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Rapid changes to health system spurred by COVID might be here to stay
The U.S. health care system is famously resistant to government-imposed change. It took decades to create Medicare and Medicaid, mostly because of opposition from the medical-industrial complex. Then it was nearly another half-century before the passage of the Affordable Care Act.
“Health care is never going back to the way it was before,” said Gail Wilensky, a health economist who ran the Medicare and Medicaid programs for President George H.W. Bush in the early 1990s.
Ms. Wilensky is far from the only longtime observer of the American health care system to marvel at the speed of some long-sought changes. But experts warn that the breakthroughs may not all make the health system work better or make it less expensive.
That said, here are three trends that seem likely to continue.
Telehealth for all
Telehealth is not new; medical professionals have used it to reach patients in rural or remote settings since the late 1980s.
But even while technology has made video visits easier, it has failed to reach critical mass, largely because of political fights. Licensing has been one main obstacle – determining how a doctor in one state can legally treat a patient in a state where the doctor is not licensed.
The other obstacle, not surprisingly, is payment. Should a video visit be reimbursed at the same rate as an in-person visit? Will making it easier for doctors and other medical professionals to use telehealth encourage unnecessary care, thus driving up the nation’s $3.6 trillion health tab even more? Or could it replace care once provided free by phone?
Still, the pandemic has pushed aside those sticking points. Almost overnight, by necessity, every health care provider who can is delivering telemedicine. A new survey from Gallup found the number of patients reporting “virtual” medical visits more than doubled, from 12% to 27%, from late March to mid-May. That is attributable, at least in part, to Medicare having made it easier for doctors to bill for virtual visits.
It’s easy to see why many patients like video visits – there’s no parking to find and pay for, and it takes far less time out of a workday than going to an office.
Doctors and other practitioners seem more ambivalent. On one hand, it can be harder to examine a patient over video and some services just can’t be done via a digital connection. On the other hand, they can see more patients in the same amount of time and may need less support staff and possibly smaller offices if more visits are conducted virtually.
Of course, telemedicine doesn’t work for everyone. Many areas and patients don’t have reliable or robust broadband connections that make video visits work. And some patients, particularly the oldest seniors, lack the technological skills needed to connect.
Primary care doctors in peril
Another trend that has suddenly accelerated is worry over the nation’s dwindling supply of primary care doctors. The exodus of practitioners performing primary care has been a concern over the past several years, as baby boomer doctors retire and others have grown weary of more and more bureaucracy from government and private payers. Having faced a difficult financial crisis during the pandemic, more family physicians may move into retirement or seek other professional options.
At the same time, fewer current medical students are choosing specialties in primary care.
“I’ve been trying to raise the alarm about the kind of perilous future of primary care,” said Farzad Mostashari, MD, a top Department of Health & Human Services official in the Obama administration. Dr. Mostashari runs Aledade, a company that helps primary care doctors make the transition from fee-for-service medicine to new payment models.
The American Academy of Family Physicians reports that 70% of primary care physicians are reporting declines in patient volume of 50% or more since March, and 40% have laid off or furloughed staff. The AAFP has joined other primary care and insurance groups in asking HHS for an infusion of cash.
“This is absolutely essential to effectively treat patients today and to maintain their ongoing operations until we overcome this public health emergency,” the groups wrote.
One easy way to help keep primary care doctors afloat would be to pay them not according to what they do, but in a lump sum to keep patients healthy. This move from fee-for-service to what’s known as capitation or value-based care has unfolded gradually and was championed in the Affordable Care Act.
But some experts argue it needs to happen more quickly and they predict that the coronavirus pandemic could finally mark the beginning of the end for doctors who still charge for each service individually. Dr. Mostashari, who spends his time helping doctors make the transition, said in times like these, it would make more sense for primary care doctors to have “a steady monthly revenue stream, and [the doctor] can decide the best way to deliver that care: unlimited texts, phone calls, video calls. The goal is to give you satisfactory outcomes and a great patient experience.”
Still, many physicians, particularly those in solo or small practices, worry about the potential financial risk – especially the possibility of getting paid less if they don’t meet certain benchmarks that the doctors may not be able to directly control.
But with many practices now ground to a halt, or just starting to reopen, those physicians who get paid per patient rather than per service are in a much better position to stay afloat. That model may gain traction as doctors ponder the next pandemic, or the next wave of this one.
Hospitals on the decline?
The pandemic also might lead to less emphasis on hospital-based care. While hospitals in many parts of the country have obviously been full of very sick COVID patients, they have closed down other nonemergency services to preserve supplies and resources to fight the pandemic. People with other ailments have stayed away in droves even when services were available, for fear of catching something worse than what they already have.
Many experts predict that care won’t just snap back when the current emergency wanes. Mark Smith, MD, former president of the California Health Care Foundation, said among consumers, a switch has been flipped. “Overnight it seems we’ve gone from high-touch to no-touch.”
Which is not great for hospitals that have spent millions trying to attract patients to their labor-and-delivery units, orthopedic centers, and other parts of the facility that once generated lots of income.
Even more concerning is that hospitals’ ability to weather the current financial shock varies widely. Those most in danger of closing are in rural and underserved areas, where patients could wind up with even less access to care that is scarce already.
All of which underscores the point that not all these changes will necessarily be good for the health system or society. Financial pressures could end up driving more consolidation, which could push up prices as large groups of hospitals and doctors gain more bargaining clout.
But the changes are definitely happening at a pace few have ever seen, said Ms. Wilensky, “When you’re forced to find different ways of doing things, and you find out they are easier and more efficient, it’s going to be hard to go back to the old way.”
A version of this article originally appeared on Kaiser Health News, which is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
The U.S. health care system is famously resistant to government-imposed change. It took decades to create Medicare and Medicaid, mostly because of opposition from the medical-industrial complex. Then it was nearly another half-century before the passage of the Affordable Care Act.
“Health care is never going back to the way it was before,” said Gail Wilensky, a health economist who ran the Medicare and Medicaid programs for President George H.W. Bush in the early 1990s.
Ms. Wilensky is far from the only longtime observer of the American health care system to marvel at the speed of some long-sought changes. But experts warn that the breakthroughs may not all make the health system work better or make it less expensive.
That said, here are three trends that seem likely to continue.
Telehealth for all
Telehealth is not new; medical professionals have used it to reach patients in rural or remote settings since the late 1980s.
But even while technology has made video visits easier, it has failed to reach critical mass, largely because of political fights. Licensing has been one main obstacle – determining how a doctor in one state can legally treat a patient in a state where the doctor is not licensed.
The other obstacle, not surprisingly, is payment. Should a video visit be reimbursed at the same rate as an in-person visit? Will making it easier for doctors and other medical professionals to use telehealth encourage unnecessary care, thus driving up the nation’s $3.6 trillion health tab even more? Or could it replace care once provided free by phone?
Still, the pandemic has pushed aside those sticking points. Almost overnight, by necessity, every health care provider who can is delivering telemedicine. A new survey from Gallup found the number of patients reporting “virtual” medical visits more than doubled, from 12% to 27%, from late March to mid-May. That is attributable, at least in part, to Medicare having made it easier for doctors to bill for virtual visits.
It’s easy to see why many patients like video visits – there’s no parking to find and pay for, and it takes far less time out of a workday than going to an office.
Doctors and other practitioners seem more ambivalent. On one hand, it can be harder to examine a patient over video and some services just can’t be done via a digital connection. On the other hand, they can see more patients in the same amount of time and may need less support staff and possibly smaller offices if more visits are conducted virtually.
Of course, telemedicine doesn’t work for everyone. Many areas and patients don’t have reliable or robust broadband connections that make video visits work. And some patients, particularly the oldest seniors, lack the technological skills needed to connect.
Primary care doctors in peril
Another trend that has suddenly accelerated is worry over the nation’s dwindling supply of primary care doctors. The exodus of practitioners performing primary care has been a concern over the past several years, as baby boomer doctors retire and others have grown weary of more and more bureaucracy from government and private payers. Having faced a difficult financial crisis during the pandemic, more family physicians may move into retirement or seek other professional options.
At the same time, fewer current medical students are choosing specialties in primary care.
“I’ve been trying to raise the alarm about the kind of perilous future of primary care,” said Farzad Mostashari, MD, a top Department of Health & Human Services official in the Obama administration. Dr. Mostashari runs Aledade, a company that helps primary care doctors make the transition from fee-for-service medicine to new payment models.
The American Academy of Family Physicians reports that 70% of primary care physicians are reporting declines in patient volume of 50% or more since March, and 40% have laid off or furloughed staff. The AAFP has joined other primary care and insurance groups in asking HHS for an infusion of cash.
“This is absolutely essential to effectively treat patients today and to maintain their ongoing operations until we overcome this public health emergency,” the groups wrote.
One easy way to help keep primary care doctors afloat would be to pay them not according to what they do, but in a lump sum to keep patients healthy. This move from fee-for-service to what’s known as capitation or value-based care has unfolded gradually and was championed in the Affordable Care Act.
But some experts argue it needs to happen more quickly and they predict that the coronavirus pandemic could finally mark the beginning of the end for doctors who still charge for each service individually. Dr. Mostashari, who spends his time helping doctors make the transition, said in times like these, it would make more sense for primary care doctors to have “a steady monthly revenue stream, and [the doctor] can decide the best way to deliver that care: unlimited texts, phone calls, video calls. The goal is to give you satisfactory outcomes and a great patient experience.”
Still, many physicians, particularly those in solo or small practices, worry about the potential financial risk – especially the possibility of getting paid less if they don’t meet certain benchmarks that the doctors may not be able to directly control.
But with many practices now ground to a halt, or just starting to reopen, those physicians who get paid per patient rather than per service are in a much better position to stay afloat. That model may gain traction as doctors ponder the next pandemic, or the next wave of this one.
Hospitals on the decline?
The pandemic also might lead to less emphasis on hospital-based care. While hospitals in many parts of the country have obviously been full of very sick COVID patients, they have closed down other nonemergency services to preserve supplies and resources to fight the pandemic. People with other ailments have stayed away in droves even when services were available, for fear of catching something worse than what they already have.
Many experts predict that care won’t just snap back when the current emergency wanes. Mark Smith, MD, former president of the California Health Care Foundation, said among consumers, a switch has been flipped. “Overnight it seems we’ve gone from high-touch to no-touch.”
Which is not great for hospitals that have spent millions trying to attract patients to their labor-and-delivery units, orthopedic centers, and other parts of the facility that once generated lots of income.
Even more concerning is that hospitals’ ability to weather the current financial shock varies widely. Those most in danger of closing are in rural and underserved areas, where patients could wind up with even less access to care that is scarce already.
All of which underscores the point that not all these changes will necessarily be good for the health system or society. Financial pressures could end up driving more consolidation, which could push up prices as large groups of hospitals and doctors gain more bargaining clout.
But the changes are definitely happening at a pace few have ever seen, said Ms. Wilensky, “When you’re forced to find different ways of doing things, and you find out they are easier and more efficient, it’s going to be hard to go back to the old way.”
A version of this article originally appeared on Kaiser Health News, which is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
The U.S. health care system is famously resistant to government-imposed change. It took decades to create Medicare and Medicaid, mostly because of opposition from the medical-industrial complex. Then it was nearly another half-century before the passage of the Affordable Care Act.
“Health care is never going back to the way it was before,” said Gail Wilensky, a health economist who ran the Medicare and Medicaid programs for President George H.W. Bush in the early 1990s.
Ms. Wilensky is far from the only longtime observer of the American health care system to marvel at the speed of some long-sought changes. But experts warn that the breakthroughs may not all make the health system work better or make it less expensive.
That said, here are three trends that seem likely to continue.
Telehealth for all
Telehealth is not new; medical professionals have used it to reach patients in rural or remote settings since the late 1980s.
But even while technology has made video visits easier, it has failed to reach critical mass, largely because of political fights. Licensing has been one main obstacle – determining how a doctor in one state can legally treat a patient in a state where the doctor is not licensed.
The other obstacle, not surprisingly, is payment. Should a video visit be reimbursed at the same rate as an in-person visit? Will making it easier for doctors and other medical professionals to use telehealth encourage unnecessary care, thus driving up the nation’s $3.6 trillion health tab even more? Or could it replace care once provided free by phone?
Still, the pandemic has pushed aside those sticking points. Almost overnight, by necessity, every health care provider who can is delivering telemedicine. A new survey from Gallup found the number of patients reporting “virtual” medical visits more than doubled, from 12% to 27%, from late March to mid-May. That is attributable, at least in part, to Medicare having made it easier for doctors to bill for virtual visits.
It’s easy to see why many patients like video visits – there’s no parking to find and pay for, and it takes far less time out of a workday than going to an office.
Doctors and other practitioners seem more ambivalent. On one hand, it can be harder to examine a patient over video and some services just can’t be done via a digital connection. On the other hand, they can see more patients in the same amount of time and may need less support staff and possibly smaller offices if more visits are conducted virtually.
Of course, telemedicine doesn’t work for everyone. Many areas and patients don’t have reliable or robust broadband connections that make video visits work. And some patients, particularly the oldest seniors, lack the technological skills needed to connect.
Primary care doctors in peril
Another trend that has suddenly accelerated is worry over the nation’s dwindling supply of primary care doctors. The exodus of practitioners performing primary care has been a concern over the past several years, as baby boomer doctors retire and others have grown weary of more and more bureaucracy from government and private payers. Having faced a difficult financial crisis during the pandemic, more family physicians may move into retirement or seek other professional options.
At the same time, fewer current medical students are choosing specialties in primary care.
