Pulmonology

An overview of five important advances in pulmonary and critical care medicine are on the agenda for the “Update in Pulmonary and Critical Care” session on Tuesday, May 4, at the virtual 2021 SHM Converge conference.

“I hope this session gives attendees a nice, broad look at advances both in the intensive care unit and in general pulmonary medicine,” said James Walter, MD, of Northwestern Medicine in Chicago, who serves as director of the session.

On the critical care medicine side, Dr. Walter will review the latest research on the efficacy of ascorbic acid in treating patients with severe sepsis and septic shock. “There was a lot of excitement and some skepticism about early results promising a really large treatment effect in giving critically ill patients with sepsis large doses of vitamin C,” Dr. Walter said. The last year has produced some high-quality randomized trials that have contributed to a better understanding of the potential effects ascorbic acid in sepsis can have, he noted.

Dr. Walter, who is also medical director of the Northwestern Lung Rescue Program, intends to discuss what he believes is a definitive trial regarding the benefit of preemptively starting critically ill patients with acute kidney injury on renal replacement therapy instead of waiting until there are specific clinical signs. “This has been another area of uncertainty in critical care and I think we finally have a very definitive answer with this high quality, randomized, controlled trial that I plan to review,” he said.

Though he said there have been a number of important advances in pulmonary medicine over the past year, Dr. Walter will highlight just two.

Up until recently, the antifibrotics nintedanib and pirfenidone have mostly been used in patients with idiopathic pulmonary fibrosis. However, recent research suggests there may be a potential benefit to using these drugs in patients with fibrotic lung disease outside of idiopathic pulmonary fibrosis. “I think this is an important advance for hospital medicine providers to be aware of,” said Dr. Walter.

He will also go over some large randomized controlled trials of the use of triple therapy – a combination of a long-acting beta agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled corticosteroid in one inhaler – in chronic obstructive pulmonary disease. The trials looked at whether triple inhaler therapy was beneficial compared to the typical therapies used for COPD.

The session wouldn’t be complete without a nod to COVID-19, which Dr. Walter said has significantly changed the landscape for hospital medicine providers. He plans to discuss what he considers the most impactful study – the RECOVERY trial. This study looked at the role of dexamethasone in patients with more severe manifestations of SARS-CoV-2.

“From the incredible amount of data that’s come out in the last year about COVID, I think this is probably the trial that’s changed practice the most and shown the largest therapeutic benefit of all the pharmacotherapies,” Dr. Walter said. “It’s an important one for providers to be aware of in terms of what the trial shows and how it informs which patients are most likely to benefit from dexamethasone therapy.”

Dr. Walter hopes clinicians who participate in the session will leave with these takeaways:

• Be able to summarize recent trials of ascorbic acid in sepsis and think about how to incorporate – or not – the use of vitamin C in critically ill sepsis patients.
• A thorough understanding of when renal replacement therapy should be offered to critically ill patients with acute kidney dysfunction.
• Be able to discuss the impact of antifibrotic therapy in interstitial lung diseases outside of idiopathic pulmonary fibrosis.
• An understanding of the role of triple inhaler combinations in COPD.
• Be able to explain when dexamethasone is most likely to benefit hypoxemic patients with COVID-19.

An overview of five important advances in pulmonary and critical care medicine are on the agenda for the “Update in Pulmonary and Critical Care” session on Tuesday, May 4, at the virtual 2021 SHM Converge conference.

“I hope this session gives attendees a nice, broad look at advances both in the intensive care unit and in general pulmonary medicine,” said James Walter, MD, of Northwestern Medicine in Chicago, who serves as director of the session.

On the critical care medicine side, Dr. Walter will review the latest research on the efficacy of ascorbic acid in treating patients with severe sepsis and septic shock. “There was a lot of excitement and some skepticism about early results promising a really large treatment effect in giving critically ill patients with sepsis large doses of vitamin C,” Dr. Walter said. The last year has produced some high-quality randomized trials that have contributed to a better understanding of the potential effects ascorbic acid in sepsis can have, he noted.

Dr. Walter, who is also medical director of the Northwestern Lung Rescue Program, intends to discuss what he believes is a definitive trial regarding the benefit of preemptively starting critically ill patients with acute kidney injury on renal replacement therapy instead of waiting until there are specific clinical signs. “This has been another area of uncertainty in critical care and I think we finally have a very definitive answer with this high quality, randomized, controlled trial that I plan to review,” he said.

Though he said there have been a number of important advances in pulmonary medicine over the past year, Dr. Walter will highlight just two.

Up until recently, the antifibrotics nintedanib and pirfenidone have mostly been used in patients with idiopathic pulmonary fibrosis. However, recent research suggests there may be a potential benefit to using these drugs in patients with fibrotic lung disease outside of idiopathic pulmonary fibrosis. “I think this is an important advance for hospital medicine providers to be aware of,” said Dr. Walter.

He will also go over some large randomized controlled trials of the use of triple therapy – a combination of a long-acting beta agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled corticosteroid in one inhaler – in chronic obstructive pulmonary disease. The trials looked at whether triple inhaler therapy was beneficial compared to the typical therapies used for COPD.

The session wouldn’t be complete without a nod to COVID-19, which Dr. Walter said has significantly changed the landscape for hospital medicine providers. He plans to discuss what he considers the most impactful study – the RECOVERY trial. This study looked at the role of dexamethasone in patients with more severe manifestations of SARS-CoV-2.

“From the incredible amount of data that’s come out in the last year about COVID, I think this is probably the trial that’s changed practice the most and shown the largest therapeutic benefit of all the pharmacotherapies,” Dr. Walter said. “It’s an important one for providers to be aware of in terms of what the trial shows and how it informs which patients are most likely to benefit from dexamethasone therapy.”

Dr. Walter hopes clinicians who participate in the session will leave with these takeaways:

• Be able to summarize recent trials of ascorbic acid in sepsis and think about how to incorporate – or not – the use of vitamin C in critically ill sepsis patients.
• A thorough understanding of when renal replacement therapy should be offered to critically ill patients with acute kidney dysfunction.
• Be able to discuss the impact of antifibrotic therapy in interstitial lung diseases outside of idiopathic pulmonary fibrosis.
• An understanding of the role of triple inhaler combinations in COPD.
• Be able to explain when dexamethasone is most likely to benefit hypoxemic patients with COVID-19.

An overview of five important advances in pulmonary and critical care medicine are on the agenda for the “Update in Pulmonary and Critical Care” session on Tuesday, May 4, at the virtual 2021 SHM Converge conference.

“I hope this session gives attendees a nice, broad look at advances both in the intensive care unit and in general pulmonary medicine,” said James Walter, MD, of Northwestern Medicine in Chicago, who serves as director of the session.

On the critical care medicine side, Dr. Walter will review the latest research on the efficacy of ascorbic acid in treating patients with severe sepsis and septic shock. “There was a lot of excitement and some skepticism about early results promising a really large treatment effect in giving critically ill patients with sepsis large doses of vitamin C,” Dr. Walter said. The last year has produced some high-quality randomized trials that have contributed to a better understanding of the potential effects ascorbic acid in sepsis can have, he noted.

Dr. Walter, who is also medical director of the Northwestern Lung Rescue Program, intends to discuss what he believes is a definitive trial regarding the benefit of preemptively starting critically ill patients with acute kidney injury on renal replacement therapy instead of waiting until there are specific clinical signs. “This has been another area of uncertainty in critical care and I think we finally have a very definitive answer with this high quality, randomized, controlled trial that I plan to review,” he said.

Though he said there have been a number of important advances in pulmonary medicine over the past year, Dr. Walter will highlight just two.

Up until recently, the antifibrotics nintedanib and pirfenidone have mostly been used in patients with idiopathic pulmonary fibrosis. However, recent research suggests there may be a potential benefit to using these drugs in patients with fibrotic lung disease outside of idiopathic pulmonary fibrosis. “I think this is an important advance for hospital medicine providers to be aware of,” said Dr. Walter.

He will also go over some large randomized controlled trials of the use of triple therapy – a combination of a long-acting beta agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled corticosteroid in one inhaler – in chronic obstructive pulmonary disease. The trials looked at whether triple inhaler therapy was beneficial compared to the typical therapies used for COPD.

The session wouldn’t be complete without a nod to COVID-19, which Dr. Walter said has significantly changed the landscape for hospital medicine providers. He plans to discuss what he considers the most impactful study – the RECOVERY trial. This study looked at the role of dexamethasone in patients with more severe manifestations of SARS-CoV-2.

“From the incredible amount of data that’s come out in the last year about COVID, I think this is probably the trial that’s changed practice the most and shown the largest therapeutic benefit of all the pharmacotherapies,” Dr. Walter said. “It’s an important one for providers to be aware of in terms of what the trial shows and how it informs which patients are most likely to benefit from dexamethasone therapy.”

Dr. Walter hopes clinicians who participate in the session will leave with these takeaways:

• Be able to summarize recent trials of ascorbic acid in sepsis and think about how to incorporate – or not – the use of vitamin C in critically ill sepsis patients.
• A thorough understanding of when renal replacement therapy should be offered to critically ill patients with acute kidney dysfunction.
• Be able to discuss the impact of antifibrotic therapy in interstitial lung diseases outside of idiopathic pulmonary fibrosis.
• An understanding of the role of triple inhaler combinations in COPD.
• Be able to explain when dexamethasone is most likely to benefit hypoxemic patients with COVID-19.

Asthma is not an independent risk factor for more severe disease or hospitalization due to COVID-19, according to recent research presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“In our cohort of patients tested for SARS-CoV-2 at Stanford between March and September, asthma was not an independent risk factor in and of itself for hospitalization or more severe disease from COVID,” Lauren E. Eggert, MD, of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University, said in a poster presentation at the meeting. “What’s more, allergic asthma actually decreased the risk of hospitalization by nearly half.”

Dr. Eggert noted that there have been conflicting data on whether comorbid asthma is or is not a risk factor for more severe COVID-19. “The general thought at the beginning of the pandemic was that because COVID-19 is predominantly a viral respiratory illness, and viral illnesses are known to cause asthma exacerbations, that patients with asthma may be at higher risk if they got COVID infection,” she explained. “But some of the data also showed that Th2 inflammation downregulates ACE2 receptor [expression], which has been shown to be the port of entry for the SARS-CoV-2 virus, so maybe allergy might have a protective effect.”

