.
Preparation is key for disaster management. It includes identifying heath-care worker capability, surge capacity, disposable medical resources, and expert consultation availability.
Staff
In disaster, the hospital transitions to a mass casualty strategy, repurposing noncritical care staff to a tiered critical care model focusing on disaster triage and mass critical care. The goal is to provide care to minimize mortality.
Stuff
Critical care supplies improve survival and are implemented quickly and easily. Essential supplies include personal protective equipment, basic modes of mechanical ventilation, hemodynamic support, antimicrobial therapy or other disease-specific countermeasures, oxygen, and prophylactic treatments.
Structure
Disaster critical care can be delivered in noncritical care areas. Hospital policies should establish surge capacity strategies.
System
Providing quality lifesaving care to appropriately triaged patients by utilizing minimal qualifications for survival, predetermined ICU admission criteria, and dynamic protocols using the highest level of evidence available scalable to local resources.
Inappropriate triage results in suboptimal care and can lead to increased mortality.
Virtual critical care can augment critical care capacity and capability.
The implementation of mass critical care requires hospitals to rapidly increase its patient volume above its normal capacity. The essential four components are staff, stuff, space, and structure. Effective mass critical care requires a different mindset than critical care in day-to-day operations.
Patrick Moon, MD; and Alexis MacDonald, MD
(Drs. Reed and Tripp's Fellows)
Mary Jane Reed, MD, FCCP, and Michael Tripp, MD, FCCP
Steering Committee Members
Practice Operations
Over the years since telemedicine (TM) was developed in the 1960s, it has transformed into more mobile, compact, and interconnected forms. However, its widespread adoption has been limited by the regulatory, compensatory, and licensing status quo. The emergence of the COVID-19 pandemic and its necessity for physical distancing has brought TM into the limelight. With restrictions on TM use lifted by CMS, the scope of TM could extend from outpatient to inpatient care to emergency triaging and management of chronic medical conditions.
In February 2020, the comprehensive 2020 COVID-19 ICD 10 coding guidelines were released. To date, CMS has approved approximately 80 codes, which can be used with telehealth and non face-face-to-face (NFTF) encounters. They include telephone calls, online digital E/M services, interprofessional telephone/internet/electric health record consultations, digitally stored data services/remote physiologic monitoring, remote reporting of self-measure blood pressure, and remote physiologic monitoring treatment management services. Some of the key "rules of the game" are highlighted below.
- For telephone visits in the outpatient setting use the codes 99441 (5-10 minutes), 99442 (11-20 minutes), and 99443 (21-30 minutes).
- For interactive real-time audio and video telecommunication (RAVT) in the outpatient setting, use the codes normally used for outpatient E/M: 99201-99215.
- For using RAVT to perform an initial visit for an inpatient, use the codes that are normally used for inpatient E/M: 99221-99223.
- For using RAVT to perform a subsequent visit for an inpatient, use the codes that are normally used for subsequent hospital care service E/M: 99231-99233.
- Seeing a critically ill patient without being in the patient's room is allowed, as a physical exam is not required for either 99291 or 99292. Be sure to use 99292 for each 30 minutes beyond the initial 74 minutes and document the time spent on the patient.
The details of the coding/billing guidelines are intricate and full of nuances and for a better understanding on how to utilize TM both in an inpatient and outpatient setting, consider the following resources:
1. CHEST Experience presentation entitled "TELE MEDICINE/TELE HEALTH IN THE ERA OF PANDEMIC" at the CHEST Annual Meeting 2020.
1. Coding and Billing Guidelines by ATS:
https://www.thoracic.org/about/newsroom/newsletters/coding-and-billing/resources/2020/mostrecentcbqapril.pdf
2. Coding specific for management of COVID patients by the AMA:
https://www.ama-assn.org/system/files/2020-05/covid-19-coding-advice.pdf
Humayun Anjum, MD, FCCP
Vice-Chair, Practice Operations
Haala Rokadia, MD, FCCP
Practice Operations NetWork Steering Committee Member
Transplant
Physical therapy teleconsultations
The COVID 19 pandemic led the health-care community to rapidly adopt telecommunication tools allowing provision of care equivalent to in-person visits. Implementation of telemedicine visits demonstrated that providers can simultaneously distance and connect with patients to provide expert care.