“I’ve been trying to raise the alarm about the kind of perilous future of primary care,” said Farzad Mostashari, MD, a top Department of Health & Human Services official in the Obama administration. Dr. Mostashari runs Aledade, a company that helps primary care doctors make the transition from fee-for-service medicine to new payment models.
The American Academy of Family Physicians reports that 70% of primary care physicians are reporting declines in patient volume of 50% or more since March, and 40% have laid off or furloughed staff. The AAFP has joined other primary care and insurance groups in asking HHS for an infusion of cash.
“This is absolutely essential to effectively treat patients today and to maintain their ongoing operations until we overcome this public health emergency,” the groups wrote.
One easy way to help keep primary care doctors afloat would be to pay them not according to what they do, but in a lump sum to keep patients healthy. This move from fee-for-service to what’s known as capitation or value-based care has unfolded gradually and was championed in the Affordable Care Act.
But some experts argue it needs to happen more quickly and they predict that the coronavirus pandemic could finally mark the beginning of the end for doctors who still charge for each service individually. Dr. Mostashari, who spends his time helping doctors make the transition, said in times like these, it would make more sense for primary care doctors to have “a steady monthly revenue stream, and [the doctor] can decide the best way to deliver that care: unlimited texts, phone calls, video calls. The goal is to give you satisfactory outcomes and a great patient experience.”
Still, many physicians, particularly those in solo or small practices, worry about the potential financial risk – especially the possibility of getting paid less if they don’t meet certain benchmarks that the doctors may not be able to directly control.
But with many practices now ground to a halt, or just starting to reopen, those physicians who get paid per patient rather than per service are in a much better position to stay afloat. That model may gain traction as doctors ponder the next pandemic, or the next wave of this one.
Hospitals on the decline?
The pandemic also might lead to less emphasis on hospital-based care. While hospitals in many parts of the country have obviously been full of very sick COVID patients, they have closed down other nonemergency services to preserve supplies and resources to fight the pandemic. People with other ailments have stayed away in droves even when services were available, for fear of catching something worse than what they already have.
Many experts predict that care won’t just snap back when the current emergency wanes. Mark Smith, MD, former president of the California Health Care Foundation, said among consumers, a switch has been flipped. “Overnight it seems we’ve gone from high-touch to no-touch.”
Which is not great for hospitals that have spent millions trying to attract patients to their labor-and-delivery units, orthopedic centers, and other parts of the facility that once generated lots of income.
Even more concerning is that hospitals’ ability to weather the current financial shock varies widely. Those most in danger of closing are in rural and underserved areas, where patients could wind up with even less access to care that is scarce already.
All of which underscores the point that not all these changes will necessarily be good for the health system or society. Financial pressures could end up driving more consolidation, which could push up prices as large groups of hospitals and doctors gain more bargaining clout.
But the changes are definitely happening at a pace few have ever seen, said Ms. Wilensky, “When you’re forced to find different ways of doing things, and you find out they are easier and more efficient, it’s going to be hard to go back to the old way.”
A version of this article originally appeared on Kaiser Health News, which is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Pandemic conditions can complicate care of patients with PAH
in these patients, according to a research article published in Pulmonary Circulation.
“The impetus for this manuscript was a recent discussion within the Pulmonary Hypertension Association (PHA) and [its] Scientific Leadership Council who expressed a need for guidelines from experts in the field,” wrote John J. Ryan, MD, of the University of Utah, Salt Lake City, and colleagues.
The authors highlight some of the unique challenges in caring for patients with pulmonary hypertension (PH), particularly pulmonary arterial hypertension (PAH), in the context of the COVID-19 pandemic.
Telemedicine and temporary visit schedules for new and returning PAH patients can help reduce risk of virus transmission, if patient accessibility to telemedicine is feasible. Protocols to reduce the risk of virus exposure or transmission in the office setting included less frequent echocardiography and 6-Minute Walk Tests (6MWTs) for patients in stable condition. In stable patients, “avoid pulmonary function of V/Q tests when possible,” the authors wrote.
New patients who have been referred for PAH present a challenge in conducting a thorough evaluation that would normally include measurement of invasive hemodynamics in keeping with current diagnostic guidelines. Clinicians will need to balance the potential risks of COVID-19 exposure during elective procedures against the benefits of full evaluations to plan PAH treatment, the authors noted.
For established patients who are clinically stable, remote visits may be an option, with a risk/benefit assessment of the need for in-person diagnostic tests at the current time, they said. However, telemedicine’s limitations include not only patient accessibility and understanding of audio and video technology, but also inability to accurately measure vital signs, they said.
As for routine testing such as echocardiograms, 6MWTs, and other laboratory testing, “it is important to consider the additive value of these sometimes comprehensive tests in the context of the risks associated with visiting the hospital or clinic to obtain them,” the authors said.
Patients who are unstable and experience worsening right heart failure (RHF) at home may have contracted a COVID-19 infection, but the differential diagnosis includes sepsis, ischemia, and PAH disease progression. “During the current pandemic, fever at home in a PAH patient should be assumed to represent a COVID-19 infection,” and patients with worsening respiratory symptoms that require hospitalization should be tested for COVID-19, the authors emphasized.
Use of ECMO or other intensive interventions should be considered in the context of risk assessment, the authors said. “As a general recommendation, practitioners should consider utilizing an established PAH-specific risk assessment tool to help identify patients who are more likely to survive heroic interventions during the COVID-19 outbreak,” they wrote.
Training and education of PH providers will continue to be limited by the pandemic, and many clinical trials and research programs have been suspended and will need to be restructured to minimize risk of transmission of the COVID-19 virus, the authors said. However, health care providers must continue to provide PAH patients and families with advice and updates in best practices, while “acknowledging that the situation changes rapidly,” they concluded.
Dr. Ryan disclosed participating on the speakers bureau, and provides consulting services for, Actelion and Bayer, as well as research support from the Reagan Corporation, the Gordon Family, and the Cushman Family.
SOURCE: Ryan JJ et al. Pulm Circ. 2020 Apr 29. doi: 10.1177/2045894020920153.
in these patients, according to a research article published in Pulmonary Circulation.
“The impetus for this manuscript was a recent discussion within the Pulmonary Hypertension Association (PHA) and [its] Scientific Leadership Council who expressed a need for guidelines from experts in the field,” wrote John J. Ryan, MD, of the University of Utah, Salt Lake City, and colleagues.
The authors highlight some of the unique challenges in caring for patients with pulmonary hypertension (PH), particularly pulmonary arterial hypertension (PAH), in the context of the COVID-19 pandemic.
Telemedicine and temporary visit schedules for new and returning PAH patients can help reduce risk of virus transmission, if patient accessibility to telemedicine is feasible. Protocols to reduce the risk of virus exposure or transmission in the office setting included less frequent echocardiography and 6-Minute Walk Tests (6MWTs) for patients in stable condition. In stable patients, “avoid pulmonary function of V/Q tests when possible,” the authors wrote.
New patients who have been referred for PAH present a challenge in conducting a thorough evaluation that would normally include measurement of invasive hemodynamics in keeping with current diagnostic guidelines. Clinicians will need to balance the potential risks of COVID-19 exposure during elective procedures against the benefits of full evaluations to plan PAH treatment, the authors noted.
For established patients who are clinically stable, remote visits may be an option, with a risk/benefit assessment of the need for in-person diagnostic tests at the current time, they said. However, telemedicine’s limitations include not only patient accessibility and understanding of audio and video technology, but also inability to accurately measure vital signs, they said.
As for routine testing such as echocardiograms, 6MWTs, and other laboratory testing, “it is important to consider the additive value of these sometimes comprehensive tests in the context of the risks associated with visiting the hospital or clinic to obtain them,” the authors said.
Patients who are unstable and experience worsening right heart failure (RHF) at home may have contracted a COVID-19 infection, but the differential diagnosis includes sepsis, ischemia, and PAH disease progression. “During the current pandemic, fever at home in a PAH patient should be assumed to represent a COVID-19 infection,” and patients with worsening respiratory symptoms that require hospitalization should be tested for COVID-19, the authors emphasized.
Use of ECMO or other intensive interventions should be considered in the context of risk assessment, the authors said. “As a general recommendation, practitioners should consider utilizing an established PAH-specific risk assessment tool to help identify patients who are more likely to survive heroic interventions during the COVID-19 outbreak,” they wrote.
Training and education of PH providers will continue to be limited by the pandemic, and many clinical trials and research programs have been suspended and will need to be restructured to minimize risk of transmission of the COVID-19 virus, the authors said. However, health care providers must continue to provide PAH patients and families with advice and updates in best practices, while “acknowledging that the situation changes rapidly,” they concluded.
Dr. Ryan disclosed participating on the speakers bureau, and provides consulting services for, Actelion and Bayer, as well as research support from the Reagan Corporation, the Gordon Family, and the Cushman Family.
SOURCE: Ryan JJ et al. Pulm Circ. 2020 Apr 29. doi: 10.1177/2045894020920153.
in these patients, according to a research article published in Pulmonary Circulation.
“The impetus for this manuscript was a recent discussion within the Pulmonary Hypertension Association (PHA) and [its] Scientific Leadership Council who expressed a need for guidelines from experts in the field,” wrote John J. Ryan, MD, of the University of Utah, Salt Lake City, and colleagues.
The authors highlight some of the unique challenges in caring for patients with pulmonary hypertension (PH), particularly pulmonary arterial hypertension (PAH), in the context of the COVID-19 pandemic.
Telemedicine and temporary visit schedules for new and returning PAH patients can help reduce risk of virus transmission, if patient accessibility to telemedicine is feasible. Protocols to reduce the risk of virus exposure or transmission in the office setting included less frequent echocardiography and 6-Minute Walk Tests (6MWTs) for patients in stable condition. In stable patients, “avoid pulmonary function of V/Q tests when possible,” the authors wrote.
New patients who have been referred for PAH present a challenge in conducting a thorough evaluation that would normally include measurement of invasive hemodynamics in keeping with current diagnostic guidelines. Clinicians will need to balance the potential risks of COVID-19 exposure during elective procedures against the benefits of full evaluations to plan PAH treatment, the authors noted.
For established patients who are clinically stable, remote visits may be an option, with a risk/benefit assessment of the need for in-person diagnostic tests at the current time, they said. However, telemedicine’s limitations include not only patient accessibility and understanding of audio and video technology, but also inability to accurately measure vital signs, they said.
As for routine testing such as echocardiograms, 6MWTs, and other laboratory testing, “it is important to consider the additive value of these sometimes comprehensive tests in the context of the risks associated with visiting the hospital or clinic to obtain them,” the authors said.
Patients who are unstable and experience worsening right heart failure (RHF) at home may have contracted a COVID-19 infection, but the differential diagnosis includes sepsis, ischemia, and PAH disease progression. “During the current pandemic, fever at home in a PAH patient should be assumed to represent a COVID-19 infection,” and patients with worsening respiratory symptoms that require hospitalization should be tested for COVID-19, the authors emphasized.
Use of ECMO or other intensive interventions should be considered in the context of risk assessment, the authors said. “As a general recommendation, practitioners should consider utilizing an established PAH-specific risk assessment tool to help identify patients who are more likely to survive heroic interventions during the COVID-19 outbreak,” they wrote.
Training and education of PH providers will continue to be limited by the pandemic, and many clinical trials and research programs have been suspended and will need to be restructured to minimize risk of transmission of the COVID-19 virus, the authors said. However, health care providers must continue to provide PAH patients and families with advice and updates in best practices, while “acknowledging that the situation changes rapidly,” they concluded.
Dr. Ryan disclosed participating on the speakers bureau, and provides consulting services for, Actelion and Bayer, as well as research support from the Reagan Corporation, the Gordon Family, and the Cushman Family.
SOURCE: Ryan JJ et al. Pulm Circ. 2020 Apr 29. doi: 10.1177/2045894020920153.
FROM PULMONARY CIRCULATION
Prolonged azithromycin Tx for asthma?
In “Asthma: Newer Tx options mean more targeted therapy” (J Fam Pract. 2020;65:135-144), Rali et al recommend azithromycin as an add-on therapy to ICS-LABA for a select group of patients with uncontrolled persistent asthma (neutrophilic phenotype)—a Grade C recommendation. However, the best available evidence demonstrates that azithromycin is equally efficacious for uncontrolled persistent eosinophilic asthma.1,2 Thus, family physicians need not refer patients for bronchoscopy to identify the inflammatory “phenotype.”
An important unanswered question is whether azithromycin needs to be administered continuously. Emerging evidence indicates that some patients may experience prolonged benefit after time-limited azithromycin treatment. This suggests that the mechanism of action, which has been described as anti-inflammatory, is (at least in part) antimicrobial.3
For azithromycin-treated asthma patients who experience a significant clinical response after 3 to 6 months of treatment, I recommend that the prescribing clinician try taking the patient off azithromycin to assess whether clinical improvement persists or wanes. Nothing is lost, and much is gained, by this approach; patients who relapse can resume azithromycin, and patients who remain improved are spared exposure to an unnecessary and prolonged treatment.
David L. Hahn, MD, MS
Madison, WI
1. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390: 659-668.
2. Gibson PG, Yang IA, Upham JW, et al. Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. ERJ Open Res. 2019;5.
3. Hahn D. When guideline treatment of asthma fails, consider a macrolide antibiotic. J Fam Pract. 2019;68:536-545.
In “Asthma: Newer Tx options mean more targeted therapy” (J Fam Pract. 2020;65:135-144), Rali et al recommend azithromycin as an add-on therapy to ICS-LABA for a select group of patients with uncontrolled persistent asthma (neutrophilic phenotype)—a Grade C recommendation. However, the best available evidence demonstrates that azithromycin is equally efficacious for uncontrolled persistent eosinophilic asthma.1,2 Thus, family physicians need not refer patients for bronchoscopy to identify the inflammatory “phenotype.”