The researchers at Stanford University identified 168,190 patients at Stanford Health Care who had a positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between March and September 2020 and collected data from their electronic medical records on their history of asthma, if they were hospitalized, comorbid conditions, and laboratory values. Patients who had no other data available except for a positive SARS-CoV-2 result, or were younger than 28 days, were excluded from the study. Dr. Eggert and colleagues used COVID-19 treatment guidelines from the National Institutes of Health to assess disease severity, which grades COVID-19 severity as asymptomatic or presymptomatic infection, mild illness, moderate illness, severe illness, and critical illness.

In total, the researchers analyzed 5,596 patients who were SARS-CoV-2 positive, with 605 patients (10.8%) hospitalized within 14 days of receiving a positive test. Of these, 100 patients (16.5%) were patients with asthma. There were no significant differences between groups hospitalized and not hospitalized due to COVID-19 in patients with asthma and with no asthma.

Among patients with asthma and COVID-19, 28.0% had asymptomatic illness, 19.0% had moderate disease, 33.0% had severe disease, and 20.0% had critical COVID-19, compared with 36.0% of patients without asthma who had asymptomatic illness, 12.0% with moderate disease, 30.0% with severe disease, and 21.0% with critical COVID-19. Dr. Eggert and colleagues performed a univariate analysis, which showed a significant association between asthma and COVID-19 related hospitalization (odds ratio, 1.53; 95% confidence interval, 1.2-1.93; P < .001), but when adjusting for factors such as diabetes, obesity coronary heart disease, and hypertension, they found there was not a significant association between asthma and hospitalization due to COVID-19 (OR, 1.12; 95% CI, 0.86-1.45; P < .40).

In a univariate analysis, asthma was associated with more severe disease in patients hospitalized for COVID-19, but the results were not significant (OR, 1.21; 95% CI, 0.8-1.85; P = .37). When analyzing allergic asthma alone in a univariate analysis, the researchers found a significant association between allergic asthma and lower hospitalization risk, compared with patients who had nonallergic asthma (OR, 0.55; 95% CI, 0.31-0.92; P = .029), and this association remained after they performed a multivariate analysis as well.

“When we stratified by allergic asthma versus nonallergic asthma, we found that having a diagnosis of allergic asthma actually conferred a protective effect, and there was almost half the risk of hospitalization in asthmatics with allergic asthma as compared to others, which we thought was very interesting,” Dr. Eggert said.

“Eosinophil levels during hospitalization, even when adjusted for systemic steroid use – and we followed patients out through September, when dexamethasone was standard of care – also correlated with better outcomes,” she explained. “This is independent of asthmatic status.”

Asthma is not an independent risk factor for more severe disease or hospitalization due to COVID-19, according to recent research presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“In our cohort of patients tested for SARS-CoV-2 at Stanford between March and September, asthma was not an independent risk factor in and of itself for hospitalization or more severe disease from COVID,” Lauren E. Eggert, MD, of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University, said in a poster presentation at the meeting. “What’s more, allergic asthma actually decreased the risk of hospitalization by nearly half.”

Dr. Eggert noted that there have been conflicting data on whether comorbid asthma is or is not a risk factor for more severe COVID-19. “The general thought at the beginning of the pandemic was that because COVID-19 is predominantly a viral respiratory illness, and viral illnesses are known to cause asthma exacerbations, that patients with asthma may be at higher risk if they got COVID infection,” she explained. “But some of the data also showed that Th2 inflammation downregulates ACE2 receptor [expression], which has been shown to be the port of entry for the SARS-CoV-2 virus, so maybe allergy might have a protective effect.”

The researchers at Stanford University identified 168,190 patients at Stanford Health Care who had a positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between March and September 2020 and collected data from their electronic medical records on their history of asthma, if they were hospitalized, comorbid conditions, and laboratory values. Patients who had no other data available except for a positive SARS-CoV-2 result, or were younger than 28 days, were excluded from the study. Dr. Eggert and colleagues used COVID-19 treatment guidelines from the National Institutes of Health to assess disease severity, which grades COVID-19 severity as asymptomatic or presymptomatic infection, mild illness, moderate illness, severe illness, and critical illness.

In total, the researchers analyzed 5,596 patients who were SARS-CoV-2 positive, with 605 patients (10.8%) hospitalized within 14 days of receiving a positive test. Of these, 100 patients (16.5%) were patients with asthma. There were no significant differences between groups hospitalized and not hospitalized due to COVID-19 in patients with asthma and with no asthma.

Among patients with asthma and COVID-19, 28.0% had asymptomatic illness, 19.0% had moderate disease, 33.0% had severe disease, and 20.0% had critical COVID-19, compared with 36.0% of patients without asthma who had asymptomatic illness, 12.0% with moderate disease, 30.0% with severe disease, and 21.0% with critical COVID-19. Dr. Eggert and colleagues performed a univariate analysis, which showed a significant association between asthma and COVID-19 related hospitalization (odds ratio, 1.53; 95% confidence interval, 1.2-1.93; P < .001), but when adjusting for factors such as diabetes, obesity coronary heart disease, and hypertension, they found there was not a significant association between asthma and hospitalization due to COVID-19 (OR, 1.12; 95% CI, 0.86-1.45; P < .40).

In a univariate analysis, asthma was associated with more severe disease in patients hospitalized for COVID-19, but the results were not significant (OR, 1.21; 95% CI, 0.8-1.85; P = .37). When analyzing allergic asthma alone in a univariate analysis, the researchers found a significant association between allergic asthma and lower hospitalization risk, compared with patients who had nonallergic asthma (OR, 0.55; 95% CI, 0.31-0.92; P = .029), and this association remained after they performed a multivariate analysis as well.

“When we stratified by allergic asthma versus nonallergic asthma, we found that having a diagnosis of allergic asthma actually conferred a protective effect, and there was almost half the risk of hospitalization in asthmatics with allergic asthma as compared to others, which we thought was very interesting,” Dr. Eggert said.

“Eosinophil levels during hospitalization, even when adjusted for systemic steroid use – and we followed patients out through September, when dexamethasone was standard of care – also correlated with better outcomes,” she explained. “This is independent of asthmatic status.”

Asthma is not an independent risk factor for more severe disease or hospitalization due to COVID-19, according to recent research presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“In our cohort of patients tested for SARS-CoV-2 at Stanford between March and September, asthma was not an independent risk factor in and of itself for hospitalization or more severe disease from COVID,” Lauren E. Eggert, MD, of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University, said in a poster presentation at the meeting. “What’s more, allergic asthma actually decreased the risk of hospitalization by nearly half.”

Dr. Eggert noted that there have been conflicting data on whether comorbid asthma is or is not a risk factor for more severe COVID-19. “The general thought at the beginning of the pandemic was that because COVID-19 is predominantly a viral respiratory illness, and viral illnesses are known to cause asthma exacerbations, that patients with asthma may be at higher risk if they got COVID infection,” she explained. “But some of the data also showed that Th2 inflammation downregulates ACE2 receptor [expression], which has been shown to be the port of entry for the SARS-CoV-2 virus, so maybe allergy might have a protective effect.”

The researchers at Stanford University identified 168,190 patients at Stanford Health Care who had a positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between March and September 2020 and collected data from their electronic medical records on their history of asthma, if they were hospitalized, comorbid conditions, and laboratory values. Patients who had no other data available except for a positive SARS-CoV-2 result, or were younger than 28 days, were excluded from the study. Dr. Eggert and colleagues used COVID-19 treatment guidelines from the National Institutes of Health to assess disease severity, which grades COVID-19 severity as asymptomatic or presymptomatic infection, mild illness, moderate illness, severe illness, and critical illness.

In total, the researchers analyzed 5,596 patients who were SARS-CoV-2 positive, with 605 patients (10.8%) hospitalized within 14 days of receiving a positive test. Of these, 100 patients (16.5%) were patients with asthma. There were no significant differences between groups hospitalized and not hospitalized due to COVID-19 in patients with asthma and with no asthma.

Among patients with asthma and COVID-19, 28.0% had asymptomatic illness, 19.0% had moderate disease, 33.0% had severe disease, and 20.0% had critical COVID-19, compared with 36.0% of patients without asthma who had asymptomatic illness, 12.0% with moderate disease, 30.0% with severe disease, and 21.0% with critical COVID-19. Dr. Eggert and colleagues performed a univariate analysis, which showed a significant association between asthma and COVID-19 related hospitalization (odds ratio, 1.53; 95% confidence interval, 1.2-1.93; P < .001), but when adjusting for factors such as diabetes, obesity coronary heart disease, and hypertension, they found there was not a significant association between asthma and hospitalization due to COVID-19 (OR, 1.12; 95% CI, 0.86-1.45; P < .40).

In a univariate analysis, asthma was associated with more severe disease in patients hospitalized for COVID-19, but the results were not significant (OR, 1.21; 95% CI, 0.8-1.85; P = .37). When analyzing allergic asthma alone in a univariate analysis, the researchers found a significant association between allergic asthma and lower hospitalization risk, compared with patients who had nonallergic asthma (OR, 0.55; 95% CI, 0.31-0.92; P = .029), and this association remained after they performed a multivariate analysis as well.

“When we stratified by allergic asthma versus nonallergic asthma, we found that having a diagnosis of allergic asthma actually conferred a protective effect, and there was almost half the risk of hospitalization in asthmatics with allergic asthma as compared to others, which we thought was very interesting,” Dr. Eggert said.

“Eosinophil levels during hospitalization, even when adjusted for systemic steroid use – and we followed patients out through September, when dexamethasone was standard of care – also correlated with better outcomes,” she explained. “This is independent of asthmatic status.”

Long-term use of continuous positive airway pressure (CPAP) was associated with higher self-reported physical activity levels in adults with co-occurring obstructive sleep apnea (OSA) and cardiovascular disease (CVD), in new research.

“The aim of this study was to determine whether long-term CPAP treatment affects self-reported physical activity among participants with moderate-severe OSA and comorbid CV disease,” wrote David Stevens, PhD, of Flinders University, Adelaide, Australia, and his colleagues. The findings were recently published in the Journal of Clinical Sleep Medicine.

Researchers conducted a secondary analysis of the Sleep apnea cardiovascular endpoints (SAVE) trial that enrolled 2,687 adults aged 45-75 years old with OSA and confirmed CVD. In the study, participants were randomized to receive either CPAP plus usual care or usual care alone.

Physical activity levels were self-reported using the Leisure-Time Exercise Questionnaire (LTEQ) at baseline and at 6-, 24-, and 48-month follow-up intervals. The physical functioning subscale of the 36-item short form questionnaire (SF-36) was used to determine if activity levels were consistent with expert recommendations and to evaluate the effects on any self-perceived limitation of physical activity.
 