The University of Pennsylvania lung transplant team adapted video communications to provide individualized physical therapy (PT) recommendations for lung transplantation candidates. The evaluation includes a systems review, musculoskeletal screen, submaximal aerobic capacity testing, and performance of the short physical performance battery test (SPPBT), a frequently used frailty evaluation tool focused on lower extremity function and balance. In the era of social distancing, telemedicine capabilities have made this crucial aspect of pretransplant evaluation possible.
In advance, patients are emailed a document outlining the telemedicine PT assessment, including the SPPBT. Patients receive videos of the SPPBT to ensure they understand the test and can prepare their home to safely perform the tasks. We are able to highlight the patient's functional capabilities and detail accurate assessments of their deficits. Our teleconsultations utilize BlueJeans for connectivity and typically last about 30 minutes. At this time, we are billing for these pretransplant visits but not for posttransplant PT follow-up.
Patient experiences with the PT teleconsultations have been overwhelmingly positive. Patients and their families appreciate the uninterrupted evaluation time and the individualized recommendations for improving their deficits. The providers can devote their full attention to the patient directly in front of them. Importantly, patients and providers report they have never felt a stronger connection than through these telemedicine encounters. Longitudinal telemedicine PT assessments will enable us to better monitor our patients throughout the lung transplantation process.
Joshua Diamond, MD
Steering Committee Member
Derek Zaleski, PT, DPT
Women's Lung Health
SARS-COV-2 and pregnancy
The SARS-COV-2 pandemic has brought on many fears and uncertainties with new information emerging daily, including the effect during pregnancy. At the time of this article,however, data pertaining to COVID-19 and pregnancy remain limited. Pregnant women do not seem to have a higher infection rate than the general population. In a correspondence where pregnant women admitted for delivery underwent universal screening in NY, 1.9% of women were symptomatic and tested positive, and 13.7% of the asymptomatic patients were found to be SARS-COV-2 positive.1 Furthermore, unlike H1NI, data suggest that pregnant women infected with SARS-COV-2 currently do not seem to have worse outcomes than the average person.2,3 As of now, there have not been any reports of maternal fetal vertical transmission from COVID-19 or any other coronavirus variants.4 Postpartum testing of infants has yielded a very small number of babies who have tested positive for virus, but this more likely represents transmission after birth. There are currently no specific FDA-approved medications for the treatment of moderate-severe infections with COVID-19 in pregnant women, although there are several clinical trials underway. Patients with moderate to severe symptoms should seek medical attention, while those with mild symptoms should continue with conservative therapies, as well as maintaining proper hygiene.5 Delivery methods and timing remain unchanged with cesarean delivery as currently indicated per established guidelines.5
Mariam Louis, MD
Steering Committee Member
Jorge Trabanco, MD
1. N Engl J Med. 2020 Apr 13;382:2163-4. April 13, 2020, DOI: 10.1056/NEJMc2009316
2. N Engl J Med. 2020 Jun 18; 382:e100. April 17, 2020 DOI: 10.1056/NEJMc2009226
3. Acta Obstet Gynecol Scand. 2020 Jul;99(7):823-829. 2020 Apr 7. doi: 10.1111/aogs.13867. [Epub ahead of print]
4. Arch Pathol Lab Med. 2020 Apr 27. doi: 10.5858/arpa.2020-0211-SA. [Epub ahead of print]
5. ACOG practice advisory, Novel Coronavirus 2019 (COVID-19) April 23, 2020.
Preparation is key for disaster management. It includes identifying heath-care worker capability, surge capacity, disposable medical resources, and expert consultation availability.
Staff
In disaster, the hospital transitions to a mass casualty strategy, repurposing noncritical care staff to a tiered critical care model focusing on disaster triage and mass critical care. The goal is to provide care to minimize mortality.
Stuff
Critical care supplies improve survival and are implemented quickly and easily. Essential supplies include personal protective equipment, basic modes of mechanical ventilation, hemodynamic support, antimicrobial therapy or other disease-specific countermeasures, oxygen, and prophylactic treatments.
