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Inhaled nitric oxide explored for COVID-19 oxygenation
The successful treatment of a patient with pulmonary arterial hypertension who contracted COVID-19 with self-administered inhaled nitrous oxide from a tankless device at home has caught the imagination of researchers investigating treatments for other patients.
It is not clear whether the team was treating the COVID or “some manifestation of her pulmonary hypertension exacerbation,” said Roham Zamanian, MD, a pulmonologist at Stanford Health in Palo Alto, California.
This is why a clinical trial is needed, he told Medscape Medical News.
“In this case, the COVID-19 respiratory infection led to a pulmonary hypertension exacerbation,” he explained. And the 34-year-old woman, who is also a physician, had demonstrated a response to nitric oxide before contracting the COVID-19 virus.
Zamanian and his colleagues describe the case in a letter published online in the American Journal of Respiratory and Critical Care. It will be discussed at the upcoming American Thoracic Society 2020 International Conference.
COVID-19 was confirmed in the patient, who had stable vasoreactive idiopathic pulmonary arterial hypertension, after she returned from a trip to Egypt. She did not want to travel the 350 miles from her home to the hospital for treatment, potentially infecting others, unless it was absolutely necessary.
“We had to make sure we were doing the right thing treating her at home, and we had to do it quickly,” Zamanian said. The patient was put on a remote routine – with vital monitoring in place – that included 6-minute walk tests twice daily and video conferencing. She also completed the EmPHasis-10 questionnaire, which is used to assess the status of patients with pulmonary hypertension.
The care team filed an Emergency Investigational New Drug application for the off-label at-home use of the tankless inhaled nitric oxide system (GENOSYL DS, VERO Biotech), which was approved by the US Food and Drug Administration. The system has so far been approved only for the treatment of newborns with persistent pulmonary hypertension.
Off-label inhaled nitric oxide has never been used in an outpatient setting. “That’s where this case is unique,” Zamanian explained.
“This case was very specific. We knew she was vasoreactive, and she knew how to use the device,” he said. “And we know nitric oxide is a quick-acting medication when it works, showing results in minutes, if not seconds.”
Within 24 hours of approval, the tankless system arrived at her home.
The patient’s therapy consisted of nitric oxide at a dose of 20 ppm plus supplemental oxygen delivered by nasal cannula at a dose of 2 L/min for 12 to 14 hours a day. After symptomatic improvement, a stepwise reduction in nitric oxide was implemented from day 13 to 17, with the dose dropping to 10 ppm, 5 ppm, and then 0 ppm.
“We quickly knew she was responding and feeling better. Without the medication, she would very likely have needed to be hospitalized,” Zamanian said.
“The real novelty of this case is demonstrating use in an outpatient system,” he pointed out. “My perspective is that this particular case was very specific, in a person who had been formally evaluated and known to be responsive to this treatment.”
The team is now preparing to launch a clinical trial of inhaled nitric oxide in COVID-19 patients without pulmonary hypertension, Zamanian reported.
Treating other patients
Nitric oxide could be useful for patients who come in with pulmonary hypertension, but “we have to test and figure that out. It could also be that patients with other underlying lung diseases could be helped with nitric oxide as well,” Zamanian said.
To treat on an outpatient basis, “we would need to make sure patients have established and reliable communications with an investigator or physician.” In addition, a protocol will have to be established that outlines how to administer the nitric oxide treatment and how to connect the nasal cannula.
“We envision patients being prescribed a certain dose and then working with either their healthcare provider or respiratory therapist to follow the standards we set,” he explained.
Although it is not a cure, nitric oxide could improve oxygenation for COIVD-19 patients in respiratory distress who have a component of abnormal pulmonary vascular function “largely driven” by ventilation perfusion – or V/Q – mismatch, he explained.
It is widely known that the gas, because it is a selective pulmonary vasodilator, can be used as rescue therapy in patients with refractory hypoxemia due to acute respiratory distress syndrome (ARDS).
“There is justification for studying it in both pulmonary hypertension and nonpulmonary hypertension patients,” Zamanian added. “The idea is that there is a component of pulmonary function and constriction with COVID-19 that may be at play here, which is not typical of regular ARDS.”
Several trials underway
In early April, an investigation into the use of high-dose nitric oxide therapy for the treatment of patients infected with SARS-CoV-2 who suffer lung complications was approved by the Therapeutic Products Directorate of Health Canada.
The NONTM – Inhaled Gaseous Nitric Oxide Antimicrobial Treatment of Difficult Bacterial and Viral Lung (COVID-19) Infections – trial will test the use of Thiolanox, a high-concentration, 5000 ppm nitric oxide canister (Mallinckrodt Pharmaceuticals) administered with the INODD delivery device (Novoteris), at Vancouver Coastal Health Authority facilities. The open-label safety study will look at whether nitric oxide can reduce the bacterial load in the lungs of adults and adolescents.
Last week, two randomized multicenter clinical trials — also focused on the potential therapeutic benefits of nitric oxide in patients with COVID-19 in a hospital setting — were launched by teams at the Massachusetts General Hospital in Boston.
The NoCovid trial will look at nitric oxide for mild to moderate COVID-19 in 240 patients treated with a noninvasive CPAP system or a nonrebreathing mask system.
The NOSARSCOVID trial will look at the use of the INOmax (Mallinckrodt) nitric oxide inhalation system in 200 COVID-19 patients with severe acute respiratory syndrome.
“Data suggest that inhaled nitric oxide may have an important role in helping patients with acute respiratory distress syndrome (ARDS) to achieve normal oxygen levels in the blood,” Lorenzo Berra, MD, from Massachusetts General Hospital, said in a news release from Mallinckrodt announcing NOSARSCOVID.
“The trial we are conducting will help us gain critical insights into the potential effectiveness of INOmax in treating ARDS in critically ill COVID-19 patients,” Berra explains.
INOmax has already been used to treat COVID-19 patients in more than 170 hospitals in the United States, according to the news release.
Still, for COVID-19 treatment, “it’s still all hypothetical, as it hasn’t been proven,” said Alex Stenzler, founder and president of Novoteris.
We’ve demonstrated that we are able to get more oxygen to the blood and that there are some pro- and anti-inflammatory properties, “but there’s no randomized evidence, and the numbers are small,” he told Medscape Medical News.
And if there is a response or benefit, “we won’t know the reason for that benefit – if it’s anti-inflammatory, antiviral, or a vascular effect,” he pointed out.
“Nitric oxide is one of the most important signaling molecules in the human body. Our own body uses it to kill organisms and cells, heal wounds,” he explained, but “we’re a long way off from knowing” whether it can help ARDS patients.
COVID-19 Ventilation Clinical Practice Guidelines, issued by the European Society of Intensive Care Medicine and the Society of Critical Care, warn that “in patients with ARDS who are on mechanical ventilation, routine use of inhaled nitric oxide is not recommended,” as reported by Medscape.
Antimicrobial, antiviral properties
Previous studies of nitric oxide have shown that it has antiviral and antimicrobial properties.
Nitric oxide was shown to reduce H1N1 in vitro in Madin-Darby canine kidney (MDCK) epithelial cells in a 2013 study conducted by Chris Miller, PhD, from the University of British Columbia in Vancouver, and colleagues. Miller is currently involved in the NONTM trial.
This could be an added benefit of treatment. “Nitric oxide has been shown to have antiviral properties,” Zamanian said. “We need to investigate it further to see how it can help us avoid negative outcomes.”
This article first appeared on Medscape.com.
The successful treatment of a patient with pulmonary arterial hypertension who contracted COVID-19 with self-administered inhaled nitrous oxide from a tankless device at home has caught the imagination of researchers investigating treatments for other patients.
It is not clear whether the team was treating the COVID or “some manifestation of her pulmonary hypertension exacerbation,” said Roham Zamanian, MD, a pulmonologist at Stanford Health in Palo Alto, California.
This is why a clinical trial is needed, he told Medscape Medical News.
“In this case, the COVID-19 respiratory infection led to a pulmonary hypertension exacerbation,” he explained. And the 34-year-old woman, who is also a physician, had demonstrated a response to nitric oxide before contracting the COVID-19 virus.
Zamanian and his colleagues describe the case in a letter published online in the American Journal of Respiratory and Critical Care. It will be discussed at the upcoming American Thoracic Society 2020 International Conference.
COVID-19 was confirmed in the patient, who had stable vasoreactive idiopathic pulmonary arterial hypertension, after she returned from a trip to Egypt. She did not want to travel the 350 miles from her home to the hospital for treatment, potentially infecting others, unless it was absolutely necessary.
“We had to make sure we were doing the right thing treating her at home, and we had to do it quickly,” Zamanian said. The patient was put on a remote routine – with vital monitoring in place – that included 6-minute walk tests twice daily and video conferencing. She also completed the EmPHasis-10 questionnaire, which is used to assess the status of patients with pulmonary hypertension.
The care team filed an Emergency Investigational New Drug application for the off-label at-home use of the tankless inhaled nitric oxide system (GENOSYL DS, VERO Biotech), which was approved by the US Food and Drug Administration. The system has so far been approved only for the treatment of newborns with persistent pulmonary hypertension.
Off-label inhaled nitric oxide has never been used in an outpatient setting. “That’s where this case is unique,” Zamanian explained.
“This case was very specific. We knew she was vasoreactive, and she knew how to use the device,” he said. “And we know nitric oxide is a quick-acting medication when it works, showing results in minutes, if not seconds.”
Within 24 hours of approval, the tankless system arrived at her home.
The patient’s therapy consisted of nitric oxide at a dose of 20 ppm plus supplemental oxygen delivered by nasal cannula at a dose of 2 L/min for 12 to 14 hours a day. After symptomatic improvement, a stepwise reduction in nitric oxide was implemented from day 13 to 17, with the dose dropping to 10 ppm, 5 ppm, and then 0 ppm.
“We quickly knew she was responding and feeling better. Without the medication, she would very likely have needed to be hospitalized,” Zamanian said.
“The real novelty of this case is demonstrating use in an outpatient system,” he pointed out. “My perspective is that this particular case was very specific, in a person who had been formally evaluated and known to be responsive to this treatment.”
The team is now preparing to launch a clinical trial of inhaled nitric oxide in COVID-19 patients without pulmonary hypertension, Zamanian reported.
Treating other patients
Nitric oxide could be useful for patients who come in with pulmonary hypertension, but “we have to test and figure that out. It could also be that patients with other underlying lung diseases could be helped with nitric oxide as well,” Zamanian said.
To treat on an outpatient basis, “we would need to make sure patients have established and reliable communications with an investigator or physician.” In addition, a protocol will have to be established that outlines how to administer the nitric oxide treatment and how to connect the nasal cannula.
“We envision patients being prescribed a certain dose and then working with either their healthcare provider or respiratory therapist to follow the standards we set,” he explained.
Although it is not a cure, nitric oxide could improve oxygenation for COIVD-19 patients in respiratory distress who have a component of abnormal pulmonary vascular function “largely driven” by ventilation perfusion – or V/Q – mismatch, he explained.
It is widely known that the gas, because it is a selective pulmonary vasodilator, can be used as rescue therapy in patients with refractory hypoxemia due to acute respiratory distress syndrome (ARDS).
“There is justification for studying it in both pulmonary hypertension and nonpulmonary hypertension patients,” Zamanian added. “The idea is that there is a component of pulmonary function and constriction with COVID-19 that may be at play here, which is not typical of regular ARDS.”
Several trials underway
In early April, an investigation into the use of high-dose nitric oxide therapy for the treatment of patients infected with SARS-CoV-2 who suffer lung complications was approved by the Therapeutic Products Directorate of Health Canada.
The NONTM – Inhaled Gaseous Nitric Oxide Antimicrobial Treatment of Difficult Bacterial and Viral Lung (COVID-19) Infections – trial will test the use of Thiolanox, a high-concentration, 5000 ppm nitric oxide canister (Mallinckrodt Pharmaceuticals) administered with the INODD delivery device (Novoteris), at Vancouver Coastal Health Authority facilities. The open-label safety study will look at whether nitric oxide can reduce the bacterial load in the lungs of adults and adolescents.
Last week, two randomized multicenter clinical trials — also focused on the potential therapeutic benefits of nitric oxide in patients with COVID-19 in a hospital setting — were launched by teams at the Massachusetts General Hospital in Boston.
The NoCovid trial will look at nitric oxide for mild to moderate COVID-19 in 240 patients treated with a noninvasive CPAP system or a nonrebreathing mask system.
The NOSARSCOVID trial will look at the use of the INOmax (Mallinckrodt) nitric oxide inhalation system in 200 COVID-19 patients with severe acute respiratory syndrome.
“Data suggest that inhaled nitric oxide may have an important role in helping patients with acute respiratory distress syndrome (ARDS) to achieve normal oxygen levels in the blood,” Lorenzo Berra, MD, from Massachusetts General Hospital, said in a news release from Mallinckrodt announcing NOSARSCOVID.
“The trial we are conducting will help us gain critical insights into the potential effectiveness of INOmax in treating ARDS in critically ill COVID-19 patients,” Berra explains.
INOmax has already been used to treat COVID-19 patients in more than 170 hospitals in the United States, according to the news release.
Still, for COVID-19 treatment, “it’s still all hypothetical, as it hasn’t been proven,” said Alex Stenzler, founder and president of Novoteris.
We’ve demonstrated that we are able to get more oxygen to the blood and that there are some pro- and anti-inflammatory properties, “but there’s no randomized evidence, and the numbers are small,” he told Medscape Medical News.
And if there is a response or benefit, “we won’t know the reason for that benefit – if it’s anti-inflammatory, antiviral, or a vascular effect,” he pointed out.
“Nitric oxide is one of the most important signaling molecules in the human body. Our own body uses it to kill organisms and cells, heal wounds,” he explained, but “we’re a long way off from knowing” whether it can help ARDS patients.
COVID-19 Ventilation Clinical Practice Guidelines, issued by the European Society of Intensive Care Medicine and the Society of Critical Care, warn that “in patients with ARDS who are on mechanical ventilation, routine use of inhaled nitric oxide is not recommended,” as reported by Medscape.
Antimicrobial, antiviral properties
Previous studies of nitric oxide have shown that it has antiviral and antimicrobial properties.
Nitric oxide was shown to reduce H1N1 in vitro in Madin-Darby canine kidney (MDCK) epithelial cells in a 2013 study conducted by Chris Miller, PhD, from the University of British Columbia in Vancouver, and colleagues. Miller is currently involved in the NONTM trial.
This could be an added benefit of treatment. “Nitric oxide has been shown to have antiviral properties,” Zamanian said. “We need to investigate it further to see how it can help us avoid negative outcomes.”
This article first appeared on Medscape.com.
The successful treatment of a patient with pulmonary arterial hypertension who contracted COVID-19 with self-administered inhaled nitrous oxide from a tankless device at home has caught the imagination of researchers investigating treatments for other patients.
It is not clear whether the team was treating the COVID or “some manifestation of her pulmonary hypertension exacerbation,” said Roham Zamanian, MD, a pulmonologist at Stanford Health in Palo Alto, California.
This is why a clinical trial is needed, he told Medscape Medical News.
“In this case, the COVID-19 respiratory infection led to a pulmonary hypertension exacerbation,” he explained. And the 34-year-old woman, who is also a physician, had demonstrated a response to nitric oxide before contracting the COVID-19 virus.
Zamanian and his colleagues describe the case in a letter published online in the American Journal of Respiratory and Critical Care. It will be discussed at the upcoming American Thoracic Society 2020 International Conference.
COVID-19 was confirmed in the patient, who had stable vasoreactive idiopathic pulmonary arterial hypertension, after she returned from a trip to Egypt. She did not want to travel the 350 miles from her home to the hospital for treatment, potentially infecting others, unless it was absolutely necessary.
“We had to make sure we were doing the right thing treating her at home, and we had to do it quickly,” Zamanian said. The patient was put on a remote routine – with vital monitoring in place – that included 6-minute walk tests twice daily and video conferencing. She also completed the EmPHasis-10 questionnaire, which is used to assess the status of patients with pulmonary hypertension.
The care team filed an Emergency Investigational New Drug application for the off-label at-home use of the tankless inhaled nitric oxide system (GENOSYL DS, VERO Biotech), which was approved by the US Food and Drug Administration. The system has so far been approved only for the treatment of newborns with persistent pulmonary hypertension.
Off-label inhaled nitric oxide has never been used in an outpatient setting. “That’s where this case is unique,” Zamanian explained.
“This case was very specific. We knew she was vasoreactive, and she knew how to use the device,” he said. “And we know nitric oxide is a quick-acting medication when it works, showing results in minutes, if not seconds.”
Within 24 hours of approval, the tankless system arrived at her home.
The patient’s therapy consisted of nitric oxide at a dose of 20 ppm plus supplemental oxygen delivered by nasal cannula at a dose of 2 L/min for 12 to 14 hours a day. After symptomatic improvement, a stepwise reduction in nitric oxide was implemented from day 13 to 17, with the dose dropping to 10 ppm, 5 ppm, and then 0 ppm.
“We quickly knew she was responding and feeling better. Without the medication, she would very likely have needed to be hospitalized,” Zamanian said.
“The real novelty of this case is demonstrating use in an outpatient system,” he pointed out. “My perspective is that this particular case was very specific, in a person who had been formally evaluated and known to be responsive to this treatment.”
The team is now preparing to launch a clinical trial of inhaled nitric oxide in COVID-19 patients without pulmonary hypertension, Zamanian reported.
Treating other patients
Nitric oxide could be useful for patients who come in with pulmonary hypertension, but “we have to test and figure that out. It could also be that patients with other underlying lung diseases could be helped with nitric oxide as well,” Zamanian said.
To treat on an outpatient basis, “we would need to make sure patients have established and reliable communications with an investigator or physician.” In addition, a protocol will have to be established that outlines how to administer the nitric oxide treatment and how to connect the nasal cannula.
“We envision patients being prescribed a certain dose and then working with either their healthcare provider or respiratory therapist to follow the standards we set,” he explained.
