Pulmonology

A new article in the Journal of Clinical Endocrinology & Metabolism (JCEM) addresses unique concerns and considerations regarding diabetic ketoacidosis (DKA) in the setting of COVID-19.

Corresponding author Marie E. McDonnell, MD, director of the diabetes program at Brigham and Women’s Hospital, Boston, Massachusetts, discussed the recommendations with Medscape Medical News and also spoke about the news this week that the corticosteroid dexamethasone reduced death rates in severely ill patients with COVID-19.

The full JCEM article, by lead author Nadine E. Palermo, DO, Division of Endocrinology, Diabetes, and Hypertension, also at Brigham and Women’s Hospital, covers DKA diagnosis and triage, and emphasizes that usual hospital protocols for DKA management may need to be adjusted during COVID-19 to help preserve personal protective equipment and ICU beds.

“Hospitals and clinicians need to be able to quickly identify and manage DKA in COVID patients to save lives. This involves determining the options for management, including when less intensive subcutaneous insulin is indicated, and understanding how to guide patients on avoiding this serious complication,” McDonnell said in an Endocrine Society statement.
 

What about dexamethasone for severe COVID-19 in diabetes?

The new article briefly touches on the fact that upward adjustments to intensive intravenous insulin therapy for DKA may be necessary in patients with COVID-19 who are receiving concomitant corticosteroids or vasopressors.

But it was written prior to the June 16 announcement of the “RECOVERY” trial results with dexamethasone. The UK National Health Service immediately approved the drug’s use in the COVID-19 setting, despite the fact that there has been no published article on the findings yet.

McDonnell told Medscape Medical News that she would need to see formal results to better understand exactly which patients were studied and which ones benefited.

“The peer review will be critical. It looks as if it only benefits people who need respiratory support, but I want to understand that in much more detail,” she said. “If they all had acute respiratory distress syndrome [ARDS],” that’s different.

“There are already some data supporting steroid use in ARDS,” she noted, but added that not all of it suggests benefit.

She pointed to one of several studies now showing that diabetes, and hyperglycemia among people without a prior diabetes diagnosis, are both strong predictors of mortality in hospitalized patients with COVID-19.

“There was a very clear relationship between hyperglycemia and outcomes. We really shouldn’t put people at risk until we have clear data,” she said.

If, once the data are reviewed and appropriate dexamethasone becomes an established treatment for severe COVID-19, hyperglycemia would be a concern among all patients, not just those with previously diagnosed diabetes, she noted.

“We know a good number of people with prediabetes develop hyperglycemia when put on steroids. They can push people over the edge. We’re not going to miss anybody, but treating steroid-induced hyperglycemia is really hard,” McDonnell explained.

She also recommended 2014 guidance from Diabetes UK and the Association of British Clinical Diabetologists, which addresses management of inpatient steroid-induced DKA in patients with and without pre-existing diabetes.

Another major concern, she said, is “patients trying to get dexamethasone when they start to get sick” because this is not the right population to use this agent.

“We worry about people who do not need this drug. If they have diabetes, they put themselves at risk of hyperglycemia, which then increases the risk of severe COVID-19. And then they’re also putting themselves at risk of DKA. It would just be bad medicine,” she said.

Managing DKA in the face of COVID-19: Flexibility is key

In the JCEM article, Palermo and colleagues emphasize that the usual hospital protocols for DKA management may need to be adjusted during COVID-19 in the interest of reducing transmission risk and preserving scare resources.

They provide evidence for alternative treatment strategies, such as the use of subcutaneous rather than intravenous insulin when appropriate.

“We wanted to outline when exactly you should consider nonintensive management strategies for DKA,” McDonnell further explained to Medscape Medical News.

“That would include those with mild or some with moderate DKA. ... The idea is to remind our colleagues about that because hospitals tend to operate on a protocol-driven algorithmic methodology, they can forget to step off the usual care pathway even if evidence supports that,” she said.   

But on the other hand, she also said that, in some very complex or severely ill patients with COVID-19, classical intravenous insulin therapy makes the most sense even if their DKA is mild.
 

The outpatient setting: Prevention and preparation

The new article also addresses several concerns regarding DKA prevention in the outpatient setting.

As with other guidelines, it includes a reminder that patients with diabetes should be advised to discontinue sodium-glucose cotransporter 2 (SGLT2) inhibitors if they become ill with COVID-19, especially if they’re not eating or drinking normally, because they raise the risk for DKA.

Also, for patients with type 1 diabetes, particularly those with a history of repeated DKA, “this is the time to make sure we reach out to patients to refill their insulin prescriptions and address issues related to cost and other access difficulties,” McDonnell said.

The authors also emphasize that insulin starts and education should not be postponed during the pandemic. “Patients identified as meeting criteria to start insulin should be referred for urgent education, either in person or, whenever possible and practical, via video teleconferencing,” they urge.

McDonnell has reported receiving research funding from Novo Nordisk. The other two authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

A new article in the Journal of Clinical Endocrinology & Metabolism (JCEM) addresses unique concerns and considerations regarding diabetic ketoacidosis (DKA) in the setting of COVID-19.

Corresponding author Marie E. McDonnell, MD, director of the diabetes program at Brigham and Women’s Hospital, Boston, Massachusetts, discussed the recommendations with Medscape Medical News and also spoke about the news this week that the corticosteroid dexamethasone reduced death rates in severely ill patients with COVID-19.

The full JCEM article, by lead author Nadine E. Palermo, DO, Division of Endocrinology, Diabetes, and Hypertension, also at Brigham and Women’s Hospital, covers DKA diagnosis and triage, and emphasizes that usual hospital protocols for DKA management may need to be adjusted during COVID-19 to help preserve personal protective equipment and ICU beds.

“Hospitals and clinicians need to be able to quickly identify and manage DKA in COVID patients to save lives. This involves determining the options for management, including when less intensive subcutaneous insulin is indicated, and understanding how to guide patients on avoiding this serious complication,” McDonnell said in an Endocrine Society statement.
 

What about dexamethasone for severe COVID-19 in diabetes?

The new article briefly touches on the fact that upward adjustments to intensive intravenous insulin therapy for DKA may be necessary in patients with COVID-19 who are receiving concomitant corticosteroids or vasopressors.

But it was written prior to the June 16 announcement of the “RECOVERY” trial results with dexamethasone. The UK National Health Service immediately approved the drug’s use in the COVID-19 setting, despite the fact that there has been no published article on the findings yet.

McDonnell told Medscape Medical News that she would need to see formal results to better understand exactly which patients were studied and which ones benefited.

“The peer review will be critical. It looks as if it only benefits people who need respiratory support, but I want to understand that in much more detail,” she said. “If they all had acute respiratory distress syndrome [ARDS],” that’s different.

“There are already some data supporting steroid use in ARDS,” she noted, but added that not all of it suggests benefit.

She pointed to one of several studies now showing that diabetes, and hyperglycemia among people without a prior diabetes diagnosis, are both strong predictors of mortality in hospitalized patients with COVID-19.

“There was a very clear relationship between hyperglycemia and outcomes. We really shouldn’t put people at risk until we have clear data,” she said.

If, once the data are reviewed and appropriate dexamethasone becomes an established treatment for severe COVID-19, hyperglycemia would be a concern among all patients, not just those with previously diagnosed diabetes, she noted.

“We know a good number of people with prediabetes develop hyperglycemia when put on steroids. They can push people over the edge. We’re not going to miss anybody, but treating steroid-induced hyperglycemia is really hard,” McDonnell explained.

She also recommended 2014 guidance from Diabetes UK and the Association of British Clinical Diabetologists, which addresses management of inpatient steroid-induced DKA in patients with and without pre-existing diabetes.

Another major concern, she said, is “patients trying to get dexamethasone when they start to get sick” because this is not the right population to use this agent.

“We worry about people who do not need this drug. If they have diabetes, they put themselves at risk of hyperglycemia, which then increases the risk of severe COVID-19. And then they’re also putting themselves at risk of DKA. It would just be bad medicine,” she said.

Managing DKA in the face of COVID-19: Flexibility is key

In the JCEM article, Palermo and colleagues emphasize that the usual hospital protocols for DKA management may need to be adjusted during COVID-19 in the interest of reducing transmission risk and preserving scare resources.

They provide evidence for alternative treatment strategies, such as the use of subcutaneous rather than intravenous insulin when appropriate.

“We wanted to outline when exactly you should consider nonintensive management strategies for DKA,” McDonnell further explained to Medscape Medical News.

“That would include those with mild or some with moderate DKA. ... The idea is to remind our colleagues about that because hospitals tend to operate on a protocol-driven algorithmic methodology, they can forget to step off the usual care pathway even if evidence supports that,” she said.   

But on the other hand, she also said that, in some very complex or severely ill patients with COVID-19, classical intravenous insulin therapy makes the most sense even if their DKA is mild.
 

The outpatient setting: Prevention and preparation

The new article also addresses several concerns regarding DKA prevention in the outpatient setting.

As with other guidelines, it includes a reminder that patients with diabetes should be advised to discontinue sodium-glucose cotransporter 2 (SGLT2) inhibitors if they become ill with COVID-19, especially if they’re not eating or drinking normally, because they raise the risk for DKA.

Also, for patients with type 1 diabetes, particularly those with a history of repeated DKA, “this is the time to make sure we reach out to patients to refill their insulin prescriptions and address issues related to cost and other access difficulties,” McDonnell said.

The authors also emphasize that insulin starts and education should not be postponed during the pandemic. “Patients identified as meeting criteria to start insulin should be referred for urgent education, either in person or, whenever possible and practical, via video teleconferencing,” they urge.

McDonnell has reported receiving research funding from Novo Nordisk. The other two authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

A new article in the Journal of Clinical Endocrinology & Metabolism (JCEM) addresses unique concerns and considerations regarding diabetic ketoacidosis (DKA) in the setting of COVID-19.

Corresponding author Marie E. McDonnell, MD, director of the diabetes program at Brigham and Women’s Hospital, Boston, Massachusetts, discussed the recommendations with Medscape Medical News and also spoke about the news this week that the corticosteroid dexamethasone reduced death rates in severely ill patients with COVID-19.

The full JCEM article, by lead author Nadine E. Palermo, DO, Division of Endocrinology, Diabetes, and Hypertension, also at Brigham and Women’s Hospital, covers DKA diagnosis and triage, and emphasizes that usual hospital protocols for DKA management may need to be adjusted during COVID-19 to help preserve personal protective equipment and ICU beds.

“Hospitals and clinicians need to be able to quickly identify and manage DKA in COVID patients to save lives. This involves determining the options for management, including when less intensive subcutaneous insulin is indicated, and understanding how to guide patients on avoiding this serious complication,” McDonnell said in an Endocrine Society statement.
 

What about dexamethasone for severe COVID-19 in diabetes?

The new article briefly touches on the fact that upward adjustments to intensive intravenous insulin therapy for DKA may be necessary in patients with COVID-19 who are receiving concomitant corticosteroids or vasopressors.

But it was written prior to the June 16 announcement of the “RECOVERY” trial results with dexamethasone. The UK National Health Service immediately approved the drug’s use in the COVID-19 setting, despite the fact that there has been no published article on the findings yet.

McDonnell told Medscape Medical News that she would need to see formal results to better understand exactly which patients were studied and which ones benefited.

“The peer review will be critical. It looks as if it only benefits people who need respiratory support, but I want to understand that in much more detail,” she said. “If they all had acute respiratory distress syndrome [ARDS],” that’s different.

“There are already some data supporting steroid use in ARDS,” she noted, but added that not all of it suggests benefit.

She pointed to one of several studies now showing that diabetes, and hyperglycemia among people without a prior diabetes diagnosis, are both strong predictors of mortality in hospitalized patients with COVID-19.

“There was a very clear relationship between hyperglycemia and outcomes. We really shouldn’t put people at risk until we have clear data,” she said.

If, once the data are reviewed and appropriate dexamethasone becomes an established treatment for severe COVID-19, hyperglycemia would be a concern among all patients, not just those with previously diagnosed diabetes, she noted.

“We know a good number of people with prediabetes develop hyperglycemia when put on steroids. They can push people over the edge. We’re not going to miss anybody, but treating steroid-induced hyperglycemia is really hard,” McDonnell explained.

She also recommended 2014 guidance from Diabetes UK and the Association of British Clinical Diabetologists, which addresses management of inpatient steroid-induced DKA in patients with and without pre-existing diabetes.

Another major concern, she said, is “patients trying to get dexamethasone when they start to get sick” because this is not the right population to use this agent.

“We worry about people who do not need this drug. If they have diabetes, they put themselves at risk of hyperglycemia, which then increases the risk of severe COVID-19. And then they’re also putting themselves at risk of DKA. It would just be bad medicine,” she said.

Managing DKA in the face of COVID-19: Flexibility is key

In the JCEM article, Palermo and colleagues emphasize that the usual hospital protocols for DKA management may need to be adjusted during COVID-19 in the interest of reducing transmission risk and preserving scare resources.

They provide evidence for alternative treatment strategies, such as the use of subcutaneous rather than intravenous insulin when appropriate.

“We wanted to outline when exactly you should consider nonintensive management strategies for DKA,” McDonnell further explained to Medscape Medical News.

“That would include those with mild or some with moderate DKA. ... The idea is to remind our colleagues about that because hospitals tend to operate on a protocol-driven algorithmic methodology, they can forget to step off the usual care pathway even if evidence supports that,” she said.   

But on the other hand, she also said that, in some very complex or severely ill patients with COVID-19, classical intravenous insulin therapy makes the most sense even if their DKA is mild.
 

The outpatient setting: Prevention and preparation

The new article also addresses several concerns regarding DKA prevention in the outpatient setting.

As with other guidelines, it includes a reminder that patients with diabetes should be advised to discontinue sodium-glucose cotransporter 2 (SGLT2) inhibitors if they become ill with COVID-19, especially if they’re not eating or drinking normally, because they raise the risk for DKA.