Structure
Disaster critical care can be delivered in noncritical care areas. Hospital policies should establish surge capacity strategies.
System
Providing quality lifesaving care to appropriately triaged patients by utilizing minimal qualifications for survival, predetermined ICU admission criteria, and dynamic protocols using the highest level of evidence available scalable to local resources.
Inappropriate triage results in suboptimal care and can lead to increased mortality.
Virtual critical care can augment critical care capacity and capability.
The implementation of mass critical care requires hospitals to rapidly increase its patient volume above its normal capacity. The essential four components are staff, stuff, space, and structure. Effective mass critical care requires a different mindset than critical care in day-to-day operations.
Patrick Moon, MD; and Alexis MacDonald, MD
(Drs. Reed and Tripp's Fellows)
Mary Jane Reed, MD, FCCP, and Michael Tripp, MD, FCCP
Steering Committee Members
Practice Operations
Over the years since telemedicine (TM) was developed in the 1960s, it has transformed into more mobile, compact, and interconnected forms. However, its widespread adoption has been limited by the regulatory, compensatory, and licensing status quo. The emergence of the COVID-19 pandemic and its necessity for physical distancing has brought TM into the limelight. With restrictions on TM use lifted by CMS, the scope of TM could extend from outpatient to inpatient care to emergency triaging and management of chronic medical conditions.
In February 2020, the comprehensive 2020 COVID-19 ICD 10 coding guidelines were released. To date, CMS has approved approximately 80 codes, which can be used with telehealth and non face-face-to-face (NFTF) encounters. They include telephone calls, online digital E/M services, interprofessional telephone/internet/electric health record consultations, digitally stored data services/remote physiologic monitoring, remote reporting of self-measure blood pressure, and remote physiologic monitoring treatment management services. Some of the key "rules of the game" are highlighted below.
- For telephone visits in the outpatient setting use the codes 99441 (5-10 minutes), 99442 (11-20 minutes), and 99443 (21-30 minutes).
- For interactive real-time audio and video telecommunication (RAVT) in the outpatient setting, use the codes normally used for outpatient E/M: 99201-99215.
- For using RAVT to perform an initial visit for an inpatient, use the codes that are normally used for inpatient E/M: 99221-99223.
- For using RAVT to perform a subsequent visit for an inpatient, use the codes that are normally used for subsequent hospital care service E/M: 99231-99233.
- Seeing a critically ill patient without being in the patient's room is allowed, as a physical exam is not required for either 99291 or 99292. Be sure to use 99292 for each 30 minutes beyond the initial 74 minutes and document the time spent on the patient.
The details of the coding/billing guidelines are intricate and full of nuances and for a better understanding on how to utilize TM both in an inpatient and outpatient setting, consider the following resources:
1. CHEST Experience presentation entitled "TELE MEDICINE/TELE HEALTH IN THE ERA OF PANDEMIC" at the CHEST Annual Meeting 2020.
1. Coding and Billing Guidelines by ATS:
https://www.thoracic.org/about/newsroom/newsletters/coding-and-billing/resources/2020/mostrecentcbqapril.pdf
2. Coding specific for management of COVID patients by the AMA:
https://www.ama-assn.org/system/files/2020-05/covid-19-coding-advice.pdf
Humayun Anjum, MD, FCCP
Vice-Chair, Practice Operations
Haala Rokadia, MD, FCCP
Practice Operations NetWork Steering Committee Member
Transplant
Physical therapy teleconsultations
The COVID 19 pandemic led the health-care community to rapidly adopt telecommunication tools allowing provision of care equivalent to in-person visits. Implementation of telemedicine visits demonstrated that providers can simultaneously distance and connect with patients to provide expert care.
The University of Pennsylvania lung transplant team adapted video communications to provide individualized physical therapy (PT) recommendations for lung transplantation candidates. The evaluation includes a systems review, musculoskeletal screen, submaximal aerobic capacity testing, and performance of the short physical performance battery test (SPPBT), a frequently used frailty evaluation tool focused on lower extremity function and balance. In the era of social distancing, telemedicine capabilities have made this crucial aspect of pretransplant evaluation possible.