Moderate physical activity was higher among CPAP users

After a mean follow-up duration of 3.7 years, participants in the CPAP arm had approximately 20% higher levels of moderate physical activity, compared with the control arm (adjusted mean scores]: 8.7 points vs. 7.3 points; 95% confidence interval, 7.5-9.9 vs. 6.1-8.5; P = .003).

However, no significant difference was observed between treatment arms for mild physical activity (adjusted mean scores, 14.4 points vs. 14.2 points; 95% CI, 13.5-15.3 vs. 13.3-15.1; P = 0.599) or vigorous physical activity (adjusted mean scores, 3.4 points vs. 2.9 points; 95% CI 2.6-4.2 vs. 2.1-3.7; P = .125).

In addition, participants in the CPAP group reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score = 1.66; 95% CI, 0.87-2.45; P < .001) and were more likely to report activity levels consistent with guideline recommendations.

“We were pleasantly surprised to find that people assigned to CPAP reported more physical activity than their counterparts who received usual care, despite being given no specific exercise instructions,” Kelly A. Loffler, PhD, a coauthor of the study, said in an interview.

“While I don’t think this will result in any immediate changes to guidelines, it is a helpful reminder to clinicians who are treating such patients, that the symptomatic benefits people experience with CPAP present a window of opportunity to improve health more holistically,” Dr. Loffler explained.

The researchers acknowledged that a key limitation of the study was the use of self-reported outcome measures. In future studies, they recommended that recent technological innovations, such as the availability of activity tracking devices, should be used to measure physical activity.

They also noted that patients with excessive sleepiness and severe hypoxemia were excluded from the SAVE trial; thus, the findings may not be generalizable to all patients.
 

Study reinforces CPAP’s health benefits

Emerson M. Wickwire, PhD, associate professor of psychiatry and medicine at the University of Maryland, Baltimore, explained that CPAP treatment is associated with well-documented health benefits among patients with CVD, as well as enhanced quality of life.

“These results provide further evidence that treating OSA can provide direct and indirect health benefits, suggesting that increased physical activity can be a vital pathway to improved cardiovascular health and enjoyment of life,” Dr. Wickwire, who is also director of the Insomnia Program at the University of Maryland Midtown Medical Center, Baltimore, said in an interview.

Steven M. Scharf, MD, a pulmonologist who is director of the Sleep Disorders Center (Adults) at the University of Maryland, also said the study findings were consistent with previous research involving patients treated for OSA.

“It is no surprise that treatment of OSA improves patient’s daily physical functioning,” explained Dr. Scharf, who is also a clinical professor, in an interview. “These results are expected, but very welcome, and I was glad to see them.”

The study was funded by the National Health and Medical Research Council of Australia, the Respironics Sleep and Respiratory Research Foundation, and Philips Respironics. Some authors reported financial affiliations with medical device and pharmaceutical companies. Dr. Loffler, Dr. Wickwire, and Dr. Scharf reported no conflicts of interest related to this work.

Long-term use of continuous positive airway pressure (CPAP) was associated with higher self-reported physical activity levels in adults with co-occurring obstructive sleep apnea (OSA) and cardiovascular disease (CVD), in new research.

“The aim of this study was to determine whether long-term CPAP treatment affects self-reported physical activity among participants with moderate-severe OSA and comorbid CV disease,” wrote David Stevens, PhD, of Flinders University, Adelaide, Australia, and his colleagues. The findings were recently published in the Journal of Clinical Sleep Medicine.

Researchers conducted a secondary analysis of the Sleep apnea cardiovascular endpoints (SAVE) trial that enrolled 2,687 adults aged 45-75 years old with OSA and confirmed CVD. In the study, participants were randomized to receive either CPAP plus usual care or usual care alone.

Physical activity levels were self-reported using the Leisure-Time Exercise Questionnaire (LTEQ) at baseline and at 6-, 24-, and 48-month follow-up intervals. The physical functioning subscale of the 36-item short form questionnaire (SF-36) was used to determine if activity levels were consistent with expert recommendations and to evaluate the effects on any self-perceived limitation of physical activity.
 

Moderate physical activity was higher among CPAP users

After a mean follow-up duration of 3.7 years, participants in the CPAP arm had approximately 20% higher levels of moderate physical activity, compared with the control arm (adjusted mean scores]: 8.7 points vs. 7.3 points; 95% confidence interval, 7.5-9.9 vs. 6.1-8.5; P = .003).

However, no significant difference was observed between treatment arms for mild physical activity (adjusted mean scores, 14.4 points vs. 14.2 points; 95% CI, 13.5-15.3 vs. 13.3-15.1; P = 0.599) or vigorous physical activity (adjusted mean scores, 3.4 points vs. 2.9 points; 95% CI 2.6-4.2 vs. 2.1-3.7; P = .125).

In addition, participants in the CPAP group reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score = 1.66; 95% CI, 0.87-2.45; P < .001) and were more likely to report activity levels consistent with guideline recommendations.

“We were pleasantly surprised to find that people assigned to CPAP reported more physical activity than their counterparts who received usual care, despite being given no specific exercise instructions,” Kelly A. Loffler, PhD, a coauthor of the study, said in an interview.

“While I don’t think this will result in any immediate changes to guidelines, it is a helpful reminder to clinicians who are treating such patients, that the symptomatic benefits people experience with CPAP present a window of opportunity to improve health more holistically,” Dr. Loffler explained.

The researchers acknowledged that a key limitation of the study was the use of self-reported outcome measures. In future studies, they recommended that recent technological innovations, such as the availability of activity tracking devices, should be used to measure physical activity.

They also noted that patients with excessive sleepiness and severe hypoxemia were excluded from the SAVE trial; thus, the findings may not be generalizable to all patients.
 

Study reinforces CPAP’s health benefits

Emerson M. Wickwire, PhD, associate professor of psychiatry and medicine at the University of Maryland, Baltimore, explained that CPAP treatment is associated with well-documented health benefits among patients with CVD, as well as enhanced quality of life.

“These results provide further evidence that treating OSA can provide direct and indirect health benefits, suggesting that increased physical activity can be a vital pathway to improved cardiovascular health and enjoyment of life,” Dr. Wickwire, who is also director of the Insomnia Program at the University of Maryland Midtown Medical Center, Baltimore, said in an interview.

Steven M. Scharf, MD, a pulmonologist who is director of the Sleep Disorders Center (Adults) at the University of Maryland, also said the study findings were consistent with previous research involving patients treated for OSA.

“It is no surprise that treatment of OSA improves patient’s daily physical functioning,” explained Dr. Scharf, who is also a clinical professor, in an interview. “These results are expected, but very welcome, and I was glad to see them.”

The study was funded by the National Health and Medical Research Council of Australia, the Respironics Sleep and Respiratory Research Foundation, and Philips Respironics. Some authors reported financial affiliations with medical device and pharmaceutical companies. Dr. Loffler, Dr. Wickwire, and Dr. Scharf reported no conflicts of interest related to this work.

Long-term use of continuous positive airway pressure (CPAP) was associated with higher self-reported physical activity levels in adults with co-occurring obstructive sleep apnea (OSA) and cardiovascular disease (CVD), in new research.

“The aim of this study was to determine whether long-term CPAP treatment affects self-reported physical activity among participants with moderate-severe OSA and comorbid CV disease,” wrote David Stevens, PhD, of Flinders University, Adelaide, Australia, and his colleagues. The findings were recently published in the Journal of Clinical Sleep Medicine.

Researchers conducted a secondary analysis of the Sleep apnea cardiovascular endpoints (SAVE) trial that enrolled 2,687 adults aged 45-75 years old with OSA and confirmed CVD. In the study, participants were randomized to receive either CPAP plus usual care or usual care alone.

Physical activity levels were self-reported using the Leisure-Time Exercise Questionnaire (LTEQ) at baseline and at 6-, 24-, and 48-month follow-up intervals. The physical functioning subscale of the 36-item short form questionnaire (SF-36) was used to determine if activity levels were consistent with expert recommendations and to evaluate the effects on any self-perceived limitation of physical activity.
 

Moderate physical activity was higher among CPAP users

After a mean follow-up duration of 3.7 years, participants in the CPAP arm had approximately 20% higher levels of moderate physical activity, compared with the control arm (adjusted mean scores]: 8.7 points vs. 7.3 points; 95% confidence interval, 7.5-9.9 vs. 6.1-8.5; P = .003).

However, no significant difference was observed between treatment arms for mild physical activity (adjusted mean scores, 14.4 points vs. 14.2 points; 95% CI, 13.5-15.3 vs. 13.3-15.1; P = 0.599) or vigorous physical activity (adjusted mean scores, 3.4 points vs. 2.9 points; 95% CI 2.6-4.2 vs. 2.1-3.7; P = .125).

In addition, participants in the CPAP group reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score = 1.66; 95% CI, 0.87-2.45; P < .001) and were more likely to report activity levels consistent with guideline recommendations.

“We were pleasantly surprised to find that people assigned to CPAP reported more physical activity than their counterparts who received usual care, despite being given no specific exercise instructions,” Kelly A. Loffler, PhD, a coauthor of the study, said in an interview.

“While I don’t think this will result in any immediate changes to guidelines, it is a helpful reminder to clinicians who are treating such patients, that the symptomatic benefits people experience with CPAP present a window of opportunity to improve health more holistically,” Dr. Loffler explained.

The researchers acknowledged that a key limitation of the study was the use of self-reported outcome measures. In future studies, they recommended that recent technological innovations, such as the availability of activity tracking devices, should be used to measure physical activity.

They also noted that patients with excessive sleepiness and severe hypoxemia were excluded from the SAVE trial; thus, the findings may not be generalizable to all patients.
 

Study reinforces CPAP’s health benefits

Emerson M. Wickwire, PhD, associate professor of psychiatry and medicine at the University of Maryland, Baltimore, explained that CPAP treatment is associated with well-documented health benefits among patients with CVD, as well as enhanced quality of life.

“These results provide further evidence that treating OSA can provide direct and indirect health benefits, suggesting that increased physical activity can be a vital pathway to improved cardiovascular health and enjoyment of life,” Dr. Wickwire, who is also director of the Insomnia Program at the University of Maryland Midtown Medical Center, Baltimore, said in an interview.

Steven M. Scharf, MD, a pulmonologist who is director of the Sleep Disorders Center (Adults) at the University of Maryland, also said the study findings were consistent with previous research involving patients treated for OSA.

“It is no surprise that treatment of OSA improves patient’s daily physical functioning,” explained Dr. Scharf, who is also a clinical professor, in an interview. “These results are expected, but very welcome, and I was glad to see them.”