An important unanswered question is whether azithromycin needs to be administered continuously. Emerging evidence indicates that some patients may experience prolonged benefit after time-limited azithromycin treatment. This suggests that the mechanism of action, which has been described as anti-inflammatory, is (at least in part) antimicrobial.3
For azithromycin-treated asthma patients who experience a significant clinical response after 3 to 6 months of treatment, I recommend that the prescribing clinician try taking the patient off azithromycin to assess whether clinical improvement persists or wanes. Nothing is lost, and much is gained, by this approach; patients who relapse can resume azithromycin, and patients who remain improved are spared exposure to an unnecessary and prolonged treatment.
David L. Hahn, MD, MS
Madison, WI
In “Asthma: Newer Tx options mean more targeted therapy” (J Fam Pract. 2020;65:135-144), Rali et al recommend azithromycin as an add-on therapy to ICS-LABA for a select group of patients with uncontrolled persistent asthma (neutrophilic phenotype)—a Grade C recommendation. However, the best available evidence demonstrates that azithromycin is equally efficacious for uncontrolled persistent eosinophilic asthma.1,2 Thus, family physicians need not refer patients for bronchoscopy to identify the inflammatory “phenotype.”
An important unanswered question is whether azithromycin needs to be administered continuously. Emerging evidence indicates that some patients may experience prolonged benefit after time-limited azithromycin treatment. This suggests that the mechanism of action, which has been described as anti-inflammatory, is (at least in part) antimicrobial.3
For azithromycin-treated asthma patients who experience a significant clinical response after 3 to 6 months of treatment, I recommend that the prescribing clinician try taking the patient off azithromycin to assess whether clinical improvement persists or wanes. Nothing is lost, and much is gained, by this approach; patients who relapse can resume azithromycin, and patients who remain improved are spared exposure to an unnecessary and prolonged treatment.
David L. Hahn, MD, MS
Madison, WI
1. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390: 659-668.
2. Gibson PG, Yang IA, Upham JW, et al. Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. ERJ Open Res. 2019;5.
3. Hahn D. When guideline treatment of asthma fails, consider a macrolide antibiotic. J Fam Pract. 2019;68:536-545.
1. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390: 659-668.
2. Gibson PG, Yang IA, Upham JW, et al. Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. ERJ Open Res. 2019;5.
3. Hahn D. When guideline treatment of asthma fails, consider a macrolide antibiotic. J Fam Pract. 2019;68:536-545.
36-year-old man • persistent dry cough • frequent sinus congestion • hemoptysis
THE CASE
A 36-year-old nonsmoking white man presented with an episodic 3-month history of dry cough and nasal allergy symptoms. He reported a past history of sinus allergies but no history of asthma. His illness began with a flu-like syndrome, and he had been treated with antibiotics (amoxicillin and azithromycin) and oral steroids (methylprednisolone) by 2 other physicians for “viral syndrome” and “bronchitis.”
The patient reported some tactile fever initially but none thereafter. Symptoms included episodic wheezing but no overt shortness of breath. In addition to the persistent dry cough, he complained of frequent sinus congestion, post-nasal drip, and sneezing. He became concerned when he noticed a fleck of blood in his phlegm.
Physical exam was unimpressive, except for nasal congestion. His breath sounds were clear. Chest x-ray showed a benign-appearing granuloma in the right lower lobe (no previous films available for comparison). Peak-flow measurements taken in the office were persistently low (58%-70%) but improved with steroids and inhaled albuterol.
Over the following 7 weeks, the patient experienced waxing and waning symptoms. At his follow-up visit, he appeared well; chest auscultation revealed normal breath sounds. He was treated with an additional round of antibiotics (levofloxacin), oral steroids, nasal steroids, and inhaled albuterol.
At 13 weeks from his initial presentation, he developed frank hemoptysis and was diagnosed with a right lower-lobe pneumonia in the emergency department. While hospitalized, his clinical status deteriorated, requiring chest tube placement for a large pleural effusion.
Shortly thereafter, he underwent right middle and lower lobectomies and decortication. Multiple organisms were cultured from the pleural fluid. Tuberculosis testing and acid-fast bacilli stains were negative. No malignant cells were identified. Pathologic examination of the resected lung tissue confirmed the chest x-ray finding of a benign calcified granuloma. Additional testing, including a thin barium esophagram, was performed.
THE DIAGNOSIS
Results of the esophagram revealed a congenital bronchoesophageal fistula (C-BEF) between the patient’s esophagus and right mainstem bronchus, located 15 cm distal to his trachea.
Continue to: DISCUSSION
DISCUSSION
Fistulous connections between the esophagus and bronchi are rare but may arise in the setting of malignancy, trauma, inflammation, or congenital malformation.1 While the precise etiology of C-BEF remains unknown, it is believed to be a consequence of failed tracheoesophageal separation during the early stages of embryonic development.
Prevalence and epidemiology. C-BEF has been reported to occur in 1 in 3000 to 4000 live births, often with concomitant esophageal atresia.2 Infants with esophageal atresia demonstrate clinically significant respiratory symptoms and failure to thrive. However, C-BEF without esophageal atresia may be asymptomatic for years to decades.
Age at diagnosis ranges from 9 days to 83 years.3 Several explanations exist for the prolonged asymptomatic phase of this disease: (1) presence of a membrane overlying the fistula during childhood that subsequently ruptures; (2) presence of a proximal fold of esophageal mucosa overlapping the orifice; (3) antigravitational or upward extension of the fistulous tract from the esophagus; and (4) spasm of the smooth muscle of the fistula.4
Four subtypes. Type I fistulas are associated with a wide-necked congenital diverticulum of the esophagus, which may become inflamed and allow perforation into the nearby lung. Type II fistulas (most common) consist of a short tract running directly from the esophagus to a nearby lobar or segmental bronchus. Type III fistulas involve a communication between the esophagus and a cystic structure within the lung parenchyma. Type IV fistulas run from the esophagus into a sequestered pulmonary segment.1 Our patient had a type II fistula.
Is there a nonspecific cough? The most common signs and symptoms of C-BEF are nonspecific cough, cough after ingestion of fluids or meals, and hemoptysis.5,6 Symptoms may persist for decades prior to diagnosis, and the indolent course of C-BEF may lead to fatal complications such as recalcitrant pneumonia, bronchiectasis, and abscess formation.
Continue to: One test bests others for diagnosis
One test bests others for diagnosis. Plain chest x-ray may indicate enlarged lymph nodes or surrounding airspace disease but will not be able to identify a C-BEF. Computed tomography (CT) of the chest may detect the presence of a C-BEF but does not rule it out. Barium esophagram is the most sensitive test for BEF. Esophagoscopy and bronchoscopy may be helpful once the BEF has been identified, but neither has demonstrated reliability as a first-line test. In this particular case, the C-BEF was not seen on chest CT but was later
To confirm the congenital nature of the fistula, histopathology should be examined. C-BEFs will have a mucosal layer and definitive muscularis layer within the fistulous tract.3,5
Treatment. The preferred method of treatment for C-BEF is thoracotomy with resection of the fistula and insertion of a pleural or muscular flap graft to close the defects in the bronchus and esophagus.7 Alternatively, obliteration of the esophageal defect can be performed using biological glue or silver nitrate. Prognosis after surgical repair is excellent.
Our patient
Two weeks after hospital discharge, the patient was re-admitted for hydropneumothorax and underwent additional surgeries. Unfortunately, he died in the ICU due to a tension pneumothorax while intubated.
THE TAKEAWAY
C-BEF is a rare, insidious condition that may remain asymptomatic into adulthood. After common causes are ruled out, patients with adult-onset nonspecific cough, episodes of coughing after eating/drinking, and hemoptysis should be evaluated for BEF. The most useful diagnostic investigation is barium esophagram. Once C-BEF is identified, prompt surgical management is warranted. Because C-BEF persisting into adulthood is so rare, recommendations regarding diagnosis and treatment are based on expert opinion.
CORRESPONDENCE
Rade N. Pejic, MD, MMM, Department of Family Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, Mailbox #8033, New Orleans, LA 70112; [email protected].
1. Braimbridge MV, Keith HI. Oesophago-bronchial fistula in the adult. Thorax. 1965;20:226-233.
2. Taira N, Kawasaki H, Atsumi E, et al. A rare case of congenital bronchoesophageal fistula in an adult. Int J Surg Case Rep. 2017;36:182-184.
3. Risher WH, Arensman RM, Ochsner JL. Congenital bronchoesophageal fistula. Ann Thorac Surg. 1990;49:500-505.
4. Paul M, John S, Ashton R. Recurrent pneumonia in a 51-year-old woman due to congenital bronchoesophageal fistula. Respir Care. 2011;56:1203-1205.
5. Rämö OJ, Salo JA, Mattila SP. Congenital bronchoesophageal fistula in the adult. Ann Thorac Surg. 1995;59:887-889.
6. Zhang B-S, Zhou N-K, Yu C-H. Congenital bronchoesophageal fistula in adults. World J Gastroenterol. 2011;17:1358-1361.
7. Su L, Wei X-Q, Zhi X-Y, et al. Congenital bronchoesophageal fistula in an adult: a case report. World J Gastroenterol. 2007;13:3776–3777.
THE CASE
A 36-year-old nonsmoking white man presented with an episodic 3-month history of dry cough and nasal allergy symptoms. He reported a past history of sinus allergies but no history of asthma. His illness began with a flu-like syndrome, and he had been treated with antibiotics (amoxicillin and azithromycin) and oral steroids (methylprednisolone) by 2 other physicians for “viral syndrome” and “bronchitis.”
The patient reported some tactile fever initially but none thereafter. Symptoms included episodic wheezing but no overt shortness of breath. In addition to the persistent dry cough, he complained of frequent sinus congestion, post-nasal drip, and sneezing. He became concerned when he noticed a fleck of blood in his phlegm.
Physical exam was unimpressive, except for nasal congestion. His breath sounds were clear. Chest x-ray showed a benign-appearing granuloma in the right lower lobe (no previous films available for comparison). Peak-flow measurements taken in the office were persistently low (58%-70%) but improved with steroids and inhaled albuterol.
Over the following 7 weeks, the patient experienced waxing and waning symptoms. At his follow-up visit, he appeared well; chest auscultation revealed normal breath sounds. He was treated with an additional round of antibiotics (levofloxacin), oral steroids, nasal steroids, and inhaled albuterol.
At 13 weeks from his initial presentation, he developed frank hemoptysis and was diagnosed with a right lower-lobe pneumonia in the emergency department. While hospitalized, his clinical status deteriorated, requiring chest tube placement for a large pleural effusion.
Shortly thereafter, he underwent right middle and lower lobectomies and decortication. Multiple organisms were cultured from the pleural fluid. Tuberculosis testing and acid-fast bacilli stains were negative. No malignant cells were identified. Pathologic examination of the resected lung tissue confirmed the chest x-ray finding of a benign calcified granuloma. Additional testing, including a thin barium esophagram, was performed.
THE DIAGNOSIS
Results of the esophagram revealed a congenital bronchoesophageal fistula (C-BEF) between the patient’s esophagus and right mainstem bronchus, located 15 cm distal to his trachea.
Continue to: DISCUSSION
DISCUSSION
Fistulous connections between the esophagus and bronchi are rare but may arise in the setting of malignancy, trauma, inflammation, or congenital malformation.1 While the precise etiology of C-BEF remains unknown, it is believed to be a consequence of failed tracheoesophageal separation during the early stages of embryonic development.
Prevalence and epidemiology. C-BEF has been reported to occur in 1 in 3000 to 4000 live births, often with concomitant esophageal atresia.2 Infants with esophageal atresia demonstrate clinically significant respiratory symptoms and failure to thrive. However, C-BEF without esophageal atresia may be asymptomatic for years to decades.
Age at diagnosis ranges from 9 days to 83 years.3 Several explanations exist for the prolonged asymptomatic phase of this disease: (1) presence of a membrane overlying the fistula during childhood that subsequently ruptures; (2) presence of a proximal fold of esophageal mucosa overlapping the orifice; (3) antigravitational or upward extension of the fistulous tract from the esophagus; and (4) spasm of the smooth muscle of the fistula.4
Four subtypes. Type I fistulas are associated with a wide-necked congenital diverticulum of the esophagus, which may become inflamed and allow perforation into the nearby lung. Type II fistulas (most common) consist of a short tract running directly from the esophagus to a nearby lobar or segmental bronchus. Type III fistulas involve a communication between the esophagus and a cystic structure within the lung parenchyma. Type IV fistulas run from the esophagus into a sequestered pulmonary segment.1 Our patient had a type II fistula.
Is there a nonspecific cough? The most common signs and symptoms of C-BEF are nonspecific cough, cough after ingestion of fluids or meals, and hemoptysis.5,6 Symptoms may persist for decades prior to diagnosis, and the indolent course of C-BEF may lead to fatal complications such as recalcitrant pneumonia, bronchiectasis, and abscess formation.