In advance, patients are emailed a document outlining the telemedicine PT assessment, including the SPPBT. Patients receive videos of the SPPBT to ensure they understand the test and can prepare their home to safely perform the tasks. We are able to highlight the patient's functional capabilities and detail accurate assessments of their deficits. Our teleconsultations utilize BlueJeans for connectivity and typically last about 30 minutes. At this time, we are billing for these pretransplant visits but not for posttransplant PT follow-up.
Patient experiences with the PT teleconsultations have been overwhelmingly positive. Patients and their families appreciate the uninterrupted evaluation time and the individualized recommendations for improving their deficits. The providers can devote their full attention to the patient directly in front of them. Importantly, patients and providers report they have never felt a stronger connection than through these telemedicine encounters. Longitudinal telemedicine PT assessments will enable us to better monitor our patients throughout the lung transplantation process.
Joshua Diamond, MD
Steering Committee Member
Derek Zaleski, PT, DPT
Women's Lung Health
SARS-COV-2 and pregnancy
The SARS-COV-2 pandemic has brought on many fears and uncertainties with new information emerging daily, including the effect during pregnancy. At the time of this article,however, data pertaining to COVID-19 and pregnancy remain limited. Pregnant women do not seem to have a higher infection rate than the general population. In a correspondence where pregnant women admitted for delivery underwent universal screening in NY, 1.9% of women were symptomatic and tested positive, and 13.7% of the asymptomatic patients were found to be SARS-COV-2 positive.1 Furthermore, unlike H1NI, data suggest that pregnant women infected with SARS-COV-2 currently do not seem to have worse outcomes than the average person.2,3 As of now, there have not been any reports of maternal fetal vertical transmission from COVID-19 or any other coronavirus variants.4 Postpartum testing of infants has yielded a very small number of babies who have tested positive for virus, but this more likely represents transmission after birth. There are currently no specific FDA-approved medications for the treatment of moderate-severe infections with COVID-19 in pregnant women, although there are several clinical trials underway. Patients with moderate to severe symptoms should seek medical attention, while those with mild symptoms should continue with conservative therapies, as well as maintaining proper hygiene.5 Delivery methods and timing remain unchanged with cesarean delivery as currently indicated per established guidelines.5
Mariam Louis, MD
Steering Committee Member
Jorge Trabanco, MD
1. N Engl J Med. 2020 Apr 13;382:2163-4. April 13, 2020, DOI: 10.1056/NEJMc2009316
2. N Engl J Med. 2020 Jun 18; 382:e100. April 17, 2020 DOI: 10.1056/NEJMc2009226
3. Acta Obstet Gynecol Scand. 2020 Jul;99(7):823-829. 2020 Apr 7. doi: 10.1111/aogs.13867. [Epub ahead of print]
4. Arch Pathol Lab Med. 2020 Apr 27. doi: 10.5858/arpa.2020-0211-SA. [Epub ahead of print]
5. ACOG practice advisory, Novel Coronavirus 2019 (COVID-19) April 23, 2020.
Telehealth in the COVID-19 era: The New York experience
Big data scientists and health-care experts have tried preparing physicians and patients for the arrival of telemedicine for years. Health tracking applications are on our smartphones. Compact ambulatory devices diagnose hypertension and atrial fibrillation. Advanced imaging modalities make the stethoscope more of a neck accessory than a practical tool. Despite these efficient technologic advancements, the idea of making the sacred in-person office visit remote and through a screen appealed to few. In fact, prior to the COVID-19 pandemic, only 15% of medical practices offered telehealth services and 8% of Americans joined in remote visits annually (Mann DM et al. J Am Med Inform Assoc. 2019 Feb 1;26[2]:106-114).
When the COVID-19 pandemic hit New York City and admissions for hypoxemic respiratory failure skyrocketed, ED and in-person clinic visits for other acute and chronic conditions plummeted. Prior to clinics officially closing their doors, doctors in New York City asked their patients to reserve office visits for emergency issues only ,with most patients willingly staying home to avoid exposure to the virus. Suddenly, after years of disinterest in adopting telehealth, hospitals and clinics were catapulted into a full-on need for this technology. Overnight, our division’s secretaries and medical assistants became IT support staff. We all learned together what worked, what didn’t work, and how to adapt our workflow to meet everyone’s needs.
