CHEST Physician

INDIANAPOLIS – Recent legislative sessions in state legislative houses across the country have yielded progress toward codifying optimal team practice (OTP) into state law. That’s according to Phil Bongiorno, BA, senior vice president of advocacy and government relations at the American Academy of Physician Associates (AAPA), who spoke at the group’s annual meeting.

OTP refers to the AAPA’s goal of improving patient access to care and lessening administrative obligations by eliminating the legal requirement that there be a specific relationship between a PA, physician, or any other health care provider. This would allow a PA to practice to the full extent of their education, training, and experience, Mr. Bongiorno said.

The second tenet of OTP is to persuade states to create a separate majority PA board to regulate PAs. An alternative to this would be for states to add PAs and physicians who work with PAs to their medical or healing arts boards, he said.

Third, in an OTP environment, each state would authorize PAs to be eligible for direct payment by all public and private insurers. “We have seen that development at the federal level, as far as Medicare is concerned,” Mr. Bongiorno said. “Now, we’re focusing on making that happen in the individual states as well.”

According to Mr. Bongiorno, this year’s state advocacy priorities are to pursue new legislation in additional states, even as efforts continue to persuade state legislatures to act on carryover bills from the previous legislative session.

Mr. Bongiorno briefly summarized what he called “OTP successes” from 2021:

• Federal government: Authorized direct payment to PAs under Medicare
• Arkansas, Delaware, Illinois, Pennsylvania: Added one or more PAs to their medical boards
• Florida, Utah: Approved direct payment to PAs
• Tennessee, Wisconsin: Created a separate PA review board
• Utah, Wisconsin: Removed the relationship/agreement requirement (Wisconsin now requires 10,000 hours of practice to remove the relationship requirement)

North Central region

In Colorado, House Bill 1095 (HB1095) would have removed requirements for a legal relationship between a PA and a physician. Initially that would have happened after 3,000 hours of practice, although changing that to 5,000 hours has been a compromise measure. PAs changing specialties must collaborate for 2,000 hours, now negotiated to 3,000 hours.

HB1095 ultimately was not successful last year or this year, said Erika Miller, director of state advocacy and outreach for the AAPA. “But we do see it as a success, because in the 2022 session, we managed to get it passed in committee by a 10-to-1 vote,” she said. “It then moved to the full house and was not successful there.”

Ms. Miller said that South Dakota Senate Bill 134 would have removed the requirement for a legal PA/physician relationship after 1,040 hours, which is the requirement for nurse practitioners. “South Dakota had introduced similar legislation the year before, but also like Colorado, they went from not getting out of committee last year to making it to the senate floor this time,” she said.

In Wisconsin, the new PA-affiliated credentialing board began on April 1. It gives PAs the authority to license, discipline, and write regulations, Ms. Miller said.
 

South Central region

Arizona Senate Bill 1367 included direct pay, removed the relationship tether with a physician, and made each PA fully responsible for the care they provide. “The bill passed out of committee successfully but did not make it to a vote due to unexpected struggles between the Arizona medical society and PA chapter,” said Shannon Morey, senior director of state advocacy and outreach at the AAPA. “They are ready to go again next year.”

In Louisiana, Senate Bill 158 is a “strong” bill that addressed all the desired aspects of OTP, Ms. Morey said; “The legislation stands subject to call on the Senate floor, but it has been killed by the sponsor.”
 

Northeast region

Massachusetts Senate Bill 740 (S740) would remove the legal tether between PA and physician, said Carson Walker, senior director of state advocacy and outreach at the AAPA. “The committee decided to extend its time in committee until June,” he said. “By next month, we expect that the committee will schedule a hearing that includes S740, and we fully plan on submitting testimony.”

In New York, Senate Bill 9233 (S9233) would remove physician supervision after 3,600 hours of practice.

“Just about 10 days ago, sponsors were able to have S9233 introduced, which is the most succinct and, I think, the most effective OTP bill I have ever seen,” Mr. Walker said.

“S9233 says that after 3,600 hours a PA can practice without the supervision of a physician, and that’s all. There’s not a lot of time left in this session, but we are hopeful that it lays the groundwork for success next year.”

New Hampshire Senate Bill 228 has passed the legislature and is awaiting the governor’s signature. It will allow direct payment, make PAs responsible for the care they provide, and shift the physician-PA relationship from supervision to collaboration, Mr. Walker said.
 

Southeast region

Stephanie Radix, senior director of state advocacy and outreach at the AAPA, discussed North Carolina’s Senate Bill 345, which passed the Senate unanimously in 2021 and has been carried over to this year’s session. The bill defines team-based settings, eliminates the relationship tether, and establishes a supervised career entry interval of 4,000 clinical hours in the state.

The legislature is slated to adjourn June 30, Ms. Radix said: “We are very hopeful that we will get it across the finish line.”

In an interview, Mr. Bongiorno said that the AAPA’s overall advocacy progress is as expected.

“Optimal team practice is about allowing each practice to make that determination on how the team should work as a true collaboration,” he said. “The bottom line is that OTP would allow us to reach more patients, serve the community, and ensure that people are able to get healthcare, especially in underserved areas.”

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

INDIANAPOLIS – Recent legislative sessions in state legislative houses across the country have yielded progress toward codifying optimal team practice (OTP) into state law. That’s according to Phil Bongiorno, BA, senior vice president of advocacy and government relations at the American Academy of Physician Associates (AAPA), who spoke at the group’s annual meeting.

OTP refers to the AAPA’s goal of improving patient access to care and lessening administrative obligations by eliminating the legal requirement that there be a specific relationship between a PA, physician, or any other health care provider. This would allow a PA to practice to the full extent of their education, training, and experience, Mr. Bongiorno said.

The second tenet of OTP is to persuade states to create a separate majority PA board to regulate PAs. An alternative to this would be for states to add PAs and physicians who work with PAs to their medical or healing arts boards, he said.

Third, in an OTP environment, each state would authorize PAs to be eligible for direct payment by all public and private insurers. “We have seen that development at the federal level, as far as Medicare is concerned,” Mr. Bongiorno said. “Now, we’re focusing on making that happen in the individual states as well.”

According to Mr. Bongiorno, this year’s state advocacy priorities are to pursue new legislation in additional states, even as efforts continue to persuade state legislatures to act on carryover bills from the previous legislative session.

Mr. Bongiorno briefly summarized what he called “OTP successes” from 2021:

• Federal government: Authorized direct payment to PAs under Medicare
• Arkansas, Delaware, Illinois, Pennsylvania: Added one or more PAs to their medical boards
• Florida, Utah: Approved direct payment to PAs
• Tennessee, Wisconsin: Created a separate PA review board
• Utah, Wisconsin: Removed the relationship/agreement requirement (Wisconsin now requires 10,000 hours of practice to remove the relationship requirement)

North Central region

In Colorado, House Bill 1095 (HB1095) would have removed requirements for a legal relationship between a PA and a physician. Initially that would have happened after 3,000 hours of practice, although changing that to 5,000 hours has been a compromise measure. PAs changing specialties must collaborate for 2,000 hours, now negotiated to 3,000 hours.

HB1095 ultimately was not successful last year or this year, said Erika Miller, director of state advocacy and outreach for the AAPA. “But we do see it as a success, because in the 2022 session, we managed to get it passed in committee by a 10-to-1 vote,” she said. “It then moved to the full house and was not successful there.”

Ms. Miller said that South Dakota Senate Bill 134 would have removed the requirement for a legal PA/physician relationship after 1,040 hours, which is the requirement for nurse practitioners. “South Dakota had introduced similar legislation the year before, but also like Colorado, they went from not getting out of committee last year to making it to the senate floor this time,” she said.

In Wisconsin, the new PA-affiliated credentialing board began on April 1. It gives PAs the authority to license, discipline, and write regulations, Ms. Miller said.
 

South Central region

Arizona Senate Bill 1367 included direct pay, removed the relationship tether with a physician, and made each PA fully responsible for the care they provide. “The bill passed out of committee successfully but did not make it to a vote due to unexpected struggles between the Arizona medical society and PA chapter,” said Shannon Morey, senior director of state advocacy and outreach at the AAPA. “They are ready to go again next year.”

In Louisiana, Senate Bill 158 is a “strong” bill that addressed all the desired aspects of OTP, Ms. Morey said; “The legislation stands subject to call on the Senate floor, but it has been killed by the sponsor.”
 

Northeast region

Massachusetts Senate Bill 740 (S740) would remove the legal tether between PA and physician, said Carson Walker, senior director of state advocacy and outreach at the AAPA. “The committee decided to extend its time in committee until June,” he said. “By next month, we expect that the committee will schedule a hearing that includes S740, and we fully plan on submitting testimony.”

In New York, Senate Bill 9233 (S9233) would remove physician supervision after 3,600 hours of practice.

“Just about 10 days ago, sponsors were able to have S9233 introduced, which is the most succinct and, I think, the most effective OTP bill I have ever seen,” Mr. Walker said.

“S9233 says that after 3,600 hours a PA can practice without the supervision of a physician, and that’s all. There’s not a lot of time left in this session, but we are hopeful that it lays the groundwork for success next year.”

New Hampshire Senate Bill 228 has passed the legislature and is awaiting the governor’s signature. It will allow direct payment, make PAs responsible for the care they provide, and shift the physician-PA relationship from supervision to collaboration, Mr. Walker said.
 

Southeast region

Stephanie Radix, senior director of state advocacy and outreach at the AAPA, discussed North Carolina’s Senate Bill 345, which passed the Senate unanimously in 2021 and has been carried over to this year’s session. The bill defines team-based settings, eliminates the relationship tether, and establishes a supervised career entry interval of 4,000 clinical hours in the state.

The legislature is slated to adjourn June 30, Ms. Radix said: “We are very hopeful that we will get it across the finish line.”

In an interview, Mr. Bongiorno said that the AAPA’s overall advocacy progress is as expected.

“Optimal team practice is about allowing each practice to make that determination on how the team should work as a true collaboration,” he said. “The bottom line is that OTP would allow us to reach more patients, serve the community, and ensure that people are able to get healthcare, especially in underserved areas.”

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

INDIANAPOLIS – Recent legislative sessions in state legislative houses across the country have yielded progress toward codifying optimal team practice (OTP) into state law. That’s according to Phil Bongiorno, BA, senior vice president of advocacy and government relations at the American Academy of Physician Associates (AAPA), who spoke at the group’s annual meeting.

OTP refers to the AAPA’s goal of improving patient access to care and lessening administrative obligations by eliminating the legal requirement that there be a specific relationship between a PA, physician, or any other health care provider. This would allow a PA to practice to the full extent of their education, training, and experience, Mr. Bongiorno said.

The second tenet of OTP is to persuade states to create a separate majority PA board to regulate PAs. An alternative to this would be for states to add PAs and physicians who work with PAs to their medical or healing arts boards, he said.

Third, in an OTP environment, each state would authorize PAs to be eligible for direct payment by all public and private insurers. “We have seen that development at the federal level, as far as Medicare is concerned,” Mr. Bongiorno said. “Now, we’re focusing on making that happen in the individual states as well.”

According to Mr. Bongiorno, this year’s state advocacy priorities are to pursue new legislation in additional states, even as efforts continue to persuade state legislatures to act on carryover bills from the previous legislative session.

Mr. Bongiorno briefly summarized what he called “OTP successes” from 2021:

• Federal government: Authorized direct payment to PAs under Medicare
• Arkansas, Delaware, Illinois, Pennsylvania: Added one or more PAs to their medical boards
• Florida, Utah: Approved direct payment to PAs
• Tennessee, Wisconsin: Created a separate PA review board
• Utah, Wisconsin: Removed the relationship/agreement requirement (Wisconsin now requires 10,000 hours of practice to remove the relationship requirement)

North Central region

In Colorado, House Bill 1095 (HB1095) would have removed requirements for a legal relationship between a PA and a physician. Initially that would have happened after 3,000 hours of practice, although changing that to 5,000 hours has been a compromise measure. PAs changing specialties must collaborate for 2,000 hours, now negotiated to 3,000 hours.

HB1095 ultimately was not successful last year or this year, said Erika Miller, director of state advocacy and outreach for the AAPA. “But we do see it as a success, because in the 2022 session, we managed to get it passed in committee by a 10-to-1 vote,” she said. “It then moved to the full house and was not successful there.”

Ms. Miller said that South Dakota Senate Bill 134 would have removed the requirement for a legal PA/physician relationship after 1,040 hours, which is the requirement for nurse practitioners. “South Dakota had introduced similar legislation the year before, but also like Colorado, they went from not getting out of committee last year to making it to the senate floor this time,” she said.

In Wisconsin, the new PA-affiliated credentialing board began on April 1. It gives PAs the authority to license, discipline, and write regulations, Ms. Miller said.
 

South Central region

Arizona Senate Bill 1367 included direct pay, removed the relationship tether with a physician, and made each PA fully responsible for the care they provide. “The bill passed out of committee successfully but did not make it to a vote due to unexpected struggles between the Arizona medical society and PA chapter,” said Shannon Morey, senior director of state advocacy and outreach at the AAPA. “They are ready to go again next year.”