The study was funded by the National Health and Medical Research Council of Australia, the Respironics Sleep and Respiratory Research Foundation, and Philips Respironics. Some authors reported financial affiliations with medical device and pharmaceutical companies. Dr. Loffler, Dr. Wickwire, and Dr. Scharf reported no conflicts of interest related to this work.

Over the past 20 years, patients with asthma and chronic obstructive pulmonary disease (COPD) have seen next to no improvement in problems of delayed care because of cost or unaffordable medications, despite wider insurance coverage since the passage of the Affordable Care Act, a new analysis shows.

The long-view analysis illuminates the ongoing problem for people with these chronic diseases despite health care legislation that was considered historic.

“That long-term scope puts recent improvements in better context – whereas we have made improvements in coverage in recent years due to the Affordable Care Act, the longer-term picture is that people with asthma and COPD are struggling to obtain needed medical care and medications despite a substantial reduction in the uninsurance rate,” said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston who authored the paper with David Himmelstein, MD, professor of public health at City University of New York–Hunter College. The findings were published in Chest.

Researchers examined data from 1997 to 2018 for 76,843 adults with asthma and 30,548 adults with COPD, from the National Health Interview Survey, an annual survey by the Centers for Disease Control that is based on in-person interviews and health questionnaires completed by an adult in each family.
 

Insurance coverage up, patients losing ground

During 1997 and 2018, there was an overall 9.3% decrease in the rate of adults with asthma who were uninsured, a significant improvement (P < .001). Between the pre- and post-ACA years, there was modest improvement in those putting off care because of cost, a drop of 3.8%, or going without prescriptions, a drop of 4.0%. But those improvements didn’t correspond to the 7.2% drop in the uninsured rate after the AC , contributing to the finding that there was no significant improvement over the 20 years.

For adults with COPD, it was a slightly different story. Over those 2 decades, the uninsured rate dropped by 9.5%. But the number of patients foregoing care due to cost actually rose by 3.4%, which wasn’t statistically significant, but the rate of those unable to afford needed medications rose significantly by 7.8%.

Researchers found there was improvement between the pre- and post-ACA years among COPD patients putting off care and going without medications (decreases of 6.9% and 4.5%, respectively). That adhered fairly closely with the improvement in the uninsured rate, which fell by 7.1%. But over the 20-year study period, the percentage of those needing medications they couldn’t afford increased significantly by 7.8%. The rate of those delaying or foregoing care also increased, though this amount was not statistically significant.

After the ACA was created, Blacks and Hispanics with asthma had greater improvement in obtaining insurance, compared with other racial and ethnic groups. But over the 20 years, like all racial and ethnic groups, they saw no statistically significant improvement in rates of “inadequate coverage,” defined in this study as either being uninsured, having to delay care because of cost, or being unable to afford needed medications.

For those with COPD, only Whites had statistically significant improvement in the number of patients with inadequate coverage after the ACA, researchers found.

So despite obtaining insurance, patients lost ground in managing their disease because of the growing cost of care and medication.

“Medication affordability has actually worsened for those with COPD – a worrisome development given that medication nonadherence worsens outcomes for these vulnerable patients,” Dr. Gaffney said. “Policy makers should return to the issue of national health care reform. Both uninsurance and underinsurance undermines pulmonologists’ ability to care for their patients with chronic disease. A health care system without financial barriers, in contrast, might well improve these patients’ outcomes, and advance health equity.”
 

Insurance is no guarantee to access

Daniel Ouellette, MD, FCCP, a pulmonary and critical care specialist at Henry Ford Health System in Detroit, said it’s not surprising that access to care remains a problem despite the Affordable Care Act.

“It covers the hospitalizations and ER visits – patients in this segment of society were getting cared for there anyway,” he said. “And what the ACA didn’t always do was provide adequate prescription coverage or cover these outpatient gaps. So even though the patients have the ACA they still have unaffordable prescriptions, they still can’t buy them, and they still can’t pay for their outpatient clinic if they have a $500 or $1,000 deductible.” These patients also continue to struggle with more fundamental issues that affect access to care, such as lack of transportation and poor health literacy.

At Henry Ford, pharmacists work with patients to identify medications covered by their insurance and work to find discounts and coupons, he said. As for the ACA, “it’s a good first start, but we really need to identify what its limitations are.” Locally driven, less expensive solutions might be a better way forward than costly federal initiatives.

Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, said the findings dovetail with what he has seen in the pediatric population.

“From my experience, the ACA has helped patients get their foot in the door and has helped patients decrease the possibility of serious financial burden in emergency situations, but the ability to afford medications has not changed very much,” he said. When patients struggle with sufficient prescription coverage, he helps patients fight for coverage and connects them with prescription assistance programs such as GoodRx.

“Instead of focusing on the access of insurance to patients, the goal of the system should be to make care as affordable as possible,” Dr. Seay said. “Access does not meet the needs of a patient if they cannot afford what they have access to. Transition to a nationalized health system where there is no question of access could help to drive down prescription drug prices by allowing the government to negotiate with pharmaceutical companies more adequately by removing the ‘middle man’ of the private insurance industry.”

The investigators reported no financial conflicts. Dr. Ouellette and Dr. Seay reported no financial conflicts.

Over the past 20 years, patients with asthma and chronic obstructive pulmonary disease (COPD) have seen next to no improvement in problems of delayed care because of cost or unaffordable medications, despite wider insurance coverage since the passage of the Affordable Care Act, a new analysis shows.

The long-view analysis illuminates the ongoing problem for people with these chronic diseases despite health care legislation that was considered historic.

“That long-term scope puts recent improvements in better context – whereas we have made improvements in coverage in recent years due to the Affordable Care Act, the longer-term picture is that people with asthma and COPD are struggling to obtain needed medical care and medications despite a substantial reduction in the uninsurance rate,” said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston who authored the paper with David Himmelstein, MD, professor of public health at City University of New York–Hunter College. The findings were published in Chest.

Researchers examined data from 1997 to 2018 for 76,843 adults with asthma and 30,548 adults with COPD, from the National Health Interview Survey, an annual survey by the Centers for Disease Control that is based on in-person interviews and health questionnaires completed by an adult in each family.
 

Insurance coverage up, patients losing ground

During 1997 and 2018, there was an overall 9.3% decrease in the rate of adults with asthma who were uninsured, a significant improvement (P < .001). Between the pre- and post-ACA years, there was modest improvement in those putting off care because of cost, a drop of 3.8%, or going without prescriptions, a drop of 4.0%. But those improvements didn’t correspond to the 7.2% drop in the uninsured rate after the AC , contributing to the finding that there was no significant improvement over the 20 years.

For adults with COPD, it was a slightly different story. Over those 2 decades, the uninsured rate dropped by 9.5%. But the number of patients foregoing care due to cost actually rose by 3.4%, which wasn’t statistically significant, but the rate of those unable to afford needed medications rose significantly by 7.8%.

Researchers found there was improvement between the pre- and post-ACA years among COPD patients putting off care and going without medications (decreases of 6.9% and 4.5%, respectively). That adhered fairly closely with the improvement in the uninsured rate, which fell by 7.1%. But over the 20-year study period, the percentage of those needing medications they couldn’t afford increased significantly by 7.8%. The rate of those delaying or foregoing care also increased, though this amount was not statistically significant.

After the ACA was created, Blacks and Hispanics with asthma had greater improvement in obtaining insurance, compared with other racial and ethnic groups. But over the 20 years, like all racial and ethnic groups, they saw no statistically significant improvement in rates of “inadequate coverage,” defined in this study as either being uninsured, having to delay care because of cost, or being unable to afford needed medications.

For those with COPD, only Whites had statistically significant improvement in the number of patients with inadequate coverage after the ACA, researchers found.

So despite obtaining insurance, patients lost ground in managing their disease because of the growing cost of care and medication.

“Medication affordability has actually worsened for those with COPD – a worrisome development given that medication nonadherence worsens outcomes for these vulnerable patients,” Dr. Gaffney said. “Policy makers should return to the issue of national health care reform. Both uninsurance and underinsurance undermines pulmonologists’ ability to care for their patients with chronic disease. A health care system without financial barriers, in contrast, might well improve these patients’ outcomes, and advance health equity.”
 

Insurance is no guarantee to access

Daniel Ouellette, MD, FCCP, a pulmonary and critical care specialist at Henry Ford Health System in Detroit, said it’s not surprising that access to care remains a problem despite the Affordable Care Act.

“It covers the hospitalizations and ER visits – patients in this segment of society were getting cared for there anyway,” he said. “And what the ACA didn’t always do was provide adequate prescription coverage or cover these outpatient gaps. So even though the patients have the ACA they still have unaffordable prescriptions, they still can’t buy them, and they still can’t pay for their outpatient clinic if they have a $500 or $1,000 deductible.” These patients also continue to struggle with more fundamental issues that affect access to care, such as lack of transportation and poor health literacy.

At Henry Ford, pharmacists work with patients to identify medications covered by their insurance and work to find discounts and coupons, he said. As for the ACA, “it’s a good first start, but we really need to identify what its limitations are.” Locally driven, less expensive solutions might be a better way forward than costly federal initiatives.

Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, said the findings dovetail with what he has seen in the pediatric population.

“From my experience, the ACA has helped patients get their foot in the door and has helped patients decrease the possibility of serious financial burden in emergency situations, but the ability to afford medications has not changed very much,” he said. When patients struggle with sufficient prescription coverage, he helps patients fight for coverage and connects them with prescription assistance programs such as GoodRx.

“Instead of focusing on the access of insurance to patients, the goal of the system should be to make care as affordable as possible,” Dr. Seay said. “Access does not meet the needs of a patient if they cannot afford what they have access to. Transition to a nationalized health system where there is no question of access could help to drive down prescription drug prices by allowing the government to negotiate with pharmaceutical companies more adequately by removing the ‘middle man’ of the private insurance industry.”

The investigators reported no financial conflicts. Dr. Ouellette and Dr. Seay reported no financial conflicts.

Over the past 20 years, patients with asthma and chronic obstructive pulmonary disease (COPD) have seen next to no improvement in problems of delayed care because of cost or unaffordable medications, despite wider insurance coverage since the passage of the Affordable Care Act, a new analysis shows.

The long-view analysis illuminates the ongoing problem for people with these chronic diseases despite health care legislation that was considered historic.