Although it is not a cure, nitric oxide could improve oxygenation for COIVD-19 patients in respiratory distress who have a component of abnormal pulmonary vascular function “largely driven” by ventilation perfusion – or V/Q – mismatch, he explained.
It is widely known that the gas, because it is a selective pulmonary vasodilator, can be used as rescue therapy in patients with refractory hypoxemia due to acute respiratory distress syndrome (ARDS).
“There is justification for studying it in both pulmonary hypertension and nonpulmonary hypertension patients,” Zamanian added. “The idea is that there is a component of pulmonary function and constriction with COVID-19 that may be at play here, which is not typical of regular ARDS.”
Several trials underway
In early April, an investigation into the use of high-dose nitric oxide therapy for the treatment of patients infected with SARS-CoV-2 who suffer lung complications was approved by the Therapeutic Products Directorate of Health Canada.
The NONTM – Inhaled Gaseous Nitric Oxide Antimicrobial Treatment of Difficult Bacterial and Viral Lung (COVID-19) Infections – trial will test the use of Thiolanox, a high-concentration, 5000 ppm nitric oxide canister (Mallinckrodt Pharmaceuticals) administered with the INODD delivery device (Novoteris), at Vancouver Coastal Health Authority facilities. The open-label safety study will look at whether nitric oxide can reduce the bacterial load in the lungs of adults and adolescents.
Last week, two randomized multicenter clinical trials — also focused on the potential therapeutic benefits of nitric oxide in patients with COVID-19 in a hospital setting — were launched by teams at the Massachusetts General Hospital in Boston.
The NoCovid trial will look at nitric oxide for mild to moderate COVID-19 in 240 patients treated with a noninvasive CPAP system or a nonrebreathing mask system.
The NOSARSCOVID trial will look at the use of the INOmax (Mallinckrodt) nitric oxide inhalation system in 200 COVID-19 patients with severe acute respiratory syndrome.
“Data suggest that inhaled nitric oxide may have an important role in helping patients with acute respiratory distress syndrome (ARDS) to achieve normal oxygen levels in the blood,” Lorenzo Berra, MD, from Massachusetts General Hospital, said in a news release from Mallinckrodt announcing NOSARSCOVID.
“The trial we are conducting will help us gain critical insights into the potential effectiveness of INOmax in treating ARDS in critically ill COVID-19 patients,” Berra explains.
INOmax has already been used to treat COVID-19 patients in more than 170 hospitals in the United States, according to the news release.
Still, for COVID-19 treatment, “it’s still all hypothetical, as it hasn’t been proven,” said Alex Stenzler, founder and president of Novoteris.
We’ve demonstrated that we are able to get more oxygen to the blood and that there are some pro- and anti-inflammatory properties, “but there’s no randomized evidence, and the numbers are small,” he told Medscape Medical News.
And if there is a response or benefit, “we won’t know the reason for that benefit – if it’s anti-inflammatory, antiviral, or a vascular effect,” he pointed out.
“Nitric oxide is one of the most important signaling molecules in the human body. Our own body uses it to kill organisms and cells, heal wounds,” he explained, but “we’re a long way off from knowing” whether it can help ARDS patients.
COVID-19 Ventilation Clinical Practice Guidelines, issued by the European Society of Intensive Care Medicine and the Society of Critical Care, warn that “in patients with ARDS who are on mechanical ventilation, routine use of inhaled nitric oxide is not recommended,” as reported by Medscape.
Antimicrobial, antiviral properties
Previous studies of nitric oxide have shown that it has antiviral and antimicrobial properties.
Nitric oxide was shown to reduce H1N1 in vitro in Madin-Darby canine kidney (MDCK) epithelial cells in a 2013 study conducted by Chris Miller, PhD, from the University of British Columbia in Vancouver, and colleagues. Miller is currently involved in the NONTM trial.
This could be an added benefit of treatment. “Nitric oxide has been shown to have antiviral properties,” Zamanian said. “We need to investigate it further to see how it can help us avoid negative outcomes.”
This article first appeared on Medscape.com.
Advice on treating rheumatic diseases from a COVID-19 epicenter
The COVID-19 pandemic continues to pose an unprecedented challenge to health care systems worldwide. In addition to the direct impact of the disease itself, there is a growing concern related to ensuring adequate health care utilization and addressing the needs of vulnerable populations, such as those with chronic illness.
Emanuel et al. have advocated a framework of fair allocation of resources, led by the principles of equity, maximizing benefits, and prioritizing the vulnerable. In these uncertain times, patients with rheumatic diseases represent a vulnerable population whose health and wellness are particularly threatened, not only by the risk of COVID-19, but also by reduced access to usual medical care (e.g., in-person clinic visits), potential treatment interruptions (e.g., planned infusion therapies), and the ongoing shortage of hydroxychloroquine, to name a few.
As rheumatologists, we are now tasked with the development of best practices for caring for patients with rheumatic conditions in this uncertain, evolving, and nearly data-free landscape. We also must maintain an active role as advocates for our patients to help them navigate this pandemic. Herein, we discuss our approach to caring for patients with rheumatic diseases within our practice in New York City, an epicenter of the COVID-19 pandemic.
Communication with patients
Maintaining an open line of communication with our patients (by phone, patient portal, telemedicine, and so on) has become more essential than ever. It is through these communications that we best understand our patients’ concerns and provide support and personalized treatment decisions. The most common questions we have received during recent weeks are:
- Should I stop my medication to lower my risk for infection?
- Are my current symptoms caused by coronavirus, and what should I do next?
- Where can I fill my hydroxychloroquine prescription?
The American College of Rheumatology has deployed a number of task forces aimed at advocating for rheumatologists and patients with rheumatic diseases and is doing an exemplary job guiding us. For patients, several other organizations (e.g., CreakyJoints, Arthritis Foundation, Lupus Research Alliance, Vasculitis Foundation, and Scleroderma Foundation) are also providing accurate information regarding hygiene practices, social distancing, management of medications, and other guidance related to specific rheumatic diseases. In line with ACR recommendations, we encourage a personalized, shared decision-making process with each of our patients.
Patients with rheumatic disease at risk for COVID-19 infection
First, for rheumatology patients who have no COVID-19 symptoms, our management approach is individualized. For patients who are able to maintain social distancing, we have not routinely stopped immunosuppressive medications, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents. However, we discuss the risks and benefits of continuing immunosuppressive therapy during this time with all of our patients.
In certain cases of stable, non–life-threatening disease, we may consider spacing or temporarily interrupting immunosuppressive therapy, using individualized, shared decision making. Yet, it is important to recognize that, for some patients, achieving adequate disease control can require a substantial amount of time.
Furthermore, it is important to acknowledge that disease flares requiring steroid therapy may increase the risk for infection even more, keeping in mind that, in some rheumatic diseases, high disease activity itself can increase infection risk. We advise patients who are continuing therapy to maintain at least a 1-month supply of their medications.
Decisions regarding infusions in the hospital and outpatient settings are similarly made on an individual basis, weighing the risk for virus exposure against that of disease flare. The more limited availability of appropriately distanced infusion chairs in some already overburdened systems must be considered in this discussion. We agree with the ACR, whose infusion guidance recommends that “possible changes might include temporary interruption of therapy, temporary initiation of a bridge therapy such as a less potent anti-inflammatory or immune-modulating agent, or temporary change to an alternative therapy.”
We also reinforce recommended behaviors for preventing infection, including social distancing, frequent handwashing, and avoiding touching one’s face.
Patients with rheumatic disease and confirmed or suspected COVID-19 infection
With the worldwide spread of COVID-19, patients with rheumatic diseases will undoubtedly be among those exposed and infected. Though current data are limited, within a cohort from China, 1% had an autoimmune disease. Testing recommendations to confirm COVID-19 and decision guidelines for outpatient versus inpatient management are evolving, and we consult the most up-to-date, local information regarding testing as individual potential cases arise.
For patients who develop COVID-19 and are currently taking DMARDs and biologics, we recommend that they discontinue these medications, with the exception of hydroxychloroquine (HCQ). HCQ may be continued because its mechanism is not expected to worsen infection, and it plays a key role in the management of patients with systemic lupus erythematosus (SLE). In addition, in vitro antiviral effects have been reported and there is growing interest for its use in the management of COVID-19. However, there are conflicting data and methodological concerns about the nonrandomized human studies that suggest a benefit of HCQ against COVID-19.
The decision regarding management of glucocorticoids in the setting of new COVID-19 infection is challenging and should be individualized. At present, expert panels recommend against the use of glucocorticoids among individuals with COVID-19 who do not have acute respiratory distress syndrome. However, adrenal insufficiency must be considered among patients with COVID-19 who are treated with chronic glucocorticoids. Again, these decisions should be made on an individual, case-by-case basis.
Implications of a hydroxychloroquine shortage
The use of HCQ in rheumatology is supported by years of research. Particularly in SLE, HCQ has been shown to reduce disease activity and damage and to improve survival. Furthermore, for pregnant patients with SLE, numerous studies have demonstrated the safety and benefit of HCQ for both the mother and fetus; thus, it is strongly recommended. By contrast, despite the growing interest for HCQ in patients with COVID-19, the evidence is inconclusive and limited.
The ACR suggests that decisions regarding HCQ dose reductions to extend individual patients supplies should be tailored to each patient’s need and risk in the unfortunate setting of medication shortages. Even in patients with stable SLE, however, disease flares at 6 months are more common among individuals who discontinue HCQ. Of note, these flares may incorporate novel and severe disease manifestations.
Unfortunately, other therapeutic options for SLE are associated with more adverse effects (including increased susceptibility to infection) or are largely unavailable (e.g., quinacrine). Thus, we strive to continue standard dosing of HCQ for patients who are currently flaring or recently flared, and we make shared, individualized decisions for those patients with stable disease as the HCQ shortage evolves.
Future research on COVID-19 and rheumatic disease
While we might expect that an underlying rheumatic disease and associated treatments may predispose individuals to developing COVID-19, current data do not indicate which, if any, rheumatic diseases and associated therapies convey the greatest risk.
To address this uncertainty, the rheumatology community created the COVID-19 Global Rheumatology Alliance, an international effort to initiate and maintain a deidentified patient registry for individuals with rheumatic disease who develop COVID-19. These efforts will allow us to gain essential insights regarding which patient demographics, underlying diseases, and medications are most common among patients who develop COVID-19.
This alliance encourages rheumatologists and those caring for patients with rheumatic diseases to report their patient cases to this registry. As we are confronted with making management decisions with a scarcity of supporting data, efforts like these will improve our ability to make individualized treatment recommendations.
The COVID-19 pandemic has presented us all with unprecedented challenges. As rheumatologists, it is our duty to lead our patients through this uncharted territory with close communication, information, advocacy, and personalized treatment decisions. Each of these is central to the management of rheumatology patients during the COVID-19 pandemic.
With the growing interest in immunomodulatory therapies for the complications of this infection, we have the unique opportunity to share our expertise, recommendations, and caution with our colleagues. As clinicians and scientists, we must advocate for data collection and studies that will allow us to develop novel, data-driven disease management approaches while providing the best care possible for our patients.
Stephen Paget, MD, is physician in chief emeritus for the Center for Rheumatology at Hospital for Special Surgery in New York. Kimberly Showalter, MD, is a third-year rheumatology fellow at Hospital for Special Surgery. Sebastian E. Sattui, MD, is a third-year rheumatology and 1-year vasculitis fellow at Hospital for Special Surgery.
A version of this article originally appeared on Medscape.com.
The COVID-19 pandemic continues to pose an unprecedented challenge to health care systems worldwide. In addition to the direct impact of the disease itself, there is a growing concern related to ensuring adequate health care utilization and addressing the needs of vulnerable populations, such as those with chronic illness.
Emanuel et al. have advocated a framework of fair allocation of resources, led by the principles of equity, maximizing benefits, and prioritizing the vulnerable. In these uncertain times, patients with rheumatic diseases represent a vulnerable population whose health and wellness are particularly threatened, not only by the risk of COVID-19, but also by reduced access to usual medical care (e.g., in-person clinic visits), potential treatment interruptions (e.g., planned infusion therapies), and the ongoing shortage of hydroxychloroquine, to name a few.
As rheumatologists, we are now tasked with the development of best practices for caring for patients with rheumatic conditions in this uncertain, evolving, and nearly data-free landscape. We also must maintain an active role as advocates for our patients to help them navigate this pandemic. Herein, we discuss our approach to caring for patients with rheumatic diseases within our practice in New York City, an epicenter of the COVID-19 pandemic.
Communication with patients
Maintaining an open line of communication with our patients (by phone, patient portal, telemedicine, and so on) has become more essential than ever. It is through these communications that we best understand our patients’ concerns and provide support and personalized treatment decisions. The most common questions we have received during recent weeks are:
- Should I stop my medication to lower my risk for infection?
- Are my current symptoms caused by coronavirus, and what should I do next?
- Where can I fill my hydroxychloroquine prescription?
The American College of Rheumatology has deployed a number of task forces aimed at advocating for rheumatologists and patients with rheumatic diseases and is doing an exemplary job guiding us. For patients, several other organizations (e.g., CreakyJoints, Arthritis Foundation, Lupus Research Alliance, Vasculitis Foundation, and Scleroderma Foundation) are also providing accurate information regarding hygiene practices, social distancing, management of medications, and other guidance related to specific rheumatic diseases. In line with ACR recommendations, we encourage a personalized, shared decision-making process with each of our patients.
Patients with rheumatic disease at risk for COVID-19 infection
First, for rheumatology patients who have no COVID-19 symptoms, our management approach is individualized. For patients who are able to maintain social distancing, we have not routinely stopped immunosuppressive medications, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents. However, we discuss the risks and benefits of continuing immunosuppressive therapy during this time with all of our patients.
In certain cases of stable, non–life-threatening disease, we may consider spacing or temporarily interrupting immunosuppressive therapy, using individualized, shared decision making. Yet, it is important to recognize that, for some patients, achieving adequate disease control can require a substantial amount of time.
Furthermore, it is important to acknowledge that disease flares requiring steroid therapy may increase the risk for infection even more, keeping in mind that, in some rheumatic diseases, high disease activity itself can increase infection risk. We advise patients who are continuing therapy to maintain at least a 1-month supply of their medications.
Decisions regarding infusions in the hospital and outpatient settings are similarly made on an individual basis, weighing the risk for virus exposure against that of disease flare. The more limited availability of appropriately distanced infusion chairs in some already overburdened systems must be considered in this discussion. We agree with the ACR, whose infusion guidance recommends that “possible changes might include temporary interruption of therapy, temporary initiation of a bridge therapy such as a less potent anti-inflammatory or immune-modulating agent, or temporary change to an alternative therapy.”
We also reinforce recommended behaviors for preventing infection, including social distancing, frequent handwashing, and avoiding touching one’s face.
Patients with rheumatic disease and confirmed or suspected COVID-19 infection
With the worldwide spread of COVID-19, patients with rheumatic diseases will undoubtedly be among those exposed and infected. Though current data are limited, within a cohort from China, 1% had an autoimmune disease. Testing recommendations to confirm COVID-19 and decision guidelines for outpatient versus inpatient management are evolving, and we consult the most up-to-date, local information regarding testing as individual potential cases arise.
For patients who develop COVID-19 and are currently taking DMARDs and biologics, we recommend that they discontinue these medications, with the exception of hydroxychloroquine (HCQ). HCQ may be continued because its mechanism is not expected to worsen infection, and it plays a key role in the management of patients with systemic lupus erythematosus (SLE). In addition, in vitro antiviral effects have been reported and there is growing interest for its use in the management of COVID-19. However, there are conflicting data and methodological concerns about the nonrandomized human studies that suggest a benefit of HCQ against COVID-19.
The decision regarding management of glucocorticoids in the setting of new COVID-19 infection is challenging and should be individualized. At present, expert panels recommend against the use of glucocorticoids among individuals with COVID-19 who do not have acute respiratory distress syndrome. However, adrenal insufficiency must be considered among patients with COVID-19 who are treated with chronic glucocorticoids. Again, these decisions should be made on an individual, case-by-case basis.
Implications of a hydroxychloroquine shortage
The use of HCQ in rheumatology is supported by years of research. Particularly in SLE, HCQ has been shown to reduce disease activity and damage and to improve survival. Furthermore, for pregnant patients with SLE, numerous studies have demonstrated the safety and benefit of HCQ for both the mother and fetus; thus, it is strongly recommended. By contrast, despite the growing interest for HCQ in patients with COVID-19, the evidence is inconclusive and limited.
The ACR suggests that decisions regarding HCQ dose reductions to extend individual patients supplies should be tailored to each patient’s need and risk in the unfortunate setting of medication shortages. Even in patients with stable SLE, however, disease flares at 6 months are more common among individuals who discontinue HCQ. Of note, these flares may incorporate novel and severe disease manifestations.
Unfortunately, other therapeutic options for SLE are associated with more adverse effects (including increased susceptibility to infection) or are largely unavailable (e.g., quinacrine). Thus, we strive to continue standard dosing of HCQ for patients who are currently flaring or recently flared, and we make shared, individualized decisions for those patients with stable disease as the HCQ shortage evolves.
Future research on COVID-19 and rheumatic disease
While we might expect that an underlying rheumatic disease and associated treatments may predispose individuals to developing COVID-19, current data do not indicate which, if any, rheumatic diseases and associated therapies convey the greatest risk.
To address this uncertainty, the rheumatology community created the COVID-19 Global Rheumatology Alliance, an international effort to initiate and maintain a deidentified patient registry for individuals with rheumatic disease who develop COVID-19. These efforts will allow us to gain essential insights regarding which patient demographics, underlying diseases, and medications are most common among patients who develop COVID-19.
This alliance encourages rheumatologists and those caring for patients with rheumatic diseases to report their patient cases to this registry. As we are confronted with making management decisions with a scarcity of supporting data, efforts like these will improve our ability to make individualized treatment recommendations.
