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PPE shortage could last years without strategic plan, experts warn
Officials said logistical challenges continue 7 months after the coronavirus reached the United States, as the flu season approaches and as some state emergency management agencies prepare for a fall surge in COVID-19 cases.
Although the disarray is not as widespread as it was this spring, hospitals said rolling shortages of supplies range from specialized beds to disposable isolation gowns to thermometers.
“A few weeks ago, we were having a very difficult time getting the sanitary wipes. You just couldn’t get them,” said Bernard Klein, MD, chief executive of Providence Holy Cross Medical Center in Mission Hills, Calif., near Los Angeles. “We actually had to manufacture our own.”
This same dynamic has played out across a number of critical supplies in his hospital. First masks, then isolation gowns and now a specialized bed that allows nurses to turn COVID-19 patients onto their bellies – equipment that helps workers with what can otherwise be a six-person job.
“We’ve seen whole families come to our hospital with COVID, and several members hospitalized at the same time,” said Dr. Klein. “It’s very, very sad.”
Testing supplies ran short as the predominantly Latino community served by Providence Holy Cross was hit hard by COVID, and even as nearby hospitals could process 15-minute tests.
“If we had a more coordinated response with a partnership between the medical field, the government and the private industry, it would help improve the supply chain to the areas that need it most,” Dr. Klein said.
Dr. Klein said he expected to deal with equipment and supply shortages throughout 2021, especially as flu season approaches.
“Most people focus on those N95 respirators,” said Carmela Coyle, CEO of the California Hospital Association, an industry group that represents more than 400 hospitals across one of America’s hardest-hit states.
She said she believed COVID-19-related supply challenges will persist through 2022.
“We have been challenged with shortages of isolation gowns, face shields, which you’re now starting to see in public places. Any one piece that’s in shortage or not available creates risk for patients and for health care workers,” said Ms. Coyle.
At the same time, trade associations representing manufacturers said persuading customers to shift to American suppliers had been difficult.
“I also have industry that’s working only at 10-20% capacity, who can make PPE in our own backyard, but have no orders,” said Kim Glas, CEO of the National Council of Textile Organizations, whose members make reusable cloth gowns.
Manufacturers in her organization have made “hundreds of millions of products,” but, without long-term government contracts, many are apprehensive to invest in the equipment needed to scale up the business and eventually lower prices.
“If there continues to be an upward trajectory of COVID-19 cases, not just in the U.S. but globally, you can see those supply chains breaking down again,” Ms. Glas said. “It is a health care security issue.”
For the past 2 decades, personal protective equipment was supplied to health care institutions in lean supply chains in the same way toilet paper was to grocery stores. Chains between major manufacturers and end users were so efficient, there was no need to stockpile goods.
But in March, the supply chain broke when major Asian PPE exporters embargoed materials or shut down just as demand increased exponentially. Thus, health care institutions were in much the same position as regular grocery shoppers, who were trying to buy great quantities of a product they never needed to stockpile before.
“I am very concerned about long-term PPE shortages for the foreseeable future,” said Susan Bailey, MD, president of the American Medical Association.
“There’s no question the situation is better than it was a couple of months ago,” said Bailey. However, many health care organizations, including her own, have struggled to obtain PPE. Bailey practices at a 10-doctor allergy clinic and was met with a 10,000-mask minimum when they tried to order N95 respirators.
“We have not seen evidence of a long-term strategic plan for the manufacture, acquisition and distribution of PPE” from the government, said Dr. Bailey. “The supply chain needs to be strengthened dramatically, and we need less dependence on foreign goods to manufacture our own PPE in the U.S.”
Some products have now come back to be made in the United States – although factories are not expected to be able to reach demand until mid-2021.
“A lot has been done in the last 6 months. We are largely out of the hole, and we have planted the seeds to render the United States self-sufficient,” said Dave Rousse, president of the Association of the Nonwoven Fabrics Industry.
In 2019, 850 tons of the material used in disposable masks was made in the United States. Around 10,000 tons is expected to be made in 2021, satisfying perhaps 80% of demand. But PPE is a suite of items – including gloves, gowns and face shields – not all of which have seen the same success.
“Thermometers are becoming a real issue,” said Cindy Juhas, chief strategy officer of CME, an American health care product distributor. “They’re expecting even a problem with needles and syringes for the amount of vaccines they have to make.”
Federal government efforts to address the supply chain have foundered. The Federal Emergency Management Agency, in charge of the COVID-19 response, told congressional interviewers in June it had “no involvement” in distributing PPE to hot spots.
Project Airbridge, an initiative headed by Jared Kushner, President Donald Trump’s son-in-law, flew PPE from international suppliers to the U.S. at taxpayer expense but was phased out. And the government has not responded to the AMA’s calls for more distribution data.
Arguably, Dr. Klein is among the best placed to weather such disruptions. He is part of a 51-hospital chain with purchasing power, and among the institutions that distributors prioritize when selling supplies. But tribulations continue even in hospitals, as shortages have pushed buyers to look directly for manufacturers, often through a swamp of companies that have sprung up overnight.
Now distributors are being called upon not just by their traditional customers – hospitals and long-term care homes – but by nearly every segment of society. First responders, schools, clinics and even food businesses are all buying medical equipment now.
“There’s going to be lots of other shortages we haven’t even thought about,” said Ms. Juhas.
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Officials said logistical challenges continue 7 months after the coronavirus reached the United States, as the flu season approaches and as some state emergency management agencies prepare for a fall surge in COVID-19 cases.
Although the disarray is not as widespread as it was this spring, hospitals said rolling shortages of supplies range from specialized beds to disposable isolation gowns to thermometers.
“A few weeks ago, we were having a very difficult time getting the sanitary wipes. You just couldn’t get them,” said Bernard Klein, MD, chief executive of Providence Holy Cross Medical Center in Mission Hills, Calif., near Los Angeles. “We actually had to manufacture our own.”
This same dynamic has played out across a number of critical supplies in his hospital. First masks, then isolation gowns and now a specialized bed that allows nurses to turn COVID-19 patients onto their bellies – equipment that helps workers with what can otherwise be a six-person job.
“We’ve seen whole families come to our hospital with COVID, and several members hospitalized at the same time,” said Dr. Klein. “It’s very, very sad.”
Testing supplies ran short as the predominantly Latino community served by Providence Holy Cross was hit hard by COVID, and even as nearby hospitals could process 15-minute tests.
“If we had a more coordinated response with a partnership between the medical field, the government and the private industry, it would help improve the supply chain to the areas that need it most,” Dr. Klein said.
Dr. Klein said he expected to deal with equipment and supply shortages throughout 2021, especially as flu season approaches.
“Most people focus on those N95 respirators,” said Carmela Coyle, CEO of the California Hospital Association, an industry group that represents more than 400 hospitals across one of America’s hardest-hit states.
She said she believed COVID-19-related supply challenges will persist through 2022.
“We have been challenged with shortages of isolation gowns, face shields, which you’re now starting to see in public places. Any one piece that’s in shortage or not available creates risk for patients and for health care workers,” said Ms. Coyle.
At the same time, trade associations representing manufacturers said persuading customers to shift to American suppliers had been difficult.
“I also have industry that’s working only at 10-20% capacity, who can make PPE in our own backyard, but have no orders,” said Kim Glas, CEO of the National Council of Textile Organizations, whose members make reusable cloth gowns.
Manufacturers in her organization have made “hundreds of millions of products,” but, without long-term government contracts, many are apprehensive to invest in the equipment needed to scale up the business and eventually lower prices.
“If there continues to be an upward trajectory of COVID-19 cases, not just in the U.S. but globally, you can see those supply chains breaking down again,” Ms. Glas said. “It is a health care security issue.”
For the past 2 decades, personal protective equipment was supplied to health care institutions in lean supply chains in the same way toilet paper was to grocery stores. Chains between major manufacturers and end users were so efficient, there was no need to stockpile goods.
But in March, the supply chain broke when major Asian PPE exporters embargoed materials or shut down just as demand increased exponentially. Thus, health care institutions were in much the same position as regular grocery shoppers, who were trying to buy great quantities of a product they never needed to stockpile before.
“I am very concerned about long-term PPE shortages for the foreseeable future,” said Susan Bailey, MD, president of the American Medical Association.
“There’s no question the situation is better than it was a couple of months ago,” said Bailey. However, many health care organizations, including her own, have struggled to obtain PPE. Bailey practices at a 10-doctor allergy clinic and was met with a 10,000-mask minimum when they tried to order N95 respirators.
“We have not seen evidence of a long-term strategic plan for the manufacture, acquisition and distribution of PPE” from the government, said Dr. Bailey. “The supply chain needs to be strengthened dramatically, and we need less dependence on foreign goods to manufacture our own PPE in the U.S.”
Some products have now come back to be made in the United States – although factories are not expected to be able to reach demand until mid-2021.
“A lot has been done in the last 6 months. We are largely out of the hole, and we have planted the seeds to render the United States self-sufficient,” said Dave Rousse, president of the Association of the Nonwoven Fabrics Industry.
In 2019, 850 tons of the material used in disposable masks was made in the United States. Around 10,000 tons is expected to be made in 2021, satisfying perhaps 80% of demand. But PPE is a suite of items – including gloves, gowns and face shields – not all of which have seen the same success.
“Thermometers are becoming a real issue,” said Cindy Juhas, chief strategy officer of CME, an American health care product distributor. “They’re expecting even a problem with needles and syringes for the amount of vaccines they have to make.”
Federal government efforts to address the supply chain have foundered. The Federal Emergency Management Agency, in charge of the COVID-19 response, told congressional interviewers in June it had “no involvement” in distributing PPE to hot spots.
Project Airbridge, an initiative headed by Jared Kushner, President Donald Trump’s son-in-law, flew PPE from international suppliers to the U.S. at taxpayer expense but was phased out. And the government has not responded to the AMA’s calls for more distribution data.
Arguably, Dr. Klein is among the best placed to weather such disruptions. He is part of a 51-hospital chain with purchasing power, and among the institutions that distributors prioritize when selling supplies. But tribulations continue even in hospitals, as shortages have pushed buyers to look directly for manufacturers, often through a swamp of companies that have sprung up overnight.
Now distributors are being called upon not just by their traditional customers – hospitals and long-term care homes – but by nearly every segment of society. First responders, schools, clinics and even food businesses are all buying medical equipment now.
“There’s going to be lots of other shortages we haven’t even thought about,” said Ms. Juhas.
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Officials said logistical challenges continue 7 months after the coronavirus reached the United States, as the flu season approaches and as some state emergency management agencies prepare for a fall surge in COVID-19 cases.
Although the disarray is not as widespread as it was this spring, hospitals said rolling shortages of supplies range from specialized beds to disposable isolation gowns to thermometers.
“A few weeks ago, we were having a very difficult time getting the sanitary wipes. You just couldn’t get them,” said Bernard Klein, MD, chief executive of Providence Holy Cross Medical Center in Mission Hills, Calif., near Los Angeles. “We actually had to manufacture our own.”
This same dynamic has played out across a number of critical supplies in his hospital. First masks, then isolation gowns and now a specialized bed that allows nurses to turn COVID-19 patients onto their bellies – equipment that helps workers with what can otherwise be a six-person job.
“We’ve seen whole families come to our hospital with COVID, and several members hospitalized at the same time,” said Dr. Klein. “It’s very, very sad.”
Testing supplies ran short as the predominantly Latino community served by Providence Holy Cross was hit hard by COVID, and even as nearby hospitals could process 15-minute tests.
“If we had a more coordinated response with a partnership between the medical field, the government and the private industry, it would help improve the supply chain to the areas that need it most,” Dr. Klein said.
Dr. Klein said he expected to deal with equipment and supply shortages throughout 2021, especially as flu season approaches.
“Most people focus on those N95 respirators,” said Carmela Coyle, CEO of the California Hospital Association, an industry group that represents more than 400 hospitals across one of America’s hardest-hit states.
She said she believed COVID-19-related supply challenges will persist through 2022.
“We have been challenged with shortages of isolation gowns, face shields, which you’re now starting to see in public places. Any one piece that’s in shortage or not available creates risk for patients and for health care workers,” said Ms. Coyle.
At the same time, trade associations representing manufacturers said persuading customers to shift to American suppliers had been difficult.
“I also have industry that’s working only at 10-20% capacity, who can make PPE in our own backyard, but have no orders,” said Kim Glas, CEO of the National Council of Textile Organizations, whose members make reusable cloth gowns.
Manufacturers in her organization have made “hundreds of millions of products,” but, without long-term government contracts, many are apprehensive to invest in the equipment needed to scale up the business and eventually lower prices.
“If there continues to be an upward trajectory of COVID-19 cases, not just in the U.S. but globally, you can see those supply chains breaking down again,” Ms. Glas said. “It is a health care security issue.”
For the past 2 decades, personal protective equipment was supplied to health care institutions in lean supply chains in the same way toilet paper was to grocery stores. Chains between major manufacturers and end users were so efficient, there was no need to stockpile goods.
But in March, the supply chain broke when major Asian PPE exporters embargoed materials or shut down just as demand increased exponentially. Thus, health care institutions were in much the same position as regular grocery shoppers, who were trying to buy great quantities of a product they never needed to stockpile before.
“I am very concerned about long-term PPE shortages for the foreseeable future,” said Susan Bailey, MD, president of the American Medical Association.
“There’s no question the situation is better than it was a couple of months ago,” said Bailey. However, many health care organizations, including her own, have struggled to obtain PPE. Bailey practices at a 10-doctor allergy clinic and was met with a 10,000-mask minimum when they tried to order N95 respirators.
“We have not seen evidence of a long-term strategic plan for the manufacture, acquisition and distribution of PPE” from the government, said Dr. Bailey. “The supply chain needs to be strengthened dramatically, and we need less dependence on foreign goods to manufacture our own PPE in the U.S.”
Some products have now come back to be made in the United States – although factories are not expected to be able to reach demand until mid-2021.
“A lot has been done in the last 6 months. We are largely out of the hole, and we have planted the seeds to render the United States self-sufficient,” said Dave Rousse, president of the Association of the Nonwoven Fabrics Industry.
In 2019, 850 tons of the material used in disposable masks was made in the United States. Around 10,000 tons is expected to be made in 2021, satisfying perhaps 80% of demand. But PPE is a suite of items – including gloves, gowns and face shields – not all of which have seen the same success.
“Thermometers are becoming a real issue,” said Cindy Juhas, chief strategy officer of CME, an American health care product distributor. “They’re expecting even a problem with needles and syringes for the amount of vaccines they have to make.”
Federal government efforts to address the supply chain have foundered. The Federal Emergency Management Agency, in charge of the COVID-19 response, told congressional interviewers in June it had “no involvement” in distributing PPE to hot spots.
Project Airbridge, an initiative headed by Jared Kushner, President Donald Trump’s son-in-law, flew PPE from international suppliers to the U.S. at taxpayer expense but was phased out. And the government has not responded to the AMA’s calls for more distribution data.
Arguably, Dr. Klein is among the best placed to weather such disruptions. He is part of a 51-hospital chain with purchasing power, and among the institutions that distributors prioritize when selling supplies. But tribulations continue even in hospitals, as shortages have pushed buyers to look directly for manufacturers, often through a swamp of companies that have sprung up overnight.
Now distributors are being called upon not just by their traditional customers – hospitals and long-term care homes – but by nearly every segment of society. First responders, schools, clinics and even food businesses are all buying medical equipment now.
“There’s going to be lots of other shortages we haven’t even thought about,” said Ms. Juhas.
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Pooled COVID-19 testing feasible, greatly reduces supply use
‘Straightforward, cost effective, and efficient’
Combining specimens from several low-risk inpatients in a single test for SARS-CoV-2 infection allowed hospital staff to stretch testing supplies and provide test results quickly for many more patients than they might have otherwise, researchers found.
“We believe this strategy conserved [personal protective equipment (PPE)], led to a marked reduction in staff and patient anxiety, and improved patient care,” wrote David Mastrianni, MD, and colleagues from Saratoga Hospital in Saratoga Springs, N.Y. “Our impression is that testing all admitted patients has also been reassuring to our community.”
The researchers published their findings July 20 in the Journal of Hospital Medicine.
“What was really important about this study was they were actually able to implement pooled testing after communication with the [Food and Drug Administration],” Samir S. Shah, MD, MSCE, SFHM, the journal’s editor-in-chief, said in an interview.
“Pooled testing combines samples from multiple people within a single test. The benefit is, if the test is negative [you know that] everyone whose sample was combined … is negative. So you’ve effectively tested anywhere from three to five people with the resources required for only one test,” Dr. Shah continued.
The challenge is that, if the test is positive, everyone in that testing group must be retested individually because one or more of them has the infection, said Dr. Shah, director of hospital medicine at Cincinnati Children’s Hospital Medical Center.
Dr. Mastrianni said early in the pandemic they started getting the “New York surge” at their hospital, located approximately 3 hours from New York City. They wanted to test all of the inpatients at their hospital for COVID-19 and they had a rapid in-house test that worked well, “but we just didn’t have enough cartridges, and we couldn’t get deliveries, and we started pooling.” In fact, they ran out of testing supplies at one point during the study but were able to replenish their supply in about a day, he noted.
For the current study, all patients admitted to the hospital, including those admitted for observation, underwent testing for SARS-CoV-2. Staff in the emergency department designated patients as low risk if they had no symptoms or other clinical evidence of COVID-19; those patients underwent pooled testing.
Patients with clinical evidence of COVID-19, such as respiratory symptoms or laboratory or radiographic findings consistent with infection, were considered high risk and were tested on an individual basis and thus excluded from the current analysis.
The pooled testing strategy required some patients to be held in the emergency department until there were three available for pooled testing. On several occasions when this was not practical, specimens from two patients were pooled.
Between April 17 and May 11, clinicians tested 530 patients via pooled testing using 179 cartridges (172 with swabs from three patients and 7 with swabs from two patients). There were four positive pooled tests, which necessitated the use of an additional 11 cartridges. Overall, the testing used 190 cartridges, which is 340 fewer than would have been used if all patients had been tested individually.
Among the low-risk patients, the positive rate was 0.8% (4/530). No patients from pools that were negative tested positive later during their hospitalization or developed evidence of the infection.
Team effort, flexibility needed
Dr. Mastrianni said he expected their study to find that pooled testing saved testing resources, but he “was surprised by the complexity of the logistics in the hospital, and how it really required getting everybody to work together. …There were a lot of details, and it really took a lot of teamwork.”
The nursing supervisor in the emergency department was in charge of the batch and coordinated with the laboratory, he explained. There were many moving parts to manage, including monitoring how many patients were being admitted, what their conditions were, whether they were high or low risk, and where they would house those patients as the emergency department became increasingly busy. “It’s a lot for them, but they’ve adapted really well,” Dr. Mastrianni said.
Pooling tests seems to work best for three to five patients at a time; larger batches increase the chance of having a positive test, and thus identifying the sick individual(s) becomes more challenging and expensive, Dr. Shah said.
“It’s a fine line between having a pool large enough that you save on testing supplies and testing costs but not having the pool so large that you dramatically increase your likelihood of having a positive test,” Dr. Shah said.
Hospitals will likely need to be flexible and adapt as the local positivity rate changes and supply levels vary, according to the authors.
“Pooled testing is mainly dependent on the COVID-19 positive rate in the population of interest in addition to the sensitivity of the [reverse transcriptase-polymerase chain reaction (RT-PCR)] method used for COVID-19 testing,” said Baha Abdalhamid, MD, PhD, of the department of pathology and microbiology at the University of Nebraska Medical Center in Omaha.
“Each laboratory and hospital needs to do their own validation testing because it is dependent on the positive rate of COVID-19,” added Dr. Abdalhamid, who was not involved in the current study.
It’s important for clinicians to “do a good history to find who’s high risk and who’s low risk,” Dr. Mastrianni said. Clinicians also need to remember that, although a patient may test negative initially, they may still have COVID-19, he warned. That test reflects a single point in time, and a patient could be infected and not yet be ill, so clinicians need to be alert to a change in the patient’s status.
Best for settings with low-risk individuals
“Pooled COVID-19 testing is a straightforward, cost-effective, and efficient approach,” Dr. Abdalhamid said. He and his colleagues found pooled testing could increase testing capability by 69% or more when the incidence rate of SARS-CoV-2 infection is 10% or lower.
He said the approach would be helpful in other settings “as long as the positive rate is equal to or less than 10%. Asymptomatic population or surveillance groups such as students, athletes, and military service members are [an] interesting population to test using pooling testing because we expect these populations to have low positive rates, which makes pooled testing ideal.”
Benefit outweighs risk
“There is risk of missing specimens with low concentration of the virus,” Dr. Abdalhamid cautioned. “These specimens might be missed due to the dilution factor of pooling [false-negative specimens]. We did not have a single false-negative specimen in our proof-of-concept study. In addition, there are practical approaches to deal with false-negative pooled specimens.
“The benefit definitely outweighs the risk of false-negative specimens because false-negative results rarely occur, if any. In addition, there is significant saving of time, reagents, and supplies in [a] pooled specimens approach as well as expansion of the test for higher number of patients,” Dr. Abdalhamid continued.
Dr. Mastrianni’s hospital currently has enough testing cartridges, but they are continuing to conduct pooled testing to conserve resources for the benefit of their own hospital and for the nation as a whole, he said.
The authors have disclosed no relevant financial relationships. Dr. Abdalhamid and Dr. Shah have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
‘Straightforward, cost effective, and efficient’
‘Straightforward, cost effective, and efficient’
Combining specimens from several low-risk inpatients in a single test for SARS-CoV-2 infection allowed hospital staff to stretch testing supplies and provide test results quickly for many more patients than they might have otherwise, researchers found.
“We believe this strategy conserved [personal protective equipment (PPE)], led to a marked reduction in staff and patient anxiety, and improved patient care,” wrote David Mastrianni, MD, and colleagues from Saratoga Hospital in Saratoga Springs, N.Y. “Our impression is that testing all admitted patients has also been reassuring to our community.”
The researchers published their findings July 20 in the Journal of Hospital Medicine.
“What was really important about this study was they were actually able to implement pooled testing after communication with the [Food and Drug Administration],” Samir S. Shah, MD, MSCE, SFHM, the journal’s editor-in-chief, said in an interview.
“Pooled testing combines samples from multiple people within a single test. The benefit is, if the test is negative [you know that] everyone whose sample was combined … is negative. So you’ve effectively tested anywhere from three to five people with the resources required for only one test,” Dr. Shah continued.
The challenge is that, if the test is positive, everyone in that testing group must be retested individually because one or more of them has the infection, said Dr. Shah, director of hospital medicine at Cincinnati Children’s Hospital Medical Center.
Dr. Mastrianni said early in the pandemic they started getting the “New York surge” at their hospital, located approximately 3 hours from New York City. They wanted to test all of the inpatients at their hospital for COVID-19 and they had a rapid in-house test that worked well, “but we just didn’t have enough cartridges, and we couldn’t get deliveries, and we started pooling.” In fact, they ran out of testing supplies at one point during the study but were able to replenish their supply in about a day, he noted.
For the current study, all patients admitted to the hospital, including those admitted for observation, underwent testing for SARS-CoV-2. Staff in the emergency department designated patients as low risk if they had no symptoms or other clinical evidence of COVID-19; those patients underwent pooled testing.
Patients with clinical evidence of COVID-19, such as respiratory symptoms or laboratory or radiographic findings consistent with infection, were considered high risk and were tested on an individual basis and thus excluded from the current analysis.
The pooled testing strategy required some patients to be held in the emergency department until there were three available for pooled testing. On several occasions when this was not practical, specimens from two patients were pooled.
Between April 17 and May 11, clinicians tested 530 patients via pooled testing using 179 cartridges (172 with swabs from three patients and 7 with swabs from two patients). There were four positive pooled tests, which necessitated the use of an additional 11 cartridges. Overall, the testing used 190 cartridges, which is 340 fewer than would have been used if all patients had been tested individually.
Among the low-risk patients, the positive rate was 0.8% (4/530). No patients from pools that were negative tested positive later during their hospitalization or developed evidence of the infection.
Team effort, flexibility needed
Dr. Mastrianni said he expected their study to find that pooled testing saved testing resources, but he “was surprised by the complexity of the logistics in the hospital, and how it really required getting everybody to work together. …There were a lot of details, and it really took a lot of teamwork.”
The nursing supervisor in the emergency department was in charge of the batch and coordinated with the laboratory, he explained. There were many moving parts to manage, including monitoring how many patients were being admitted, what their conditions were, whether they were high or low risk, and where they would house those patients as the emergency department became increasingly busy. “It’s a lot for them, but they’ve adapted really well,” Dr. Mastrianni said.
Pooling tests seems to work best for three to five patients at a time; larger batches increase the chance of having a positive test, and thus identifying the sick individual(s) becomes more challenging and expensive, Dr. Shah said.
“It’s a fine line between having a pool large enough that you save on testing supplies and testing costs but not having the pool so large that you dramatically increase your likelihood of having a positive test,” Dr. Shah said.
Hospitals will likely need to be flexible and adapt as the local positivity rate changes and supply levels vary, according to the authors.
“Pooled testing is mainly dependent on the COVID-19 positive rate in the population of interest in addition to the sensitivity of the [reverse transcriptase-polymerase chain reaction (RT-PCR)] method used for COVID-19 testing,” said Baha Abdalhamid, MD, PhD, of the department of pathology and microbiology at the University of Nebraska Medical Center in Omaha.
“Each laboratory and hospital needs to do their own validation testing because it is dependent on the positive rate of COVID-19,” added Dr. Abdalhamid, who was not involved in the current study.
It’s important for clinicians to “do a good history to find who’s high risk and who’s low risk,” Dr. Mastrianni said. Clinicians also need to remember that, although a patient may test negative initially, they may still have COVID-19, he warned. That test reflects a single point in time, and a patient could be infected and not yet be ill, so clinicians need to be alert to a change in the patient’s status.
Best for settings with low-risk individuals
“Pooled COVID-19 testing is a straightforward, cost-effective, and efficient approach,” Dr. Abdalhamid said. He and his colleagues found pooled testing could increase testing capability by 69% or more when the incidence rate of SARS-CoV-2 infection is 10% or lower.
He said the approach would be helpful in other settings “as long as the positive rate is equal to or less than 10%. Asymptomatic population or surveillance groups such as students, athletes, and military service members are [an] interesting population to test using pooling testing because we expect these populations to have low positive rates, which makes pooled testing ideal.”
Benefit outweighs risk
“There is risk of missing specimens with low concentration of the virus,” Dr. Abdalhamid cautioned. “These specimens might be missed due to the dilution factor of pooling [false-negative specimens]. We did not have a single false-negative specimen in our proof-of-concept study. In addition, there are practical approaches to deal with false-negative pooled specimens.
“The benefit definitely outweighs the risk of false-negative specimens because false-negative results rarely occur, if any. In addition, there is significant saving of time, reagents, and supplies in [a] pooled specimens approach as well as expansion of the test for higher number of patients,” Dr. Abdalhamid continued.
Dr. Mastrianni’s hospital currently has enough testing cartridges, but they are continuing to conduct pooled testing to conserve resources for the benefit of their own hospital and for the nation as a whole, he said.
The authors have disclosed no relevant financial relationships. Dr. Abdalhamid and Dr. Shah have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Combining specimens from several low-risk inpatients in a single test for SARS-CoV-2 infection allowed hospital staff to stretch testing supplies and provide test results quickly for many more patients than they might have otherwise, researchers found.
“We believe this strategy conserved [personal protective equipment (PPE)], led to a marked reduction in staff and patient anxiety, and improved patient care,” wrote David Mastrianni, MD, and colleagues from Saratoga Hospital in Saratoga Springs, N.Y. “Our impression is that testing all admitted patients has also been reassuring to our community.”
The researchers published their findings July 20 in the Journal of Hospital Medicine.
“What was really important about this study was they were actually able to implement pooled testing after communication with the [Food and Drug Administration],” Samir S. Shah, MD, MSCE, SFHM, the journal’s editor-in-chief, said in an interview.
“Pooled testing combines samples from multiple people within a single test. The benefit is, if the test is negative [you know that] everyone whose sample was combined … is negative. So you’ve effectively tested anywhere from three to five people with the resources required for only one test,” Dr. Shah continued.
The challenge is that, if the test is positive, everyone in that testing group must be retested individually because one or more of them has the infection, said Dr. Shah, director of hospital medicine at Cincinnati Children’s Hospital Medical Center.
Dr. Mastrianni said early in the pandemic they started getting the “New York surge” at their hospital, located approximately 3 hours from New York City. They wanted to test all of the inpatients at their hospital for COVID-19 and they had a rapid in-house test that worked well, “but we just didn’t have enough cartridges, and we couldn’t get deliveries, and we started pooling.” In fact, they ran out of testing supplies at one point during the study but were able to replenish their supply in about a day, he noted.
For the current study, all patients admitted to the hospital, including those admitted for observation, underwent testing for SARS-CoV-2. Staff in the emergency department designated patients as low risk if they had no symptoms or other clinical evidence of COVID-19; those patients underwent pooled testing.
Patients with clinical evidence of COVID-19, such as respiratory symptoms or laboratory or radiographic findings consistent with infection, were considered high risk and were tested on an individual basis and thus excluded from the current analysis.
The pooled testing strategy required some patients to be held in the emergency department until there were three available for pooled testing. On several occasions when this was not practical, specimens from two patients were pooled.
Between April 17 and May 11, clinicians tested 530 patients via pooled testing using 179 cartridges (172 with swabs from three patients and 7 with swabs from two patients). There were four positive pooled tests, which necessitated the use of an additional 11 cartridges. Overall, the testing used 190 cartridges, which is 340 fewer than would have been used if all patients had been tested individually.
Among the low-risk patients, the positive rate was 0.8% (4/530). No patients from pools that were negative tested positive later during their hospitalization or developed evidence of the infection.
Team effort, flexibility needed
Dr. Mastrianni said he expected their study to find that pooled testing saved testing resources, but he “was surprised by the complexity of the logistics in the hospital, and how it really required getting everybody to work together. …There were a lot of details, and it really took a lot of teamwork.”
The nursing supervisor in the emergency department was in charge of the batch and coordinated with the laboratory, he explained. There were many moving parts to manage, including monitoring how many patients were being admitted, what their conditions were, whether they were high or low risk, and where they would house those patients as the emergency department became increasingly busy. “It’s a lot for them, but they’ve adapted really well,” Dr. Mastrianni said.
Pooling tests seems to work best for three to five patients at a time; larger batches increase the chance of having a positive test, and thus identifying the sick individual(s) becomes more challenging and expensive, Dr. Shah said.
“It’s a fine line between having a pool large enough that you save on testing supplies and testing costs but not having the pool so large that you dramatically increase your likelihood of having a positive test,” Dr. Shah said.
Hospitals will likely need to be flexible and adapt as the local positivity rate changes and supply levels vary, according to the authors.
“Pooled testing is mainly dependent on the COVID-19 positive rate in the population of interest in addition to the sensitivity of the [reverse transcriptase-polymerase chain reaction (RT-PCR)] method used for COVID-19 testing,” said Baha Abdalhamid, MD, PhD, of the department of pathology and microbiology at the University of Nebraska Medical Center in Omaha.
“Each laboratory and hospital needs to do their own validation testing because it is dependent on the positive rate of COVID-19,” added Dr. Abdalhamid, who was not involved in the current study.
It’s important for clinicians to “do a good history to find who’s high risk and who’s low risk,” Dr. Mastrianni said. Clinicians also need to remember that, although a patient may test negative initially, they may still have COVID-19, he warned. That test reflects a single point in time, and a patient could be infected and not yet be ill, so clinicians need to be alert to a change in the patient’s status.
Best for settings with low-risk individuals
“Pooled COVID-19 testing is a straightforward, cost-effective, and efficient approach,” Dr. Abdalhamid said. He and his colleagues found pooled testing could increase testing capability by 69% or more when the incidence rate of SARS-CoV-2 infection is 10% or lower.
He said the approach would be helpful in other settings “as long as the positive rate is equal to or less than 10%. Asymptomatic population or surveillance groups such as students, athletes, and military service members are [an] interesting population to test using pooling testing because we expect these populations to have low positive rates, which makes pooled testing ideal.”
Benefit outweighs risk
“There is risk of missing specimens with low concentration of the virus,” Dr. Abdalhamid cautioned. “These specimens might be missed due to the dilution factor of pooling [false-negative specimens]. We did not have a single false-negative specimen in our proof-of-concept study. In addition, there are practical approaches to deal with false-negative pooled specimens.
“The benefit definitely outweighs the risk of false-negative specimens because false-negative results rarely occur, if any. In addition, there is significant saving of time, reagents, and supplies in [a] pooled specimens approach as well as expansion of the test for higher number of patients,” Dr. Abdalhamid continued.
Dr. Mastrianni’s hospital currently has enough testing cartridges, but they are continuing to conduct pooled testing to conserve resources for the benefit of their own hospital and for the nation as a whole, he said.
The authors have disclosed no relevant financial relationships. Dr. Abdalhamid and Dr. Shah have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Does metformin reduce risk for death in COVID-19?
Accumulating observational data suggest that metformin use in patients with type 2 diabetes might reduce the risk for death from COVID-19, but the randomized trials needed to prove this are unlikely to be carried out, according to experts.
The latest results, which are not yet peer reviewed, were published online July 31. The study was conducted by Andrew B. Crouse, PhD, of the Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, and colleagues.
The researchers found that among more than 600 patients with diabetes and COVID-19, use of metformin was associated with a nearly 70% reduction in mortality after adjustment for multiple confounders.
Data from four previous studies that also show a reduction in mortality among metformin users compared to nonusers were summarized in a “mini review” by André J. Scheen, MD, PhD, published Aug. 1 in Diabetes and Metabolism.
Dr. Scheen, of the division of diabetes, nutrition, and metabolic disorders and the division of clinical pharmacology at Liège (Belgium) University, discussed possible mechanisms behind this observation.
“Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects, it may be speculated that this biguanide might positively influence the prognosis of patients with [type 2 diabetes] hospitalized for COVID-19,” he said.
“However, given the potential confounders inherently found in observational studies, caution is required before drawing any firm conclusions in the absence of randomized controlled trials,” Dr. Scheen wrote.
Indeed, when asked to comment, endocrinologist Kasia Lipska, MD, of Yale University, New Haven, Conn., said in an interview: “Metformin users tend to do better in many different settings with respect to many different outcomes. To me, it is still unclear whether metformin is truly a miracle drug or whether it is simply used more often among people who are healthier and who do not have contraindications to its use.”
She added, “I don’t think we have enough data to suggest metformin use for COVID-19 mitigation at this point.”
Alabama authors say confounding effects ‘unlikely’
In the retrospective analysis of electronic health records from their institution, Dr. Crouse and colleagues reviewed data from 604 patients who were confirmed to have tested positive for COVID-19 between Feb. 25 and June 22, 2020. Of those individuals, 40% had diabetes.
Death occurred in 11% (n = 67); the odds ratio (OR) for death among those with, vs. without, diabetes was 3.62 (P < .0001).
Individuals with diabetes accounted for >60% of all deaths. In multiple logistic regression, age 50-70 vs. <50, male sex, and diabetes emerged as independent predictors of death.
Of the 42 patients with diabetes who died, 8 (19%) had used metformin, and 34 (81%) had not*, a significant difference (OR, 0.38; P = .0221). Insulin use, on the other hand, had no effect on mortality (P = .5728).
“In fact, with 11% [being] the mortality of metformin users, [this] was comparable to that of the general COVID-19-positive population and dramatically lower than the 23% mortality observed in subjects with diabetes and not on metformin,” the authors said.
The survival benefit observed with metformin remained after exclusion of patients with classic metformin contraindications, such as chronic kidney disease and heart failure (OR, 0.17; P = .0231).
“This makes any potential confounding effects from skewing metformin users toward healthier subjects without these additional comorbidities very unlikely,” Dr. Crouse and colleagues contended.
After further analysis that controlled for other covariates (age, sex, obesity status, and hypertension), age, sex, and metformin use remained independent predictors of mortality.
For metformin, the odds ratio was 0.33 (P = .0210).
But, Dr. Lipska pointed out, “Observational studies can take into account confounders that are measured. However, unmeasured confounders may still affect the conclusions of these studies ... Propensity score matching to account for the likelihood of use of metformin could be used to better account for differences between metformin users and nonusers.”
If metformin does reduce COVID-19 deaths, multiple mechanisms likely
In his article, Dr. Scheen noted that several mechanisms have been proposed for the possible beneficial effect of metformin on COVID-19 outcomes, including direct improvements in glucose control, body weight, and insulin resistance; reduction in inflammation; inhibition of virus penetration via phosphorylation of ACE2; inhibition of an immune hyperactivation pathway; and neutrophil reduction. All remain theoretical, he emphasized.
He noted that some authors have raised concerns about possible harms from the use of metformin by patients with type 2 diabetes who are hospitalized for COVID-19, particularly because of the potential risk for lactic acidosis in cases of multiple organ failure.
In totality, four studies suggest 25% death reduction with metformin
Taken together, the four observational studies that Dr. Scheen reviewed showed that metformin had a positive effect, with an overall 25% reduction in death (P < .00001), albeit with relatively high heterogeneity (I² = 61%).
The largest of these, from the United States, included 6,256 patients hospitalized with COVID-19 and involved propensity matching. A significant reduction in mortality with metformin use was seen in women but not men (odds ratio, 0.759).
The French Coronavirus-SARS-CoV-2 and Diabetes Outcomes (CORONADO) study of 1,317 patients with diabetes and confirmed COVID-19 who were admitted to 53 French hospitals also showed a significant survival benefit for metformin, although the study wasn’t designed to address that issue.
In that study, the odds ratio for death on day 7 in prior metformin users compared to nonusers was 0.59. This finding lost significance but remained a trend after full adjustments (0.80).
Two smaller observational studies produced similar trends toward survival benefit with metformin.
Nonetheless, Dr. Scheen cautioned: “Firm conclusions about the impact of metformin therapy can only be drawn from double-blind randomized controlled trials (RCTs), and such trials are almost impossible in the context of COVID-19.”
He added: “Because metformin is out of patent and very inexpensive, no pharmaceutical company is likely to be interested in planning a study to demonstrate the benefits of metformin on COVID-19-related clinical outcomes.”
Dr. Lipska agreed: “RCTs are unlikely to be conducted to settle these issues. In their absence, metformin use should be based on its safety and effectiveness profile.”
Dr. Scheen concluded, however, that “there are at least no negative safety indications, so there is no reason to stop metformin therapy during COVID-19 infection except in cases of severe gastrointestinal symptoms, hypoxia and/or multiple organ failure.”
Dr. Lipska has received grants from the National Institutes of Health and works under contract for the Centers for Medicare & Medicaid Services to develop publicly reported quality measures. Dr. Scheen has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
*A previous version reversed these two outcomes in error.
Accumulating observational data suggest that metformin use in patients with type 2 diabetes might reduce the risk for death from COVID-19, but the randomized trials needed to prove this are unlikely to be carried out, according to experts.
The latest results, which are not yet peer reviewed, were published online July 31. The study was conducted by Andrew B. Crouse, PhD, of the Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, and colleagues.
The researchers found that among more than 600 patients with diabetes and COVID-19, use of metformin was associated with a nearly 70% reduction in mortality after adjustment for multiple confounders.
Data from four previous studies that also show a reduction in mortality among metformin users compared to nonusers were summarized in a “mini review” by André J. Scheen, MD, PhD, published Aug. 1 in Diabetes and Metabolism.
Dr. Scheen, of the division of diabetes, nutrition, and metabolic disorders and the division of clinical pharmacology at Liège (Belgium) University, discussed possible mechanisms behind this observation.
“Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects, it may be speculated that this biguanide might positively influence the prognosis of patients with [type 2 diabetes] hospitalized for COVID-19,” he said.
“However, given the potential confounders inherently found in observational studies, caution is required before drawing any firm conclusions in the absence of randomized controlled trials,” Dr. Scheen wrote.
Indeed, when asked to comment, endocrinologist Kasia Lipska, MD, of Yale University, New Haven, Conn., said in an interview: “Metformin users tend to do better in many different settings with respect to many different outcomes. To me, it is still unclear whether metformin is truly a miracle drug or whether it is simply used more often among people who are healthier and who do not have contraindications to its use.”
She added, “I don’t think we have enough data to suggest metformin use for COVID-19 mitigation at this point.”
Alabama authors say confounding effects ‘unlikely’
In the retrospective analysis of electronic health records from their institution, Dr. Crouse and colleagues reviewed data from 604 patients who were confirmed to have tested positive for COVID-19 between Feb. 25 and June 22, 2020. Of those individuals, 40% had diabetes.
Death occurred in 11% (n = 67); the odds ratio (OR) for death among those with, vs. without, diabetes was 3.62 (P < .0001).
Individuals with diabetes accounted for >60% of all deaths. In multiple logistic regression, age 50-70 vs. <50, male sex, and diabetes emerged as independent predictors of death.
Of the 42 patients with diabetes who died, 8 (19%) had used metformin, and 34 (81%) had not*, a significant difference (OR, 0.38; P = .0221). Insulin use, on the other hand, had no effect on mortality (P = .5728).
“In fact, with 11% [being] the mortality of metformin users, [this] was comparable to that of the general COVID-19-positive population and dramatically lower than the 23% mortality observed in subjects with diabetes and not on metformin,” the authors said.
The survival benefit observed with metformin remained after exclusion of patients with classic metformin contraindications, such as chronic kidney disease and heart failure (OR, 0.17; P = .0231).
“This makes any potential confounding effects from skewing metformin users toward healthier subjects without these additional comorbidities very unlikely,” Dr. Crouse and colleagues contended.
After further analysis that controlled for other covariates (age, sex, obesity status, and hypertension), age, sex, and metformin use remained independent predictors of mortality.
For metformin, the odds ratio was 0.33 (P = .0210).
But, Dr. Lipska pointed out, “Observational studies can take into account confounders that are measured. However, unmeasured confounders may still affect the conclusions of these studies ... Propensity score matching to account for the likelihood of use of metformin could be used to better account for differences between metformin users and nonusers.”
If metformin does reduce COVID-19 deaths, multiple mechanisms likely
In his article, Dr. Scheen noted that several mechanisms have been proposed for the possible beneficial effect of metformin on COVID-19 outcomes, including direct improvements in glucose control, body weight, and insulin resistance; reduction in inflammation; inhibition of virus penetration via phosphorylation of ACE2; inhibition of an immune hyperactivation pathway; and neutrophil reduction. All remain theoretical, he emphasized.
He noted that some authors have raised concerns about possible harms from the use of metformin by patients with type 2 diabetes who are hospitalized for COVID-19, particularly because of the potential risk for lactic acidosis in cases of multiple organ failure.
In totality, four studies suggest 25% death reduction with metformin
Taken together, the four observational studies that Dr. Scheen reviewed showed that metformin had a positive effect, with an overall 25% reduction in death (P < .00001), albeit with relatively high heterogeneity (I² = 61%).
The largest of these, from the United States, included 6,256 patients hospitalized with COVID-19 and involved propensity matching. A significant reduction in mortality with metformin use was seen in women but not men (odds ratio, 0.759).
The French Coronavirus-SARS-CoV-2 and Diabetes Outcomes (CORONADO) study of 1,317 patients with diabetes and confirmed COVID-19 who were admitted to 53 French hospitals also showed a significant survival benefit for metformin, although the study wasn’t designed to address that issue.
In that study, the odds ratio for death on day 7 in prior metformin users compared to nonusers was 0.59. This finding lost significance but remained a trend after full adjustments (0.80).
Two smaller observational studies produced similar trends toward survival benefit with metformin.
Nonetheless, Dr. Scheen cautioned: “Firm conclusions about the impact of metformin therapy can only be drawn from double-blind randomized controlled trials (RCTs), and such trials are almost impossible in the context of COVID-19.”
He added: “Because metformin is out of patent and very inexpensive, no pharmaceutical company is likely to be interested in planning a study to demonstrate the benefits of metformin on COVID-19-related clinical outcomes.”
Dr. Lipska agreed: “RCTs are unlikely to be conducted to settle these issues. In their absence, metformin use should be based on its safety and effectiveness profile.”
Dr. Scheen concluded, however, that “there are at least no negative safety indications, so there is no reason to stop metformin therapy during COVID-19 infection except in cases of severe gastrointestinal symptoms, hypoxia and/or multiple organ failure.”
Dr. Lipska has received grants from the National Institutes of Health and works under contract for the Centers for Medicare & Medicaid Services to develop publicly reported quality measures. Dr. Scheen has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
*A previous version reversed these two outcomes in error.
Accumulating observational data suggest that metformin use in patients with type 2 diabetes might reduce the risk for death from COVID-19, but the randomized trials needed to prove this are unlikely to be carried out, according to experts.
The latest results, which are not yet peer reviewed, were published online July 31. The study was conducted by Andrew B. Crouse, PhD, of the Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, and colleagues.
The researchers found that among more than 600 patients with diabetes and COVID-19, use of metformin was associated with a nearly 70% reduction in mortality after adjustment for multiple confounders.
Data from four previous studies that also show a reduction in mortality among metformin users compared to nonusers were summarized in a “mini review” by André J. Scheen, MD, PhD, published Aug. 1 in Diabetes and Metabolism.
Dr. Scheen, of the division of diabetes, nutrition, and metabolic disorders and the division of clinical pharmacology at Liège (Belgium) University, discussed possible mechanisms behind this observation.
“Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects, it may be speculated that this biguanide might positively influence the prognosis of patients with [type 2 diabetes] hospitalized for COVID-19,” he said.
“However, given the potential confounders inherently found in observational studies, caution is required before drawing any firm conclusions in the absence of randomized controlled trials,” Dr. Scheen wrote.
Indeed, when asked to comment, endocrinologist Kasia Lipska, MD, of Yale University, New Haven, Conn., said in an interview: “Metformin users tend to do better in many different settings with respect to many different outcomes. To me, it is still unclear whether metformin is truly a miracle drug or whether it is simply used more often among people who are healthier and who do not have contraindications to its use.”
She added, “I don’t think we have enough data to suggest metformin use for COVID-19 mitigation at this point.”
Alabama authors say confounding effects ‘unlikely’
In the retrospective analysis of electronic health records from their institution, Dr. Crouse and colleagues reviewed data from 604 patients who were confirmed to have tested positive for COVID-19 between Feb. 25 and June 22, 2020. Of those individuals, 40% had diabetes.
Death occurred in 11% (n = 67); the odds ratio (OR) for death among those with, vs. without, diabetes was 3.62 (P < .0001).
Individuals with diabetes accounted for >60% of all deaths. In multiple logistic regression, age 50-70 vs. <50, male sex, and diabetes emerged as independent predictors of death.
Of the 42 patients with diabetes who died, 8 (19%) had used metformin, and 34 (81%) had not*, a significant difference (OR, 0.38; P = .0221). Insulin use, on the other hand, had no effect on mortality (P = .5728).
“In fact, with 11% [being] the mortality of metformin users, [this] was comparable to that of the general COVID-19-positive population and dramatically lower than the 23% mortality observed in subjects with diabetes and not on metformin,” the authors said.
The survival benefit observed with metformin remained after exclusion of patients with classic metformin contraindications, such as chronic kidney disease and heart failure (OR, 0.17; P = .0231).
“This makes any potential confounding effects from skewing metformin users toward healthier subjects without these additional comorbidities very unlikely,” Dr. Crouse and colleagues contended.
After further analysis that controlled for other covariates (age, sex, obesity status, and hypertension), age, sex, and metformin use remained independent predictors of mortality.
For metformin, the odds ratio was 0.33 (P = .0210).
But, Dr. Lipska pointed out, “Observational studies can take into account confounders that are measured. However, unmeasured confounders may still affect the conclusions of these studies ... Propensity score matching to account for the likelihood of use of metformin could be used to better account for differences between metformin users and nonusers.”
If metformin does reduce COVID-19 deaths, multiple mechanisms likely
In his article, Dr. Scheen noted that several mechanisms have been proposed for the possible beneficial effect of metformin on COVID-19 outcomes, including direct improvements in glucose control, body weight, and insulin resistance; reduction in inflammation; inhibition of virus penetration via phosphorylation of ACE2; inhibition of an immune hyperactivation pathway; and neutrophil reduction. All remain theoretical, he emphasized.
He noted that some authors have raised concerns about possible harms from the use of metformin by patients with type 2 diabetes who are hospitalized for COVID-19, particularly because of the potential risk for lactic acidosis in cases of multiple organ failure.
In totality, four studies suggest 25% death reduction with metformin
Taken together, the four observational studies that Dr. Scheen reviewed showed that metformin had a positive effect, with an overall 25% reduction in death (P < .00001), albeit with relatively high heterogeneity (I² = 61%).
The largest of these, from the United States, included 6,256 patients hospitalized with COVID-19 and involved propensity matching. A significant reduction in mortality with metformin use was seen in women but not men (odds ratio, 0.759).
The French Coronavirus-SARS-CoV-2 and Diabetes Outcomes (CORONADO) study of 1,317 patients with diabetes and confirmed COVID-19 who were admitted to 53 French hospitals also showed a significant survival benefit for metformin, although the study wasn’t designed to address that issue.
In that study, the odds ratio for death on day 7 in prior metformin users compared to nonusers was 0.59. This finding lost significance but remained a trend after full adjustments (0.80).
Two smaller observational studies produced similar trends toward survival benefit with metformin.
Nonetheless, Dr. Scheen cautioned: “Firm conclusions about the impact of metformin therapy can only be drawn from double-blind randomized controlled trials (RCTs), and such trials are almost impossible in the context of COVID-19.”
He added: “Because metformin is out of patent and very inexpensive, no pharmaceutical company is likely to be interested in planning a study to demonstrate the benefits of metformin on COVID-19-related clinical outcomes.”
Dr. Lipska agreed: “RCTs are unlikely to be conducted to settle these issues. In their absence, metformin use should be based on its safety and effectiveness profile.”
Dr. Scheen concluded, however, that “there are at least no negative safety indications, so there is no reason to stop metformin therapy during COVID-19 infection except in cases of severe gastrointestinal symptoms, hypoxia and/or multiple organ failure.”
Dr. Lipska has received grants from the National Institutes of Health and works under contract for the Centers for Medicare & Medicaid Services to develop publicly reported quality measures. Dr. Scheen has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
*A previous version reversed these two outcomes in error.
COVID-19 and masks: Doctor, may I be excused?
In the last 2 months, at least 10 patients have asked Constantine George, MD, for a written medical exemption so they won’t have to wear a mask in public. Dr. George, the chief medical officer of Vedius, an app for a travelers’ concierge medical service in Las Vegas, turned them all down.
Elena Christofides, MD, an endocrinologist in Columbus, Ohio, has also refused patients’ requests for exemptions.
“It’s very rare for someone to need an exemption,” says Albert Rizzo, MD, chief medical officer for the American Lung Association and a lung specialist at ChristianaCare Health System in Newark, Del.
The opposition is sometimes strong. Recently, a video of Lenka Koloma of Laguna Niguel, Calif., who founded the antimask Freedom to Breathe Agency, went viral. She was in a California supermarket, maskless, telling an employee she was breaking the law by requiring patrons to wear masks.
“People need oxygen,” she said. “That alone is a medical condition.” Her webpage has a “Face Mask Exempt Card” that cites the Americans with Disabilities Act and posts a Department of Justice ADA violation reporting number. The DOJ issued a statement calling the cards fraudulent.
Figuring out if a patient’s request to opt out of wearing a mask is legitimate is a ‘’new frontier” for doctors, says Mical Raz, MD, a professor in public policy and health at the University of Rochester (N.Y.), and a hospitalist at the university medical center.
Should some people skip masks?
Experts say there are very few medical reasons for people to skip masks. “If you look at the research, patients with COPD [chronic obstructive pulmonary disorder], those with reactive airway, even those can breathe through a mask,” Dr. George said. Requests for exemptions due to medical reasons are usually without basis. “Obviously, if someone is incapacitated, for example, with mental health issues, that’s case by case.”
Dr. Christofides said one of her patients cited anxiety and the other cited headaches as reasons not to wear a mask. “I told the one who asked for anxiety [reasons] that she could wear ones that were less tight.” The patient with headaches told Dr. Christofides that she had a buildup of carbon dioxide in the mask because of industrial exposure. Baloney, Dr. Christofides told her.
Dr. Rizzo says one rare example of someone who can’t wear a mask might be a patient with an advanced lung condition so severe, they need extra oxygen. “These are the extreme patients where any change in oxygen and carbon dioxide could make a difference,” he said. But “that’s also the population that shouldn’t be going out in the first place.”
Dr. Raz cowrote a commentary about mask exemptions, saying doctors are faced with difficult decisions and must keep a delicate balance between public health and individual disability needs. “Inappropriate medical exemptions may inadvertently hasten viral spread and threaten public health,” she wrote.
In an interview, she says that some people do have a hard time tolerating a mask. “Probably the most common reasons are mental health issues, such as anxiety, panic and PTSD, and children with sensory processing disorders (making them oversensitive to their environment). I think there are very few pulmonary reasons.”
CDC, professional organization guidelines
The CDC says people should wear masks in public and when around people who don’t live in the same household. Beyond that, it simply says masks should not be worn by children under age 2, “or anyone who has trouble breathing, is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.”
In mid-July, four professional organizations released a statement in response to the CDC recommendation for facial coverings. Jointly issued by the American College of Chest Physicians, the American Lung Association, the American Thoracic Society and the COPD Foundation, it states in part that people with normal lungs and “even many individuals with underlying chronic lung disease should be able to wear a non-N95 facial covering without affecting their oxygen or carbon dioxide levels.”
It acknowledges that some people will seek an exemption and doctors must weigh the patient’s concerns against the need to stop the spread of the virus. “In some instances, physician reassurance regarding the safety of the facial coverings may be all that is needed,” it states.
Addressing the excuses
Here are some of the common medical reasons people give for not being able to tolerate a mask:
Claustrophobia or anxiety. Dr. Raz and others suggests a “desensitizing” period, wearing the mask for longer and longer periods of time to get used to it. Parents could suggest kids wear a mask when doing something they like, such as watching television, so they equate it with something pleasant. Switching to a different kind of mask or one that fits better could also help.
Masks cause Legionnaires’ disease. Not true, experts say. Legionnaires’ is a severe form of pneumonia, the result of inhaling tiny water droplets with legionella bacteria.
It’s difficult to read lips. People can buy masks with a clear window that makes their mouth and lips visible.
Trouble breathing. Brief periods of mask use won’t have a bad effect on oxygen levels for most people.
“There is not an inherent right to be out in a pandemic with an unmasked face,” Dr. Raz says. But “you are entitled to an accommodation.” That might be using curbside pickup for food and medication. That requires much less time wearing a mask than entering a store would.
There are no “boilerplate” cards or letters to excuse people provided by the four organizations that addressed the issue, Dr. Rizzo said. If he were to write a letter asking for an exemption, he would personalize it for an individual patient’s medical condition. As to whether a state would honor it, he cannot say. The states have a patchwork of recommendations, making it difficult to say.
Dr. Rizzo tells lung disease patients who are able to go out that wearing a mask for 15-20 minutes to do an errand won’t harm their oxygen levels. And he reminds them that having an exemption, in the form of a doctor’s letter, may bring more problems. “Even with an exemption, someone may confront them” for their lack of a face covering. People with COPD have a higher risk of getting a severe illness from COVID-19, according to the CDC.
This article first appeared on WebMD.com.
In the last 2 months, at least 10 patients have asked Constantine George, MD, for a written medical exemption so they won’t have to wear a mask in public. Dr. George, the chief medical officer of Vedius, an app for a travelers’ concierge medical service in Las Vegas, turned them all down.
Elena Christofides, MD, an endocrinologist in Columbus, Ohio, has also refused patients’ requests for exemptions.
“It’s very rare for someone to need an exemption,” says Albert Rizzo, MD, chief medical officer for the American Lung Association and a lung specialist at ChristianaCare Health System in Newark, Del.
The opposition is sometimes strong. Recently, a video of Lenka Koloma of Laguna Niguel, Calif., who founded the antimask Freedom to Breathe Agency, went viral. She was in a California supermarket, maskless, telling an employee she was breaking the law by requiring patrons to wear masks.
“People need oxygen,” she said. “That alone is a medical condition.” Her webpage has a “Face Mask Exempt Card” that cites the Americans with Disabilities Act and posts a Department of Justice ADA violation reporting number. The DOJ issued a statement calling the cards fraudulent.
Figuring out if a patient’s request to opt out of wearing a mask is legitimate is a ‘’new frontier” for doctors, says Mical Raz, MD, a professor in public policy and health at the University of Rochester (N.Y.), and a hospitalist at the university medical center.
Should some people skip masks?
Experts say there are very few medical reasons for people to skip masks. “If you look at the research, patients with COPD [chronic obstructive pulmonary disorder], those with reactive airway, even those can breathe through a mask,” Dr. George said. Requests for exemptions due to medical reasons are usually without basis. “Obviously, if someone is incapacitated, for example, with mental health issues, that’s case by case.”
Dr. Christofides said one of her patients cited anxiety and the other cited headaches as reasons not to wear a mask. “I told the one who asked for anxiety [reasons] that she could wear ones that were less tight.” The patient with headaches told Dr. Christofides that she had a buildup of carbon dioxide in the mask because of industrial exposure. Baloney, Dr. Christofides told her.
Dr. Rizzo says one rare example of someone who can’t wear a mask might be a patient with an advanced lung condition so severe, they need extra oxygen. “These are the extreme patients where any change in oxygen and carbon dioxide could make a difference,” he said. But “that’s also the population that shouldn’t be going out in the first place.”
Dr. Raz cowrote a commentary about mask exemptions, saying doctors are faced with difficult decisions and must keep a delicate balance between public health and individual disability needs. “Inappropriate medical exemptions may inadvertently hasten viral spread and threaten public health,” she wrote.
In an interview, she says that some people do have a hard time tolerating a mask. “Probably the most common reasons are mental health issues, such as anxiety, panic and PTSD, and children with sensory processing disorders (making them oversensitive to their environment). I think there are very few pulmonary reasons.”
CDC, professional organization guidelines
The CDC says people should wear masks in public and when around people who don’t live in the same household. Beyond that, it simply says masks should not be worn by children under age 2, “or anyone who has trouble breathing, is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.”
In mid-July, four professional organizations released a statement in response to the CDC recommendation for facial coverings. Jointly issued by the American College of Chest Physicians, the American Lung Association, the American Thoracic Society and the COPD Foundation, it states in part that people with normal lungs and “even many individuals with underlying chronic lung disease should be able to wear a non-N95 facial covering without affecting their oxygen or carbon dioxide levels.”
It acknowledges that some people will seek an exemption and doctors must weigh the patient’s concerns against the need to stop the spread of the virus. “In some instances, physician reassurance regarding the safety of the facial coverings may be all that is needed,” it states.
Addressing the excuses
Here are some of the common medical reasons people give for not being able to tolerate a mask:
Claustrophobia or anxiety. Dr. Raz and others suggests a “desensitizing” period, wearing the mask for longer and longer periods of time to get used to it. Parents could suggest kids wear a mask when doing something they like, such as watching television, so they equate it with something pleasant. Switching to a different kind of mask or one that fits better could also help.
Masks cause Legionnaires’ disease. Not true, experts say. Legionnaires’ is a severe form of pneumonia, the result of inhaling tiny water droplets with legionella bacteria.
It’s difficult to read lips. People can buy masks with a clear window that makes their mouth and lips visible.
Trouble breathing. Brief periods of mask use won’t have a bad effect on oxygen levels for most people.
“There is not an inherent right to be out in a pandemic with an unmasked face,” Dr. Raz says. But “you are entitled to an accommodation.” That might be using curbside pickup for food and medication. That requires much less time wearing a mask than entering a store would.
There are no “boilerplate” cards or letters to excuse people provided by the four organizations that addressed the issue, Dr. Rizzo said. If he were to write a letter asking for an exemption, he would personalize it for an individual patient’s medical condition. As to whether a state would honor it, he cannot say. The states have a patchwork of recommendations, making it difficult to say.
Dr. Rizzo tells lung disease patients who are able to go out that wearing a mask for 15-20 minutes to do an errand won’t harm their oxygen levels. And he reminds them that having an exemption, in the form of a doctor’s letter, may bring more problems. “Even with an exemption, someone may confront them” for their lack of a face covering. People with COPD have a higher risk of getting a severe illness from COVID-19, according to the CDC.
This article first appeared on WebMD.com.
In the last 2 months, at least 10 patients have asked Constantine George, MD, for a written medical exemption so they won’t have to wear a mask in public. Dr. George, the chief medical officer of Vedius, an app for a travelers’ concierge medical service in Las Vegas, turned them all down.
Elena Christofides, MD, an endocrinologist in Columbus, Ohio, has also refused patients’ requests for exemptions.
“It’s very rare for someone to need an exemption,” says Albert Rizzo, MD, chief medical officer for the American Lung Association and a lung specialist at ChristianaCare Health System in Newark, Del.
The opposition is sometimes strong. Recently, a video of Lenka Koloma of Laguna Niguel, Calif., who founded the antimask Freedom to Breathe Agency, went viral. She was in a California supermarket, maskless, telling an employee she was breaking the law by requiring patrons to wear masks.
“People need oxygen,” she said. “That alone is a medical condition.” Her webpage has a “Face Mask Exempt Card” that cites the Americans with Disabilities Act and posts a Department of Justice ADA violation reporting number. The DOJ issued a statement calling the cards fraudulent.
Figuring out if a patient’s request to opt out of wearing a mask is legitimate is a ‘’new frontier” for doctors, says Mical Raz, MD, a professor in public policy and health at the University of Rochester (N.Y.), and a hospitalist at the university medical center.
Should some people skip masks?
Experts say there are very few medical reasons for people to skip masks. “If you look at the research, patients with COPD [chronic obstructive pulmonary disorder], those with reactive airway, even those can breathe through a mask,” Dr. George said. Requests for exemptions due to medical reasons are usually without basis. “Obviously, if someone is incapacitated, for example, with mental health issues, that’s case by case.”
Dr. Christofides said one of her patients cited anxiety and the other cited headaches as reasons not to wear a mask. “I told the one who asked for anxiety [reasons] that she could wear ones that were less tight.” The patient with headaches told Dr. Christofides that she had a buildup of carbon dioxide in the mask because of industrial exposure. Baloney, Dr. Christofides told her.
Dr. Rizzo says one rare example of someone who can’t wear a mask might be a patient with an advanced lung condition so severe, they need extra oxygen. “These are the extreme patients where any change in oxygen and carbon dioxide could make a difference,” he said. But “that’s also the population that shouldn’t be going out in the first place.”
Dr. Raz cowrote a commentary about mask exemptions, saying doctors are faced with difficult decisions and must keep a delicate balance between public health and individual disability needs. “Inappropriate medical exemptions may inadvertently hasten viral spread and threaten public health,” she wrote.
In an interview, she says that some people do have a hard time tolerating a mask. “Probably the most common reasons are mental health issues, such as anxiety, panic and PTSD, and children with sensory processing disorders (making them oversensitive to their environment). I think there are very few pulmonary reasons.”
CDC, professional organization guidelines
The CDC says people should wear masks in public and when around people who don’t live in the same household. Beyond that, it simply says masks should not be worn by children under age 2, “or anyone who has trouble breathing, is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.”
In mid-July, four professional organizations released a statement in response to the CDC recommendation for facial coverings. Jointly issued by the American College of Chest Physicians, the American Lung Association, the American Thoracic Society and the COPD Foundation, it states in part that people with normal lungs and “even many individuals with underlying chronic lung disease should be able to wear a non-N95 facial covering without affecting their oxygen or carbon dioxide levels.”
It acknowledges that some people will seek an exemption and doctors must weigh the patient’s concerns against the need to stop the spread of the virus. “In some instances, physician reassurance regarding the safety of the facial coverings may be all that is needed,” it states.
Addressing the excuses
Here are some of the common medical reasons people give for not being able to tolerate a mask:
Claustrophobia or anxiety. Dr. Raz and others suggests a “desensitizing” period, wearing the mask for longer and longer periods of time to get used to it. Parents could suggest kids wear a mask when doing something they like, such as watching television, so they equate it with something pleasant. Switching to a different kind of mask or one that fits better could also help.
Masks cause Legionnaires’ disease. Not true, experts say. Legionnaires’ is a severe form of pneumonia, the result of inhaling tiny water droplets with legionella bacteria.
It’s difficult to read lips. People can buy masks with a clear window that makes their mouth and lips visible.
Trouble breathing. Brief periods of mask use won’t have a bad effect on oxygen levels for most people.
“There is not an inherent right to be out in a pandemic with an unmasked face,” Dr. Raz says. But “you are entitled to an accommodation.” That might be using curbside pickup for food and medication. That requires much less time wearing a mask than entering a store would.
There are no “boilerplate” cards or letters to excuse people provided by the four organizations that addressed the issue, Dr. Rizzo said. If he were to write a letter asking for an exemption, he would personalize it for an individual patient’s medical condition. As to whether a state would honor it, he cannot say. The states have a patchwork of recommendations, making it difficult to say.
Dr. Rizzo tells lung disease patients who are able to go out that wearing a mask for 15-20 minutes to do an errand won’t harm their oxygen levels. And he reminds them that having an exemption, in the form of a doctor’s letter, may bring more problems. “Even with an exemption, someone may confront them” for their lack of a face covering. People with COPD have a higher risk of getting a severe illness from COVID-19, according to the CDC.
This article first appeared on WebMD.com.
FDA approves viltolarsen (Viltepso) for Duchenne muscular dystrophy
The FDA approved golodirsen (Vyondys 53, Sarepta Therapeutics) for this indication last year.
“The FDA is committed to fostering drug development for serious neurological disorders like Duchenne muscular dystrophy,” Billy Dunn, MD, director, Office of Neuroscience of the FDA’s Center for Drug Evaluation and Research, said in a statement.
The approval of viltolarsen provides “an important treatment option for Duchenne muscular dystrophy patients with this confirmed mutation,” Dr. Dunn said.
Viltolarsen is an antisense oligonucleotide that promotes production of functional dystrophin by masking exon 53 in the dystrophin gene. It was evaluated in two studies involving 32 male patients.
In one study of 16 patients, the increase in dystrophin production was established in eight patients receiving viltolarsen at the recommended dose. In this study, dystrophin levels increased, on average, from 0.6% of normal at baseline to 5.9% of normal at week 25.
The increase in dystrophin production is “reasonably likely to predict clinical benefit,” but a “clinical benefit of the drug has not been established,” the FDA said.
In making the decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of available therapies.
Viltolarsen was approved under the FDA’s accelerated approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally offer a meaningful advantage over existing treatments.
As part of the accelerated approval, the FDA requires the company to do a clinical trial to confirm the drug’s clinical benefit. If the trial fails to verify clinical benefit, the FDA may start proceedings to withdraw approval of the drug, the agency said.
The most common side effects with viltolarsen are upper respiratory tract infection, injection-site reaction, cough, and fever.
Kidney toxicity was not observed in the clinical studies, but the clinical experience with the drug is limited, and kidney toxicity, including potentially fatal glomerulonephritis, has been observed with some antisense oligonucleotides.
“Kidney function should be monitored in patients taking Viltepso,” the FDA advises.
A version of this article originally appeared on Medscape.com.
The FDA approved golodirsen (Vyondys 53, Sarepta Therapeutics) for this indication last year.
“The FDA is committed to fostering drug development for serious neurological disorders like Duchenne muscular dystrophy,” Billy Dunn, MD, director, Office of Neuroscience of the FDA’s Center for Drug Evaluation and Research, said in a statement.
The approval of viltolarsen provides “an important treatment option for Duchenne muscular dystrophy patients with this confirmed mutation,” Dr. Dunn said.
Viltolarsen is an antisense oligonucleotide that promotes production of functional dystrophin by masking exon 53 in the dystrophin gene. It was evaluated in two studies involving 32 male patients.
In one study of 16 patients, the increase in dystrophin production was established in eight patients receiving viltolarsen at the recommended dose. In this study, dystrophin levels increased, on average, from 0.6% of normal at baseline to 5.9% of normal at week 25.
The increase in dystrophin production is “reasonably likely to predict clinical benefit,” but a “clinical benefit of the drug has not been established,” the FDA said.
In making the decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of available therapies.
Viltolarsen was approved under the FDA’s accelerated approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally offer a meaningful advantage over existing treatments.
As part of the accelerated approval, the FDA requires the company to do a clinical trial to confirm the drug’s clinical benefit. If the trial fails to verify clinical benefit, the FDA may start proceedings to withdraw approval of the drug, the agency said.
The most common side effects with viltolarsen are upper respiratory tract infection, injection-site reaction, cough, and fever.
Kidney toxicity was not observed in the clinical studies, but the clinical experience with the drug is limited, and kidney toxicity, including potentially fatal glomerulonephritis, has been observed with some antisense oligonucleotides.
“Kidney function should be monitored in patients taking Viltepso,” the FDA advises.
A version of this article originally appeared on Medscape.com.
The FDA approved golodirsen (Vyondys 53, Sarepta Therapeutics) for this indication last year.
“The FDA is committed to fostering drug development for serious neurological disorders like Duchenne muscular dystrophy,” Billy Dunn, MD, director, Office of Neuroscience of the FDA’s Center for Drug Evaluation and Research, said in a statement.
The approval of viltolarsen provides “an important treatment option for Duchenne muscular dystrophy patients with this confirmed mutation,” Dr. Dunn said.
Viltolarsen is an antisense oligonucleotide that promotes production of functional dystrophin by masking exon 53 in the dystrophin gene. It was evaluated in two studies involving 32 male patients.
In one study of 16 patients, the increase in dystrophin production was established in eight patients receiving viltolarsen at the recommended dose. In this study, dystrophin levels increased, on average, from 0.6% of normal at baseline to 5.9% of normal at week 25.
The increase in dystrophin production is “reasonably likely to predict clinical benefit,” but a “clinical benefit of the drug has not been established,” the FDA said.
In making the decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of available therapies.
Viltolarsen was approved under the FDA’s accelerated approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally offer a meaningful advantage over existing treatments.
As part of the accelerated approval, the FDA requires the company to do a clinical trial to confirm the drug’s clinical benefit. If the trial fails to verify clinical benefit, the FDA may start proceedings to withdraw approval of the drug, the agency said.
The most common side effects with viltolarsen are upper respiratory tract infection, injection-site reaction, cough, and fever.
Kidney toxicity was not observed in the clinical studies, but the clinical experience with the drug is limited, and kidney toxicity, including potentially fatal glomerulonephritis, has been observed with some antisense oligonucleotides.
“Kidney function should be monitored in patients taking Viltepso,” the FDA advises.
A version of this article originally appeared on Medscape.com.
Determining cause of skin lesions in COVID-19 patients remains challenging
published in the Journal of the American Academy of Dermatology.
SARS-CoV-2 infection has been associated with a range of skin conditions, wrote Antonio Martinez-Lopez, MD, of Virgen de las Nieves University Hospital, Granada, Spain, and colleagues, who provided an overview of the cutaneous side effects associated with drugs used to treat COVID-19 infection.
“Cutaneous manifestations have recently been described in patients with the new coronavirus infection, similar to cutaneous involvement occurring in common viral infections,” they said. Infected individuals have experienced maculopapular eruption, pseudo-chilblain lesions, urticaria, monomorphic disseminated vesicular lesions, acral vesicular-pustulous lesions, and livedo or necrosis, they noted.
Diagnosing skin manifestations in patients with COVID-19 remains a challenge, because it is unclear whether the skin lesions are related to the virus, the authors said. “Skin diseases not related to coronavirus, other seasonal viral infections, and drug reactions should be considered in the differential diagnosis, especially in those patients suffering from nonspecific manifestations such as urticaria or maculopapular eruptions,” they wrote.
However, “urticarial lesions and maculopapular eruptions in SARS-CoV-2 infections usually appear at the same time as the systemic symptoms, while drug adverse reactions are likely to arise hours to days after the start of the treatment,” they said.
The reviewers noted several cutaneous side effects associated with several of the often-prescribed drugs for COVID-19 infection. The antimalarials hydroxychloroquine and chloroquine had been authorized for COVID-19 treatment by the Food and Drug Administration, but this emergency authorization was rescinded in June. They noted that up to 11.5% of patients on these drugs may experience cutaneous adverse effects, including some that “can be mistaken for skin manifestations of SARS-CoV-2, especially those with maculopapular rash or exanthematous reactions.” Another side effect is exacerbation of psoriasis, which has been described in patients with COVID-19, the authors said.
The oral antiretroviral combination lopinavir/ritonavir, under investigation in clinical trials for COVID-19, has been associated with skin rashes in as many as 5% of adults in HIV studies. Usually appearing after treatment is started, the maculopapular pruritic rash is “usually well tolerated,” they said, although there have been reports of Stevens-Johnson syndrome. Alopecia areata is among the other side effects reported.
Remdesivir also has been authorized for emergency treatment of COVID-19, and the small amount of data available suggest that cutaneous manifestations may be infrequent, the reviewers said. In a recent study of 53 patients treated with remdesivir for 10 days, approximately 8% developed a rash, but the study did not include any information “about rash morphology, distribution, or timeline in relation to remdesivir that may help clinicians differentiate from cutaneous manifestations of COVID-19,” they said.
Other potential treatments for complications of COVID-19 include imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine, and low molecular weight heparins; all have the potential for association with skin reactions, but data on skin manifestations associated with COVID-19 are limited, the authors wrote.
Notably, data on the use of systemic corticosteroids for COVID-19 patients are controversial, although preliminary data showed some reduced mortality in COVID-19 patients who were on respiratory support, they noted. “With regard to differential diagnosis of cutaneous manifestations of COVID-19, the vascular fragility associated with corticosteroid use, especially in elderly patients, may be similar to the thrombotic complications of COVID-19 infection.”
Knowledge about the virology of COVID-19 continues to evolve rapidly, and the number of drugs being studied as treatments continues to expand, the authors pointed out.
“By considering adverse drug reactions in the differential diagnosis, dermatologists can be useful in assisting in the care of these patients,” they wrote. Drugs, rather than the infection, may be the cause of skin reactions in some COVID-19 patients, and “management is often symptomatic, but it is sometimes necessary to modify or discontinue the treatment, and some conditions can even be life-threatening,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Martinez-Lopez A et al. J Am Acad Dermatol. 2020 doi: 10.1016/j.jaad.2020.08.006.
published in the Journal of the American Academy of Dermatology.
SARS-CoV-2 infection has been associated with a range of skin conditions, wrote Antonio Martinez-Lopez, MD, of Virgen de las Nieves University Hospital, Granada, Spain, and colleagues, who provided an overview of the cutaneous side effects associated with drugs used to treat COVID-19 infection.
“Cutaneous manifestations have recently been described in patients with the new coronavirus infection, similar to cutaneous involvement occurring in common viral infections,” they said. Infected individuals have experienced maculopapular eruption, pseudo-chilblain lesions, urticaria, monomorphic disseminated vesicular lesions, acral vesicular-pustulous lesions, and livedo or necrosis, they noted.
Diagnosing skin manifestations in patients with COVID-19 remains a challenge, because it is unclear whether the skin lesions are related to the virus, the authors said. “Skin diseases not related to coronavirus, other seasonal viral infections, and drug reactions should be considered in the differential diagnosis, especially in those patients suffering from nonspecific manifestations such as urticaria or maculopapular eruptions,” they wrote.
However, “urticarial lesions and maculopapular eruptions in SARS-CoV-2 infections usually appear at the same time as the systemic symptoms, while drug adverse reactions are likely to arise hours to days after the start of the treatment,” they said.
The reviewers noted several cutaneous side effects associated with several of the often-prescribed drugs for COVID-19 infection. The antimalarials hydroxychloroquine and chloroquine had been authorized for COVID-19 treatment by the Food and Drug Administration, but this emergency authorization was rescinded in June. They noted that up to 11.5% of patients on these drugs may experience cutaneous adverse effects, including some that “can be mistaken for skin manifestations of SARS-CoV-2, especially those with maculopapular rash or exanthematous reactions.” Another side effect is exacerbation of psoriasis, which has been described in patients with COVID-19, the authors said.
The oral antiretroviral combination lopinavir/ritonavir, under investigation in clinical trials for COVID-19, has been associated with skin rashes in as many as 5% of adults in HIV studies. Usually appearing after treatment is started, the maculopapular pruritic rash is “usually well tolerated,” they said, although there have been reports of Stevens-Johnson syndrome. Alopecia areata is among the other side effects reported.
Remdesivir also has been authorized for emergency treatment of COVID-19, and the small amount of data available suggest that cutaneous manifestations may be infrequent, the reviewers said. In a recent study of 53 patients treated with remdesivir for 10 days, approximately 8% developed a rash, but the study did not include any information “about rash morphology, distribution, or timeline in relation to remdesivir that may help clinicians differentiate from cutaneous manifestations of COVID-19,” they said.
Other potential treatments for complications of COVID-19 include imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine, and low molecular weight heparins; all have the potential for association with skin reactions, but data on skin manifestations associated with COVID-19 are limited, the authors wrote.
Notably, data on the use of systemic corticosteroids for COVID-19 patients are controversial, although preliminary data showed some reduced mortality in COVID-19 patients who were on respiratory support, they noted. “With regard to differential diagnosis of cutaneous manifestations of COVID-19, the vascular fragility associated with corticosteroid use, especially in elderly patients, may be similar to the thrombotic complications of COVID-19 infection.”
Knowledge about the virology of COVID-19 continues to evolve rapidly, and the number of drugs being studied as treatments continues to expand, the authors pointed out.
“By considering adverse drug reactions in the differential diagnosis, dermatologists can be useful in assisting in the care of these patients,” they wrote. Drugs, rather than the infection, may be the cause of skin reactions in some COVID-19 patients, and “management is often symptomatic, but it is sometimes necessary to modify or discontinue the treatment, and some conditions can even be life-threatening,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Martinez-Lopez A et al. J Am Acad Dermatol. 2020 doi: 10.1016/j.jaad.2020.08.006.
published in the Journal of the American Academy of Dermatology.
SARS-CoV-2 infection has been associated with a range of skin conditions, wrote Antonio Martinez-Lopez, MD, of Virgen de las Nieves University Hospital, Granada, Spain, and colleagues, who provided an overview of the cutaneous side effects associated with drugs used to treat COVID-19 infection.
“Cutaneous manifestations have recently been described in patients with the new coronavirus infection, similar to cutaneous involvement occurring in common viral infections,” they said. Infected individuals have experienced maculopapular eruption, pseudo-chilblain lesions, urticaria, monomorphic disseminated vesicular lesions, acral vesicular-pustulous lesions, and livedo or necrosis, they noted.
Diagnosing skin manifestations in patients with COVID-19 remains a challenge, because it is unclear whether the skin lesions are related to the virus, the authors said. “Skin diseases not related to coronavirus, other seasonal viral infections, and drug reactions should be considered in the differential diagnosis, especially in those patients suffering from nonspecific manifestations such as urticaria or maculopapular eruptions,” they wrote.
However, “urticarial lesions and maculopapular eruptions in SARS-CoV-2 infections usually appear at the same time as the systemic symptoms, while drug adverse reactions are likely to arise hours to days after the start of the treatment,” they said.
The reviewers noted several cutaneous side effects associated with several of the often-prescribed drugs for COVID-19 infection. The antimalarials hydroxychloroquine and chloroquine had been authorized for COVID-19 treatment by the Food and Drug Administration, but this emergency authorization was rescinded in June. They noted that up to 11.5% of patients on these drugs may experience cutaneous adverse effects, including some that “can be mistaken for skin manifestations of SARS-CoV-2, especially those with maculopapular rash or exanthematous reactions.” Another side effect is exacerbation of psoriasis, which has been described in patients with COVID-19, the authors said.
The oral antiretroviral combination lopinavir/ritonavir, under investigation in clinical trials for COVID-19, has been associated with skin rashes in as many as 5% of adults in HIV studies. Usually appearing after treatment is started, the maculopapular pruritic rash is “usually well tolerated,” they said, although there have been reports of Stevens-Johnson syndrome. Alopecia areata is among the other side effects reported.
Remdesivir also has been authorized for emergency treatment of COVID-19, and the small amount of data available suggest that cutaneous manifestations may be infrequent, the reviewers said. In a recent study of 53 patients treated with remdesivir for 10 days, approximately 8% developed a rash, but the study did not include any information “about rash morphology, distribution, or timeline in relation to remdesivir that may help clinicians differentiate from cutaneous manifestations of COVID-19,” they said.
Other potential treatments for complications of COVID-19 include imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine, and low molecular weight heparins; all have the potential for association with skin reactions, but data on skin manifestations associated with COVID-19 are limited, the authors wrote.
Notably, data on the use of systemic corticosteroids for COVID-19 patients are controversial, although preliminary data showed some reduced mortality in COVID-19 patients who were on respiratory support, they noted. “With regard to differential diagnosis of cutaneous manifestations of COVID-19, the vascular fragility associated with corticosteroid use, especially in elderly patients, may be similar to the thrombotic complications of COVID-19 infection.”
Knowledge about the virology of COVID-19 continues to evolve rapidly, and the number of drugs being studied as treatments continues to expand, the authors pointed out.
“By considering adverse drug reactions in the differential diagnosis, dermatologists can be useful in assisting in the care of these patients,” they wrote. Drugs, rather than the infection, may be the cause of skin reactions in some COVID-19 patients, and “management is often symptomatic, but it is sometimes necessary to modify or discontinue the treatment, and some conditions can even be life-threatening,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Martinez-Lopez A et al. J Am Acad Dermatol. 2020 doi: 10.1016/j.jaad.2020.08.006.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Since COVID-19 onset, admissions for MI are down, mortality rates are up
A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.
Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.
The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.
When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.
The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.
The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
Differences in mortality, patients, treatment
In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).
The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).
The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.
Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
More than fear of COVID-19?
One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.
“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.
In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.
“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”
Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.
More data gathered by other centers might provide information about what it all means.
“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”
The investigators reported having no financial conflicts of interest.
SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.
A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.
Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.
The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.
When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.
The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.
The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
Differences in mortality, patients, treatment
In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).
The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).
The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.
Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
More than fear of COVID-19?
One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.
“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.
In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.
“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”
Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.
More data gathered by other centers might provide information about what it all means.
“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”
The investigators reported having no financial conflicts of interest.
SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.
A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.
Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.
The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.
When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.
The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.
The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
Differences in mortality, patients, treatment
In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).
The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).
The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.
Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
More than fear of COVID-19?
One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.
“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.
In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.
“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”
Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.
More data gathered by other centers might provide information about what it all means.
“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”
The investigators reported having no financial conflicts of interest.
SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.
FROM JAMA CARDIOLOGY
Pandemic effect: Telemedicine is now a ‘must-have’ service
If people try telemedicine, they’ll like telemedicine. And if they want to avoid a doctor’s office, as most people do these days, they’ll try telemedicine. That is the message coming from 1,000 people surveyed for DocASAP, a provider of online patient access and engagement systems.
Here are a couple of numbers: 92% of those who made a telemedicine visit said they were satisfied with the overall appointment experience, and 91% said that they are more likely to schedule a telemedicine visit instead of an in-person appointment. All of the survey respondents had visited a health care provider in the past year, and 40% already had made a telemedicine visit, DocASAP reported.
Puneet Maheshwari, DocASAP cofounder and CEO, said in a statement. “As providers continue to adopt innovative technology to power a more seamless, end-to-end digital consumer experience, I expect telehealth to become fully integrated into overall care management.”
For now, though, COVID-19 is an overriding concern and health care facilities are suspect. When respondents were asked to identify the types of public facilities where they felt safe, hospitals were named by 32%, doctors’ offices by 26%, and ED/urgent care by just 12%, the DocASAP report said. Even public transportation got 13%.
The safest place to be, according to 42% of the respondents? The grocery store.
Of those surveyed, 43% “indicated they will not feel safe entering any health care setting until at least the fall,” the company said. An even higher share of patients, 68%, canceled or postponed an in-person appointment during the pandemic.
“No longer are remote health services viewed as ‘nice to have’ – they are now a must-have care delivery option,” DocASAP said in their report.
Safety concerns involving COVID-19, named by 47% of the sample, were the leading factor that would influence patients’ decision to schedule a telemedicine visit. Insurance coverage was next at 43%, followed by “ease of accessing quality care” at 40%, the report said.
Among those who had made a telemedicine visit, scheduling the appointment was the most satisfying aspect of the experience, according to 54% of respondents, with day-of-appointment wait time next at 38% and quality of the video/audio technology tied with preappointment communication at almost 33%, the survey data show.
Conversely, scheduling the appointment also was declared the most frustrating aspect of the telemedicine experience, although the total in that category was a much lower 29%.
“The pandemic has thrust profound change on every aspect of life, particularly health care. … Innovations – like digital and telehealth solutions – designed to meet patient needs will likely become embedded into the health care delivery system,” DocASAP said.
The survey was commissioned by DocASAP and conducted by marketing research company OnePoll on June 29-30, 2020.
If people try telemedicine, they’ll like telemedicine. And if they want to avoid a doctor’s office, as most people do these days, they’ll try telemedicine. That is the message coming from 1,000 people surveyed for DocASAP, a provider of online patient access and engagement systems.
Here are a couple of numbers: 92% of those who made a telemedicine visit said they were satisfied with the overall appointment experience, and 91% said that they are more likely to schedule a telemedicine visit instead of an in-person appointment. All of the survey respondents had visited a health care provider in the past year, and 40% already had made a telemedicine visit, DocASAP reported.
Puneet Maheshwari, DocASAP cofounder and CEO, said in a statement. “As providers continue to adopt innovative technology to power a more seamless, end-to-end digital consumer experience, I expect telehealth to become fully integrated into overall care management.”
For now, though, COVID-19 is an overriding concern and health care facilities are suspect. When respondents were asked to identify the types of public facilities where they felt safe, hospitals were named by 32%, doctors’ offices by 26%, and ED/urgent care by just 12%, the DocASAP report said. Even public transportation got 13%.
The safest place to be, according to 42% of the respondents? The grocery store.
Of those surveyed, 43% “indicated they will not feel safe entering any health care setting until at least the fall,” the company said. An even higher share of patients, 68%, canceled or postponed an in-person appointment during the pandemic.
“No longer are remote health services viewed as ‘nice to have’ – they are now a must-have care delivery option,” DocASAP said in their report.
Safety concerns involving COVID-19, named by 47% of the sample, were the leading factor that would influence patients’ decision to schedule a telemedicine visit. Insurance coverage was next at 43%, followed by “ease of accessing quality care” at 40%, the report said.
Among those who had made a telemedicine visit, scheduling the appointment was the most satisfying aspect of the experience, according to 54% of respondents, with day-of-appointment wait time next at 38% and quality of the video/audio technology tied with preappointment communication at almost 33%, the survey data show.
Conversely, scheduling the appointment also was declared the most frustrating aspect of the telemedicine experience, although the total in that category was a much lower 29%.
“The pandemic has thrust profound change on every aspect of life, particularly health care. … Innovations – like digital and telehealth solutions – designed to meet patient needs will likely become embedded into the health care delivery system,” DocASAP said.
The survey was commissioned by DocASAP and conducted by marketing research company OnePoll on June 29-30, 2020.
If people try telemedicine, they’ll like telemedicine. And if they want to avoid a doctor’s office, as most people do these days, they’ll try telemedicine. That is the message coming from 1,000 people surveyed for DocASAP, a provider of online patient access and engagement systems.
Here are a couple of numbers: 92% of those who made a telemedicine visit said they were satisfied with the overall appointment experience, and 91% said that they are more likely to schedule a telemedicine visit instead of an in-person appointment. All of the survey respondents had visited a health care provider in the past year, and 40% already had made a telemedicine visit, DocASAP reported.
Puneet Maheshwari, DocASAP cofounder and CEO, said in a statement. “As providers continue to adopt innovative technology to power a more seamless, end-to-end digital consumer experience, I expect telehealth to become fully integrated into overall care management.”
For now, though, COVID-19 is an overriding concern and health care facilities are suspect. When respondents were asked to identify the types of public facilities where they felt safe, hospitals were named by 32%, doctors’ offices by 26%, and ED/urgent care by just 12%, the DocASAP report said. Even public transportation got 13%.
The safest place to be, according to 42% of the respondents? The grocery store.
Of those surveyed, 43% “indicated they will not feel safe entering any health care setting until at least the fall,” the company said. An even higher share of patients, 68%, canceled or postponed an in-person appointment during the pandemic.
“No longer are remote health services viewed as ‘nice to have’ – they are now a must-have care delivery option,” DocASAP said in their report.
Safety concerns involving COVID-19, named by 47% of the sample, were the leading factor that would influence patients’ decision to schedule a telemedicine visit. Insurance coverage was next at 43%, followed by “ease of accessing quality care” at 40%, the report said.
Among those who had made a telemedicine visit, scheduling the appointment was the most satisfying aspect of the experience, according to 54% of respondents, with day-of-appointment wait time next at 38% and quality of the video/audio technology tied with preappointment communication at almost 33%, the survey data show.
Conversely, scheduling the appointment also was declared the most frustrating aspect of the telemedicine experience, although the total in that category was a much lower 29%.
“The pandemic has thrust profound change on every aspect of life, particularly health care. … Innovations – like digital and telehealth solutions – designed to meet patient needs will likely become embedded into the health care delivery system,” DocASAP said.
The survey was commissioned by DocASAP and conducted by marketing research company OnePoll on June 29-30, 2020.
Developing COVID-19 hospital protocols during the pandemic
As hospitalists and other physicians at the University of Texas at Austin considered how to treat COVID-19 patients in the early weeks of the pandemic, one question they had to consider was: What about convalescent plasma?
All they had to go on were small case series in Ebola, SARS, and MERS and a few small, nonrandomized COVID-19 studies showing a possible benefit and minimal risk, but the evidence was only “toward the middle or bottom” of the evidence pyramid, said Johanna Busch, MD, of the department of internal medicine at Dell Medical Center at the university.
The center’s COVID-19 committee asked a few of its members – infectious disease and internal medicine physicians – to analyze the literature and other factors. In the end, the committee – which meets regularly and also includes pulmonology–critical care experts, nursing experts, and others – recommended using convalescent plasma because of the evidence and the available supply. But in subsequent meetings, as the pandemic surged in the South and the supply dwindled, the committee changed its recommendation for convalescent plasma to more limited use, she said during the virtual annual meeting of the Society of Hospital Medicine.
“It’s all about teamwork,” said W. Michael Brode, MD, of the department of internal medicine at Dell. “The interprofessional team members know their roles and have shared expectations because they have a common understanding of the protocol.” It’s okay to deviate from the protocol, he said, as long as the language exists to communicate these deviations.
“Maybe the approach is more important than the actual content,” he said.
What Dr. Brode and Dr. Busch described was in large part a fine-tuning of communication – being available to communicate in real time and being aware of when certain specialists should be contacted – for instance, to determine at what oxygenation level internal medicine staff should get in touch with the pulmonary–critical care team.
Dr. Brode said that the groundwork is laid for productive meetings, with agendas announced ahead of time and readings assigned and presenters ready with near-finished products at meeting time, “with a clear path for operationalizing it.”
“We don’t want people kind of riffing off the top of their heads,” he said.
Committee members are encouraged to be as specific as possible when giving input into COVID-19 care decisions, he said.
“We’re so used to dealing with uncertainty, but that doesn’t really help when we’re trying to make tough decisions,” Dr. Brode said. They might be asked, “What are you going to write in your consult note template?” or “It’s 1:00 a.m. and your intern’s panicked and calling you – what are you going to tell them to do over the phone?”
The recommendations have to go into writing and are incorporated into the electronic medical record, a process that required some workarounds, he said. He also noted that the committee learned early on that they should assume that no one reads the e-mails – especially after being off for a period of time – so they likely won’t digest updates on an email-by-email basis.
“We quickly learned,” Dr. Brode said, “that this information needs to live on a Web site or [be] linked to the most up-to-date version in a cloud-sharing platform.”
In a question-and-answer discussion, session viewers expressed enthusiasm for the presenters’ one-page summary of protocols – much more, they said, and it could feel overwhelming.
Dr. Busch and Dr. Brode were asked how standardized order sets for COVID patients could be justified without comparison to a control group that didn’t use the standard order set.
Dr. Busch responded that, while there was no controlled trial, the order sets they use have evolved based on experience.
“At the beginning, we were following every inflammatory marker known to mankind, and then we realized as we gained more experience with COVID and COVID patients that some of those markers were not really informing any of our clinical decisions,” she said. “Obviously, as literature comes out we may reevaluate what goes into that standard order set and how frequently we follow labs.”
Dr. Brode said the context – a pandemic – has to be considered.
“In an ideal world, we could show that the intervention is superior through a randomized fashion with a control group, but really our thought process behind it is just, what is the default?” he said. “I looked at the order sets [as] not that they’re going to be dictating care, but it’s really like the guardrails of what’s reasonable. And when you’re in the middle of a surge, what is usually reasonable and easiest is what is going to be done.”
Dr. Busch and Dr. Brode reported no relevant financial relationships.
As hospitalists and other physicians at the University of Texas at Austin considered how to treat COVID-19 patients in the early weeks of the pandemic, one question they had to consider was: What about convalescent plasma?
All they had to go on were small case series in Ebola, SARS, and MERS and a few small, nonrandomized COVID-19 studies showing a possible benefit and minimal risk, but the evidence was only “toward the middle or bottom” of the evidence pyramid, said Johanna Busch, MD, of the department of internal medicine at Dell Medical Center at the university.
The center’s COVID-19 committee asked a few of its members – infectious disease and internal medicine physicians – to analyze the literature and other factors. In the end, the committee – which meets regularly and also includes pulmonology–critical care experts, nursing experts, and others – recommended using convalescent plasma because of the evidence and the available supply. But in subsequent meetings, as the pandemic surged in the South and the supply dwindled, the committee changed its recommendation for convalescent plasma to more limited use, she said during the virtual annual meeting of the Society of Hospital Medicine.
“It’s all about teamwork,” said W. Michael Brode, MD, of the department of internal medicine at Dell. “The interprofessional team members know their roles and have shared expectations because they have a common understanding of the protocol.” It’s okay to deviate from the protocol, he said, as long as the language exists to communicate these deviations.
“Maybe the approach is more important than the actual content,” he said.
What Dr. Brode and Dr. Busch described was in large part a fine-tuning of communication – being available to communicate in real time and being aware of when certain specialists should be contacted – for instance, to determine at what oxygenation level internal medicine staff should get in touch with the pulmonary–critical care team.
Dr. Brode said that the groundwork is laid for productive meetings, with agendas announced ahead of time and readings assigned and presenters ready with near-finished products at meeting time, “with a clear path for operationalizing it.”
“We don’t want people kind of riffing off the top of their heads,” he said.
Committee members are encouraged to be as specific as possible when giving input into COVID-19 care decisions, he said.
“We’re so used to dealing with uncertainty, but that doesn’t really help when we’re trying to make tough decisions,” Dr. Brode said. They might be asked, “What are you going to write in your consult note template?” or “It’s 1:00 a.m. and your intern’s panicked and calling you – what are you going to tell them to do over the phone?”
The recommendations have to go into writing and are incorporated into the electronic medical record, a process that required some workarounds, he said. He also noted that the committee learned early on that they should assume that no one reads the e-mails – especially after being off for a period of time – so they likely won’t digest updates on an email-by-email basis.
“We quickly learned,” Dr. Brode said, “that this information needs to live on a Web site or [be] linked to the most up-to-date version in a cloud-sharing platform.”
In a question-and-answer discussion, session viewers expressed enthusiasm for the presenters’ one-page summary of protocols – much more, they said, and it could feel overwhelming.
Dr. Busch and Dr. Brode were asked how standardized order sets for COVID patients could be justified without comparison to a control group that didn’t use the standard order set.
Dr. Busch responded that, while there was no controlled trial, the order sets they use have evolved based on experience.
“At the beginning, we were following every inflammatory marker known to mankind, and then we realized as we gained more experience with COVID and COVID patients that some of those markers were not really informing any of our clinical decisions,” she said. “Obviously, as literature comes out we may reevaluate what goes into that standard order set and how frequently we follow labs.”
Dr. Brode said the context – a pandemic – has to be considered.
“In an ideal world, we could show that the intervention is superior through a randomized fashion with a control group, but really our thought process behind it is just, what is the default?” he said. “I looked at the order sets [as] not that they’re going to be dictating care, but it’s really like the guardrails of what’s reasonable. And when you’re in the middle of a surge, what is usually reasonable and easiest is what is going to be done.”
Dr. Busch and Dr. Brode reported no relevant financial relationships.
As hospitalists and other physicians at the University of Texas at Austin considered how to treat COVID-19 patients in the early weeks of the pandemic, one question they had to consider was: What about convalescent plasma?
All they had to go on were small case series in Ebola, SARS, and MERS and a few small, nonrandomized COVID-19 studies showing a possible benefit and minimal risk, but the evidence was only “toward the middle or bottom” of the evidence pyramid, said Johanna Busch, MD, of the department of internal medicine at Dell Medical Center at the university.
The center’s COVID-19 committee asked a few of its members – infectious disease and internal medicine physicians – to analyze the literature and other factors. In the end, the committee – which meets regularly and also includes pulmonology–critical care experts, nursing experts, and others – recommended using convalescent plasma because of the evidence and the available supply. But in subsequent meetings, as the pandemic surged in the South and the supply dwindled, the committee changed its recommendation for convalescent plasma to more limited use, she said during the virtual annual meeting of the Society of Hospital Medicine.
“It’s all about teamwork,” said W. Michael Brode, MD, of the department of internal medicine at Dell. “The interprofessional team members know their roles and have shared expectations because they have a common understanding of the protocol.” It’s okay to deviate from the protocol, he said, as long as the language exists to communicate these deviations.
“Maybe the approach is more important than the actual content,” he said.
What Dr. Brode and Dr. Busch described was in large part a fine-tuning of communication – being available to communicate in real time and being aware of when certain specialists should be contacted – for instance, to determine at what oxygenation level internal medicine staff should get in touch with the pulmonary–critical care team.
Dr. Brode said that the groundwork is laid for productive meetings, with agendas announced ahead of time and readings assigned and presenters ready with near-finished products at meeting time, “with a clear path for operationalizing it.”
“We don’t want people kind of riffing off the top of their heads,” he said.
Committee members are encouraged to be as specific as possible when giving input into COVID-19 care decisions, he said.
“We’re so used to dealing with uncertainty, but that doesn’t really help when we’re trying to make tough decisions,” Dr. Brode said. They might be asked, “What are you going to write in your consult note template?” or “It’s 1:00 a.m. and your intern’s panicked and calling you – what are you going to tell them to do over the phone?”
The recommendations have to go into writing and are incorporated into the electronic medical record, a process that required some workarounds, he said. He also noted that the committee learned early on that they should assume that no one reads the e-mails – especially after being off for a period of time – so they likely won’t digest updates on an email-by-email basis.
“We quickly learned,” Dr. Brode said, “that this information needs to live on a Web site or [be] linked to the most up-to-date version in a cloud-sharing platform.”
In a question-and-answer discussion, session viewers expressed enthusiasm for the presenters’ one-page summary of protocols – much more, they said, and it could feel overwhelming.
Dr. Busch and Dr. Brode were asked how standardized order sets for COVID patients could be justified without comparison to a control group that didn’t use the standard order set.
Dr. Busch responded that, while there was no controlled trial, the order sets they use have evolved based on experience.
“At the beginning, we were following every inflammatory marker known to mankind, and then we realized as we gained more experience with COVID and COVID patients that some of those markers were not really informing any of our clinical decisions,” she said. “Obviously, as literature comes out we may reevaluate what goes into that standard order set and how frequently we follow labs.”
Dr. Brode said the context – a pandemic – has to be considered.
“In an ideal world, we could show that the intervention is superior through a randomized fashion with a control group, but really our thought process behind it is just, what is the default?” he said. “I looked at the order sets [as] not that they’re going to be dictating care, but it’s really like the guardrails of what’s reasonable. And when you’re in the middle of a surge, what is usually reasonable and easiest is what is going to be done.”
Dr. Busch and Dr. Brode reported no relevant financial relationships.
FROM HM20 VIRTUAL
‘Doubling down’ on hydroxychloroquine QT prolongation in COVID-19
A new analysis from Michigan’s largest health system provides sobering verification of the risks for QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin (HCQ/AZM).
One in five patients (21%) had a corrected QT (QTc) interval of at least 500 msec, a value that increases the risk for torsade de pointes in the general population and at which cardiovascular leaders have suggested withholding HCQ/AZM in COVID-19 patients.
“One of the most striking findings was when we looked at the other drugs being administered to these patients; 61% were being administered drugs that had QT-prolonging effects concomitantly with the HCQ and AZM therapy. So they were inadvertently doubling down on the QT-prolonging effects of these drugs,” senior author David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital, Royal Oak, Mich., said in an interview.
A total of 34 medications overlapped with HCQ/AZM therapy are known or suspected to increase the risk for torsade de pointes, a potentially life-threatening ventricular tachycardia. The most common of these were propofol coadministered in 123 patients, ondansetron in 114, dexmedetomidine in 54, haloperidol in 44, amiodarone in 43, and tramadol in 26.
“This speaks to the medical complexity of this patient population, but also suggests inadequate awareness of the QT-prolonging effects of many common medications,” the researchers say.
The study was published Aug. 5 in JACC Clinical Electrophysiology.
Both hydroxychloroquine and azithromycin increase the risk for QTc-interval prolongation by blocking the KCHN2-encoded hERG potassium channel. Several reports have linked the drugs to a triggering of QT prolongation in patients with COVID-19.
For the present study, Dr. Haines and colleagues examined data from 586 consecutive patients admitted with COVID-19 to the Beaumont Hospitals in Royal Oak and Troy, Mich., between March 13 and April 6. A baseline QTc interval was measured with 12-lead ECG prior to treatment initiation with hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily for 4 days, and azithromycin 500 mg once followed by 250 mg daily for 4 days.
Because of limited availability at the time, lead II ECG telemetry monitoring over the 5-day course of HCQ/AZM was recommended only in patients with baseline QTc intervals of at least 440 msec.
Patients without an interpretable baseline ECG or available telemetry/ECG monitoring for at least 1 day were also excluded, leaving 415 patients (mean age, 64 years; 45% female) in the study population. More than half (52%) were Black, 52% had hypertension, 30% had diabetes, and 14% had cancer.
As seen in previous studies, the QTc interval increased progressively and significantly after the administration of HCQ/AZM, from 443 msec to 473 msec.
The average time to maximum QTc was 2.9 days in a subset of 135 patients with QTc measurements prior to starting therapy and on days 1 through 5.
In multivariate analysis, independent predictors of a potentially hazardous QTc interval of at least 500 msec were:
- Age older than 65 years (odds ratio, 3.0; 95% confidence interval, 1.62-5.54).
- History of (OR, 4.65; 95% CI, 2.01-10.74).
- Admission of at least 1.5 mg/dL (OR, 2.22; 95% CI, 1.28-3.84).
- Peak troponin I level above 0.04 mg/mL (OR, 3.89; 95% CI, 2.22-6.83).
- Body mass index below 30 kg/m2 (OR for a BMI of 30 kg/m2 or higher, 0.45; 95% CI, 0.26-0.78).
Concomitant use of drugs with known risk for torsade de pointes was a significant risk factor in univariate analysis (OR, 1.73; P = .036), but fell out in the multivariate model.
No patients experienced high-grade arrhythmias during the study. In all, 112 of the 586 patients died during hospitalization, including 85 (21%) of the 415 study patients.
The change in QTc interval from baseline was greater in patients who died. Despite this, the only independent predictor of mortality was older age. One possible explanation is that the decision to monitor patients with baseline QTc intervals of at least 440 msec may have skewed the study population toward people with moderate or slightly long QTc intervals prior to the initiation of HCQ/AZM, Dr. Haines suggested. Monitoring and treatment duration were short, and clinicians also likely adjusted medications when excess QTc prolongation was observed.