In Louisiana, Senate Bill 158 is a “strong” bill that addressed all the desired aspects of OTP, Ms. Morey said; “The legislation stands subject to call on the Senate floor, but it has been killed by the sponsor.”
 

Northeast region

Massachusetts Senate Bill 740 (S740) would remove the legal tether between PA and physician, said Carson Walker, senior director of state advocacy and outreach at the AAPA. “The committee decided to extend its time in committee until June,” he said. “By next month, we expect that the committee will schedule a hearing that includes S740, and we fully plan on submitting testimony.”

In New York, Senate Bill 9233 (S9233) would remove physician supervision after 3,600 hours of practice.

“Just about 10 days ago, sponsors were able to have S9233 introduced, which is the most succinct and, I think, the most effective OTP bill I have ever seen,” Mr. Walker said.

“S9233 says that after 3,600 hours a PA can practice without the supervision of a physician, and that’s all. There’s not a lot of time left in this session, but we are hopeful that it lays the groundwork for success next year.”

New Hampshire Senate Bill 228 has passed the legislature and is awaiting the governor’s signature. It will allow direct payment, make PAs responsible for the care they provide, and shift the physician-PA relationship from supervision to collaboration, Mr. Walker said.
 

Southeast region

Stephanie Radix, senior director of state advocacy and outreach at the AAPA, discussed North Carolina’s Senate Bill 345, which passed the Senate unanimously in 2021 and has been carried over to this year’s session. The bill defines team-based settings, eliminates the relationship tether, and establishes a supervised career entry interval of 4,000 clinical hours in the state.

The legislature is slated to adjourn June 30, Ms. Radix said: “We are very hopeful that we will get it across the finish line.”

In an interview, Mr. Bongiorno said that the AAPA’s overall advocacy progress is as expected.

“Optimal team practice is about allowing each practice to make that determination on how the team should work as a true collaboration,” he said. “The bottom line is that OTP would allow us to reach more patients, serve the community, and ensure that people are able to get healthcare, especially in underserved areas.”

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

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

Why it might be better to be a dog person

Here’s that old debate again: Dogs or cats? You probably have your own opinion, but research presented at this year’s Digestive Disease Week may have tipped the scale by showing that children who lived with dogs may be less likely to have Crohn’s disease as adults.

The research was done by having approximately 4,300 people closely related to patients with Crohn’s disease fill out an environmental questionnaire. Using these data, the research team looked into environmental factors such as size of the families, where the home was, how many bathrooms the homes had, and quality of drinking water.

Piqsels

The researchers found that those who had or were exposed to dogs between the ages of 5 and 15 years were more likely to have healthy gut permeability and balanced microbes, which increased their protection against Crohn’s disease.

“Our study seems to add to others that have explored the ‘hygiene hypothesis’ which suggests that the lack of exposure to microbes early in life may lead to lack of immune regulation toward environmental microbes,” senior author Williams Turpin, PhD, said in the written statement.

The researchers aren’t sure why they didn’t get the same findings with cats, but Dr. Turpin theorized that dog owners tend to be outside more with their dogs or live in places with more green space, which are good protectors against Crohn’s disease.

It’s all good for dog owners, but do their pets’ parasites make you more attractive? Just more fuel for the ongoing debate.
 

Come for the history, stay for the fossilized parasites

Another week, another analysis of old British poop. LOTME really is your one-stop shop for all the important, hard-hitting news about historic parasites. You’re welcome, Internet.

Lisa-Marie Shillito

The news this week is from Stonehenge, which is apparently kind of a big deal. Rocks in a circle, celestial calendar, cultural significance, whatever. We’re not here to talk about rocks. We’re here to talk about, uh, rocks. Smaller rocks. Specifically, coprolites, which are essentially poop turned into a rock. (Though now we’re imagining Stonehenge made out of fossilized poop rocks. Would it still be a big tourist destination? We can see both sides of the argument on that one.)

Archaeologists from the University of Cambridge have conducted an analysis of coprolites from Durrington Walls, a Neolithic settlement just a few kilometers from Stonehenge. The town dates to the same time that Stonehenge was constructed, and it’s believed that the residents were responsible for building the landmark. These coprolites, depending on what’s inside, can tell us a lot about how the builders of Stonehenge lived and, more specifically, how they ate.

In this case, the coprolites of one human and three dogs contained capillariid worm eggs. These worms come from cows, and when a human is typically infected, the eggs embed in the liver and do not pass through the body. Finding them in excrement indicates that the people were eating raw cow organs and feeding leftovers to their dogs. This is interesting, because a preponderance of pottery and cooking implements also found at the site indicates that the residents of Durrington Walls were spit-roasting or boiling their beef and pork. So the meat was cooked, but not the organs. That is an interesting dietary decision, ancient British people. Then again, modern British cuisine exists. At least now we know where they got it from.

This new research raises one other very important question: When are we going to get a full-on guided tour of all the important coprolite sites in Britain? They’ve clearly got plenty of them, and the tourist demand for ancient parasites must be sky-high. Come on, capitalism, follow through on this. We’d go.
 

Everyone lies: Food intake edition

Do you have any patients on special diets? Do you ask them if they are following those diets? Don’t bother, because they’re lying. Everyone lies about the food they eat. Everyone. Obese people lie, and nonobese people lie.

Peter Timmerhues/Pixabay

Investigators at the University of Essex in England asked 221 adults to keep food diaries, and then they checked on energy consumption by analyzing radioactive water levels in the participants’ urine over a 10-day period.

Underreporting of food consumption was rampant, even among those who were not obese. The obese subjects did underreport by a greater extent (1,200 calories per day) than did those who were not obese, who were off by only 800 calories, but the obese participants burned about 400 calories more each day than did the nonobese, so the difference was a wash.

Everyone ended up underreporting their calorie consumption by an average of about 900 calories, and the investigators were good enough to provide some food equivalents, tops on the list being three MacDonald’s cheeseburgers.

“Public health recommendations have historically relied heavily on self-reported energy intake values,” senior author Gavin Sandercock, PhD, said in a EurekAlert statement, and “recognising that the measures of energy intake are incorrect might result in the setting of more realistic targets.”

Maybe you can be more realistic with your patients, too. Go ahead and ask Mr. Smith about the burger sticking out of his coat pocket, because there are probably two more you can’t see. We’ve each got 900 calories hiding on us somewhere. Ours is usually pizza.
 

The art of the gallbladder

Ever thought you would see a portrait of a gallbladder hanging up in a gallery? Not just an artist’s rendition, but an actual photo from an actual patient? Well, you can at the Soloway Gallery in Brooklyn, N.Y., at least until June 12.

PxHere

The artist? K.C. Joseph, MD, a general surgeon from St. Marie, Pa., who died in 2015. His daughter Melissa is the curator of the show and told ARTnews about the interesting connection her father had with art and surgery.

In 2010, Dr. Joseph gave his daughter a box of photos and said “Make me a famous artist,” she recalled. At first, “I was like, ‘These are weird,’ and then I put them under my bed for 10 years.”

Apparently he had been making art with his patients’ organs for about 15 years and had a system in which he put each one together. Before a surgery Dr. Joseph would make a note card with the patient’s name handwritten in calligraphy with a couple of pages taken out of the magazine from the waiting room as the backdrop. Afterward, when the patient was in recovery, the removed organ would be placed among the pages and the name card. A photo was taken with the same endoscope that was used for the procedure.

After the show’s debut, people reached out expressing their love for their photos. “I wish, before he died, I had asked him more questions about it,” Ms. Joseph told ARTnews. “I’m regretting it so much now, kicking myself.”

Who gets to take home an artsy photo of their gallbladder after getting it removed? Not us, that’s who. Each collage is a one-of-a-kind piece. They definitely should be framed and shown in an art gallery. Oh, right. Never mind.

Why it might be better to be a dog person

Here’s that old debate again: Dogs or cats? You probably have your own opinion, but research presented at this year’s Digestive Disease Week may have tipped the scale by showing that children who lived with dogs may be less likely to have Crohn’s disease as adults.

The research was done by having approximately 4,300 people closely related to patients with Crohn’s disease fill out an environmental questionnaire. Using these data, the research team looked into environmental factors such as size of the families, where the home was, how many bathrooms the homes had, and quality of drinking water.

Piqsels

The researchers found that those who had or were exposed to dogs between the ages of 5 and 15 years were more likely to have healthy gut permeability and balanced microbes, which increased their protection against Crohn’s disease.

“Our study seems to add to others that have explored the ‘hygiene hypothesis’ which suggests that the lack of exposure to microbes early in life may lead to lack of immune regulation toward environmental microbes,” senior author Williams Turpin, PhD, said in the written statement.

The researchers aren’t sure why they didn’t get the same findings with cats, but Dr. Turpin theorized that dog owners tend to be outside more with their dogs or live in places with more green space, which are good protectors against Crohn’s disease.

It’s all good for dog owners, but do their pets’ parasites make you more attractive? Just more fuel for the ongoing debate.
 

Come for the history, stay for the fossilized parasites

Another week, another analysis of old British poop. LOTME really is your one-stop shop for all the important, hard-hitting news about historic parasites. You’re welcome, Internet.

Lisa-Marie Shillito

The news this week is from Stonehenge, which is apparently kind of a big deal. Rocks in a circle, celestial calendar, cultural significance, whatever. We’re not here to talk about rocks. We’re here to talk about, uh, rocks. Smaller rocks. Specifically, coprolites, which are essentially poop turned into a rock. (Though now we’re imagining Stonehenge made out of fossilized poop rocks. Would it still be a big tourist destination? We can see both sides of the argument on that one.)

Archaeologists from the University of Cambridge have conducted an analysis of coprolites from Durrington Walls, a Neolithic settlement just a few kilometers from Stonehenge. The town dates to the same time that Stonehenge was constructed, and it’s believed that the residents were responsible for building the landmark. These coprolites, depending on what’s inside, can tell us a lot about how the builders of Stonehenge lived and, more specifically, how they ate.

In this case, the coprolites of one human and three dogs contained capillariid worm eggs. These worms come from cows, and when a human is typically infected, the eggs embed in the liver and do not pass through the body. Finding them in excrement indicates that the people were eating raw cow organs and feeding leftovers to their dogs. This is interesting, because a preponderance of pottery and cooking implements also found at the site indicates that the residents of Durrington Walls were spit-roasting or boiling their beef and pork. So the meat was cooked, but not the organs. That is an interesting dietary decision, ancient British people. Then again, modern British cuisine exists. At least now we know where they got it from.

This new research raises one other very important question: When are we going to get a full-on guided tour of all the important coprolite sites in Britain? They’ve clearly got plenty of them, and the tourist demand for ancient parasites must be sky-high. Come on, capitalism, follow through on this. We’d go.
 

Everyone lies: Food intake edition

Do you have any patients on special diets? Do you ask them if they are following those diets? Don’t bother, because they’re lying. Everyone lies about the food they eat. Everyone. Obese people lie, and nonobese people lie.

Peter Timmerhues/Pixabay

Investigators at the University of Essex in England asked 221 adults to keep food diaries, and then they checked on energy consumption by analyzing radioactive water levels in the participants’ urine over a 10-day period.

Underreporting of food consumption was rampant, even among those who were not obese. The obese subjects did underreport by a greater extent (1,200 calories per day) than did those who were not obese, who were off by only 800 calories, but the obese participants burned about 400 calories more each day than did the nonobese, so the difference was a wash.

Everyone ended up underreporting their calorie consumption by an average of about 900 calories, and the investigators were good enough to provide some food equivalents, tops on the list being three MacDonald’s cheeseburgers.

“Public health recommendations have historically relied heavily on self-reported energy intake values,” senior author Gavin Sandercock, PhD, said in a EurekAlert statement, and “recognising that the measures of energy intake are incorrect might result in the setting of more realistic targets.”

Maybe you can be more realistic with your patients, too. Go ahead and ask Mr. Smith about the burger sticking out of his coat pocket, because there are probably two more you can’t see. We’ve each got 900 calories hiding on us somewhere. Ours is usually pizza.
 

The art of the gallbladder

Ever thought you would see a portrait of a gallbladder hanging up in a gallery? Not just an artist’s rendition, but an actual photo from an actual patient? Well, you can at the Soloway Gallery in Brooklyn, N.Y., at least until June 12.

PxHere

The artist? K.C. Joseph, MD, a general surgeon from St. Marie, Pa., who died in 2015. His daughter Melissa is the curator of the show and told ARTnews about the interesting connection her father had with art and surgery.

In 2010, Dr. Joseph gave his daughter a box of photos and said “Make me a famous artist,” she recalled. At first, “I was like, ‘These are weird,’ and then I put them under my bed for 10 years.”

Apparently he had been making art with his patients’ organs for about 15 years and had a system in which he put each one together. Before a surgery Dr. Joseph would make a note card with the patient’s name handwritten in calligraphy with a couple of pages taken out of the magazine from the waiting room as the backdrop. Afterward, when the patient was in recovery, the removed organ would be placed among the pages and the name card. A photo was taken with the same endoscope that was used for the procedure.

After the show’s debut, people reached out expressing their love for their photos. “I wish, before he died, I had asked him more questions about it,” Ms. Joseph told ARTnews. “I’m regretting it so much now, kicking myself.”