Previously, longstanding issues with accessibility and reimbursement presented barriers to widespread adoption of telemedicine. Once the pandemic hit, though, many regulatory changes were quickly made to accommodate telehealth.
Three such changes are worth highlighting (Centers for Medicare and Medicaid Services. COVID-19 emergency declaration blanket waivers for health care providers. March 30, 2020).
First, patient privacy rules became more lenient. Prior to the pandemic, HIPAA mandated that both doctor and patient use embedded video interfaces with high levels of security. Now, health-care providers can use commonplace video chat applications such as FaceTime, Google Hangouts, Zoom, or Skype to provide telehealth without risk of penalty for HIPAA noncompliance. When connectivity concerns arose with our EMR’s embedded telehealth application, a quick transition to one of these platforms mitigated patient and provider frustration.
Second, prior to the pandemic, some private insurance providers reimbursed for televisits, but there were stipulations on how the visit could be conducted. Now, many of the commercial insurers plus Medicare and Medicaid in New York State reimburse the same amount for televisits as in-person visits (fee-for-service rate). Reimbursement rates of audio-only encounters were increased. If these changes are continued postpandemic, it will have an expansive impact on the future of an outpatient practice.
Third, restrictive government regulations relaxed with regard to telehealth deployment. Gone are the demands on providers and patients to be physically face-to-face. Many colleagues worked from home, safely social distancing.
Even though remote medical visits were a crucial part of flattening the curve during the peak of the pandemic in New York City, the telehealth experience is not without flaws.
An informal survey of providers in our own division garnered diverse and spirited viewpoints about seeing patients remotely. Instead of using a stethoscope to pick up a subtle finding, telehealth visits require the use of our eyes to scan a patient’s home environment for insights explaining their chronic cough (Where is the mold? Where is the water damage? Where is the bird?). We use our ears to hear the intonation of our patient’s voice to know when he or she is concerned, anxious, or are at their baselines. We would implore patients to put on their pulse oximeter and perform activities of daily living and/or exertion. On multiple occasions, patients would perform their own, unsolicited walks about their home to show us what they could and couldn’t do, where they place their concentrators, and where they are likely to trip over oxygen tubing. We learned to depend on them to reach the conclusion that they were at their normal state of health.
For straight-forward encounters with existing patients, most of our colleagues appreciated the simplicity and efficiency of telemedicine. But when it came to new patients, some colleagues struggled with whether they should see them for the first time over video. Universally, providers felt feelings of inadequacy without an in-person examination and review of diagnostic information.
Along those lines, many of our colleagues worried about their ability to perform the most fundamental role of a physician over the phone/internet for all patients: building trust with a patient. Eye contact, the physical exam, and verbal and nonv
Providers also noted that telehealth implementation is not the same for all individuals. Just as COVID-19 disproportionately affects the most vulnerable populations (NYC Health. COVID-19: data. Accessed July 1, 2020. https://www1.nyc.gov/site/doh/covid/covid-19-data.page), practicing telehealth has uncovered more ways in which racial/ethnic minorities, low income communities, and older patients are at a disadvantage (Garg S, et al. MMWR Morb Mortal Wkly Rep. 2020;69[15]:458). The relatively quick transition to telemedicine revealed that many of our patients don’t have emails or home computers to connect with online platforms. Similarly, some do not have smart phones with internet capabilities. Many do not speak English and cannot partake in video visits since translators are not yet embedded into the EMR’s video system. Elderly patients were frequently very anxious with telemedicine because of unfamiliarity with the technology, and many preferred a phone conversation. Thus, while more fortunate patients get to use a video interface and its association with higher patient understanding and satisfaction, our most vulnerable populations are often denied the same access to such care (Voils CI et al. J Genet Couns. 2018;27[2]:339).