The COVID-19 pandemic has presented us all with unprecedented challenges. As rheumatologists, it is our duty to lead our patients through this uncharted territory with close communication, information, advocacy, and personalized treatment decisions. Each of these is central to the management of rheumatology patients during the COVID-19 pandemic.
With the growing interest in immunomodulatory therapies for the complications of this infection, we have the unique opportunity to share our expertise, recommendations, and caution with our colleagues. As clinicians and scientists, we must advocate for data collection and studies that will allow us to develop novel, data-driven disease management approaches while providing the best care possible for our patients.
Stephen Paget, MD, is physician in chief emeritus for the Center for Rheumatology at Hospital for Special Surgery in New York. Kimberly Showalter, MD, is a third-year rheumatology fellow at Hospital for Special Surgery. Sebastian E. Sattui, MD, is a third-year rheumatology and 1-year vasculitis fellow at Hospital for Special Surgery.
A version of this article originally appeared on Medscape.com.
The COVID-19 pandemic continues to pose an unprecedented challenge to health care systems worldwide. In addition to the direct impact of the disease itself, there is a growing concern related to ensuring adequate health care utilization and addressing the needs of vulnerable populations, such as those with chronic illness.
Emanuel et al. have advocated a framework of fair allocation of resources, led by the principles of equity, maximizing benefits, and prioritizing the vulnerable. In these uncertain times, patients with rheumatic diseases represent a vulnerable population whose health and wellness are particularly threatened, not only by the risk of COVID-19, but also by reduced access to usual medical care (e.g., in-person clinic visits), potential treatment interruptions (e.g., planned infusion therapies), and the ongoing shortage of hydroxychloroquine, to name a few.
As rheumatologists, we are now tasked with the development of best practices for caring for patients with rheumatic conditions in this uncertain, evolving, and nearly data-free landscape. We also must maintain an active role as advocates for our patients to help them navigate this pandemic. Herein, we discuss our approach to caring for patients with rheumatic diseases within our practice in New York City, an epicenter of the COVID-19 pandemic.
Communication with patients
Maintaining an open line of communication with our patients (by phone, patient portal, telemedicine, and so on) has become more essential than ever. It is through these communications that we best understand our patients’ concerns and provide support and personalized treatment decisions. The most common questions we have received during recent weeks are:
- Should I stop my medication to lower my risk for infection?
- Are my current symptoms caused by coronavirus, and what should I do next?
- Where can I fill my hydroxychloroquine prescription?
The American College of Rheumatology has deployed a number of task forces aimed at advocating for rheumatologists and patients with rheumatic diseases and is doing an exemplary job guiding us. For patients, several other organizations (e.g., CreakyJoints, Arthritis Foundation, Lupus Research Alliance, Vasculitis Foundation, and Scleroderma Foundation) are also providing accurate information regarding hygiene practices, social distancing, management of medications, and other guidance related to specific rheumatic diseases. In line with ACR recommendations, we encourage a personalized, shared decision-making process with each of our patients.
Patients with rheumatic disease at risk for COVID-19 infection
First, for rheumatology patients who have no COVID-19 symptoms, our management approach is individualized. For patients who are able to maintain social distancing, we have not routinely stopped immunosuppressive medications, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents. However, we discuss the risks and benefits of continuing immunosuppressive therapy during this time with all of our patients.
In certain cases of stable, non–life-threatening disease, we may consider spacing or temporarily interrupting immunosuppressive therapy, using individualized, shared decision making. Yet, it is important to recognize that, for some patients, achieving adequate disease control can require a substantial amount of time.
Furthermore, it is important to acknowledge that disease flares requiring steroid therapy may increase the risk for infection even more, keeping in mind that, in some rheumatic diseases, high disease activity itself can increase infection risk. We advise patients who are continuing therapy to maintain at least a 1-month supply of their medications.
Decisions regarding infusions in the hospital and outpatient settings are similarly made on an individual basis, weighing the risk for virus exposure against that of disease flare. The more limited availability of appropriately distanced infusion chairs in some already overburdened systems must be considered in this discussion. We agree with the ACR, whose infusion guidance recommends that “possible changes might include temporary interruption of therapy, temporary initiation of a bridge therapy such as a less potent anti-inflammatory or immune-modulating agent, or temporary change to an alternative therapy.”
We also reinforce recommended behaviors for preventing infection, including social distancing, frequent handwashing, and avoiding touching one’s face.
Patients with rheumatic disease and confirmed or suspected COVID-19 infection
With the worldwide spread of COVID-19, patients with rheumatic diseases will undoubtedly be among those exposed and infected. Though current data are limited, within a cohort from China, 1% had an autoimmune disease. Testing recommendations to confirm COVID-19 and decision guidelines for outpatient versus inpatient management are evolving, and we consult the most up-to-date, local information regarding testing as individual potential cases arise.
For patients who develop COVID-19 and are currently taking DMARDs and biologics, we recommend that they discontinue these medications, with the exception of hydroxychloroquine (HCQ). HCQ may be continued because its mechanism is not expected to worsen infection, and it plays a key role in the management of patients with systemic lupus erythematosus (SLE). In addition, in vitro antiviral effects have been reported and there is growing interest for its use in the management of COVID-19. However, there are conflicting data and methodological concerns about the nonrandomized human studies that suggest a benefit of HCQ against COVID-19.
The decision regarding management of glucocorticoids in the setting of new COVID-19 infection is challenging and should be individualized. At present, expert panels recommend against the use of glucocorticoids among individuals with COVID-19 who do not have acute respiratory distress syndrome. However, adrenal insufficiency must be considered among patients with COVID-19 who are treated with chronic glucocorticoids. Again, these decisions should be made on an individual, case-by-case basis.
Implications of a hydroxychloroquine shortage
The use of HCQ in rheumatology is supported by years of research. Particularly in SLE, HCQ has been shown to reduce disease activity and damage and to improve survival. Furthermore, for pregnant patients with SLE, numerous studies have demonstrated the safety and benefit of HCQ for both the mother and fetus; thus, it is strongly recommended. By contrast, despite the growing interest for HCQ in patients with COVID-19, the evidence is inconclusive and limited.
The ACR suggests that decisions regarding HCQ dose reductions to extend individual patients supplies should be tailored to each patient’s need and risk in the unfortunate setting of medication shortages. Even in patients with stable SLE, however, disease flares at 6 months are more common among individuals who discontinue HCQ. Of note, these flares may incorporate novel and severe disease manifestations.
Unfortunately, other therapeutic options for SLE are associated with more adverse effects (including increased susceptibility to infection) or are largely unavailable (e.g., quinacrine). Thus, we strive to continue standard dosing of HCQ for patients who are currently flaring or recently flared, and we make shared, individualized decisions for those patients with stable disease as the HCQ shortage evolves.
Future research on COVID-19 and rheumatic disease
While we might expect that an underlying rheumatic disease and associated treatments may predispose individuals to developing COVID-19, current data do not indicate which, if any, rheumatic diseases and associated therapies convey the greatest risk.
To address this uncertainty, the rheumatology community created the COVID-19 Global Rheumatology Alliance, an international effort to initiate and maintain a deidentified patient registry for individuals with rheumatic disease who develop COVID-19. These efforts will allow us to gain essential insights regarding which patient demographics, underlying diseases, and medications are most common among patients who develop COVID-19.
This alliance encourages rheumatologists and those caring for patients with rheumatic diseases to report their patient cases to this registry. As we are confronted with making management decisions with a scarcity of supporting data, efforts like these will improve our ability to make individualized treatment recommendations.
The COVID-19 pandemic has presented us all with unprecedented challenges. As rheumatologists, it is our duty to lead our patients through this uncharted territory with close communication, information, advocacy, and personalized treatment decisions. Each of these is central to the management of rheumatology patients during the COVID-19 pandemic.
With the growing interest in immunomodulatory therapies for the complications of this infection, we have the unique opportunity to share our expertise, recommendations, and caution with our colleagues. As clinicians and scientists, we must advocate for data collection and studies that will allow us to develop novel, data-driven disease management approaches while providing the best care possible for our patients.
Stephen Paget, MD, is physician in chief emeritus for the Center for Rheumatology at Hospital for Special Surgery in New York. Kimberly Showalter, MD, is a third-year rheumatology fellow at Hospital for Special Surgery. Sebastian E. Sattui, MD, is a third-year rheumatology and 1-year vasculitis fellow at Hospital for Special Surgery.
A version of this article originally appeared on Medscape.com.
COVID fatigue is setting in
The slow-moving game of viral roulette is wearing on everyone. Eventually, we may all become fatigued and say, “well, let’s just take our chances,” the isolation being worse than the disease. I must say, however, the sight of the local funeral director loading lumber into his van at the hardware store last week made me snug up my mask a bit. We have had a surge of COVID-19 deaths in local nursing homes and I heard refrigerated space is tight. Who knows, though, maybe he just needed more shelf space in his garage.
The most exasperating thing is not knowing who has had the virus and who hasn’t, and what medicine might or might not work. My son, quartered in the sardine-tin bunks of an aircraft carrier has “it,” as do all his mates, is in total isolation except for fever checks once a day, and is having a tough time. His eagerness to receive our phone calls was sweet at first, but is now starting to worry me. Today, I received a letter from him, which I dutifully steam-microwaved for 5 minutes and am letting dry in the sun. He is asymptomatic by the way. This was not the case for one of my buddies in New York. He suffered through 10 days of shaking chills so bad he thought he had chipped his teeth, and weeks later he still has no sense of smell.
My practice has been completely disrupted, but we are open a couple of days a week. I have kept all my employees, doing busy things mostly. There will be long hours for everyone because of widely spaced appointments and a certain amount of friction with patients who miss appointments. My fellow is going to take a long trip in July. Who knows when he will have a month off again? I wonder where he plans to go.
We have rearranged the waiting room furniture, so everyone is 6 feet apart, though I am not confident this makes a difference. We all have masks, and use alcohol gel before and after patient encounters, and spritz all fixtures and handles with alcohol after encounters. I have a large exhaust fan in the lab that creates a negative pressure gradient in the office. Somehow, I don’t think it is quite the same as in the hospital.
One slick trick we’ve enacted is running an ozone generator in the office at night, which will kill all things on all surfaces and in the air. It also is probably eroding the insides of my computers, but hey, the insects and burglars hate it too.
We heard the fighter jets fly over today saluting the frontline health care workers, but did not go out and wave. I feel a little guilt about this. Treating cancer is important, but we are not in the ICU or ED immersed in virus. That is who the jets are for.
My daughter, a high school senior, is taking the loss of graduation, prom, and pomp and circumstance quite well. I am relieved I don’t have to worry about the after-prom parties. She is gearing up for college, I just hope they allow classes to start.
The future is cloudy and uncertain, despite this beautiful spring day as I write this column. Surely the way we practice medicine is going to change, and for a long while. I am thinking of taking a part-time job out of town for a year or so, and my wife is considering closing her practice altogether. If we were a few years older, there is little doubt we would just move it down the line and retire.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. He has no disclosures. Write to him at [email protected].
The slow-moving game of viral roulette is wearing on everyone. Eventually, we may all become fatigued and say, “well, let’s just take our chances,” the isolation being worse than the disease. I must say, however, the sight of the local funeral director loading lumber into his van at the hardware store last week made me snug up my mask a bit. We have had a surge of COVID-19 deaths in local nursing homes and I heard refrigerated space is tight. Who knows, though, maybe he just needed more shelf space in his garage.
The most exasperating thing is not knowing who has had the virus and who hasn’t, and what medicine might or might not work. My son, quartered in the sardine-tin bunks of an aircraft carrier has “it,” as do all his mates, is in total isolation except for fever checks once a day, and is having a tough time. His eagerness to receive our phone calls was sweet at first, but is now starting to worry me. Today, I received a letter from him, which I dutifully steam-microwaved for 5 minutes and am letting dry in the sun. He is asymptomatic by the way. This was not the case for one of my buddies in New York. He suffered through 10 days of shaking chills so bad he thought he had chipped his teeth, and weeks later he still has no sense of smell.
My practice has been completely disrupted, but we are open a couple of days a week. I have kept all my employees, doing busy things mostly. There will be long hours for everyone because of widely spaced appointments and a certain amount of friction with patients who miss appointments. My fellow is going to take a long trip in July. Who knows when he will have a month off again? I wonder where he plans to go.
We have rearranged the waiting room furniture, so everyone is 6 feet apart, though I am not confident this makes a difference. We all have masks, and use alcohol gel before and after patient encounters, and spritz all fixtures and handles with alcohol after encounters. I have a large exhaust fan in the lab that creates a negative pressure gradient in the office. Somehow, I don’t think it is quite the same as in the hospital.
One slick trick we’ve enacted is running an ozone generator in the office at night, which will kill all things on all surfaces and in the air. It also is probably eroding the insides of my computers, but hey, the insects and burglars hate it too.
We heard the fighter jets fly over today saluting the frontline health care workers, but did not go out and wave. I feel a little guilt about this. Treating cancer is important, but we are not in the ICU or ED immersed in virus. That is who the jets are for.
My daughter, a high school senior, is taking the loss of graduation, prom, and pomp and circumstance quite well. I am relieved I don’t have to worry about the after-prom parties. She is gearing up for college, I just hope they allow classes to start.
The future is cloudy and uncertain, despite this beautiful spring day as I write this column. Surely the way we practice medicine is going to change, and for a long while. I am thinking of taking a part-time job out of town for a year or so, and my wife is considering closing her practice altogether. If we were a few years older, there is little doubt we would just move it down the line and retire.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. He has no disclosures. Write to him at [email protected].
The slow-moving game of viral roulette is wearing on everyone. Eventually, we may all become fatigued and say, “well, let’s just take our chances,” the isolation being worse than the disease. I must say, however, the sight of the local funeral director loading lumber into his van at the hardware store last week made me snug up my mask a bit. We have had a surge of COVID-19 deaths in local nursing homes and I heard refrigerated space is tight. Who knows, though, maybe he just needed more shelf space in his garage.
The most exasperating thing is not knowing who has had the virus and who hasn’t, and what medicine might or might not work. My son, quartered in the sardine-tin bunks of an aircraft carrier has “it,” as do all his mates, is in total isolation except for fever checks once a day, and is having a tough time. His eagerness to receive our phone calls was sweet at first, but is now starting to worry me. Today, I received a letter from him, which I dutifully steam-microwaved for 5 minutes and am letting dry in the sun. He is asymptomatic by the way. This was not the case for one of my buddies in New York. He suffered through 10 days of shaking chills so bad he thought he had chipped his teeth, and weeks later he still has no sense of smell.
My practice has been completely disrupted, but we are open a couple of days a week. I have kept all my employees, doing busy things mostly. There will be long hours for everyone because of widely spaced appointments and a certain amount of friction with patients who miss appointments. My fellow is going to take a long trip in July. Who knows when he will have a month off again? I wonder where he plans to go.
We have rearranged the waiting room furniture, so everyone is 6 feet apart, though I am not confident this makes a difference. We all have masks, and use alcohol gel before and after patient encounters, and spritz all fixtures and handles with alcohol after encounters. I have a large exhaust fan in the lab that creates a negative pressure gradient in the office. Somehow, I don’t think it is quite the same as in the hospital.
One slick trick we’ve enacted is running an ozone generator in the office at night, which will kill all things on all surfaces and in the air. It also is probably eroding the insides of my computers, but hey, the insects and burglars hate it too.
We heard the fighter jets fly over today saluting the frontline health care workers, but did not go out and wave. I feel a little guilt about this. Treating cancer is important, but we are not in the ICU or ED immersed in virus. That is who the jets are for.
My daughter, a high school senior, is taking the loss of graduation, prom, and pomp and circumstance quite well. I am relieved I don’t have to worry about the after-prom parties. She is gearing up for college, I just hope they allow classes to start.
The future is cloudy and uncertain, despite this beautiful spring day as I write this column. Surely the way we practice medicine is going to change, and for a long while. I am thinking of taking a part-time job out of town for a year or so, and my wife is considering closing her practice altogether. If we were a few years older, there is little doubt we would just move it down the line and retire.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. He has no disclosures. Write to him at [email protected].
A surge in PTSD may be the ‘new normal’
The prolonged and unique stresses imparted by the COVID-19 pandemic has many predicting a significant rise in mental health issues in the weeks, months, and years ahead.
To understand how health care workers can best get ahead of this emerging crisis within a crisis, Medscape Psychiatry editorial director Bret Stetka, MD, spoke with Sheila Rauch, PhD, who’s with the Department of Psychiatry and Behavioral Sciences at the Emory University, Atlanta. The director of Mental Health Research and Program Evaluation at the Atlanta VA Medical Center, Dr. Rauch has studied the effects of and best treatments for posttraumatic stress disorder (PTSD) and anxiety disorders over the past 20 years.
Are we going to see a PTSD or anxiety epidemic as a result of the pandemic?
First, I think it’s really important that we prepare for the worst but hope for the best. But I would expect that, given the high levels of stress, the impact on resources, and other factors, we are going to see a pretty significant mental health impact over time. This could be the new normal for a while. Some of that will be PTSD, but there will also be other things. I would suspect that the resulting increase in rates of depression, traumatic grief, and loss is probably going to be a significant issue for years to come.
What will the anxiety we see as a result of COVID-19 look like compared with that seen in past disasters, like 9/11?
Most disasters in recent history, like 9/11, are single incidents. Something horrible happened, it impacted people at different levels, and we were able to start putting the pieces back together right away. The prolonged nature of this pandemic makes it even more variable given that the impact is going to be extended over time.
We’re also going to see a lot more people with compound impact – people who’ve lost their jobs, loved ones, maybe even their homes. All of those financial and resource losses put people in a higher risk category for negative mental health outcomes.
Is this analogous to the prolonged trauma that can occur with military service during war?
There is some similarity there. Combat is kind of an overarching context in which people experience trauma and, much like this pandemic, may or may not have traumatic exposures during it.
We’re asking health care workers to actually be in a role similar to what we ask of our military: going into danger, sometimes even without proper protective equipment, in order to save the lives of others. That’s also something we need to be factoring in as we plan to support those people and their families.