Continue to: One test bests others for diagnosis
One test bests others for diagnosis. Plain chest x-ray may indicate enlarged lymph nodes or surrounding airspace disease but will not be able to identify a C-BEF. Computed tomography (CT) of the chest may detect the presence of a C-BEF but does not rule it out. Barium esophagram is the most sensitive test for BEF. Esophagoscopy and bronchoscopy may be helpful once the BEF has been identified, but neither has demonstrated reliability as a first-line test. In this particular case, the C-BEF was not seen on chest CT but was later
To confirm the congenital nature of the fistula, histopathology should be examined. C-BEFs will have a mucosal layer and definitive muscularis layer within the fistulous tract.3,5
Treatment. The preferred method of treatment for C-BEF is thoracotomy with resection of the fistula and insertion of a pleural or muscular flap graft to close the defects in the bronchus and esophagus.7 Alternatively, obliteration of the esophageal defect can be performed using biological glue or silver nitrate. Prognosis after surgical repair is excellent.
Our patient
Two weeks after hospital discharge, the patient was re-admitted for hydropneumothorax and underwent additional surgeries. Unfortunately, he died in the ICU due to a tension pneumothorax while intubated.
THE TAKEAWAY
C-BEF is a rare, insidious condition that may remain asymptomatic into adulthood. After common causes are ruled out, patients with adult-onset nonspecific cough, episodes of coughing after eating/drinking, and hemoptysis should be evaluated for BEF. The most useful diagnostic investigation is barium esophagram. Once C-BEF is identified, prompt surgical management is warranted. Because C-BEF persisting into adulthood is so rare, recommendations regarding diagnosis and treatment are based on expert opinion.
CORRESPONDENCE
Rade N. Pejic, MD, MMM, Department of Family Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, Mailbox #8033, New Orleans, LA 70112; [email protected].
THE CASE
A 36-year-old nonsmoking white man presented with an episodic 3-month history of dry cough and nasal allergy symptoms. He reported a past history of sinus allergies but no history of asthma. His illness began with a flu-like syndrome, and he had been treated with antibiotics (amoxicillin and azithromycin) and oral steroids (methylprednisolone) by 2 other physicians for “viral syndrome” and “bronchitis.”
The patient reported some tactile fever initially but none thereafter. Symptoms included episodic wheezing but no overt shortness of breath. In addition to the persistent dry cough, he complained of frequent sinus congestion, post-nasal drip, and sneezing. He became concerned when he noticed a fleck of blood in his phlegm.
Physical exam was unimpressive, except for nasal congestion. His breath sounds were clear. Chest x-ray showed a benign-appearing granuloma in the right lower lobe (no previous films available for comparison). Peak-flow measurements taken in the office were persistently low (58%-70%) but improved with steroids and inhaled albuterol.
Over the following 7 weeks, the patient experienced waxing and waning symptoms. At his follow-up visit, he appeared well; chest auscultation revealed normal breath sounds. He was treated with an additional round of antibiotics (levofloxacin), oral steroids, nasal steroids, and inhaled albuterol.
At 13 weeks from his initial presentation, he developed frank hemoptysis and was diagnosed with a right lower-lobe pneumonia in the emergency department. While hospitalized, his clinical status deteriorated, requiring chest tube placement for a large pleural effusion.
Shortly thereafter, he underwent right middle and lower lobectomies and decortication. Multiple organisms were cultured from the pleural fluid. Tuberculosis testing and acid-fast bacilli stains were negative. No malignant cells were identified. Pathologic examination of the resected lung tissue confirmed the chest x-ray finding of a benign calcified granuloma. Additional testing, including a thin barium esophagram, was performed.
THE DIAGNOSIS
Results of the esophagram revealed a congenital bronchoesophageal fistula (C-BEF) between the patient’s esophagus and right mainstem bronchus, located 15 cm distal to his trachea.
Continue to: DISCUSSION
DISCUSSION
Fistulous connections between the esophagus and bronchi are rare but may arise in the setting of malignancy, trauma, inflammation, or congenital malformation.1 While the precise etiology of C-BEF remains unknown, it is believed to be a consequence of failed tracheoesophageal separation during the early stages of embryonic development.
Prevalence and epidemiology. C-BEF has been reported to occur in 1 in 3000 to 4000 live births, often with concomitant esophageal atresia.2 Infants with esophageal atresia demonstrate clinically significant respiratory symptoms and failure to thrive. However, C-BEF without esophageal atresia may be asymptomatic for years to decades.
Age at diagnosis ranges from 9 days to 83 years.3 Several explanations exist for the prolonged asymptomatic phase of this disease: (1) presence of a membrane overlying the fistula during childhood that subsequently ruptures; (2) presence of a proximal fold of esophageal mucosa overlapping the orifice; (3) antigravitational or upward extension of the fistulous tract from the esophagus; and (4) spasm of the smooth muscle of the fistula.4
Four subtypes. Type I fistulas are associated with a wide-necked congenital diverticulum of the esophagus, which may become inflamed and allow perforation into the nearby lung. Type II fistulas (most common) consist of a short tract running directly from the esophagus to a nearby lobar or segmental bronchus. Type III fistulas involve a communication between the esophagus and a cystic structure within the lung parenchyma. Type IV fistulas run from the esophagus into a sequestered pulmonary segment.1 Our patient had a type II fistula.
Is there a nonspecific cough? The most common signs and symptoms of C-BEF are nonspecific cough, cough after ingestion of fluids or meals, and hemoptysis.5,6 Symptoms may persist for decades prior to diagnosis, and the indolent course of C-BEF may lead to fatal complications such as recalcitrant pneumonia, bronchiectasis, and abscess formation.
Continue to: One test bests others for diagnosis
One test bests others for diagnosis. Plain chest x-ray may indicate enlarged lymph nodes or surrounding airspace disease but will not be able to identify a C-BEF. Computed tomography (CT) of the chest may detect the presence of a C-BEF but does not rule it out. Barium esophagram is the most sensitive test for BEF. Esophagoscopy and bronchoscopy may be helpful once the BEF has been identified, but neither has demonstrated reliability as a first-line test. In this particular case, the C-BEF was not seen on chest CT but was later
To confirm the congenital nature of the fistula, histopathology should be examined. C-BEFs will have a mucosal layer and definitive muscularis layer within the fistulous tract.3,5
Treatment. The preferred method of treatment for C-BEF is thoracotomy with resection of the fistula and insertion of a pleural or muscular flap graft to close the defects in the bronchus and esophagus.7 Alternatively, obliteration of the esophageal defect can be performed using biological glue or silver nitrate. Prognosis after surgical repair is excellent.
Our patient
Two weeks after hospital discharge, the patient was re-admitted for hydropneumothorax and underwent additional surgeries. Unfortunately, he died in the ICU due to a tension pneumothorax while intubated.
THE TAKEAWAY
C-BEF is a rare, insidious condition that may remain asymptomatic into adulthood. After common causes are ruled out, patients with adult-onset nonspecific cough, episodes of coughing after eating/drinking, and hemoptysis should be evaluated for BEF. The most useful diagnostic investigation is barium esophagram. Once C-BEF is identified, prompt surgical management is warranted. Because C-BEF persisting into adulthood is so rare, recommendations regarding diagnosis and treatment are based on expert opinion.
CORRESPONDENCE
Rade N. Pejic, MD, MMM, Department of Family Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, Mailbox #8033, New Orleans, LA 70112; [email protected].
1. Braimbridge MV, Keith HI. Oesophago-bronchial fistula in the adult. Thorax. 1965;20:226-233.
2. Taira N, Kawasaki H, Atsumi E, et al. A rare case of congenital bronchoesophageal fistula in an adult. Int J Surg Case Rep. 2017;36:182-184.
3. Risher WH, Arensman RM, Ochsner JL. Congenital bronchoesophageal fistula. Ann Thorac Surg. 1990;49:500-505.
4. Paul M, John S, Ashton R. Recurrent pneumonia in a 51-year-old woman due to congenital bronchoesophageal fistula. Respir Care. 2011;56:1203-1205.
5. Rämö OJ, Salo JA, Mattila SP. Congenital bronchoesophageal fistula in the adult. Ann Thorac Surg. 1995;59:887-889.
6. Zhang B-S, Zhou N-K, Yu C-H. Congenital bronchoesophageal fistula in adults. World J Gastroenterol. 2011;17:1358-1361.
7. Su L, Wei X-Q, Zhi X-Y, et al. Congenital bronchoesophageal fistula in an adult: a case report. World J Gastroenterol. 2007;13:3776–3777.
1. Braimbridge MV, Keith HI. Oesophago-bronchial fistula in the adult. Thorax. 1965;20:226-233.
2. Taira N, Kawasaki H, Atsumi E, et al. A rare case of congenital bronchoesophageal fistula in an adult. Int J Surg Case Rep. 2017;36:182-184.
3. Risher WH, Arensman RM, Ochsner JL. Congenital bronchoesophageal fistula. Ann Thorac Surg. 1990;49:500-505.
4. Paul M, John S, Ashton R. Recurrent pneumonia in a 51-year-old woman due to congenital bronchoesophageal fistula. Respir Care. 2011;56:1203-1205.
5. Rämö OJ, Salo JA, Mattila SP. Congenital bronchoesophageal fistula in the adult. Ann Thorac Surg. 1995;59:887-889.
6. Zhang B-S, Zhou N-K, Yu C-H. Congenital bronchoesophageal fistula in adults. World J Gastroenterol. 2011;17:1358-1361.
7. Su L, Wei X-Q, Zhi X-Y, et al. Congenital bronchoesophageal fistula in an adult: a case report. World J Gastroenterol. 2007;13:3776–3777.
WHO: Asymptomatic COVID-19 spread deemed ‘rare’
An official with the World Health Organization (WHO) has stated that it appears to be “rare” that an asymptomatic individual can pass SARS-CoV-2 to someone else.
“From the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, said June 8 at a news briefing from the agency’s Geneva headquarters.
This announcement came on the heels of the publication of an analysis in the Annals of Internal Medicine, which suggested that as many as 40-45% of COVID-19 cases may be asymptomatic. In this paper, the authors, Daniel P. Oran, AM, and Eric J. Topol, MD, of the Scripps Research Translational Institute in La Jolla, Calif stated: “The likelihood that approximately 40%-45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.”
"The early data that we have assembled on the prevalence of asymptomatic SARS-CoV-2 infection suggest that this is a significant factor in the rapid progression of the COVID-19 pandemic," the authors concluded.
Dr. Van Kerkhove also made comments suggesting otherwise on Twitter, citing a new summary by WHO: “@WHO recently published a summary of transmission of #COVID19, incl. symptomatic, pre-symptomatic and asymptomatic transmission.”
She also tweeted the following lines from the WHO summary: “Comprehensive studies on transmission from asymptomatic individuals are difficult to conduct, but the available evidence from contact tracing reported by Member States suggests that asymptomatically-infected individuals are much less likely to transmit the virus than those who develop symptoms.”
In an additional post, Dr. Van Kerkhove added: “In these data, it is important to breakdown truly asymptomatic vs pre-symptomatic vs mildly symptomatic... also to note that the [percentage] reported or estimated to be ‘asymptomatic’ is not the same as the [percentage] that are asymptomatic that actually transmit.”
In the paper published in the Annals of Internal Medicine, Mr. Oran and Dr. Topol analyzed data of asymptomatic individuals from 16 cohorts between April 19 and May 26, 2020 – a wide-ranging group consisting of residents of cities, health care workers, individuals in homeless shelters, obstetric patients, residents of a nursing home, crew members of aircraft carriers, passengers on cruise ships, and inmates in correctional facilities. Each cohort had varying rates of asymptomatic or presymptomatic cases..
When residents of Iceland were tested, 43 of 100 individuals who tested positive for SARS-CoV-2 did not show symptoms. In Vo’, Italy, 30 of 73 people (41.1%) with positive SARS-CoV-2 test results did not have symptoms in a first round of testing, and 13 of 29 (44.8%) had no symptoms in a second round of testing. Over half of residents of San Francisco’s Mission District who received testing (39 of 74; 52.7%) did not have symptoms, while slightly less than half of Indiana residents tested showed no symptoms (35 of 78; 44.8%).
A majority of 41 individuals (65.9%) who were mostly health care workers at Rutgers University reported no symptoms of COVID-19 at the time of testing. Data from homeless shelters in Boston (129 of 147; 87.7%) and Los Angeles (27 of 43; 62.7%) also showed a high rate of individuals without symptoms. Among 33 obstetric patients in New York City who tested positive for SARS-CoV-2, 29 women (87.9%) were asymptomatic during a median 2-day length of stay. In a Washington state nursing facility, 12 of 23 individuals (52.1%) were positive for SARS-CoV-2 without showing symptoms in a first round of testing, with another 15 of 24 residents (62.5%) not showing symptoms in a second round of testing. Of these residents, 24 individuals (88.9%) later went on to show symptoms of COVID-19.
Most of the 783 Greek citizens who tested positive for SARS-CoV-2 after being evacuated from Spain, Turkey, and the United Kingdom showed no symptoms of COVID-19 (35 of 40; 87.5%). A group of 565 Japanese citizens evacuated from Wuhan, China, had a lower number of cases without initial symptoms – 13 people were positive for SARS-CoV-2, and 4 of 13 (30.8%) had no symptoms.
In closed cohorts, there appeared to also be a high rate of COVID-19 cases without initial symptoms. Of 3,277 inmates from correctional facilities in Arkansas, North Carolina, Ohio, and Virginia, 3,146 individuals (96%) had no symptoms at the time of testing. There was also a large percentage of passengers and crew of the Diamond Princess cruise ship (331 of 712; 46.5%) and an Argentine cruise ship (104 of 128; 81.3%) who were positive for SARS-CoV-2 without symptoms. On the aircraft carrier U.S.S. Theodore Roosevelt, 60% of 856 individuals, while on the French aircraft carrier Charles de Gaulle, nearly 50% of individuals were asymptomatic.