Telemedicine will continue to have a significant impact on the future of health care long after the COVID-19 pandemic abates. There will be growing pains, refinement of technology, improvements in policy, and an ongoing general evolution of the system. Patients and providers will grow together as its utilization continues. We suspect patient surveys about their attitudes and preferences for telemedicine will be as varied as the providers surveyed here. A recent survey of 1000 patients about their telehealth experiences during the pandemic reported that over 75% were very or completely satisfied with their virtual care experiences and over 50% indicated they would be willing to switch providers to have virtual visits on a regular basis (Patient Perspectives on Virtual Care Report, Accessed July 7, 2020, https://www.kyruus.com/2020-virtual-care-report).
One hopes that with time and on-going feedback, the fundamental purpose of the physician-patient relationship can be maintained and both sides can still appreciate the conveniences and power of telehealth technology.
Dr. Fedyna and Dr. McGroder are affiliated with the Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY.
Big data scientists and health-care experts have tried preparing physicians and patients for the arrival of telemedicine for years. Health tracking applications are on our smartphones. Compact ambulatory devices diagnose hypertension and atrial fibrillation. Advanced imaging modalities make the stethoscope more of a neck accessory than a practical tool. Despite these efficient technologic advancements, the idea of making the sacred in-person office visit remote and through a screen appealed to few. In fact, prior to the COVID-19 pandemic, only 15% of medical practices offered telehealth services and 8% of Americans joined in remote visits annually (Mann DM et al. J Am Med Inform Assoc. 2019 Feb 1;26[2]:106-114).
When the COVID-19 pandemic hit New York City and admissions for hypoxemic respiratory failure skyrocketed, ED and in-person clinic visits for other acute and chronic conditions plummeted. Prior to clinics officially closing their doors, doctors in New York City asked their patients to reserve office visits for emergency issues only ,with most patients willingly staying home to avoid exposure to the virus. Suddenly, after years of disinterest in adopting telehealth, hospitals and clinics were catapulted into a full-on need for this technology. Overnight, our division’s secretaries and medical assistants became IT support staff. We all learned together what worked, what didn’t work, and how to adapt our workflow to meet everyone’s needs.
Previously, longstanding issues with accessibility and reimbursement presented barriers to widespread adoption of telemedicine. Once the pandemic hit, though, many regulatory changes were quickly made to accommodate telehealth.
Three such changes are worth highlighting (Centers for Medicare and Medicaid Services. COVID-19 emergency declaration blanket waivers for health care providers. March 30, 2020).
First, patient privacy rules became more lenient. Prior to the pandemic, HIPAA mandated that both doctor and patient use embedded video interfaces with high levels of security. Now, health-care providers can use commonplace video chat applications such as FaceTime, Google Hangouts, Zoom, or Skype to provide telehealth without risk of penalty for HIPAA noncompliance. When connectivity concerns arose with our EMR’s embedded telehealth application, a quick transition to one of these platforms mitigated patient and provider frustration.
Second, prior to the pandemic, some private insurance providers reimbursed for televisits, but there were stipulations on how the visit could be conducted. Now, many of the commercial insurers plus Medicare and Medicaid in New York State reimburse the same amount for televisits as in-person visits (fee-for-service rate). Reimbursement rates of audio-only encounters were increased. If these changes are continued postpandemic, it will have an expansive impact on the future of an outpatient practice.
Third, restrictive government regulations relaxed with regard to telehealth deployment. Gone are the demands on providers and patients to be physically face-to-face. Many colleagues worked from home, safely social distancing.
Even though remote medical visits were a crucial part of flattening the curve during the peak of the pandemic in New York City, the telehealth experience is not without flaws.
An informal survey of providers in our own division garnered diverse and spirited viewpoints about seeing patients remotely. Instead of using a stethoscope to pick up a subtle finding, telehealth visits require the use of our eyes to scan a patient’s home environment for insights explaining their chronic cough (Where is the mold? Where is the water damage? Where is the bird?). We use our ears to hear the intonation of our patient’s voice to know when he or she is concerned, anxious, or are at their baselines. We would implore patients to put on their pulse oximeter and perform activities of daily living and/or exertion. On multiple occasions, patients would perform their own, unsolicited walks about their home to show us what they could and couldn’t do, where they place their concentrators, and where they are likely to trip over oxygen tubing. We learned to depend on them to reach the conclusion that they were at their normal state of health.