Also, for patients with type 1 diabetes, particularly those with a history of repeated DKA, “this is the time to make sure we reach out to patients to refill their insulin prescriptions and address issues related to cost and other access difficulties,” McDonnell said.

The authors also emphasize that insulin starts and education should not be postponed during the pandemic. “Patients identified as meeting criteria to start insulin should be referred for urgent education, either in person or, whenever possible and practical, via video teleconferencing,” they urge.

McDonnell has reported receiving research funding from Novo Nordisk. The other two authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Hospital charges for the treatment of children with asthma made up nearly half of all potentially avoidable pediatric inpatient costs in 2017, according to the Agency for Healthcare Research and Quality.

The cost of potentially avoidable visits for asthma that year was $278 million, versus $284 million combined for the other three conditions “that evidence suggests may be avoidable, in part, through timely and quality primary and preventive care,” Kimberly W. McDermott, PhD, and H. Joanna Jiang, PhD, said in an AHRQ statistical brief.

Those three other conditions are diabetes short-term complications, gastroenteritis, and urinary tract infections (UTIs). Neonatal stays were excluded from the analysis, Dr. McDermott of IBM Watson Health and Dr. Jiang of the AHRQ noted.

The state inpatient databases of the AHRQ’s Healthcare Cost and Utilization Project included 1.4 million inpatient stays among children aged 3 months to 17 years in 2017, of which 8% (108,300) were deemed potentially preventable. Hospital charges for the preventable stays came to $561.6 million, or 3% of the $20 billion in total costs for all nonneonatal stays, they said.

Rates of potentially avoidable stays for asthma (159 per 100,000 population), gastroenteritis (90 per 100,000), and UTIs (41 per 100,000) were highest for children aged 0-4 years and generally decreased with age, but diabetes stays increased with age, rising from 12 per 100,000 in children aged 5-9 years to 38 per 100,000 for those 15-17 years old, the researchers said.

Black children had a much higher rate of potentially avoidable stays for asthma (218 per 100,000) than did Hispanic children (74), Asian/Pacific Islander children (46), or white children (43), but children classified as other race/ethnicity were higher still: 380 per 100,000. Rates for children classified as other race/ethnicity were highest for the other three conditions as well, they reported.

Comparisons by sex for the four conditions ended up in a 2-2 tie: Girls had higher rates for diabetes (28 vs. 23) and UTIs (35 vs. 8), and boys had higher rates for asthma (96 vs. 67) and gastroenteritis (38 vs. 35), Dr. McDermott and Dr. Jiang reported.

[email protected]

SOURCE: McDermott KW, Jiang HJ. HCUP Statistical Brief #259. June 2020.

Hospital charges for the treatment of children with asthma made up nearly half of all potentially avoidable pediatric inpatient costs in 2017, according to the Agency for Healthcare Research and Quality.

The cost of potentially avoidable visits for asthma that year was $278 million, versus $284 million combined for the other three conditions “that evidence suggests may be avoidable, in part, through timely and quality primary and preventive care,” Kimberly W. McDermott, PhD, and H. Joanna Jiang, PhD, said in an AHRQ statistical brief.

Those three other conditions are diabetes short-term complications, gastroenteritis, and urinary tract infections (UTIs). Neonatal stays were excluded from the analysis, Dr. McDermott of IBM Watson Health and Dr. Jiang of the AHRQ noted.

The state inpatient databases of the AHRQ’s Healthcare Cost and Utilization Project included 1.4 million inpatient stays among children aged 3 months to 17 years in 2017, of which 8% (108,300) were deemed potentially preventable. Hospital charges for the preventable stays came to $561.6 million, or 3% of the $20 billion in total costs for all nonneonatal stays, they said.

Rates of potentially avoidable stays for asthma (159 per 100,000 population), gastroenteritis (90 per 100,000), and UTIs (41 per 100,000) were highest for children aged 0-4 years and generally decreased with age, but diabetes stays increased with age, rising from 12 per 100,000 in children aged 5-9 years to 38 per 100,000 for those 15-17 years old, the researchers said.

Black children had a much higher rate of potentially avoidable stays for asthma (218 per 100,000) than did Hispanic children (74), Asian/Pacific Islander children (46), or white children (43), but children classified as other race/ethnicity were higher still: 380 per 100,000. Rates for children classified as other race/ethnicity were highest for the other three conditions as well, they reported.

Comparisons by sex for the four conditions ended up in a 2-2 tie: Girls had higher rates for diabetes (28 vs. 23) and UTIs (35 vs. 8), and boys had higher rates for asthma (96 vs. 67) and gastroenteritis (38 vs. 35), Dr. McDermott and Dr. Jiang reported.

[email protected]

SOURCE: McDermott KW, Jiang HJ. HCUP Statistical Brief #259. June 2020.

Hospital charges for the treatment of children with asthma made up nearly half of all potentially avoidable pediatric inpatient costs in 2017, according to the Agency for Healthcare Research and Quality.

The cost of potentially avoidable visits for asthma that year was $278 million, versus $284 million combined for the other three conditions “that evidence suggests may be avoidable, in part, through timely and quality primary and preventive care,” Kimberly W. McDermott, PhD, and H. Joanna Jiang, PhD, said in an AHRQ statistical brief.

Those three other conditions are diabetes short-term complications, gastroenteritis, and urinary tract infections (UTIs). Neonatal stays were excluded from the analysis, Dr. McDermott of IBM Watson Health and Dr. Jiang of the AHRQ noted.

The state inpatient databases of the AHRQ’s Healthcare Cost and Utilization Project included 1.4 million inpatient stays among children aged 3 months to 17 years in 2017, of which 8% (108,300) were deemed potentially preventable. Hospital charges for the preventable stays came to $561.6 million, or 3% of the $20 billion in total costs for all nonneonatal stays, they said.

Rates of potentially avoidable stays for asthma (159 per 100,000 population), gastroenteritis (90 per 100,000), and UTIs (41 per 100,000) were highest for children aged 0-4 years and generally decreased with age, but diabetes stays increased with age, rising from 12 per 100,000 in children aged 5-9 years to 38 per 100,000 for those 15-17 years old, the researchers said.

Black children had a much higher rate of potentially avoidable stays for asthma (218 per 100,000) than did Hispanic children (74), Asian/Pacific Islander children (46), or white children (43), but children classified as other race/ethnicity were higher still: 380 per 100,000. Rates for children classified as other race/ethnicity were highest for the other three conditions as well, they reported.

Comparisons by sex for the four conditions ended up in a 2-2 tie: Girls had higher rates for diabetes (28 vs. 23) and UTIs (35 vs. 8), and boys had higher rates for asthma (96 vs. 67) and gastroenteritis (38 vs. 35), Dr. McDermott and Dr. Jiang reported.

[email protected]

SOURCE: McDermott KW, Jiang HJ. HCUP Statistical Brief #259. June 2020.

When sterilizing face masks, the type of face mask and the method of sterilization have a bearing on subsequent filtration efficiency, according to researchers. The greatest reduction in filtration efficiency after sterilization occurred with surgical face masks.

With plasma vapor hydrogen peroxide (H₂O₂) sterilization, filtration efficiency of N95 and KN95 masks was maintained at more than 95%, but for surgical face masks, filtration efficiency was reduced to less than 95%. With chlorine dioxide (ClO₂) sterilization, on the other hand, filtration efficiency was maintained at above 95% for N95 masks, but for KN95 and surgical face masks, filtration efficiency was reduced to less than 80%.

In a research letter published online June 15 in JAMA Network Open, researchers from the University of Oklahoma Health Sciences Center, Oklahoma City, report the results of a study of the two sterilization techniques on the pressure drop and filtration efficiency of N95, KN95, and surgical face masks.

“The H₂O₂ treatment showed a small effect on the overall filtration efficiency of the tested masks, but the ClO₂ treatment showed marked reduction in the overall filtration efficiency of the KN95s and surgical face masks. All pressure drop changes were within the acceptable range,” the researchers write.

The study did not evaluate the effect of repeated sterilizations on face masks.

Five masks of each type were sterilized with either H₂O₂ or ClO₂. Masks were then placed in a test chamber, and a salt aerosol was nebulized to assess both upstream and downstream filtration as well as pressure drop. The researchers used a mobility particle sizer to measure particle number concentration from 16.8 nm to 514 nm. An acceptable pressure drop was defined as a drop of less than 1.38 inches of water (35 mm) for inhalation.

Although pressure drop changes were within the acceptable range for all three mask types following sterilization with either method, H₂O₂ sterilization yielded the least reduction in filtration efficacy in all cases. After sterilization with H₂O₂, filtration efficiencies were 96.6%, 97.1%, and 91.6% for the N95s, KN95s, and the surgical face masks, respectively. In contrast, filtration efficiencies after ClO₂ sterilization were 95.1%, 76.2%, and 77.9%, respectively.

The researchers note that, although overall filtration efficiency was maintained with ClO₂ sterilization, there was a significant drop in efficiency with respect to particles of approximately 300 nm (0.3 microns) in size. For particles of that size, mean filtration efficiency decreased to 86.2% for N95s, 40.8% for KN95s, and 47.1% for surgical face masks.

The testing described in the report is “quite affordable at $350 per mask type, so it is hard to imagine any health care provider cannot set aside a small budget to conduct such an important test,” author Evan Floyd, PhD, told Medscape Medical News.

Given the high demand for effective face masks and the current risk for counterfeit products, Floyd suggested that individual facilities test all masks intended for use by healthcare workers before and after sterilization procedures.

“However, if for some reason testing is not an option, we would recommend sticking to established brands and suppliers, perhaps reach out to your state health department or a local representative of the strategic stockpile of PPE,” he noted.

The authors acknowledge that further studies using a larger sample size and a greater variety of masks, as well as studies to evaluate different sterilization techniques, are required. Further, “measuring the respirator’s filtration efficiency by aerosol size instead of only measuring the overall filtration efficiency” should also be considered. Such an approach would enable researchers to evaluate the degree to which masks protect against specific infectious agents.

This article first appeared on Medscape.com.

When sterilizing face masks, the type of face mask and the method of sterilization have a bearing on subsequent filtration efficiency, according to researchers. The greatest reduction in filtration efficiency after sterilization occurred with surgical face masks.

With plasma vapor hydrogen peroxide (H₂O₂) sterilization, filtration efficiency of N95 and KN95 masks was maintained at more than 95%, but for surgical face masks, filtration efficiency was reduced to less than 95%. With chlorine dioxide (ClO₂) sterilization, on the other hand, filtration efficiency was maintained at above 95% for N95 masks, but for KN95 and surgical face masks, filtration efficiency was reduced to less than 80%.

In a research letter published online June 15 in JAMA Network Open, researchers from the University of Oklahoma Health Sciences Center, Oklahoma City, report the results of a study of the two sterilization techniques on the pressure drop and filtration efficiency of N95, KN95, and surgical face masks.

“The H₂O₂ treatment showed a small effect on the overall filtration efficiency of the tested masks, but the ClO₂ treatment showed marked reduction in the overall filtration efficiency of the KN95s and surgical face masks. All pressure drop changes were within the acceptable range,” the researchers write.

The study did not evaluate the effect of repeated sterilizations on face masks.

Five masks of each type were sterilized with either H₂O₂ or ClO₂. Masks were then placed in a test chamber, and a salt aerosol was nebulized to assess both upstream and downstream filtration as well as pressure drop. The researchers used a mobility particle sizer to measure particle number concentration from 16.8 nm to 514 nm. An acceptable pressure drop was defined as a drop of less than 1.38 inches of water (35 mm) for inhalation.

Although pressure drop changes were within the acceptable range for all three mask types following sterilization with either method, H₂O₂ sterilization yielded the least reduction in filtration efficacy in all cases. After sterilization with H₂O₂, filtration efficiencies were 96.6%, 97.1%, and 91.6% for the N95s, KN95s, and the surgical face masks, respectively. In contrast, filtration efficiencies after ClO₂ sterilization were 95.1%, 76.2%, and 77.9%, respectively.

The researchers note that, although overall filtration efficiency was maintained with ClO₂ sterilization, there was a significant drop in efficiency with respect to particles of approximately 300 nm (0.3 microns) in size. For particles of that size, mean filtration efficiency decreased to 86.2% for N95s, 40.8% for KN95s, and 47.1% for surgical face masks.

The testing described in the report is “quite affordable at $350 per mask type, so it is hard to imagine any health care provider cannot set aside a small budget to conduct such an important test,” author Evan Floyd, PhD, told Medscape Medical News.

Given the high demand for effective face masks and the current risk for counterfeit products, Floyd suggested that individual facilities test all masks intended for use by healthcare workers before and after sterilization procedures.

“However, if for some reason testing is not an option, we would recommend sticking to established brands and suppliers, perhaps reach out to your state health department or a local representative of the strategic stockpile of PPE,” he noted.

The authors acknowledge that further studies using a larger sample size and a greater variety of masks, as well as studies to evaluate different sterilization techniques, are required. Further, “measuring the respirator’s filtration efficiency by aerosol size instead of only measuring the overall filtration efficiency” should also be considered. Such an approach would enable researchers to evaluate the degree to which masks protect against specific infectious agents.

This article first appeared on Medscape.com.

When sterilizing face masks, the type of face mask and the method of sterilization have a bearing on subsequent filtration efficiency, according to researchers. The greatest reduction in filtration efficiency after sterilization occurred with surgical face masks.

With plasma vapor hydrogen peroxide (H₂O₂) sterilization, filtration efficiency of N95 and KN95 masks was maintained at more than 95%, but for surgical face masks, filtration efficiency was reduced to less than 95%. With chlorine dioxide (ClO₂) sterilization, on the other hand, filtration efficiency was maintained at above 95% for N95 masks, but for KN95 and surgical face masks, filtration efficiency was reduced to less than 80%.