It is difficult to tell the difference between people who are presymptomatic and will later go on to develop symptoms of COVID-19 and those who will remain asymptomatic. “The simple solution to this conundrum is longitudinal testing – that is, repeated observations of the individual over time,” but only 5 of 16 cohorts studied had longitudinal data on individuals, Mr. Oran and Dr. Topol said.
Seth Trueger, MD, an emergency physician and assistant professor of emergency medicine at Northwestern University, Chicago, who was not involved in the study, said it was important to see this information all in one place, even if the data isn’t new.
“I think we’ve certainly kind of seen from the beginning there’s some level of asymptomatic and presymptomatic spread,” Dr. Trueger said. “In health care, we’ve been lucky to get those lessons early on and start to think of things like universal masking in hospitals, and unfortunate things like limiting visitors.”
A more nuanced understanding of how SARS-CoV-2 spreads has been difficult to capture, in part because of operating under a shortened time frame and handicapped testing capacity, he noted. “[Even] in the best of possible circumstances, trying to figure out epidemiology in people who don’t have symptoms is really tough,” Dr. Truegar said.
“Even the best studies are still relatively decent samples, and not totally representative,” he added.
Another limitation to capturing accurate data is method of testing. Real-time reverse transcriptase polymerase chain reaction using nasopharyngeal swabs can detect RNA fragments from SARS-CoV-2, which could potentially affect the results. “It’s really hard to know what is actually infected virus versus just fragments of RNA that make the test positive,” Dr. Trueger said.
If the rate of asymptomatic cases is higher than previously thought, it’s a “double-edged sword,” he noted. It may mean the infection fatality rate is lower than predicted, but “even at high levels of what we think community levels might be, we’re far from herd immunity.”
The study authors and Dr. Trueger reported no relevant conflicts of interest.
SOURCE: Oran DP, Topol EJ. Ann Intern Med. 2020 Jun 3. doi: 10.7326/M20-3012.
This article was updated 6/8/20.
An official with the World Health Organization (WHO) has stated that it appears to be “rare” that an asymptomatic individual can pass SARS-CoV-2 to someone else.
“From the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, said June 8 at a news briefing from the agency’s Geneva headquarters.
This announcement came on the heels of the publication of an analysis in the Annals of Internal Medicine, which suggested that as many as 40-45% of COVID-19 cases may be asymptomatic. In this paper, the authors, Daniel P. Oran, AM, and Eric J. Topol, MD, of the Scripps Research Translational Institute in La Jolla, Calif stated: “The likelihood that approximately 40%-45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.”
"The early data that we have assembled on the prevalence of asymptomatic SARS-CoV-2 infection suggest that this is a significant factor in the rapid progression of the COVID-19 pandemic," the authors concluded.
Dr. Van Kerkhove also made comments suggesting otherwise on Twitter, citing a new summary by WHO: “@WHO recently published a summary of transmission of #COVID19, incl. symptomatic, pre-symptomatic and asymptomatic transmission.”
She also tweeted the following lines from the WHO summary: “Comprehensive studies on transmission from asymptomatic individuals are difficult to conduct, but the available evidence from contact tracing reported by Member States suggests that asymptomatically-infected individuals are much less likely to transmit the virus than those who develop symptoms.”
In an additional post, Dr. Van Kerkhove added: “In these data, it is important to breakdown truly asymptomatic vs pre-symptomatic vs mildly symptomatic... also to note that the [percentage] reported or estimated to be ‘asymptomatic’ is not the same as the [percentage] that are asymptomatic that actually transmit.”
In the paper published in the Annals of Internal Medicine, Mr. Oran and Dr. Topol analyzed data of asymptomatic individuals from 16 cohorts between April 19 and May 26, 2020 – a wide-ranging group consisting of residents of cities, health care workers, individuals in homeless shelters, obstetric patients, residents of a nursing home, crew members of aircraft carriers, passengers on cruise ships, and inmates in correctional facilities. Each cohort had varying rates of asymptomatic or presymptomatic cases..
When residents of Iceland were tested, 43 of 100 individuals who tested positive for SARS-CoV-2 did not show symptoms. In Vo’, Italy, 30 of 73 people (41.1%) with positive SARS-CoV-2 test results did not have symptoms in a first round of testing, and 13 of 29 (44.8%) had no symptoms in a second round of testing. Over half of residents of San Francisco’s Mission District who received testing (39 of 74; 52.7%) did not have symptoms, while slightly less than half of Indiana residents tested showed no symptoms (35 of 78; 44.8%).
A majority of 41 individuals (65.9%) who were mostly health care workers at Rutgers University reported no symptoms of COVID-19 at the time of testing. Data from homeless shelters in Boston (129 of 147; 87.7%) and Los Angeles (27 of 43; 62.7%) also showed a high rate of individuals without symptoms. Among 33 obstetric patients in New York City who tested positive for SARS-CoV-2, 29 women (87.9%) were asymptomatic during a median 2-day length of stay. In a Washington state nursing facility, 12 of 23 individuals (52.1%) were positive for SARS-CoV-2 without showing symptoms in a first round of testing, with another 15 of 24 residents (62.5%) not showing symptoms in a second round of testing. Of these residents, 24 individuals (88.9%) later went on to show symptoms of COVID-19.
Most of the 783 Greek citizens who tested positive for SARS-CoV-2 after being evacuated from Spain, Turkey, and the United Kingdom showed no symptoms of COVID-19 (35 of 40; 87.5%). A group of 565 Japanese citizens evacuated from Wuhan, China, had a lower number of cases without initial symptoms – 13 people were positive for SARS-CoV-2, and 4 of 13 (30.8%) had no symptoms.
In closed cohorts, there appeared to also be a high rate of COVID-19 cases without initial symptoms. Of 3,277 inmates from correctional facilities in Arkansas, North Carolina, Ohio, and Virginia, 3,146 individuals (96%) had no symptoms at the time of testing. There was also a large percentage of passengers and crew of the Diamond Princess cruise ship (331 of 712; 46.5%) and an Argentine cruise ship (104 of 128; 81.3%) who were positive for SARS-CoV-2 without symptoms. On the aircraft carrier U.S.S. Theodore Roosevelt, 60% of 856 individuals, while on the French aircraft carrier Charles de Gaulle, nearly 50% of individuals were asymptomatic.
It is difficult to tell the difference between people who are presymptomatic and will later go on to develop symptoms of COVID-19 and those who will remain asymptomatic. “The simple solution to this conundrum is longitudinal testing – that is, repeated observations of the individual over time,” but only 5 of 16 cohorts studied had longitudinal data on individuals, Mr. Oran and Dr. Topol said.
Seth Trueger, MD, an emergency physician and assistant professor of emergency medicine at Northwestern University, Chicago, who was not involved in the study, said it was important to see this information all in one place, even if the data isn’t new.
“I think we’ve certainly kind of seen from the beginning there’s some level of asymptomatic and presymptomatic spread,” Dr. Trueger said. “In health care, we’ve been lucky to get those lessons early on and start to think of things like universal masking in hospitals, and unfortunate things like limiting visitors.”
A more nuanced understanding of how SARS-CoV-2 spreads has been difficult to capture, in part because of operating under a shortened time frame and handicapped testing capacity, he noted. “[Even] in the best of possible circumstances, trying to figure out epidemiology in people who don’t have symptoms is really tough,” Dr. Truegar said.
“Even the best studies are still relatively decent samples, and not totally representative,” he added.
Another limitation to capturing accurate data is method of testing. Real-time reverse transcriptase polymerase chain reaction using nasopharyngeal swabs can detect RNA fragments from SARS-CoV-2, which could potentially affect the results. “It’s really hard to know what is actually infected virus versus just fragments of RNA that make the test positive,” Dr. Trueger said.
If the rate of asymptomatic cases is higher than previously thought, it’s a “double-edged sword,” he noted. It may mean the infection fatality rate is lower than predicted, but “even at high levels of what we think community levels might be, we’re far from herd immunity.”
The study authors and Dr. Trueger reported no relevant conflicts of interest.
SOURCE: Oran DP, Topol EJ. Ann Intern Med. 2020 Jun 3. doi: 10.7326/M20-3012.
This article was updated 6/8/20.
An official with the World Health Organization (WHO) has stated that it appears to be “rare” that an asymptomatic individual can pass SARS-CoV-2 to someone else.
“From the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, said June 8 at a news briefing from the agency’s Geneva headquarters.
This announcement came on the heels of the publication of an analysis in the Annals of Internal Medicine, which suggested that as many as 40-45% of COVID-19 cases may be asymptomatic. In this paper, the authors, Daniel P. Oran, AM, and Eric J. Topol, MD, of the Scripps Research Translational Institute in La Jolla, Calif stated: “The likelihood that approximately 40%-45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.”
"The early data that we have assembled on the prevalence of asymptomatic SARS-CoV-2 infection suggest that this is a significant factor in the rapid progression of the COVID-19 pandemic," the authors concluded.
Dr. Van Kerkhove also made comments suggesting otherwise on Twitter, citing a new summary by WHO: “@WHO recently published a summary of transmission of #COVID19, incl. symptomatic, pre-symptomatic and asymptomatic transmission.”
She also tweeted the following lines from the WHO summary: “Comprehensive studies on transmission from asymptomatic individuals are difficult to conduct, but the available evidence from contact tracing reported by Member States suggests that asymptomatically-infected individuals are much less likely to transmit the virus than those who develop symptoms.”
In an additional post, Dr. Van Kerkhove added: “In these data, it is important to breakdown truly asymptomatic vs pre-symptomatic vs mildly symptomatic... also to note that the [percentage] reported or estimated to be ‘asymptomatic’ is not the same as the [percentage] that are asymptomatic that actually transmit.”
In the paper published in the Annals of Internal Medicine, Mr. Oran and Dr. Topol analyzed data of asymptomatic individuals from 16 cohorts between April 19 and May 26, 2020 – a wide-ranging group consisting of residents of cities, health care workers, individuals in homeless shelters, obstetric patients, residents of a nursing home, crew members of aircraft carriers, passengers on cruise ships, and inmates in correctional facilities. Each cohort had varying rates of asymptomatic or presymptomatic cases..
When residents of Iceland were tested, 43 of 100 individuals who tested positive for SARS-CoV-2 did not show symptoms. In Vo’, Italy, 30 of 73 people (41.1%) with positive SARS-CoV-2 test results did not have symptoms in a first round of testing, and 13 of 29 (44.8%) had no symptoms in a second round of testing. Over half of residents of San Francisco’s Mission District who received testing (39 of 74; 52.7%) did not have symptoms, while slightly less than half of Indiana residents tested showed no symptoms (35 of 78; 44.8%).
A majority of 41 individuals (65.9%) who were mostly health care workers at Rutgers University reported no symptoms of COVID-19 at the time of testing. Data from homeless shelters in Boston (129 of 147; 87.7%) and Los Angeles (27 of 43; 62.7%) also showed a high rate of individuals without symptoms. Among 33 obstetric patients in New York City who tested positive for SARS-CoV-2, 29 women (87.9%) were asymptomatic during a median 2-day length of stay. In a Washington state nursing facility, 12 of 23 individuals (52.1%) were positive for SARS-CoV-2 without showing symptoms in a first round of testing, with another 15 of 24 residents (62.5%) not showing symptoms in a second round of testing. Of these residents, 24 individuals (88.9%) later went on to show symptoms of COVID-19.
Most of the 783 Greek citizens who tested positive for SARS-CoV-2 after being evacuated from Spain, Turkey, and the United Kingdom showed no symptoms of COVID-19 (35 of 40; 87.5%). A group of 565 Japanese citizens evacuated from Wuhan, China, had a lower number of cases without initial symptoms – 13 people were positive for SARS-CoV-2, and 4 of 13 (30.8%) had no symptoms.
In closed cohorts, there appeared to also be a high rate of COVID-19 cases without initial symptoms. Of 3,277 inmates from correctional facilities in Arkansas, North Carolina, Ohio, and Virginia, 3,146 individuals (96%) had no symptoms at the time of testing. There was also a large percentage of passengers and crew of the Diamond Princess cruise ship (331 of 712; 46.5%) and an Argentine cruise ship (104 of 128; 81.3%) who were positive for SARS-CoV-2 without symptoms. On the aircraft carrier U.S.S. Theodore Roosevelt, 60% of 856 individuals, while on the French aircraft carrier Charles de Gaulle, nearly 50% of individuals were asymptomatic.
It is difficult to tell the difference between people who are presymptomatic and will later go on to develop symptoms of COVID-19 and those who will remain asymptomatic. “The simple solution to this conundrum is longitudinal testing – that is, repeated observations of the individual over time,” but only 5 of 16 cohorts studied had longitudinal data on individuals, Mr. Oran and Dr. Topol said.
Seth Trueger, MD, an emergency physician and assistant professor of emergency medicine at Northwestern University, Chicago, who was not involved in the study, said it was important to see this information all in one place, even if the data isn’t new.
“I think we’ve certainly kind of seen from the beginning there’s some level of asymptomatic and presymptomatic spread,” Dr. Trueger said. “In health care, we’ve been lucky to get those lessons early on and start to think of things like universal masking in hospitals, and unfortunate things like limiting visitors.”
A more nuanced understanding of how SARS-CoV-2 spreads has been difficult to capture, in part because of operating under a shortened time frame and handicapped testing capacity, he noted. “[Even] in the best of possible circumstances, trying to figure out epidemiology in people who don’t have symptoms is really tough,” Dr. Truegar said.