Who gets to take home an artsy photo of their gallbladder after getting it removed? Not us, that’s who. Each collage is a one-of-a-kind piece. They definitely should be framed and shown in an art gallery. Oh, right. Never mind.

Why it might be better to be a dog person

Here’s that old debate again: Dogs or cats? You probably have your own opinion, but research presented at this year’s Digestive Disease Week may have tipped the scale by showing that children who lived with dogs may be less likely to have Crohn’s disease as adults.

The research was done by having approximately 4,300 people closely related to patients with Crohn’s disease fill out an environmental questionnaire. Using these data, the research team looked into environmental factors such as size of the families, where the home was, how many bathrooms the homes had, and quality of drinking water.

Piqsels

The researchers found that those who had or were exposed to dogs between the ages of 5 and 15 years were more likely to have healthy gut permeability and balanced microbes, which increased their protection against Crohn’s disease.

“Our study seems to add to others that have explored the ‘hygiene hypothesis’ which suggests that the lack of exposure to microbes early in life may lead to lack of immune regulation toward environmental microbes,” senior author Williams Turpin, PhD, said in the written statement.

The researchers aren’t sure why they didn’t get the same findings with cats, but Dr. Turpin theorized that dog owners tend to be outside more with their dogs or live in places with more green space, which are good protectors against Crohn’s disease.

It’s all good for dog owners, but do their pets’ parasites make you more attractive? Just more fuel for the ongoing debate.
 

Come for the history, stay for the fossilized parasites

Another week, another analysis of old British poop. LOTME really is your one-stop shop for all the important, hard-hitting news about historic parasites. You’re welcome, Internet.

Lisa-Marie Shillito

The news this week is from Stonehenge, which is apparently kind of a big deal. Rocks in a circle, celestial calendar, cultural significance, whatever. We’re not here to talk about rocks. We’re here to talk about, uh, rocks. Smaller rocks. Specifically, coprolites, which are essentially poop turned into a rock. (Though now we’re imagining Stonehenge made out of fossilized poop rocks. Would it still be a big tourist destination? We can see both sides of the argument on that one.)

Archaeologists from the University of Cambridge have conducted an analysis of coprolites from Durrington Walls, a Neolithic settlement just a few kilometers from Stonehenge. The town dates to the same time that Stonehenge was constructed, and it’s believed that the residents were responsible for building the landmark. These coprolites, depending on what’s inside, can tell us a lot about how the builders of Stonehenge lived and, more specifically, how they ate.

In this case, the coprolites of one human and three dogs contained capillariid worm eggs. These worms come from cows, and when a human is typically infected, the eggs embed in the liver and do not pass through the body. Finding them in excrement indicates that the people were eating raw cow organs and feeding leftovers to their dogs. This is interesting, because a preponderance of pottery and cooking implements also found at the site indicates that the residents of Durrington Walls were spit-roasting or boiling their beef and pork. So the meat was cooked, but not the organs. That is an interesting dietary decision, ancient British people. Then again, modern British cuisine exists. At least now we know where they got it from.

This new research raises one other very important question: When are we going to get a full-on guided tour of all the important coprolite sites in Britain? They’ve clearly got plenty of them, and the tourist demand for ancient parasites must be sky-high. Come on, capitalism, follow through on this. We’d go.
 

Everyone lies: Food intake edition

Do you have any patients on special diets? Do you ask them if they are following those diets? Don’t bother, because they’re lying. Everyone lies about the food they eat. Everyone. Obese people lie, and nonobese people lie.

Peter Timmerhues/Pixabay

Investigators at the University of Essex in England asked 221 adults to keep food diaries, and then they checked on energy consumption by analyzing radioactive water levels in the participants’ urine over a 10-day period.

Underreporting of food consumption was rampant, even among those who were not obese. The obese subjects did underreport by a greater extent (1,200 calories per day) than did those who were not obese, who were off by only 800 calories, but the obese participants burned about 400 calories more each day than did the nonobese, so the difference was a wash.

Everyone ended up underreporting their calorie consumption by an average of about 900 calories, and the investigators were good enough to provide some food equivalents, tops on the list being three MacDonald’s cheeseburgers.

“Public health recommendations have historically relied heavily on self-reported energy intake values,” senior author Gavin Sandercock, PhD, said in a EurekAlert statement, and “recognising that the measures of energy intake are incorrect might result in the setting of more realistic targets.”

Maybe you can be more realistic with your patients, too. Go ahead and ask Mr. Smith about the burger sticking out of his coat pocket, because there are probably two more you can’t see. We’ve each got 900 calories hiding on us somewhere. Ours is usually pizza.
 

The art of the gallbladder

Ever thought you would see a portrait of a gallbladder hanging up in a gallery? Not just an artist’s rendition, but an actual photo from an actual patient? Well, you can at the Soloway Gallery in Brooklyn, N.Y., at least until June 12.

PxHere

The artist? K.C. Joseph, MD, a general surgeon from St. Marie, Pa., who died in 2015. His daughter Melissa is the curator of the show and told ARTnews about the interesting connection her father had with art and surgery.

In 2010, Dr. Joseph gave his daughter a box of photos and said “Make me a famous artist,” she recalled. At first, “I was like, ‘These are weird,’ and then I put them under my bed for 10 years.”

Apparently he had been making art with his patients’ organs for about 15 years and had a system in which he put each one together. Before a surgery Dr. Joseph would make a note card with the patient’s name handwritten in calligraphy with a couple of pages taken out of the magazine from the waiting room as the backdrop. Afterward, when the patient was in recovery, the removed organ would be placed among the pages and the name card. A photo was taken with the same endoscope that was used for the procedure.

After the show’s debut, people reached out expressing their love for their photos. “I wish, before he died, I had asked him more questions about it,” Ms. Joseph told ARTnews. “I’m regretting it so much now, kicking myself.”

Who gets to take home an artsy photo of their gallbladder after getting it removed? Not us, that’s who. Each collage is a one-of-a-kind piece. They definitely should be framed and shown in an art gallery. Oh, right. Never mind.

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

Weekly COVID-19 cases in children passed 100,000 in the United States for the first time since late February as pediatric incidence rose for the 6th consecutive week, according to the American Academy of Pediatrics and the Children’s Hospital Association.

New cases were up by 14.6% over the previous week to just over 107,000 reported during May 13-16, marking the sixth straight increase since April 1-7, when the count was almost 26,000. Over that period, weekly cases rose 313%, based on data in the latest weekly COVID report from the AAP and CHA.

Rates reported by the Centers for Disease Control and Prevention show the same trend. Weekly cases per 100,000 population, which were down to 34.9 in children aged 0-4 years and 43.1 for those aged 5-11 on March 26, were up to 49.5 and 52.2, respectively, by April 16. The pace picked up right after that, and as of May 14, the rates of new cases were 125.4 per 100,000 in children aged 0-4 years and 143.1 in those aged 5-11, the CDC said.

Hospital admissions continue to rise as well. The rate of new admissions in children aged 0-17 was up to 0.25 per 100,000 population on May 18, nearly double the 0.13 per 100,000 recorded as late as April 13. The latest 7-day average count for new admissions, 163 per day from May 15-21, is down from the previous week’s 175 per day, but the CDC also acknowledges potential reporting delays in the most recent 7-day period.

Both of those weekly averages, however, are far below the peak rate for the pandemic, 914 per day, which occurred Jan. 10-16, 2022, during the Omicron surge. Since the CDC began keeping count at the beginning of August 2020, more than 125,000 children aged 0-17 years have been admitted with confirmed COVID-19, which is about 2.7% of all admissions over that period, the CDC’s data show.
 

Booster gets the green light

The week brought some positive news on the prevention side, though, as the CDC officially approved a COVID vaccine booster dose for children aged 5-11 years.

Even that good news came with a caveat, however. The vote by the CDC’s Advisory Committee on Immunization Practices was 11:1 in favor, with the negative vote cast by Helen Keipp Talbot, MD, of Vanderbilt University, Nashville, Tenn., who said that “boosters are great once we’ve gotten everyone their first round. That needs to be our priority in this.”

Nationally, in fact, just 35.7% of children aged 5-11 years have received at least one dose of the vaccine and only 29.0% are fully vaccinated. Those figures are nearly doubled among 12- to 17-year-olds: 69.3% have received at least one dose and 59.4% are fully vaccinated, the CDC said on its COVID Data Tracker.

Some states, meanwhile, are well below those national rates. In Wyoming, only 40% of children aged 12-17 have received an initial vaccine dose, and eight other states are below 50%. Among children aged 5-12, there are still five states below 20% in that measure, while the states on the other end of the spectrum – Vermont and Massachusetts – are above 60%, the AAP said in its separate vaccination report.

Weekly COVID-19 cases in children passed 100,000 in the United States for the first time since late February as pediatric incidence rose for the 6th consecutive week, according to the American Academy of Pediatrics and the Children’s Hospital Association.

New cases were up by 14.6% over the previous week to just over 107,000 reported during May 13-16, marking the sixth straight increase since April 1-7, when the count was almost 26,000. Over that period, weekly cases rose 313%, based on data in the latest weekly COVID report from the AAP and CHA.

Rates reported by the Centers for Disease Control and Prevention show the same trend. Weekly cases per 100,000 population, which were down to 34.9 in children aged 0-4 years and 43.1 for those aged 5-11 on March 26, were up to 49.5 and 52.2, respectively, by April 16. The pace picked up right after that, and as of May 14, the rates of new cases were 125.4 per 100,000 in children aged 0-4 years and 143.1 in those aged 5-11, the CDC said.

Hospital admissions continue to rise as well. The rate of new admissions in children aged 0-17 was up to 0.25 per 100,000 population on May 18, nearly double the 0.13 per 100,000 recorded as late as April 13. The latest 7-day average count for new admissions, 163 per day from May 15-21, is down from the previous week’s 175 per day, but the CDC also acknowledges potential reporting delays in the most recent 7-day period.

Both of those weekly averages, however, are far below the peak rate for the pandemic, 914 per day, which occurred Jan. 10-16, 2022, during the Omicron surge. Since the CDC began keeping count at the beginning of August 2020, more than 125,000 children aged 0-17 years have been admitted with confirmed COVID-19, which is about 2.7% of all admissions over that period, the CDC’s data show.
 

Booster gets the green light

The week brought some positive news on the prevention side, though, as the CDC officially approved a COVID vaccine booster dose for children aged 5-11 years.

Even that good news came with a caveat, however. The vote by the CDC’s Advisory Committee on Immunization Practices was 11:1 in favor, with the negative vote cast by Helen Keipp Talbot, MD, of Vanderbilt University, Nashville, Tenn., who said that “boosters are great once we’ve gotten everyone their first round. That needs to be our priority in this.”

Nationally, in fact, just 35.7% of children aged 5-11 years have received at least one dose of the vaccine and only 29.0% are fully vaccinated. Those figures are nearly doubled among 12- to 17-year-olds: 69.3% have received at least one dose and 59.4% are fully vaccinated, the CDC said on its COVID Data Tracker.

Some states, meanwhile, are well below those national rates. In Wyoming, only 40% of children aged 12-17 have received an initial vaccine dose, and eight other states are below 50%. Among children aged 5-12, there are still five states below 20% in that measure, while the states on the other end of the spectrum – Vermont and Massachusetts – are above 60%, the AAP said in its separate vaccination report.

Weekly COVID-19 cases in children passed 100,000 in the United States for the first time since late February as pediatric incidence rose for the 6th consecutive week, according to the American Academy of Pediatrics and the Children’s Hospital Association.

New cases were up by 14.6% over the previous week to just over 107,000 reported during May 13-16, marking the sixth straight increase since April 1-7, when the count was almost 26,000. Over that period, weekly cases rose 313%, based on data in the latest weekly COVID report from the AAP and CHA.

Rates reported by the Centers for Disease Control and Prevention show the same trend. Weekly cases per 100,000 population, which were down to 34.9 in children aged 0-4 years and 43.1 for those aged 5-11 on March 26, were up to 49.5 and 52.2, respectively, by April 16. The pace picked up right after that, and as of May 14, the rates of new cases were 125.4 per 100,000 in children aged 0-4 years and 143.1 in those aged 5-11, the CDC said.

Hospital admissions continue to rise as well. The rate of new admissions in children aged 0-17 was up to 0.25 per 100,000 population on May 18, nearly double the 0.13 per 100,000 recorded as late as April 13. The latest 7-day average count for new admissions, 163 per day from May 15-21, is down from the previous week’s 175 per day, but the CDC also acknowledges potential reporting delays in the most recent 7-day period.

Both of those weekly averages, however, are far below the peak rate for the pandemic, 914 per day, which occurred Jan. 10-16, 2022, during the Omicron surge. Since the CDC began keeping count at the beginning of August 2020, more than 125,000 children aged 0-17 years have been admitted with confirmed COVID-19, which is about 2.7% of all admissions over that period, the CDC’s data show.
 

Booster gets the green light

The week brought some positive news on the prevention side, though, as the CDC officially approved a COVID vaccine booster dose for children aged 5-11 years.