In a research letter published online June 15 in JAMA Network Open, researchers from the University of Oklahoma Health Sciences Center, Oklahoma City, report the results of a study of the two sterilization techniques on the pressure drop and filtration efficiency of N95, KN95, and surgical face masks.

“The H₂O₂ treatment showed a small effect on the overall filtration efficiency of the tested masks, but the ClO₂ treatment showed marked reduction in the overall filtration efficiency of the KN95s and surgical face masks. All pressure drop changes were within the acceptable range,” the researchers write.

The study did not evaluate the effect of repeated sterilizations on face masks.

Five masks of each type were sterilized with either H₂O₂ or ClO₂. Masks were then placed in a test chamber, and a salt aerosol was nebulized to assess both upstream and downstream filtration as well as pressure drop. The researchers used a mobility particle sizer to measure particle number concentration from 16.8 nm to 514 nm. An acceptable pressure drop was defined as a drop of less than 1.38 inches of water (35 mm) for inhalation.

Although pressure drop changes were within the acceptable range for all three mask types following sterilization with either method, H₂O₂ sterilization yielded the least reduction in filtration efficacy in all cases. After sterilization with H₂O₂, filtration efficiencies were 96.6%, 97.1%, and 91.6% for the N95s, KN95s, and the surgical face masks, respectively. In contrast, filtration efficiencies after ClO₂ sterilization were 95.1%, 76.2%, and 77.9%, respectively.

The researchers note that, although overall filtration efficiency was maintained with ClO₂ sterilization, there was a significant drop in efficiency with respect to particles of approximately 300 nm (0.3 microns) in size. For particles of that size, mean filtration efficiency decreased to 86.2% for N95s, 40.8% for KN95s, and 47.1% for surgical face masks.

The testing described in the report is “quite affordable at $350 per mask type, so it is hard to imagine any health care provider cannot set aside a small budget to conduct such an important test,” author Evan Floyd, PhD, told Medscape Medical News.

Given the high demand for effective face masks and the current risk for counterfeit products, Floyd suggested that individual facilities test all masks intended for use by healthcare workers before and after sterilization procedures.

“However, if for some reason testing is not an option, we would recommend sticking to established brands and suppliers, perhaps reach out to your state health department or a local representative of the strategic stockpile of PPE,” he noted.

The authors acknowledge that further studies using a larger sample size and a greater variety of masks, as well as studies to evaluate different sterilization techniques, are required. Further, “measuring the respirator’s filtration efficiency by aerosol size instead of only measuring the overall filtration efficiency” should also be considered. Such an approach would enable researchers to evaluate the degree to which masks protect against specific infectious agents.

This article first appeared on Medscape.com.

About 6% of parents in the United States are hesitant about routine childhood vaccination, whereas 26% are hesitant about yearly influenza vaccination, according to a nationally representative survey.

MarianVejcik/Getty Images

Influenza vaccination hesitancy may be driven by concerns about vaccine effectiveness, researchers wrote in Pediatrics. These findings “underscore the importance of better communicating to providers and parents the effectiveness of influenza vaccines in reducing severity and morbidity from influenza, even in years when the vaccine has relatively low effectiveness,” noted Allison Kempe, MD, MPH, professor of pediatrics and director of the Adult and Child Consortium for Health Outcomes Research and Delivery Science at the University of Colorado at Denver, Aurora, and colleagues.

The World Health Organization considers vaccine hesitancy a leading threat to global health, but national data about vaccine hesitancy in the United States are limited. To assess hesitancy about routine childhood and influenza vaccinations and related factors, Dr. Kempe and colleagues surveyed more than 2,000 parents in February 2019.

The investigators used an online panel to survey a nationally representative sample of families with children aged between 6 months and 18 years. Parents completed a modified version of the Vaccine Hesitancy Scale, which measures confidence in and concerns about vaccines. Parents with an average score greater than 3 on the scale were considered hesitant.

Factors associated with vaccine hesitancy

Of 4,445 parents sampled, 2,176 completed the survey and 2,052 were eligible respondents. For routine childhood vaccines, the average score on the modified Vaccine Hesitancy Scale was 2 and the percentage of hesitant parents was 6%. For influenza vaccine, the average score was 2 and the percentage of hesitant parents was 26%.

Among hesitant parents, 68% had deferred or refused routine childhood vaccination, compared with 9% of nonhesitant parents (risk ratio, 8.0). For the influenza vaccine, 70% of hesitant parents had deferred or refused influenza vaccination for their child versus 10% of nonhesitant parents (RR, 7.0). Parents were more likely to strongly agree that routine childhood vaccines are effective, compared with the influenza vaccine (70% vs. 26%). “Hesitancy about influenza vaccination is largely driven by concerns about low vaccine effectiveness,” Dr. Kempe and associates wrote.

Although concern about serious side effects was the factor most associated with hesitancy, the percentage of parents who were strongly (12%) or somewhat (27%) concerned about serious side effects was the same for routine childhood vaccines and influenza vaccines. Other factors associated with hesitancy for both routine childhood vaccines and influenza vaccines included lower educational level and household income less than 400% of the federal poverty level.

The survey data may be subject to reporting bias based on social desirability, the authors noted. In addition, the exclusion of infants younger than 6 months may have resulted in an underestimate of hesitancy.

“Although influenza vaccine could be included as a ‘routine’ vaccine, in that it is recommended yearly, we hypothesized that parents view it differently from other childhood vaccines because each year it needs to be given again, its content and effectiveness vary, and it addresses a disease that is often perceived as minor, compared with other childhood diseases,” Dr. Kempe and colleagues wrote. Interventions to counter hesitancy have “a surprising lack of evidence,” and “more work needs to be done to develop methods that are practical and effective for convincing vaccine-hesitant parents to vaccinate.”
 

Logical next step

“From the pragmatic standpoint of improving immunization rates and disease control, determining the correct evidence-based messaging to counter these perceptions is the next logical step,” Annabelle de St. Maurice, MD, MPH, an assistant professor of pediatrics in the division of infectious diseases at University of California, Los Angeles, and Kathryn Edwards, MD, a professor of pediatrics and director of the vaccine research program at Vanderbilt University, Nashville, wrote in an accompanying editorial.

“Communications should be focused on the burden of influenza in children, rebranding influenza vaccine as a ‘routine’ childhood immunization, reassurance on influenza vaccine safety, and discussion of the efficacy of influenza vaccine in preventing severe disease,” they wrote. “Even in the years when there is a poor match, the vaccine is impactful.”

The research was supported by the National Institutes of Health. Two study authors disclosed financial ties to Sanofi Pasteur, with one also disclosing financial ties to Merck, for work related to vaccinations. The remaining investigators had no relevant financial disclosures. Dr. de St. Maurice indicated that she had no relevant financial disclosures. Dr. Edwards disclosed grants from the Centers for Disease Control and Prevention and the NIH; consulting for Merck, Bionet, and IBM; and serving on data safety and monitoring boards for Sanofi, X4 Pharmaceuticals, Seqirus, Moderna, and Pfizer.

[email protected]

SOURCE: Kempe A et al. Pediatrics. 2020 Jun 15. doi: 10.1542/peds.2019-3852.
 

About 6% of parents in the United States are hesitant about routine childhood vaccination, whereas 26% are hesitant about yearly influenza vaccination, according to a nationally representative survey.

MarianVejcik/Getty Images

Influenza vaccination hesitancy may be driven by concerns about vaccine effectiveness, researchers wrote in Pediatrics. These findings “underscore the importance of better communicating to providers and parents the effectiveness of influenza vaccines in reducing severity and morbidity from influenza, even in years when the vaccine has relatively low effectiveness,” noted Allison Kempe, MD, MPH, professor of pediatrics and director of the Adult and Child Consortium for Health Outcomes Research and Delivery Science at the University of Colorado at Denver, Aurora, and colleagues.

The World Health Organization considers vaccine hesitancy a leading threat to global health, but national data about vaccine hesitancy in the United States are limited. To assess hesitancy about routine childhood and influenza vaccinations and related factors, Dr. Kempe and colleagues surveyed more than 2,000 parents in February 2019.

The investigators used an online panel to survey a nationally representative sample of families with children aged between 6 months and 18 years. Parents completed a modified version of the Vaccine Hesitancy Scale, which measures confidence in and concerns about vaccines. Parents with an average score greater than 3 on the scale were considered hesitant.

Factors associated with vaccine hesitancy

Of 4,445 parents sampled, 2,176 completed the survey and 2,052 were eligible respondents. For routine childhood vaccines, the average score on the modified Vaccine Hesitancy Scale was 2 and the percentage of hesitant parents was 6%. For influenza vaccine, the average score was 2 and the percentage of hesitant parents was 26%.

Among hesitant parents, 68% had deferred or refused routine childhood vaccination, compared with 9% of nonhesitant parents (risk ratio, 8.0). For the influenza vaccine, 70% of hesitant parents had deferred or refused influenza vaccination for their child versus 10% of nonhesitant parents (RR, 7.0). Parents were more likely to strongly agree that routine childhood vaccines are effective, compared with the influenza vaccine (70% vs. 26%). “Hesitancy about influenza vaccination is largely driven by concerns about low vaccine effectiveness,” Dr. Kempe and associates wrote.

Although concern about serious side effects was the factor most associated with hesitancy, the percentage of parents who were strongly (12%) or somewhat (27%) concerned about serious side effects was the same for routine childhood vaccines and influenza vaccines. Other factors associated with hesitancy for both routine childhood vaccines and influenza vaccines included lower educational level and household income less than 400% of the federal poverty level.

The survey data may be subject to reporting bias based on social desirability, the authors noted. In addition, the exclusion of infants younger than 6 months may have resulted in an underestimate of hesitancy.

“Although influenza vaccine could be included as a ‘routine’ vaccine, in that it is recommended yearly, we hypothesized that parents view it differently from other childhood vaccines because each year it needs to be given again, its content and effectiveness vary, and it addresses a disease that is often perceived as minor, compared with other childhood diseases,” Dr. Kempe and colleagues wrote. Interventions to counter hesitancy have “a surprising lack of evidence,” and “more work needs to be done to develop methods that are practical and effective for convincing vaccine-hesitant parents to vaccinate.”
 

Logical next step

“From the pragmatic standpoint of improving immunization rates and disease control, determining the correct evidence-based messaging to counter these perceptions is the next logical step,” Annabelle de St. Maurice, MD, MPH, an assistant professor of pediatrics in the division of infectious diseases at University of California, Los Angeles, and Kathryn Edwards, MD, a professor of pediatrics and director of the vaccine research program at Vanderbilt University, Nashville, wrote in an accompanying editorial.

“Communications should be focused on the burden of influenza in children, rebranding influenza vaccine as a ‘routine’ childhood immunization, reassurance on influenza vaccine safety, and discussion of the efficacy of influenza vaccine in preventing severe disease,” they wrote. “Even in the years when there is a poor match, the vaccine is impactful.”

The research was supported by the National Institutes of Health. Two study authors disclosed financial ties to Sanofi Pasteur, with one also disclosing financial ties to Merck, for work related to vaccinations. The remaining investigators had no relevant financial disclosures. Dr. de St. Maurice indicated that she had no relevant financial disclosures. Dr. Edwards disclosed grants from the Centers for Disease Control and Prevention and the NIH; consulting for Merck, Bionet, and IBM; and serving on data safety and monitoring boards for Sanofi, X4 Pharmaceuticals, Seqirus, Moderna, and Pfizer.

[email protected]

SOURCE: Kempe A et al. Pediatrics. 2020 Jun 15. doi: 10.1542/peds.2019-3852.
 

About 6% of parents in the United States are hesitant about routine childhood vaccination, whereas 26% are hesitant about yearly influenza vaccination, according to a nationally representative survey.

MarianVejcik/Getty Images

Influenza vaccination hesitancy may be driven by concerns about vaccine effectiveness, researchers wrote in Pediatrics. These findings “underscore the importance of better communicating to providers and parents the effectiveness of influenza vaccines in reducing severity and morbidity from influenza, even in years when the vaccine has relatively low effectiveness,” noted Allison Kempe, MD, MPH, professor of pediatrics and director of the Adult and Child Consortium for Health Outcomes Research and Delivery Science at the University of Colorado at Denver, Aurora, and colleagues.

The World Health Organization considers vaccine hesitancy a leading threat to global health, but national data about vaccine hesitancy in the United States are limited. To assess hesitancy about routine childhood and influenza vaccinations and related factors, Dr. Kempe and colleagues surveyed more than 2,000 parents in February 2019.

The investigators used an online panel to survey a nationally representative sample of families with children aged between 6 months and 18 years. Parents completed a modified version of the Vaccine Hesitancy Scale, which measures confidence in and concerns about vaccines. Parents with an average score greater than 3 on the scale were considered hesitant.

Factors associated with vaccine hesitancy

Of 4,445 parents sampled, 2,176 completed the survey and 2,052 were eligible respondents. For routine childhood vaccines, the average score on the modified Vaccine Hesitancy Scale was 2 and the percentage of hesitant parents was 6%. For influenza vaccine, the average score was 2 and the percentage of hesitant parents was 26%.

Among hesitant parents, 68% had deferred or refused routine childhood vaccination, compared with 9% of nonhesitant parents (risk ratio, 8.0). For the influenza vaccine, 70% of hesitant parents had deferred or refused influenza vaccination for their child versus 10% of nonhesitant parents (RR, 7.0). Parents were more likely to strongly agree that routine childhood vaccines are effective, compared with the influenza vaccine (70% vs. 26%). “Hesitancy about influenza vaccination is largely driven by concerns about low vaccine effectiveness,” Dr. Kempe and associates wrote.

Although concern about serious side effects was the factor most associated with hesitancy, the percentage of parents who were strongly (12%) or somewhat (27%) concerned about serious side effects was the same for routine childhood vaccines and influenza vaccines. Other factors associated with hesitancy for both routine childhood vaccines and influenza vaccines included lower educational level and household income less than 400% of the federal poverty level.