“Even the best studies are still relatively decent samples, and not totally representative,” he added.
Another limitation to capturing accurate data is method of testing. Real-time reverse transcriptase polymerase chain reaction using nasopharyngeal swabs can detect RNA fragments from SARS-CoV-2, which could potentially affect the results. “It’s really hard to know what is actually infected virus versus just fragments of RNA that make the test positive,” Dr. Trueger said.
If the rate of asymptomatic cases is higher than previously thought, it’s a “double-edged sword,” he noted. It may mean the infection fatality rate is lower than predicted, but “even at high levels of what we think community levels might be, we’re far from herd immunity.”
The study authors and Dr. Trueger reported no relevant conflicts of interest.
SOURCE: Oran DP, Topol EJ. Ann Intern Med. 2020 Jun 3. doi: 10.7326/M20-3012.
This article was updated 6/8/20.
FROM ANNALS OF INTERNAL MEDICINE
COVID-19-related inflammatory condition more common in black children in small study
More evidence has linked the Kawasaki-like multisystem inflammatory syndrome in children to COVID-19 and suggests that black children have a greater risk of the condition, according to a study published in the BMJ.
A small observational study in Paris found more than half of the 21 children who were admitted for the condition at the city’s pediatric hospital for COVID-19 patients were of African ancestry.
“The observation of a higher proportion of patients of African ancestry is consistent with recent findings, suggesting an effect of either social and living conditions or genetic susceptibility,” wrote Julie Toubiana, MD, PhD, of the University of Paris and the Pasteur Institute, and colleagues.
The findings did not surprise Edward M. Behrens, MD, chief of the division of rheumatology at Children’s Hospital of Philadelphia, whose institution has seen similar disparities that he attributes to social disadvantages.
“Infection rate will be higher in vulnerable populations that are less able to socially distance, have disproportionate numbers of essential workers, and have less access to health care and other resources,” Dr. Behrens said in an interview. “While there may be a role for genetics, environment – including social disparities – is almost certainly playing a role.”
Although the study’s small size is a limitation, he said, “the features described seem to mirror the experience of our center and what has been discussed more broadly amongst U.S. physicians.”
Byron Whyte, MD, a pediatrician in private practice in southeast Washington, found the differences in race interesting, but said the study was too small to draw any conclusions or generalize to the United States. But social disparities related to race are likely similar in France as they are in the United States, he said.
The prospective observational study assessed the clinical and demographic characteristics of all patients under age 18 who met the criteria for Kawasaki disease and were admitted between April 27 and May 20 to the Necker Hospital for Sick Children in Paris.
The 21 children had an average age of 8 years (ranging from 3 to 16), and 57% had at least one parent from sub-Saharan Africa or a Caribbean island; 14% had parents from Asia (two from China and one from Sri Lanka). The authors noted in their discussion that past U.S. and U.K. studies of Kawasaki disease have found a 2.5 times greater risk in Asian-American children and 1.5 times greater risk in African-American children compared with children with European ancestry.
Most of the patients (81%) needed intensive care, with 57% presenting with Kawasaki disease shock syndrome and 67% with myocarditis. Dr. Toubiana and associates also noted that “gastrointestinal symptoms were also unusually common, affecting all of our 21 patients.”
Only nine of the children reported having symptoms of a viral-like illness when they were admitted, primarily headache, cough, coryza, and fever, plus anosmia in one child. Among those children, the Kawasaki symptoms began a median 45 days after onset of the viral symptoms (range 18-79 days).
Only two children showed no positive test result for current COVID-19 infection or antibodies. Eight (38%) of the children had positive PCR tests for SARS-CoV2, and 19 (90%) had positive tests for IgG antibodies. The two patients with both negative tests did not require intensive care and did not have myocarditis.
About half the patients (52%) met all the criteria of Kawasaki disease, and the other 10 had “incomplete Kawasaki disease.” The most common Kawasaki symptoms were the polymorphous skin rash, occurring in 76% of the patients, changes to the lips and oral cavity (76%), and bilateral bulbar conjunctival injection (81%). Three patients (14%) had pleural effusion, and 10 of them (48%) had pericardial effusion, Dr. Toubiana and associates reported.
But Dr. Behrens said he disagrees with the assertion that the illness described in the paper and what he is seeing at Children’s Hospital of Philadelphia is related to Kawasaki disease.
“Most experts here in the U.S. seem to agree this is not Kawasaki disease, but a distinct clinical syndrome called multisystem inflammatory syndrome in children, or MIS-C, that seems to have some overlap with the most nonspecific features of Kawasaki disease,” said Dr. Behrens, who is the Joseph Lee Hollander Chair in Pediatric Rheumatology at Children’s Hospital of Philadelphia. He has coauthored a study currently under review and available as a preprint soon that examines the biologic mechanisms underlying MIS-C.
Neither Dr. Behrens nor Dr. Whyte believed the findings had clinical implications that might change practice, but Dr. Whyte said he will be paying closer attention to the black children he treats – 99% of his practice – who are recovering from COVID-19.
“And, because we know that the concerns of African Americans are often overlooked in health care,” Dr. Whyte said, physicians should “pay a little more attention to symptom reporting on those kids, since there is a possibility that those kids would need hospitalization.”
All the patients in the study were treated with intravenous immunoglobulin, and corticosteroids were administered to 10 of them (48%). Their median hospital stay was 8 days (5 days in intensive care), and all were discharged without any deaths.
“Only one patient had symptoms suggestive of acute covid-19 and most had positive serum test results for IgG antibodies, suggesting that the development of Kawasaki disease in these patients is more likely to be the result of a postviral immunological reaction,” Dr. Toubiana and associates said.
The research received no external funding, and neither the authors nor other quoted physicians had any relevant financial disclosures.
SOURCE: Toubiana J et al. BMJ. 2020 Jun 3, doi: 10.1136 bmj.m2094.
More evidence has linked the Kawasaki-like multisystem inflammatory syndrome in children to COVID-19 and suggests that black children have a greater risk of the condition, according to a study published in the BMJ.
A small observational study in Paris found more than half of the 21 children who were admitted for the condition at the city’s pediatric hospital for COVID-19 patients were of African ancestry.
“The observation of a higher proportion of patients of African ancestry is consistent with recent findings, suggesting an effect of either social and living conditions or genetic susceptibility,” wrote Julie Toubiana, MD, PhD, of the University of Paris and the Pasteur Institute, and colleagues.
The findings did not surprise Edward M. Behrens, MD, chief of the division of rheumatology at Children’s Hospital of Philadelphia, whose institution has seen similar disparities that he attributes to social disadvantages.
“Infection rate will be higher in vulnerable populations that are less able to socially distance, have disproportionate numbers of essential workers, and have less access to health care and other resources,” Dr. Behrens said in an interview. “While there may be a role for genetics, environment – including social disparities – is almost certainly playing a role.”
Although the study’s small size is a limitation, he said, “the features described seem to mirror the experience of our center and what has been discussed more broadly amongst U.S. physicians.”
Byron Whyte, MD, a pediatrician in private practice in southeast Washington, found the differences in race interesting, but said the study was too small to draw any conclusions or generalize to the United States. But social disparities related to race are likely similar in France as they are in the United States, he said.
The prospective observational study assessed the clinical and demographic characteristics of all patients under age 18 who met the criteria for Kawasaki disease and were admitted between April 27 and May 20 to the Necker Hospital for Sick Children in Paris.
The 21 children had an average age of 8 years (ranging from 3 to 16), and 57% had at least one parent from sub-Saharan Africa or a Caribbean island; 14% had parents from Asia (two from China and one from Sri Lanka). The authors noted in their discussion that past U.S. and U.K. studies of Kawasaki disease have found a 2.5 times greater risk in Asian-American children and 1.5 times greater risk in African-American children compared with children with European ancestry.
Most of the patients (81%) needed intensive care, with 57% presenting with Kawasaki disease shock syndrome and 67% with myocarditis. Dr. Toubiana and associates also noted that “gastrointestinal symptoms were also unusually common, affecting all of our 21 patients.”
Only nine of the children reported having symptoms of a viral-like illness when they were admitted, primarily headache, cough, coryza, and fever, plus anosmia in one child. Among those children, the Kawasaki symptoms began a median 45 days after onset of the viral symptoms (range 18-79 days).
Only two children showed no positive test result for current COVID-19 infection or antibodies. Eight (38%) of the children had positive PCR tests for SARS-CoV2, and 19 (90%) had positive tests for IgG antibodies. The two patients with both negative tests did not require intensive care and did not have myocarditis.
About half the patients (52%) met all the criteria of Kawasaki disease, and the other 10 had “incomplete Kawasaki disease.” The most common Kawasaki symptoms were the polymorphous skin rash, occurring in 76% of the patients, changes to the lips and oral cavity (76%), and bilateral bulbar conjunctival injection (81%). Three patients (14%) had pleural effusion, and 10 of them (48%) had pericardial effusion, Dr. Toubiana and associates reported.
But Dr. Behrens said he disagrees with the assertion that the illness described in the paper and what he is seeing at Children’s Hospital of Philadelphia is related to Kawasaki disease.
“Most experts here in the U.S. seem to agree this is not Kawasaki disease, but a distinct clinical syndrome called multisystem inflammatory syndrome in children, or MIS-C, that seems to have some overlap with the most nonspecific features of Kawasaki disease,” said Dr. Behrens, who is the Joseph Lee Hollander Chair in Pediatric Rheumatology at Children’s Hospital of Philadelphia. He has coauthored a study currently under review and available as a preprint soon that examines the biologic mechanisms underlying MIS-C.
Neither Dr. Behrens nor Dr. Whyte believed the findings had clinical implications that might change practice, but Dr. Whyte said he will be paying closer attention to the black children he treats – 99% of his practice – who are recovering from COVID-19.
“And, because we know that the concerns of African Americans are often overlooked in health care,” Dr. Whyte said, physicians should “pay a little more attention to symptom reporting on those kids, since there is a possibility that those kids would need hospitalization.”
All the patients in the study were treated with intravenous immunoglobulin, and corticosteroids were administered to 10 of them (48%). Their median hospital stay was 8 days (5 days in intensive care), and all were discharged without any deaths.
“Only one patient had symptoms suggestive of acute covid-19 and most had positive serum test results for IgG antibodies, suggesting that the development of Kawasaki disease in these patients is more likely to be the result of a postviral immunological reaction,” Dr. Toubiana and associates said.
The research received no external funding, and neither the authors nor other quoted physicians had any relevant financial disclosures.
SOURCE: Toubiana J et al. BMJ. 2020 Jun 3, doi: 10.1136 bmj.m2094.
More evidence has linked the Kawasaki-like multisystem inflammatory syndrome in children to COVID-19 and suggests that black children have a greater risk of the condition, according to a study published in the BMJ.
A small observational study in Paris found more than half of the 21 children who were admitted for the condition at the city’s pediatric hospital for COVID-19 patients were of African ancestry.
“The observation of a higher proportion of patients of African ancestry is consistent with recent findings, suggesting an effect of either social and living conditions or genetic susceptibility,” wrote Julie Toubiana, MD, PhD, of the University of Paris and the Pasteur Institute, and colleagues.
The findings did not surprise Edward M. Behrens, MD, chief of the division of rheumatology at Children’s Hospital of Philadelphia, whose institution has seen similar disparities that he attributes to social disadvantages.
“Infection rate will be higher in vulnerable populations that are less able to socially distance, have disproportionate numbers of essential workers, and have less access to health care and other resources,” Dr. Behrens said in an interview. “While there may be a role for genetics, environment – including social disparities – is almost certainly playing a role.”
Although the study’s small size is a limitation, he said, “the features described seem to mirror the experience of our center and what has been discussed more broadly amongst U.S. physicians.”
Byron Whyte, MD, a pediatrician in private practice in southeast Washington, found the differences in race interesting, but said the study was too small to draw any conclusions or generalize to the United States. But social disparities related to race are likely similar in France as they are in the United States, he said.
The prospective observational study assessed the clinical and demographic characteristics of all patients under age 18 who met the criteria for Kawasaki disease and were admitted between April 27 and May 20 to the Necker Hospital for Sick Children in Paris.
The 21 children had an average age of 8 years (ranging from 3 to 16), and 57% had at least one parent from sub-Saharan Africa or a Caribbean island; 14% had parents from Asia (two from China and one from Sri Lanka). The authors noted in their discussion that past U.S. and U.K. studies of Kawasaki disease have found a 2.5 times greater risk in Asian-American children and 1.5 times greater risk in African-American children compared with children with European ancestry.
Most of the patients (81%) needed intensive care, with 57% presenting with Kawasaki disease shock syndrome and 67% with myocarditis. Dr. Toubiana and associates also noted that “gastrointestinal symptoms were also unusually common, affecting all of our 21 patients.”
Only nine of the children reported having symptoms of a viral-like illness when they were admitted, primarily headache, cough, coryza, and fever, plus anosmia in one child. Among those children, the Kawasaki symptoms began a median 45 days after onset of the viral symptoms (range 18-79 days).
Only two children showed no positive test result for current COVID-19 infection or antibodies. Eight (38%) of the children had positive PCR tests for SARS-CoV2, and 19 (90%) had positive tests for IgG antibodies. The two patients with both negative tests did not require intensive care and did not have myocarditis.
About half the patients (52%) met all the criteria of Kawasaki disease, and the other 10 had “incomplete Kawasaki disease.” The most common Kawasaki symptoms were the polymorphous skin rash, occurring in 76% of the patients, changes to the lips and oral cavity (76%), and bilateral bulbar conjunctival injection (81%). Three patients (14%) had pleural effusion, and 10 of them (48%) had pericardial effusion, Dr. Toubiana and associates reported.