Even that good news came with a caveat, however. The vote by the CDC’s Advisory Committee on Immunization Practices was 11:1 in favor, with the negative vote cast by Helen Keipp Talbot, MD, of Vanderbilt University, Nashville, Tenn., who said that “boosters are great once we’ve gotten everyone their first round. That needs to be our priority in this.”

Nationally, in fact, just 35.7% of children aged 5-11 years have received at least one dose of the vaccine and only 29.0% are fully vaccinated. Those figures are nearly doubled among 12- to 17-year-olds: 69.3% have received at least one dose and 59.4% are fully vaccinated, the CDC said on its COVID Data Tracker.

Some states, meanwhile, are well below those national rates. In Wyoming, only 40% of children aged 12-17 have received an initial vaccine dose, and eight other states are below 50%. Among children aged 5-12, there are still five states below 20% in that measure, while the states on the other end of the spectrum – Vermont and Massachusetts – are above 60%, the AAP said in its separate vaccination report.

Misinformation about nirmatrelvir/ritonavir (Paxlovid, Pfizer) for treating mild to moderate COVID-19 in patients at high risk for severe disease is feeding misunderstanding among prescribers and patients, two experts from the Infectious Diseases Society of America (IDSA) have said.

They briefed reporters on potential drug interactions and uncommon cases of a “rebound” effect with the drug, which was granted emergency use authorization by the Food and Drug Administration last December for patients at least 12 years old.

The drug combination works “like a pair of scissors chopping up proteins that are made as the virus replicates inside of cells. Inhibiting that enzyme leads to the cessation of replication,” said Jason C. Gallagher, PharmD, of Temple University School of Pharmacy, Philadelphia.

That’s important because other treatments that target the spike protein, such as monoclonal antibodies, can lose their efficacy as the virus changes. He said that while that’s not impossible for Paxlovid, “we have not seen variants emerging that are resistant to it.”
 

Potential drug interactions

IDSA recently published updated guidance on potential interactions between Paxlovid and the top 100 drugs, and important considerations for prescribing.

“There is a concern that people have not been prescribing it because of fear of these interactions,” Dr. Gallagher said, explaining that, while in some cases those fears may be valid, in many instances the interaction is manageable.

One example is in two popular statins for heart disease, lovastatin and simvastatin.

“That’s an interaction that can be managed by holding [those drugs] for the 5 days that someone receives Paxlovid,” he said.

Misinformation also is circulating about distribution status of Paxlovid, Dr. Gallagher said.

“We’re in a very different state from that standpoint than we were a month or 2 months ago,” he said, adding that it is widely available in not all but a large number of pharmacies throughout the United States.

He emphasized the importance of drug reconciliation, as many patients will go to a different pharmacy for Paxlovid than they might for their usual prescriptions, so without a full accounting of prescriptions and supplements potential interactions may be missed.
 

Important interactions to watch

Melanie Thompson, MD, cochair of the HIVMA/IDSA HIV Primary Care Guidance Panel, highlighted some classes of drugs to watch, among them the antiarrhythmics, most of which are contraindicated with Paxlovid.

There are also important interactions with a number of cancer drugs, and consults with oncologists will be critical, she said.

“Likewise, people who have had transplants are likely to be on drugs that have significant ritonavir interactions,” Dr. Thompson said.

People on ergot drugs for migraine cannot take Paxlovid, she said, and “people who take colchicine for gout have to be very careful.”

She said it’s better not to use colchicine while taking Paxlovid, as it is contraindicated, “but it can be managed in certain circumstances with substantial dose reduction.”

A number of mental health drugs can be managed with Paxlovid, Dr. Thompson said. For the antipsychotic drug quetiapine, (Seroquel), a “substantial decrease in dose is required.”
 

Viagra for ED can be managed

Use of Viagra depends on why it’s being used, Dr. Thompson said. If it’s used for pulmonary hypertension, it is used at a very high dose and that is contraindicated. But if used for erectile dysfunction, the dose needs to be managed when people are on Paxlovid.

She said prescribers must know the kidney function of patients.

“There is a dose reduction that is required if people have impaired kidney function but below a certain level of function, which is 30 mL/min, it’s not recommended to give Paxlovid.”

Dr. Thompson highlighted two other websites for thorough, printable information on drug-drug interactions with Paxlovid: the University of Liverpool’s drug interaction checker and a printable handout from the University of Waterloo in Ontario, Canada.

“We need a 24/7 clinician hotline for Paxlovid to really make it accessible,” she said.
 

No data yet on ‘rebound’ effect

As to a few recent reports of a “rebound” effect, of people developing COVID-19 symptoms after completing a course of Paxlovid, there are not enough data yet to determine a clear pattern or cause.

“All we have are anecdotal data,” Dr. Thompson said. Current questions for study include whether the 5-day course is not long enough, she said, and whether people more at risk should be given a second course of Paxlovid if they do rebound.

Dr. Gallagher said it’s important to remember that the therapy goal of the drug is to prevent hospitalizations and deaths, and while any rebound is problematic, “it’s possible the use of the medication has already saved a life.”

Dr. Gallagher and Dr. Thompson report no relevant financial relationships.

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

Misinformation about nirmatrelvir/ritonavir (Paxlovid, Pfizer) for treating mild to moderate COVID-19 in patients at high risk for severe disease is feeding misunderstanding among prescribers and patients, two experts from the Infectious Diseases Society of America (IDSA) have said.

They briefed reporters on potential drug interactions and uncommon cases of a “rebound” effect with the drug, which was granted emergency use authorization by the Food and Drug Administration last December for patients at least 12 years old.

The drug combination works “like a pair of scissors chopping up proteins that are made as the virus replicates inside of cells. Inhibiting that enzyme leads to the cessation of replication,” said Jason C. Gallagher, PharmD, of Temple University School of Pharmacy, Philadelphia.

That’s important because other treatments that target the spike protein, such as monoclonal antibodies, can lose their efficacy as the virus changes. He said that while that’s not impossible for Paxlovid, “we have not seen variants emerging that are resistant to it.”
 

Potential drug interactions

IDSA recently published updated guidance on potential interactions between Paxlovid and the top 100 drugs, and important considerations for prescribing.

“There is a concern that people have not been prescribing it because of fear of these interactions,” Dr. Gallagher said, explaining that, while in some cases those fears may be valid, in many instances the interaction is manageable.

One example is in two popular statins for heart disease, lovastatin and simvastatin.

“That’s an interaction that can be managed by holding [those drugs] for the 5 days that someone receives Paxlovid,” he said.

Misinformation also is circulating about distribution status of Paxlovid, Dr. Gallagher said.

“We’re in a very different state from that standpoint than we were a month or 2 months ago,” he said, adding that it is widely available in not all but a large number of pharmacies throughout the United States.

He emphasized the importance of drug reconciliation, as many patients will go to a different pharmacy for Paxlovid than they might for their usual prescriptions, so without a full accounting of prescriptions and supplements potential interactions may be missed.
 

Important interactions to watch

Melanie Thompson, MD, cochair of the HIVMA/IDSA HIV Primary Care Guidance Panel, highlighted some classes of drugs to watch, among them the antiarrhythmics, most of which are contraindicated with Paxlovid.

There are also important interactions with a number of cancer drugs, and consults with oncologists will be critical, she said.

“Likewise, people who have had transplants are likely to be on drugs that have significant ritonavir interactions,” Dr. Thompson said.

People on ergot drugs for migraine cannot take Paxlovid, she said, and “people who take colchicine for gout have to be very careful.”

She said it’s better not to use colchicine while taking Paxlovid, as it is contraindicated, “but it can be managed in certain circumstances with substantial dose reduction.”

A number of mental health drugs can be managed with Paxlovid, Dr. Thompson said. For the antipsychotic drug quetiapine, (Seroquel), a “substantial decrease in dose is required.”
 

Viagra for ED can be managed

Use of Viagra depends on why it’s being used, Dr. Thompson said. If it’s used for pulmonary hypertension, it is used at a very high dose and that is contraindicated. But if used for erectile dysfunction, the dose needs to be managed when people are on Paxlovid.

She said prescribers must know the kidney function of patients.

“There is a dose reduction that is required if people have impaired kidney function but below a certain level of function, which is 30 mL/min, it’s not recommended to give Paxlovid.”

Dr. Thompson highlighted two other websites for thorough, printable information on drug-drug interactions with Paxlovid: the University of Liverpool’s drug interaction checker and a printable handout from the University of Waterloo in Ontario, Canada.

“We need a 24/7 clinician hotline for Paxlovid to really make it accessible,” she said.
 

No data yet on ‘rebound’ effect

As to a few recent reports of a “rebound” effect, of people developing COVID-19 symptoms after completing a course of Paxlovid, there are not enough data yet to determine a clear pattern or cause.

“All we have are anecdotal data,” Dr. Thompson said. Current questions for study include whether the 5-day course is not long enough, she said, and whether people more at risk should be given a second course of Paxlovid if they do rebound.

Dr. Gallagher said it’s important to remember that the therapy goal of the drug is to prevent hospitalizations and deaths, and while any rebound is problematic, “it’s possible the use of the medication has already saved a life.”

Dr. Gallagher and Dr. Thompson report no relevant financial relationships.

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

Misinformation about nirmatrelvir/ritonavir (Paxlovid, Pfizer) for treating mild to moderate COVID-19 in patients at high risk for severe disease is feeding misunderstanding among prescribers and patients, two experts from the Infectious Diseases Society of America (IDSA) have said.

They briefed reporters on potential drug interactions and uncommon cases of a “rebound” effect with the drug, which was granted emergency use authorization by the Food and Drug Administration last December for patients at least 12 years old.

The drug combination works “like a pair of scissors chopping up proteins that are made as the virus replicates inside of cells. Inhibiting that enzyme leads to the cessation of replication,” said Jason C. Gallagher, PharmD, of Temple University School of Pharmacy, Philadelphia.

That’s important because other treatments that target the spike protein, such as monoclonal antibodies, can lose their efficacy as the virus changes. He said that while that’s not impossible for Paxlovid, “we have not seen variants emerging that are resistant to it.”
 

Potential drug interactions

IDSA recently published updated guidance on potential interactions between Paxlovid and the top 100 drugs, and important considerations for prescribing.

“There is a concern that people have not been prescribing it because of fear of these interactions,” Dr. Gallagher said, explaining that, while in some cases those fears may be valid, in many instances the interaction is manageable.

One example is in two popular statins for heart disease, lovastatin and simvastatin.

“That’s an interaction that can be managed by holding [those drugs] for the 5 days that someone receives Paxlovid,” he said.

Misinformation also is circulating about distribution status of Paxlovid, Dr. Gallagher said.

“We’re in a very different state from that standpoint than we were a month or 2 months ago,” he said, adding that it is widely available in not all but a large number of pharmacies throughout the United States.

He emphasized the importance of drug reconciliation, as many patients will go to a different pharmacy for Paxlovid than they might for their usual prescriptions, so without a full accounting of prescriptions and supplements potential interactions may be missed.
 

Important interactions to watch

Melanie Thompson, MD, cochair of the HIVMA/IDSA HIV Primary Care Guidance Panel, highlighted some classes of drugs to watch, among them the antiarrhythmics, most of which are contraindicated with Paxlovid.

There are also important interactions with a number of cancer drugs, and consults with oncologists will be critical, she said.

“Likewise, people who have had transplants are likely to be on drugs that have significant ritonavir interactions,” Dr. Thompson said.

People on ergot drugs for migraine cannot take Paxlovid, she said, and “people who take colchicine for gout have to be very careful.”

She said it’s better not to use colchicine while taking Paxlovid, as it is contraindicated, “but it can be managed in certain circumstances with substantial dose reduction.”

A number of mental health drugs can be managed with Paxlovid, Dr. Thompson said. For the antipsychotic drug quetiapine, (Seroquel), a “substantial decrease in dose is required.”
 

Viagra for ED can be managed

Use of Viagra depends on why it’s being used, Dr. Thompson said. If it’s used for pulmonary hypertension, it is used at a very high dose and that is contraindicated. But if used for erectile dysfunction, the dose needs to be managed when people are on Paxlovid.

She said prescribers must know the kidney function of patients.

“There is a dose reduction that is required if people have impaired kidney function but below a certain level of function, which is 30 mL/min, it’s not recommended to give Paxlovid.”

Dr. Thompson highlighted two other websites for thorough, printable information on drug-drug interactions with Paxlovid: the University of Liverpool’s drug interaction checker and a printable handout from the University of Waterloo in Ontario, Canada.

“We need a 24/7 clinician hotline for Paxlovid to really make it accessible,” she said.
 

No data yet on ‘rebound’ effect

As to a few recent reports of a “rebound” effect, of people developing COVID-19 symptoms after completing a course of Paxlovid, there are not enough data yet to determine a clear pattern or cause.

“All we have are anecdotal data,” Dr. Thompson said. Current questions for study include whether the 5-day course is not long enough, she said, and whether people more at risk should be given a second course of Paxlovid if they do rebound.

Dr. Gallagher said it’s important to remember that the therapy goal of the drug is to prevent hospitalizations and deaths, and while any rebound is problematic, “it’s possible the use of the medication has already saved a life.”