The survey data may be subject to reporting bias based on social desirability, the authors noted. In addition, the exclusion of infants younger than 6 months may have resulted in an underestimate of hesitancy.

“Although influenza vaccine could be included as a ‘routine’ vaccine, in that it is recommended yearly, we hypothesized that parents view it differently from other childhood vaccines because each year it needs to be given again, its content and effectiveness vary, and it addresses a disease that is often perceived as minor, compared with other childhood diseases,” Dr. Kempe and colleagues wrote. Interventions to counter hesitancy have “a surprising lack of evidence,” and “more work needs to be done to develop methods that are practical and effective for convincing vaccine-hesitant parents to vaccinate.”
 

Logical next step

“From the pragmatic standpoint of improving immunization rates and disease control, determining the correct evidence-based messaging to counter these perceptions is the next logical step,” Annabelle de St. Maurice, MD, MPH, an assistant professor of pediatrics in the division of infectious diseases at University of California, Los Angeles, and Kathryn Edwards, MD, a professor of pediatrics and director of the vaccine research program at Vanderbilt University, Nashville, wrote in an accompanying editorial.

“Communications should be focused on the burden of influenza in children, rebranding influenza vaccine as a ‘routine’ childhood immunization, reassurance on influenza vaccine safety, and discussion of the efficacy of influenza vaccine in preventing severe disease,” they wrote. “Even in the years when there is a poor match, the vaccine is impactful.”

The research was supported by the National Institutes of Health. Two study authors disclosed financial ties to Sanofi Pasteur, with one also disclosing financial ties to Merck, for work related to vaccinations. The remaining investigators had no relevant financial disclosures. Dr. de St. Maurice indicated that she had no relevant financial disclosures. Dr. Edwards disclosed grants from the Centers for Disease Control and Prevention and the NIH; consulting for Merck, Bionet, and IBM; and serving on data safety and monitoring boards for Sanofi, X4 Pharmaceuticals, Seqirus, Moderna, and Pfizer.

[email protected]

SOURCE: Kempe A et al. Pediatrics. 2020 Jun 15. doi: 10.1542/peds.2019-3852.
 

COVID-19 now. The urban phase of the U.S. pandemic is leveling somewhat, while the rural phase is accelerating – in part because of food processing and handling industries. The pediatric burden has been surprisingly small, with the multisystem inflammatory disease (MIS-c) in children noted in several hundred cases now being seen across the country.

CDC

Next wave? Given ongoing COVID-19 disease, controversy rages about when and how to re-open the country. Regardless how more reopening occurs over the next months, we should expect a next or ongoing COVID-19 wave, particularly given loss of social distancing during social justice protests. A sawtooth disease prevalence pattern is predicted by many experts: a drop in prevalence leading to reopening, leading to scattered prevalence increases and regional if not local restriction tightening, followed by another drop in prevalence. Then “rinse and repeat” until 70% of the population is immune either by disease experience or vaccine-induced immunity, likely sometime in 2021.

Influenza too. A COVID-19 up-cycle is likely during influenza season, although influenza season’s onset could be altered because of whatever social distancing rules are in place in November and December. That said, we need to consider the worst. We have seen what happens if we fail to prepare and then react only after a prevalent respiratory infection has surged into the overall population. Best estimates are that at most 20% of the U.S. population is currently immune to SARS-CoV-2. Given that at least some of that 20% of individuals currently immune to SARS-CoV-2 will lose their neutralizing antibody over the next 4-6 months, we can still expect 70%-80% of the U.S. population to be susceptible to SARS-CoV-2 infection in the fall of 2020.

Pediatric preparedness. As pediatric providers, we have struggled with lower patient loads and dramatic income losses/declines. Many clinics/offices’ attendance remain less than 50% of pre–COVID-19 levels, with necessary furloughs of personnel and spotty office hours. But influenza is coming, and SARS-CoV-2 will not be gone yet. How do we prepare for concurrent influenza and COVID-19?

The annual purchase/administration of influenza vaccine in summer/fall is expensive, time consuming, and logistically difficult even in the best times. Given the loss of income, likely reluctance of patients to come to clinics/offices if COVID-19 is still circulating, and likely need for some form of social distancing during late summer and early fall, how will providers, health departments, and hospitals implement influenza vaccine administration this year?

Minimize double whammy infections. Maximizing influenza vaccine uptake during the COVID-19 pandemic is super important. It is easy to understand why we should maximize influenza protection in SARS-CoV-2 vulnerables (elderly or persons with existing comorbidities). But is it as critical for otherwise healthy children? My answer is yes.

Children are not currently known as SARS-CoV-2 vectors, but children are excellent influenza vectors, shedding higher titers for longer than other age groups. As with SARS-CoV-2, influenza exposure is cumulative, i.e., the more intense and more frequently a person is exposed, the more likely that infection/disease will result. So, the fewer who get and can transmit influenza during the COVID-19 pandemic, the fewer people are likely to get a double whammy of SARS-CoV-2 concurrent or in tandem with influenza. Double whammy infections likely would further increase the medical care burden and return us to March-April crisis mode.

One alarming new question is whether recent influenza could make children vulnerable to SARS-CoV-2 and trigger hospitalizations. A surge in pediatric plus adult COVID-19 disease plus a surge in all-ages influenza disease would likely break the medical care system, at least in some areas.

CDC

Staggering COVID-19 burden. As of June 8, we have had approximately 2 million SARS-CoV-2 cases with 500,000 hospitalizations and 120,000 deaths. Over the past 10 years, total annual U.S. influenza hospitalizations ranged from 180,000 (2011-2012) to 825,000 (2017-2018). The interquartile range for hospitalization length of stay for influenza is 4-6 days¹ vs. 15-23 days² for SARS-CoV-2. One COVID-19 hospitalization uses hospital resources roughly equal to four influenza hospitalizations. To date COVID-19 hospitalizations have used resources equal to an estimated 1.9 million influenza hospitalizations – over twice the worst influenza season in this century – and we are still on the rise. We are likely not even halfway to truly controlling the U.S. pandemic, so expect another 500,000 hospitalizations – equal to another 1.9 million influenza hospitalizations. Further, pneumonia deaths have skyrocketed this year when COVID-19 was superimposed on the last third of influenza season. One hope is that widespread use of antivirals (for example, new antivirals, convalescent plasma, or other interventions) can reduce length of stay by 30% for COVID-19 hospitalizations, yet even with that the numbers remain grim.

Less influenza disease can free up medical resources. Planning ahead could prevent a bad influenza season (for example, up to 850,000 hospitalizations just for influenza). Can we preemptively use vaccine to reduce influenza hospitalizations below 2011-2012 levels – less than 150,000 hospitalizations? Perhaps, if we start by reducing pediatric influenza.

1. Aim to exceed 75% influenza vaccine uptake in your patients.

a. It is ambitious, but if there was ever a year that needed influenza herd immunity, it is 2020-2021.

2. Review practice/group/institution plans for vaccine purchase and ensure adequate personnel to administer vaccine.

3. Plan safe and efficient processes to vaccinate large numbers in August through November.

a. Consider that routine and influenza vaccines can be given concurrently with the annual uptick in school and sports physical examinations.

b. What social distancing and masking rules will be needed?

i. Will patients need to bring their own masks, or will you supply them?

c. What extra supplies and efforts are needed, e.g. hand sanitizer, new signage, 6-foot interval markings on floors or sidewalks, families calling from parking lot to announce their arrivals, etc.?

d. Remember younger patients need two doses before Dec 1, 2020.

e. Be creative, for example, are parking-lot tents for influenza vaccination feasible?

f. Can we partner with other providers to implement influenza vaccine–specific mass clinics?

Ramping up to give seasonal influenza vaccine in 2020 is daunting. But if we do not prepare, it will be even more difficult. Let’s make this the mildest influenza season in memory by vaccinating more than any time in memory – and by doing so, we can hope to blunt medical care burdens despite ongoing COVID-19 disease.
 

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Kansas City (Mo.). Children’s Mercy receives funding from GlaxoSmithKline, Merck, and Pfizer for vaccine research studies on which Dr. Harrison is an investigator. Email him at [email protected].
 

References

1.. HCUP Statistical Brief #253. 2019 Oct.

2. medrxiv. 2020 Apr 10. doi: 10.1101/2020.04.07.20057299.
 

COVID-19 now. The urban phase of the U.S. pandemic is leveling somewhat, while the rural phase is accelerating – in part because of food processing and handling industries. The pediatric burden has been surprisingly small, with the multisystem inflammatory disease (MIS-c) in children noted in several hundred cases now being seen across the country.

CDC

Next wave? Given ongoing COVID-19 disease, controversy rages about when and how to re-open the country. Regardless how more reopening occurs over the next months, we should expect a next or ongoing COVID-19 wave, particularly given loss of social distancing during social justice protests. A sawtooth disease prevalence pattern is predicted by many experts: a drop in prevalence leading to reopening, leading to scattered prevalence increases and regional if not local restriction tightening, followed by another drop in prevalence. Then “rinse and repeat” until 70% of the population is immune either by disease experience or vaccine-induced immunity, likely sometime in 2021.

Influenza too. A COVID-19 up-cycle is likely during influenza season, although influenza season’s onset could be altered because of whatever social distancing rules are in place in November and December. That said, we need to consider the worst. We have seen what happens if we fail to prepare and then react only after a prevalent respiratory infection has surged into the overall population. Best estimates are that at most 20% of the U.S. population is currently immune to SARS-CoV-2. Given that at least some of that 20% of individuals currently immune to SARS-CoV-2 will lose their neutralizing antibody over the next 4-6 months, we can still expect 70%-80% of the U.S. population to be susceptible to SARS-CoV-2 infection in the fall of 2020.

Pediatric preparedness. As pediatric providers, we have struggled with lower patient loads and dramatic income losses/declines. Many clinics/offices’ attendance remain less than 50% of pre–COVID-19 levels, with necessary furloughs of personnel and spotty office hours. But influenza is coming, and SARS-CoV-2 will not be gone yet. How do we prepare for concurrent influenza and COVID-19?

The annual purchase/administration of influenza vaccine in summer/fall is expensive, time consuming, and logistically difficult even in the best times. Given the loss of income, likely reluctance of patients to come to clinics/offices if COVID-19 is still circulating, and likely need for some form of social distancing during late summer and early fall, how will providers, health departments, and hospitals implement influenza vaccine administration this year?

Minimize double whammy infections. Maximizing influenza vaccine uptake during the COVID-19 pandemic is super important. It is easy to understand why we should maximize influenza protection in SARS-CoV-2 vulnerables (elderly or persons with existing comorbidities). But is it as critical for otherwise healthy children? My answer is yes.

Children are not currently known as SARS-CoV-2 vectors, but children are excellent influenza vectors, shedding higher titers for longer than other age groups. As with SARS-CoV-2, influenza exposure is cumulative, i.e., the more intense and more frequently a person is exposed, the more likely that infection/disease will result. So, the fewer who get and can transmit influenza during the COVID-19 pandemic, the fewer people are likely to get a double whammy of SARS-CoV-2 concurrent or in tandem with influenza. Double whammy infections likely would further increase the medical care burden and return us to March-April crisis mode.

One alarming new question is whether recent influenza could make children vulnerable to SARS-CoV-2 and trigger hospitalizations. A surge in pediatric plus adult COVID-19 disease plus a surge in all-ages influenza disease would likely break the medical care system, at least in some areas.

CDC

Staggering COVID-19 burden. As of June 8, we have had approximately 2 million SARS-CoV-2 cases with 500,000 hospitalizations and 120,000 deaths. Over the past 10 years, total annual U.S. influenza hospitalizations ranged from 180,000 (2011-2012) to 825,000 (2017-2018). The interquartile range for hospitalization length of stay for influenza is 4-6 days¹ vs. 15-23 days² for SARS-CoV-2. One COVID-19 hospitalization uses hospital resources roughly equal to four influenza hospitalizations. To date COVID-19 hospitalizations have used resources equal to an estimated 1.9 million influenza hospitalizations – over twice the worst influenza season in this century – and we are still on the rise. We are likely not even halfway to truly controlling the U.S. pandemic, so expect another 500,000 hospitalizations – equal to another 1.9 million influenza hospitalizations. Further, pneumonia deaths have skyrocketed this year when COVID-19 was superimposed on the last third of influenza season. One hope is that widespread use of antivirals (for example, new antivirals, convalescent plasma, or other interventions) can reduce length of stay by 30% for COVID-19 hospitalizations, yet even with that the numbers remain grim.

Less influenza disease can free up medical resources. Planning ahead could prevent a bad influenza season (for example, up to 850,000 hospitalizations just for influenza). Can we preemptively use vaccine to reduce influenza hospitalizations below 2011-2012 levels – less than 150,000 hospitalizations? Perhaps, if we start by reducing pediatric influenza.

1. Aim to exceed 75% influenza vaccine uptake in your patients.

a. It is ambitious, but if there was ever a year that needed influenza herd immunity, it is 2020-2021.

2. Review practice/group/institution plans for vaccine purchase and ensure adequate personnel to administer vaccine.

3. Plan safe and efficient processes to vaccinate large numbers in August through November.

a. Consider that routine and influenza vaccines can be given concurrently with the annual uptick in school and sports physical examinations.

b. What social distancing and masking rules will be needed?

i. Will patients need to bring their own masks, or will you supply them?

c. What extra supplies and efforts are needed, e.g. hand sanitizer, new signage, 6-foot interval markings on floors or sidewalks, families calling from parking lot to announce their arrivals, etc.?

d. Remember younger patients need two doses before Dec 1, 2020.

e. Be creative, for example, are parking-lot tents for influenza vaccination feasible?

f. Can we partner with other providers to implement influenza vaccine–specific mass clinics?

Ramping up to give seasonal influenza vaccine in 2020 is daunting. But if we do not prepare, it will be even more difficult. Let’s make this the mildest influenza season in memory by vaccinating more than any time in memory – and by doing so, we can hope to blunt medical care burdens despite ongoing COVID-19 disease.
 