This is an ongoing incident, but is there a time window we need to be particularly worried about for seeing spikes in anxiety and PTSD?
I think we’re going to see variability on that. PTSD is a disorder that’s related to a specific incident or a couple of incidents that are similar. It’s a memory that’s haunting you.
For instance, typically if you have a combat veteran who has PTSD, they’ve been exposed to the overarching context of combat but then they have specific memories that are stuck. If they don’t have PTSD about 3-6 months after those incidents happen, then we would expect that they will not develop it, or it’s much less common that they would.
Depression has a very different course. It’s more prolonged and tends to grow with time.
Are you already seeing increased symptoms in your patients?
This is pretty similar to what we see in combat veterans. They’ll often be unhappy with the leadership decisions that were made as they were being deployed.
We’re also seeing lots more anger, sadness, and isolation now. Especially over the past couple of weeks, we’ve seen a rise in things like people reaching out for help in our intakes because we’re still open and doing phone assessments and telehealth with veterans and the veterans program.
In terms of interventions for this, what should psychiatrists, psychologists, and other clinicians be thinking about?
Right now, the best thing that we can do as mental health providers for people affected by the trauma is provide crisis intervention for those saying they are a danger to themselves and others. That means providing coping strategies and support. It also means making sure people are taking breaks and taking care of themselves, taking that little bit of time off so that they can go back, fully recharged, to their jobs and really stay there.
As we move forward, it will be clearer whether people are going to naturally recover, which most people will. For those who are going to have ongoing problems with time, we need to be getting ready as a system and as a country for those long-term mental health issues that are going to be coming up. And when I say long-term, it means the next 1-3 months. We want to be providing preventive interventions, versions of prolonged exposure, and other things that have shown some help in preventing PTSD. Psychological first aid is helpful.
There’s also an app called COVID Coach that the National Center for PTSD has created. That features a lot of positive coping resources together in one source.
Then when we get to the middle of that point and beyond it, we need to be ready to provide those evidence-based interventions for PTSD, depression, panic disorder, and other issues that are going to come out of this current situation.
But we were already short-staffed as far as mental health resources in general across the country, and especially in rural areas. So that means finding ways to efficiently use what we have through potentially briefer versions of interventions, through primary care, mental health, and other staff.
In what ways can primary care providers help?
There are versions of prolonged exposure therapy for primary care. That’s one of my big areas of research – increasing access. That would be something that we need to be building, by training and embedding mental health providers in primary care settings so that they can help to accommodate the increased need for access that’s going to be showing up for the next, I would suspect, several years with the pandemic.
Is there evidence that a prior episode of PTSD or traumatic experience like combat influences a subsequent reaction to a trauma like this?
It depends on how they manage. Research suggests that veterans or other people who have experienced trauma and naturally recovered, or who have gotten good treatment and remitted from that issue, are probably at no higher risk. But people who have subsyndromal PTSD or depression, or who are still experiencing symptoms from a history of trauma exposure, are maybe at a higher risk of having problems over time.
Do you have any guidance for healthcare providers on how to approach the pandemic with their patients, and also on how they can look after their own mental health?
In talking to patients, make sure that they have what they need. Ask if they’ve thought through how they’re going to cope if things get harder for them.
For people who have preexisting mental health issues, I’m talking with them about whether things have gotten worse. If they’re at high risk for suicide, I’m checking in to make sure that they’ve got new plans and ways to connect with people to reduce isolation, keeping in mind the social distancing that we’re asked to engage in so that they can do that safely.
It’s important to check and see if they have had any losses, whether it’s a financial loss or a personal loss of people that they care about. Also have them think through ways to stay entertained, which tends to help manage their own anxiety.
Every coping strategy we outline for patients also applies to mental health professionals. However, you would add to it the real need to take time to recharge, to take breaks, time off. It can feel overwhelming and like you need to just keep going. But the more that you get stuck in that mode of overdoing it, the less effective you’re going to be in helping people and also the more likely that you’ll be at risk of perhaps being one of the people that needs help.
It’s also important to make sure you’re staying connected with family and friends virtually, in whatever ways you can safely do that with social distancing.
So take a break to watch some Netflix now and then?
Yes!
A version of this article originally appeared on Medscape.com.
The prolonged and unique stresses imparted by the COVID-19 pandemic has many predicting a significant rise in mental health issues in the weeks, months, and years ahead.
To understand how health care workers can best get ahead of this emerging crisis within a crisis, Medscape Psychiatry editorial director Bret Stetka, MD, spoke with Sheila Rauch, PhD, who’s with the Department of Psychiatry and Behavioral Sciences at the Emory University, Atlanta. The director of Mental Health Research and Program Evaluation at the Atlanta VA Medical Center, Dr. Rauch has studied the effects of and best treatments for posttraumatic stress disorder (PTSD) and anxiety disorders over the past 20 years.
Are we going to see a PTSD or anxiety epidemic as a result of the pandemic?
First, I think it’s really important that we prepare for the worst but hope for the best. But I would expect that, given the high levels of stress, the impact on resources, and other factors, we are going to see a pretty significant mental health impact over time. This could be the new normal for a while. Some of that will be PTSD, but there will also be other things. I would suspect that the resulting increase in rates of depression, traumatic grief, and loss is probably going to be a significant issue for years to come.
What will the anxiety we see as a result of COVID-19 look like compared with that seen in past disasters, like 9/11?
Most disasters in recent history, like 9/11, are single incidents. Something horrible happened, it impacted people at different levels, and we were able to start putting the pieces back together right away. The prolonged nature of this pandemic makes it even more variable given that the impact is going to be extended over time.
We’re also going to see a lot more people with compound impact – people who’ve lost their jobs, loved ones, maybe even their homes. All of those financial and resource losses put people in a higher risk category for negative mental health outcomes.
Is this analogous to the prolonged trauma that can occur with military service during war?
There is some similarity there. Combat is kind of an overarching context in which people experience trauma and, much like this pandemic, may or may not have traumatic exposures during it.
We’re asking health care workers to actually be in a role similar to what we ask of our military: going into danger, sometimes even without proper protective equipment, in order to save the lives of others. That’s also something we need to be factoring in as we plan to support those people and their families.
This is an ongoing incident, but is there a time window we need to be particularly worried about for seeing spikes in anxiety and PTSD?
I think we’re going to see variability on that. PTSD is a disorder that’s related to a specific incident or a couple of incidents that are similar. It’s a memory that’s haunting you.
For instance, typically if you have a combat veteran who has PTSD, they’ve been exposed to the overarching context of combat but then they have specific memories that are stuck. If they don’t have PTSD about 3-6 months after those incidents happen, then we would expect that they will not develop it, or it’s much less common that they would.
Depression has a very different course. It’s more prolonged and tends to grow with time.
Are you already seeing increased symptoms in your patients?
This is pretty similar to what we see in combat veterans. They’ll often be unhappy with the leadership decisions that were made as they were being deployed.
We’re also seeing lots more anger, sadness, and isolation now. Especially over the past couple of weeks, we’ve seen a rise in things like people reaching out for help in our intakes because we’re still open and doing phone assessments and telehealth with veterans and the veterans program.
In terms of interventions for this, what should psychiatrists, psychologists, and other clinicians be thinking about?
Right now, the best thing that we can do as mental health providers for people affected by the trauma is provide crisis intervention for those saying they are a danger to themselves and others. That means providing coping strategies and support. It also means making sure people are taking breaks and taking care of themselves, taking that little bit of time off so that they can go back, fully recharged, to their jobs and really stay there.
As we move forward, it will be clearer whether people are going to naturally recover, which most people will. For those who are going to have ongoing problems with time, we need to be getting ready as a system and as a country for those long-term mental health issues that are going to be coming up. And when I say long-term, it means the next 1-3 months. We want to be providing preventive interventions, versions of prolonged exposure, and other things that have shown some help in preventing PTSD. Psychological first aid is helpful.
There’s also an app called COVID Coach that the National Center for PTSD has created. That features a lot of positive coping resources together in one source.
Then when we get to the middle of that point and beyond it, we need to be ready to provide those evidence-based interventions for PTSD, depression, panic disorder, and other issues that are going to come out of this current situation.
But we were already short-staffed as far as mental health resources in general across the country, and especially in rural areas. So that means finding ways to efficiently use what we have through potentially briefer versions of interventions, through primary care, mental health, and other staff.
In what ways can primary care providers help?
There are versions of prolonged exposure therapy for primary care. That’s one of my big areas of research – increasing access. That would be something that we need to be building, by training and embedding mental health providers in primary care settings so that they can help to accommodate the increased need for access that’s going to be showing up for the next, I would suspect, several years with the pandemic.
Is there evidence that a prior episode of PTSD or traumatic experience like combat influences a subsequent reaction to a trauma like this?
It depends on how they manage. Research suggests that veterans or other people who have experienced trauma and naturally recovered, or who have gotten good treatment and remitted from that issue, are probably at no higher risk. But people who have subsyndromal PTSD or depression, or who are still experiencing symptoms from a history of trauma exposure, are maybe at a higher risk of having problems over time.
Do you have any guidance for healthcare providers on how to approach the pandemic with their patients, and also on how they can look after their own mental health?
In talking to patients, make sure that they have what they need. Ask if they’ve thought through how they’re going to cope if things get harder for them.
For people who have preexisting mental health issues, I’m talking with them about whether things have gotten worse. If they’re at high risk for suicide, I’m checking in to make sure that they’ve got new plans and ways to connect with people to reduce isolation, keeping in mind the social distancing that we’re asked to engage in so that they can do that safely.
It’s important to check and see if they have had any losses, whether it’s a financial loss or a personal loss of people that they care about. Also have them think through ways to stay entertained, which tends to help manage their own anxiety.
Every coping strategy we outline for patients also applies to mental health professionals. However, you would add to it the real need to take time to recharge, to take breaks, time off. It can feel overwhelming and like you need to just keep going. But the more that you get stuck in that mode of overdoing it, the less effective you’re going to be in helping people and also the more likely that you’ll be at risk of perhaps being one of the people that needs help.
It’s also important to make sure you’re staying connected with family and friends virtually, in whatever ways you can safely do that with social distancing.
So take a break to watch some Netflix now and then?
Yes!
A version of this article originally appeared on Medscape.com.
The prolonged and unique stresses imparted by the COVID-19 pandemic has many predicting a significant rise in mental health issues in the weeks, months, and years ahead.
To understand how health care workers can best get ahead of this emerging crisis within a crisis, Medscape Psychiatry editorial director Bret Stetka, MD, spoke with Sheila Rauch, PhD, who’s with the Department of Psychiatry and Behavioral Sciences at the Emory University, Atlanta. The director of Mental Health Research and Program Evaluation at the Atlanta VA Medical Center, Dr. Rauch has studied the effects of and best treatments for posttraumatic stress disorder (PTSD) and anxiety disorders over the past 20 years.
Are we going to see a PTSD or anxiety epidemic as a result of the pandemic?
First, I think it’s really important that we prepare for the worst but hope for the best. But I would expect that, given the high levels of stress, the impact on resources, and other factors, we are going to see a pretty significant mental health impact over time. This could be the new normal for a while. Some of that will be PTSD, but there will also be other things. I would suspect that the resulting increase in rates of depression, traumatic grief, and loss is probably going to be a significant issue for years to come.
What will the anxiety we see as a result of COVID-19 look like compared with that seen in past disasters, like 9/11?
Most disasters in recent history, like 9/11, are single incidents. Something horrible happened, it impacted people at different levels, and we were able to start putting the pieces back together right away. The prolonged nature of this pandemic makes it even more variable given that the impact is going to be extended over time.
We’re also going to see a lot more people with compound impact – people who’ve lost their jobs, loved ones, maybe even their homes. All of those financial and resource losses put people in a higher risk category for negative mental health outcomes.
Is this analogous to the prolonged trauma that can occur with military service during war?
There is some similarity there. Combat is kind of an overarching context in which people experience trauma and, much like this pandemic, may or may not have traumatic exposures during it.
We’re asking health care workers to actually be in a role similar to what we ask of our military: going into danger, sometimes even without proper protective equipment, in order to save the lives of others. That’s also something we need to be factoring in as we plan to support those people and their families.
This is an ongoing incident, but is there a time window we need to be particularly worried about for seeing spikes in anxiety and PTSD?
I think we’re going to see variability on that. PTSD is a disorder that’s related to a specific incident or a couple of incidents that are similar. It’s a memory that’s haunting you.
For instance, typically if you have a combat veteran who has PTSD, they’ve been exposed to the overarching context of combat but then they have specific memories that are stuck. If they don’t have PTSD about 3-6 months after those incidents happen, then we would expect that they will not develop it, or it’s much less common that they would.
Depression has a very different course. It’s more prolonged and tends to grow with time.
Are you already seeing increased symptoms in your patients?
This is pretty similar to what we see in combat veterans. They’ll often be unhappy with the leadership decisions that were made as they were being deployed.
We’re also seeing lots more anger, sadness, and isolation now. Especially over the past couple of weeks, we’ve seen a rise in things like people reaching out for help in our intakes because we’re still open and doing phone assessments and telehealth with veterans and the veterans program.
In terms of interventions for this, what should psychiatrists, psychologists, and other clinicians be thinking about?
Right now, the best thing that we can do as mental health providers for people affected by the trauma is provide crisis intervention for those saying they are a danger to themselves and others. That means providing coping strategies and support. It also means making sure people are taking breaks and taking care of themselves, taking that little bit of time off so that they can go back, fully recharged, to their jobs and really stay there.
As we move forward, it will be clearer whether people are going to naturally recover, which most people will. For those who are going to have ongoing problems with time, we need to be getting ready as a system and as a country for those long-term mental health issues that are going to be coming up. And when I say long-term, it means the next 1-3 months. We want to be providing preventive interventions, versions of prolonged exposure, and other things that have shown some help in preventing PTSD. Psychological first aid is helpful.
There’s also an app called COVID Coach that the National Center for PTSD has created. That features a lot of positive coping resources together in one source.
Then when we get to the middle of that point and beyond it, we need to be ready to provide those evidence-based interventions for PTSD, depression, panic disorder, and other issues that are going to come out of this current situation.
But we were already short-staffed as far as mental health resources in general across the country, and especially in rural areas. So that means finding ways to efficiently use what we have through potentially briefer versions of interventions, through primary care, mental health, and other staff.
In what ways can primary care providers help?
There are versions of prolonged exposure therapy for primary care. That’s one of my big areas of research – increasing access. That would be something that we need to be building, by training and embedding mental health providers in primary care settings so that they can help to accommodate the increased need for access that’s going to be showing up for the next, I would suspect, several years with the pandemic.
Is there evidence that a prior episode of PTSD or traumatic experience like combat influences a subsequent reaction to a trauma like this?
It depends on how they manage. Research suggests that veterans or other people who have experienced trauma and naturally recovered, or who have gotten good treatment and remitted from that issue, are probably at no higher risk. But people who have subsyndromal PTSD or depression, or who are still experiencing symptoms from a history of trauma exposure, are maybe at a higher risk of having problems over time.
Do you have any guidance for healthcare providers on how to approach the pandemic with their patients, and also on how they can look after their own mental health?
In talking to patients, make sure that they have what they need. Ask if they’ve thought through how they’re going to cope if things get harder for them.
For people who have preexisting mental health issues, I’m talking with them about whether things have gotten worse. If they’re at high risk for suicide, I’m checking in to make sure that they’ve got new plans and ways to connect with people to reduce isolation, keeping in mind the social distancing that we’re asked to engage in so that they can do that safely.
It’s important to check and see if they have had any losses, whether it’s a financial loss or a personal loss of people that they care about. Also have them think through ways to stay entertained, which tends to help manage their own anxiety.
Every coping strategy we outline for patients also applies to mental health professionals. However, you would add to it the real need to take time to recharge, to take breaks, time off. It can feel overwhelming and like you need to just keep going. But the more that you get stuck in that mode of overdoing it, the less effective you’re going to be in helping people and also the more likely that you’ll be at risk of perhaps being one of the people that needs help.
It’s also important to make sure you’re staying connected with family and friends virtually, in whatever ways you can safely do that with social distancing.
So take a break to watch some Netflix now and then?
Yes!
A version of this article originally appeared on Medscape.com.
Modify risk factors to manage ICU delirium in patients with COVID-19
Several factors can contribute to an increased risk of ICU delirium in COVID-19 patients, wrote Katarzyna Kotfis, MD, of Pomeranian Medical University, Szczecin, Poland, and colleagues.
“In patients with COVID-19, delirium may be a manifestation of direct central nervous system invasion, induction of CNS inflammatory mediators, a secondary effect of other organ system failure, an effect of sedative strategies, prolonged mechanical ventilation time, or environmental factors, including social isolation,” they said.
Delirium in the context of COVID-19 can mean an early sign of infection, so patients should be screened using dedicated psychometric tools, the researchers wrote. Also, COVID-19 has been shown to cause pneumonia in elderly patients, who are at high risk for severe pulmonary disease related to COVID-19 and for ICU delirium generally, they said.
In addition, don’t underestimate the impact of social isolation created by quarantines, the researchers said.
“What is needed now, is not only high-quality ICU care, concentrated on providing adequate respiratory support to critically ill patients, but an identification of the source and degree of mental and spiritual suffering of patients as well as their families to provide the most ethical and person-centered care during this humanitarian crisis,” they emphasized. However, they acknowledged that nonpharmacologic interventions such as mobility outside the ICU room and interactions with family members are limited by the COVID-19 situation.
The researchers noted several mechanisms by which the COVID-19 virus may cause brain damage, including through the dysfunction of the renin-angiotensin system.
“Inflammatory response of the CNS to viral infection seems to be another important reason for poor neurological outcome and occurrence of delirium,” in COVID-19 patients, they said.
As for risk-reduction strategies, the researchers noted that “delirium in mechanically ventilated patients can be reduced dramatically to 50% using a culture of lighter sedation and mobilization via the implementation of the safety bundle called the ABCDEFs promoted by the Society of Critical Care Medicine in their ICU Liberation Collaborative,” although COVID-19 isolation is a barrier, they said.