“That long-term scope puts recent improvements in better context – whereas we have made improvements in coverage in recent years due to the Affordable Care Act, the longer-term picture is that people with asthma and COPD are struggling to obtain needed medical care and medications despite a substantial reduction in the uninsurance rate,” said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston who authored the paper with David Himmelstein, MD, professor of public health at City University of New York–Hunter College. The findings were published in Chest.

Researchers examined data from 1997 to 2018 for 76,843 adults with asthma and 30,548 adults with COPD, from the National Health Interview Survey, an annual survey by the Centers for Disease Control that is based on in-person interviews and health questionnaires completed by an adult in each family.
 

Insurance coverage up, patients losing ground

During 1997 and 2018, there was an overall 9.3% decrease in the rate of adults with asthma who were uninsured, a significant improvement (P < .001). Between the pre- and post-ACA years, there was modest improvement in those putting off care because of cost, a drop of 3.8%, or going without prescriptions, a drop of 4.0%. But those improvements didn’t correspond to the 7.2% drop in the uninsured rate after the AC , contributing to the finding that there was no significant improvement over the 20 years.

For adults with COPD, it was a slightly different story. Over those 2 decades, the uninsured rate dropped by 9.5%. But the number of patients foregoing care due to cost actually rose by 3.4%, which wasn’t statistically significant, but the rate of those unable to afford needed medications rose significantly by 7.8%.

Researchers found there was improvement between the pre- and post-ACA years among COPD patients putting off care and going without medications (decreases of 6.9% and 4.5%, respectively). That adhered fairly closely with the improvement in the uninsured rate, which fell by 7.1%. But over the 20-year study period, the percentage of those needing medications they couldn’t afford increased significantly by 7.8%. The rate of those delaying or foregoing care also increased, though this amount was not statistically significant.

After the ACA was created, Blacks and Hispanics with asthma had greater improvement in obtaining insurance, compared with other racial and ethnic groups. But over the 20 years, like all racial and ethnic groups, they saw no statistically significant improvement in rates of “inadequate coverage,” defined in this study as either being uninsured, having to delay care because of cost, or being unable to afford needed medications.

For those with COPD, only Whites had statistically significant improvement in the number of patients with inadequate coverage after the ACA, researchers found.

So despite obtaining insurance, patients lost ground in managing their disease because of the growing cost of care and medication.

“Medication affordability has actually worsened for those with COPD – a worrisome development given that medication nonadherence worsens outcomes for these vulnerable patients,” Dr. Gaffney said. “Policy makers should return to the issue of national health care reform. Both uninsurance and underinsurance undermines pulmonologists’ ability to care for their patients with chronic disease. A health care system without financial barriers, in contrast, might well improve these patients’ outcomes, and advance health equity.”
 

Insurance is no guarantee to access

Daniel Ouellette, MD, FCCP, a pulmonary and critical care specialist at Henry Ford Health System in Detroit, said it’s not surprising that access to care remains a problem despite the Affordable Care Act.

“It covers the hospitalizations and ER visits – patients in this segment of society were getting cared for there anyway,” he said. “And what the ACA didn’t always do was provide adequate prescription coverage or cover these outpatient gaps. So even though the patients have the ACA they still have unaffordable prescriptions, they still can’t buy them, and they still can’t pay for their outpatient clinic if they have a $500 or $1,000 deductible.” These patients also continue to struggle with more fundamental issues that affect access to care, such as lack of transportation and poor health literacy.

At Henry Ford, pharmacists work with patients to identify medications covered by their insurance and work to find discounts and coupons, he said. As for the ACA, “it’s a good first start, but we really need to identify what its limitations are.” Locally driven, less expensive solutions might be a better way forward than costly federal initiatives.

Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, said the findings dovetail with what he has seen in the pediatric population.

“From my experience, the ACA has helped patients get their foot in the door and has helped patients decrease the possibility of serious financial burden in emergency situations, but the ability to afford medications has not changed very much,” he said. When patients struggle with sufficient prescription coverage, he helps patients fight for coverage and connects them with prescription assistance programs such as GoodRx.

“Instead of focusing on the access of insurance to patients, the goal of the system should be to make care as affordable as possible,” Dr. Seay said. “Access does not meet the needs of a patient if they cannot afford what they have access to. Transition to a nationalized health system where there is no question of access could help to drive down prescription drug prices by allowing the government to negotiate with pharmaceutical companies more adequately by removing the ‘middle man’ of the private insurance industry.”

The investigators reported no financial conflicts. Dr. Ouellette and Dr. Seay reported no financial conflicts.

The Food and Drug Administration has approved the first device to help reduce snoring and mild obstructive sleep apnea (OSA) that is used during the day while the patient is awake.

eXciteOSA (Signifier Medical Technologies) is a prescription-only, neuromuscular stimulation device designed to improve tongue muscle function, which, over time, can help prevent the tongue from collapsing backwards and obstructing the airway during sleep, the FDA said.

The eXciteOSA mouthpiece has four electrodes that deliver a series of electrical pulses with rest periods in between. Two electrodes are located above the tongue and two are located below the tongue.

The patient uses the device for 20 minutes once a day while awake for 6 weeks, and once a week thereafter. It is indicated for adults aged 18 and older with snoring and mild OSA.

OSA is marked by the recurring collapse of the upper airways during sleep, intermittently reducing or completely blocking airflow. Common symptoms include snoring, restless sleep and daytime sleepiness. Untreated OSA can lead to serious complications such as cardiovascular disease and cognitive and behavioral disorders.

Continuous positive airway pressure therapy, administered through a face mask that is worn while asleep, is a first-line treatment for OSA.

The eXciteOSA device “offers a new option for the thousands of individuals who experience snoring or mild sleep apnea,” Malvina Eydelman, MD, director, FDA Office of Ophthalmic, Anesthesia, Respiratory, ENT, and Dental Devices, said in a news release.

The FDA reviewed data on the safety and effectiveness of the eXciteOSA device in 115 patients with snoring, including 48 patients with snoring and mild OSA. All patients used the device for 20 minutes once a day for 6 weeks, then stopped using it for 2 weeks before they were reassessed.

Overall, the percentage of time spent snoring at levels louder than 40 decibels was reduced by more than 20% in 87 out of the 115 patients.

In the subset of patients with snoring and mild OSA, the average apnea-hypopnea index score was reduced by 48%, from 10.21 to 5.27, in 41 of 48 patients. Mild OSA is defined as an AHI score greater than 5 but less than 15.

The most common adverse events were excessive salivation, tongue or tooth discomfort, tongue tingling, dental filling sensitivity, metallic taste, gagging, and tight jaw.

Before using the eXciteOSA device, patients should receive a comprehensive dental examination, the FDA said. 

The device should not be used in patients with pacemakers or implanted pacing leads, or women who are pregnant. The device is also contraindicated in patients with temporary or permanent implants, dental braces, intraoral metal prosthesis/restorations, or ulcerations in or around the mouth.

The eXciteOSA device was approved under the de novo premarket review pathway for new low- to moderate-risk devices. More information on the device is available online.

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

The Food and Drug Administration has approved the first device to help reduce snoring and mild obstructive sleep apnea (OSA) that is used during the day while the patient is awake.

eXciteOSA (Signifier Medical Technologies) is a prescription-only, neuromuscular stimulation device designed to improve tongue muscle function, which, over time, can help prevent the tongue from collapsing backwards and obstructing the airway during sleep, the FDA said.

The eXciteOSA mouthpiece has four electrodes that deliver a series of electrical pulses with rest periods in between. Two electrodes are located above the tongue and two are located below the tongue.

The patient uses the device for 20 minutes once a day while awake for 6 weeks, and once a week thereafter. It is indicated for adults aged 18 and older with snoring and mild OSA.

OSA is marked by the recurring collapse of the upper airways during sleep, intermittently reducing or completely blocking airflow. Common symptoms include snoring, restless sleep and daytime sleepiness. Untreated OSA can lead to serious complications such as cardiovascular disease and cognitive and behavioral disorders.

Continuous positive airway pressure therapy, administered through a face mask that is worn while asleep, is a first-line treatment for OSA.

The eXciteOSA device “offers a new option for the thousands of individuals who experience snoring or mild sleep apnea,” Malvina Eydelman, MD, director, FDA Office of Ophthalmic, Anesthesia, Respiratory, ENT, and Dental Devices, said in a news release.

The FDA reviewed data on the safety and effectiveness of the eXciteOSA device in 115 patients with snoring, including 48 patients with snoring and mild OSA. All patients used the device for 20 minutes once a day for 6 weeks, then stopped using it for 2 weeks before they were reassessed.

Overall, the percentage of time spent snoring at levels louder than 40 decibels was reduced by more than 20% in 87 out of the 115 patients.

In the subset of patients with snoring and mild OSA, the average apnea-hypopnea index score was reduced by 48%, from 10.21 to 5.27, in 41 of 48 patients. Mild OSA is defined as an AHI score greater than 5 but less than 15.

The most common adverse events were excessive salivation, tongue or tooth discomfort, tongue tingling, dental filling sensitivity, metallic taste, gagging, and tight jaw.

Before using the eXciteOSA device, patients should receive a comprehensive dental examination, the FDA said. 

The device should not be used in patients with pacemakers or implanted pacing leads, or women who are pregnant. The device is also contraindicated in patients with temporary or permanent implants, dental braces, intraoral metal prosthesis/restorations, or ulcerations in or around the mouth.

The eXciteOSA device was approved under the de novo premarket review pathway for new low- to moderate-risk devices. More information on the device is available online.

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

The Food and Drug Administration has approved the first device to help reduce snoring and mild obstructive sleep apnea (OSA) that is used during the day while the patient is awake.

eXciteOSA (Signifier Medical Technologies) is a prescription-only, neuromuscular stimulation device designed to improve tongue muscle function, which, over time, can help prevent the tongue from collapsing backwards and obstructing the airway during sleep, the FDA said.

The eXciteOSA mouthpiece has four electrodes that deliver a series of electrical pulses with rest periods in between. Two electrodes are located above the tongue and two are located below the tongue.

The patient uses the device for 20 minutes once a day while awake for 6 weeks, and once a week thereafter. It is indicated for adults aged 18 and older with snoring and mild OSA.

OSA is marked by the recurring collapse of the upper airways during sleep, intermittently reducing or completely blocking airflow. Common symptoms include snoring, restless sleep and daytime sleepiness. Untreated OSA can lead to serious complications such as cardiovascular disease and cognitive and behavioral disorders.

Continuous positive airway pressure therapy, administered through a face mask that is worn while asleep, is a first-line treatment for OSA.