But Dr. Behrens said he disagrees with the assertion that the illness described in the paper and what he is seeing at Children’s Hospital of Philadelphia is related to Kawasaki disease.
“Most experts here in the U.S. seem to agree this is not Kawasaki disease, but a distinct clinical syndrome called multisystem inflammatory syndrome in children, or MIS-C, that seems to have some overlap with the most nonspecific features of Kawasaki disease,” said Dr. Behrens, who is the Joseph Lee Hollander Chair in Pediatric Rheumatology at Children’s Hospital of Philadelphia. He has coauthored a study currently under review and available as a preprint soon that examines the biologic mechanisms underlying MIS-C.
Neither Dr. Behrens nor Dr. Whyte believed the findings had clinical implications that might change practice, but Dr. Whyte said he will be paying closer attention to the black children he treats – 99% of his practice – who are recovering from COVID-19.
“And, because we know that the concerns of African Americans are often overlooked in health care,” Dr. Whyte said, physicians should “pay a little more attention to symptom reporting on those kids, since there is a possibility that those kids would need hospitalization.”
All the patients in the study were treated with intravenous immunoglobulin, and corticosteroids were administered to 10 of them (48%). Their median hospital stay was 8 days (5 days in intensive care), and all were discharged without any deaths.
“Only one patient had symptoms suggestive of acute covid-19 and most had positive serum test results for IgG antibodies, suggesting that the development of Kawasaki disease in these patients is more likely to be the result of a postviral immunological reaction,” Dr. Toubiana and associates said.
The research received no external funding, and neither the authors nor other quoted physicians had any relevant financial disclosures.
SOURCE: Toubiana J et al. BMJ. 2020 Jun 3, doi: 10.1136 bmj.m2094.
FROM BMJ
COVID-19 neurologic effects: Does the virus directly attack the brain?
A new review article summarizes what is known so far, and what clinicians need to look out for.
“We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response – a bystander effect of people being severely ill. It is probably a combination of both,” said senior author Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology; division chief of neurological infections & global neurology; and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.
“Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences,” she said.
The review was published online May 29 in JAMA Neurology.
Brain changes linked to loss of smell
In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell – the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.
“Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway,” conclude the researchers, led by first author Letterio S. Politi, MD, of the department of neuroradiology at IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.
Can coronaviruses enter the CNS?
Dr. Spudich described this case report as “compelling evidence suggesting that loss of smell is a neurologic effect.”
“Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement,” Dr. Spudich commented. “While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects,” she added.
In their review article, Dr. Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.
“We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects,” she said. “There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain.”
Complications of other systemic effects?
Dr. Spudich is a neurologist specializing in neurologic consequences of infectious disease. “We don’t normally have such vast numbers of patients but in the last 3 months there has been an avalanche,” she says. From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.
“Reports from China suggested that serious neurologic effects were present in about one-third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that – maybe around 10%,” she noted.
Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Dr. Spudich reported. “Medical staff need to be aware of this – a severe headache in a patient who doesn’t normally get headaches could be a sign of the virus.”
Some of the neurologic symptoms could be caused by autoimmunity. Dr. Spudich explained that, in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. “This is well described in HIV, but we are also now seeing this in COVID-19 patients too,” she said. “A panoply of conditions can be caused by autoimmunity.”
On the increase in strokes that has been reported in COVID-19 patients, Dr. Spudich said, “this could be due to direct effects of the virus (e.g., causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway.”
There have been some very high-profile reports of younger patients with major strokes, she said, “but we haven’t seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven’t seen a preponderance of strokes in young, otherwise healthy people.”
Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.
“We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don’t know where in this [cluster] COVID-19 virus falls,” Dr. Spudich said.
Much is still unknown
“The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging.” Dr. Spudich urged clinicians to try to collect such information in patients with neurologic symptoms.
Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Dr. Spudich suggested that some changes in procedure may help. “In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator.”
It is also unclear whether the neurologic effects seen during COVID-19 infection will last long term.
Dr. Spudich noted that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. “This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this,” she said.
This article first appeared on Medscape.com.
A new review article summarizes what is known so far, and what clinicians need to look out for.
“We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response – a bystander effect of people being severely ill. It is probably a combination of both,” said senior author Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology; division chief of neurological infections & global neurology; and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.
“Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences,” she said.
The review was published online May 29 in JAMA Neurology.
Brain changes linked to loss of smell
In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell – the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.
“Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway,” conclude the researchers, led by first author Letterio S. Politi, MD, of the department of neuroradiology at IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.
Can coronaviruses enter the CNS?
Dr. Spudich described this case report as “compelling evidence suggesting that loss of smell is a neurologic effect.”
“Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement,” Dr. Spudich commented. “While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects,” she added.
In their review article, Dr. Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.
“We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects,” she said. “There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain.”
Complications of other systemic effects?
Dr. Spudich is a neurologist specializing in neurologic consequences of infectious disease. “We don’t normally have such vast numbers of patients but in the last 3 months there has been an avalanche,” she says. From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.
“Reports from China suggested that serious neurologic effects were present in about one-third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that – maybe around 10%,” she noted.
Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Dr. Spudich reported. “Medical staff need to be aware of this – a severe headache in a patient who doesn’t normally get headaches could be a sign of the virus.”
Some of the neurologic symptoms could be caused by autoimmunity. Dr. Spudich explained that, in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. “This is well described in HIV, but we are also now seeing this in COVID-19 patients too,” she said. “A panoply of conditions can be caused by autoimmunity.”
On the increase in strokes that has been reported in COVID-19 patients, Dr. Spudich said, “this could be due to direct effects of the virus (e.g., causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway.”
There have been some very high-profile reports of younger patients with major strokes, she said, “but we haven’t seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven’t seen a preponderance of strokes in young, otherwise healthy people.”
Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.
“We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don’t know where in this [cluster] COVID-19 virus falls,” Dr. Spudich said.
Much is still unknown
“The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging.” Dr. Spudich urged clinicians to try to collect such information in patients with neurologic symptoms.
Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Dr. Spudich suggested that some changes in procedure may help. “In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator.”
It is also unclear whether the neurologic effects seen during COVID-19 infection will last long term.
Dr. Spudich noted that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. “This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this,” she said.
This article first appeared on Medscape.com.
A new review article summarizes what is known so far, and what clinicians need to look out for.
“We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response – a bystander effect of people being severely ill. It is probably a combination of both,” said senior author Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology; division chief of neurological infections & global neurology; and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.
“Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences,” she said.
The review was published online May 29 in JAMA Neurology.
Brain changes linked to loss of smell
In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell – the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.
“Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway,” conclude the researchers, led by first author Letterio S. Politi, MD, of the department of neuroradiology at IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.
Can coronaviruses enter the CNS?
Dr. Spudich described this case report as “compelling evidence suggesting that loss of smell is a neurologic effect.”
“Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement,” Dr. Spudich commented. “While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects,” she added.
In their review article, Dr. Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.
“We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects,” she said. “There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain.”
Complications of other systemic effects?
Dr. Spudich is a neurologist specializing in neurologic consequences of infectious disease. “We don’t normally have such vast numbers of patients but in the last 3 months there has been an avalanche,” she says. From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.
“Reports from China suggested that serious neurologic effects were present in about one-third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that – maybe around 10%,” she noted.
Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Dr. Spudich reported. “Medical staff need to be aware of this – a severe headache in a patient who doesn’t normally get headaches could be a sign of the virus.”
Some of the neurologic symptoms could be caused by autoimmunity. Dr. Spudich explained that, in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. “This is well described in HIV, but we are also now seeing this in COVID-19 patients too,” she said. “A panoply of conditions can be caused by autoimmunity.”
On the increase in strokes that has been reported in COVID-19 patients, Dr. Spudich said, “this could be due to direct effects of the virus (e.g., causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway.”
There have been some very high-profile reports of younger patients with major strokes, she said, “but we haven’t seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven’t seen a preponderance of strokes in young, otherwise healthy people.”
Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.
“We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don’t know where in this [cluster] COVID-19 virus falls,” Dr. Spudich said.
Much is still unknown
“The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging.” Dr. Spudich urged clinicians to try to collect such information in patients with neurologic symptoms.
Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Dr. Spudich suggested that some changes in procedure may help. “In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator.”
It is also unclear whether the neurologic effects seen during COVID-19 infection will last long term.
Dr. Spudich noted that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. “This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this,” she said.
This article first appeared on Medscape.com.
FDA approves new antibiotic for HABP/VABP treatment
in people aged 18 years and older.
Approval for Recarbrio was based on results of a randomized, controlled clinical trial of 535 hospitalized adults with hospital-acquired and ventilator-associated bacterial pneumonia who received either Recarbrio or piperacillin-tazobactam. After 28 days, 16% of patients who received Recarbrio and 21% of patients who received piperacillin-tazobactam had died.
The most common adverse events associated with Recarbrio are increased alanine aminotransferase/ aspartate aminotransferase, anemia, diarrhea, hypokalemia, and hyponatremia. Recarbrio was previously approved by the FDA to treat patients with complicated urinary tract infections and complicated intra-abdominal infections who have limited or no alternative treatment options, according to an FDA press release.
“As a public health agency, the FDA addresses the threat of antimicrobial-resistant infections by facilitating the development of safe and effective new treatments. These efforts provide more options to fight serious bacterial infections and get new, safe and effective therapies to patients as soon as possible,” said Sumathi Nambiar, MD, MPH, director of the division of anti-infectives within the office of infectious disease at the Center for Drug Evaluation and Research.
in people aged 18 years and older.
Approval for Recarbrio was based on results of a randomized, controlled clinical trial of 535 hospitalized adults with hospital-acquired and ventilator-associated bacterial pneumonia who received either Recarbrio or piperacillin-tazobactam. After 28 days, 16% of patients who received Recarbrio and 21% of patients who received piperacillin-tazobactam had died.
The most common adverse events associated with Recarbrio are increased alanine aminotransferase/ aspartate aminotransferase, anemia, diarrhea, hypokalemia, and hyponatremia. Recarbrio was previously approved by the FDA to treat patients with complicated urinary tract infections and complicated intra-abdominal infections who have limited or no alternative treatment options, according to an FDA press release.
“As a public health agency, the FDA addresses the threat of antimicrobial-resistant infections by facilitating the development of safe and effective new treatments. These efforts provide more options to fight serious bacterial infections and get new, safe and effective therapies to patients as soon as possible,” said Sumathi Nambiar, MD, MPH, director of the division of anti-infectives within the office of infectious disease at the Center for Drug Evaluation and Research.
in people aged 18 years and older.
Approval for Recarbrio was based on results of a randomized, controlled clinical trial of 535 hospitalized adults with hospital-acquired and ventilator-associated bacterial pneumonia who received either Recarbrio or piperacillin-tazobactam. After 28 days, 16% of patients who received Recarbrio and 21% of patients who received piperacillin-tazobactam had died.
The most common adverse events associated with Recarbrio are increased alanine aminotransferase/ aspartate aminotransferase, anemia, diarrhea, hypokalemia, and hyponatremia. Recarbrio was previously approved by the FDA to treat patients with complicated urinary tract infections and complicated intra-abdominal infections who have limited or no alternative treatment options, according to an FDA press release.
“As a public health agency, the FDA addresses the threat of antimicrobial-resistant infections by facilitating the development of safe and effective new treatments. These efforts provide more options to fight serious bacterial infections and get new, safe and effective therapies to patients as soon as possible,” said Sumathi Nambiar, MD, MPH, director of the division of anti-infectives within the office of infectious disease at the Center for Drug Evaluation and Research.
COVID-19: Use these strategies to help parents with and without special needs children
Most people can cope, to some degree, with the multiple weeks of social distancing and stressors related to the pandemic. But what if those stressors became a way of life for a year – or longer? What sorts of skills would be essential not only to survive but to have a renewed sense of resilience?
I know of one group that has had experiences that mirror the challenges faced by the parents of children: the parents of special needs children. As I argued previously, those parents have faced many of the challenges presented by COVID-19. Among those challenges are social distancing and difficulty accessing everyday common experiences. These parents know that they have to manage more areas of their children’s rearing than do their counterparts.
In addition to having to plan for how to deal with acute urgent or emergent medical situations involving their special needs children, these parents also must prepare for the long-term effects of managing children who require ongoing daily care, attention, and dedication.
These strategies can help the parents of special needs kids find a sense of mastery and comfort. The hope is that, after practicing them for long periods of time, the strategies become second nature.
Here are several strategies that might help patients with children during this pandemic:
- Take time to reset: Sometimes it is helpful for parents to take a minute away from a difficult impasse with their kids to reset and take their own “time out.” A few seconds of mental time away from the “scene” provides space and a mental reminder that the minute that just happened is finite, and that a whole new one is coming up next. The break provides a sense of hope. This cognitive reframing could be practiced often.
- Re-enter the challenging scene with a warm voice: Parents model for their children, but they also are telling their own brains that they, too, can calm down. This approach also de-escalates the situation and allows children to get used to hearing directions from someone who is in control – without hostility or irritability.
- Keep a sense of humor; it might come in handy: This is especially the case when tension is in the home, or when facing a set of challenging bad news. As an example, consider how some situations are so repetitive that they border on the ridiculous – such as a grown child having a tantrum at a store. Encourage the children to give themselves permission to cry first so they can laugh second, and then move on.