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Kansas City (Mo.). Children’s Mercy receives funding from GlaxoSmithKline, Merck, and Pfizer for vaccine research studies on which Dr. Harrison is an investigator. Email him at [email protected].
 

References

1.. HCUP Statistical Brief #253. 2019 Oct.

2. medrxiv. 2020 Apr 10. doi: 10.1101/2020.04.07.20057299.
 

COVID-19 now. The urban phase of the U.S. pandemic is leveling somewhat, while the rural phase is accelerating – in part because of food processing and handling industries. The pediatric burden has been surprisingly small, with the multisystem inflammatory disease (MIS-c) in children noted in several hundred cases now being seen across the country.

CDC

Next wave? Given ongoing COVID-19 disease, controversy rages about when and how to re-open the country. Regardless how more reopening occurs over the next months, we should expect a next or ongoing COVID-19 wave, particularly given loss of social distancing during social justice protests. A sawtooth disease prevalence pattern is predicted by many experts: a drop in prevalence leading to reopening, leading to scattered prevalence increases and regional if not local restriction tightening, followed by another drop in prevalence. Then “rinse and repeat” until 70% of the population is immune either by disease experience or vaccine-induced immunity, likely sometime in 2021.

Influenza too. A COVID-19 up-cycle is likely during influenza season, although influenza season’s onset could be altered because of whatever social distancing rules are in place in November and December. That said, we need to consider the worst. We have seen what happens if we fail to prepare and then react only after a prevalent respiratory infection has surged into the overall population. Best estimates are that at most 20% of the U.S. population is currently immune to SARS-CoV-2. Given that at least some of that 20% of individuals currently immune to SARS-CoV-2 will lose their neutralizing antibody over the next 4-6 months, we can still expect 70%-80% of the U.S. population to be susceptible to SARS-CoV-2 infection in the fall of 2020.

Pediatric preparedness. As pediatric providers, we have struggled with lower patient loads and dramatic income losses/declines. Many clinics/offices’ attendance remain less than 50% of pre–COVID-19 levels, with necessary furloughs of personnel and spotty office hours. But influenza is coming, and SARS-CoV-2 will not be gone yet. How do we prepare for concurrent influenza and COVID-19?

The annual purchase/administration of influenza vaccine in summer/fall is expensive, time consuming, and logistically difficult even in the best times. Given the loss of income, likely reluctance of patients to come to clinics/offices if COVID-19 is still circulating, and likely need for some form of social distancing during late summer and early fall, how will providers, health departments, and hospitals implement influenza vaccine administration this year?

Minimize double whammy infections. Maximizing influenza vaccine uptake during the COVID-19 pandemic is super important. It is easy to understand why we should maximize influenza protection in SARS-CoV-2 vulnerables (elderly or persons with existing comorbidities). But is it as critical for otherwise healthy children? My answer is yes.

Children are not currently known as SARS-CoV-2 vectors, but children are excellent influenza vectors, shedding higher titers for longer than other age groups. As with SARS-CoV-2, influenza exposure is cumulative, i.e., the more intense and more frequently a person is exposed, the more likely that infection/disease will result. So, the fewer who get and can transmit influenza during the COVID-19 pandemic, the fewer people are likely to get a double whammy of SARS-CoV-2 concurrent or in tandem with influenza. Double whammy infections likely would further increase the medical care burden and return us to March-April crisis mode.

One alarming new question is whether recent influenza could make children vulnerable to SARS-CoV-2 and trigger hospitalizations. A surge in pediatric plus adult COVID-19 disease plus a surge in all-ages influenza disease would likely break the medical care system, at least in some areas.

CDC

Staggering COVID-19 burden. As of June 8, we have had approximately 2 million SARS-CoV-2 cases with 500,000 hospitalizations and 120,000 deaths. Over the past 10 years, total annual U.S. influenza hospitalizations ranged from 180,000 (2011-2012) to 825,000 (2017-2018). The interquartile range for hospitalization length of stay for influenza is 4-6 days¹ vs. 15-23 days² for SARS-CoV-2. One COVID-19 hospitalization uses hospital resources roughly equal to four influenza hospitalizations. To date COVID-19 hospitalizations have used resources equal to an estimated 1.9 million influenza hospitalizations – over twice the worst influenza season in this century – and we are still on the rise. We are likely not even halfway to truly controlling the U.S. pandemic, so expect another 500,000 hospitalizations – equal to another 1.9 million influenza hospitalizations. Further, pneumonia deaths have skyrocketed this year when COVID-19 was superimposed on the last third of influenza season. One hope is that widespread use of antivirals (for example, new antivirals, convalescent plasma, or other interventions) can reduce length of stay by 30% for COVID-19 hospitalizations, yet even with that the numbers remain grim.

Less influenza disease can free up medical resources. Planning ahead could prevent a bad influenza season (for example, up to 850,000 hospitalizations just for influenza). Can we preemptively use vaccine to reduce influenza hospitalizations below 2011-2012 levels – less than 150,000 hospitalizations? Perhaps, if we start by reducing pediatric influenza.

1. Aim to exceed 75% influenza vaccine uptake in your patients.

a. It is ambitious, but if there was ever a year that needed influenza herd immunity, it is 2020-2021.

2. Review practice/group/institution plans for vaccine purchase and ensure adequate personnel to administer vaccine.

3. Plan safe and efficient processes to vaccinate large numbers in August through November.

a. Consider that routine and influenza vaccines can be given concurrently with the annual uptick in school and sports physical examinations.

b. What social distancing and masking rules will be needed?

i. Will patients need to bring their own masks, or will you supply them?

c. What extra supplies and efforts are needed, e.g. hand sanitizer, new signage, 6-foot interval markings on floors or sidewalks, families calling from parking lot to announce their arrivals, etc.?

d. Remember younger patients need two doses before Dec 1, 2020.

e. Be creative, for example, are parking-lot tents for influenza vaccination feasible?

f. Can we partner with other providers to implement influenza vaccine–specific mass clinics?

Ramping up to give seasonal influenza vaccine in 2020 is daunting. But if we do not prepare, it will be even more difficult. Let’s make this the mildest influenza season in memory by vaccinating more than any time in memory – and by doing so, we can hope to blunt medical care burdens despite ongoing COVID-19 disease.
 

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Kansas City (Mo.). Children’s Mercy receives funding from GlaxoSmithKline, Merck, and Pfizer for vaccine research studies on which Dr. Harrison is an investigator. Email him at [email protected].
 

References

1.. HCUP Statistical Brief #253. 2019 Oct.

2. medrxiv. 2020 Apr 10. doi: 10.1101/2020.04.07.20057299.
 

Seropositive rheumatoid arthritis (RA) patients had twice the risk for developing pneumonia, compared with seronegative patients, in a study of more than 4,000 RA patients from a single U.S. medical system.

“Patients with seropositive RA, particularly RF [rheumatoid factor]-positive RA, had increased risk for pneumonia throughout the RA disease course that was not explained by measured confounders, including smoking status, multimorbidity, medications, and [erythrocyte sedimentation rate] level,” Jeffrey A. Sparks, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

“There has been much interest about the relationship between lung inflammation and the generation of RF and CCP [cyclic citrullinated protein] prior to the onset of RA. We hypothesized that patients with seropositive RA might have subclinical lung injury that could predispose them to pneumonia after clinical RA onset,” Dr. Sparks said in an interview. “Pneumonia is one of the most common serious infections in both patients with RA and the general population, and it causes serious morbidity and mortality.”

The doubled relative risk for pneumonia seen in the findings “translates into a clinically meaningful finding when considering the high rate and the many patients at risk since RA is relatively common,” said Dr. Sparks, a rheumatologist at Brigham and Women’s Hospital in Boston.

“Patients with RF-positive RA who present with symptoms concerning for pneumonia should be evaluated carefully for this and for other possible pulmonary manifestations of RA. Vaccination for pneumonia should be strongly considered for patients with RA who are on disease-modifying antirheumatic drugs, and we hope that our report encourages clinicians and patients” to undertake vaccination, he said.

His study used a database of more than 60,000 patients diagnosed with RA as of November 2013 in the records of a large Boston-area medical system that includes physicians affiliated with Brigham and Women’s Hospital and Massachusetts General Hospital. The researchers applied a validated algorithm for calculating a patient’s probability of having RA, and at the level of 97% probability they narrowed the cohort down to just under 10,000 patients. Additional winnowing because of missing data or a history of pneumonia yielded a study group of 4,110, which included 3,279 (80%) who were seropositive for either or both CCP and RF, and 831 (20%) who were seronegative. During a median follow-up of 7.8 years and total follow-up of more than 32,000 patient-years, the overall pneumonia incidence was 5.8%, with a 2.8% rate among the seronegatives and a 6.6% rate among seropositives. After adjustment for age, sex, glucocorticoid use, disease-modifying antirheumatic drug use, and several other possible confounders, the researchers calculated a 99% relative increased rate of pneumonia among all seropositive patients, compared with the seronegatives.

Further analysis looked at pneumonia incidence rates among patients positive only for CCP antibody, positive only for RF antibody, or both, compared with seronegative patients. This showed that CCP seropositivity had no statistically significant link with incident pneumonia, while RF seropositivity linked with a statistically significant, roughly twofold higher rate. Only 6% of all seropositive patients were positive only for CCP antibody, 59% were positive specifically for RF antibody, and 35% for both.

The data Dr. Sparks presented did not include information on pneumonia type, the timing of the pneumonia, compared with the onset of RA, disease activity, or smoking intensity.

“We anticipated that both RF positive and CCP positive would each be associated with pneumonia, so it was somewhat surprising that we only detected this for RF,” Dr. Sparks said. But he added that, because the number of patients with only CCP positivity was relatively so small, “it is still possible that CCP [antibody] could also increase pneumonia risk.”

The study had no commercial funding. Dr. Sparks had no disclosures.

[email protected]

SOURCE: Sparks JA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:73, Abstract OP0111.

Seropositive rheumatoid arthritis (RA) patients had twice the risk for developing pneumonia, compared with seronegative patients, in a study of more than 4,000 RA patients from a single U.S. medical system.

“Patients with seropositive RA, particularly RF [rheumatoid factor]-positive RA, had increased risk for pneumonia throughout the RA disease course that was not explained by measured confounders, including smoking status, multimorbidity, medications, and [erythrocyte sedimentation rate] level,” Jeffrey A. Sparks, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

“There has been much interest about the relationship between lung inflammation and the generation of RF and CCP [cyclic citrullinated protein] prior to the onset of RA. We hypothesized that patients with seropositive RA might have subclinical lung injury that could predispose them to pneumonia after clinical RA onset,” Dr. Sparks said in an interview. “Pneumonia is one of the most common serious infections in both patients with RA and the general population, and it causes serious morbidity and mortality.”

The doubled relative risk for pneumonia seen in the findings “translates into a clinically meaningful finding when considering the high rate and the many patients at risk since RA is relatively common,” said Dr. Sparks, a rheumatologist at Brigham and Women’s Hospital in Boston.

“Patients with RF-positive RA who present with symptoms concerning for pneumonia should be evaluated carefully for this and for other possible pulmonary manifestations of RA. Vaccination for pneumonia should be strongly considered for patients with RA who are on disease-modifying antirheumatic drugs, and we hope that our report encourages clinicians and patients” to undertake vaccination, he said.

His study used a database of more than 60,000 patients diagnosed with RA as of November 2013 in the records of a large Boston-area medical system that includes physicians affiliated with Brigham and Women’s Hospital and Massachusetts General Hospital. The researchers applied a validated algorithm for calculating a patient’s probability of having RA, and at the level of 97% probability they narrowed the cohort down to just under 10,000 patients. Additional winnowing because of missing data or a history of pneumonia yielded a study group of 4,110, which included 3,279 (80%) who were seropositive for either or both CCP and RF, and 831 (20%) who were seronegative. During a median follow-up of 7.8 years and total follow-up of more than 32,000 patient-years, the overall pneumonia incidence was 5.8%, with a 2.8% rate among the seronegatives and a 6.6% rate among seropositives. After adjustment for age, sex, glucocorticoid use, disease-modifying antirheumatic drug use, and several other possible confounders, the researchers calculated a 99% relative increased rate of pneumonia among all seropositive patients, compared with the seronegatives.

Further analysis looked at pneumonia incidence rates among patients positive only for CCP antibody, positive only for RF antibody, or both, compared with seronegative patients. This showed that CCP seropositivity had no statistically significant link with incident pneumonia, while RF seropositivity linked with a statistically significant, roughly twofold higher rate. Only 6% of all seropositive patients were positive only for CCP antibody, 59% were positive specifically for RF antibody, and 35% for both.

The data Dr. Sparks presented did not include information on pneumonia type, the timing of the pneumonia, compared with the onset of RA, disease activity, or smoking intensity.

“We anticipated that both RF positive and CCP positive would each be associated with pneumonia, so it was somewhat surprising that we only detected this for RF,” Dr. Sparks said. But he added that, because the number of patients with only CCP positivity was relatively so small, “it is still possible that CCP [antibody] could also increase pneumonia risk.”

The study had no commercial funding. Dr. Sparks had no disclosures.

[email protected]

SOURCE: Sparks JA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:73, Abstract OP0111.

Seropositive rheumatoid arthritis (RA) patients had twice the risk for developing pneumonia, compared with seronegative patients, in a study of more than 4,000 RA patients from a single U.S. medical system.

“Patients with seropositive RA, particularly RF [rheumatoid factor]-positive RA, had increased risk for pneumonia throughout the RA disease course that was not explained by measured confounders, including smoking status, multimorbidity, medications, and [erythrocyte sedimentation rate] level,” Jeffrey A. Sparks, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

“There has been much interest about the relationship between lung inflammation and the generation of RF and CCP [cyclic citrullinated protein] prior to the onset of RA. We hypothesized that patients with seropositive RA might have subclinical lung injury that could predispose them to pneumonia after clinical RA onset,” Dr. Sparks said in an interview. “Pneumonia is one of the most common serious infections in both patients with RA and the general population, and it causes serious morbidity and mortality.”

The doubled relative risk for pneumonia seen in the findings “translates into a clinically meaningful finding when considering the high rate and the many patients at risk since RA is relatively common,” said Dr. Sparks, a rheumatologist at Brigham and Women’s Hospital in Boston.

“Patients with RF-positive RA who present with symptoms concerning for pneumonia should be evaluated carefully for this and for other possible pulmonary manifestations of RA. Vaccination for pneumonia should be strongly considered for patients with RA who are on disease-modifying antirheumatic drugs, and we hope that our report encourages clinicians and patients” to undertake vaccination, he said.

His study used a database of more than 60,000 patients diagnosed with RA as of November 2013 in the records of a large Boston-area medical system that includes physicians affiliated with Brigham and Women’s Hospital and Massachusetts General Hospital. The researchers applied a validated algorithm for calculating a patient’s probability of having RA, and at the level of 97% probability they narrowed the cohort down to just under 10,000 patients. Additional winnowing because of missing data or a history of pneumonia yielded a study group of 4,110, which included 3,279 (80%) who were seropositive for either or both CCP and RF, and 831 (20%) who were seronegative. During a median follow-up of 7.8 years and total follow-up of more than 32,000 patient-years, the overall pneumonia incidence was 5.8%, with a 2.8% rate among the seronegatives and a 6.6% rate among seropositives. After adjustment for age, sex, glucocorticoid use, disease-modifying antirheumatic drug use, and several other possible confounders, the researchers calculated a 99% relative increased rate of pneumonia among all seropositive patients, compared with the seronegatives.

Further analysis looked at pneumonia incidence rates among patients positive only for CCP antibody, positive only for RF antibody, or both, compared with seronegative patients. This showed that CCP seropositivity had no statistically significant link with incident pneumonia, while RF seropositivity linked with a statistically significant, roughly twofold higher rate. Only 6% of all seropositive patients were positive only for CCP antibody, 59% were positive specifically for RF antibody, and 35% for both.

The data Dr. Sparks presented did not include information on pneumonia type, the timing of the pneumonia, compared with the onset of RA, disease activity, or smoking intensity.

“We anticipated that both RF positive and CCP positive would each be associated with pneumonia, so it was somewhat surprising that we only detected this for RF,” Dr. Sparks said. But he added that, because the number of patients with only CCP positivity was relatively so small, “it is still possible that CCP [antibody] could also increase pneumonia risk.”

The study had no commercial funding. Dr. Sparks had no disclosures.

[email protected]

SOURCE: Sparks JA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:73, Abstract OP0111.

Children with cystic fibrosis have inadequate sleep even during times of normal lung function, according to results from a new study.

Children aged 6-12 years had more sleep issues compared with preschoolers or teenagers, researchers also found, and the quality of sleep among caregivers was seen strongly linked to that of their children with CF.

For research published in the Journal of Cystic Fibrosis, Kelly C. Byars, PsyD, and colleagues at Cincinnati Children’s Medical Center and the University of Cincinnati surveyed parents of 91 medically stable patients with cystic fibrosis aged 18 and younger at a single CF treatment center between 2016 and 2017.

Fifty-four percent of the children in the study were female, the mean age was 9 years, and 90% of the caregivers were mothers. In addition to the sleep questionnaires, the researchers looked at the children’s available lung function data from around the time of the survey. Forced expiratory volume in one second (FEV₁) measures showed the vast majority had no obstructive lung disease (73% of the cohort) or only mild symptoms (18%) at the time their caregivers were surveyed.

Overall, some 40% of caregivers said they had concerns about their own sleep, while 29% said they were concerned for their children’s sleep. Parents reported night waking, daytime sleepiness, and difficulty falling asleep as their main problems, and difficulty falling asleep as the top issue for their children, along with daytime sleepiness, night waking, and mouth breathing.

Sleep issues were most pronounced for children aged 6-12 and their caregivers, a group for which 44% of caregivers said they were concerned for their children’s sleep and 55% for their own sleep. For this same group only 8% of parents reported their children having nocturnal cough, and just 5% reported gastrointestinal problems at night.

Overall, the caregivers in the study reported inadequate sleep, with more than half saying they got less than 7 hours per night. Similarly, more than half of the school-age and adolescent patients with CF were getting less than the nightly minimum recommended by the American Academy of Sleep Medicine.

The researchers noted “large effects for parent and child associations for insomnia symptoms that may be amenable to treatment,” especially trouble returning to sleep and daytime sleepiness.

The study “is the first to examine parent reported sleep disturbances and sleep duration in both parents and their children with CF spanning a broad age range and including patients who were medically stable and predominantly free of lung dysfunction,” Dr. Byars and colleagues wrote in their analysis, adding that sleep health should be integrated into care protocols for CF patients and their families, and families of children with other chronic illnesses.

In a comment on Dr. Byars and colleagues’ study, Hovig Artinian, MD, a pediatric pulmonary and sleep medicine specialist at Helen DeVos Children’s Hospital in Grand Rapids, Mich., said the findings “highlight for all of us that we must regularly assess and address sleep disturbances in our children with CF specifically, but also in all children with chronic conditions.”

Children with CF “carry a heavy burden,” Dr. Artinian said, “balancing living their lives with daily interruptions to their typical day to complete multiple treatments. As a result, sleep can be impacted even when there are no other clinical or objective signs of illness, so that was not an entirely surprising finding.” Difficulties with sleep onset and maintenance can be prevalent in the absence of changes in children’s daytime behavior or any other psychological signs, Dr. Artinian said, noting that in his practice he routinely asks families whether children snore (something recommended by the American Academy of Pediatrics for all well-child checks) and whether they have any other concerns about their sleep.

“Even if the answer is ‘no’ the first time, the act of asking plants a seed in their minds to keep an eye open and to know they can discuss it with us at a future visit if concerns come up,” Dr. Artinian said.

Dr. Byars and colleagues noted several limitations to their study including its cross-sectional, single-center design, potential participant selection bias, reliance on parent reports of child sleep, and use of a novel, nonvalidated survey instrument.

The researchers received funding from the Boomer Esiason Foundation for their study and disclosed no financial conflicts of interest. Dr. Artinian had no relevant disclosures.
 

SOURCE: Byars K et al. J Cyst Fibros. 2020 May. doi: 10.1016/j.jcf.2020.04.003.

Children with cystic fibrosis have inadequate sleep even during times of normal lung function, according to results from a new study.

Children aged 6-12 years had more sleep issues compared with preschoolers or teenagers, researchers also found, and the quality of sleep among caregivers was seen strongly linked to that of their children with CF.

For research published in the Journal of Cystic Fibrosis, Kelly C. Byars, PsyD, and colleagues at Cincinnati Children’s Medical Center and the University of Cincinnati surveyed parents of 91 medically stable patients with cystic fibrosis aged 18 and younger at a single CF treatment center between 2016 and 2017.

Fifty-four percent of the children in the study were female, the mean age was 9 years, and 90% of the caregivers were mothers. In addition to the sleep questionnaires, the researchers looked at the children’s available lung function data from around the time of the survey. Forced expiratory volume in one second (FEV₁) measures showed the vast majority had no obstructive lung disease (73% of the cohort) or only mild symptoms (18%) at the time their caregivers were surveyed.

Overall, some 40% of caregivers said they had concerns about their own sleep, while 29% said they were concerned for their children’s sleep. Parents reported night waking, daytime sleepiness, and difficulty falling asleep as their main problems, and difficulty falling asleep as the top issue for their children, along with daytime sleepiness, night waking, and mouth breathing.

Sleep issues were most pronounced for children aged 6-12 and their caregivers, a group for which 44% of caregivers said they were concerned for their children’s sleep and 55% for their own sleep. For this same group only 8% of parents reported their children having nocturnal cough, and just 5% reported gastrointestinal problems at night.

Overall, the caregivers in the study reported inadequate sleep, with more than half saying they got less than 7 hours per night. Similarly, more than half of the school-age and adolescent patients with CF were getting less than the nightly minimum recommended by the American Academy of Sleep Medicine.

The researchers noted “large effects for parent and child associations for insomnia symptoms that may be amenable to treatment,” especially trouble returning to sleep and daytime sleepiness.

The study “is the first to examine parent reported sleep disturbances and sleep duration in both parents and their children with CF spanning a broad age range and including patients who were medically stable and predominantly free of lung dysfunction,” Dr. Byars and colleagues wrote in their analysis, adding that sleep health should be integrated into care protocols for CF patients and their families, and families of children with other chronic illnesses.

In a comment on Dr. Byars and colleagues’ study, Hovig Artinian, MD, a pediatric pulmonary and sleep medicine specialist at Helen DeVos Children’s Hospital in Grand Rapids, Mich., said the findings “highlight for all of us that we must regularly assess and address sleep disturbances in our children with CF specifically, but also in all children with chronic conditions.”

Children with CF “carry a heavy burden,” Dr. Artinian said, “balancing living their lives with daily interruptions to their typical day to complete multiple treatments. As a result, sleep can be impacted even when there are no other clinical or objective signs of illness, so that was not an entirely surprising finding.” Difficulties with sleep onset and maintenance can be prevalent in the absence of changes in children’s daytime behavior or any other psychological signs, Dr. Artinian said, noting that in his practice he routinely asks families whether children snore (something recommended by the American Academy of Pediatrics for all well-child checks) and whether they have any other concerns about their sleep.

“Even if the answer is ‘no’ the first time, the act of asking plants a seed in their minds to keep an eye open and to know they can discuss it with us at a future visit if concerns come up,” Dr. Artinian said.

Dr. Byars and colleagues noted several limitations to their study including its cross-sectional, single-center design, potential participant selection bias, reliance on parent reports of child sleep, and use of a novel, nonvalidated survey instrument.

The researchers received funding from the Boomer Esiason Foundation for their study and disclosed no financial conflicts of interest. Dr. Artinian had no relevant disclosures.
 

SOURCE: Byars K et al. J Cyst Fibros. 2020 May. doi: 10.1016/j.jcf.2020.04.003.

Children with cystic fibrosis have inadequate sleep even during times of normal lung function, according to results from a new study.

Children aged 6-12 years had more sleep issues compared with preschoolers or teenagers, researchers also found, and the quality of sleep among caregivers was seen strongly linked to that of their children with CF.

For research published in the Journal of Cystic Fibrosis, Kelly C. Byars, PsyD, and colleagues at Cincinnati Children’s Medical Center and the University of Cincinnati surveyed parents of 91 medically stable patients with cystic fibrosis aged 18 and younger at a single CF treatment center between 2016 and 2017.

Fifty-four percent of the children in the study were female, the mean age was 9 years, and 90% of the caregivers were mothers. In addition to the sleep questionnaires, the researchers looked at the children’s available lung function data from around the time of the survey. Forced expiratory volume in one second (FEV₁) measures showed the vast majority had no obstructive lung disease (73% of the cohort) or only mild symptoms (18%) at the time their caregivers were surveyed.

Overall, some 40% of caregivers said they had concerns about their own sleep, while 29% said they were concerned for their children’s sleep. Parents reported night waking, daytime sleepiness, and difficulty falling asleep as their main problems, and difficulty falling asleep as the top issue for their children, along with daytime sleepiness, night waking, and mouth breathing.

Sleep issues were most pronounced for children aged 6-12 and their caregivers, a group for which 44% of caregivers said they were concerned for their children’s sleep and 55% for their own sleep. For this same group only 8% of parents reported their children having nocturnal cough, and just 5% reported gastrointestinal problems at night.

Overall, the caregivers in the study reported inadequate sleep, with more than half saying they got less than 7 hours per night. Similarly, more than half of the school-age and adolescent patients with CF were getting less than the nightly minimum recommended by the American Academy of Sleep Medicine.

The researchers noted “large effects for parent and child associations for insomnia symptoms that may be amenable to treatment,” especially trouble returning to sleep and daytime sleepiness.

The study “is the first to examine parent reported sleep disturbances and sleep duration in both parents and their children with CF spanning a broad age range and including patients who were medically stable and predominantly free of lung dysfunction,” Dr. Byars and colleagues wrote in their analysis, adding that sleep health should be integrated into care protocols for CF patients and their families, and families of children with other chronic illnesses.

In a comment on Dr. Byars and colleagues’ study, Hovig Artinian, MD, a pediatric pulmonary and sleep medicine specialist at Helen DeVos Children’s Hospital in Grand Rapids, Mich., said the findings “highlight for all of us that we must regularly assess and address sleep disturbances in our children with CF specifically, but also in all children with chronic conditions.”

Children with CF “carry a heavy burden,” Dr. Artinian said, “balancing living their lives with daily interruptions to their typical day to complete multiple treatments. As a result, sleep can be impacted even when there are no other clinical or objective signs of illness, so that was not an entirely surprising finding.” Difficulties with sleep onset and maintenance can be prevalent in the absence of changes in children’s daytime behavior or any other psychological signs, Dr. Artinian said, noting that in his practice he routinely asks families whether children snore (something recommended by the American Academy of Pediatrics for all well-child checks) and whether they have any other concerns about their sleep.

“Even if the answer is ‘no’ the first time, the act of asking plants a seed in their minds to keep an eye open and to know they can discuss it with us at a future visit if concerns come up,” Dr. Artinian said.

Dr. Byars and colleagues noted several limitations to their study including its cross-sectional, single-center design, potential participant selection bias, reliance on parent reports of child sleep, and use of a novel, nonvalidated survey instrument.

The researchers received funding from the Boomer Esiason Foundation for their study and disclosed no financial conflicts of interest. Dr. Artinian had no relevant disclosures.
 

SOURCE: Byars K et al. J Cyst Fibros. 2020 May. doi: 10.1016/j.jcf.2020.04.003.