Although it’s been months since data collection was completed in April, and the paper was written in record-breaking time, the study “is still very relevant because the drug is still out there,” observed Dr. Haines. “Even though it may not be used in as widespread a fashion as it had been when we first submitted the paper, it is still being used routinely by many hospitals and many practitioners.”
The use of hydroxychloroquine is “going through the roof” because of COVID-19, commented Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, HCA Midwest Health, Overland Park, Kan., who was not involved in the study.
“This study is very relevant, and I’m glad they shared their experience, and it’s pretty consistent with the data presented by other people. The question of whether hydroxychloroquine helps people with COVID is up for debate, but there is more evidence today that it is not as helpful as it was 3 months ago,” said Dr. Lakkireddy, who is also chair of the American College of Cardiology Electrophysiology Council.
He expressed concern for patients who may be taking HCQ with other medications that have QT-prolonging effects, and for the lack of long-term protocols in place for the drug.
In the coming weeks, however, the ACC and rheumatology leaders will be publishing an expert consensus statement that addresses key issues, such as how to best to use HCQ, maintenance HCQ, electrolyte monitoring, the optimal timing of electrocardiography and cardiac magnetic imaging, and symptoms to look for if cardiac involvement is suspected, Dr. Lakkireddy said.
Asked whether HCQ and AZM should be used in COVID-19 patients, Dr. Haines said in an interview that the “QT-prolonging effects are real, the arrhythmogenic potential is real, and the benefit to patients is nil or marginal. So I think that use of these drugs is appropriate and reasonable if it is done in a setting of a controlled trial, and I support that. But the routine use of these drugs probably is not warranted based on the data that we have available.”
Still, hydroxychloroquine continues to be dragged into the spotlight in recent days as an effective treatment for COVID-19, despite discredited research and the U.S. Food and Drug Administration’s June 15 revocation of its emergency-use authorization to allow use of HCQ and chloroquine to treat certain hospitalized COVID-19 patients.
“The unfortunate politicization of this issue has really muddied the waters because the general public doesn’t know what to believe or who to believe. The fact that treatment for a disease as serious as COVID should be modulated by political affiliation is just crazy to me,” said Dr. Haines. “We should be using the best science and taking careful observations, and whatever the recommendations derived from that should be uniformly adopted by everybody, irrespective of your political affiliation.”
Dr. Haines has received honoraria from Biosense Webster, Farapulse, and Sagentia, and is a consultant for Affera, Boston Scientific, Integer, Medtronic, Philips Healthcare, and Zoll. Dr. Lakkireddy has served as a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.
A version of this article originally appeared on Medscape.com.
A new analysis from Michigan’s largest health system provides sobering verification of the risks for QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin (HCQ/AZM).
One in five patients (21%) had a corrected QT (QTc) interval of at least 500 msec, a value that increases the risk for torsade de pointes in the general population and at which cardiovascular leaders have suggested withholding HCQ/AZM in COVID-19 patients.
“One of the most striking findings was when we looked at the other drugs being administered to these patients; 61% were being administered drugs that had QT-prolonging effects concomitantly with the HCQ and AZM therapy. So they were inadvertently doubling down on the QT-prolonging effects of these drugs,” senior author David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital, Royal Oak, Mich., said in an interview.
A total of 34 medications overlapped with HCQ/AZM therapy are known or suspected to increase the risk for torsade de pointes, a potentially life-threatening ventricular tachycardia. The most common of these were propofol coadministered in 123 patients, ondansetron in 114, dexmedetomidine in 54, haloperidol in 44, amiodarone in 43, and tramadol in 26.
“This speaks to the medical complexity of this patient population, but also suggests inadequate awareness of the QT-prolonging effects of many common medications,” the researchers say.
The study was published Aug. 5 in JACC Clinical Electrophysiology.
Both hydroxychloroquine and azithromycin increase the risk for QTc-interval prolongation by blocking the KCHN2-encoded hERG potassium channel. Several reports have linked the drugs to a triggering of QT prolongation in patients with COVID-19.
For the present study, Dr. Haines and colleagues examined data from 586 consecutive patients admitted with COVID-19 to the Beaumont Hospitals in Royal Oak and Troy, Mich., between March 13 and April 6. A baseline QTc interval was measured with 12-lead ECG prior to treatment initiation with hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily for 4 days, and azithromycin 500 mg once followed by 250 mg daily for 4 days.
Because of limited availability at the time, lead II ECG telemetry monitoring over the 5-day course of HCQ/AZM was recommended only in patients with baseline QTc intervals of at least 440 msec.
Patients without an interpretable baseline ECG or available telemetry/ECG monitoring for at least 1 day were also excluded, leaving 415 patients (mean age, 64 years; 45% female) in the study population. More than half (52%) were Black, 52% had hypertension, 30% had diabetes, and 14% had cancer.
As seen in previous studies, the QTc interval increased progressively and significantly after the administration of HCQ/AZM, from 443 msec to 473 msec.
The average time to maximum QTc was 2.9 days in a subset of 135 patients with QTc measurements prior to starting therapy and on days 1 through 5.
In multivariate analysis, independent predictors of a potentially hazardous QTc interval of at least 500 msec were:
- Age older than 65 years (odds ratio, 3.0; 95% confidence interval, 1.62-5.54).
- History of (OR, 4.65; 95% CI, 2.01-10.74).
- Admission of at least 1.5 mg/dL (OR, 2.22; 95% CI, 1.28-3.84).
- Peak troponin I level above 0.04 mg/mL (OR, 3.89; 95% CI, 2.22-6.83).
- Body mass index below 30 kg/m2 (OR for a BMI of 30 kg/m2 or higher, 0.45; 95% CI, 0.26-0.78).
Concomitant use of drugs with known risk for torsade de pointes was a significant risk factor in univariate analysis (OR, 1.73; P = .036), but fell out in the multivariate model.
No patients experienced high-grade arrhythmias during the study. In all, 112 of the 586 patients died during hospitalization, including 85 (21%) of the 415 study patients.
The change in QTc interval from baseline was greater in patients who died. Despite this, the only independent predictor of mortality was older age. One possible explanation is that the decision to monitor patients with baseline QTc intervals of at least 440 msec may have skewed the study population toward people with moderate or slightly long QTc intervals prior to the initiation of HCQ/AZM, Dr. Haines suggested. Monitoring and treatment duration were short, and clinicians also likely adjusted medications when excess QTc prolongation was observed.
Although it’s been months since data collection was completed in April, and the paper was written in record-breaking time, the study “is still very relevant because the drug is still out there,” observed Dr. Haines. “Even though it may not be used in as widespread a fashion as it had been when we first submitted the paper, it is still being used routinely by many hospitals and many practitioners.”
The use of hydroxychloroquine is “going through the roof” because of COVID-19, commented Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, HCA Midwest Health, Overland Park, Kan., who was not involved in the study.
“This study is very relevant, and I’m glad they shared their experience, and it’s pretty consistent with the data presented by other people. The question of whether hydroxychloroquine helps people with COVID is up for debate, but there is more evidence today that it is not as helpful as it was 3 months ago,” said Dr. Lakkireddy, who is also chair of the American College of Cardiology Electrophysiology Council.
He expressed concern for patients who may be taking HCQ with other medications that have QT-prolonging effects, and for the lack of long-term protocols in place for the drug.
In the coming weeks, however, the ACC and rheumatology leaders will be publishing an expert consensus statement that addresses key issues, such as how to best to use HCQ, maintenance HCQ, electrolyte monitoring, the optimal timing of electrocardiography and cardiac magnetic imaging, and symptoms to look for if cardiac involvement is suspected, Dr. Lakkireddy said.
Asked whether HCQ and AZM should be used in COVID-19 patients, Dr. Haines said in an interview that the “QT-prolonging effects are real, the arrhythmogenic potential is real, and the benefit to patients is nil or marginal. So I think that use of these drugs is appropriate and reasonable if it is done in a setting of a controlled trial, and I support that. But the routine use of these drugs probably is not warranted based on the data that we have available.”
Still, hydroxychloroquine continues to be dragged into the spotlight in recent days as an effective treatment for COVID-19, despite discredited research and the U.S. Food and Drug Administration’s June 15 revocation of its emergency-use authorization to allow use of HCQ and chloroquine to treat certain hospitalized COVID-19 patients.
“The unfortunate politicization of this issue has really muddied the waters because the general public doesn’t know what to believe or who to believe. The fact that treatment for a disease as serious as COVID should be modulated by political affiliation is just crazy to me,” said Dr. Haines. “We should be using the best science and taking careful observations, and whatever the recommendations derived from that should be uniformly adopted by everybody, irrespective of your political affiliation.”
Dr. Haines has received honoraria from Biosense Webster, Farapulse, and Sagentia, and is a consultant for Affera, Boston Scientific, Integer, Medtronic, Philips Healthcare, and Zoll. Dr. Lakkireddy has served as a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.
A version of this article originally appeared on Medscape.com.
A new analysis from Michigan’s largest health system provides sobering verification of the risks for QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin (HCQ/AZM).
One in five patients (21%) had a corrected QT (QTc) interval of at least 500 msec, a value that increases the risk for torsade de pointes in the general population and at which cardiovascular leaders have suggested withholding HCQ/AZM in COVID-19 patients.
“One of the most striking findings was when we looked at the other drugs being administered to these patients; 61% were being administered drugs that had QT-prolonging effects concomitantly with the HCQ and AZM therapy. So they were inadvertently doubling down on the QT-prolonging effects of these drugs,” senior author David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital, Royal Oak, Mich., said in an interview.
A total of 34 medications overlapped with HCQ/AZM therapy are known or suspected to increase the risk for torsade de pointes, a potentially life-threatening ventricular tachycardia. The most common of these were propofol coadministered in 123 patients, ondansetron in 114, dexmedetomidine in 54, haloperidol in 44, amiodarone in 43, and tramadol in 26.
“This speaks to the medical complexity of this patient population, but also suggests inadequate awareness of the QT-prolonging effects of many common medications,” the researchers say.
The study was published Aug. 5 in JACC Clinical Electrophysiology.
Both hydroxychloroquine and azithromycin increase the risk for QTc-interval prolongation by blocking the KCHN2-encoded hERG potassium channel. Several reports have linked the drugs to a triggering of QT prolongation in patients with COVID-19.
For the present study, Dr. Haines and colleagues examined data from 586 consecutive patients admitted with COVID-19 to the Beaumont Hospitals in Royal Oak and Troy, Mich., between March 13 and April 6. A baseline QTc interval was measured with 12-lead ECG prior to treatment initiation with hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily for 4 days, and azithromycin 500 mg once followed by 250 mg daily for 4 days.
Because of limited availability at the time, lead II ECG telemetry monitoring over the 5-day course of HCQ/AZM was recommended only in patients with baseline QTc intervals of at least 440 msec.
Patients without an interpretable baseline ECG or available telemetry/ECG monitoring for at least 1 day were also excluded, leaving 415 patients (mean age, 64 years; 45% female) in the study population. More than half (52%) were Black, 52% had hypertension, 30% had diabetes, and 14% had cancer.
As seen in previous studies, the QTc interval increased progressively and significantly after the administration of HCQ/AZM, from 443 msec to 473 msec.
The average time to maximum QTc was 2.9 days in a subset of 135 patients with QTc measurements prior to starting therapy and on days 1 through 5.
In multivariate analysis, independent predictors of a potentially hazardous QTc interval of at least 500 msec were:
- Age older than 65 years (odds ratio, 3.0; 95% confidence interval, 1.62-5.54).
- History of (OR, 4.65; 95% CI, 2.01-10.74).
- Admission of at least 1.5 mg/dL (OR, 2.22; 95% CI, 1.28-3.84).
- Peak troponin I level above 0.04 mg/mL (OR, 3.89; 95% CI, 2.22-6.83).
- Body mass index below 30 kg/m2 (OR for a BMI of 30 kg/m2 or higher, 0.45; 95% CI, 0.26-0.78).
Concomitant use of drugs with known risk for torsade de pointes was a significant risk factor in univariate analysis (OR, 1.73; P = .036), but fell out in the multivariate model.
No patients experienced high-grade arrhythmias during the study. In all, 112 of the 586 patients died during hospitalization, including 85 (21%) of the 415 study patients.
The change in QTc interval from baseline was greater in patients who died. Despite this, the only independent predictor of mortality was older age. One possible explanation is that the decision to monitor patients with baseline QTc intervals of at least 440 msec may have skewed the study population toward people with moderate or slightly long QTc intervals prior to the initiation of HCQ/AZM, Dr. Haines suggested. Monitoring and treatment duration were short, and clinicians also likely adjusted medications when excess QTc prolongation was observed.
Although it’s been months since data collection was completed in April, and the paper was written in record-breaking time, the study “is still very relevant because the drug is still out there,” observed Dr. Haines. “Even though it may not be used in as widespread a fashion as it had been when we first submitted the paper, it is still being used routinely by many hospitals and many practitioners.”
The use of hydroxychloroquine is “going through the roof” because of COVID-19, commented Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, HCA Midwest Health, Overland Park, Kan., who was not involved in the study.
“This study is very relevant, and I’m glad they shared their experience, and it’s pretty consistent with the data presented by other people. The question of whether hydroxychloroquine helps people with COVID is up for debate, but there is more evidence today that it is not as helpful as it was 3 months ago,” said Dr. Lakkireddy, who is also chair of the American College of Cardiology Electrophysiology Council.
He expressed concern for patients who may be taking HCQ with other medications that have QT-prolonging effects, and for the lack of long-term protocols in place for the drug.
In the coming weeks, however, the ACC and rheumatology leaders will be publishing an expert consensus statement that addresses key issues, such as how to best to use HCQ, maintenance HCQ, electrolyte monitoring, the optimal timing of electrocardiography and cardiac magnetic imaging, and symptoms to look for if cardiac involvement is suspected, Dr. Lakkireddy said.
Asked whether HCQ and AZM should be used in COVID-19 patients, Dr. Haines said in an interview that the “QT-prolonging effects are real, the arrhythmogenic potential is real, and the benefit to patients is nil or marginal. So I think that use of these drugs is appropriate and reasonable if it is done in a setting of a controlled trial, and I support that. But the routine use of these drugs probably is not warranted based on the data that we have available.”
Still, hydroxychloroquine continues to be dragged into the spotlight in recent days as an effective treatment for COVID-19, despite discredited research and the U.S. Food and Drug Administration’s June 15 revocation of its emergency-use authorization to allow use of HCQ and chloroquine to treat certain hospitalized COVID-19 patients.
“The unfortunate politicization of this issue has really muddied the waters because the general public doesn’t know what to believe or who to believe. The fact that treatment for a disease as serious as COVID should be modulated by political affiliation is just crazy to me,” said Dr. Haines. “We should be using the best science and taking careful observations, and whatever the recommendations derived from that should be uniformly adopted by everybody, irrespective of your political affiliation.”
Dr. Haines has received honoraria from Biosense Webster, Farapulse, and Sagentia, and is a consultant for Affera, Boston Scientific, Integer, Medtronic, Philips Healthcare, and Zoll. Dr. Lakkireddy has served as a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.
A version of this article originally appeared on Medscape.com.