Dr. Gallagher and Dr. Thompson report no relevant financial relationships.

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

A study shows that, over a 4-year period, 15 teenagers were injured from exploding e-cigarettes, according to surgeons who have treated young people at nine hospitals in the United States.

“It definitely was an injury we were seeing frequently,” Shannon Acker, MD, an assistant professor of pediatric surgery at the University of Colorado at Denver, Aurora, and a pediatric surgeon at Children’s Hospital Colorado, said in a statement.

Reporting in the Journal of Surgical Research, doctors detail injuries from e-cigarette explosions from January 2016 through December 2019. Ten teens were hospitalized, including three who were admitted to ICUs.

“When we think about e-cigarettes, vaping, and the problems of marketing cigarettes to teenagers, it usually has to do with addiction and lung injury,” said Dr. Acker, a coauthor of the new study. “Whereas we, as trauma surgeons, were seeing these other traumatic injuries.”

Six of the teens had facial burns, five of them lost multiple teeth, five had burns around the thighs and groin, four burned their hands, and four burned their eyes. One teen injured their radial nerve, which runs through the arm. Another cut their face, and one fractured their jaw.

Overall, six teens needed surgery, including one who needed multiple operations for a severe hand injury.

Three of the teenagers had never used e-cigarettes before the day they were hurt.

Vaping has become far more common than smoking traditional cigarettes among U.S. teens in recent years. More than 2 million of them currently use e-cigarettes, according to the Food and Drug Administration, including more than 11% of high school students and almost 3% of middle schoolers.

Most e-cigarettes contain nicotine, which is highly addictive and can impair healthy brain development in adolescents, according to the CDC. Other chemicals and flavorings in the liquids that are heated during vaping can also damage the lungs. Fires and explosions, while rare, are also a risk that’s been previously documented by the FDA, the Centers for Disease Control and Prevention, and the Federal Emergency Management Agency.

Nationwide, there were 195 reported explosions and fires involving e-cigarettes in all ages between 2009 and 2016, according to a FEMA report. While no deaths were reported, 29% of these cases involved severe injuries.

“The shape and construction of electronic cigarettes” can make them behave like “flaming rockets when a battery fails,” according to FEMA.

Vaping devices typically use a rechargeable lithium-ion battery that vaporizes the liquid nicotine solution, Dr. Acker said. “They are not highly regulated, and the batteries may be of inferior quality and prone to explosion.”

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

A study shows that, over a 4-year period, 15 teenagers were injured from exploding e-cigarettes, according to surgeons who have treated young people at nine hospitals in the United States.

“It definitely was an injury we were seeing frequently,” Shannon Acker, MD, an assistant professor of pediatric surgery at the University of Colorado at Denver, Aurora, and a pediatric surgeon at Children’s Hospital Colorado, said in a statement.

Reporting in the Journal of Surgical Research, doctors detail injuries from e-cigarette explosions from January 2016 through December 2019. Ten teens were hospitalized, including three who were admitted to ICUs.

“When we think about e-cigarettes, vaping, and the problems of marketing cigarettes to teenagers, it usually has to do with addiction and lung injury,” said Dr. Acker, a coauthor of the new study. “Whereas we, as trauma surgeons, were seeing these other traumatic injuries.”

Six of the teens had facial burns, five of them lost multiple teeth, five had burns around the thighs and groin, four burned their hands, and four burned their eyes. One teen injured their radial nerve, which runs through the arm. Another cut their face, and one fractured their jaw.

Overall, six teens needed surgery, including one who needed multiple operations for a severe hand injury.

Three of the teenagers had never used e-cigarettes before the day they were hurt.

Vaping has become far more common than smoking traditional cigarettes among U.S. teens in recent years. More than 2 million of them currently use e-cigarettes, according to the Food and Drug Administration, including more than 11% of high school students and almost 3% of middle schoolers.

Most e-cigarettes contain nicotine, which is highly addictive and can impair healthy brain development in adolescents, according to the CDC. Other chemicals and flavorings in the liquids that are heated during vaping can also damage the lungs. Fires and explosions, while rare, are also a risk that’s been previously documented by the FDA, the Centers for Disease Control and Prevention, and the Federal Emergency Management Agency.

Nationwide, there were 195 reported explosions and fires involving e-cigarettes in all ages between 2009 and 2016, according to a FEMA report. While no deaths were reported, 29% of these cases involved severe injuries.

“The shape and construction of electronic cigarettes” can make them behave like “flaming rockets when a battery fails,” according to FEMA.

Vaping devices typically use a rechargeable lithium-ion battery that vaporizes the liquid nicotine solution, Dr. Acker said. “They are not highly regulated, and the batteries may be of inferior quality and prone to explosion.”

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

A study shows that, over a 4-year period, 15 teenagers were injured from exploding e-cigarettes, according to surgeons who have treated young people at nine hospitals in the United States.

“It definitely was an injury we were seeing frequently,” Shannon Acker, MD, an assistant professor of pediatric surgery at the University of Colorado at Denver, Aurora, and a pediatric surgeon at Children’s Hospital Colorado, said in a statement.

Reporting in the Journal of Surgical Research, doctors detail injuries from e-cigarette explosions from January 2016 through December 2019. Ten teens were hospitalized, including three who were admitted to ICUs.

“When we think about e-cigarettes, vaping, and the problems of marketing cigarettes to teenagers, it usually has to do with addiction and lung injury,” said Dr. Acker, a coauthor of the new study. “Whereas we, as trauma surgeons, were seeing these other traumatic injuries.”

Six of the teens had facial burns, five of them lost multiple teeth, five had burns around the thighs and groin, four burned their hands, and four burned their eyes. One teen injured their radial nerve, which runs through the arm. Another cut their face, and one fractured their jaw.

Overall, six teens needed surgery, including one who needed multiple operations for a severe hand injury.

Three of the teenagers had never used e-cigarettes before the day they were hurt.

Vaping has become far more common than smoking traditional cigarettes among U.S. teens in recent years. More than 2 million of them currently use e-cigarettes, according to the Food and Drug Administration, including more than 11% of high school students and almost 3% of middle schoolers.

Most e-cigarettes contain nicotine, which is highly addictive and can impair healthy brain development in adolescents, according to the CDC. Other chemicals and flavorings in the liquids that are heated during vaping can also damage the lungs. Fires and explosions, while rare, are also a risk that’s been previously documented by the FDA, the Centers for Disease Control and Prevention, and the Federal Emergency Management Agency.

Nationwide, there were 195 reported explosions and fires involving e-cigarettes in all ages between 2009 and 2016, according to a FEMA report. While no deaths were reported, 29% of these cases involved severe injuries.

“The shape and construction of electronic cigarettes” can make them behave like “flaming rockets when a battery fails,” according to FEMA.

Vaping devices typically use a rechargeable lithium-ion battery that vaporizes the liquid nicotine solution, Dr. Acker said. “They are not highly regulated, and the batteries may be of inferior quality and prone to explosion.”

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

SAN FRANCISCO – Along with first responders, health care workers in pulmonary and critical care have borne the brunt of the COVID-19 pandemic, and it’s not surprising that a large proportion have suffered from burnout, a syndrome characterized by chronic workplace stress, emotional exhaustion, cynicism about the job, and a reduced sense of personal accomplishment.

“Prior to the pandemic, 50% of providers reported burnout, and that, of course, has been exacerbated, with recent surveys showing up to 80% of health care workers reporting burnout,” said Sangeeta Joshi, MD, of the division of pulmonary, allergy, and critical care medicine at Duke University in Durham, N.C.

In a randomized clinical trial, Dr. Joshi and colleagues showed that transcendental meditation (TM) can significantly improve burnout symptoms of emotional exhaustion, anxiety, and insomnia compared with other interventions, albeit without significant improvement in acute psychological distress.

Dr. Joshi reported the results of the trial at the American Thoracic Society’s international conference.
 

Mind-body intervention

TM, popularized in the 1960s by the Beatles and their guru, Maharishi Mahesh Yogi, is a nonpharmacologic mind-body intervention that has been shown to reduce sympathetic arousal and to promote a state of relaxation, Dr. Joshi said.

Although the mechanism of action is not fully understood, proposed explanations for its efficacy include increased alpha coherence, as seen on electroencephalography, and increases in blood flow to the prefrontal cortex, as visualized on functional MRI.

TM has been shown to be effective for reducing symptoms of posttraumatic stress disorder in veterans and for reducing stress and burnout symptoms in teachers, Dr. Joshi noted.
 

Randomized trial

To see whether TM could make a difference for health care providers, Dr. Joshi and colleagues screened candidates for burnout with the single-item Columbia–Suicide Severity Rating Scale and digital autonomic reactivity, a measure of the depth of physiologic stimulus.

Their study included 80 eligible participants, who were randomly assigned to receive either TM or treatment as usual.

The participants who received the intervention were assigned to attend four TM instruction sessions over 4 consecutive days, followed by four virtual follow-up sessions over the 3-month period. The investigators hypothesized that these participants would have significant improvements in symptoms of burnout over baseline compared with those assigned to standard treatments. Participants who underwent the intervention were encouraged to perform TM at home for 20 minutes twice each day.

Participants were evaluated at baseline and at 3-month follow-up with the Brief Symptom Inventory–18 (BSI), the Maslach Burnout Inventory (MBI), the Patient Health Questionnaire–9 (PHQ-9), the Generalized Anxiety Disorder–7, the Insomnia Severity Index (ISI), and the Connor Davidson Resilience Scale (CD-RISC)–25.

At baseline, 70% of all participants reported a history of visiting a psychiatrist or other mental health worker, and 91% reported onset of a mental health condition. Only 30% reported that they had had a mental health condition that resolved with treatment.

At 3 months, there were significant improvements over baseline in the TM group compared with the treatment-as-usual group for the MBI emotional exhaustion item (P = .005), insomnia (P = .029), and anxiety (P = .010). There was trend toward significance on the PHQ-9 (P = .057), but no significant difference in the Global Severity Index (the total score of BSI items).

There were improvements in both study arms in both the MBI professional accomplishment item and in the CD-RISC scale, but the between-group differences were not significant.

The results show that “TM is a feasible, efficacious intervention in health care workers, especially during a pandemic,” Dr. Joshi said.

Future studies of TM in this setting should expand the number of participants and recruitment sites so as to have the necessary power to detect statistically significant changes in the numerical scales, she said.
 

Integrating TM into employee wellness

“These results are really encouraging,” said Seppo Rinne, MD, PhD, assistant professor of medicine at Boston University, who comoderated the oral abstract session in which the data were presented but was not involved in the study.

Commenting on the fact that TM is not more widely offered as part of a package of services for treating employees with symptoms of burnout, he noted that “in the burnout literature, we have a tendency to dichotomize these individual vs. organizational interventions, and the reality is that they are probably more integrated, and it’s not really helpful for us to think about these as totally separate.

“We need organizational interventions that support individual wellness,” he said.

The trial was sponsored by Duke University. Dr. Joshi and Dr. Rinne reported no relevant financial relationships.

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

SAN FRANCISCO – Along with first responders, health care workers in pulmonary and critical care have borne the brunt of the COVID-19 pandemic, and it’s not surprising that a large proportion have suffered from burnout, a syndrome characterized by chronic workplace stress, emotional exhaustion, cynicism about the job, and a reduced sense of personal accomplishment.

“Prior to the pandemic, 50% of providers reported burnout, and that, of course, has been exacerbated, with recent surveys showing up to 80% of health care workers reporting burnout,” said Sangeeta Joshi, MD, of the division of pulmonary, allergy, and critical care medicine at Duke University in Durham, N.C.

In a randomized clinical trial, Dr. Joshi and colleagues showed that transcendental meditation (TM) can significantly improve burnout symptoms of emotional exhaustion, anxiety, and insomnia compared with other interventions, albeit without significant improvement in acute psychological distress.

Dr. Joshi reported the results of the trial at the American Thoracic Society’s international conference.
 

Mind-body intervention

TM, popularized in the 1960s by the Beatles and their guru, Maharishi Mahesh Yogi, is a nonpharmacologic mind-body intervention that has been shown to reduce sympathetic arousal and to promote a state of relaxation, Dr. Joshi said.

Although the mechanism of action is not fully understood, proposed explanations for its efficacy include increased alpha coherence, as seen on electroencephalography, and increases in blood flow to the prefrontal cortex, as visualized on functional MRI.

TM has been shown to be effective for reducing symptoms of posttraumatic stress disorder in veterans and for reducing stress and burnout symptoms in teachers, Dr. Joshi noted.
 

Randomized trial

To see whether TM could make a difference for health care providers, Dr. Joshi and colleagues screened candidates for burnout with the single-item Columbia–Suicide Severity Rating Scale and digital autonomic reactivity, a measure of the depth of physiologic stimulus.

Their study included 80 eligible participants, who were randomly assigned to receive either TM or treatment as usual.

The participants who received the intervention were assigned to attend four TM instruction sessions over 4 consecutive days, followed by four virtual follow-up sessions over the 3-month period. The investigators hypothesized that these participants would have significant improvements in symptoms of burnout over baseline compared with those assigned to standard treatments. Participants who underwent the intervention were encouraged to perform TM at home for 20 minutes twice each day.