The ABCDEF bundle consists of Assessment of pain, Both spontaneous awakening trials and spontaneous breathing trials, Choice of sedation, Delirium (hyperactive or hypoactive), Early mobility, and Family presence; all of which are challenging in the COVID-19 environment, the researchers said.
They advised implementing easy screening methods for delirium to reduce the burden on medical staff, and emphasized the importance of regular patient orientation, despite social separation from family and caregivers.
“No drugs can be recommended for the prevention or treatment of ICU delirium other than avoidance of overuse of potent psychoactive agents like sedatives and neuromuscular blockers (NMB) unless patients absolutely require such management,” they added.
“Delirium is so common and so hard to manage in the COVID-19 population,” Mangala Narasimhan, DO, of Northwell Health in New Hyde Park, N.Y., said in an interview. Delirium is impacted by many sources including a viral encephalopathy, the amount and duration of sedation medications, and prolonged intubation and hypoxemia, she said. “Managing the delirium allows you to wake the patient up successfully and without a lot of discoordination. This will help with weaning,” she noted. Barriers to delirium management for COVID-19 patients include the length of time on a ventilator, as well as amount of sedatives and paralytics, and the added issues of renal insufficiency, she noted. “How they can be addressed is thoughtful plans on the addition of long-term sedation for withdrawal symptoms, and anxiolytics for the profound anxiety associated with arousal from this type of sedation on ventilators, she said. The take-home message for clinicians is the need to perform weaning trials to manage delirium in the ICU. “We have to combat this delirium in order to be successful in taking these patients off of ventilators,” she said. Dr. Narasimhan added that more research is needed on areas including drug-to-drug interactions, duration of efficacy of various drugs, and how the virus affects the brain.
“Adherence to the ABCDEF bundle can reduce the incidence of delirium, from approximately 75% of mechanically ventilated patients to 50% or less,” David L. Bowton, MD, of Wake Forest Baptist Health in Winston-Salem, N.C., said in an interview.
“Importantly, in most studies, bundle adherence reduces mortality and ICU length of stay and lowers the total cost of care. However, isolation of patients and protection of staff, visitor restrictions, and potentially stressed staffing will likely alter how most institutions approach bundle compliance,” he said. “Gathering input from infection control clinicians and bedside providers from multiple disciplines that consider these factors to critically examine current bundle procedures and workflow will be essential to the creation and/or revision of bundle processes of care that maintain the integrity of the ABCDEF bundle yet preserve staff, patient, and family safety,” he said.
“We did not have strong evidence to suggest an optimal approach to treating delirium before the advent of the COVID-19 pandemic, so I do not believe we know what the best approach is in the current environment,” Dr. Bowton added. “Further, vigilance will be necessary to ensure that altered consciousness or cognition is ICU delirium and not attributable to another cause such as drug withdrawal, drug adverse effect, or primary central nervous system infection or immune response that mandates specific therapy,” he emphasized.
For clinicians, “this study reminds us of the importance of the ABCDEF bundle to improve outcomes of critical illness,” said Dr. Bowton. “It highlights the difficulties of providing frequent reassessment of pain, comfort, reassurance, and reorientation to critically ill patients. To me, it underscores the importance of each institution critically examining staffing needs and staffing roles to mitigate these difficulties and to explore novel methods of maintaining staff-patient and family-patient interactions to enhance compliance with all elements of the ABCDEF bundle while maintaining the safety of staff and families.”
Dr. Bowton added, “When necessary, explicit modifications to existing ABCDEF bundles should be developed and disseminated to provide realistic, readily understood guidance to achieve the best possible compliance with each bundle element. One potentially underrecognized issue will be the large, hopefully temporary, number of people requiring post–critical illness rehabilitation and mental health services,” he said. “In many regions these services are already underfunded and ill-equipped to handle an increased demand for these services,” he noted.
Additional research is needed in many areas, said Dr. Bowton. “While compliance with the ABCDEF bundle decreases the incidence and duration of delirium, decreases ICU length of stay, decreases duration of mechanical ventilation, and improves mortality, many questions remain. Individual elements of the bundle have been inconsistently associated with improved outcomes,” he said. “What is the relative importance of specific elements and what are the mechanisms by which they improve outcomes?” he asked. “We still do not know how to best achieve physical/functional recovery following critical illness, which, in light of these authors’ studies relating persisting physical debility to depression (Lancet Respir Med. 2014; 2[5]:369-79), may be a key component to improving long-term outcomes,” he said.
The study received no specific funding, although several coauthors disclosed grants from agencies including the National Center for Advancing Translational Sciences, National Institute of General Medical Sciences, National Heart, Lung, and Blood Institute, and National Institute on Aging. Dr. Narasimhan and Dr. Bowton had no financial conflicts to disclose.
SOURCE: Kotfis K et al. Critical Care. 2020 Apr 28. doi: 10.1186/s13054-020-02882-x.
Several factors can contribute to an increased risk of ICU delirium in COVID-19 patients, wrote Katarzyna Kotfis, MD, of Pomeranian Medical University, Szczecin, Poland, and colleagues.
“In patients with COVID-19, delirium may be a manifestation of direct central nervous system invasion, induction of CNS inflammatory mediators, a secondary effect of other organ system failure, an effect of sedative strategies, prolonged mechanical ventilation time, or environmental factors, including social isolation,” they said.
Delirium in the context of COVID-19 can mean an early sign of infection, so patients should be screened using dedicated psychometric tools, the researchers wrote. Also, COVID-19 has been shown to cause pneumonia in elderly patients, who are at high risk for severe pulmonary disease related to COVID-19 and for ICU delirium generally, they said.
In addition, don’t underestimate the impact of social isolation created by quarantines, the researchers said.
“What is needed now, is not only high-quality ICU care, concentrated on providing adequate respiratory support to critically ill patients, but an identification of the source and degree of mental and spiritual suffering of patients as well as their families to provide the most ethical and person-centered care during this humanitarian crisis,” they emphasized. However, they acknowledged that nonpharmacologic interventions such as mobility outside the ICU room and interactions with family members are limited by the COVID-19 situation.
The researchers noted several mechanisms by which the COVID-19 virus may cause brain damage, including through the dysfunction of the renin-angiotensin system.
“Inflammatory response of the CNS to viral infection seems to be another important reason for poor neurological outcome and occurrence of delirium,” in COVID-19 patients, they said.
As for risk-reduction strategies, the researchers noted that “delirium in mechanically ventilated patients can be reduced dramatically to 50% using a culture of lighter sedation and mobilization via the implementation of the safety bundle called the ABCDEFs promoted by the Society of Critical Care Medicine in their ICU Liberation Collaborative,” although COVID-19 isolation is a barrier, they said.
The ABCDEF bundle consists of Assessment of pain, Both spontaneous awakening trials and spontaneous breathing trials, Choice of sedation, Delirium (hyperactive or hypoactive), Early mobility, and Family presence; all of which are challenging in the COVID-19 environment, the researchers said.
They advised implementing easy screening methods for delirium to reduce the burden on medical staff, and emphasized the importance of regular patient orientation, despite social separation from family and caregivers.
“No drugs can be recommended for the prevention or treatment of ICU delirium other than avoidance of overuse of potent psychoactive agents like sedatives and neuromuscular blockers (NMB) unless patients absolutely require such management,” they added.
“Delirium is so common and so hard to manage in the COVID-19 population,” Mangala Narasimhan, DO, of Northwell Health in New Hyde Park, N.Y., said in an interview. Delirium is impacted by many sources including a viral encephalopathy, the amount and duration of sedation medications, and prolonged intubation and hypoxemia, she said. “Managing the delirium allows you to wake the patient up successfully and without a lot of discoordination. This will help with weaning,” she noted. Barriers to delirium management for COVID-19 patients include the length of time on a ventilator, as well as amount of sedatives and paralytics, and the added issues of renal insufficiency, she noted. “How they can be addressed is thoughtful plans on the addition of long-term sedation for withdrawal symptoms, and anxiolytics for the profound anxiety associated with arousal from this type of sedation on ventilators, she said. The take-home message for clinicians is the need to perform weaning trials to manage delirium in the ICU. “We have to combat this delirium in order to be successful in taking these patients off of ventilators,” she said. Dr. Narasimhan added that more research is needed on areas including drug-to-drug interactions, duration of efficacy of various drugs, and how the virus affects the brain.
“Adherence to the ABCDEF bundle can reduce the incidence of delirium, from approximately 75% of mechanically ventilated patients to 50% or less,” David L. Bowton, MD, of Wake Forest Baptist Health in Winston-Salem, N.C., said in an interview.
“Importantly, in most studies, bundle adherence reduces mortality and ICU length of stay and lowers the total cost of care. However, isolation of patients and protection of staff, visitor restrictions, and potentially stressed staffing will likely alter how most institutions approach bundle compliance,” he said. “Gathering input from infection control clinicians and bedside providers from multiple disciplines that consider these factors to critically examine current bundle procedures and workflow will be essential to the creation and/or revision of bundle processes of care that maintain the integrity of the ABCDEF bundle yet preserve staff, patient, and family safety,” he said.
“We did not have strong evidence to suggest an optimal approach to treating delirium before the advent of the COVID-19 pandemic, so I do not believe we know what the best approach is in the current environment,” Dr. Bowton added. “Further, vigilance will be necessary to ensure that altered consciousness or cognition is ICU delirium and not attributable to another cause such as drug withdrawal, drug adverse effect, or primary central nervous system infection or immune response that mandates specific therapy,” he emphasized.
For clinicians, “this study reminds us of the importance of the ABCDEF bundle to improve outcomes of critical illness,” said Dr. Bowton. “It highlights the difficulties of providing frequent reassessment of pain, comfort, reassurance, and reorientation to critically ill patients. To me, it underscores the importance of each institution critically examining staffing needs and staffing roles to mitigate these difficulties and to explore novel methods of maintaining staff-patient and family-patient interactions to enhance compliance with all elements of the ABCDEF bundle while maintaining the safety of staff and families.”
Dr. Bowton added, “When necessary, explicit modifications to existing ABCDEF bundles should be developed and disseminated to provide realistic, readily understood guidance to achieve the best possible compliance with each bundle element. One potentially underrecognized issue will be the large, hopefully temporary, number of people requiring post–critical illness rehabilitation and mental health services,” he said. “In many regions these services are already underfunded and ill-equipped to handle an increased demand for these services,” he noted.
Additional research is needed in many areas, said Dr. Bowton. “While compliance with the ABCDEF bundle decreases the incidence and duration of delirium, decreases ICU length of stay, decreases duration of mechanical ventilation, and improves mortality, many questions remain. Individual elements of the bundle have been inconsistently associated with improved outcomes,” he said. “What is the relative importance of specific elements and what are the mechanisms by which they improve outcomes?” he asked. “We still do not know how to best achieve physical/functional recovery following critical illness, which, in light of these authors’ studies relating persisting physical debility to depression (Lancet Respir Med. 2014; 2[5]:369-79), may be a key component to improving long-term outcomes,” he said.
The study received no specific funding, although several coauthors disclosed grants from agencies including the National Center for Advancing Translational Sciences, National Institute of General Medical Sciences, National Heart, Lung, and Blood Institute, and National Institute on Aging. Dr. Narasimhan and Dr. Bowton had no financial conflicts to disclose.
SOURCE: Kotfis K et al. Critical Care. 2020 Apr 28. doi: 10.1186/s13054-020-02882-x.
Several factors can contribute to an increased risk of ICU delirium in COVID-19 patients, wrote Katarzyna Kotfis, MD, of Pomeranian Medical University, Szczecin, Poland, and colleagues.
“In patients with COVID-19, delirium may be a manifestation of direct central nervous system invasion, induction of CNS inflammatory mediators, a secondary effect of other organ system failure, an effect of sedative strategies, prolonged mechanical ventilation time, or environmental factors, including social isolation,” they said.
Delirium in the context of COVID-19 can mean an early sign of infection, so patients should be screened using dedicated psychometric tools, the researchers wrote. Also, COVID-19 has been shown to cause pneumonia in elderly patients, who are at high risk for severe pulmonary disease related to COVID-19 and for ICU delirium generally, they said.
In addition, don’t underestimate the impact of social isolation created by quarantines, the researchers said.
“What is needed now, is not only high-quality ICU care, concentrated on providing adequate respiratory support to critically ill patients, but an identification of the source and degree of mental and spiritual suffering of patients as well as their families to provide the most ethical and person-centered care during this humanitarian crisis,” they emphasized. However, they acknowledged that nonpharmacologic interventions such as mobility outside the ICU room and interactions with family members are limited by the COVID-19 situation.
The researchers noted several mechanisms by which the COVID-19 virus may cause brain damage, including through the dysfunction of the renin-angiotensin system.
“Inflammatory response of the CNS to viral infection seems to be another important reason for poor neurological outcome and occurrence of delirium,” in COVID-19 patients, they said.
As for risk-reduction strategies, the researchers noted that “delirium in mechanically ventilated patients can be reduced dramatically to 50% using a culture of lighter sedation and mobilization via the implementation of the safety bundle called the ABCDEFs promoted by the Society of Critical Care Medicine in their ICU Liberation Collaborative,” although COVID-19 isolation is a barrier, they said.
The ABCDEF bundle consists of Assessment of pain, Both spontaneous awakening trials and spontaneous breathing trials, Choice of sedation, Delirium (hyperactive or hypoactive), Early mobility, and Family presence; all of which are challenging in the COVID-19 environment, the researchers said.
They advised implementing easy screening methods for delirium to reduce the burden on medical staff, and emphasized the importance of regular patient orientation, despite social separation from family and caregivers.
“No drugs can be recommended for the prevention or treatment of ICU delirium other than avoidance of overuse of potent psychoactive agents like sedatives and neuromuscular blockers (NMB) unless patients absolutely require such management,” they added.
“Delirium is so common and so hard to manage in the COVID-19 population,” Mangala Narasimhan, DO, of Northwell Health in New Hyde Park, N.Y., said in an interview. Delirium is impacted by many sources including a viral encephalopathy, the amount and duration of sedation medications, and prolonged intubation and hypoxemia, she said. “Managing the delirium allows you to wake the patient up successfully and without a lot of discoordination. This will help with weaning,” she noted. Barriers to delirium management for COVID-19 patients include the length of time on a ventilator, as well as amount of sedatives and paralytics, and the added issues of renal insufficiency, she noted. “How they can be addressed is thoughtful plans on the addition of long-term sedation for withdrawal symptoms, and anxiolytics for the profound anxiety associated with arousal from this type of sedation on ventilators, she said. The take-home message for clinicians is the need to perform weaning trials to manage delirium in the ICU. “We have to combat this delirium in order to be successful in taking these patients off of ventilators,” she said. Dr. Narasimhan added that more research is needed on areas including drug-to-drug interactions, duration of efficacy of various drugs, and how the virus affects the brain.
“Adherence to the ABCDEF bundle can reduce the incidence of delirium, from approximately 75% of mechanically ventilated patients to 50% or less,” David L. Bowton, MD, of Wake Forest Baptist Health in Winston-Salem, N.C., said in an interview.
“Importantly, in most studies, bundle adherence reduces mortality and ICU length of stay and lowers the total cost of care. However, isolation of patients and protection of staff, visitor restrictions, and potentially stressed staffing will likely alter how most institutions approach bundle compliance,” he said. “Gathering input from infection control clinicians and bedside providers from multiple disciplines that consider these factors to critically examine current bundle procedures and workflow will be essential to the creation and/or revision of bundle processes of care that maintain the integrity of the ABCDEF bundle yet preserve staff, patient, and family safety,” he said.
“We did not have strong evidence to suggest an optimal approach to treating delirium before the advent of the COVID-19 pandemic, so I do not believe we know what the best approach is in the current environment,” Dr. Bowton added. “Further, vigilance will be necessary to ensure that altered consciousness or cognition is ICU delirium and not attributable to another cause such as drug withdrawal, drug adverse effect, or primary central nervous system infection or immune response that mandates specific therapy,” he emphasized.
For clinicians, “this study reminds us of the importance of the ABCDEF bundle to improve outcomes of critical illness,” said Dr. Bowton. “It highlights the difficulties of providing frequent reassessment of pain, comfort, reassurance, and reorientation to critically ill patients. To me, it underscores the importance of each institution critically examining staffing needs and staffing roles to mitigate these difficulties and to explore novel methods of maintaining staff-patient and family-patient interactions to enhance compliance with all elements of the ABCDEF bundle while maintaining the safety of staff and families.”
Dr. Bowton added, “When necessary, explicit modifications to existing ABCDEF bundles should be developed and disseminated to provide realistic, readily understood guidance to achieve the best possible compliance with each bundle element. One potentially underrecognized issue will be the large, hopefully temporary, number of people requiring post–critical illness rehabilitation and mental health services,” he said. “In many regions these services are already underfunded and ill-equipped to handle an increased demand for these services,” he noted.
Additional research is needed in many areas, said Dr. Bowton. “While compliance with the ABCDEF bundle decreases the incidence and duration of delirium, decreases ICU length of stay, decreases duration of mechanical ventilation, and improves mortality, many questions remain. Individual elements of the bundle have been inconsistently associated with improved outcomes,” he said. “What is the relative importance of specific elements and what are the mechanisms by which they improve outcomes?” he asked. “We still do not know how to best achieve physical/functional recovery following critical illness, which, in light of these authors’ studies relating persisting physical debility to depression (Lancet Respir Med. 2014; 2[5]:369-79), may be a key component to improving long-term outcomes,” he said.
The study received no specific funding, although several coauthors disclosed grants from agencies including the National Center for Advancing Translational Sciences, National Institute of General Medical Sciences, National Heart, Lung, and Blood Institute, and National Institute on Aging. Dr. Narasimhan and Dr. Bowton had no financial conflicts to disclose.
SOURCE: Kotfis K et al. Critical Care. 2020 Apr 28. doi: 10.1186/s13054-020-02882-x.