Oral baloxavir marboxil is effective and well tolerated at alleviating symptoms in otherwise healthy children with acute influenza, according to Jeffrey Baker, MD, of Clinical Research Prime, Idaho Falls, and associates.

In the double-blind, randomized, controlled MiniSTONE-2 phase 3 trial, the investigators randomized 112 children aged 1-12 years to baloxavir and 57 to oseltamivir. The predominant influenza A subtype was H3N2 for both groups, followed by H1N1pdm09. Demographics and baseline characteristics were similar between treatment groups, the investigators wrote in the Pediatric Infectious Disease Journal.

The time to alleviation of signs and symptoms was a median 138 hours for those receiving baloxavir and 150 hours for those receiving oseltamivir, a nonsignificant difference. Duration of fever and of all symptoms also were similar between groups, as was the time to return to normal health and activity.

A total of 122 adverse events were reported in 84 children, with 95% of adverse events being resolved or resolving by the end of the study. The incidence of adverse events was 46% in those receiving baloxavir and 53% in those receiving oseltamivir, a nonsignificant difference, with the most common adverse event in both groups being gastrointestinal disorders. No deaths, serious adverse events, or hospitalizations were reported, but two patients receiving oseltamivir discontinued because of adverse events.

The study was funded by F. Hoffmann-La Roche. Dr. Baker and a coauthor received funding through their institutions for the conduct of the study; several coauthors reported being employed by and owning stocks in F. Hoffmann–La Roche. One coauthor reported receiving consultancy fees from F. Hoffmann–La Roche and grants from Shionogi.

[email protected]

SOURCE: Baker J et al. Pediatr Infect Dis J. 2020 Jun 5. doi: 10.1097/INF.0000000000002747.

Oral baloxavir marboxil is effective and well tolerated at alleviating symptoms in otherwise healthy children with acute influenza, according to Jeffrey Baker, MD, of Clinical Research Prime, Idaho Falls, and associates.

In the double-blind, randomized, controlled MiniSTONE-2 phase 3 trial, the investigators randomized 112 children aged 1-12 years to baloxavir and 57 to oseltamivir. The predominant influenza A subtype was H3N2 for both groups, followed by H1N1pdm09. Demographics and baseline characteristics were similar between treatment groups, the investigators wrote in the Pediatric Infectious Disease Journal.

The time to alleviation of signs and symptoms was a median 138 hours for those receiving baloxavir and 150 hours for those receiving oseltamivir, a nonsignificant difference. Duration of fever and of all symptoms also were similar between groups, as was the time to return to normal health and activity.

A total of 122 adverse events were reported in 84 children, with 95% of adverse events being resolved or resolving by the end of the study. The incidence of adverse events was 46% in those receiving baloxavir and 53% in those receiving oseltamivir, a nonsignificant difference, with the most common adverse event in both groups being gastrointestinal disorders. No deaths, serious adverse events, or hospitalizations were reported, but two patients receiving oseltamivir discontinued because of adverse events.

The study was funded by F. Hoffmann-La Roche. Dr. Baker and a coauthor received funding through their institutions for the conduct of the study; several coauthors reported being employed by and owning stocks in F. Hoffmann–La Roche. One coauthor reported receiving consultancy fees from F. Hoffmann–La Roche and grants from Shionogi.

[email protected]

SOURCE: Baker J et al. Pediatr Infect Dis J. 2020 Jun 5. doi: 10.1097/INF.0000000000002747.

Oral baloxavir marboxil is effective and well tolerated at alleviating symptoms in otherwise healthy children with acute influenza, according to Jeffrey Baker, MD, of Clinical Research Prime, Idaho Falls, and associates.

In the double-blind, randomized, controlled MiniSTONE-2 phase 3 trial, the investigators randomized 112 children aged 1-12 years to baloxavir and 57 to oseltamivir. The predominant influenza A subtype was H3N2 for both groups, followed by H1N1pdm09. Demographics and baseline characteristics were similar between treatment groups, the investigators wrote in the Pediatric Infectious Disease Journal.

The time to alleviation of signs and symptoms was a median 138 hours for those receiving baloxavir and 150 hours for those receiving oseltamivir, a nonsignificant difference. Duration of fever and of all symptoms also were similar between groups, as was the time to return to normal health and activity.

A total of 122 adverse events were reported in 84 children, with 95% of adverse events being resolved or resolving by the end of the study. The incidence of adverse events was 46% in those receiving baloxavir and 53% in those receiving oseltamivir, a nonsignificant difference, with the most common adverse event in both groups being gastrointestinal disorders. No deaths, serious adverse events, or hospitalizations were reported, but two patients receiving oseltamivir discontinued because of adverse events.

The study was funded by F. Hoffmann-La Roche. Dr. Baker and a coauthor received funding through their institutions for the conduct of the study; several coauthors reported being employed by and owning stocks in F. Hoffmann–La Roche. One coauthor reported receiving consultancy fees from F. Hoffmann–La Roche and grants from Shionogi.

[email protected]

SOURCE: Baker J et al. Pediatr Infect Dis J. 2020 Jun 5. doi: 10.1097/INF.0000000000002747.

Patients with rheumatoid arthritis (RA) have an elevated risk of interstitial lung disease (ILD), but methotrexate does not accentuate that risk and may in fact be protective, new data show. These were among key findings of a pair of studies reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Although a guideline-recommended cornerstone in the management of RA, methotrexate has been associated with both hypersensitivity pneumonitis and diffuse lung disease. However, its involvement in the development of ILD among patients with RA is unclear.

A Danish study of more than 30,000 RA patients reported at the congress found that their risk of ILD was about three to five times that of the general population. However, risk did not differ significantly whether they had filled a methotrexate prescription or not.

In addition, a multinational case-control study of more than 1,000 RA patients also reported at the congress found that, compared with never-users of methotrexate, ever-users actually had a 59% lower likelihood of developing ILD.

However, both studies were limited by their retrospective design, Elizabeth R. Volkmann, MD, codirector of the connective tissue disease–related interstitial lung disease program at the University of California, Los Angeles, cautioned in an interview. Hence, there was likely systematic bias and confounding.

“I would interpret the conclusions of both studies with caution,” she maintained. “To understand how a particular intervention, such as methotrexate use, affects the outcome of ILD development, a prospective design is needed, which adequately adjusts for known ILD risk factors, such as male sex and smoking.”

As to whether the new findings are practice changing and how they might affect patient counseling, “the answers to these questions are not straightforward and depend on other patient-related factors,” according to Dr. Volkmann.
 

Danish nationwide study

René Cordtz, MD, a clinical assistant at the Center for Rheumatology and Spine Diseases, Rigshospitalet‐Gentofte, Copenhagen, and colleagues conducted a nationwide population-based cohort study using registry data from 1997 to 2015 to assess lung disease among patients with RA by prescriptions filled.

Results based on 30,512 RA patients showed that, compared with peers filling no methotrexate prescriptions, patients filling at least one did not have a significantly elevated risk of ILD at either 1 year of follow-up (hazard ratio, 1.03) or 5 years of follow-up (HR, 1.00). (Findings were similar for sulfasalazine, with respective nonsignificant HRs of 0.88 and 1.14.)

In addition, patients with RA had a similarly sharply elevated 5-year risk of ILD relative to the general population regardless of whether they had filled neither methotrexate nor sulfasalazine prescriptions (standardized incidence ratio, 3.38) or had filled prescriptions for methotrexate only (SIR, 3.63), sulfasalazine only (SIR, 4.12), or both (SIR, 5.45).

“RA patients have an increased risk of ILD, compared to the general population, which was not surprising, but very importantly, that risk was not further exacerbated in those treated with methotrexate,” Dr. Cordtz concluded. “We do acknowledge that purchasing your medicine is different from taking your medicine, which is why we found it extra reassuring that when requiring at least two methotrexate prescriptions to be considered exposed, it did not change our results.”

Multinational study

Pierre-Antoine Juge, MD, a rheumatologist at Bichat-Claude Bernard Hospital, Paris, and colleagues performed a case-control study among 482 RA patients with ILD and 741 RA patients without ILD in three cohorts: a French discovery cohort, a multinational (Brazilian, Italian, Mexican, United Kingdom, and United States) replication cohort, and a combined cohort. Those with methotrexate hypersensitivity pneumonitis were excluded.

Results showed that relative to peers without ILD, patients with ILD had a lower prevalence of ever having used methotrexate and had received a lower cumulative methotrexate dose, findings that were consistent across all three cohorts.

Methotrexate ever-use was associated with a significantly lower adjusted likelihood of ILD in the discovery cohort (odds ratio, 0.46), the replication cohort (OR, 0.38), and the combined cohort (OR, 0.41). Furthermore, ever-users were less commonly represented among patients with ILD regardless of chest high-resolution CT pattern (usual interstitial pneumonia pattern vs. not).

Finally, methotrexate use appeared to delay the adjusted time to onset of ILD by 3.5 years in the discovery cohort (P = .001), by 3.2 years in the replication cohort (P < .0001), and by 3.5 years in the combined cohort (P < .0001).

“Outside of methotrexate hypersensitivity pneumonitis, methotrexate was not a risk factor for RA-associated ILD in our study. We observed an inverse relationship that was similar whatever the high-resolution CT pattern,” Dr. Juge commented. “But this possible protective effect should be confirmed through a dedicated prospective, randomized, controlled trial.”

“Methotrexate should not be considered as a causal factor for RA-associated ILD, and its [discontinuation] should be discussed through a multidisciplinary discussion,” he recommended. In addition, “this study does not investigate the impact of methotrexate use on RA-associated ILD prognosis.”

The Danish study did not receive any specific funding, and none of its authors reported having any financial disclosures. The multinational study did not receive any specific funding. Dr. Juge disclosed that he had no relevant conflicts of interest, but many of his coauthors reported financial relationships with industry. Dr. Volkmann disclosed consulting for Boehringer Ingelheim and Forbius, and receiving grant support from Forbius and Corbus.

SOURCES: Cordtz R et al. Ann Rheum Dis. 2020;79[suppl 1]:147-8, Abstract OP0232; Juge P-A et al. Ann Rheum Dis. 2020;79[suppl 1]:25, Abstract OP0236.

Patients with rheumatoid arthritis (RA) have an elevated risk of interstitial lung disease (ILD), but methotrexate does not accentuate that risk and may in fact be protective, new data show. These were among key findings of a pair of studies reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Although a guideline-recommended cornerstone in the management of RA, methotrexate has been associated with both hypersensitivity pneumonitis and diffuse lung disease. However, its involvement in the development of ILD among patients with RA is unclear.

A Danish study of more than 30,000 RA patients reported at the congress found that their risk of ILD was about three to five times that of the general population. However, risk did not differ significantly whether they had filled a methotrexate prescription or not.

In addition, a multinational case-control study of more than 1,000 RA patients also reported at the congress found that, compared with never-users of methotrexate, ever-users actually had a 59% lower likelihood of developing ILD.

However, both studies were limited by their retrospective design, Elizabeth R. Volkmann, MD, codirector of the connective tissue disease–related interstitial lung disease program at the University of California, Los Angeles, cautioned in an interview. Hence, there was likely systematic bias and confounding.

“I would interpret the conclusions of both studies with caution,” she maintained. “To understand how a particular intervention, such as methotrexate use, affects the outcome of ILD development, a prospective design is needed, which adequately adjusts for known ILD risk factors, such as male sex and smoking.”

As to whether the new findings are practice changing and how they might affect patient counseling, “the answers to these questions are not straightforward and depend on other patient-related factors,” according to Dr. Volkmann.
 

Danish nationwide study

René Cordtz, MD, a clinical assistant at the Center for Rheumatology and Spine Diseases, Rigshospitalet‐Gentofte, Copenhagen, and colleagues conducted a nationwide population-based cohort study using registry data from 1997 to 2015 to assess lung disease among patients with RA by prescriptions filled.

Results based on 30,512 RA patients showed that, compared with peers filling no methotrexate prescriptions, patients filling at least one did not have a significantly elevated risk of ILD at either 1 year of follow-up (hazard ratio, 1.03) or 5 years of follow-up (HR, 1.00). (Findings were similar for sulfasalazine, with respective nonsignificant HRs of 0.88 and 1.14.)

In addition, patients with RA had a similarly sharply elevated 5-year risk of ILD relative to the general population regardless of whether they had filled neither methotrexate nor sulfasalazine prescriptions (standardized incidence ratio, 3.38) or had filled prescriptions for methotrexate only (SIR, 3.63), sulfasalazine only (SIR, 4.12), or both (SIR, 5.45).

“RA patients have an increased risk of ILD, compared to the general population, which was not surprising, but very importantly, that risk was not further exacerbated in those treated with methotrexate,” Dr. Cordtz concluded. “We do acknowledge that purchasing your medicine is different from taking your medicine, which is why we found it extra reassuring that when requiring at least two methotrexate prescriptions to be considered exposed, it did not change our results.”

Multinational study

Pierre-Antoine Juge, MD, a rheumatologist at Bichat-Claude Bernard Hospital, Paris, and colleagues performed a case-control study among 482 RA patients with ILD and 741 RA patients without ILD in three cohorts: a French discovery cohort, a multinational (Brazilian, Italian, Mexican, United Kingdom, and United States) replication cohort, and a combined cohort. Those with methotrexate hypersensitivity pneumonitis were excluded.

Results showed that relative to peers without ILD, patients with ILD had a lower prevalence of ever having used methotrexate and had received a lower cumulative methotrexate dose, findings that were consistent across all three cohorts.

Methotrexate ever-use was associated with a significantly lower adjusted likelihood of ILD in the discovery cohort (odds ratio, 0.46), the replication cohort (OR, 0.38), and the combined cohort (OR, 0.41). Furthermore, ever-users were less commonly represented among patients with ILD regardless of chest high-resolution CT pattern (usual interstitial pneumonia pattern vs. not).

Finally, methotrexate use appeared to delay the adjusted time to onset of ILD by 3.5 years in the discovery cohort (P = .001), by 3.2 years in the replication cohort (P < .0001), and by 3.5 years in the combined cohort (P < .0001).