Participants were evaluated at baseline and at 3-month follow-up with the Brief Symptom Inventory–18 (BSI), the Maslach Burnout Inventory (MBI), the Patient Health Questionnaire–9 (PHQ-9), the Generalized Anxiety Disorder–7, the Insomnia Severity Index (ISI), and the Connor Davidson Resilience Scale (CD-RISC)–25.

At baseline, 70% of all participants reported a history of visiting a psychiatrist or other mental health worker, and 91% reported onset of a mental health condition. Only 30% reported that they had had a mental health condition that resolved with treatment.

At 3 months, there were significant improvements over baseline in the TM group compared with the treatment-as-usual group for the MBI emotional exhaustion item (P = .005), insomnia (P = .029), and anxiety (P = .010). There was trend toward significance on the PHQ-9 (P = .057), but no significant difference in the Global Severity Index (the total score of BSI items).

There were improvements in both study arms in both the MBI professional accomplishment item and in the CD-RISC scale, but the between-group differences were not significant.

The results show that “TM is a feasible, efficacious intervention in health care workers, especially during a pandemic,” Dr. Joshi said.

Future studies of TM in this setting should expand the number of participants and recruitment sites so as to have the necessary power to detect statistically significant changes in the numerical scales, she said.
 

Integrating TM into employee wellness

“These results are really encouraging,” said Seppo Rinne, MD, PhD, assistant professor of medicine at Boston University, who comoderated the oral abstract session in which the data were presented but was not involved in the study.

Commenting on the fact that TM is not more widely offered as part of a package of services for treating employees with symptoms of burnout, he noted that “in the burnout literature, we have a tendency to dichotomize these individual vs. organizational interventions, and the reality is that they are probably more integrated, and it’s not really helpful for us to think about these as totally separate.

“We need organizational interventions that support individual wellness,” he said.

The trial was sponsored by Duke University. Dr. Joshi and Dr. Rinne reported no relevant financial relationships.

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

SAN FRANCISCO – Along with first responders, health care workers in pulmonary and critical care have borne the brunt of the COVID-19 pandemic, and it’s not surprising that a large proportion have suffered from burnout, a syndrome characterized by chronic workplace stress, emotional exhaustion, cynicism about the job, and a reduced sense of personal accomplishment.

“Prior to the pandemic, 50% of providers reported burnout, and that, of course, has been exacerbated, with recent surveys showing up to 80% of health care workers reporting burnout,” said Sangeeta Joshi, MD, of the division of pulmonary, allergy, and critical care medicine at Duke University in Durham, N.C.

In a randomized clinical trial, Dr. Joshi and colleagues showed that transcendental meditation (TM) can significantly improve burnout symptoms of emotional exhaustion, anxiety, and insomnia compared with other interventions, albeit without significant improvement in acute psychological distress.

Dr. Joshi reported the results of the trial at the American Thoracic Society’s international conference.
 

Mind-body intervention

TM, popularized in the 1960s by the Beatles and their guru, Maharishi Mahesh Yogi, is a nonpharmacologic mind-body intervention that has been shown to reduce sympathetic arousal and to promote a state of relaxation, Dr. Joshi said.

Although the mechanism of action is not fully understood, proposed explanations for its efficacy include increased alpha coherence, as seen on electroencephalography, and increases in blood flow to the prefrontal cortex, as visualized on functional MRI.

TM has been shown to be effective for reducing symptoms of posttraumatic stress disorder in veterans and for reducing stress and burnout symptoms in teachers, Dr. Joshi noted.
 

Randomized trial

To see whether TM could make a difference for health care providers, Dr. Joshi and colleagues screened candidates for burnout with the single-item Columbia–Suicide Severity Rating Scale and digital autonomic reactivity, a measure of the depth of physiologic stimulus.

Their study included 80 eligible participants, who were randomly assigned to receive either TM or treatment as usual.

The participants who received the intervention were assigned to attend four TM instruction sessions over 4 consecutive days, followed by four virtual follow-up sessions over the 3-month period. The investigators hypothesized that these participants would have significant improvements in symptoms of burnout over baseline compared with those assigned to standard treatments. Participants who underwent the intervention were encouraged to perform TM at home for 20 minutes twice each day.

Participants were evaluated at baseline and at 3-month follow-up with the Brief Symptom Inventory–18 (BSI), the Maslach Burnout Inventory (MBI), the Patient Health Questionnaire–9 (PHQ-9), the Generalized Anxiety Disorder–7, the Insomnia Severity Index (ISI), and the Connor Davidson Resilience Scale (CD-RISC)–25.

At baseline, 70% of all participants reported a history of visiting a psychiatrist or other mental health worker, and 91% reported onset of a mental health condition. Only 30% reported that they had had a mental health condition that resolved with treatment.

At 3 months, there were significant improvements over baseline in the TM group compared with the treatment-as-usual group for the MBI emotional exhaustion item (P = .005), insomnia (P = .029), and anxiety (P = .010). There was trend toward significance on the PHQ-9 (P = .057), but no significant difference in the Global Severity Index (the total score of BSI items).

There were improvements in both study arms in both the MBI professional accomplishment item and in the CD-RISC scale, but the between-group differences were not significant.

The results show that “TM is a feasible, efficacious intervention in health care workers, especially during a pandemic,” Dr. Joshi said.

Future studies of TM in this setting should expand the number of participants and recruitment sites so as to have the necessary power to detect statistically significant changes in the numerical scales, she said.
 

Integrating TM into employee wellness

“These results are really encouraging,” said Seppo Rinne, MD, PhD, assistant professor of medicine at Boston University, who comoderated the oral abstract session in which the data were presented but was not involved in the study.

Commenting on the fact that TM is not more widely offered as part of a package of services for treating employees with symptoms of burnout, he noted that “in the burnout literature, we have a tendency to dichotomize these individual vs. organizational interventions, and the reality is that they are probably more integrated, and it’s not really helpful for us to think about these as totally separate.

“We need organizational interventions that support individual wellness,” he said.

The trial was sponsored by Duke University. Dr. Joshi and Dr. Rinne reported no relevant financial relationships.

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

Respiratory syncytial virus (RSV) caused more than 100,000 deaths in children under age 5 years globally in 2019, according to an analysis published online in The Lancet.

Researchers, led by You Li, PhD, of Nanjing (China) Medical University, found that nearly half of those (more than 45,000) occurred in children younger than 6 months old.

They estimated that RSV causes 1 in 50 deaths among children under 5 years old, and 1 in 28 deaths in children under 6 months old.

Additionally, RSV is responsible for an estimated 3.6 million hospital admissions globally each year, according to the report.

This analysis is the first to sift RSV disease burden into narrow age brackets, the authors said.

The numbers highlight that almost all of the deaths (97%) were in low- and middle-income countries.
 

Messages for prevention

Tina Hartert, MD, MPH, a professor in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., who was not part of the study, wrote in an invited commentary that these findings will be important in RSV prevention.

Among the most notable findings, she wrote, is the heavy mortality in the 0- to 6-month age group, which she notes is “the age group targeted by vaccination during pregnancy and birth-dose immunoprophylaxis.”

Dr. Hartert, who coauthored the commentary with Justin R. Ortiz, MD, MS, with the Center for Vaccine Development and Global Health, University of Maryland, Baltimore, told this news organization, “RSV is a respiratory virus that infects nearly every child by the time they are 2-3 years of age, with severe infection and death most common in the youngest infants. Vaccines that prevent the most severe infections in these young infants will likely be one of the best ways to prevent these severe infections and death.”

Though the authors found most deaths occur in low- and middle-income countries, RSV is one of the most common reasons for infant hospitalization in the US and affects 1% to 3% of infants, half of whom are full-term and otherwise healthy, Dr. Hartert said.

It is also one of the most common causes of infant lower respiratory tract infection in young children in the United States, she said, and it causes the most severe disease at the age extremes, with older adults experiencing significant morbidity with RSV.

Dr. Li said in an interview that although the team did not focus on reporting country-specific estimates in this work, their previous work, resulted in estimates of 98,000-155,000 RSV-related hospitalizations in children under 5 years old in the United States in 2019. Between 65,000 and 86,000 were in infants less than 1 year old.

Currently, he said, the only available RSV prophylaxis is palivizumab (Synagis), which is expensive and given only to high-risk infants in high-income countries, including the United States.

“There have been a number of promising RSV prophylactic products including maternal vaccine and monoclonal antibodies that have the potential for targeting the general infant population – not just high-risk infants – in late-phase clinical trials,” he said. “Our estimates of RSV-related disease burden will help anticipate the impact of future RSV immunization programs.”
 

Pandemic changed patterns

This research was completed before the COVID-19 pandemic, and it is not yet known how that could affect RSV disease burden long term.

However, Dr. Hartert said, RSV circulation has been significantly changed during the pandemic, both in intensity and timing, likely because of a combination of COVID and the public health preventive measures.

“As people return to normal activities and the public health measures put in place to stop the spread of COVID are eased, we are likely to see increases in circulation of RSV and return to its circulation during the winter months – typically similar to circulation of flu – from November through March in temperate climates in the northern hemisphere,” she said.

A coauthor of the paper, Harish Nair, PhD, with the Centre for Global Health, Usher Institute, University of Edinburgh, said in a press release that their findings have particular significance as COVID restrictions ease around the globe.

“The majority of the young children born in the last 2 years have never been exposed to RSV (and therefore have no immunity against this virus),” Nair wrote.
 

Most deaths occurring outside hospitals

A challenge in reducing the deaths in those 5 years old and younger is that most (76%) of deaths are happening in the community outside hospitals.

The authors wrote: “For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community.”

The percentage dying outside hospitals is even larger (81%) in low- to middle-income countries.

This work built on a previous review by the team that analyzed 317 studies. They updated their search with 113 new eligible studies and unpublished data from 51 papers published between Jan. 1, 2017, and Dec. 31, 2020.

The authors acknowledged some limitations, including variations in study settings and in definitions for acute lower respiratory infection, healthcare access, and eligibility for RSV testing.

The study was funded by EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe. Dr. Li reported grants from Wellcome Trust and the World Health Organization outside the submitted work. Dr. Hartert, Dr. Ortiz, and Dr. Nair disclosed no relevant financial relationships.

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

Respiratory syncytial virus (RSV) caused more than 100,000 deaths in children under age 5 years globally in 2019, according to an analysis published online in The Lancet.

Researchers, led by You Li, PhD, of Nanjing (China) Medical University, found that nearly half of those (more than 45,000) occurred in children younger than 6 months old.

They estimated that RSV causes 1 in 50 deaths among children under 5 years old, and 1 in 28 deaths in children under 6 months old.

Additionally, RSV is responsible for an estimated 3.6 million hospital admissions globally each year, according to the report.

This analysis is the first to sift RSV disease burden into narrow age brackets, the authors said.

The numbers highlight that almost all of the deaths (97%) were in low- and middle-income countries.
 

Messages for prevention

Tina Hartert, MD, MPH, a professor in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., who was not part of the study, wrote in an invited commentary that these findings will be important in RSV prevention.

Among the most notable findings, she wrote, is the heavy mortality in the 0- to 6-month age group, which she notes is “the age group targeted by vaccination during pregnancy and birth-dose immunoprophylaxis.”

Dr. Hartert, who coauthored the commentary with Justin R. Ortiz, MD, MS, with the Center for Vaccine Development and Global Health, University of Maryland, Baltimore, told this news organization, “RSV is a respiratory virus that infects nearly every child by the time they are 2-3 years of age, with severe infection and death most common in the youngest infants. Vaccines that prevent the most severe infections in these young infants will likely be one of the best ways to prevent these severe infections and death.”

Though the authors found most deaths occur in low- and middle-income countries, RSV is one of the most common reasons for infant hospitalization in the US and affects 1% to 3% of infants, half of whom are full-term and otherwise healthy, Dr. Hartert said.

It is also one of the most common causes of infant lower respiratory tract infection in young children in the United States, she said, and it causes the most severe disease at the age extremes, with older adults experiencing significant morbidity with RSV.

Dr. Li said in an interview that although the team did not focus on reporting country-specific estimates in this work, their previous work, resulted in estimates of 98,000-155,000 RSV-related hospitalizations in children under 5 years old in the United States in 2019. Between 65,000 and 86,000 were in infants less than 1 year old.

Currently, he said, the only available RSV prophylaxis is palivizumab (Synagis), which is expensive and given only to high-risk infants in high-income countries, including the United States.

“There have been a number of promising RSV prophylactic products including maternal vaccine and monoclonal antibodies that have the potential for targeting the general infant population – not just high-risk infants – in late-phase clinical trials,” he said. “Our estimates of RSV-related disease burden will help anticipate the impact of future RSV immunization programs.”
 

Pandemic changed patterns

This research was completed before the COVID-19 pandemic, and it is not yet known how that could affect RSV disease burden long term.

However, Dr. Hartert said, RSV circulation has been significantly changed during the pandemic, both in intensity and timing, likely because of a combination of COVID and the public health preventive measures.