For straight-forward encounters with existing patients, most of our colleagues appreciated the simplicity and efficiency of telemedicine. But when it came to new patients, some colleagues struggled with whether they should see them for the first time over video. Universally, providers felt feelings of inadequacy without an in-person examination and review of diagnostic information.
Along those lines, many of our colleagues worried about their ability to perform the most fundamental role of a physician over the phone/internet for all patients: building trust with a patient. Eye contact, the physical exam, and verbal and nonv
Providers also noted that telehealth implementation is not the same for all individuals. Just as COVID-19 disproportionately affects the most vulnerable populations (NYC Health. COVID-19: data. Accessed July 1, 2020. https://www1.nyc.gov/site/doh/covid/covid-19-data.page), practicing telehealth has uncovered more ways in which racial/ethnic minorities, low income communities, and older patients are at a disadvantage (Garg S, et al. MMWR Morb Mortal Wkly Rep. 2020;69[15]:458). The relatively quick transition to telemedicine revealed that many of our patients don’t have emails or home computers to connect with online platforms. Similarly, some do not have smart phones with internet capabilities. Many do not speak English and cannot partake in video visits since translators are not yet embedded into the EMR’s video system. Elderly patients were frequently very anxious with telemedicine because of unfamiliarity with the technology, and many preferred a phone conversation. Thus, while more fortunate patients get to use a video interface and its association with higher patient understanding and satisfaction, our most vulnerable populations are often denied the same access to such care (Voils CI et al. J Genet Couns. 2018;27[2]:339).
Telemedicine will continue to have a significant impact on the future of health care long after the COVID-19 pandemic abates. There will be growing pains, refinement of technology, improvements in policy, and an ongoing general evolution of the system. Patients and providers will grow together as its utilization continues. We suspect patient surveys about their attitudes and preferences for telemedicine will be as varied as the providers surveyed here. A recent survey of 1000 patients about their telehealth experiences during the pandemic reported that over 75% were very or completely satisfied with their virtual care experiences and over 50% indicated they would be willing to switch providers to have virtual visits on a regular basis (Patient Perspectives on Virtual Care Report, Accessed July 7, 2020, https://www.kyruus.com/2020-virtual-care-report).
One hopes that with time and on-going feedback, the fundamental purpose of the physician-patient relationship can be maintained and both sides can still appreciate the conveniences and power of telehealth technology.
Dr. Fedyna and Dr. McGroder are affiliated with the Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY.
Big data scientists and health-care experts have tried preparing physicians and patients for the arrival of telemedicine for years. Health tracking applications are on our smartphones. Compact ambulatory devices diagnose hypertension and atrial fibrillation. Advanced imaging modalities make the stethoscope more of a neck accessory than a practical tool. Despite these efficient technologic advancements, the idea of making the sacred in-person office visit remote and through a screen appealed to few. In fact, prior to the COVID-19 pandemic, only 15% of medical practices offered telehealth services and 8% of Americans joined in remote visits annually (Mann DM et al. J Am Med Inform Assoc. 2019 Feb 1;26[2]:106-114).
When the COVID-19 pandemic hit New York City and admissions for hypoxemic respiratory failure skyrocketed, ED and in-person clinic visits for other acute and chronic conditions plummeted. Prior to clinics officially closing their doors, doctors in New York City asked their patients to reserve office visits for emergency issues only ,with most patients willingly staying home to avoid exposure to the virus. Suddenly, after years of disinterest in adopting telehealth, hospitals and clinics were catapulted into a full-on need for this technology. Overnight, our division’s secretaries and medical assistants became IT support staff. We all learned together what worked, what didn’t work, and how to adapt our workflow to meet everyone’s needs.
Previously, longstanding issues with accessibility and reimbursement presented barriers to widespread adoption of telemedicine. Once the pandemic hit, though, many regulatory changes were quickly made to accommodate telehealth.
Three such changes are worth highlighting (Centers for Medicare and Medicaid Services. COVID-19 emergency declaration blanket waivers for health care providers. March 30, 2020).