FROM CRITICAL CARE
U.S. is poised to produce a COVID-19 vaccine, but don’t expect it soon
Manufacturers will begin producing COVID-19 vaccine doses in anticipation of approval so that if a product gets the okay for usage, distribution can begin quickly, according to Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
“We will be producing vaccine at risk, which means we’ll be [investing] considerable resources in developing doses even before we know any given candidate or candidates work,” he testified during a May 12, 2020, hearing of the Senate Health, Education, Labor, and Pensions Committee.
During the hearing, Dr. Fauci did not elaborate on how the production at risk would be undertaken, what criteria would be in place for selecting which candidates would be in the pipeline, or how much would be spent on the advanced production of these vaccines.
And while Dr. Fauci, a member of the White House coronavirus task force, remained optimistic that one or more vaccine candidates would ultimately be viable, he cautioned that there remain many unknowns that could slow the development of a vaccine for COVID-19.
“I must warn that there’s also the possibility of negative consequences that certain vaccines can actually enhance the negative effect of the infection,” he said. “The big unknown is efficacy. Will it be present or absent and how durable will it be?”
It’s unlikely that either a vaccine or an effective treatment will be available in the next 3 months, Dr. Fauci told the committee.
Sen. Lamar Alexander (R-Tenn.), the committee chairman, asked Dr. Fauci what he would say to college, primary, and secondary school administrators about how the availability of treatments and vaccines could influence the ability to reopen campuses to students. Dr. Fauci replied that the idea of having treatments or a vaccine available to facilitate the reentry of students in the fall term would be “a bit of a bridge too far.”
The emphasis in the coming months should be on testing, contact tracing, and isolation of those infected with the virus, Dr. Fauci said.
Manufacturers will begin producing COVID-19 vaccine doses in anticipation of approval so that if a product gets the okay for usage, distribution can begin quickly, according to Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
“We will be producing vaccine at risk, which means we’ll be [investing] considerable resources in developing doses even before we know any given candidate or candidates work,” he testified during a May 12, 2020, hearing of the Senate Health, Education, Labor, and Pensions Committee.
During the hearing, Dr. Fauci did not elaborate on how the production at risk would be undertaken, what criteria would be in place for selecting which candidates would be in the pipeline, or how much would be spent on the advanced production of these vaccines.
And while Dr. Fauci, a member of the White House coronavirus task force, remained optimistic that one or more vaccine candidates would ultimately be viable, he cautioned that there remain many unknowns that could slow the development of a vaccine for COVID-19.
“I must warn that there’s also the possibility of negative consequences that certain vaccines can actually enhance the negative effect of the infection,” he said. “The big unknown is efficacy. Will it be present or absent and how durable will it be?”
It’s unlikely that either a vaccine or an effective treatment will be available in the next 3 months, Dr. Fauci told the committee.
Sen. Lamar Alexander (R-Tenn.), the committee chairman, asked Dr. Fauci what he would say to college, primary, and secondary school administrators about how the availability of treatments and vaccines could influence the ability to reopen campuses to students. Dr. Fauci replied that the idea of having treatments or a vaccine available to facilitate the reentry of students in the fall term would be “a bit of a bridge too far.”
The emphasis in the coming months should be on testing, contact tracing, and isolation of those infected with the virus, Dr. Fauci said.
Manufacturers will begin producing COVID-19 vaccine doses in anticipation of approval so that if a product gets the okay for usage, distribution can begin quickly, according to Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.
“We will be producing vaccine at risk, which means we’ll be [investing] considerable resources in developing doses even before we know any given candidate or candidates work,” he testified during a May 12, 2020, hearing of the Senate Health, Education, Labor, and Pensions Committee.
During the hearing, Dr. Fauci did not elaborate on how the production at risk would be undertaken, what criteria would be in place for selecting which candidates would be in the pipeline, or how much would be spent on the advanced production of these vaccines.
And while Dr. Fauci, a member of the White House coronavirus task force, remained optimistic that one or more vaccine candidates would ultimately be viable, he cautioned that there remain many unknowns that could slow the development of a vaccine for COVID-19.
“I must warn that there’s also the possibility of negative consequences that certain vaccines can actually enhance the negative effect of the infection,” he said. “The big unknown is efficacy. Will it be present or absent and how durable will it be?”
It’s unlikely that either a vaccine or an effective treatment will be available in the next 3 months, Dr. Fauci told the committee.
Sen. Lamar Alexander (R-Tenn.), the committee chairman, asked Dr. Fauci what he would say to college, primary, and secondary school administrators about how the availability of treatments and vaccines could influence the ability to reopen campuses to students. Dr. Fauci replied that the idea of having treatments or a vaccine available to facilitate the reentry of students in the fall term would be “a bit of a bridge too far.”
The emphasis in the coming months should be on testing, contact tracing, and isolation of those infected with the virus, Dr. Fauci said.
States vary in vulnerability to COVID-19 impact
West Virginia’s large elderly population and high rates of chronic kidney disease, cardiovascular disease, diabetes, and COPD make it the most vulnerable state to the coronavirus, according to a new analysis.
Vulnerability to the virus “isn’t just health related, though, as many people are harmed by the economic effects of the pandemic,” personal finance website WalletHub said May 12.
“It’s important for the U.S. to dedicate a large portion of its resources to providing medical support during the coronavirus pandemic, but we should also support people who don’t have adequate housing or enough money to survive the pandemic,” said WalletHub analyst Jill Gonzalez.
WalletHub graded each state on 28 measures – including share of obese adults, share of homes lacking access to basic hygienic facilities, and biggest increases in unemployment because of COVID-19 – grouped into three dimensions of vulnerability: medical (60% of the total score), housing (15%), and financial (25%).
Using those measures, Louisiana is the most vulnerable state after West Virginia, followed by Mississippi, Arkansas, and Alabama. All 5 states finished in the top 6 for medical vulnerability, and 4 were in the top 10 for financial vulnerability, but only 1 (Arkansas) was in the top 10 for housing vulnerability, WalletHub said.
Among the three vulnerability dimensions, West Virginia was first in medical, Hawaii (33rd overall) was first in housing, and Louisiana was first in financial. Utah is the least vulnerable state, overall, and the least vulnerable states in each dimension are, respectively, Colorado (50th overall), the District of Columbia (29th overall), and Iowa (45th overall), the report showed.
A look at the individual metrics WalletHub used shows some serious disparities:
- New Jersey’s unemployment recipiency rate of 57.2%, the highest in the country, is 6.1 times higher than North Carolina’s 9.3%.
- The highest uninsured rate, 17.4% in Texas, is 6.2 times higher than in Massachusetts, which is the lowest at 2.8%.
- In California, the share of the homeless population that is unsheltered (71.7%) is more than 33 times higher than in North Dakota (2.2%).
“The financial damage caused by COVID-19 is leaving many Americans without the means to pay their bills and purchase necessities. … The U.S. must continue to support its financially vulnerable populations even after the virus has subsided,” Ms. Gonzalez said.
West Virginia’s large elderly population and high rates of chronic kidney disease, cardiovascular disease, diabetes, and COPD make it the most vulnerable state to the coronavirus, according to a new analysis.
Vulnerability to the virus “isn’t just health related, though, as many people are harmed by the economic effects of the pandemic,” personal finance website WalletHub said May 12.
“It’s important for the U.S. to dedicate a large portion of its resources to providing medical support during the coronavirus pandemic, but we should also support people who don’t have adequate housing or enough money to survive the pandemic,” said WalletHub analyst Jill Gonzalez.
WalletHub graded each state on 28 measures – including share of obese adults, share of homes lacking access to basic hygienic facilities, and biggest increases in unemployment because of COVID-19 – grouped into three dimensions of vulnerability: medical (60% of the total score), housing (15%), and financial (25%).
Using those measures, Louisiana is the most vulnerable state after West Virginia, followed by Mississippi, Arkansas, and Alabama. All 5 states finished in the top 6 for medical vulnerability, and 4 were in the top 10 for financial vulnerability, but only 1 (Arkansas) was in the top 10 for housing vulnerability, WalletHub said.
Among the three vulnerability dimensions, West Virginia was first in medical, Hawaii (33rd overall) was first in housing, and Louisiana was first in financial. Utah is the least vulnerable state, overall, and the least vulnerable states in each dimension are, respectively, Colorado (50th overall), the District of Columbia (29th overall), and Iowa (45th overall), the report showed.
A look at the individual metrics WalletHub used shows some serious disparities:
- New Jersey’s unemployment recipiency rate of 57.2%, the highest in the country, is 6.1 times higher than North Carolina’s 9.3%.
- The highest uninsured rate, 17.4% in Texas, is 6.2 times higher than in Massachusetts, which is the lowest at 2.8%.
- In California, the share of the homeless population that is unsheltered (71.7%) is more than 33 times higher than in North Dakota (2.2%).
“The financial damage caused by COVID-19 is leaving many Americans without the means to pay their bills and purchase necessities. … The U.S. must continue to support its financially vulnerable populations even after the virus has subsided,” Ms. Gonzalez said.
West Virginia’s large elderly population and high rates of chronic kidney disease, cardiovascular disease, diabetes, and COPD make it the most vulnerable state to the coronavirus, according to a new analysis.
Vulnerability to the virus “isn’t just health related, though, as many people are harmed by the economic effects of the pandemic,” personal finance website WalletHub said May 12.
“It’s important for the U.S. to dedicate a large portion of its resources to providing medical support during the coronavirus pandemic, but we should also support people who don’t have adequate housing or enough money to survive the pandemic,” said WalletHub analyst Jill Gonzalez.
WalletHub graded each state on 28 measures – including share of obese adults, share of homes lacking access to basic hygienic facilities, and biggest increases in unemployment because of COVID-19 – grouped into three dimensions of vulnerability: medical (60% of the total score), housing (15%), and financial (25%).
Using those measures, Louisiana is the most vulnerable state after West Virginia, followed by Mississippi, Arkansas, and Alabama. All 5 states finished in the top 6 for medical vulnerability, and 4 were in the top 10 for financial vulnerability, but only 1 (Arkansas) was in the top 10 for housing vulnerability, WalletHub said.
Among the three vulnerability dimensions, West Virginia was first in medical, Hawaii (33rd overall) was first in housing, and Louisiana was first in financial. Utah is the least vulnerable state, overall, and the least vulnerable states in each dimension are, respectively, Colorado (50th overall), the District of Columbia (29th overall), and Iowa (45th overall), the report showed.
A look at the individual metrics WalletHub used shows some serious disparities:
- New Jersey’s unemployment recipiency rate of 57.2%, the highest in the country, is 6.1 times higher than North Carolina’s 9.3%.
- The highest uninsured rate, 17.4% in Texas, is 6.2 times higher than in Massachusetts, which is the lowest at 2.8%.
- In California, the share of the homeless population that is unsheltered (71.7%) is more than 33 times higher than in North Dakota (2.2%).
“The financial damage caused by COVID-19 is leaving many Americans without the means to pay their bills and purchase necessities. … The U.S. must continue to support its financially vulnerable populations even after the virus has subsided,” Ms. Gonzalez said.
ACR gives guidance on rheumatic disease management during pandemic
When COVID-19 is suspected or confirmed in a patient with a rheumatic disease, treatment with hydroxychloroquine may be continued, but other treatments may need to be stopped or held temporarily, according to new guidance issued by the American College of Rheumatology.
That includes disease-modifying treatment with antirheumatic drugs such as sulfasalazine, methotrexate, leflunomide, and the Janus kinase (JAK) inhibitors, as well as immunosuppressants and non-interleukin (IL)-6 biologics, and this is regardless of how severe the COVID-19 illness is. NSAIDs should also be stopped if there are respiratory symptoms.
The advice is slightly less drastic if someone with stable rheumatic disease has probably been exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or are asymptomatic. In those patients, DMARDs may be continued, although there is uncertainty over whether there is a need to temporarily stop methotrexate or leflunomide. Interruption of immunosuppressive, non–IL-6, and JAK inhibitor treatment is advised pending a negative SARS-CoV-2 test result, assuming the patient’s rheumatic disease is stable.
Impetus for ACR COVID-19 guidance
“One of the earliest challenges for rheumatologists during the COVID-19 pandemic was determining how to advise our patients who were taking immunosuppressive medications and were concerned as to whether or not to discontinue their therapy,” ACR President Ellen Gravallese, MD, said in an interview about the ACR Clinical Guidance Document, which is published online in Arthritis & Rheumatology.
“A second challenge was keeping our patients safe from exposure to the virus, while still seeing those patients in person who required office visits,” added Dr. Gravallese, who is chief of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital in Boston.
She continued: “The ACR Clinical Guidance Document was prepared in order to assist rheumatologists with decisions as to how to handle current medications during different phases of a patient’s exposure to the SARS-CoV-2 virus.”
But with very little evidence available on how to manage COVID-19 patients generally, let alone specifically in those with rheumatic diseases, “it became evident that any recommendations made would need to be done in a thoughtful and organized manner, evaluating the evidence that was available and obtaining the advice of experts in infectious disease, epidemiology, and in the use of biologic and nonbiologic agents for rheumatic disease,” she said.
As such, the ACR convened a task force of 10 rheumatologists and 4 infectious disease specialists from North America to look at how best to manage patients with rheumatic disease during the COVID-19 pandemic.
“Our charge was to develop a guidance document for the care of adult rheumatic disease patients in the context of COVID-19 and not per se to provide guidance for the treatment of COVID-19,” explained task force member and the corresponding author for the guidance, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center, Omaha.
Dr. Mikuls, who was speaking at a virtual town hall meeting hosted by the ACR on May 6, noted that the guidance was obviously based on the best consensus of the available data and as such represented a “living document” that “would change and be added to” as necessary.
General recommendations for adult rheumatic disease management
In terms of general recommendations for the management of adult rheumatic disease patients, Dr. Mikuls said that six statements had been made “specific to risk assessment, prevention of infection, and best practices related to glucocorticoid use and the use of ACE [angiotensin-converting enzyme] inhibitors and ARBs [angiotensin II receptor blockers] during the pandemic.”
For example, general advice is to counsel patients to keep up general preventive measures such as social distancing and regular hand washing, reducing the number of in-person health care visits, and undertaking other means to try to prevent potential SARS-CoV-2 exposure. As for general treatment advice, glucocorticoids should be used at their lowest doses possible and should not be abruptly stopped, and antihypertensive treatment should be used as indicated.
Additional guidance statements include those that address the treatment of patients with stable rheumatic disease in the absence of infection or known exposure to SARS-CoV-2, with guidance specific to the treatment of systemic lupus erythematosus (SLE), and those with newly diagnosed or active rheumatic disease.
SLE and inflammatory arthritis recommendations
“There are several sections within the guidance document that address the treatment of patients with systemic lupus erythematosus during this pandemic,” Dr. Gravallese pointed out. “In general, it is recommended that lupus patients who are currently taking hydroxychloroquine can remain on the therapy prior to and during infection and that newly diagnosed patients with lupus can be placed on this medication at full dose. It is recommended that pregnant patients with lupus remain on therapy with this drug.”
She also observed that, for the treatment of active inflammatory arthritis, “the recommendations were written to address specific medications that could be used in this setting. In general, the task force recommendations were guided by the importance of controlling inflammation prior to exposure to the virus, even during this pandemic.
Guidance raises questions
During the ACR’s town hall meeting, the task force answered several questions raised by the guidance, such as the reasoning behind recommending that the use of traditional DMARDs be discontinued in patients with confirmed SARS-CoV-2 infection.
Dr. Mikuls observed: “Maybe if you just read the guidance statements it isn’t terribly intuitive.” There was a lot of discussion about whether or not conventional DMARDs were immunosuppressive, and even though they may not have such effects, it was decided to err on the side of caution.
“I think the task force felt that, with a COVID-19–positive patient, there is a concern of potentially confusing adverse effects related to medicines or conflate those with problems from the infection,” he said. Although rare, examples of those issues could be drug-induced hypersensitivity, hypersensitivity pneumonitis, or gastrointestinal side effects of hepatitis, all of which have been described in COVID-19. “Not only could it cause confusion, but it could maybe worsen those sequalae of COVID-19,” he said.
“I think the other part of this answer was that the panel really felt that the risk in terms of the flaring of the underlying rheumatic disease was likely to be pretty low given the finite time frame you’d be taking about – usually a time frame of 2-3 weeks you’d be holding the agent – so I think that is really why the task force ended up with that recommendation.”
Similarly, for the JAK inhibitors, the decision was to err on the side of caution when COVID-19 was suspected or confirmed. “Not so much because of the risk of thromboembolic disease, but concerns over immunosuppression that these drugs carry with them and also the fact the JAK inhibitors are probably inhibitors of type 1 interferons, which play a significant role in viral immunity and could potentially have a negative impact,” said Stanley Cohen, MD, who practices rheumatology in the Dallas area.
“On the flipside, there is interest in some of the JAK inhibitors as a potential treatment for COVID-19,” Dr. Cohen said, referring to anecdotal evidence for baricitinib (Olumiant).
Michael Weinblatt, MD, of Brigham and Women’s Hospital, addressed the recent concern over the use of NSAIDs by the public.
“There’s been a lot in the lay press that NSAIDs – because of the effects on receptors in the lung – could lead to deleterious outcomes in patients with COVID and there’s very little data to support this.
“We did recommend that NSAIDs be held in the hospitalized patient and that wasn’t because of the COVID-19 issue, it really was just medical practice, and we didn’t want to confound the care of these really sick patients with potential toxicities from NSAIDs. But as far as routine rheumatological care in your outpatients, we did not recommend that nonsteroidals be stopped if they were tolerated.”
One part of the guidance that might already need revision is the recommendation on the continued use of hydroxychloroquine in patients who develop COVID-19.
“Our guidance document says it’s OK; we were all in very strong agreement to continue hydroxychloroquine in our patients with COVID-19 because at that point, just a couple of weeks ago, we thought it was part of the potential treatment,” Karen Costenbader, MD, MPH, of Brigham and Women’s Hospital, said during the town hall meeting.