“As people return to normal activities and the public health measures put in place to stop the spread of COVID are eased, we are likely to see increases in circulation of RSV and return to its circulation during the winter months – typically similar to circulation of flu – from November through March in temperate climates in the northern hemisphere,” she said.

A coauthor of the paper, Harish Nair, PhD, with the Centre for Global Health, Usher Institute, University of Edinburgh, said in a press release that their findings have particular significance as COVID restrictions ease around the globe.

“The majority of the young children born in the last 2 years have never been exposed to RSV (and therefore have no immunity against this virus),” Nair wrote.
 

Most deaths occurring outside hospitals

A challenge in reducing the deaths in those 5 years old and younger is that most (76%) of deaths are happening in the community outside hospitals.

The authors wrote: “For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community.”

The percentage dying outside hospitals is even larger (81%) in low- to middle-income countries.

This work built on a previous review by the team that analyzed 317 studies. They updated their search with 113 new eligible studies and unpublished data from 51 papers published between Jan. 1, 2017, and Dec. 31, 2020.

The authors acknowledged some limitations, including variations in study settings and in definitions for acute lower respiratory infection, healthcare access, and eligibility for RSV testing.

The study was funded by EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe. Dr. Li reported grants from Wellcome Trust and the World Health Organization outside the submitted work. Dr. Hartert, Dr. Ortiz, and Dr. Nair disclosed no relevant financial relationships.

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

Respiratory syncytial virus (RSV) caused more than 100,000 deaths in children under age 5 years globally in 2019, according to an analysis published online in The Lancet.

Researchers, led by You Li, PhD, of Nanjing (China) Medical University, found that nearly half of those (more than 45,000) occurred in children younger than 6 months old.

They estimated that RSV causes 1 in 50 deaths among children under 5 years old, and 1 in 28 deaths in children under 6 months old.

Additionally, RSV is responsible for an estimated 3.6 million hospital admissions globally each year, according to the report.

This analysis is the first to sift RSV disease burden into narrow age brackets, the authors said.

The numbers highlight that almost all of the deaths (97%) were in low- and middle-income countries.
 

Messages for prevention

Tina Hartert, MD, MPH, a professor in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., who was not part of the study, wrote in an invited commentary that these findings will be important in RSV prevention.

Among the most notable findings, she wrote, is the heavy mortality in the 0- to 6-month age group, which she notes is “the age group targeted by vaccination during pregnancy and birth-dose immunoprophylaxis.”

Dr. Hartert, who coauthored the commentary with Justin R. Ortiz, MD, MS, with the Center for Vaccine Development and Global Health, University of Maryland, Baltimore, told this news organization, “RSV is a respiratory virus that infects nearly every child by the time they are 2-3 years of age, with severe infection and death most common in the youngest infants. Vaccines that prevent the most severe infections in these young infants will likely be one of the best ways to prevent these severe infections and death.”

Though the authors found most deaths occur in low- and middle-income countries, RSV is one of the most common reasons for infant hospitalization in the US and affects 1% to 3% of infants, half of whom are full-term and otherwise healthy, Dr. Hartert said.

It is also one of the most common causes of infant lower respiratory tract infection in young children in the United States, she said, and it causes the most severe disease at the age extremes, with older adults experiencing significant morbidity with RSV.

Dr. Li said in an interview that although the team did not focus on reporting country-specific estimates in this work, their previous work, resulted in estimates of 98,000-155,000 RSV-related hospitalizations in children under 5 years old in the United States in 2019. Between 65,000 and 86,000 were in infants less than 1 year old.

Currently, he said, the only available RSV prophylaxis is palivizumab (Synagis), which is expensive and given only to high-risk infants in high-income countries, including the United States.

“There have been a number of promising RSV prophylactic products including maternal vaccine and monoclonal antibodies that have the potential for targeting the general infant population – not just high-risk infants – in late-phase clinical trials,” he said. “Our estimates of RSV-related disease burden will help anticipate the impact of future RSV immunization programs.”
 

Pandemic changed patterns

This research was completed before the COVID-19 pandemic, and it is not yet known how that could affect RSV disease burden long term.

However, Dr. Hartert said, RSV circulation has been significantly changed during the pandemic, both in intensity and timing, likely because of a combination of COVID and the public health preventive measures.

“As people return to normal activities and the public health measures put in place to stop the spread of COVID are eased, we are likely to see increases in circulation of RSV and return to its circulation during the winter months – typically similar to circulation of flu – from November through March in temperate climates in the northern hemisphere,” she said.

A coauthor of the paper, Harish Nair, PhD, with the Centre for Global Health, Usher Institute, University of Edinburgh, said in a press release that their findings have particular significance as COVID restrictions ease around the globe.

“The majority of the young children born in the last 2 years have never been exposed to RSV (and therefore have no immunity against this virus),” Nair wrote.
 

Most deaths occurring outside hospitals

A challenge in reducing the deaths in those 5 years old and younger is that most (76%) of deaths are happening in the community outside hospitals.

The authors wrote: “For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community.”

The percentage dying outside hospitals is even larger (81%) in low- to middle-income countries.

This work built on a previous review by the team that analyzed 317 studies. They updated their search with 113 new eligible studies and unpublished data from 51 papers published between Jan. 1, 2017, and Dec. 31, 2020.

The authors acknowledged some limitations, including variations in study settings and in definitions for acute lower respiratory infection, healthcare access, and eligibility for RSV testing.

The study was funded by EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe. Dr. Li reported grants from Wellcome Trust and the World Health Organization outside the submitted work. Dr. Hartert, Dr. Ortiz, and Dr. Nair disclosed no relevant financial relationships.

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

MADRID – There is increasing evidence of the impact that SARS-CoV-2 infection has on patients with diabetes. It involves the relationship between COVID-19 and new diagnoses of diabetes and blood glucose disorders, among others, in the post–COVID-19 period. These topics were addressed at the XXXIII National Congress of the Spanish Diabetes Society. They were also the central theme of the inaugural conference, Pancreatic Involvement During COVID-19: From Preclinical Studies to Clinical Relevance, which was led by Alexander Kleger, MD, PhD, head of the department of pancreatology at the Ulm (Germany) University Clinic for Internal Medicine.

The chair of the scientific committee of the congress, Franz Martín, MD, launched the conference by noting that the work of Dr. Kleger and his team has made it possible to ascertain that SARS-CoV-2 can infect pancreatic beta cells that produce insulin. This observation may help in understanding why patients with COVID-19 sometimes experience symptoms related to greater difficulty regulating blood glucose.

“In addition, the German expert and his group have described the abnormalities that occur in beta cells when they are infected by SARS-CoV-2, something especially important, given that knowledge of these abnormalities may be of great importance to understanding the possible appearance of more cases of diabetes in the future,” Dr. Martín added.

“Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that pancreatic beta cell involvement could contribute to the metabolic dysregulation seen in COVID-19 patients,” Dr. Kleger pointed out.

In his speech, Dr. Kleger reviewed the evidence on the effects of SARS-CoV-2 that has been garnered since the start of the pandemic, and he presented his research group’s findings on the impact at the pancreatic level.

“Since March 2020, it has been seen that COVID-19 affected the pancreas, and studies published in August of that same year clearly spoke of both a worsening of diabetes and an increase in new cases of this disease diagnosed after SARS-CoV-2 infection. Also, the data showed how hospitalized patients with no previous history of diabetes experienced rapid increases in glucose levels 5 days after admission,” Dr. Kleger said.
 

Angiotensin-converting enzyme 2

As an example of the pace at which evidence on the pancreatic impact of this virus has been evolving, Dr. Kleger referred to early studies that found no angiotensin-converting enzyme 2 receptor on cells of the endocrine and exocrine pancreas. “To our surprise, in our work, we did observe the obvious presence of angiotensin-converting enzyme 2 specifically expressed in human pancreatic beta cells, something confirmed by other investigations. Another surprising aspect was verifying that the viral infection lasts longer in the pancreas than in the lungs,” said the expert.

These findings caused the researchers to realize that SARS-CoV-2 may be directly or indirectly associated with diabetes. “It is currently the subject of debate whether it may be a direct effect, infecting or directly reaching the pancreatic beta cells, or whether this involvement is a result of the effect of the infection at systemic level, in the context of the cytokine storm and the proinflammatory environment derived from it. Our current challenge is to confirm whether this virus can really replicate in pancreatic beta cells and to assess the possible existence of reinfections, among other aspects,” said Dr. Kleger.

Along with these “developing areas of knowledge,” there are several certainties regarding the link between diabetes and COVID-19. Dr. Kleger summarized the most relevant one. “Preexisting diabetes is known to be a highly prevalent comorbidity seen in 11%-22% of patients and increases the risk of severe disease and mortality.

“SARS-CoV-2 infection has also been shown to affect the exocrine pancreas, manifesting as pancreatitis in 5% of critically ill patients with COVID-19, as well as enlargement of the pancreas and abnormal levels of amylase or lipase in 7.5%-17% of patients.

“Furthermore, it is obvious that SARS-CoV-2 infection produces glycometabolic dysfunction in these patients, with increased hyperglycemia in people with type 2 diabetes and ketoacidosis in 2%-6.4% of patients with and without diabetes.”
 

After recovery

The most recent research reveals the persistence of this dysregulation long after recovery from COVID-19. “We’ve seen that in a significant proportion of patients, hyperglycemia is maintained for some time; in the specific case of hospitalized patients [without the need for assisted ventilation or other intensive care requirements], for up to more than 2 months after overcoming the illness.

“In the same way, there are studies that have shown that insulin resistance and hyperstimulation of pancreatic beta cells remain at pathological levels in the post–COVID-19 phase. And in line with increased insulin resistance, signs of hyperinflammation have also been detected in these patients.”

Dr. Kleger noted that another research area is the increased incidence of newly diagnosed diabetes after recovery from SARS-CoV-2 infection, “something that seems to be correlated with how severely the disease has been experienced and also depending on whether hospitalization or intensive care was needed. Likewise, retrospective studies have shown that the risk of developing type 2 diabetes is higher in COVID-19 patients, compared with those with other respiratory infections. Regarding the incidence of type 1 diabetes, there is evidence, particularly in the case of children, of a clear correlation between the pandemic waves and the increase in cases.

“Therefore, and in view of this data, we could say that, with regard to the involvement of SARS-CoV-2 in pancreatic beta cells, something is up, but we are not yet able to fully understand what it is. What can be confirmed based on the numerous studies carried out in this regard is that COVID-19 produces a metabolic dysregulation [hyperglycemia, insulin resistance, diabetic ketoacidosis] which in turn favors the development of diabetes in patients with no history of this disease,” said Dr. Kleger.

“Likewise, everything points to the existence of a definitively feasible infection in pancreatic beta cells associated with SARS-CoV-2, but there are still unknown aspects of the physiology that explain this effect that remain the subject of debate and deserve future studies,” he concluded.
 

Consequences of the pandemic

The experts agreed that, although COVID-19 is no longer at the center of specialist care, it is still a subject of investigation. On the conference’s opening day, an update was made on the approach to diabetes.

Care activity is gradually recovering as the time that professionals devote to COVID-19 care is reduced, “but it will take time to catch up with the care activities not carried out during the pandemic, and, unfortunately, in the coming years, we will see the repercussion of the lack or reduction of care during these years,” stressed the SED chair, Antonio Pérez Pérez, MD, director of endocrinology and nutrition of Hospital de la Santa Creu i Sant Pau, Barcelona.

Dr. Pérez stressed that the pandemic has revealed health system deficiencies in diabetes care. He added that the impact of COVID-19 on diabetes (resulting from the effects of the infection itself or from the inadequacy of prevention, diagnosis, and treatment measures) fostered a deterioration of metabolic control and a delay in the diagnosis of the disease and its complications.

“All this contributes to the fact that we currently continue to see patients with complications, especially in the case of type 2 diabetes, with more serious decompensations and diagnoses in more advanced stages of the disease. This impact has been more significant in older people from disadvantaged areas and with less capacity for self-monitoring and self-adjustment of treatment,” he added.

Describing lessons learned through the experiences accumulated in diabetes care during the pandemic, Dr. Pérez highlighted the push for virtual consultations, accessibility to drugs prescribed in electronic prescriptions, and the use of educational resources online and of telemedicine tools. “The need to invest in the health sector has also been assumed, endowing it with robustness in well-trained health personnel, to promote health education, boost efficient health organization, and invest in innovation aimed at facilitating care.”

Dr. Kleger and Dr. Pérez disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

MADRID – There is increasing evidence of the impact that SARS-CoV-2 infection has on patients with diabetes. It involves the relationship between COVID-19 and new diagnoses of diabetes and blood glucose disorders, among others, in the post–COVID-19 period. These topics were addressed at the XXXIII National Congress of the Spanish Diabetes Society. They were also the central theme of the inaugural conference, Pancreatic Involvement During COVID-19: From Preclinical Studies to Clinical Relevance, which was led by Alexander Kleger, MD, PhD, head of the department of pancreatology at the Ulm (Germany) University Clinic for Internal Medicine.