The eXciteOSA device “offers a new option for the thousands of individuals who experience snoring or mild sleep apnea,” Malvina Eydelman, MD, director, FDA Office of Ophthalmic, Anesthesia, Respiratory, ENT, and Dental Devices, said in a news release.

The FDA reviewed data on the safety and effectiveness of the eXciteOSA device in 115 patients with snoring, including 48 patients with snoring and mild OSA. All patients used the device for 20 minutes once a day for 6 weeks, then stopped using it for 2 weeks before they were reassessed.

Overall, the percentage of time spent snoring at levels louder than 40 decibels was reduced by more than 20% in 87 out of the 115 patients.

In the subset of patients with snoring and mild OSA, the average apnea-hypopnea index score was reduced by 48%, from 10.21 to 5.27, in 41 of 48 patients. Mild OSA is defined as an AHI score greater than 5 but less than 15.

The most common adverse events were excessive salivation, tongue or tooth discomfort, tongue tingling, dental filling sensitivity, metallic taste, gagging, and tight jaw.

Before using the eXciteOSA device, patients should receive a comprehensive dental examination, the FDA said. 

The device should not be used in patients with pacemakers or implanted pacing leads, or women who are pregnant. The device is also contraindicated in patients with temporary or permanent implants, dental braces, intraoral metal prosthesis/restorations, or ulcerations in or around the mouth.

The eXciteOSA device was approved under the de novo premarket review pathway for new low- to moderate-risk devices. More information on the device is available online.

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

Survival rates for patients with pulmonary arterial hypertension associated with connective tissue diseases have improved significantly in recent years, and there is growing evidence that treatments for idiopathic pulmonary arterial hypertension can also benefit this group.

In an article published online Feb. 3, 2021, in Arthritis & Rheumatology, researchers report the outcomes of a meta-analysis to explore the effect of more modern pulmonary arterial hypertension treatments on patients with conditions such as systemic sclerosis.

First author Dinesh Khanna, MBBS, MSc, of the division of rheumatology at the University of Michigan, Ann Arbor, said in an interview that connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) was a leading cause of death, but earlier clinical trials had found poor outcomes in patients with CTD, compared with those with idiopathic PAH.

“Recent clinical trial data show that aggressive, up-front PAH treatments have better outcomes in those with CTD-PAH, and we wanted to explore these observations carefully in a systematic review and meta-analysis,” Dr. Khanna said.

The analysis included 11 randomized, controlled trials, involving 4,329 patients with PAH (1,267 with CTD), and 19 registries with a total of 9,739 patients with PAH, including 4,008 with CTD. Trials were required to report long-term clinical outcomes with a median enrollment time of greater than 6 months, and outcomes measured between 3-6 months after the patients started treatment.

Patients with CTDs had an older mean age and a lower 6-minute walk distance than did those with idiopathic PAH.

Five randomized, controlled trials – involving 3,172 patients, 941 of whom had a CTD – found that additional PAH treatment was associated with a 36% reduction in the risk of morbidity or mortality events, compared with controls both in the overall PAH group and in those with CTD.

Additional therapy was also associated with a 34.6-meter increase in 6-minute walk distance in the general PAH population, and a 20.4-meter increase in those with CTD.

The authors commented that the smaller improvement in 6-minute walk distance among patients with CTD may be influenced by comorbidities such as musculoskeletal involvement that would be independent of their cardiopulmonary function.
 

Differential patient survival among PAH etiologies

“Our meta-analysis of RCTs demonstrated that patients with CTD-PAH derive a clinically significant benefit from currently available PAH therapies which, in many patients, comprised the addition of a drug targeting a second or third pathway involved in the pathophysiology of PAH,” the authors wrote.

When researchers analyzed data from nine registries that included a wide range of PAH etiologies, they found the overall survival rates were lower among patients with CTD, compared with the overall population. The analysis also suggested that patients with systemic sclerosis and PAH had lower survival rates than did those with systemic lupus erythematosus.

Dr. Khanna said this may relate to different pathophysiology of PAH in patients with CTDs, but could also be a reflection of other differences, such as older age and the involvement of other comorbidities, including lung fibrosis and heart involvement.

Data across all 19 registries also showed that survival rates among those with CTD were higher in registries where more than 50% of the registry study period was during or after 2010, compared with registries where 50% or more of the study period was before 2010.

The authors suggested the differences in survival rates may relate to increased screening for PAH, particularly among people with CTDs. They noted that increased screening leads to earlier diagnosis, which could introduce a lead-time bias such that later registries would have younger participants with less severe disease. However, their analysis found that the later registries had older patients but also with less severe disease, and they suggested that it wasn’t possible to determine if lead-time bias was playing a role in their results.

Improvements in treatment options could also account for differences in survival over time, although the authors commented that only six registries in the study included patients from 2015 or later, when currently available treatments came into use and early combination therapy was used more.

“These data also support the 2018 World Symposium on Pulmonary Hypertension recommendations to initiate up-front combination pulmonary arterial hypertension therapy in majority of cases with CTD-PAH,” Dr. Khanna said.

‘Still have to be aggressive at identifying the high-risk patients’

Commenting on the findings, Virginia Steen, MD, of the division of rheumatology at Georgetown University, Washington, said clinicians were finally seeing some significant changes over time in scleroderma-associated PAH.

“Although some of it may be just early diagnosis, I think that the combination of early diagnosis and more aggressive treatment with combination medication is definitely making a difference,” Dr. Steen said in an interview. “The bottom line is that we as rheumatologists still have to be aggressive at identifying the high-risk patients, making an early diagnosis, and working with our pulmonary hypertension colleagues and aggressively treating these patients so we can make a long-term difference.”

The authors of an accompanying editorial said the meta-analysis’ findings showed the positive impact of early combination therapy and early diagnosis through proactive screening.

“It is notable because the present analysis again confirms that outcomes are worse in CTD-PAH than in idiopathic or familial forms of PAH, the impact of treatments should no longer be regarded as insignificant,” the editorial’s authors wrote. “This is a practice changing observation, especially now that many of the drugs are available in generic formulations and so the cost of modern PAH treatment has fallen at the same time as its true value is convincingly demonstrated.”

They also argued there was strong evidence for the value of combination therapies, both for PAH-targeted drugs used in combination and concurrent use of immunosuppression and drugs specifically for PAH in some patients with CTD-PAH.

However, they pointed out that not all treatments for idiopathic PAH were suitable for patients with CTDs, highlighting the example of anticoagulation that can improve survival in the first but worsen it in the second.

The study was funded by Actelion. Six authors declared funding and grants from the pharmaceutical sector, including the study sponsor, and three authors were employees of Actelion.

Survival rates for patients with pulmonary arterial hypertension associated with connective tissue diseases have improved significantly in recent years, and there is growing evidence that treatments for idiopathic pulmonary arterial hypertension can also benefit this group.

In an article published online Feb. 3, 2021, in Arthritis & Rheumatology, researchers report the outcomes of a meta-analysis to explore the effect of more modern pulmonary arterial hypertension treatments on patients with conditions such as systemic sclerosis.

First author Dinesh Khanna, MBBS, MSc, of the division of rheumatology at the University of Michigan, Ann Arbor, said in an interview that connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) was a leading cause of death, but earlier clinical trials had found poor outcomes in patients with CTD, compared with those with idiopathic PAH.

“Recent clinical trial data show that aggressive, up-front PAH treatments have better outcomes in those with CTD-PAH, and we wanted to explore these observations carefully in a systematic review and meta-analysis,” Dr. Khanna said.

The analysis included 11 randomized, controlled trials, involving 4,329 patients with PAH (1,267 with CTD), and 19 registries with a total of 9,739 patients with PAH, including 4,008 with CTD. Trials were required to report long-term clinical outcomes with a median enrollment time of greater than 6 months, and outcomes measured between 3-6 months after the patients started treatment.

Patients with CTDs had an older mean age and a lower 6-minute walk distance than did those with idiopathic PAH.

Five randomized, controlled trials – involving 3,172 patients, 941 of whom had a CTD – found that additional PAH treatment was associated with a 36% reduction in the risk of morbidity or mortality events, compared with controls both in the overall PAH group and in those with CTD.

Additional therapy was also associated with a 34.6-meter increase in 6-minute walk distance in the general PAH population, and a 20.4-meter increase in those with CTD.

The authors commented that the smaller improvement in 6-minute walk distance among patients with CTD may be influenced by comorbidities such as musculoskeletal involvement that would be independent of their cardiopulmonary function.
 

Differential patient survival among PAH etiologies

“Our meta-analysis of RCTs demonstrated that patients with CTD-PAH derive a clinically significant benefit from currently available PAH therapies which, in many patients, comprised the addition of a drug targeting a second or third pathway involved in the pathophysiology of PAH,” the authors wrote.

When researchers analyzed data from nine registries that included a wide range of PAH etiologies, they found the overall survival rates were lower among patients with CTD, compared with the overall population. The analysis also suggested that patients with systemic sclerosis and PAH had lower survival rates than did those with systemic lupus erythematosus.

Dr. Khanna said this may relate to different pathophysiology of PAH in patients with CTDs, but could also be a reflection of other differences, such as older age and the involvement of other comorbidities, including lung fibrosis and heart involvement.

Data across all 19 registries also showed that survival rates among those with CTD were higher in registries where more than 50% of the registry study period was during or after 2010, compared with registries where 50% or more of the study period was before 2010.

The authors suggested the differences in survival rates may relate to increased screening for PAH, particularly among people with CTDs. They noted that increased screening leads to earlier diagnosis, which could introduce a lead-time bias such that later registries would have younger participants with less severe disease. However, their analysis found that the later registries had older patients but also with less severe disease, and they suggested that it wasn’t possible to determine if lead-time bias was playing a role in their results.

Improvements in treatment options could also account for differences in survival over time, although the authors commented that only six registries in the study included patients from 2015 or later, when currently available treatments came into use and early combination therapy was used more.

“These data also support the 2018 World Symposium on Pulmonary Hypertension recommendations to initiate up-front combination pulmonary arterial hypertension therapy in majority of cases with CTD-PAH,” Dr. Khanna said.

‘Still have to be aggressive at identifying the high-risk patients’

Commenting on the findings, Virginia Steen, MD, of the division of rheumatology at Georgetown University, Washington, said clinicians were finally seeing some significant changes over time in scleroderma-associated PAH.

“Although some of it may be just early diagnosis, I think that the combination of early diagnosis and more aggressive treatment with combination medication is definitely making a difference,” Dr. Steen said in an interview. “The bottom line is that we as rheumatologists still have to be aggressive at identifying the high-risk patients, making an early diagnosis, and working with our pulmonary hypertension colleagues and aggressively treating these patients so we can make a long-term difference.”