“Now the pendulum has swung the other way, and we’re worried about maybe we shouldn’t be continuing it because COVID-19 patients will be getting many other medications,” Dr. Costenbader said, and these may affect the QT-interval. “They will not be getting azithromycin because the pendulum swung the other way on that one too, but definitely on many other medications when they are sick.”
Potentially, she added, “if the rheumatic disease is under good control the inpatient physicians could decide whether they should continue [hydroxychloroquine] or not. If the COVID-19 is a mild disease, I would say we probably could continue in accordance with what we put in the document, but we will have to revisit this as well.”
Guidance is a ‘living document’
“We will be providing updates to the Clinical Guidance Document as the need arises,” Dr. Gravallese emphasized. While the general recommendations are unlikely to change very much, “the task force will be interested in seeing the results of all new data, but the results of randomized, clinical trials will be particularly important as they become available,” she said. In particular, randomized, controlled trials of glucocorticoids and IL-6 receptor blockade for use in COVID-19 will be of great importance.
“In this initial document, we could not take on all of the medical scenarios our members will face. For example, we could not take on recommendations for the pediatric population as this group of patients has a very different response than adults to the SARS-CoV-2 virus,” Dr. Gravallese acknowledged. The plan is to provide guidance for that group of patients soon.
In addition, the ACR Executive Committee has appointed a Practice and Advocacy Task Force that will “address issues rheumatologists face on the practice side, including advice regarding how to effectively use telemedicine, address the frequency and safety of infusions, determine urgent versus nonurgent issues that would or would not require face-to-face visits, and help with financial challenges.”
The American College of Rheumatology supported the guidance-development process. Dr. Mikuls, Dr. Weinblatt, Dr. Cohen, and Dr. Costenbader each disclosed research support or consultancies with multiple pharmaceutical companies. Dr. Gravallese had no disclosures.
SOURCE: Mikuls TR et al. Arthritis Rheumatol. 2020 Apr 29. doi: 10.1002/art.41301.
When COVID-19 is suspected or confirmed in a patient with a rheumatic disease, treatment with hydroxychloroquine may be continued, but other treatments may need to be stopped or held temporarily, according to new guidance issued by the American College of Rheumatology.
That includes disease-modifying treatment with antirheumatic drugs such as sulfasalazine, methotrexate, leflunomide, and the Janus kinase (JAK) inhibitors, as well as immunosuppressants and non-interleukin (IL)-6 biologics, and this is regardless of how severe the COVID-19 illness is. NSAIDs should also be stopped if there are respiratory symptoms.
The advice is slightly less drastic if someone with stable rheumatic disease has probably been exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or are asymptomatic. In those patients, DMARDs may be continued, although there is uncertainty over whether there is a need to temporarily stop methotrexate or leflunomide. Interruption of immunosuppressive, non–IL-6, and JAK inhibitor treatment is advised pending a negative SARS-CoV-2 test result, assuming the patient’s rheumatic disease is stable.
Impetus for ACR COVID-19 guidance
“One of the earliest challenges for rheumatologists during the COVID-19 pandemic was determining how to advise our patients who were taking immunosuppressive medications and were concerned as to whether or not to discontinue their therapy,” ACR President Ellen Gravallese, MD, said in an interview about the ACR Clinical Guidance Document, which is published online in Arthritis & Rheumatology.
“A second challenge was keeping our patients safe from exposure to the virus, while still seeing those patients in person who required office visits,” added Dr. Gravallese, who is chief of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital in Boston.
She continued: “The ACR Clinical Guidance Document was prepared in order to assist rheumatologists with decisions as to how to handle current medications during different phases of a patient’s exposure to the SARS-CoV-2 virus.”
But with very little evidence available on how to manage COVID-19 patients generally, let alone specifically in those with rheumatic diseases, “it became evident that any recommendations made would need to be done in a thoughtful and organized manner, evaluating the evidence that was available and obtaining the advice of experts in infectious disease, epidemiology, and in the use of biologic and nonbiologic agents for rheumatic disease,” she said.
As such, the ACR convened a task force of 10 rheumatologists and 4 infectious disease specialists from North America to look at how best to manage patients with rheumatic disease during the COVID-19 pandemic.
“Our charge was to develop a guidance document for the care of adult rheumatic disease patients in the context of COVID-19 and not per se to provide guidance for the treatment of COVID-19,” explained task force member and the corresponding author for the guidance, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center, Omaha.
Dr. Mikuls, who was speaking at a virtual town hall meeting hosted by the ACR on May 6, noted that the guidance was obviously based on the best consensus of the available data and as such represented a “living document” that “would change and be added to” as necessary.
General recommendations for adult rheumatic disease management
In terms of general recommendations for the management of adult rheumatic disease patients, Dr. Mikuls said that six statements had been made “specific to risk assessment, prevention of infection, and best practices related to glucocorticoid use and the use of ACE [angiotensin-converting enzyme] inhibitors and ARBs [angiotensin II receptor blockers] during the pandemic.”
For example, general advice is to counsel patients to keep up general preventive measures such as social distancing and regular hand washing, reducing the number of in-person health care visits, and undertaking other means to try to prevent potential SARS-CoV-2 exposure. As for general treatment advice, glucocorticoids should be used at their lowest doses possible and should not be abruptly stopped, and antihypertensive treatment should be used as indicated.
Additional guidance statements include those that address the treatment of patients with stable rheumatic disease in the absence of infection or known exposure to SARS-CoV-2, with guidance specific to the treatment of systemic lupus erythematosus (SLE), and those with newly diagnosed or active rheumatic disease.
SLE and inflammatory arthritis recommendations
“There are several sections within the guidance document that address the treatment of patients with systemic lupus erythematosus during this pandemic,” Dr. Gravallese pointed out. “In general, it is recommended that lupus patients who are currently taking hydroxychloroquine can remain on the therapy prior to and during infection and that newly diagnosed patients with lupus can be placed on this medication at full dose. It is recommended that pregnant patients with lupus remain on therapy with this drug.”
She also observed that, for the treatment of active inflammatory arthritis, “the recommendations were written to address specific medications that could be used in this setting. In general, the task force recommendations were guided by the importance of controlling inflammation prior to exposure to the virus, even during this pandemic.
Guidance raises questions
During the ACR’s town hall meeting, the task force answered several questions raised by the guidance, such as the reasoning behind recommending that the use of traditional DMARDs be discontinued in patients with confirmed SARS-CoV-2 infection.
Dr. Mikuls observed: “Maybe if you just read the guidance statements it isn’t terribly intuitive.” There was a lot of discussion about whether or not conventional DMARDs were immunosuppressive, and even though they may not have such effects, it was decided to err on the side of caution.
“I think the task force felt that, with a COVID-19–positive patient, there is a concern of potentially confusing adverse effects related to medicines or conflate those with problems from the infection,” he said. Although rare, examples of those issues could be drug-induced hypersensitivity, hypersensitivity pneumonitis, or gastrointestinal side effects of hepatitis, all of which have been described in COVID-19. “Not only could it cause confusion, but it could maybe worsen those sequalae of COVID-19,” he said.
“I think the other part of this answer was that the panel really felt that the risk in terms of the flaring of the underlying rheumatic disease was likely to be pretty low given the finite time frame you’d be taking about – usually a time frame of 2-3 weeks you’d be holding the agent – so I think that is really why the task force ended up with that recommendation.”
Similarly, for the JAK inhibitors, the decision was to err on the side of caution when COVID-19 was suspected or confirmed. “Not so much because of the risk of thromboembolic disease, but concerns over immunosuppression that these drugs carry with them and also the fact the JAK inhibitors are probably inhibitors of type 1 interferons, which play a significant role in viral immunity and could potentially have a negative impact,” said Stanley Cohen, MD, who practices rheumatology in the Dallas area.
“On the flipside, there is interest in some of the JAK inhibitors as a potential treatment for COVID-19,” Dr. Cohen said, referring to anecdotal evidence for baricitinib (Olumiant).
Michael Weinblatt, MD, of Brigham and Women’s Hospital, addressed the recent concern over the use of NSAIDs by the public.
“There’s been a lot in the lay press that NSAIDs – because of the effects on receptors in the lung – could lead to deleterious outcomes in patients with COVID and there’s very little data to support this.
“We did recommend that NSAIDs be held in the hospitalized patient and that wasn’t because of the COVID-19 issue, it really was just medical practice, and we didn’t want to confound the care of these really sick patients with potential toxicities from NSAIDs. But as far as routine rheumatological care in your outpatients, we did not recommend that nonsteroidals be stopped if they were tolerated.”
One part of the guidance that might already need revision is the recommendation on the continued use of hydroxychloroquine in patients who develop COVID-19.
“Our guidance document says it’s OK; we were all in very strong agreement to continue hydroxychloroquine in our patients with COVID-19 because at that point, just a couple of weeks ago, we thought it was part of the potential treatment,” Karen Costenbader, MD, MPH, of Brigham and Women’s Hospital, said during the town hall meeting.
“Now the pendulum has swung the other way, and we’re worried about maybe we shouldn’t be continuing it because COVID-19 patients will be getting many other medications,” Dr. Costenbader said, and these may affect the QT-interval. “They will not be getting azithromycin because the pendulum swung the other way on that one too, but definitely on many other medications when they are sick.”
Potentially, she added, “if the rheumatic disease is under good control the inpatient physicians could decide whether they should continue [hydroxychloroquine] or not. If the COVID-19 is a mild disease, I would say we probably could continue in accordance with what we put in the document, but we will have to revisit this as well.”
Guidance is a ‘living document’
“We will be providing updates to the Clinical Guidance Document as the need arises,” Dr. Gravallese emphasized. While the general recommendations are unlikely to change very much, “the task force will be interested in seeing the results of all new data, but the results of randomized, clinical trials will be particularly important as they become available,” she said. In particular, randomized, controlled trials of glucocorticoids and IL-6 receptor blockade for use in COVID-19 will be of great importance.
“In this initial document, we could not take on all of the medical scenarios our members will face. For example, we could not take on recommendations for the pediatric population as this group of patients has a very different response than adults to the SARS-CoV-2 virus,” Dr. Gravallese acknowledged. The plan is to provide guidance for that group of patients soon.
In addition, the ACR Executive Committee has appointed a Practice and Advocacy Task Force that will “address issues rheumatologists face on the practice side, including advice regarding how to effectively use telemedicine, address the frequency and safety of infusions, determine urgent versus nonurgent issues that would or would not require face-to-face visits, and help with financial challenges.”
The American College of Rheumatology supported the guidance-development process. Dr. Mikuls, Dr. Weinblatt, Dr. Cohen, and Dr. Costenbader each disclosed research support or consultancies with multiple pharmaceutical companies. Dr. Gravallese had no disclosures.
SOURCE: Mikuls TR et al. Arthritis Rheumatol. 2020 Apr 29. doi: 10.1002/art.41301.
When COVID-19 is suspected or confirmed in a patient with a rheumatic disease, treatment with hydroxychloroquine may be continued, but other treatments may need to be stopped or held temporarily, according to new guidance issued by the American College of Rheumatology.
That includes disease-modifying treatment with antirheumatic drugs such as sulfasalazine, methotrexate, leflunomide, and the Janus kinase (JAK) inhibitors, as well as immunosuppressants and non-interleukin (IL)-6 biologics, and this is regardless of how severe the COVID-19 illness is. NSAIDs should also be stopped if there are respiratory symptoms.
The advice is slightly less drastic if someone with stable rheumatic disease has probably been exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or are asymptomatic. In those patients, DMARDs may be continued, although there is uncertainty over whether there is a need to temporarily stop methotrexate or leflunomide. Interruption of immunosuppressive, non–IL-6, and JAK inhibitor treatment is advised pending a negative SARS-CoV-2 test result, assuming the patient’s rheumatic disease is stable.
Impetus for ACR COVID-19 guidance
“One of the earliest challenges for rheumatologists during the COVID-19 pandemic was determining how to advise our patients who were taking immunosuppressive medications and were concerned as to whether or not to discontinue their therapy,” ACR President Ellen Gravallese, MD, said in an interview about the ACR Clinical Guidance Document, which is published online in Arthritis & Rheumatology.
“A second challenge was keeping our patients safe from exposure to the virus, while still seeing those patients in person who required office visits,” added Dr. Gravallese, who is chief of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital in Boston.
She continued: “The ACR Clinical Guidance Document was prepared in order to assist rheumatologists with decisions as to how to handle current medications during different phases of a patient’s exposure to the SARS-CoV-2 virus.”
But with very little evidence available on how to manage COVID-19 patients generally, let alone specifically in those with rheumatic diseases, “it became evident that any recommendations made would need to be done in a thoughtful and organized manner, evaluating the evidence that was available and obtaining the advice of experts in infectious disease, epidemiology, and in the use of biologic and nonbiologic agents for rheumatic disease,” she said.
As such, the ACR convened a task force of 10 rheumatologists and 4 infectious disease specialists from North America to look at how best to manage patients with rheumatic disease during the COVID-19 pandemic.
“Our charge was to develop a guidance document for the care of adult rheumatic disease patients in the context of COVID-19 and not per se to provide guidance for the treatment of COVID-19,” explained task force member and the corresponding author for the guidance, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center, Omaha.
Dr. Mikuls, who was speaking at a virtual town hall meeting hosted by the ACR on May 6, noted that the guidance was obviously based on the best consensus of the available data and as such represented a “living document” that “would change and be added to” as necessary.
General recommendations for adult rheumatic disease management
In terms of general recommendations for the management of adult rheumatic disease patients, Dr. Mikuls said that six statements had been made “specific to risk assessment, prevention of infection, and best practices related to glucocorticoid use and the use of ACE [angiotensin-converting enzyme] inhibitors and ARBs [angiotensin II receptor blockers] during the pandemic.”
For example, general advice is to counsel patients to keep up general preventive measures such as social distancing and regular hand washing, reducing the number of in-person health care visits, and undertaking other means to try to prevent potential SARS-CoV-2 exposure. As for general treatment advice, glucocorticoids should be used at their lowest doses possible and should not be abruptly stopped, and antihypertensive treatment should be used as indicated.
Additional guidance statements include those that address the treatment of patients with stable rheumatic disease in the absence of infection or known exposure to SARS-CoV-2, with guidance specific to the treatment of systemic lupus erythematosus (SLE), and those with newly diagnosed or active rheumatic disease.
SLE and inflammatory arthritis recommendations
“There are several sections within the guidance document that address the treatment of patients with systemic lupus erythematosus during this pandemic,” Dr. Gravallese pointed out. “In general, it is recommended that lupus patients who are currently taking hydroxychloroquine can remain on the therapy prior to and during infection and that newly diagnosed patients with lupus can be placed on this medication at full dose. It is recommended that pregnant patients with lupus remain on therapy with this drug.”
She also observed that, for the treatment of active inflammatory arthritis, “the recommendations were written to address specific medications that could be used in this setting. In general, the task force recommendations were guided by the importance of controlling inflammation prior to exposure to the virus, even during this pandemic.
Guidance raises questions
During the ACR’s town hall meeting, the task force answered several questions raised by the guidance, such as the reasoning behind recommending that the use of traditional DMARDs be discontinued in patients with confirmed SARS-CoV-2 infection.
Dr. Mikuls observed: “Maybe if you just read the guidance statements it isn’t terribly intuitive.” There was a lot of discussion about whether or not conventional DMARDs were immunosuppressive, and even though they may not have such effects, it was decided to err on the side of caution.
“I think the task force felt that, with a COVID-19–positive patient, there is a concern of potentially confusing adverse effects related to medicines or conflate those with problems from the infection,” he said. Although rare, examples of those issues could be drug-induced hypersensitivity, hypersensitivity pneumonitis, or gastrointestinal side effects of hepatitis, all of which have been described in COVID-19. “Not only could it cause confusion, but it could maybe worsen those sequalae of COVID-19,” he said.
“I think the other part of this answer was that the panel really felt that the risk in terms of the flaring of the underlying rheumatic disease was likely to be pretty low given the finite time frame you’d be taking about – usually a time frame of 2-3 weeks you’d be holding the agent – so I think that is really why the task force ended up with that recommendation.”
Similarly, for the JAK inhibitors, the decision was to err on the side of caution when COVID-19 was suspected or confirmed. “Not so much because of the risk of thromboembolic disease, but concerns over immunosuppression that these drugs carry with them and also the fact the JAK inhibitors are probably inhibitors of type 1 interferons, which play a significant role in viral immunity and could potentially have a negative impact,” said Stanley Cohen, MD, who practices rheumatology in the Dallas area.
“On the flipside, there is interest in some of the JAK inhibitors as a potential treatment for COVID-19,” Dr. Cohen said, referring to anecdotal evidence for baricitinib (Olumiant).
Michael Weinblatt, MD, of Brigham and Women’s Hospital, addressed the recent concern over the use of NSAIDs by the public.
“There’s been a lot in the lay press that NSAIDs – because of the effects on receptors in the lung – could lead to deleterious outcomes in patients with COVID and there’s very little data to support this.
“We did recommend that NSAIDs be held in the hospitalized patient and that wasn’t because of the COVID-19 issue, it really was just medical practice, and we didn’t want to confound the care of these really sick patients with potential toxicities from NSAIDs. But as far as routine rheumatological care in your outpatients, we did not recommend that nonsteroidals be stopped if they were tolerated.”
One part of the guidance that might already need revision is the recommendation on the continued use of hydroxychloroquine in patients who develop COVID-19.
“Our guidance document says it’s OK; we were all in very strong agreement to continue hydroxychloroquine in our patients with COVID-19 because at that point, just a couple of weeks ago, we thought it was part of the potential treatment,” Karen Costenbader, MD, MPH, of Brigham and Women’s Hospital, said during the town hall meeting.
“Now the pendulum has swung the other way, and we’re worried about maybe we shouldn’t be continuing it because COVID-19 patients will be getting many other medications,” Dr. Costenbader said, and these may affect the QT-interval. “They will not be getting azithromycin because the pendulum swung the other way on that one too, but definitely on many other medications when they are sick.”
Potentially, she added, “if the rheumatic disease is under good control the inpatient physicians could decide whether they should continue [hydroxychloroquine] or not. If the COVID-19 is a mild disease, I would say we probably could continue in accordance with what we put in the document, but we will have to revisit this as well.”
Guidance is a ‘living document’
“We will be providing updates to the Clinical Guidance Document as the need arises,” Dr. Gravallese emphasized. While the general recommendations are unlikely to change very much, “the task force will be interested in seeing the results of all new data, but the results of randomized, clinical trials will be particularly important as they become available,” she said. In particular, randomized, controlled trials of glucocorticoids and IL-6 receptor blockade for use in COVID-19 will be of great importance.
“In this initial document, we could not take on all of the medical scenarios our members will face. For example, we could not take on recommendations for the pediatric population as this group of patients has a very different response than adults to the SARS-CoV-2 virus,” Dr. Gravallese acknowledged. The plan is to provide guidance for that group of patients soon.
In addition, the ACR Executive Committee has appointed a Practice and Advocacy Task Force that will “address issues rheumatologists face on the practice side, including advice regarding how to effectively use telemedicine, address the frequency and safety of infusions, determine urgent versus nonurgent issues that would or would not require face-to-face visits, and help with financial challenges.”
The American College of Rheumatology supported the guidance-development process. Dr. Mikuls, Dr. Weinblatt, Dr. Cohen, and Dr. Costenbader each disclosed research support or consultancies with multiple pharmaceutical companies. Dr. Gravallese had no disclosures.
SOURCE: Mikuls TR et al. Arthritis Rheumatol. 2020 Apr 29. doi: 10.1002/art.41301.
FROM ARTHRITIS & RHEUMATOLOGY
Bronchoscopy guideline for COVID-19 pandemic: Use sparingly
With little evidence available on the role of bronchoscopy during the COVID-19 pandemic, an expert panel has published a guideline recommending its spare use in COVID-19 patients and those with suspected COVID-19 infection.
The panel stated that in the context of the COVID-19 crisis, bronchoscopy and other aerosol-generating procedures put health care workers (HCWs) at particularly high risk of exposure and infection. They recommended deferring bronchoscopy in nonurgent cases, and advised practitioners to wear personal protective equipment when performing bronchoscopy, even on asymptomatic patients.
The guideline and expert panel report have been published online in the journal Chest. CHEST and the American Association for Bronchology and Interventional Pulmonology participated in selecting the 14 panelists. “The recommendation and suggestions outlined in this document were specifically created to address what were felt to be clinically common and urgent questions that frontline clinicians are likely to face,” wrote lead author and panel cochair Momen M. Wahidi, MD, MBA, of Duke University, Durham, N.C., and colleagues.
Only one of the six recommendations is based on graded evidence; the remainder are ungraded consensus-based statements. The guideline consists of the following recommendations for performing or using bronchoscopy:
- HCWs in the procedure or recovery rooms should wear either an N-95 respirator or powered air-purifying respirator (PAPR) when performing bronchoscopy on patients suspected or confirmed to have COVID-19. They should wear personal protective equipment (PPE) that includes a face shield, gown, and gloves, and they should discard N-95 respirators after performing bronchoscopy.
- A nasopharyngeal specimen in COVID-19 suspects should be obtained before performing bronchoscopy. If the patient has severe or progressive disease that requires intubation but an additional specimen is needed to confirm COVID-19 or another diagnosis that could change the treatment course, an option would be lower-respiratory specimen from the endotracheal aspirate or bronchoscopy with bronchoalveolar lavage.
- HCWs should wear an N-95 or PAPR when doing bronchoscopy on asymptomatic patients in an area with community spread of COVID-19 – again, with the PPE designated in the first recommendation.
- Test for COVID-19 before doing bronchoscopy on asymptomatic patients. Defer nonurgent bronchoscopy if the test is positive. If it’s negative, follow the recommendations regarding respirators and PPE when doing bronchoscopy.
- Perform timely bronchoscopy when indicated even in an area with known community spread of COVID-19. This is the only graded recommendation among the six (Grade 2C) and may be the most nuanced. Local teams should develop strategies for using bronchoscopy in their setting, taking into account local resources and availability of PPE, and they should send noninfected cancer patients from resource-depleted hospitals to other centers.
- Base the timing of bronchoscopy in patients recovering after COVID-19 on the indication for the procedure, disease severity, and time duration since symptoms resolved. The recommendation noted that the exact timing is still unknown, but that a wait of at least 30 days after symptoms recede is “reasonable.”
The expert panel added a noteworthy caveat to the recommendations. “We would like to stress that these protective strategies can be rendered completely ineffective if proper training on donning and doffing is not provided to HCW,” Dr. Wahidi and colleagues wrote. “Proper personnel instruction and practice for wearing PPE should receive as much attention by health facilities as the chosen strategy for protection.”
Dr. Wahidi and colleagues have no financial relationships to disclose.
SOURCE: Wahidi MM et al. CHEST. 2020 Apr 30. doi: 10.1016/j.chest.2020.04.036.
With little evidence available on the role of bronchoscopy during the COVID-19 pandemic, an expert panel has published a guideline recommending its spare use in COVID-19 patients and those with suspected COVID-19 infection.
The panel stated that in the context of the COVID-19 crisis, bronchoscopy and other aerosol-generating procedures put health care workers (HCWs) at particularly high risk of exposure and infection. They recommended deferring bronchoscopy in nonurgent cases, and advised practitioners to wear personal protective equipment when performing bronchoscopy, even on asymptomatic patients.
The guideline and expert panel report have been published online in the journal Chest. CHEST and the American Association for Bronchology and Interventional Pulmonology participated in selecting the 14 panelists. “The recommendation and suggestions outlined in this document were specifically created to address what were felt to be clinically common and urgent questions that frontline clinicians are likely to face,” wrote lead author and panel cochair Momen M. Wahidi, MD, MBA, of Duke University, Durham, N.C., and colleagues.
Only one of the six recommendations is based on graded evidence; the remainder are ungraded consensus-based statements. The guideline consists of the following recommendations for performing or using bronchoscopy:
- HCWs in the procedure or recovery rooms should wear either an N-95 respirator or powered air-purifying respirator (PAPR) when performing bronchoscopy on patients suspected or confirmed to have COVID-19. They should wear personal protective equipment (PPE) that includes a face shield, gown, and gloves, and they should discard N-95 respirators after performing bronchoscopy.
- A nasopharyngeal specimen in COVID-19 suspects should be obtained before performing bronchoscopy. If the patient has severe or progressive disease that requires intubation but an additional specimen is needed to confirm COVID-19 or another diagnosis that could change the treatment course, an option would be lower-respiratory specimen from the endotracheal aspirate or bronchoscopy with bronchoalveolar lavage.
- HCWs should wear an N-95 or PAPR when doing bronchoscopy on asymptomatic patients in an area with community spread of COVID-19 – again, with the PPE designated in the first recommendation.
- Test for COVID-19 before doing bronchoscopy on asymptomatic patients. Defer nonurgent bronchoscopy if the test is positive. If it’s negative, follow the recommendations regarding respirators and PPE when doing bronchoscopy.
- Perform timely bronchoscopy when indicated even in an area with known community spread of COVID-19. This is the only graded recommendation among the six (Grade 2C) and may be the most nuanced. Local teams should develop strategies for using bronchoscopy in their setting, taking into account local resources and availability of PPE, and they should send noninfected cancer patients from resource-depleted hospitals to other centers.
- Base the timing of bronchoscopy in patients recovering after COVID-19 on the indication for the procedure, disease severity, and time duration since symptoms resolved. The recommendation noted that the exact timing is still unknown, but that a wait of at least 30 days after symptoms recede is “reasonable.”
The expert panel added a noteworthy caveat to the recommendations. “We would like to stress that these protective strategies can be rendered completely ineffective if proper training on donning and doffing is not provided to HCW,” Dr. Wahidi and colleagues wrote. “Proper personnel instruction and practice for wearing PPE should receive as much attention by health facilities as the chosen strategy for protection.”
Dr. Wahidi and colleagues have no financial relationships to disclose.
SOURCE: Wahidi MM et al. CHEST. 2020 Apr 30. doi: 10.1016/j.chest.2020.04.036.
With little evidence available on the role of bronchoscopy during the COVID-19 pandemic, an expert panel has published a guideline recommending its spare use in COVID-19 patients and those with suspected COVID-19 infection.
The panel stated that in the context of the COVID-19 crisis, bronchoscopy and other aerosol-generating procedures put health care workers (HCWs) at particularly high risk of exposure and infection. They recommended deferring bronchoscopy in nonurgent cases, and advised practitioners to wear personal protective equipment when performing bronchoscopy, even on asymptomatic patients.
The guideline and expert panel report have been published online in the journal Chest. CHEST and the American Association for Bronchology and Interventional Pulmonology participated in selecting the 14 panelists. “The recommendation and suggestions outlined in this document were specifically created to address what were felt to be clinically common and urgent questions that frontline clinicians are likely to face,” wrote lead author and panel cochair Momen M. Wahidi, MD, MBA, of Duke University, Durham, N.C., and colleagues.
Only one of the six recommendations is based on graded evidence; the remainder are ungraded consensus-based statements. The guideline consists of the following recommendations for performing or using bronchoscopy:
- HCWs in the procedure or recovery rooms should wear either an N-95 respirator or powered air-purifying respirator (PAPR) when performing bronchoscopy on patients suspected or confirmed to have COVID-19. They should wear personal protective equipment (PPE) that includes a face shield, gown, and gloves, and they should discard N-95 respirators after performing bronchoscopy.
- A nasopharyngeal specimen in COVID-19 suspects should be obtained before performing bronchoscopy. If the patient has severe or progressive disease that requires intubation but an additional specimen is needed to confirm COVID-19 or another diagnosis that could change the treatment course, an option would be lower-respiratory specimen from the endotracheal aspirate or bronchoscopy with bronchoalveolar lavage.
- HCWs should wear an N-95 or PAPR when doing bronchoscopy on asymptomatic patients in an area with community spread of COVID-19 – again, with the PPE designated in the first recommendation.
- Test for COVID-19 before doing bronchoscopy on asymptomatic patients. Defer nonurgent bronchoscopy if the test is positive. If it’s negative, follow the recommendations regarding respirators and PPE when doing bronchoscopy.
- Perform timely bronchoscopy when indicated even in an area with known community spread of COVID-19. This is the only graded recommendation among the six (Grade 2C) and may be the most nuanced. Local teams should develop strategies for using bronchoscopy in their setting, taking into account local resources and availability of PPE, and they should send noninfected cancer patients from resource-depleted hospitals to other centers.
- Base the timing of bronchoscopy in patients recovering after COVID-19 on the indication for the procedure, disease severity, and time duration since symptoms resolved. The recommendation noted that the exact timing is still unknown, but that a wait of at least 30 days after symptoms recede is “reasonable.”
The expert panel added a noteworthy caveat to the recommendations. “We would like to stress that these protective strategies can be rendered completely ineffective if proper training on donning and doffing is not provided to HCW,” Dr. Wahidi and colleagues wrote. “Proper personnel instruction and practice for wearing PPE should receive as much attention by health facilities as the chosen strategy for protection.”
Dr. Wahidi and colleagues have no financial relationships to disclose.
SOURCE: Wahidi MM et al. CHEST. 2020 Apr 30. doi: 10.1016/j.chest.2020.04.036.
FROM CHEST
Many hydroxychloroquine COVID-19 prophylaxis trials lack ECG screening
Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.
Hydroxychloroquine, the related agent chloroquine, and azithromycin have all recently received attention as potentially effective but unproven agents for both reducing the severity and duration of established COVID-19 infection as well as possibly preventing or mitigating an incident infection. As of April 30, 155 randomized, control trials listed on a major index for pending and in-progress trials, clinicaltrials.gov, had designs that intended to randomized an overall total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis, Michael H. Gollob, MD, said in an article posted by the Journal of the American College of Cardiology (2020 May 11. doi: 10.1016/j.jacc.2020.05.008).
The problem is that all three agents are documented to potentially produce lengthening of the corrected QT interval (QTc), and if this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation from drug treatment could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob, a cardiac arrhythmia researcher at Toronto General Hospital and the University of Toronto. As a consequence, he recommended excluding from these prophylaxis trials anyone with a resting QTc at baseline assessment of greater than 450 msec, as well as discontinuing treatment from anyone who develops a resting QTc of more than 480 ms while on treatment.
“Though this may seem like a conservative value for subject withdrawal from a study, this is a prudent QTc cut-off, particularly when the severity of the adverse event, sudden death, may be worse than the study endpoint” of reduced incidence of COVID-19 infection, he wrote in his opinion piece.
“We cannot provide an accurate number for elevated risk” faced by people whose QTc climbs above these thresholds, “but we know that events will occur, which is why most trials that involve QT-prolonging drugs typically have an ECG exclusion criterion of QTc greater than 450 msec,” Dr. Gollob said in an interview.
His analysis of the 155 planned randomized prophylaxis trials on clinicaltrials.gov that he examined in detail had enrollment goals that would translate into more than 85,000 uninfected people who would receive hydroxychloroquine or chloroquine plus, in come cases, azithromycin. Only six relatively small studies from among these 155 included a plan for ECG screening and monitoring in its design, he noted. “It is reasonable to estimate that among the 80,000 patients randomized to a QT-prolonging drug [without ECG screening or monitoring] there will certainly be arrhythmic events.” If some of these people were to then die from a drug-induced arrhythmic event that could have been prevented by ECG screening or monitoring, it would be a “tragedy,” Dr. Gollob said.
“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.
“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.
In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.
Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.
“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.
In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.
Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.
Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.
Hydroxychloroquine, the related agent chloroquine, and azithromycin have all recently received attention as potentially effective but unproven agents for both reducing the severity and duration of established COVID-19 infection as well as possibly preventing or mitigating an incident infection. As of April 30, 155 randomized, control trials listed on a major index for pending and in-progress trials, clinicaltrials.gov, had designs that intended to randomized an overall total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis, Michael H. Gollob, MD, said in an article posted by the Journal of the American College of Cardiology (2020 May 11. doi: 10.1016/j.jacc.2020.05.008).
The problem is that all three agents are documented to potentially produce lengthening of the corrected QT interval (QTc), and if this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation from drug treatment could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob, a cardiac arrhythmia researcher at Toronto General Hospital and the University of Toronto. As a consequence, he recommended excluding from these prophylaxis trials anyone with a resting QTc at baseline assessment of greater than 450 msec, as well as discontinuing treatment from anyone who develops a resting QTc of more than 480 ms while on treatment.
“Though this may seem like a conservative value for subject withdrawal from a study, this is a prudent QTc cut-off, particularly when the severity of the adverse event, sudden death, may be worse than the study endpoint” of reduced incidence of COVID-19 infection, he wrote in his opinion piece.
“We cannot provide an accurate number for elevated risk” faced by people whose QTc climbs above these thresholds, “but we know that events will occur, which is why most trials that involve QT-prolonging drugs typically have an ECG exclusion criterion of QTc greater than 450 msec,” Dr. Gollob said in an interview.
His analysis of the 155 planned randomized prophylaxis trials on clinicaltrials.gov that he examined in detail had enrollment goals that would translate into more than 85,000 uninfected people who would receive hydroxychloroquine or chloroquine plus, in come cases, azithromycin. Only six relatively small studies from among these 155 included a plan for ECG screening and monitoring in its design, he noted. “It is reasonable to estimate that among the 80,000 patients randomized to a QT-prolonging drug [without ECG screening or monitoring] there will certainly be arrhythmic events.” If some of these people were to then die from a drug-induced arrhythmic event that could have been prevented by ECG screening or monitoring, it would be a “tragedy,” Dr. Gollob said.
“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.
“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.
In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.
Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.
“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.
In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.
Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.
Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.
Hydroxychloroquine, the related agent chloroquine, and azithromycin have all recently received attention as potentially effective but unproven agents for both reducing the severity and duration of established COVID-19 infection as well as possibly preventing or mitigating an incident infection. As of April 30, 155 randomized, control trials listed on a major index for pending and in-progress trials, clinicaltrials.gov, had designs that intended to randomized an overall total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis, Michael H. Gollob, MD, said in an article posted by the Journal of the American College of Cardiology (2020 May 11. doi: 10.1016/j.jacc.2020.05.008).
The problem is that all three agents are documented to potentially produce lengthening of the corrected QT interval (QTc), and if this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation from drug treatment could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob, a cardiac arrhythmia researcher at Toronto General Hospital and the University of Toronto. As a consequence, he recommended excluding from these prophylaxis trials anyone with a resting QTc at baseline assessment of greater than 450 msec, as well as discontinuing treatment from anyone who develops a resting QTc of more than 480 ms while on treatment.
“Though this may seem like a conservative value for subject withdrawal from a study, this is a prudent QTc cut-off, particularly when the severity of the adverse event, sudden death, may be worse than the study endpoint” of reduced incidence of COVID-19 infection, he wrote in his opinion piece.
“We cannot provide an accurate number for elevated risk” faced by people whose QTc climbs above these thresholds, “but we know that events will occur, which is why most trials that involve QT-prolonging drugs typically have an ECG exclusion criterion of QTc greater than 450 msec,” Dr. Gollob said in an interview.
His analysis of the 155 planned randomized prophylaxis trials on clinicaltrials.gov that he examined in detail had enrollment goals that would translate into more than 85,000 uninfected people who would receive hydroxychloroquine or chloroquine plus, in come cases, azithromycin. Only six relatively small studies from among these 155 included a plan for ECG screening and monitoring in its design, he noted. “It is reasonable to estimate that among the 80,000 patients randomized to a QT-prolonging drug [without ECG screening or monitoring] there will certainly be arrhythmic events.” If some of these people were to then die from a drug-induced arrhythmic event that could have been prevented by ECG screening or monitoring, it would be a “tragedy,” Dr. Gollob said.
“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.
“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.
In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.
Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.
“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.
In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.
Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.
REPORTING FROM JACC