First, patient privacy rules became more lenient. Prior to the pandemic, HIPAA mandated that both doctor and patient use embedded video interfaces with high levels of security. Now, health-care providers can use commonplace video chat applications such as FaceTime, Google Hangouts, Zoom, or Skype to provide telehealth without risk of penalty for HIPAA noncompliance. When connectivity concerns arose with our EMR’s embedded telehealth application, a quick transition to one of these platforms mitigated patient and provider frustration.
Second, prior to the pandemic, some private insurance providers reimbursed for televisits, but there were stipulations on how the visit could be conducted. Now, many of the commercial insurers plus Medicare and Medicaid in New York State reimburse the same amount for televisits as in-person visits (fee-for-service rate). Reimbursement rates of audio-only encounters were increased. If these changes are continued postpandemic, it will have an expansive impact on the future of an outpatient practice.
Third, restrictive government regulations relaxed with regard to telehealth deployment. Gone are the demands on providers and patients to be physically face-to-face. Many colleagues worked from home, safely social distancing.
Even though remote medical visits were a crucial part of flattening the curve during the peak of the pandemic in New York City, the telehealth experience is not without flaws.
An informal survey of providers in our own division garnered diverse and spirited viewpoints about seeing patients remotely. Instead of using a stethoscope to pick up a subtle finding, telehealth visits require the use of our eyes to scan a patient’s home environment for insights explaining their chronic cough (Where is the mold? Where is the water damage? Where is the bird?). We use our ears to hear the intonation of our patient’s voice to know when he or she is concerned, anxious, or are at their baselines. We would implore patients to put on their pulse oximeter and perform activities of daily living and/or exertion. On multiple occasions, patients would perform their own, unsolicited walks about their home to show us what they could and couldn’t do, where they place their concentrators, and where they are likely to trip over oxygen tubing. We learned to depend on them to reach the conclusion that they were at their normal state of health.
For straight-forward encounters with existing patients, most of our colleagues appreciated the simplicity and efficiency of telemedicine. But when it came to new patients, some colleagues struggled with whether they should see them for the first time over video. Universally, providers felt feelings of inadequacy without an in-person examination and review of diagnostic information.
Along those lines, many of our colleagues worried about their ability to perform the most fundamental role of a physician over the phone/internet for all patients: building trust with a patient. Eye contact, the physical exam, and verbal and nonv
Providers also noted that telehealth implementation is not the same for all individuals. Just as COVID-19 disproportionately affects the most vulnerable populations (NYC Health. COVID-19: data. Accessed July 1, 2020. https://www1.nyc.gov/site/doh/covid/covid-19-data.page), practicing telehealth has uncovered more ways in which racial/ethnic minorities, low income communities, and older patients are at a disadvantage (Garg S, et al. MMWR Morb Mortal Wkly Rep. 2020;69[15]:458). The relatively quick transition to telemedicine revealed that many of our patients don’t have emails or home computers to connect with online platforms. Similarly, some do not have smart phones with internet capabilities. Many do not speak English and cannot partake in video visits since translators are not yet embedded into the EMR’s video system. Elderly patients were frequently very anxious with telemedicine because of unfamiliarity with the technology, and many preferred a phone conversation. Thus, while more fortunate patients get to use a video interface and its association with higher patient understanding and satisfaction, our most vulnerable populations are often denied the same access to such care (Voils CI et al. J Genet Couns. 2018;27[2]:339).
Telemedicine will continue to have a significant impact on the future of health care long after the COVID-19 pandemic abates. There will be growing pains, refinement of technology, improvements in policy, and an ongoing general evolution of the system. Patients and providers will grow together as its utilization continues. We suspect patient surveys about their attitudes and preferences for telemedicine will be as varied as the providers surveyed here. A recent survey of 1000 patients about their telehealth experiences during the pandemic reported that over 75% were very or completely satisfied with their virtual care experiences and over 50% indicated they would be willing to switch providers to have virtual visits on a regular basis (Patient Perspectives on Virtual Care Report, Accessed July 7, 2020, https://www.kyruus.com/2020-virtual-care-report).
One hopes that with time and on-going feedback, the fundamental purpose of the physician-patient relationship can be maintained and both sides can still appreciate the conveniences and power of telehealth technology.
Dr. Fedyna and Dr. McGroder are affiliated with the Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY.