MDedge Emergency Medicine

A fourth dose of the Pfizer-BioNTech vaccine is effective in reducing the short-term risk for COVID-19 infection, hospitalization, and death in people who got a third dose at least 4 months before, a large study shows.

However, Paul Offit, MD, author of an editorial accompanying the study, told this news organization, “I would argue, without fear of contradiction, that this is going to have no impact on this pandemic.”

“We are still in the midst of a zero-tolerance policy for this virus. We don’t accept mild illness and if we’re not going to accept mild illness, we think we have to boost it away, which would mean probably about two doses every year. That’s not a reasonable public health strategy,” said Dr. Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
 

Booster confusion

Results of the research out of Israel, published in the New England Journal of Medicine, make a case for a fourth booster for people 60 and over.

Researchers, led by Ori Magen, MD, Clalit Research Institute, innovation division, Clalit Health Services, Tel Aviv, analyzed data comparing 182,122 matched pairs recorded by the largest health care organization in Israel from Jan. 3 to Feb. 18, 2022. With more than 4.7 million members, Clalit Health Services covers more than half of the population of Israel.

The researchers compared outcomes in people 60 or older (average age, 72 years) who got a fourth dose with outcomes in those who had only a third dose. They individually matched people from the two groups, considering factors such as age, health status, and ethnicity.

Relative vaccine effectiveness in days 7-30 after the fourth dose was estimated to be 45% (95% confidence interval, 44%-47%) against confirmed SARS-CoV-2 infection, 55% (95% CI, 53%-58%) against symptomatic COVID-19, 68% (95% CI, 59%-74%) against hospitalization, 62% (95% CI, 50%-74%) against severe COVID, and 74% (95% CI, 50%-90%) against COVID-related death.

Several countries, including the United States, have begun offering a fourth vaccine dose for higher-risk populations in light of evidence of waning immunity after the third dose and waves of infection, driven by Omicron and its variants, in some parts of the world. But the recommended age groups differ considerably.

In the United States, for instance, the Food and Drug Administration in late March approved a fourth dose of the Pfizer or Moderna vaccine for anyone over 50 and people over 18 who have gotten a solid organ transplant or have a similar level of immune risk.

Dr. Offit pointed out that Israel offers the fourth vaccine for people 60 and over and the European Medical Association offers it for those over 80. No surprise that confusion over the fourth dose is rampant.
 

Booster advice

Dr. Offit offered this perspective: People who are immunocompromised could reasonably get a fourth dose, depending on the manner in which they are compromised.

“Someone who has a solid organ transplant is not the same as someone who is getting a monoclonal antibody for their rheumatoid arthritis,” Dr. Offit said, adding that people could also make a reasonable argument for the fourth dose if they are over 65 and have multiple comorbidities.

“I’m over 65,” Dr. Offit said. “I’m generally healthy. I’m not going to get a fourth dose.”

People with multiple comorbidities over age 12 could reasonably get a third dose, he said. “For everybody else – healthy people less than 65 – I would argue this is a two-dose vaccine.”

CHOP, he noted as an example, mandates the vaccine but doesn’t mandate three doses and he says that’s not unusual for hospital systems.

“How many lives are you really saving with that fourth dose? If you really want to have an effect on this pandemic, vaccinate the unvaccinated,” Dr. Offit said.
 

Focus on the memory cells

Dr. Offit wrote in the editorial: “Arguably, the most disappointing error surrounding the use of COVID-19 vaccines was the labeling of mild illnesses or asymptomatic infections after vaccination as ‘breakthroughs.’ As is true for all mucosal vaccines, the goal is to protect against serious illness – to keep people out of the hospital, intensive care unit, and morgue. The term ‘breakthrough,’ which implies failure, created unrealistic expectations and led to the adoption of a zero-tolerance strategy for this virus.”

Dr. Offit said that the focus should be on the memory cells, not the neutralizing antibodies.

Regarding mRNA vaccines, Dr. Offit said “the surprise of this vaccine – it surprised me and other vaccine researchers – is that with these two doses of mRNA separated by 3-4 weeks, you actually appear to have long-lived memory response.

“That’s not the history of vaccines. If you look at the inactivated polio vaccine or the inactivated hepatitis A vaccine, you really do need a 4- to 6-month interval between doses to get high frequencies of memory cells. That doesn’t appear to be the case here. It looks like two doses given close together do just that. Memory cells last for years if not, sometimes, decades.”

Neutralizing antibodies, on the other hand, protect against mild illness and their effectiveness wanes after months.

“At some point we are going to have to get used to mild illness,” Dr. Offit said.

The Centers for Disease Control and Prevention must now determine who will benefit most from booster dosing and educate the public about the limits of mucosal vaccines, Dr. Offit wrote in the editorial.

“Otherwise, a zero-tolerance strategy for mild or asymptomatic infection, which can be implemented only with frequent booster doses, will continue to mislead the public about what COVID-19 vaccines can and cannot do.”

The work was funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.

A version of this article first appeared on Medscape.com.

A fourth dose of the Pfizer-BioNTech vaccine is effective in reducing the short-term risk for COVID-19 infection, hospitalization, and death in people who got a third dose at least 4 months before, a large study shows.

However, Paul Offit, MD, author of an editorial accompanying the study, told this news organization, “I would argue, without fear of contradiction, that this is going to have no impact on this pandemic.”

“We are still in the midst of a zero-tolerance policy for this virus. We don’t accept mild illness and if we’re not going to accept mild illness, we think we have to boost it away, which would mean probably about two doses every year. That’s not a reasonable public health strategy,” said Dr. Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
 

Booster confusion

Results of the research out of Israel, published in the New England Journal of Medicine, make a case for a fourth booster for people 60 and over.

Researchers, led by Ori Magen, MD, Clalit Research Institute, innovation division, Clalit Health Services, Tel Aviv, analyzed data comparing 182,122 matched pairs recorded by the largest health care organization in Israel from Jan. 3 to Feb. 18, 2022. With more than 4.7 million members, Clalit Health Services covers more than half of the population of Israel.

The researchers compared outcomes in people 60 or older (average age, 72 years) who got a fourth dose with outcomes in those who had only a third dose. They individually matched people from the two groups, considering factors such as age, health status, and ethnicity.

Relative vaccine effectiveness in days 7-30 after the fourth dose was estimated to be 45% (95% confidence interval, 44%-47%) against confirmed SARS-CoV-2 infection, 55% (95% CI, 53%-58%) against symptomatic COVID-19, 68% (95% CI, 59%-74%) against hospitalization, 62% (95% CI, 50%-74%) against severe COVID, and 74% (95% CI, 50%-90%) against COVID-related death.

Several countries, including the United States, have begun offering a fourth vaccine dose for higher-risk populations in light of evidence of waning immunity after the third dose and waves of infection, driven by Omicron and its variants, in some parts of the world. But the recommended age groups differ considerably.

In the United States, for instance, the Food and Drug Administration in late March approved a fourth dose of the Pfizer or Moderna vaccine for anyone over 50 and people over 18 who have gotten a solid organ transplant or have a similar level of immune risk.

Dr. Offit pointed out that Israel offers the fourth vaccine for people 60 and over and the European Medical Association offers it for those over 80. No surprise that confusion over the fourth dose is rampant.
 

Booster advice

Dr. Offit offered this perspective: People who are immunocompromised could reasonably get a fourth dose, depending on the manner in which they are compromised.

“Someone who has a solid organ transplant is not the same as someone who is getting a monoclonal antibody for their rheumatoid arthritis,” Dr. Offit said, adding that people could also make a reasonable argument for the fourth dose if they are over 65 and have multiple comorbidities.

“I’m over 65,” Dr. Offit said. “I’m generally healthy. I’m not going to get a fourth dose.”

People with multiple comorbidities over age 12 could reasonably get a third dose, he said. “For everybody else – healthy people less than 65 – I would argue this is a two-dose vaccine.”

CHOP, he noted as an example, mandates the vaccine but doesn’t mandate three doses and he says that’s not unusual for hospital systems.

“How many lives are you really saving with that fourth dose? If you really want to have an effect on this pandemic, vaccinate the unvaccinated,” Dr. Offit said.
 

Focus on the memory cells

Dr. Offit wrote in the editorial: “Arguably, the most disappointing error surrounding the use of COVID-19 vaccines was the labeling of mild illnesses or asymptomatic infections after vaccination as ‘breakthroughs.’ As is true for all mucosal vaccines, the goal is to protect against serious illness – to keep people out of the hospital, intensive care unit, and morgue. The term ‘breakthrough,’ which implies failure, created unrealistic expectations and led to the adoption of a zero-tolerance strategy for this virus.”

Dr. Offit said that the focus should be on the memory cells, not the neutralizing antibodies.

Regarding mRNA vaccines, Dr. Offit said “the surprise of this vaccine – it surprised me and other vaccine researchers – is that with these two doses of mRNA separated by 3-4 weeks, you actually appear to have long-lived memory response.

“That’s not the history of vaccines. If you look at the inactivated polio vaccine or the inactivated hepatitis A vaccine, you really do need a 4- to 6-month interval between doses to get high frequencies of memory cells. That doesn’t appear to be the case here. It looks like two doses given close together do just that. Memory cells last for years if not, sometimes, decades.”

Neutralizing antibodies, on the other hand, protect against mild illness and their effectiveness wanes after months.

“At some point we are going to have to get used to mild illness,” Dr. Offit said.

The Centers for Disease Control and Prevention must now determine who will benefit most from booster dosing and educate the public about the limits of mucosal vaccines, Dr. Offit wrote in the editorial.

“Otherwise, a zero-tolerance strategy for mild or asymptomatic infection, which can be implemented only with frequent booster doses, will continue to mislead the public about what COVID-19 vaccines can and cannot do.”

The work was funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.

A version of this article first appeared on Medscape.com.

A fourth dose of the Pfizer-BioNTech vaccine is effective in reducing the short-term risk for COVID-19 infection, hospitalization, and death in people who got a third dose at least 4 months before, a large study shows.

However, Paul Offit, MD, author of an editorial accompanying the study, told this news organization, “I would argue, without fear of contradiction, that this is going to have no impact on this pandemic.”

“We are still in the midst of a zero-tolerance policy for this virus. We don’t accept mild illness and if we’re not going to accept mild illness, we think we have to boost it away, which would mean probably about two doses every year. That’s not a reasonable public health strategy,” said Dr. Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
 

Booster confusion

Results of the research out of Israel, published in the New England Journal of Medicine, make a case for a fourth booster for people 60 and over.

Researchers, led by Ori Magen, MD, Clalit Research Institute, innovation division, Clalit Health Services, Tel Aviv, analyzed data comparing 182,122 matched pairs recorded by the largest health care organization in Israel from Jan. 3 to Feb. 18, 2022. With more than 4.7 million members, Clalit Health Services covers more than half of the population of Israel.

The researchers compared outcomes in people 60 or older (average age, 72 years) who got a fourth dose with outcomes in those who had only a third dose. They individually matched people from the two groups, considering factors such as age, health status, and ethnicity.

Relative vaccine effectiveness in days 7-30 after the fourth dose was estimated to be 45% (95% confidence interval, 44%-47%) against confirmed SARS-CoV-2 infection, 55% (95% CI, 53%-58%) against symptomatic COVID-19, 68% (95% CI, 59%-74%) against hospitalization, 62% (95% CI, 50%-74%) against severe COVID, and 74% (95% CI, 50%-90%) against COVID-related death.

Several countries, including the United States, have begun offering a fourth vaccine dose for higher-risk populations in light of evidence of waning immunity after the third dose and waves of infection, driven by Omicron and its variants, in some parts of the world. But the recommended age groups differ considerably.

In the United States, for instance, the Food and Drug Administration in late March approved a fourth dose of the Pfizer or Moderna vaccine for anyone over 50 and people over 18 who have gotten a solid organ transplant or have a similar level of immune risk.

Dr. Offit pointed out that Israel offers the fourth vaccine for people 60 and over and the European Medical Association offers it for those over 80. No surprise that confusion over the fourth dose is rampant.
 

Booster advice

Dr. Offit offered this perspective: People who are immunocompromised could reasonably get a fourth dose, depending on the manner in which they are compromised.

“Someone who has a solid organ transplant is not the same as someone who is getting a monoclonal antibody for their rheumatoid arthritis,” Dr. Offit said, adding that people could also make a reasonable argument for the fourth dose if they are over 65 and have multiple comorbidities.

“I’m over 65,” Dr. Offit said. “I’m generally healthy. I’m not going to get a fourth dose.”

People with multiple comorbidities over age 12 could reasonably get a third dose, he said. “For everybody else – healthy people less than 65 – I would argue this is a two-dose vaccine.”

CHOP, he noted as an example, mandates the vaccine but doesn’t mandate three doses and he says that’s not unusual for hospital systems.

“How many lives are you really saving with that fourth dose? If you really want to have an effect on this pandemic, vaccinate the unvaccinated,” Dr. Offit said.
 

Focus on the memory cells

Dr. Offit wrote in the editorial: “Arguably, the most disappointing error surrounding the use of COVID-19 vaccines was the labeling of mild illnesses or asymptomatic infections after vaccination as ‘breakthroughs.’ As is true for all mucosal vaccines, the goal is to protect against serious illness – to keep people out of the hospital, intensive care unit, and morgue. The term ‘breakthrough,’ which implies failure, created unrealistic expectations and led to the adoption of a zero-tolerance strategy for this virus.”

Dr. Offit said that the focus should be on the memory cells, not the neutralizing antibodies.

Regarding mRNA vaccines, Dr. Offit said “the surprise of this vaccine – it surprised me and other vaccine researchers – is that with these two doses of mRNA separated by 3-4 weeks, you actually appear to have long-lived memory response.

“That’s not the history of vaccines. If you look at the inactivated polio vaccine or the inactivated hepatitis A vaccine, you really do need a 4- to 6-month interval between doses to get high frequencies of memory cells. That doesn’t appear to be the case here. It looks like two doses given close together do just that. Memory cells last for years if not, sometimes, decades.”

Neutralizing antibodies, on the other hand, protect against mild illness and their effectiveness wanes after months.

“At some point we are going to have to get used to mild illness,” Dr. Offit said.

The Centers for Disease Control and Prevention must now determine who will benefit most from booster dosing and educate the public about the limits of mucosal vaccines, Dr. Offit wrote in the editorial.

“Otherwise, a zero-tolerance strategy for mild or asymptomatic infection, which can be implemented only with frequent booster doses, will continue to mislead the public about what COVID-19 vaccines can and cannot do.”

The work was funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.

A version of this article first appeared on Medscape.com.

New research suggests that the casirivimab-imdevimab monoclonal antibody treatment for COVID-19 could have been delivered via injection instead of intravenously. There was no statistically significant difference in 28-day hospitalization or death in those treated intravenously and via subcutaneous injection.

The findings, published in JAMA Network Open, aren’t directly relevant at the moment, since the casirivimab-imdevimab treatment was abandoned when it failed to work during the Omicron outbreak. However, they point toward the importance of studying multiple routes of administration, said study lead author and pharmacist Erin K. McCreary, PharmD, of the University of Pittsburgh, in an interview.

“It would be beneficial for all future monoclonal antibodies for COVID-19 to be studied subcutaneously or intramuscularly, if possible, since that’s logistically easier than IV in the outpatient setting,” she said.

According to Dr. McCreary, an outpatient casirivimab-imdevimab treatment was used from 2020 to 2022 to treat higher-risk patients with mild to moderate COVID-19. The treatment was typically given intravenously as recommended by the federal government’s Emergency Use Authorization, she said. Clinical trials of the treatment, according to the study, allowed only IV administration.

“However, during the Delta surge, we were faced with so many patient referrals for treatment and staffing shortages that we couldn’t accommodate every patient unless we switched to [the] subcutaneous route,” Dr. McCreary said. This approach shortened appointment times by 30 minutes vs. infusion, she said.

There are many benefits to subcutaneous administration versus IV, Dr. McCreary said. “You don’t need to start an intravenous line, so you avoid the line kit and the nursing time needed for that. You draw up the drug directly into syringes and inject under the skin, so you avoid the need for a fluid bag to mix the drug in and run intravenously,” she said. “The appointment times are shorter, so you can accommodate more patients per day. Pharmacy interns can give subcutaneous injections, so you avoid the need for a nurse trained in placing intravenous lines.”

The researchers prospectively assigned 1,959 matched adults with mild to moderate COVID-19 to subcutaneous or intravenous treatment. Of 969 patients who received the subcutaneous treatment (mean age, 53.8; 56.4% women), the 28-day rate of hospitalization or death was 3.4%. Of 1,216 patients who received intravenous treatment (mean age, 54.3; 54.4% women), the rate was 1.7%. The difference was not statistically significant (P = .16).

Among 1,306 nontreated controls, 7.0% were hospitalized or died within 28 days (risk ratio = 0.48 vs. subcutaneous treatment group; 95% confidence interval, 0.30-0.80; P = .002).

“We did not find any patients where IV is a must,” Dr. McCreary said. “However, our study wasn’t powered to see a difference in certain subgroups.”

In an interview, University of Toronto internal medicine and pharmacology/toxicology physician Peter Wu, MD, said he agrees that the study has value because it emphasizes the importance of testing whether monoclonal antibodies can be administered in ways other than intravenously.

However, in the larger picture, he said, this may be irrelevant since it’s clear that anti-spike treatments are not holding up against COVID-19 variants.

No study funding is reported. Some study authors reported disclosures outside the submitted work. Dr. Wu has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New research suggests that the casirivimab-imdevimab monoclonal antibody treatment for COVID-19 could have been delivered via injection instead of intravenously. There was no statistically significant difference in 28-day hospitalization or death in those treated intravenously and via subcutaneous injection.

The findings, published in JAMA Network Open, aren’t directly relevant at the moment, since the casirivimab-imdevimab treatment was abandoned when it failed to work during the Omicron outbreak. However, they point toward the importance of studying multiple routes of administration, said study lead author and pharmacist Erin K. McCreary, PharmD, of the University of Pittsburgh, in an interview.

“It would be beneficial for all future monoclonal antibodies for COVID-19 to be studied subcutaneously or intramuscularly, if possible, since that’s logistically easier than IV in the outpatient setting,” she said.

According to Dr. McCreary, an outpatient casirivimab-imdevimab treatment was used from 2020 to 2022 to treat higher-risk patients with mild to moderate COVID-19. The treatment was typically given intravenously as recommended by the federal government’s Emergency Use Authorization, she said. Clinical trials of the treatment, according to the study, allowed only IV administration.

“However, during the Delta surge, we were faced with so many patient referrals for treatment and staffing shortages that we couldn’t accommodate every patient unless we switched to [the] subcutaneous route,” Dr. McCreary said. This approach shortened appointment times by 30 minutes vs. infusion, she said.

There are many benefits to subcutaneous administration versus IV, Dr. McCreary said. “You don’t need to start an intravenous line, so you avoid the line kit and the nursing time needed for that. You draw up the drug directly into syringes and inject under the skin, so you avoid the need for a fluid bag to mix the drug in and run intravenously,” she said. “The appointment times are shorter, so you can accommodate more patients per day. Pharmacy interns can give subcutaneous injections, so you avoid the need for a nurse trained in placing intravenous lines.”

The researchers prospectively assigned 1,959 matched adults with mild to moderate COVID-19 to subcutaneous or intravenous treatment. Of 969 patients who received the subcutaneous treatment (mean age, 53.8; 56.4% women), the 28-day rate of hospitalization or death was 3.4%. Of 1,216 patients who received intravenous treatment (mean age, 54.3; 54.4% women), the rate was 1.7%. The difference was not statistically significant (P = .16).

Among 1,306 nontreated controls, 7.0% were hospitalized or died within 28 days (risk ratio = 0.48 vs. subcutaneous treatment group; 95% confidence interval, 0.30-0.80; P = .002).

“We did not find any patients where IV is a must,” Dr. McCreary said. “However, our study wasn’t powered to see a difference in certain subgroups.”

In an interview, University of Toronto internal medicine and pharmacology/toxicology physician Peter Wu, MD, said he agrees that the study has value because it emphasizes the importance of testing whether monoclonal antibodies can be administered in ways other than intravenously.

However, in the larger picture, he said, this may be irrelevant since it’s clear that anti-spike treatments are not holding up against COVID-19 variants.

No study funding is reported. Some study authors reported disclosures outside the submitted work. Dr. Wu has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New research suggests that the casirivimab-imdevimab monoclonal antibody treatment for COVID-19 could have been delivered via injection instead of intravenously. There was no statistically significant difference in 28-day hospitalization or death in those treated intravenously and via subcutaneous injection.

The findings, published in JAMA Network Open, aren’t directly relevant at the moment, since the casirivimab-imdevimab treatment was abandoned when it failed to work during the Omicron outbreak. However, they point toward the importance of studying multiple routes of administration, said study lead author and pharmacist Erin K. McCreary, PharmD, of the University of Pittsburgh, in an interview.

“It would be beneficial for all future monoclonal antibodies for COVID-19 to be studied subcutaneously or intramuscularly, if possible, since that’s logistically easier than IV in the outpatient setting,” she said.

According to Dr. McCreary, an outpatient casirivimab-imdevimab treatment was used from 2020 to 2022 to treat higher-risk patients with mild to moderate COVID-19. The treatment was typically given intravenously as recommended by the federal government’s Emergency Use Authorization, she said. Clinical trials of the treatment, according to the study, allowed only IV administration.

“However, during the Delta surge, we were faced with so many patient referrals for treatment and staffing shortages that we couldn’t accommodate every patient unless we switched to [the] subcutaneous route,” Dr. McCreary said. This approach shortened appointment times by 30 minutes vs. infusion, she said.

There are many benefits to subcutaneous administration versus IV, Dr. McCreary said. “You don’t need to start an intravenous line, so you avoid the line kit and the nursing time needed for that. You draw up the drug directly into syringes and inject under the skin, so you avoid the need for a fluid bag to mix the drug in and run intravenously,” she said. “The appointment times are shorter, so you can accommodate more patients per day. Pharmacy interns can give subcutaneous injections, so you avoid the need for a nurse trained in placing intravenous lines.”

The researchers prospectively assigned 1,959 matched adults with mild to moderate COVID-19 to subcutaneous or intravenous treatment. Of 969 patients who received the subcutaneous treatment (mean age, 53.8; 56.4% women), the 28-day rate of hospitalization or death was 3.4%. Of 1,216 patients who received intravenous treatment (mean age, 54.3; 54.4% women), the rate was 1.7%. The difference was not statistically significant (P = .16).

Among 1,306 nontreated controls, 7.0% were hospitalized or died within 28 days (risk ratio = 0.48 vs. subcutaneous treatment group; 95% confidence interval, 0.30-0.80; P = .002).

“We did not find any patients where IV is a must,” Dr. McCreary said. “However, our study wasn’t powered to see a difference in certain subgroups.”

In an interview, University of Toronto internal medicine and pharmacology/toxicology physician Peter Wu, MD, said he agrees that the study has value because it emphasizes the importance of testing whether monoclonal antibodies can be administered in ways other than intravenously.

However, in the larger picture, he said, this may be irrelevant since it’s clear that anti-spike treatments are not holding up against COVID-19 variants.

No study funding is reported. Some study authors reported disclosures outside the submitted work. Dr. Wu has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

No need to ‘guess what size horse you are’

Is COVID-19 warming up for yet another surge? Maybe. That means it’s also time for the return of its remora-like follower, ivermectin. Our thanks go out to the Tennessee state legislature for bringing the proven-to-be-ineffective treatment for COVID back into our hearts and minds and emergency rooms.

StockPlanets/Getty Images

Both the state House and Senate have approved a bill that allows pharmacists to dispense the antiparasitic drug without a prescription while shielding them “from any liability that could arise from dispensing ivermectin,” Nashville Public Radio reported.

The drug’s manufacturer, Merck, said over a year ago that there is “no scientific basis for a potential therapeutic effect against COVID-19 from preclinical studies … and a concerning lack of safety data.” More recently, a study published in the New England Journal of Medicine showed that ivermectin treatment had no important benefits in patients with COVID.

Last week, the bill’s Senate sponsor, Frank Niceley of Strawberry Plains, said that it was all about safety, as he explained to NPR station WPLN: “It’s a lot safer to go to your pharmacist and let him tell you how much ivermectin to take than it is to go to the co-op and guess what size horse you are.”

And on that note, here are a few more items of business that just might end up on the legislature’s calendar:

• Horses will be allowed to “share” their unused ivermectin with humans and other mammals.
• An apple a day not only keeps the doctor away, but the IRS and the FDA as well.
• Colon cleansing is more fun than humans should be allowed to have.
• TikTok videos qualify as CME.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

Speak louder, I can’t see you

With the introduction of FaceTime and the pandemic pushing work and social events to Zoom, video calls have become ubiquitous. Along the way, however, we’ve had to learn to adjust to technical difficulties. Often by yelling at the screen when the video quality is disrupted. Waving our hands and arms, speaking louder. Sound like you?

Tumisu/Pixabay

Well, a new study published in Royal Society Open Science shows that it sounds like a lot of us.

James Trujillo of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who was lead author of the paper, said on Eurekalert that “previous research has shown that speech and gestures are linked, but ours is the first to look into how visuals impact our behavior in those fields.”

He and his associates set up 40 participants in separate rooms to have conversations in pairs over a video chat. Over the course of 40 minutes, the video quality started to deteriorate from clear to extremely blurry. When the video quality was affected, participants started with gestures but as the quality continued to lessen the gestures increased and so did the decibels of their voices.

Even when the participants could barely see each other, they still gestured and their voices were even louder, positively supporting the idea that gestures and speech are a dynamically linked when it comes to communication. Even on regular phone calls, when we can’t see each other at all, people make small movements and gestures, Mr. Trujillo said.

So, the next time the Wifi is terrible and your video calls keep cutting out, don’t worry about looking foolish screaming at the computer. We’ve all been there.
 

Seek a doctor if standing at attention for more than 4 hours

Imbrochável. In Brazil, it means “unfloppable” or “flaccid proof.” It’s also a word that Brazilian president Jair Bolsonaro likes to use when referring to himself. Gives you a good idea of what he’s all about. Imagine his embarrassment when news recently broke about more than 30,000 pills of Viagra that had been secretly distributed to the Brazilian military.

PublicDomainPictures/Pixabay

The military offered a simple and plausible explanation: The Viagra had been prescribed to treat pulmonary hypertension. Fair, but when a Brazilian newspaper dug a little deeper, they found that this was not the case. The Viagra was, in general, being used for its, shall we say, traditional purpose.

Many Brazilians reacted poorly to the news that their tax dollars were being used to provide Brazilian soldiers with downstairs assistance, with the standard associated furor on social media. A rival politician, Ciro Gomes, who is planning on challenging the president in an upcoming election, had perhaps the best remark on the situation: “Unless they’re able to prove they’re developing some kind of secret weapon – capable of revolutionizing the international arms industry – it’ll be tough to justify the purchase of 35,000 units of a erectile dysfunction drug.”

Hmm, secret weapon. Well, a certain Russian fellow has made a bit of a thrust into world affairs recently. Does anyone know if Putin is sitting on a big Viagra stash?
 

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

No need to ‘guess what size horse you are’

Is COVID-19 warming up for yet another surge? Maybe. That means it’s also time for the return of its remora-like follower, ivermectin. Our thanks go out to the Tennessee state legislature for bringing the proven-to-be-ineffective treatment for COVID back into our hearts and minds and emergency rooms.

StockPlanets/Getty Images

Both the state House and Senate have approved a bill that allows pharmacists to dispense the antiparasitic drug without a prescription while shielding them “from any liability that could arise from dispensing ivermectin,” Nashville Public Radio reported.

The drug’s manufacturer, Merck, said over a year ago that there is “no scientific basis for a potential therapeutic effect against COVID-19 from preclinical studies … and a concerning lack of safety data.” More recently, a study published in the New England Journal of Medicine showed that ivermectin treatment had no important benefits in patients with COVID.

Last week, the bill’s Senate sponsor, Frank Niceley of Strawberry Plains, said that it was all about safety, as he explained to NPR station WPLN: “It’s a lot safer to go to your pharmacist and let him tell you how much ivermectin to take than it is to go to the co-op and guess what size horse you are.”

And on that note, here are a few more items of business that just might end up on the legislature’s calendar:

• Horses will be allowed to “share” their unused ivermectin with humans and other mammals.
• An apple a day not only keeps the doctor away, but the IRS and the FDA as well.
• Colon cleansing is more fun than humans should be allowed to have.
• TikTok videos qualify as CME.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

Speak louder, I can’t see you

With the introduction of FaceTime and the pandemic pushing work and social events to Zoom, video calls have become ubiquitous. Along the way, however, we’ve had to learn to adjust to technical difficulties. Often by yelling at the screen when the video quality is disrupted. Waving our hands and arms, speaking louder. Sound like you?

Tumisu/Pixabay

Well, a new study published in Royal Society Open Science shows that it sounds like a lot of us.

James Trujillo of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who was lead author of the paper, said on Eurekalert that “previous research has shown that speech and gestures are linked, but ours is the first to look into how visuals impact our behavior in those fields.”

He and his associates set up 40 participants in separate rooms to have conversations in pairs over a video chat. Over the course of 40 minutes, the video quality started to deteriorate from clear to extremely blurry. When the video quality was affected, participants started with gestures but as the quality continued to lessen the gestures increased and so did the decibels of their voices.

Even when the participants could barely see each other, they still gestured and their voices were even louder, positively supporting the idea that gestures and speech are a dynamically linked when it comes to communication. Even on regular phone calls, when we can’t see each other at all, people make small movements and gestures, Mr. Trujillo said.

So, the next time the Wifi is terrible and your video calls keep cutting out, don’t worry about looking foolish screaming at the computer. We’ve all been there.
 

Seek a doctor if standing at attention for more than 4 hours

Imbrochável. In Brazil, it means “unfloppable” or “flaccid proof.” It’s also a word that Brazilian president Jair Bolsonaro likes to use when referring to himself. Gives you a good idea of what he’s all about. Imagine his embarrassment when news recently broke about more than 30,000 pills of Viagra that had been secretly distributed to the Brazilian military.

PublicDomainPictures/Pixabay

The military offered a simple and plausible explanation: The Viagra had been prescribed to treat pulmonary hypertension. Fair, but when a Brazilian newspaper dug a little deeper, they found that this was not the case. The Viagra was, in general, being used for its, shall we say, traditional purpose.

Many Brazilians reacted poorly to the news that their tax dollars were being used to provide Brazilian soldiers with downstairs assistance, with the standard associated furor on social media. A rival politician, Ciro Gomes, who is planning on challenging the president in an upcoming election, had perhaps the best remark on the situation: “Unless they’re able to prove they’re developing some kind of secret weapon – capable of revolutionizing the international arms industry – it’ll be tough to justify the purchase of 35,000 units of a erectile dysfunction drug.”

Hmm, secret weapon. Well, a certain Russian fellow has made a bit of a thrust into world affairs recently. Does anyone know if Putin is sitting on a big Viagra stash?
 

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

No need to ‘guess what size horse you are’

Is COVID-19 warming up for yet another surge? Maybe. That means it’s also time for the return of its remora-like follower, ivermectin. Our thanks go out to the Tennessee state legislature for bringing the proven-to-be-ineffective treatment for COVID back into our hearts and minds and emergency rooms.

StockPlanets/Getty Images

Both the state House and Senate have approved a bill that allows pharmacists to dispense the antiparasitic drug without a prescription while shielding them “from any liability that could arise from dispensing ivermectin,” Nashville Public Radio reported.

The drug’s manufacturer, Merck, said over a year ago that there is “no scientific basis for a potential therapeutic effect against COVID-19 from preclinical studies … and a concerning lack of safety data.” More recently, a study published in the New England Journal of Medicine showed that ivermectin treatment had no important benefits in patients with COVID.

Last week, the bill’s Senate sponsor, Frank Niceley of Strawberry Plains, said that it was all about safety, as he explained to NPR station WPLN: “It’s a lot safer to go to your pharmacist and let him tell you how much ivermectin to take than it is to go to the co-op and guess what size horse you are.”

And on that note, here are a few more items of business that just might end up on the legislature’s calendar:

• Horses will be allowed to “share” their unused ivermectin with humans and other mammals.
• An apple a day not only keeps the doctor away, but the IRS and the FDA as well.
• Colon cleansing is more fun than humans should be allowed to have.
• TikTok videos qualify as CME.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

Speak louder, I can’t see you

With the introduction of FaceTime and the pandemic pushing work and social events to Zoom, video calls have become ubiquitous. Along the way, however, we’ve had to learn to adjust to technical difficulties. Often by yelling at the screen when the video quality is disrupted. Waving our hands and arms, speaking louder. Sound like you?

Tumisu/Pixabay

Well, a new study published in Royal Society Open Science shows that it sounds like a lot of us.

James Trujillo of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who was lead author of the paper, said on Eurekalert that “previous research has shown that speech and gestures are linked, but ours is the first to look into how visuals impact our behavior in those fields.”

He and his associates set up 40 participants in separate rooms to have conversations in pairs over a video chat. Over the course of 40 minutes, the video quality started to deteriorate from clear to extremely blurry. When the video quality was affected, participants started with gestures but as the quality continued to lessen the gestures increased and so did the decibels of their voices.

Even when the participants could barely see each other, they still gestured and their voices were even louder, positively supporting the idea that gestures and speech are a dynamically linked when it comes to communication. Even on regular phone calls, when we can’t see each other at all, people make small movements and gestures, Mr. Trujillo said.

So, the next time the Wifi is terrible and your video calls keep cutting out, don’t worry about looking foolish screaming at the computer. We’ve all been there.
 

Seek a doctor if standing at attention for more than 4 hours

Imbrochável. In Brazil, it means “unfloppable” or “flaccid proof.” It’s also a word that Brazilian president Jair Bolsonaro likes to use when referring to himself. Gives you a good idea of what he’s all about. Imagine his embarrassment when news recently broke about more than 30,000 pills of Viagra that had been secretly distributed to the Brazilian military.

PublicDomainPictures/Pixabay

The military offered a simple and plausible explanation: The Viagra had been prescribed to treat pulmonary hypertension. Fair, but when a Brazilian newspaper dug a little deeper, they found that this was not the case. The Viagra was, in general, being used for its, shall we say, traditional purpose.

Many Brazilians reacted poorly to the news that their tax dollars were being used to provide Brazilian soldiers with downstairs assistance, with the standard associated furor on social media. A rival politician, Ciro Gomes, who is planning on challenging the president in an upcoming election, had perhaps the best remark on the situation: “Unless they’re able to prove they’re developing some kind of secret weapon – capable of revolutionizing the international arms industry – it’ll be tough to justify the purchase of 35,000 units of a erectile dysfunction drug.”

Hmm, secret weapon. Well, a certain Russian fellow has made a bit of a thrust into world affairs recently. Does anyone know if Putin is sitting on a big Viagra stash?
 

A recently published set of treatment flow diagrams uses simplified diagnosis and management pathways to help primary care providers (PCPs) in Europe, the United States, and elsewhere treat patients with allergies.

Most patients with allergy problems first see PCPs, not allergists, the authors write in Allergy. The new flow diagrams help PCPs treat anaphylaxis, asthma, drug allergy, food allergy, and urticaria.

“The European Academy of Allergy and Clinical Immunology established the Logogram Task Force to create a set of simple flow diagrams to assist allergy nonspecialist, generalist, and primary care teams in the diagnosis of five common allergic diseases encountered in primary care,” lead author Dermot Ryan, MB BCh, BAO, FRGCP, of the University of Edinburgh told this news organization.

“The source documents were mainstream guidelines coupled with ancillary literature,” he added in an email. “A multi-disciplinary taskforce ... distilled these guidelines into accessible, comprehensible, usable, and context-specific flow diagrams.”
 

The flow diagrams developed in Europe can be used by providers in the United States and elsewhere

“These diagrams are consistent with practices in the U.S.,” Christina E. Ciaccio, MD, an associate professor of pediatrics and the section chief of pediatric allergy and immunology at the University of Chicago Medicine, said in an email. “They will prove helpful to PCPs in the U.S. and elsewhere, particularly to young physicians new to practice.

“Treating allergies is part of the ‘bread-and-butter’ practice of primary care physicians in the U.S.,” Dr. Ciaccio, who was not involved in developing the flow diagrams, explained. “Up to 30% of Americans are atopic, and the vast majority seek treatment advice from their PCP first.”

The flow diagrams can help providers in developing countries, where allergic diseases are common, provide the best patient care possible, she said.
 

At some point, a PCP may need to think beyond flow diagrams and refer the patient to an allergist

“If the treatment plan for a patient falls outside first- or second-line medications, or if a diagnosis is unclear with preliminary testing, a PCP may reach out to an allergy/immunology specialist to assist in providing care,” Dr. Ciaccio advised. “Allergists may provide treatment options, such as immunotherapy, that the PCP does not offer. PCPs also often reach out to allergy team members for help with patients whose allergies are not ‘run-of-the-mill.’

“The flow diagrams are complex and may not be practical in the middle of a busy clinic,” she cautioned. “However, when a patient comes into a primary care clinic with an atypical presentation of an allergic disease, the diagrams are likely to help a physician feel confident that an allergist is the right physician for consultation.”

Patricia Lynne Lugar, MD, an associate professor of medicine in pulmonary, allergy, and critical care medicine at Duke University in Durham, N.C., noted that providers in the U.S. can use the flow diagrams because the definitions, differential diagnosis, and treatments for the conditions they cover are similar.

“The flow diagrams are comprehensive, and they attempt to condense a great deal of information into summary points. They are very useful in the U.S., and not just for generalists,” Dr. Lugar, who also was not involved in the project, said. “Even emergency rooms would benefit from these flow diagrams, especially regarding the recognition of symptoms and differential diagnosis.”

Asthma and seasonal and environmental allergies are often managed by PCPs, and the flow diagrams would help them decide when to refer their patients to an allergist, she added in an email.

Dr. Lugar advises PCPs to “recognize the symptoms of an allergic condition, offer treatment based on confidence the diagnosis is correct, and offer a referral for testing to confirm the allergy.

“Because 50% or more of asthmatics are allergic, all asthmatics should be offered an allergy evaluation to determine their allergies and avoid exacerbating the asthma,” she added. “I do not see the flow diagrams as comprehensive enough to manage chronic urticaria, asthma, venom allergy, and drug allergy.”

With food allergy, environmental allergy, venom allergy, or anaphylaxis, “allergists are experts at considering the differential diagnosis and providing the next steps in the diagnostic workup,” Dr. Lugar said. “Allergists can also provide special treatments, such as allergen-specific immunotherapy or desensitization.”

The flow diagrams guide nonspecialists in diagnosis and treatment of their patients with allergy, with supplementary information as needed. The diagrams recommend referral to a specialist when appropriate, as in cases of anaphylaxis, or chronic urticaria.

A version of this article first appeared on Medscape.com.

A recently published set of treatment flow diagrams uses simplified diagnosis and management pathways to help primary care providers (PCPs) in Europe, the United States, and elsewhere treat patients with allergies.

Most patients with allergy problems first see PCPs, not allergists, the authors write in Allergy. The new flow diagrams help PCPs treat anaphylaxis, asthma, drug allergy, food allergy, and urticaria.

“The European Academy of Allergy and Clinical Immunology established the Logogram Task Force to create a set of simple flow diagrams to assist allergy nonspecialist, generalist, and primary care teams in the diagnosis of five common allergic diseases encountered in primary care,” lead author Dermot Ryan, MB BCh, BAO, FRGCP, of the University of Edinburgh told this news organization.

“The source documents were mainstream guidelines coupled with ancillary literature,” he added in an email. “A multi-disciplinary taskforce ... distilled these guidelines into accessible, comprehensible, usable, and context-specific flow diagrams.”
 

The flow diagrams developed in Europe can be used by providers in the United States and elsewhere

“These diagrams are consistent with practices in the U.S.,” Christina E. Ciaccio, MD, an associate professor of pediatrics and the section chief of pediatric allergy and immunology at the University of Chicago Medicine, said in an email. “They will prove helpful to PCPs in the U.S. and elsewhere, particularly to young physicians new to practice.

“Treating allergies is part of the ‘bread-and-butter’ practice of primary care physicians in the U.S.,” Dr. Ciaccio, who was not involved in developing the flow diagrams, explained. “Up to 30% of Americans are atopic, and the vast majority seek treatment advice from their PCP first.”

The flow diagrams can help providers in developing countries, where allergic diseases are common, provide the best patient care possible, she said.
 

At some point, a PCP may need to think beyond flow diagrams and refer the patient to an allergist

“If the treatment plan for a patient falls outside first- or second-line medications, or if a diagnosis is unclear with preliminary testing, a PCP may reach out to an allergy/immunology specialist to assist in providing care,” Dr. Ciaccio advised. “Allergists may provide treatment options, such as immunotherapy, that the PCP does not offer. PCPs also often reach out to allergy team members for help with patients whose allergies are not ‘run-of-the-mill.’

“The flow diagrams are complex and may not be practical in the middle of a busy clinic,” she cautioned. “However, when a patient comes into a primary care clinic with an atypical presentation of an allergic disease, the diagrams are likely to help a physician feel confident that an allergist is the right physician for consultation.”

Patricia Lynne Lugar, MD, an associate professor of medicine in pulmonary, allergy, and critical care medicine at Duke University in Durham, N.C., noted that providers in the U.S. can use the flow diagrams because the definitions, differential diagnosis, and treatments for the conditions they cover are similar.

“The flow diagrams are comprehensive, and they attempt to condense a great deal of information into summary points. They are very useful in the U.S., and not just for generalists,” Dr. Lugar, who also was not involved in the project, said. “Even emergency rooms would benefit from these flow diagrams, especially regarding the recognition of symptoms and differential diagnosis.”

Asthma and seasonal and environmental allergies are often managed by PCPs, and the flow diagrams would help them decide when to refer their patients to an allergist, she added in an email.

Dr. Lugar advises PCPs to “recognize the symptoms of an allergic condition, offer treatment based on confidence the diagnosis is correct, and offer a referral for testing to confirm the allergy.

“Because 50% or more of asthmatics are allergic, all asthmatics should be offered an allergy evaluation to determine their allergies and avoid exacerbating the asthma,” she added. “I do not see the flow diagrams as comprehensive enough to manage chronic urticaria, asthma, venom allergy, and drug allergy.”

With food allergy, environmental allergy, venom allergy, or anaphylaxis, “allergists are experts at considering the differential diagnosis and providing the next steps in the diagnostic workup,” Dr. Lugar said. “Allergists can also provide special treatments, such as allergen-specific immunotherapy or desensitization.”

The flow diagrams guide nonspecialists in diagnosis and treatment of their patients with allergy, with supplementary information as needed. The diagrams recommend referral to a specialist when appropriate, as in cases of anaphylaxis, or chronic urticaria.

A version of this article first appeared on Medscape.com.

A recently published set of treatment flow diagrams uses simplified diagnosis and management pathways to help primary care providers (PCPs) in Europe, the United States, and elsewhere treat patients with allergies.

Most patients with allergy problems first see PCPs, not allergists, the authors write in Allergy. The new flow diagrams help PCPs treat anaphylaxis, asthma, drug allergy, food allergy, and urticaria.

“The European Academy of Allergy and Clinical Immunology established the Logogram Task Force to create a set of simple flow diagrams to assist allergy nonspecialist, generalist, and primary care teams in the diagnosis of five common allergic diseases encountered in primary care,” lead author Dermot Ryan, MB BCh, BAO, FRGCP, of the University of Edinburgh told this news organization.

“The source documents were mainstream guidelines coupled with ancillary literature,” he added in an email. “A multi-disciplinary taskforce ... distilled these guidelines into accessible, comprehensible, usable, and context-specific flow diagrams.”
 

The flow diagrams developed in Europe can be used by providers in the United States and elsewhere

“These diagrams are consistent with practices in the U.S.,” Christina E. Ciaccio, MD, an associate professor of pediatrics and the section chief of pediatric allergy and immunology at the University of Chicago Medicine, said in an email. “They will prove helpful to PCPs in the U.S. and elsewhere, particularly to young physicians new to practice.

“Treating allergies is part of the ‘bread-and-butter’ practice of primary care physicians in the U.S.,” Dr. Ciaccio, who was not involved in developing the flow diagrams, explained. “Up to 30% of Americans are atopic, and the vast majority seek treatment advice from their PCP first.”

The flow diagrams can help providers in developing countries, where allergic diseases are common, provide the best patient care possible, she said.
 

At some point, a PCP may need to think beyond flow diagrams and refer the patient to an allergist

“If the treatment plan for a patient falls outside first- or second-line medications, or if a diagnosis is unclear with preliminary testing, a PCP may reach out to an allergy/immunology specialist to assist in providing care,” Dr. Ciaccio advised. “Allergists may provide treatment options, such as immunotherapy, that the PCP does not offer. PCPs also often reach out to allergy team members for help with patients whose allergies are not ‘run-of-the-mill.’

“The flow diagrams are complex and may not be practical in the middle of a busy clinic,” she cautioned. “However, when a patient comes into a primary care clinic with an atypical presentation of an allergic disease, the diagrams are likely to help a physician feel confident that an allergist is the right physician for consultation.”

Patricia Lynne Lugar, MD, an associate professor of medicine in pulmonary, allergy, and critical care medicine at Duke University in Durham, N.C., noted that providers in the U.S. can use the flow diagrams because the definitions, differential diagnosis, and treatments for the conditions they cover are similar.

“The flow diagrams are comprehensive, and they attempt to condense a great deal of information into summary points. They are very useful in the U.S., and not just for generalists,” Dr. Lugar, who also was not involved in the project, said. “Even emergency rooms would benefit from these flow diagrams, especially regarding the recognition of symptoms and differential diagnosis.”

Asthma and seasonal and environmental allergies are often managed by PCPs, and the flow diagrams would help them decide when to refer their patients to an allergist, she added in an email.

Dr. Lugar advises PCPs to “recognize the symptoms of an allergic condition, offer treatment based on confidence the diagnosis is correct, and offer a referral for testing to confirm the allergy.

“Because 50% or more of asthmatics are allergic, all asthmatics should be offered an allergy evaluation to determine their allergies and avoid exacerbating the asthma,” she added. “I do not see the flow diagrams as comprehensive enough to manage chronic urticaria, asthma, venom allergy, and drug allergy.”

With food allergy, environmental allergy, venom allergy, or anaphylaxis, “allergists are experts at considering the differential diagnosis and providing the next steps in the diagnostic workup,” Dr. Lugar said. “Allergists can also provide special treatments, such as allergen-specific immunotherapy or desensitization.”

The flow diagrams guide nonspecialists in diagnosis and treatment of their patients with allergy, with supplementary information as needed. The diagrams recommend referral to a specialist when appropriate, as in cases of anaphylaxis, or chronic urticaria.

A version of this article first appeared on Medscape.com.

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

People who use phosphodiesterase type 5 inhibitors (PDE5Is), a class of medications most often prescribed for erectile dysfunction, may run an increased risk of vision-threatening ocular conditions, researchers say.

Patients in an insurance database who were prescribed sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), or avanafil (Stendra) were almost twice as likely as were patients not prescribed the drugs to have ischemic optic neuropathy, retinal vascular occlusion, or serous retinal detachment.

In 2020, physicians wrote about 20 million monthly prescriptions for PDE5Is in the United States alone, said Mahyar Etminan, PharmD, associate professor of ophthalmology at the University of British Columbia, Vancouver.

“We don’t want to alarm people taking them, but generally speaking, if they experience visual problems or changes in vision, then these drugs may be the culprits, and they should check it out,” he said in an interview.

The study was published in JAMA Ophthalmology.

Previous reports, including postmarketing studies by the drug makers, have documented ocular events. The monographs for sildenafil, tadalafil, vardenafil, and avanafil warn users about ischemic optic neuropathy, the researchers found.

The monographs for sildenafil, tadalafil, and vardenafil list retinal vascular occlusion as a potential adverse event but do not quantify the risk. None of the drug monographs mention serous retinal detachment.

Previous research has associated PDE5Is with compromised perfusion of the optic nerve. Some researchers have speculated that the choroid blood vessels can undergo smooth muscle relaxation through a cyclic guanosine monophosphate pathway that can lead to choroidal congestion.

To get a better handle on the ocular risks of PDE51s, Dr. Etminan and his colleagues analyzed health insurance claim records from the PharMetrics Plus database of 213,033 men who had not experienced any of the three ocular conditions in the year before they became regular users of the medications.

They identified 1,146 patients who had been diagnosed with at least one of the three conditions.

The overall number of conditions diagnosed was small relative to the size of the population, 15.5 cases per 10,000 person-years. “So that’s still relatively rare, but the problem is that these are very heavily used medications,” Dr. Etminan said.

For each man diagnosed with one of the ocular conditions, the researchers matched four control persons who were the same age and could be followed for the same length of time. There was a total of 4,584 control persons.

The researchers compared regular users of PDE5Is (those who had received at least one prescription for a PDE5I every 3 months in the year before the ocular diagnosis) with nonusers (those who had not received a PDE5I prescription during that time).

Patients with the ocular conditions were more likely than were those in the control group to have hypertension, diabetes, cardiovascular disease, or sleep apnea. After controlling for these covariates, the researchers found that the users were overall 85% more likely to be diagnosed with one or more of them (incidence rate ratio [IRR], 1.85).

A version of this article first appeared on Medscape.com

People who use phosphodiesterase type 5 inhibitors (PDE5Is), a class of medications most often prescribed for erectile dysfunction, may run an increased risk of vision-threatening ocular conditions, researchers say.

Patients in an insurance database who were prescribed sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), or avanafil (Stendra) were almost twice as likely as were patients not prescribed the drugs to have ischemic optic neuropathy, retinal vascular occlusion, or serous retinal detachment.

In 2020, physicians wrote about 20 million monthly prescriptions for PDE5Is in the United States alone, said Mahyar Etminan, PharmD, associate professor of ophthalmology at the University of British Columbia, Vancouver.

“We don’t want to alarm people taking them, but generally speaking, if they experience visual problems or changes in vision, then these drugs may be the culprits, and they should check it out,” he said in an interview.

The study was published in JAMA Ophthalmology.

Previous reports, including postmarketing studies by the drug makers, have documented ocular events. The monographs for sildenafil, tadalafil, vardenafil, and avanafil warn users about ischemic optic neuropathy, the researchers found.

The monographs for sildenafil, tadalafil, and vardenafil list retinal vascular occlusion as a potential adverse event but do not quantify the risk. None of the drug monographs mention serous retinal detachment.

Previous research has associated PDE5Is with compromised perfusion of the optic nerve. Some researchers have speculated that the choroid blood vessels can undergo smooth muscle relaxation through a cyclic guanosine monophosphate pathway that can lead to choroidal congestion.

To get a better handle on the ocular risks of PDE51s, Dr. Etminan and his colleagues analyzed health insurance claim records from the PharMetrics Plus database of 213,033 men who had not experienced any of the three ocular conditions in the year before they became regular users of the medications.

They identified 1,146 patients who had been diagnosed with at least one of the three conditions.

The overall number of conditions diagnosed was small relative to the size of the population, 15.5 cases per 10,000 person-years. “So that’s still relatively rare, but the problem is that these are very heavily used medications,” Dr. Etminan said.

For each man diagnosed with one of the ocular conditions, the researchers matched four control persons who were the same age and could be followed for the same length of time. There was a total of 4,584 control persons.

The researchers compared regular users of PDE5Is (those who had received at least one prescription for a PDE5I every 3 months in the year before the ocular diagnosis) with nonusers (those who had not received a PDE5I prescription during that time).

Patients with the ocular conditions were more likely than were those in the control group to have hypertension, diabetes, cardiovascular disease, or sleep apnea. After controlling for these covariates, the researchers found that the users were overall 85% more likely to be diagnosed with one or more of them (incidence rate ratio [IRR], 1.85).

A version of this article first appeared on Medscape.com

People who use phosphodiesterase type 5 inhibitors (PDE5Is), a class of medications most often prescribed for erectile dysfunction, may run an increased risk of vision-threatening ocular conditions, researchers say.

Patients in an insurance database who were prescribed sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), or avanafil (Stendra) were almost twice as likely as were patients not prescribed the drugs to have ischemic optic neuropathy, retinal vascular occlusion, or serous retinal detachment.

In 2020, physicians wrote about 20 million monthly prescriptions for PDE5Is in the United States alone, said Mahyar Etminan, PharmD, associate professor of ophthalmology at the University of British Columbia, Vancouver.

“We don’t want to alarm people taking them, but generally speaking, if they experience visual problems or changes in vision, then these drugs may be the culprits, and they should check it out,” he said in an interview.

The study was published in JAMA Ophthalmology.

Previous reports, including postmarketing studies by the drug makers, have documented ocular events. The monographs for sildenafil, tadalafil, vardenafil, and avanafil warn users about ischemic optic neuropathy, the researchers found.

The monographs for sildenafil, tadalafil, and vardenafil list retinal vascular occlusion as a potential adverse event but do not quantify the risk. None of the drug monographs mention serous retinal detachment.

Previous research has associated PDE5Is with compromised perfusion of the optic nerve. Some researchers have speculated that the choroid blood vessels can undergo smooth muscle relaxation through a cyclic guanosine monophosphate pathway that can lead to choroidal congestion.

To get a better handle on the ocular risks of PDE51s, Dr. Etminan and his colleagues analyzed health insurance claim records from the PharMetrics Plus database of 213,033 men who had not experienced any of the three ocular conditions in the year before they became regular users of the medications.

They identified 1,146 patients who had been diagnosed with at least one of the three conditions.

The overall number of conditions diagnosed was small relative to the size of the population, 15.5 cases per 10,000 person-years. “So that’s still relatively rare, but the problem is that these are very heavily used medications,” Dr. Etminan said.

For each man diagnosed with one of the ocular conditions, the researchers matched four control persons who were the same age and could be followed for the same length of time. There was a total of 4,584 control persons.

The researchers compared regular users of PDE5Is (those who had received at least one prescription for a PDE5I every 3 months in the year before the ocular diagnosis) with nonusers (those who had not received a PDE5I prescription during that time).

Patients with the ocular conditions were more likely than were those in the control group to have hypertension, diabetes, cardiovascular disease, or sleep apnea. After controlling for these covariates, the researchers found that the users were overall 85% more likely to be diagnosed with one or more of them (incidence rate ratio [IRR], 1.85).

A version of this article first appeared on Medscape.com

Vaccinated patients with cancer are more likely than those without cancer to contract a breakthrough COVID-19 infection, which puts them at a much higher risk for hospitalization and death, according to a study published in JAMA Oncology.

The risks were highest among patients who had certain cancers and those who had received cancer treatment within the past year.

“These results emphasize the need for patients with cancer to maintain mitigation practice, especially with the emergence of different virus variants and the waning immunity of vaccines,” the study authors wrote.

Researchers at Case Western Reserve University in Cleveland analyzed electronic health record data for more than 636,000 vaccinated patients, including more than 45,000 vaccinated patients with cancer. They looked for the time trends, risks, and outcomes of breakthrough COVID-19 infections for vaccinated cancer patients in the United States between December 2020 and November 2021.

Overall, the cumulative risk of breakthrough infections in vaccinated cancer patients was 13.6%, with the highest risk for pancreatic (24.7%), liver (22.8%), lung (20.4%), and colorectal (17.5%) cancers and the lowest risk for thyroid (10.3%), endometrial (11.9%), and breast (11.9%) cancers, versus 4.9% in vaccinated patients without cancer.

Patients who had medical encounters for their cancer within the past year had a higher risk for a breakthrough infection, particularly those with breast cancer, blood cancers, colorectal cancer, bladder cancer, and pancreatic cancer.

Among patients with cancer, the overall risk for hospitalization after a breakthrough infection was 31.6%, as compared with 3.9% in those without a breakthrough infection. In addition, the risk of death was 6.7% after a breakthrough infection, as compared with 1.3% in those without a breakthrough infection.

Among patients who didn’t have cancer, the overall hospitalization risk was 25.9% in patients with a breakthrough infection, as compared with 3% in those without a breakthrough infection. The overall risk of death was 2.7% after a breakthrough infection, as compared with 0.5% in those without a breakthrough infection.

In addition, breakthrough infections continuously increased for all patients from December 2020 to November 2021, with the numbers consistently higher among patients with cancer.

“This increasing time trend may reflect waning immunity of vaccines, the emergence of different virus variants, and varied measures taken by individuals and communities over time during the pandemic,” the study authors wrote.

Vaccines are likely less protective against coronavirus infection in cancer patients, and in turn, cancer patients may be more susceptible to COVID-19 infections, the researchers wrote. As breakthrough infections continue to increase for everyone, patients with cancer will face increased risks for severe breakthroughs, hospitalization, and death, they concluded.

A version of this article first appeared on WebMD.com.

Vaccinated patients with cancer are more likely than those without cancer to contract a breakthrough COVID-19 infection, which puts them at a much higher risk for hospitalization and death, according to a study published in JAMA Oncology.

The risks were highest among patients who had certain cancers and those who had received cancer treatment within the past year.

“These results emphasize the need for patients with cancer to maintain mitigation practice, especially with the emergence of different virus variants and the waning immunity of vaccines,” the study authors wrote.

Researchers at Case Western Reserve University in Cleveland analyzed electronic health record data for more than 636,000 vaccinated patients, including more than 45,000 vaccinated patients with cancer. They looked for the time trends, risks, and outcomes of breakthrough COVID-19 infections for vaccinated cancer patients in the United States between December 2020 and November 2021.

Overall, the cumulative risk of breakthrough infections in vaccinated cancer patients was 13.6%, with the highest risk for pancreatic (24.7%), liver (22.8%), lung (20.4%), and colorectal (17.5%) cancers and the lowest risk for thyroid (10.3%), endometrial (11.9%), and breast (11.9%) cancers, versus 4.9% in vaccinated patients without cancer.

Patients who had medical encounters for their cancer within the past year had a higher risk for a breakthrough infection, particularly those with breast cancer, blood cancers, colorectal cancer, bladder cancer, and pancreatic cancer.

Among patients with cancer, the overall risk for hospitalization after a breakthrough infection was 31.6%, as compared with 3.9% in those without a breakthrough infection. In addition, the risk of death was 6.7% after a breakthrough infection, as compared with 1.3% in those without a breakthrough infection.

Among patients who didn’t have cancer, the overall hospitalization risk was 25.9% in patients with a breakthrough infection, as compared with 3% in those without a breakthrough infection. The overall risk of death was 2.7% after a breakthrough infection, as compared with 0.5% in those without a breakthrough infection.

In addition, breakthrough infections continuously increased for all patients from December 2020 to November 2021, with the numbers consistently higher among patients with cancer.

“This increasing time trend may reflect waning immunity of vaccines, the emergence of different virus variants, and varied measures taken by individuals and communities over time during the pandemic,” the study authors wrote.

Vaccines are likely less protective against coronavirus infection in cancer patients, and in turn, cancer patients may be more susceptible to COVID-19 infections, the researchers wrote. As breakthrough infections continue to increase for everyone, patients with cancer will face increased risks for severe breakthroughs, hospitalization, and death, they concluded.

A version of this article first appeared on WebMD.com.

Vaccinated patients with cancer are more likely than those without cancer to contract a breakthrough COVID-19 infection, which puts them at a much higher risk for hospitalization and death, according to a study published in JAMA Oncology.

The risks were highest among patients who had certain cancers and those who had received cancer treatment within the past year.

“These results emphasize the need for patients with cancer to maintain mitigation practice, especially with the emergence of different virus variants and the waning immunity of vaccines,” the study authors wrote.

Researchers at Case Western Reserve University in Cleveland analyzed electronic health record data for more than 636,000 vaccinated patients, including more than 45,000 vaccinated patients with cancer. They looked for the time trends, risks, and outcomes of breakthrough COVID-19 infections for vaccinated cancer patients in the United States between December 2020 and November 2021.

Overall, the cumulative risk of breakthrough infections in vaccinated cancer patients was 13.6%, with the highest risk for pancreatic (24.7%), liver (22.8%), lung (20.4%), and colorectal (17.5%) cancers and the lowest risk for thyroid (10.3%), endometrial (11.9%), and breast (11.9%) cancers, versus 4.9% in vaccinated patients without cancer.

Patients who had medical encounters for their cancer within the past year had a higher risk for a breakthrough infection, particularly those with breast cancer, blood cancers, colorectal cancer, bladder cancer, and pancreatic cancer.

Among patients with cancer, the overall risk for hospitalization after a breakthrough infection was 31.6%, as compared with 3.9% in those without a breakthrough infection. In addition, the risk of death was 6.7% after a breakthrough infection, as compared with 1.3% in those without a breakthrough infection.

Among patients who didn’t have cancer, the overall hospitalization risk was 25.9% in patients with a breakthrough infection, as compared with 3% in those without a breakthrough infection. The overall risk of death was 2.7% after a breakthrough infection, as compared with 0.5% in those without a breakthrough infection.

In addition, breakthrough infections continuously increased for all patients from December 2020 to November 2021, with the numbers consistently higher among patients with cancer.

“This increasing time trend may reflect waning immunity of vaccines, the emergence of different virus variants, and varied measures taken by individuals and communities over time during the pandemic,” the study authors wrote.

Vaccines are likely less protective against coronavirus infection in cancer patients, and in turn, cancer patients may be more susceptible to COVID-19 infections, the researchers wrote. As breakthrough infections continue to increase for everyone, patients with cancer will face increased risks for severe breakthroughs, hospitalization, and death, they concluded.

A version of this article first appeared on WebMD.com.

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

U.K. scientists said microplastics may pose even more of a threat than previously thought after confirming their presence in lung tissue taken from living people.

Microplastics were identified in all lung regions, but significantly higher levels were found in the lower lung.

The results supported inhalation as an exposure risk, according to the team from the University of Hull and Hull York Medical School (England), who said their findings could support further investigations into the effects of airborne microplastics on respiratory health.

The study, published in Science of the Total Environment, used lung tissue collected from surgical procedures on patients during routine medical care at Castle Hill Hospital in East Yorkshire.
 

Polypropylene and polyethylene

It found 39 microplastics in 11 of the 13 lung tissue samples tested using micro-Fourier-transform infrared (μFTIR) analysis, which the scientists said was considerably higher than results from previous laboratory tests.

Of microplastics detected, 12 polymer types were identified, of which the most common were polypropylene, (23%) polyethylene terephthalate (18%), and resin (15%). The fibers are commonly found in packaging, bottles, clothing, rope and twine manufacture, and other industries, the scientists said.

Microplastics with dimensions as small as 4 μm were found, but the scientists said they were surprised to discover samples as large as greater than 2 mm within all lung region samples, with the majority being fibrous and fragmented.

The study identified 11 microplastics in the upper part of the lung, seven in the mid part, and 21 in the lower part of the lung.

Laura Sadofsky, the study’s lead author, said: “Microplastics have previously been found in human cadaver autopsy samples. This is the first robust study to show microplastics in lungs from live people. It also shows that they are in the lower parts of the lung. Lung airways are very narrow, so no one thought they could possibly get there, but they clearly have.”

There were also considerably higher levels of microplastics found in male patients, compared with female patients.
 

Future investigations into health implications

“The characterization of types and levels of microplastics we have found can now inform realistic conditions for laboratory exposure experiments with the aim of determining health impacts,” said Laura Sadofsky, who is a senior lecturer in respiratory medicine in the Centre for Atherothrombotic and Metabolic Research at Hull York Medical School.

The latest investigation followed previous research by the medical school and the University of Hull, which found high levels of atmospheric microplastics within the Humber region.

That study, published in Atmosphere, identified resins, which could have originated from degraded roads, paint marking, or tire rubber, as well as polyethylene fibers.

A version of this article first appeared on Medscape UK.

U.K. scientists said microplastics may pose even more of a threat than previously thought after confirming their presence in lung tissue taken from living people.

Microplastics were identified in all lung regions, but significantly higher levels were found in the lower lung.

The results supported inhalation as an exposure risk, according to the team from the University of Hull and Hull York Medical School (England), who said their findings could support further investigations into the effects of airborne microplastics on respiratory health.

The study, published in Science of the Total Environment, used lung tissue collected from surgical procedures on patients during routine medical care at Castle Hill Hospital in East Yorkshire.
 

Polypropylene and polyethylene

It found 39 microplastics in 11 of the 13 lung tissue samples tested using micro-Fourier-transform infrared (μFTIR) analysis, which the scientists said was considerably higher than results from previous laboratory tests.

Of microplastics detected, 12 polymer types were identified, of which the most common were polypropylene, (23%) polyethylene terephthalate (18%), and resin (15%). The fibers are commonly found in packaging, bottles, clothing, rope and twine manufacture, and other industries, the scientists said.

Microplastics with dimensions as small as 4 μm were found, but the scientists said they were surprised to discover samples as large as greater than 2 mm within all lung region samples, with the majority being fibrous and fragmented.

The study identified 11 microplastics in the upper part of the lung, seven in the mid part, and 21 in the lower part of the lung.

Laura Sadofsky, the study’s lead author, said: “Microplastics have previously been found in human cadaver autopsy samples. This is the first robust study to show microplastics in lungs from live people. It also shows that they are in the lower parts of the lung. Lung airways are very narrow, so no one thought they could possibly get there, but they clearly have.”

There were also considerably higher levels of microplastics found in male patients, compared with female patients.
 

Future investigations into health implications

“The characterization of types and levels of microplastics we have found can now inform realistic conditions for laboratory exposure experiments with the aim of determining health impacts,” said Laura Sadofsky, who is a senior lecturer in respiratory medicine in the Centre for Atherothrombotic and Metabolic Research at Hull York Medical School.

The latest investigation followed previous research by the medical school and the University of Hull, which found high levels of atmospheric microplastics within the Humber region.

That study, published in Atmosphere, identified resins, which could have originated from degraded roads, paint marking, or tire rubber, as well as polyethylene fibers.

A version of this article first appeared on Medscape UK.

U.K. scientists said microplastics may pose even more of a threat than previously thought after confirming their presence in lung tissue taken from living people.

Microplastics were identified in all lung regions, but significantly higher levels were found in the lower lung.

The results supported inhalation as an exposure risk, according to the team from the University of Hull and Hull York Medical School (England), who said their findings could support further investigations into the effects of airborne microplastics on respiratory health.