The chair of the scientific committee of the congress, Franz Martín, MD, launched the conference by noting that the work of Dr. Kleger and his team has made it possible to ascertain that SARS-CoV-2 can infect pancreatic beta cells that produce insulin. This observation may help in understanding why patients with COVID-19 sometimes experience symptoms related to greater difficulty regulating blood glucose.

“In addition, the German expert and his group have described the abnormalities that occur in beta cells when they are infected by SARS-CoV-2, something especially important, given that knowledge of these abnormalities may be of great importance to understanding the possible appearance of more cases of diabetes in the future,” Dr. Martín added.

“Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that pancreatic beta cell involvement could contribute to the metabolic dysregulation seen in COVID-19 patients,” Dr. Kleger pointed out.

In his speech, Dr. Kleger reviewed the evidence on the effects of SARS-CoV-2 that has been garnered since the start of the pandemic, and he presented his research group’s findings on the impact at the pancreatic level.

“Since March 2020, it has been seen that COVID-19 affected the pancreas, and studies published in August of that same year clearly spoke of both a worsening of diabetes and an increase in new cases of this disease diagnosed after SARS-CoV-2 infection. Also, the data showed how hospitalized patients with no previous history of diabetes experienced rapid increases in glucose levels 5 days after admission,” Dr. Kleger said.
 

Angiotensin-converting enzyme 2

As an example of the pace at which evidence on the pancreatic impact of this virus has been evolving, Dr. Kleger referred to early studies that found no angiotensin-converting enzyme 2 receptor on cells of the endocrine and exocrine pancreas. “To our surprise, in our work, we did observe the obvious presence of angiotensin-converting enzyme 2 specifically expressed in human pancreatic beta cells, something confirmed by other investigations. Another surprising aspect was verifying that the viral infection lasts longer in the pancreas than in the lungs,” said the expert.

These findings caused the researchers to realize that SARS-CoV-2 may be directly or indirectly associated with diabetes. “It is currently the subject of debate whether it may be a direct effect, infecting or directly reaching the pancreatic beta cells, or whether this involvement is a result of the effect of the infection at systemic level, in the context of the cytokine storm and the proinflammatory environment derived from it. Our current challenge is to confirm whether this virus can really replicate in pancreatic beta cells and to assess the possible existence of reinfections, among other aspects,” said Dr. Kleger.

Along with these “developing areas of knowledge,” there are several certainties regarding the link between diabetes and COVID-19. Dr. Kleger summarized the most relevant one. “Preexisting diabetes is known to be a highly prevalent comorbidity seen in 11%-22% of patients and increases the risk of severe disease and mortality.

“SARS-CoV-2 infection has also been shown to affect the exocrine pancreas, manifesting as pancreatitis in 5% of critically ill patients with COVID-19, as well as enlargement of the pancreas and abnormal levels of amylase or lipase in 7.5%-17% of patients.

“Furthermore, it is obvious that SARS-CoV-2 infection produces glycometabolic dysfunction in these patients, with increased hyperglycemia in people with type 2 diabetes and ketoacidosis in 2%-6.4% of patients with and without diabetes.”
 

After recovery

The most recent research reveals the persistence of this dysregulation long after recovery from COVID-19. “We’ve seen that in a significant proportion of patients, hyperglycemia is maintained for some time; in the specific case of hospitalized patients [without the need for assisted ventilation or other intensive care requirements], for up to more than 2 months after overcoming the illness.

“In the same way, there are studies that have shown that insulin resistance and hyperstimulation of pancreatic beta cells remain at pathological levels in the post–COVID-19 phase. And in line with increased insulin resistance, signs of hyperinflammation have also been detected in these patients.”

Dr. Kleger noted that another research area is the increased incidence of newly diagnosed diabetes after recovery from SARS-CoV-2 infection, “something that seems to be correlated with how severely the disease has been experienced and also depending on whether hospitalization or intensive care was needed. Likewise, retrospective studies have shown that the risk of developing type 2 diabetes is higher in COVID-19 patients, compared with those with other respiratory infections. Regarding the incidence of type 1 diabetes, there is evidence, particularly in the case of children, of a clear correlation between the pandemic waves and the increase in cases.

“Therefore, and in view of this data, we could say that, with regard to the involvement of SARS-CoV-2 in pancreatic beta cells, something is up, but we are not yet able to fully understand what it is. What can be confirmed based on the numerous studies carried out in this regard is that COVID-19 produces a metabolic dysregulation [hyperglycemia, insulin resistance, diabetic ketoacidosis] which in turn favors the development of diabetes in patients with no history of this disease,” said Dr. Kleger.

“Likewise, everything points to the existence of a definitively feasible infection in pancreatic beta cells associated with SARS-CoV-2, but there are still unknown aspects of the physiology that explain this effect that remain the subject of debate and deserve future studies,” he concluded.
 

Consequences of the pandemic

The experts agreed that, although COVID-19 is no longer at the center of specialist care, it is still a subject of investigation. On the conference’s opening day, an update was made on the approach to diabetes.

Care activity is gradually recovering as the time that professionals devote to COVID-19 care is reduced, “but it will take time to catch up with the care activities not carried out during the pandemic, and, unfortunately, in the coming years, we will see the repercussion of the lack or reduction of care during these years,” stressed the SED chair, Antonio Pérez Pérez, MD, director of endocrinology and nutrition of Hospital de la Santa Creu i Sant Pau, Barcelona.

Dr. Pérez stressed that the pandemic has revealed health system deficiencies in diabetes care. He added that the impact of COVID-19 on diabetes (resulting from the effects of the infection itself or from the inadequacy of prevention, diagnosis, and treatment measures) fostered a deterioration of metabolic control and a delay in the diagnosis of the disease and its complications.

“All this contributes to the fact that we currently continue to see patients with complications, especially in the case of type 2 diabetes, with more serious decompensations and diagnoses in more advanced stages of the disease. This impact has been more significant in older people from disadvantaged areas and with less capacity for self-monitoring and self-adjustment of treatment,” he added.

Describing lessons learned through the experiences accumulated in diabetes care during the pandemic, Dr. Pérez highlighted the push for virtual consultations, accessibility to drugs prescribed in electronic prescriptions, and the use of educational resources online and of telemedicine tools. “The need to invest in the health sector has also been assumed, endowing it with robustness in well-trained health personnel, to promote health education, boost efficient health organization, and invest in innovation aimed at facilitating care.”

Dr. Kleger and Dr. Pérez disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

MADRID – There is increasing evidence of the impact that SARS-CoV-2 infection has on patients with diabetes. It involves the relationship between COVID-19 and new diagnoses of diabetes and blood glucose disorders, among others, in the post–COVID-19 period. These topics were addressed at the XXXIII National Congress of the Spanish Diabetes Society. They were also the central theme of the inaugural conference, Pancreatic Involvement During COVID-19: From Preclinical Studies to Clinical Relevance, which was led by Alexander Kleger, MD, PhD, head of the department of pancreatology at the Ulm (Germany) University Clinic for Internal Medicine.

The chair of the scientific committee of the congress, Franz Martín, MD, launched the conference by noting that the work of Dr. Kleger and his team has made it possible to ascertain that SARS-CoV-2 can infect pancreatic beta cells that produce insulin. This observation may help in understanding why patients with COVID-19 sometimes experience symptoms related to greater difficulty regulating blood glucose.

“In addition, the German expert and his group have described the abnormalities that occur in beta cells when they are infected by SARS-CoV-2, something especially important, given that knowledge of these abnormalities may be of great importance to understanding the possible appearance of more cases of diabetes in the future,” Dr. Martín added.

“Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that pancreatic beta cell involvement could contribute to the metabolic dysregulation seen in COVID-19 patients,” Dr. Kleger pointed out.

In his speech, Dr. Kleger reviewed the evidence on the effects of SARS-CoV-2 that has been garnered since the start of the pandemic, and he presented his research group’s findings on the impact at the pancreatic level.

“Since March 2020, it has been seen that COVID-19 affected the pancreas, and studies published in August of that same year clearly spoke of both a worsening of diabetes and an increase in new cases of this disease diagnosed after SARS-CoV-2 infection. Also, the data showed how hospitalized patients with no previous history of diabetes experienced rapid increases in glucose levels 5 days after admission,” Dr. Kleger said.
 

Angiotensin-converting enzyme 2

As an example of the pace at which evidence on the pancreatic impact of this virus has been evolving, Dr. Kleger referred to early studies that found no angiotensin-converting enzyme 2 receptor on cells of the endocrine and exocrine pancreas. “To our surprise, in our work, we did observe the obvious presence of angiotensin-converting enzyme 2 specifically expressed in human pancreatic beta cells, something confirmed by other investigations. Another surprising aspect was verifying that the viral infection lasts longer in the pancreas than in the lungs,” said the expert.

These findings caused the researchers to realize that SARS-CoV-2 may be directly or indirectly associated with diabetes. “It is currently the subject of debate whether it may be a direct effect, infecting or directly reaching the pancreatic beta cells, or whether this involvement is a result of the effect of the infection at systemic level, in the context of the cytokine storm and the proinflammatory environment derived from it. Our current challenge is to confirm whether this virus can really replicate in pancreatic beta cells and to assess the possible existence of reinfections, among other aspects,” said Dr. Kleger.

Along with these “developing areas of knowledge,” there are several certainties regarding the link between diabetes and COVID-19. Dr. Kleger summarized the most relevant one. “Preexisting diabetes is known to be a highly prevalent comorbidity seen in 11%-22% of patients and increases the risk of severe disease and mortality.

“SARS-CoV-2 infection has also been shown to affect the exocrine pancreas, manifesting as pancreatitis in 5% of critically ill patients with COVID-19, as well as enlargement of the pancreas and abnormal levels of amylase or lipase in 7.5%-17% of patients.

“Furthermore, it is obvious that SARS-CoV-2 infection produces glycometabolic dysfunction in these patients, with increased hyperglycemia in people with type 2 diabetes and ketoacidosis in 2%-6.4% of patients with and without diabetes.”
 

After recovery

The most recent research reveals the persistence of this dysregulation long after recovery from COVID-19. “We’ve seen that in a significant proportion of patients, hyperglycemia is maintained for some time; in the specific case of hospitalized patients [without the need for assisted ventilation or other intensive care requirements], for up to more than 2 months after overcoming the illness.

“In the same way, there are studies that have shown that insulin resistance and hyperstimulation of pancreatic beta cells remain at pathological levels in the post–COVID-19 phase. And in line with increased insulin resistance, signs of hyperinflammation have also been detected in these patients.”

Dr. Kleger noted that another research area is the increased incidence of newly diagnosed diabetes after recovery from SARS-CoV-2 infection, “something that seems to be correlated with how severely the disease has been experienced and also depending on whether hospitalization or intensive care was needed. Likewise, retrospective studies have shown that the risk of developing type 2 diabetes is higher in COVID-19 patients, compared with those with other respiratory infections. Regarding the incidence of type 1 diabetes, there is evidence, particularly in the case of children, of a clear correlation between the pandemic waves and the increase in cases.

“Therefore, and in view of this data, we could say that, with regard to the involvement of SARS-CoV-2 in pancreatic beta cells, something is up, but we are not yet able to fully understand what it is. What can be confirmed based on the numerous studies carried out in this regard is that COVID-19 produces a metabolic dysregulation [hyperglycemia, insulin resistance, diabetic ketoacidosis] which in turn favors the development of diabetes in patients with no history of this disease,” said Dr. Kleger.

“Likewise, everything points to the existence of a definitively feasible infection in pancreatic beta cells associated with SARS-CoV-2, but there are still unknown aspects of the physiology that explain this effect that remain the subject of debate and deserve future studies,” he concluded.
 

Consequences of the pandemic

The experts agreed that, although COVID-19 is no longer at the center of specialist care, it is still a subject of investigation. On the conference’s opening day, an update was made on the approach to diabetes.

Care activity is gradually recovering as the time that professionals devote to COVID-19 care is reduced, “but it will take time to catch up with the care activities not carried out during the pandemic, and, unfortunately, in the coming years, we will see the repercussion of the lack or reduction of care during these years,” stressed the SED chair, Antonio Pérez Pérez, MD, director of endocrinology and nutrition of Hospital de la Santa Creu i Sant Pau, Barcelona.

Dr. Pérez stressed that the pandemic has revealed health system deficiencies in diabetes care. He added that the impact of COVID-19 on diabetes (resulting from the effects of the infection itself or from the inadequacy of prevention, diagnosis, and treatment measures) fostered a deterioration of metabolic control and a delay in the diagnosis of the disease and its complications.

“All this contributes to the fact that we currently continue to see patients with complications, especially in the case of type 2 diabetes, with more serious decompensations and diagnoses in more advanced stages of the disease. This impact has been more significant in older people from disadvantaged areas and with less capacity for self-monitoring and self-adjustment of treatment,” he added.

Describing lessons learned through the experiences accumulated in diabetes care during the pandemic, Dr. Pérez highlighted the push for virtual consultations, accessibility to drugs prescribed in electronic prescriptions, and the use of educational resources online and of telemedicine tools. “The need to invest in the health sector has also been assumed, endowing it with robustness in well-trained health personnel, to promote health education, boost efficient health organization, and invest in innovation aimed at facilitating care.”

Dr. Kleger and Dr. Pérez disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.