The authors of an accompanying editorial said the meta-analysis’ findings showed the positive impact of early combination therapy and early diagnosis through proactive screening.

“It is notable because the present analysis again confirms that outcomes are worse in CTD-PAH than in idiopathic or familial forms of PAH, the impact of treatments should no longer be regarded as insignificant,” the editorial’s authors wrote. “This is a practice changing observation, especially now that many of the drugs are available in generic formulations and so the cost of modern PAH treatment has fallen at the same time as its true value is convincingly demonstrated.”

They also argued there was strong evidence for the value of combination therapies, both for PAH-targeted drugs used in combination and concurrent use of immunosuppression and drugs specifically for PAH in some patients with CTD-PAH.

However, they pointed out that not all treatments for idiopathic PAH were suitable for patients with CTDs, highlighting the example of anticoagulation that can improve survival in the first but worsen it in the second.

The study was funded by Actelion. Six authors declared funding and grants from the pharmaceutical sector, including the study sponsor, and three authors were employees of Actelion.

Survival rates for patients with pulmonary arterial hypertension associated with connective tissue diseases have improved significantly in recent years, and there is growing evidence that treatments for idiopathic pulmonary arterial hypertension can also benefit this group.

In an article published online Feb. 3, 2021, in Arthritis & Rheumatology, researchers report the outcomes of a meta-analysis to explore the effect of more modern pulmonary arterial hypertension treatments on patients with conditions such as systemic sclerosis.

First author Dinesh Khanna, MBBS, MSc, of the division of rheumatology at the University of Michigan, Ann Arbor, said in an interview that connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) was a leading cause of death, but earlier clinical trials had found poor outcomes in patients with CTD, compared with those with idiopathic PAH.

“Recent clinical trial data show that aggressive, up-front PAH treatments have better outcomes in those with CTD-PAH, and we wanted to explore these observations carefully in a systematic review and meta-analysis,” Dr. Khanna said.

The analysis included 11 randomized, controlled trials, involving 4,329 patients with PAH (1,267 with CTD), and 19 registries with a total of 9,739 patients with PAH, including 4,008 with CTD. Trials were required to report long-term clinical outcomes with a median enrollment time of greater than 6 months, and outcomes measured between 3-6 months after the patients started treatment.

Patients with CTDs had an older mean age and a lower 6-minute walk distance than did those with idiopathic PAH.

Five randomized, controlled trials – involving 3,172 patients, 941 of whom had a CTD – found that additional PAH treatment was associated with a 36% reduction in the risk of morbidity or mortality events, compared with controls both in the overall PAH group and in those with CTD.

Additional therapy was also associated with a 34.6-meter increase in 6-minute walk distance in the general PAH population, and a 20.4-meter increase in those with CTD.

The authors commented that the smaller improvement in 6-minute walk distance among patients with CTD may be influenced by comorbidities such as musculoskeletal involvement that would be independent of their cardiopulmonary function.
 

Differential patient survival among PAH etiologies

“Our meta-analysis of RCTs demonstrated that patients with CTD-PAH derive a clinically significant benefit from currently available PAH therapies which, in many patients, comprised the addition of a drug targeting a second or third pathway involved in the pathophysiology of PAH,” the authors wrote.

When researchers analyzed data from nine registries that included a wide range of PAH etiologies, they found the overall survival rates were lower among patients with CTD, compared with the overall population. The analysis also suggested that patients with systemic sclerosis and PAH had lower survival rates than did those with systemic lupus erythematosus.

Dr. Khanna said this may relate to different pathophysiology of PAH in patients with CTDs, but could also be a reflection of other differences, such as older age and the involvement of other comorbidities, including lung fibrosis and heart involvement.

Data across all 19 registries also showed that survival rates among those with CTD were higher in registries where more than 50% of the registry study period was during or after 2010, compared with registries where 50% or more of the study period was before 2010.

The authors suggested the differences in survival rates may relate to increased screening for PAH, particularly among people with CTDs. They noted that increased screening leads to earlier diagnosis, which could introduce a lead-time bias such that later registries would have younger participants with less severe disease. However, their analysis found that the later registries had older patients but also with less severe disease, and they suggested that it wasn’t possible to determine if lead-time bias was playing a role in their results.

Improvements in treatment options could also account for differences in survival over time, although the authors commented that only six registries in the study included patients from 2015 or later, when currently available treatments came into use and early combination therapy was used more.

“These data also support the 2018 World Symposium on Pulmonary Hypertension recommendations to initiate up-front combination pulmonary arterial hypertension therapy in majority of cases with CTD-PAH,” Dr. Khanna said.

‘Still have to be aggressive at identifying the high-risk patients’

Commenting on the findings, Virginia Steen, MD, of the division of rheumatology at Georgetown University, Washington, said clinicians were finally seeing some significant changes over time in scleroderma-associated PAH.

“Although some of it may be just early diagnosis, I think that the combination of early diagnosis and more aggressive treatment with combination medication is definitely making a difference,” Dr. Steen said in an interview. “The bottom line is that we as rheumatologists still have to be aggressive at identifying the high-risk patients, making an early diagnosis, and working with our pulmonary hypertension colleagues and aggressively treating these patients so we can make a long-term difference.”

The authors of an accompanying editorial said the meta-analysis’ findings showed the positive impact of early combination therapy and early diagnosis through proactive screening.

“It is notable because the present analysis again confirms that outcomes are worse in CTD-PAH than in idiopathic or familial forms of PAH, the impact of treatments should no longer be regarded as insignificant,” the editorial’s authors wrote. “This is a practice changing observation, especially now that many of the drugs are available in generic formulations and so the cost of modern PAH treatment has fallen at the same time as its true value is convincingly demonstrated.”

They also argued there was strong evidence for the value of combination therapies, both for PAH-targeted drugs used in combination and concurrent use of immunosuppression and drugs specifically for PAH in some patients with CTD-PAH.

However, they pointed out that not all treatments for idiopathic PAH were suitable for patients with CTDs, highlighting the example of anticoagulation that can improve survival in the first but worsen it in the second.

The study was funded by Actelion. Six authors declared funding and grants from the pharmaceutical sector, including the study sponsor, and three authors were employees of Actelion.

Treatment with tocilizumab (Actemra) could stabilize or improve lung function in people with early interstitial lung disease associated with systemic sclerosis (SSc-ILD), a new study has found.

goa_novi/ThinkStock

A paper published online Feb. 3 in Arthritis & Rheumatology presents the results of a post hoc analysis of data from a phase 3, placebo-controlled, double-blind trial of subcutaneous tocilizumab in patients with SSc and progressive skin disease, which included high-resolution chest CT to assess lung involvement and fibrosis.

Tocilizumab is a monoclonal antibody that targets interleukin-6 and is currently approved for the treatment of immune-mediated diseases such as rheumatoid arthritis, giant cell arteritis, cytokine release syndrome, and systemic and polyarticular course juvenile idiopathic arthritis.

Two previous studies of tocilizumab in patients with early, diffuse cutaneous SSc had also found that the treatment was associated with preservation of lung function but did not characterize that effect using radiography.

Of the 210 participants in the trial, called focuSSced, 136 were found to have interstitial lung disease at baseline and were randomized to 162 mg tocilizumab weekly or placebo for 48 weeks.

At baseline, around three-quarters of those with interstitial lung disease had moderate to severe lung involvement, defined as ground glass opacities, honeycombing, and fibrotic reticulation across at least 20% of the whole lung.

Those in the tocilizumab group showed a 0.1% mean decline in forced vital capacity (FVC) over the 48-week study, while those in the placebo group had a mean decline of 6.3%.

When stratified by severity of lung involvement, those with mild lung disease group treated with tocilizumab had a 4.1% decline in FVC, compared with a 10% decline in the placebo group; those with moderate disease in the treatment group had an 0.7% mean increase in FVC, compared with a 5.7% decrease in the placebo group, and those with severe lung involvement in the treatment arm had a 2.1% increase in FVC, compared with a 6.7% decrease in the placebo arm.

Those treated with tocilizumab also showed a statistically significant 1.8% improvement in the amount of lung involvement, which was largely seen in those with more extensive lung involvement at baseline. Those with more than 20% of the lung affected had a significant 4.9% reduction in lung area affected, while those in the placebo arm showed a significant increase in fibrosis.

First author David Roofeh, MD, of the University of Michigan Scleroderma Program, and colleagues wrote that most patients with SSc will develop interstitial lung disease – particularly those with early, diffuse cutaneous SSc and elevated markers such as C-reactive protein.

“Patients with these high-risk features, especially those with disease in the initial phase of development, represent an important target for early intervention as ILD is largely irreversible in SSc,” the authors wrote.

Findings from a specific patient population may not be generalizable

Commenting on the findings, Lorinda Chung, MD, of Stanford (Calif.) University, said in an interview that the study demonstrated that tocilizumab could prevent radiographic progression of ILD in early diffuse SSc patients with mild to severe lung disease and evidence of active skin disease, as well as elevated inflammatory markers.

“This was a very specific patient population who was studied in the focuSSced clinical trial, and this paper only evaluated a subset of these patients,” Dr. Chung said. “The results may not be generalizable to all SSc-ILD patients and further studies are needed.”

The authors suggested that the patients with progressive skin disease and elevated acute phase reactants may represent a group in the immunoinflammatory phase of the disease rather than the advanced fibrotic stage, and that this might be a “window of therapeutic opportunity to preserve lung function.”

Dr. Chung noted that the radiographic improvement induced by tocilizumab treatment was greatest in those with the most radiographic disease at baseline.

“This may reflect tocilizumab’s impact on decreasing inflammation, but we are not provided the data on the effects of tocilizumab on the individual components of the QILD [quantitative ILD: summation of ground glass opacities, honeycombing, and fibrotic reticulation],” she said.

The study’s authors also made a point about the utility of screening patients with high-resolution chest CT to detect early signs of ILD.

“Our data demonstrate the value of obtaining HRCT at the time of diagnosis: PFTs [pulmonary function tests] are not sensitive enough to accurately assess the presence of ILD and delays in treatment initiation may lead to irreversible disease,” they wrote.

Describing the results as ‘hypothesis-generating’ owing to the post hoc nature of the analysis, the authors said that FVC was an indirect measure of the flow-resistive properties of the lung, and that other aspects of SSc – such as hide-bound chest thickness – could cause thoracic restriction.

Two authors were funded by the National Institutes of Health. Six authors declared grants, funding, and other support from the pharmaceutical sector, including Roche, which sponsored the original focuSSced trial.