The study, published in Science of the Total Environment, used lung tissue collected from surgical procedures on patients during routine medical care at Castle Hill Hospital in East Yorkshire.
 

Polypropylene and polyethylene

It found 39 microplastics in 11 of the 13 lung tissue samples tested using micro-Fourier-transform infrared (μFTIR) analysis, which the scientists said was considerably higher than results from previous laboratory tests.

Of microplastics detected, 12 polymer types were identified, of which the most common were polypropylene, (23%) polyethylene terephthalate (18%), and resin (15%). The fibers are commonly found in packaging, bottles, clothing, rope and twine manufacture, and other industries, the scientists said.

Microplastics with dimensions as small as 4 μm were found, but the scientists said they were surprised to discover samples as large as greater than 2 mm within all lung region samples, with the majority being fibrous and fragmented.

The study identified 11 microplastics in the upper part of the lung, seven in the mid part, and 21 in the lower part of the lung.

Laura Sadofsky, the study’s lead author, said: “Microplastics have previously been found in human cadaver autopsy samples. This is the first robust study to show microplastics in lungs from live people. It also shows that they are in the lower parts of the lung. Lung airways are very narrow, so no one thought they could possibly get there, but they clearly have.”

There were also considerably higher levels of microplastics found in male patients, compared with female patients.
 

Future investigations into health implications

“The characterization of types and levels of microplastics we have found can now inform realistic conditions for laboratory exposure experiments with the aim of determining health impacts,” said Laura Sadofsky, who is a senior lecturer in respiratory medicine in the Centre for Atherothrombotic and Metabolic Research at Hull York Medical School.

The latest investigation followed previous research by the medical school and the University of Hull, which found high levels of atmospheric microplastics within the Humber region.

That study, published in Atmosphere, identified resins, which could have originated from degraded roads, paint marking, or tire rubber, as well as polyethylene fibers.

A version of this article first appeared on Medscape UK.

The decline in new cases of child COVID-19 in the last week continued at about the same, somewhat slower pace as the week before, but admissions have moved upward slightly, according to the most recent data.

The total number of new cases came to 25,915 for the week of April 1-7, down by 5.8% from the previous week’s 27,521, which, in turn, was 5.2% lower than a week earlier, according to the American Academy of Pediatrics and the Children’s Hospital Association, which have been collecting COVID-related data from state and territorial health departments since the early stages of the pandemic. New case declines in previous weeks had ranged from 9.3% to 46%.

The nearly 26,000 cases reported during the first week of April represent a fall of 97.7% from the peak of the Omicron surge in mid-January, when weekly cases hit 1.15 million, and they represent the lowest weekly count since mid-July of 2021. Cumulative cases in children now number close to 12.9 million over the course of the pandemic, which is 19.0% of cases among all ages, the AAP and CHA said in their weekly COVID report.

Data on new-case rates from the Centers for Disease Control and Prevention show the same continued decline, but the CDC acknowledges the possibility of reporting delays in recent weeks. The numbers for the latest week, April 3-9, maintain the larger overall decline, but there have been a couple of small, temporary increases over the last month, the CDC reported on its COVID Data Tracker.

Daily new admissions of children aged 0-17 years with confirmed COVID were right around 0.14 per 100,000 population for April 3-9, compared with 0.13 per 100,000 during the week ending April 2, the CDC said, with reporting delays making it possible that the 0.14 figure could be revised upward in the near future. The highest admission rate, 1.25 children per 100,000 population, occurred on Jan. 15 and 16.

The latest on vaccination

New vaccinations slipped a bit in the last week, with the drop slightly larger among those aged 12-17 years – from 47,000 for the week of March 24-30 to 43,000 during March 31 to April 6 – than in children aged 5-11, who went from 70,000 initial doses to 69,000 over the same 2-week period, the AAP said in its weekly report on vaccination trends.

Among the states, Vermont has fully vaccinated more children aged 5-11 (58%) than any other state, while Hawaii is the leader in fully vaccinated 12- to 17-year-olds at 86%. The lowest comparable figures for both groups can be found in Alabama, where 10% of children aged 5-11 are fully vaccinated and 34% of those aged 12-17 have received both doses of the Pfizer-BioNTech vaccine, the AAP said.

National figures show equally large COVID vaccination gaps between the two age groups. As of April 11, 68% of all children aged 12-17 years had received at least one dose, compared with 34.6% of those aged 5-11, and 58.5% of the older group was fully vaccinated, versus 28.0% of the 5- to 11-year-olds, the CDC reported.

[email protected]

The decline in new cases of child COVID-19 in the last week continued at about the same, somewhat slower pace as the week before, but admissions have moved upward slightly, according to the most recent data.

The total number of new cases came to 25,915 for the week of April 1-7, down by 5.8% from the previous week’s 27,521, which, in turn, was 5.2% lower than a week earlier, according to the American Academy of Pediatrics and the Children’s Hospital Association, which have been collecting COVID-related data from state and territorial health departments since the early stages of the pandemic. New case declines in previous weeks had ranged from 9.3% to 46%.

The nearly 26,000 cases reported during the first week of April represent a fall of 97.7% from the peak of the Omicron surge in mid-January, when weekly cases hit 1.15 million, and they represent the lowest weekly count since mid-July of 2021. Cumulative cases in children now number close to 12.9 million over the course of the pandemic, which is 19.0% of cases among all ages, the AAP and CHA said in their weekly COVID report.

Data on new-case rates from the Centers for Disease Control and Prevention show the same continued decline, but the CDC acknowledges the possibility of reporting delays in recent weeks. The numbers for the latest week, April 3-9, maintain the larger overall decline, but there have been a couple of small, temporary increases over the last month, the CDC reported on its COVID Data Tracker.

Daily new admissions of children aged 0-17 years with confirmed COVID were right around 0.14 per 100,000 population for April 3-9, compared with 0.13 per 100,000 during the week ending April 2, the CDC said, with reporting delays making it possible that the 0.14 figure could be revised upward in the near future. The highest admission rate, 1.25 children per 100,000 population, occurred on Jan. 15 and 16.

The latest on vaccination

New vaccinations slipped a bit in the last week, with the drop slightly larger among those aged 12-17 years – from 47,000 for the week of March 24-30 to 43,000 during March 31 to April 6 – than in children aged 5-11, who went from 70,000 initial doses to 69,000 over the same 2-week period, the AAP said in its weekly report on vaccination trends.

Among the states, Vermont has fully vaccinated more children aged 5-11 (58%) than any other state, while Hawaii is the leader in fully vaccinated 12- to 17-year-olds at 86%. The lowest comparable figures for both groups can be found in Alabama, where 10% of children aged 5-11 are fully vaccinated and 34% of those aged 12-17 have received both doses of the Pfizer-BioNTech vaccine, the AAP said.

National figures show equally large COVID vaccination gaps between the two age groups. As of April 11, 68% of all children aged 12-17 years had received at least one dose, compared with 34.6% of those aged 5-11, and 58.5% of the older group was fully vaccinated, versus 28.0% of the 5- to 11-year-olds, the CDC reported.

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The decline in new cases of child COVID-19 in the last week continued at about the same, somewhat slower pace as the week before, but admissions have moved upward slightly, according to the most recent data.

The total number of new cases came to 25,915 for the week of April 1-7, down by 5.8% from the previous week’s 27,521, which, in turn, was 5.2% lower than a week earlier, according to the American Academy of Pediatrics and the Children’s Hospital Association, which have been collecting COVID-related data from state and territorial health departments since the early stages of the pandemic. New case declines in previous weeks had ranged from 9.3% to 46%.

The nearly 26,000 cases reported during the first week of April represent a fall of 97.7% from the peak of the Omicron surge in mid-January, when weekly cases hit 1.15 million, and they represent the lowest weekly count since mid-July of 2021. Cumulative cases in children now number close to 12.9 million over the course of the pandemic, which is 19.0% of cases among all ages, the AAP and CHA said in their weekly COVID report.

Data on new-case rates from the Centers for Disease Control and Prevention show the same continued decline, but the CDC acknowledges the possibility of reporting delays in recent weeks. The numbers for the latest week, April 3-9, maintain the larger overall decline, but there have been a couple of small, temporary increases over the last month, the CDC reported on its COVID Data Tracker.

Daily new admissions of children aged 0-17 years with confirmed COVID were right around 0.14 per 100,000 population for April 3-9, compared with 0.13 per 100,000 during the week ending April 2, the CDC said, with reporting delays making it possible that the 0.14 figure could be revised upward in the near future. The highest admission rate, 1.25 children per 100,000 population, occurred on Jan. 15 and 16.

The latest on vaccination

New vaccinations slipped a bit in the last week, with the drop slightly larger among those aged 12-17 years – from 47,000 for the week of March 24-30 to 43,000 during March 31 to April 6 – than in children aged 5-11, who went from 70,000 initial doses to 69,000 over the same 2-week period, the AAP said in its weekly report on vaccination trends.

Among the states, Vermont has fully vaccinated more children aged 5-11 (58%) than any other state, while Hawaii is the leader in fully vaccinated 12- to 17-year-olds at 86%. The lowest comparable figures for both groups can be found in Alabama, where 10% of children aged 5-11 are fully vaccinated and 34% of those aged 12-17 have received both doses of the Pfizer-BioNTech vaccine, the AAP said.

National figures show equally large COVID vaccination gaps between the two age groups. As of April 11, 68% of all children aged 12-17 years had received at least one dose, compared with 34.6% of those aged 5-11, and 58.5% of the older group was fully vaccinated, versus 28.0% of the 5- to 11-year-olds, the CDC reported.

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