- Establish a routine for children that is self-reinforcing, and allows for together and separate times: They can, as an example: A) Get ready for the day all by themselves, or as much as they can do independently, before they come down and then B) have breakfast. Then, the child can C) do homework, and then D) go play outside. The routine would then continue on its own without outside reinforcers.
- Tell the children that they can get to the reinforcing activity only after completing the previous one. Over time, they learn to take pride in completing the first activity and doing so more independently. Not having to wait to be told what to do all the time fosters a sense of independence.
- Plan for meals and fun tasks together, and separate for individual work. This creates a sense of change and gives the day a certain flow. Establish routines that are predictable for the children that can be easily documented for the whole family on a calendar. Establish a beginning and an end time to the work day. Mark the end of the day with a chalk line establishing when the family can engage in a certain activity, for example, going for a family bike ride. Let the routine honor healthy circadian rhythms for sleep/wakeful times, and be consistent.
- Feed the brain and body the “good stuff”: Limit negative news, and surround the children with people who bring them joy or provide hope. Listen to inspirational messages and uplifting music. Give the children food that nourishes and energizes their bodies. Take in the view outside, the greenery, or the sky if there is no green around. Connect with family/friends who are far away.
- Make time to replenish with something that is meaningful/productive/helpful: Parents have very little time for themselves when they are “on,” so when they can actually take a little time to recharge, the activity should check many boxes. For example, encourage them to go for a walk (exercise) while listening to music (relax), make a phone call to someone who can relate to their situation (socialize), pray with someone (be spiritual), or sit in their rooms to get some alone quiet time (meditate). Reach out to those who are lonely. Network. Mentor. Volunteer.
- Develop an eye for noticing the positive: Instead of hoping for things to go back to the way they were, tell your patients to practice embracing without judgment the new norm. Get them to notice the time they spend with their families. Break all tasks into many smaller tasks, so there is more possibility of observing progress, and it is evident for everyone to see. Learn to notice the small changes that they want to see in their children. Celebrate all that can be celebrated by stating the obvious: “You wiped your face after eating. You are observant; you are noticing when you have something on your face.”
- State when a child is forgiving, helpful, or puts forward some effort. Label the growth witnessed. The child will learn that that is who they are over time (“observant”). Verbalizing these behaviors also will provide patients with a sense of mastery over parenting, because they are driving the emotional and behavioral development of their children in a way that also complements their family values.
- Make everyone in the family a contributor and foster a sense of gratitude: Give everyone a reason to claim that their collaboration and effort are a big part of the plan’s success. Take turns to lessen everyone’s burden and to thank them for their contributions. Older children can take on leadership roles, even in small ways. Younger children can practice being good listeners, following directions, and helping. Reverse the roles when possible.
Special needs families sometimes have to work harder than others to overcome obstacles, grow, and learn to support one another. Since the pandemic, many parents have been just as challenged. Mastering the above skills might provide a sense of fulfillment and agency, as well as an appreciation for the unexpected gifts that special children – and all children – have to offer.
Dr. Sotir is a psychiatrist with a private practice in Wheaton, Ill. As a parent of three children, one with special needs, she has extensive experience helping parents challenged by having special needs children find balance, support, direction, and joy in all dimensions of individual and family life. This area is the focus of her practice and public speaking. She has no disclosures.
Most people can cope, to some degree, with the multiple weeks of social distancing and stressors related to the pandemic. But what if those stressors became a way of life for a year – or longer? What sorts of skills would be essential not only to survive but to have a renewed sense of resilience?
I know of one group that has had experiences that mirror the challenges faced by the parents of children: the parents of special needs children. As I argued previously, those parents have faced many of the challenges presented by COVID-19. Among those challenges are social distancing and difficulty accessing everyday common experiences. These parents know that they have to manage more areas of their children’s rearing than do their counterparts.
In addition to having to plan for how to deal with acute urgent or emergent medical situations involving their special needs children, these parents also must prepare for the long-term effects of managing children who require ongoing daily care, attention, and dedication.
These strategies can help the parents of special needs kids find a sense of mastery and comfort. The hope is that, after practicing them for long periods of time, the strategies become second nature.
Here are several strategies that might help patients with children during this pandemic:
- Take time to reset: Sometimes it is helpful for parents to take a minute away from a difficult impasse with their kids to reset and take their own “time out.” A few seconds of mental time away from the “scene” provides space and a mental reminder that the minute that just happened is finite, and that a whole new one is coming up next. The break provides a sense of hope. This cognitive reframing could be practiced often.
- Re-enter the challenging scene with a warm voice: Parents model for their children, but they also are telling their own brains that they, too, can calm down. This approach also de-escalates the situation and allows children to get used to hearing directions from someone who is in control – without hostility or irritability.
- Keep a sense of humor; it might come in handy: This is especially the case when tension is in the home, or when facing a set of challenging bad news. As an example, consider how some situations are so repetitive that they border on the ridiculous – such as a grown child having a tantrum at a store. Encourage the children to give themselves permission to cry first so they can laugh second, and then move on.
- Establish a routine for children that is self-reinforcing, and allows for together and separate times: They can, as an example: A) Get ready for the day all by themselves, or as much as they can do independently, before they come down and then B) have breakfast. Then, the child can C) do homework, and then D) go play outside. The routine would then continue on its own without outside reinforcers.
- Tell the children that they can get to the reinforcing activity only after completing the previous one. Over time, they learn to take pride in completing the first activity and doing so more independently. Not having to wait to be told what to do all the time fosters a sense of independence.
- Plan for meals and fun tasks together, and separate for individual work. This creates a sense of change and gives the day a certain flow. Establish routines that are predictable for the children that can be easily documented for the whole family on a calendar. Establish a beginning and an end time to the work day. Mark the end of the day with a chalk line establishing when the family can engage in a certain activity, for example, going for a family bike ride. Let the routine honor healthy circadian rhythms for sleep/wakeful times, and be consistent.
- Feed the brain and body the “good stuff”: Limit negative news, and surround the children with people who bring them joy or provide hope. Listen to inspirational messages and uplifting music. Give the children food that nourishes and energizes their bodies. Take in the view outside, the greenery, or the sky if there is no green around. Connect with family/friends who are far away.
- Make time to replenish with something that is meaningful/productive/helpful: Parents have very little time for themselves when they are “on,” so when they can actually take a little time to recharge, the activity should check many boxes. For example, encourage them to go for a walk (exercise) while listening to music (relax), make a phone call to someone who can relate to their situation (socialize), pray with someone (be spiritual), or sit in their rooms to get some alone quiet time (meditate). Reach out to those who are lonely. Network. Mentor. Volunteer.
- Develop an eye for noticing the positive: Instead of hoping for things to go back to the way they were, tell your patients to practice embracing without judgment the new norm. Get them to notice the time they spend with their families. Break all tasks into many smaller tasks, so there is more possibility of observing progress, and it is evident for everyone to see. Learn to notice the small changes that they want to see in their children. Celebrate all that can be celebrated by stating the obvious: “You wiped your face after eating. You are observant; you are noticing when you have something on your face.”
- State when a child is forgiving, helpful, or puts forward some effort. Label the growth witnessed. The child will learn that that is who they are over time (“observant”). Verbalizing these behaviors also will provide patients with a sense of mastery over parenting, because they are driving the emotional and behavioral development of their children in a way that also complements their family values.
- Make everyone in the family a contributor and foster a sense of gratitude: Give everyone a reason to claim that their collaboration and effort are a big part of the plan’s success. Take turns to lessen everyone’s burden and to thank them for their contributions. Older children can take on leadership roles, even in small ways. Younger children can practice being good listeners, following directions, and helping. Reverse the roles when possible.
Special needs families sometimes have to work harder than others to overcome obstacles, grow, and learn to support one another. Since the pandemic, many parents have been just as challenged. Mastering the above skills might provide a sense of fulfillment and agency, as well as an appreciation for the unexpected gifts that special children – and all children – have to offer.
Dr. Sotir is a psychiatrist with a private practice in Wheaton, Ill. As a parent of three children, one with special needs, she has extensive experience helping parents challenged by having special needs children find balance, support, direction, and joy in all dimensions of individual and family life. This area is the focus of her practice and public speaking. She has no disclosures.
Most people can cope, to some degree, with the multiple weeks of social distancing and stressors related to the pandemic. But what if those stressors became a way of life for a year – or longer? What sorts of skills would be essential not only to survive but to have a renewed sense of resilience?
I know of one group that has had experiences that mirror the challenges faced by the parents of children: the parents of special needs children. As I argued previously, those parents have faced many of the challenges presented by COVID-19. Among those challenges are social distancing and difficulty accessing everyday common experiences. These parents know that they have to manage more areas of their children’s rearing than do their counterparts.
In addition to having to plan for how to deal with acute urgent or emergent medical situations involving their special needs children, these parents also must prepare for the long-term effects of managing children who require ongoing daily care, attention, and dedication.
These strategies can help the parents of special needs kids find a sense of mastery and comfort. The hope is that, after practicing them for long periods of time, the strategies become second nature.
Here are several strategies that might help patients with children during this pandemic:
- Take time to reset: Sometimes it is helpful for parents to take a minute away from a difficult impasse with their kids to reset and take their own “time out.” A few seconds of mental time away from the “scene” provides space and a mental reminder that the minute that just happened is finite, and that a whole new one is coming up next. The break provides a sense of hope. This cognitive reframing could be practiced often.
- Re-enter the challenging scene with a warm voice: Parents model for their children, but they also are telling their own brains that they, too, can calm down. This approach also de-escalates the situation and allows children to get used to hearing directions from someone who is in control – without hostility or irritability.
- Keep a sense of humor; it might come in handy: This is especially the case when tension is in the home, or when facing a set of challenging bad news. As an example, consider how some situations are so repetitive that they border on the ridiculous – such as a grown child having a tantrum at a store. Encourage the children to give themselves permission to cry first so they can laugh second, and then move on.
- Establish a routine for children that is self-reinforcing, and allows for together and separate times: They can, as an example: A) Get ready for the day all by themselves, or as much as they can do independently, before they come down and then B) have breakfast. Then, the child can C) do homework, and then D) go play outside. The routine would then continue on its own without outside reinforcers.
- Tell the children that they can get to the reinforcing activity only after completing the previous one. Over time, they learn to take pride in completing the first activity and doing so more independently. Not having to wait to be told what to do all the time fosters a sense of independence.
- Plan for meals and fun tasks together, and separate for individual work. This creates a sense of change and gives the day a certain flow. Establish routines that are predictable for the children that can be easily documented for the whole family on a calendar. Establish a beginning and an end time to the work day. Mark the end of the day with a chalk line establishing when the family can engage in a certain activity, for example, going for a family bike ride. Let the routine honor healthy circadian rhythms for sleep/wakeful times, and be consistent.
- Feed the brain and body the “good stuff”: Limit negative news, and surround the children with people who bring them joy or provide hope. Listen to inspirational messages and uplifting music. Give the children food that nourishes and energizes their bodies. Take in the view outside, the greenery, or the sky if there is no green around. Connect with family/friends who are far away.
- Make time to replenish with something that is meaningful/productive/helpful: Parents have very little time for themselves when they are “on,” so when they can actually take a little time to recharge, the activity should check many boxes. For example, encourage them to go for a walk (exercise) while listening to music (relax), make a phone call to someone who can relate to their situation (socialize), pray with someone (be spiritual), or sit in their rooms to get some alone quiet time (meditate). Reach out to those who are lonely. Network. Mentor. Volunteer.
- Develop an eye for noticing the positive: Instead of hoping for things to go back to the way they were, tell your patients to practice embracing without judgment the new norm. Get them to notice the time they spend with their families. Break all tasks into many smaller tasks, so there is more possibility of observing progress, and it is evident for everyone to see. Learn to notice the small changes that they want to see in their children. Celebrate all that can be celebrated by stating the obvious: “You wiped your face after eating. You are observant; you are noticing when you have something on your face.”
- State when a child is forgiving, helpful, or puts forward some effort. Label the growth witnessed. The child will learn that that is who they are over time (“observant”). Verbalizing these behaviors also will provide patients with a sense of mastery over parenting, because they are driving the emotional and behavioral development of their children in a way that also complements their family values.
- Make everyone in the family a contributor and foster a sense of gratitude: Give everyone a reason to claim that their collaboration and effort are a big part of the plan’s success. Take turns to lessen everyone’s burden and to thank them for their contributions. Older children can take on leadership roles, even in small ways. Younger children can practice being good listeners, following directions, and helping. Reverse the roles when possible.
Special needs families sometimes have to work harder than others to overcome obstacles, grow, and learn to support one another. Since the pandemic, many parents have been just as challenged. Mastering the above skills might provide a sense of fulfillment and agency, as well as an appreciation for the unexpected gifts that special children – and all children – have to offer.
Dr. Sotir is a psychiatrist with a private practice in Wheaton, Ill. As a parent of three children, one with special needs, she has extensive experience helping parents challenged by having special needs children find balance, support, direction, and joy in all dimensions of individual and family life. This area is the focus of her practice and public speaking. She has no disclosures.
Lancet, NEJM retract studies on hydroxychloroquine for COVID-19
The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.
The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.
Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.
The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.
“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.
Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.
The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”
The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.
“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”
In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”
Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.
A version of this article originally appeared on Medscape.com.
The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.
The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.
Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.
The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.
“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.
Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.
The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”
The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.
“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”
In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”
Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.
A version of this article originally appeared on Medscape.com.
The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.
The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.
Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.
The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.
“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.
Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.
The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”
The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.
“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”
In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”
Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.
A version of this article originally appeared on Medscape.com.