“Outside of methotrexate hypersensitivity pneumonitis, methotrexate was not a risk factor for RA-associated ILD in our study. We observed an inverse relationship that was similar whatever the high-resolution CT pattern,” Dr. Juge commented. “But this possible protective effect should be confirmed through a dedicated prospective, randomized, controlled trial.”

“Methotrexate should not be considered as a causal factor for RA-associated ILD, and its [discontinuation] should be discussed through a multidisciplinary discussion,” he recommended. In addition, “this study does not investigate the impact of methotrexate use on RA-associated ILD prognosis.”

The Danish study did not receive any specific funding, and none of its authors reported having any financial disclosures. The multinational study did not receive any specific funding. Dr. Juge disclosed that he had no relevant conflicts of interest, but many of his coauthors reported financial relationships with industry. Dr. Volkmann disclosed consulting for Boehringer Ingelheim and Forbius, and receiving grant support from Forbius and Corbus.

SOURCES: Cordtz R et al. Ann Rheum Dis. 2020;79[suppl 1]:147-8, Abstract OP0232; Juge P-A et al. Ann Rheum Dis. 2020;79[suppl 1]:25, Abstract OP0236.

Patients with rheumatoid arthritis (RA) have an elevated risk of interstitial lung disease (ILD), but methotrexate does not accentuate that risk and may in fact be protective, new data show. These were among key findings of a pair of studies reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Although a guideline-recommended cornerstone in the management of RA, methotrexate has been associated with both hypersensitivity pneumonitis and diffuse lung disease. However, its involvement in the development of ILD among patients with RA is unclear.

A Danish study of more than 30,000 RA patients reported at the congress found that their risk of ILD was about three to five times that of the general population. However, risk did not differ significantly whether they had filled a methotrexate prescription or not.

In addition, a multinational case-control study of more than 1,000 RA patients also reported at the congress found that, compared with never-users of methotrexate, ever-users actually had a 59% lower likelihood of developing ILD.

However, both studies were limited by their retrospective design, Elizabeth R. Volkmann, MD, codirector of the connective tissue disease–related interstitial lung disease program at the University of California, Los Angeles, cautioned in an interview. Hence, there was likely systematic bias and confounding.

“I would interpret the conclusions of both studies with caution,” she maintained. “To understand how a particular intervention, such as methotrexate use, affects the outcome of ILD development, a prospective design is needed, which adequately adjusts for known ILD risk factors, such as male sex and smoking.”

As to whether the new findings are practice changing and how they might affect patient counseling, “the answers to these questions are not straightforward and depend on other patient-related factors,” according to Dr. Volkmann.
 

Danish nationwide study

René Cordtz, MD, a clinical assistant at the Center for Rheumatology and Spine Diseases, Rigshospitalet‐Gentofte, Copenhagen, and colleagues conducted a nationwide population-based cohort study using registry data from 1997 to 2015 to assess lung disease among patients with RA by prescriptions filled.

Results based on 30,512 RA patients showed that, compared with peers filling no methotrexate prescriptions, patients filling at least one did not have a significantly elevated risk of ILD at either 1 year of follow-up (hazard ratio, 1.03) or 5 years of follow-up (HR, 1.00). (Findings were similar for sulfasalazine, with respective nonsignificant HRs of 0.88 and 1.14.)

In addition, patients with RA had a similarly sharply elevated 5-year risk of ILD relative to the general population regardless of whether they had filled neither methotrexate nor sulfasalazine prescriptions (standardized incidence ratio, 3.38) or had filled prescriptions for methotrexate only (SIR, 3.63), sulfasalazine only (SIR, 4.12), or both (SIR, 5.45).

“RA patients have an increased risk of ILD, compared to the general population, which was not surprising, but very importantly, that risk was not further exacerbated in those treated with methotrexate,” Dr. Cordtz concluded. “We do acknowledge that purchasing your medicine is different from taking your medicine, which is why we found it extra reassuring that when requiring at least two methotrexate prescriptions to be considered exposed, it did not change our results.”

Multinational study

Pierre-Antoine Juge, MD, a rheumatologist at Bichat-Claude Bernard Hospital, Paris, and colleagues performed a case-control study among 482 RA patients with ILD and 741 RA patients without ILD in three cohorts: a French discovery cohort, a multinational (Brazilian, Italian, Mexican, United Kingdom, and United States) replication cohort, and a combined cohort. Those with methotrexate hypersensitivity pneumonitis were excluded.

Results showed that relative to peers without ILD, patients with ILD had a lower prevalence of ever having used methotrexate and had received a lower cumulative methotrexate dose, findings that were consistent across all three cohorts.

Methotrexate ever-use was associated with a significantly lower adjusted likelihood of ILD in the discovery cohort (odds ratio, 0.46), the replication cohort (OR, 0.38), and the combined cohort (OR, 0.41). Furthermore, ever-users were less commonly represented among patients with ILD regardless of chest high-resolution CT pattern (usual interstitial pneumonia pattern vs. not).

Finally, methotrexate use appeared to delay the adjusted time to onset of ILD by 3.5 years in the discovery cohort (P = .001), by 3.2 years in the replication cohort (P < .0001), and by 3.5 years in the combined cohort (P < .0001).

“Outside of methotrexate hypersensitivity pneumonitis, methotrexate was not a risk factor for RA-associated ILD in our study. We observed an inverse relationship that was similar whatever the high-resolution CT pattern,” Dr. Juge commented. “But this possible protective effect should be confirmed through a dedicated prospective, randomized, controlled trial.”

“Methotrexate should not be considered as a causal factor for RA-associated ILD, and its [discontinuation] should be discussed through a multidisciplinary discussion,” he recommended. In addition, “this study does not investigate the impact of methotrexate use on RA-associated ILD prognosis.”

The Danish study did not receive any specific funding, and none of its authors reported having any financial disclosures. The multinational study did not receive any specific funding. Dr. Juge disclosed that he had no relevant conflicts of interest, but many of his coauthors reported financial relationships with industry. Dr. Volkmann disclosed consulting for Boehringer Ingelheim and Forbius, and receiving grant support from Forbius and Corbus.

SOURCES: Cordtz R et al. Ann Rheum Dis. 2020;79[suppl 1]:147-8, Abstract OP0232; Juge P-A et al. Ann Rheum Dis. 2020;79[suppl 1]:25, Abstract OP0236.

The use of electronic nicotine delivery systems is associated with increased risk of cigarette smoking relapse among former smokers, results from a large longitudinal cohort study demonstrated.

ArminStautBerlin/Thinkstock

“For the many clinicians treating former smokers who have successfully quit all nicotine products, the implications are that use of [electronic nicotine delivery systems] should be discouraged, just as use of all other tobacco products is discouraged,” researchers led by Colm D. Everard, PhD, reported in a study published in JAMA Network Open (2020 Jun 5. doi: 10.1001/jamanetworkopen.2020.4813).

Dr. Everard, of the National Institute on Drug Abuse, and colleagues based their comments on results from a survey of adult former smokers who participated in Waves 1-4 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2018). They limited the analysis to 2,273 former cigarette smokers who self-reported reported no tobacco product use at Wave 1, and categorized them as recent former smokers (defined as having last smoked within the past 12 previous months) or as long-term former smokers (defined as having last smoked for longer ago than in the previous 12 months). The main outcome of interest was the self-reported current use of cigarettes at follow-up interviews, which was defined as every day or some days. Electronic nicotine delivery systems (ENDS) comprised e-cigarettes, e-cigars, e-pipes, and e-hookahs. Other tobacco products included cigars, pipe tobacco, hookahs, snus tobacco, other smokeless tobacco, and dissolvable tobacco.

Of the 2,273 adult former smokers, 52% were women, 60% were older than age 50, and 80% were non-Hispanic white. Adjusted hazard ratio (AHR) analysis revealed that the use of ENDS was associated with significant risk of cigarette smoking relapse among recent former smokers (AHR 1.63) and among long-term former smokers (AHR 3.79). The use of other tobacco products was associated with significant risk for cigarette smoking relapse among recent former smokers (AHR 1.97) and among long-term former smokers (AHR 3.82).

The authors acknowledged certain limitations of the study, including the fact that it did not assess different ENDS devices, different e-liquid nicotine levels, or frequency of ENDS use and their associations with cigarette smoking relapse. It also did not explore the mechanism by which ENDS use may lead to reestablishing or reinforcing nicotine-seeking behavior among former cigarette users. “Determining pharmacologic, behavioral, or some other explanation for these findings may require laboratory-based research,” they wrote.

The PATH Study is supported with federal funds from the National Institute on Drug Abuse, the National Institutes of Health, and the Food and Drug Administration and Department of Health and Human Services under a contract to Westat. One of the study authors, Wilson M. Compton, MD, reported having long-term stock holdings in General Electric, 3M, and Pfizer. The other authors reported having no financial disclosures.

[email protected]

The use of electronic nicotine delivery systems is associated with increased risk of cigarette smoking relapse among former smokers, results from a large longitudinal cohort study demonstrated.

ArminStautBerlin/Thinkstock

“For the many clinicians treating former smokers who have successfully quit all nicotine products, the implications are that use of [electronic nicotine delivery systems] should be discouraged, just as use of all other tobacco products is discouraged,” researchers led by Colm D. Everard, PhD, reported in a study published in JAMA Network Open (2020 Jun 5. doi: 10.1001/jamanetworkopen.2020.4813).

Dr. Everard, of the National Institute on Drug Abuse, and colleagues based their comments on results from a survey of adult former smokers who participated in Waves 1-4 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2018). They limited the analysis to 2,273 former cigarette smokers who self-reported reported no tobacco product use at Wave 1, and categorized them as recent former smokers (defined as having last smoked within the past 12 previous months) or as long-term former smokers (defined as having last smoked for longer ago than in the previous 12 months). The main outcome of interest was the self-reported current use of cigarettes at follow-up interviews, which was defined as every day or some days. Electronic nicotine delivery systems (ENDS) comprised e-cigarettes, e-cigars, e-pipes, and e-hookahs. Other tobacco products included cigars, pipe tobacco, hookahs, snus tobacco, other smokeless tobacco, and dissolvable tobacco.

Of the 2,273 adult former smokers, 52% were women, 60% were older than age 50, and 80% were non-Hispanic white. Adjusted hazard ratio (AHR) analysis revealed that the use of ENDS was associated with significant risk of cigarette smoking relapse among recent former smokers (AHR 1.63) and among long-term former smokers (AHR 3.79). The use of other tobacco products was associated with significant risk for cigarette smoking relapse among recent former smokers (AHR 1.97) and among long-term former smokers (AHR 3.82).

The authors acknowledged certain limitations of the study, including the fact that it did not assess different ENDS devices, different e-liquid nicotine levels, or frequency of ENDS use and their associations with cigarette smoking relapse. It also did not explore the mechanism by which ENDS use may lead to reestablishing or reinforcing nicotine-seeking behavior among former cigarette users. “Determining pharmacologic, behavioral, or some other explanation for these findings may require laboratory-based research,” they wrote.

The PATH Study is supported with federal funds from the National Institute on Drug Abuse, the National Institutes of Health, and the Food and Drug Administration and Department of Health and Human Services under a contract to Westat. One of the study authors, Wilson M. Compton, MD, reported having long-term stock holdings in General Electric, 3M, and Pfizer. The other authors reported having no financial disclosures.

[email protected]

The use of electronic nicotine delivery systems is associated with increased risk of cigarette smoking relapse among former smokers, results from a large longitudinal cohort study demonstrated.

ArminStautBerlin/Thinkstock

“For the many clinicians treating former smokers who have successfully quit all nicotine products, the implications are that use of [electronic nicotine delivery systems] should be discouraged, just as use of all other tobacco products is discouraged,” researchers led by Colm D. Everard, PhD, reported in a study published in JAMA Network Open (2020 Jun 5. doi: 10.1001/jamanetworkopen.2020.4813).

Dr. Everard, of the National Institute on Drug Abuse, and colleagues based their comments on results from a survey of adult former smokers who participated in Waves 1-4 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2018). They limited the analysis to 2,273 former cigarette smokers who self-reported reported no tobacco product use at Wave 1, and categorized them as recent former smokers (defined as having last smoked within the past 12 previous months) or as long-term former smokers (defined as having last smoked for longer ago than in the previous 12 months). The main outcome of interest was the self-reported current use of cigarettes at follow-up interviews, which was defined as every day or some days. Electronic nicotine delivery systems (ENDS) comprised e-cigarettes, e-cigars, e-pipes, and e-hookahs. Other tobacco products included cigars, pipe tobacco, hookahs, snus tobacco, other smokeless tobacco, and dissolvable tobacco.

Of the 2,273 adult former smokers, 52% were women, 60% were older than age 50, and 80% were non-Hispanic white. Adjusted hazard ratio (AHR) analysis revealed that the use of ENDS was associated with significant risk of cigarette smoking relapse among recent former smokers (AHR 1.63) and among long-term former smokers (AHR 3.79). The use of other tobacco products was associated with significant risk for cigarette smoking relapse among recent former smokers (AHR 1.97) and among long-term former smokers (AHR 3.82).

The authors acknowledged certain limitations of the study, including the fact that it did not assess different ENDS devices, different e-liquid nicotine levels, or frequency of ENDS use and their associations with cigarette smoking relapse. It also did not explore the mechanism by which ENDS use may lead to reestablishing or reinforcing nicotine-seeking behavior among former cigarette users. “Determining pharmacologic, behavioral, or some other explanation for these findings may require laboratory-based research,” they wrote.

The PATH Study is supported with federal funds from the National Institute on Drug Abuse, the National Institutes of Health, and the Food and Drug Administration and Department of Health and Human Services under a contract to Westat. One of the study authors, Wilson M. Compton, MD, reported having long-term stock holdings in General Electric, 3M, and Pfizer. The other authors reported having no financial disclosures.

[email protected]