Treatment with tocilizumab (Actemra) could stabilize or improve lung function in people with early interstitial lung disease associated with systemic sclerosis (SSc-ILD), a new study has found.

goa_novi/ThinkStock

A paper published online Feb. 3 in Arthritis & Rheumatology presents the results of a post hoc analysis of data from a phase 3, placebo-controlled, double-blind trial of subcutaneous tocilizumab in patients with SSc and progressive skin disease, which included high-resolution chest CT to assess lung involvement and fibrosis.

Tocilizumab is a monoclonal antibody that targets interleukin-6 and is currently approved for the treatment of immune-mediated diseases such as rheumatoid arthritis, giant cell arteritis, cytokine release syndrome, and systemic and polyarticular course juvenile idiopathic arthritis.

Two previous studies of tocilizumab in patients with early, diffuse cutaneous SSc had also found that the treatment was associated with preservation of lung function but did not characterize that effect using radiography.

Of the 210 participants in the trial, called focuSSced, 136 were found to have interstitial lung disease at baseline and were randomized to 162 mg tocilizumab weekly or placebo for 48 weeks.

At baseline, around three-quarters of those with interstitial lung disease had moderate to severe lung involvement, defined as ground glass opacities, honeycombing, and fibrotic reticulation across at least 20% of the whole lung.

Those in the tocilizumab group showed a 0.1% mean decline in forced vital capacity (FVC) over the 48-week study, while those in the placebo group had a mean decline of 6.3%.

When stratified by severity of lung involvement, those with mild lung disease group treated with tocilizumab had a 4.1% decline in FVC, compared with a 10% decline in the placebo group; those with moderate disease in the treatment group had an 0.7% mean increase in FVC, compared with a 5.7% decrease in the placebo group, and those with severe lung involvement in the treatment arm had a 2.1% increase in FVC, compared with a 6.7% decrease in the placebo arm.

Those treated with tocilizumab also showed a statistically significant 1.8% improvement in the amount of lung involvement, which was largely seen in those with more extensive lung involvement at baseline. Those with more than 20% of the lung affected had a significant 4.9% reduction in lung area affected, while those in the placebo arm showed a significant increase in fibrosis.

First author David Roofeh, MD, of the University of Michigan Scleroderma Program, and colleagues wrote that most patients with SSc will develop interstitial lung disease – particularly those with early, diffuse cutaneous SSc and elevated markers such as C-reactive protein.

“Patients with these high-risk features, especially those with disease in the initial phase of development, represent an important target for early intervention as ILD is largely irreversible in SSc,” the authors wrote.

Findings from a specific patient population may not be generalizable

Commenting on the findings, Lorinda Chung, MD, of Stanford (Calif.) University, said in an interview that the study demonstrated that tocilizumab could prevent radiographic progression of ILD in early diffuse SSc patients with mild to severe lung disease and evidence of active skin disease, as well as elevated inflammatory markers.

“This was a very specific patient population who was studied in the focuSSced clinical trial, and this paper only evaluated a subset of these patients,” Dr. Chung said. “The results may not be generalizable to all SSc-ILD patients and further studies are needed.”

The authors suggested that the patients with progressive skin disease and elevated acute phase reactants may represent a group in the immunoinflammatory phase of the disease rather than the advanced fibrotic stage, and that this might be a “window of therapeutic opportunity to preserve lung function.”

Dr. Chung noted that the radiographic improvement induced by tocilizumab treatment was greatest in those with the most radiographic disease at baseline.

“This may reflect tocilizumab’s impact on decreasing inflammation, but we are not provided the data on the effects of tocilizumab on the individual components of the QILD [quantitative ILD: summation of ground glass opacities, honeycombing, and fibrotic reticulation],” she said.

The study’s authors also made a point about the utility of screening patients with high-resolution chest CT to detect early signs of ILD.

“Our data demonstrate the value of obtaining HRCT at the time of diagnosis: PFTs [pulmonary function tests] are not sensitive enough to accurately assess the presence of ILD and delays in treatment initiation may lead to irreversible disease,” they wrote.

Describing the results as ‘hypothesis-generating’ owing to the post hoc nature of the analysis, the authors said that FVC was an indirect measure of the flow-resistive properties of the lung, and that other aspects of SSc – such as hide-bound chest thickness – could cause thoracic restriction.

Two authors were funded by the National Institutes of Health. Six authors declared grants, funding, and other support from the pharmaceutical sector, including Roche, which sponsored the original focuSSced trial.

Treatment with tocilizumab (Actemra) could stabilize or improve lung function in people with early interstitial lung disease associated with systemic sclerosis (SSc-ILD), a new study has found.

goa_novi/ThinkStock

A paper published online Feb. 3 in Arthritis & Rheumatology presents the results of a post hoc analysis of data from a phase 3, placebo-controlled, double-blind trial of subcutaneous tocilizumab in patients with SSc and progressive skin disease, which included high-resolution chest CT to assess lung involvement and fibrosis.

Tocilizumab is a monoclonal antibody that targets interleukin-6 and is currently approved for the treatment of immune-mediated diseases such as rheumatoid arthritis, giant cell arteritis, cytokine release syndrome, and systemic and polyarticular course juvenile idiopathic arthritis.

Two previous studies of tocilizumab in patients with early, diffuse cutaneous SSc had also found that the treatment was associated with preservation of lung function but did not characterize that effect using radiography.

Of the 210 participants in the trial, called focuSSced, 136 were found to have interstitial lung disease at baseline and were randomized to 162 mg tocilizumab weekly or placebo for 48 weeks.

At baseline, around three-quarters of those with interstitial lung disease had moderate to severe lung involvement, defined as ground glass opacities, honeycombing, and fibrotic reticulation across at least 20% of the whole lung.

Those in the tocilizumab group showed a 0.1% mean decline in forced vital capacity (FVC) over the 48-week study, while those in the placebo group had a mean decline of 6.3%.

When stratified by severity of lung involvement, those with mild lung disease group treated with tocilizumab had a 4.1% decline in FVC, compared with a 10% decline in the placebo group; those with moderate disease in the treatment group had an 0.7% mean increase in FVC, compared with a 5.7% decrease in the placebo group, and those with severe lung involvement in the treatment arm had a 2.1% increase in FVC, compared with a 6.7% decrease in the placebo arm.

Those treated with tocilizumab also showed a statistically significant 1.8% improvement in the amount of lung involvement, which was largely seen in those with more extensive lung involvement at baseline. Those with more than 20% of the lung affected had a significant 4.9% reduction in lung area affected, while those in the placebo arm showed a significant increase in fibrosis.

First author David Roofeh, MD, of the University of Michigan Scleroderma Program, and colleagues wrote that most patients with SSc will develop interstitial lung disease – particularly those with early, diffuse cutaneous SSc and elevated markers such as C-reactive protein.

“Patients with these high-risk features, especially those with disease in the initial phase of development, represent an important target for early intervention as ILD is largely irreversible in SSc,” the authors wrote.

Findings from a specific patient population may not be generalizable

Commenting on the findings, Lorinda Chung, MD, of Stanford (Calif.) University, said in an interview that the study demonstrated that tocilizumab could prevent radiographic progression of ILD in early diffuse SSc patients with mild to severe lung disease and evidence of active skin disease, as well as elevated inflammatory markers.

“This was a very specific patient population who was studied in the focuSSced clinical trial, and this paper only evaluated a subset of these patients,” Dr. Chung said. “The results may not be generalizable to all SSc-ILD patients and further studies are needed.”

The authors suggested that the patients with progressive skin disease and elevated acute phase reactants may represent a group in the immunoinflammatory phase of the disease rather than the advanced fibrotic stage, and that this might be a “window of therapeutic opportunity to preserve lung function.”

Dr. Chung noted that the radiographic improvement induced by tocilizumab treatment was greatest in those with the most radiographic disease at baseline.

“This may reflect tocilizumab’s impact on decreasing inflammation, but we are not provided the data on the effects of tocilizumab on the individual components of the QILD [quantitative ILD: summation of ground glass opacities, honeycombing, and fibrotic reticulation],” she said.

The study’s authors also made a point about the utility of screening patients with high-resolution chest CT to detect early signs of ILD.

“Our data demonstrate the value of obtaining HRCT at the time of diagnosis: PFTs [pulmonary function tests] are not sensitive enough to accurately assess the presence of ILD and delays in treatment initiation may lead to irreversible disease,” they wrote.

Describing the results as ‘hypothesis-generating’ owing to the post hoc nature of the analysis, the authors said that FVC was an indirect measure of the flow-resistive properties of the lung, and that other aspects of SSc – such as hide-bound chest thickness – could cause thoracic restriction.

Two authors were funded by the National Institutes of Health. Six authors declared grants, funding, and other support from the pharmaceutical sector, including Roche, which sponsored the original focuSSced trial.

Nearly 60% of those working in a large health care system expressed their intent to roll up their sleeves to receive the COVID-19 vaccine, but about one-third were unsure of doing so.

Moreover, 54% of direct care providers indicated that they would take the vaccine if offered, compared with 60% of noncare providers.

The findings come from what is believed to be the largest survey of health care provider attitudes toward COVID-19 vaccination, published online Jan. 25 in Clinical Infectious Diseases.

“We have shown that self-reported willingness to receive vaccination against COVID-19 differs by age, gender, race and hospital role, with physicians and research scientists showing the highest acceptance,” Jana Shaw, MD, MPH, State University of New York, Syracuse, N.Y, the study’s corresponding author, told this news organization. “Building trust in authorities and confidence in vaccines is a complex and time-consuming process that requires commitment and resources. We have to make those investments as hesitancy can severely undermine vaccination coverage. Because health care providers are members of our communities, it is possible that their views are shared by the public at large. Our findings can assist public health professionals as a starting point of discussion and engagement with communities to ensure that we vaccinate at least 80% of the public to end the pandemic.”

For the study, Dr. Shaw and her colleagues emailed an anonymous survey to 9,565 employees of State University of New York Upstate Medical University, Syracuse, an academic medical center that cares for an estimated 1.8 million people. The survey, which contained questions intended to evaluate attitudes, belief, and willingness to get vaccinated, took place between Nov. 23 and Dec. 5, about a week before the U.S. Food and Drug Administration granted the first emergency use authorization for the Pfizer-BioNTech BNT162b2 mRNA vaccine.

Survey recipients included physicians, nurse practitioners, physician assistants, nurses, pharmacists, medical and nursing students, allied health professionals, and nonclinical ancillary staff.

Of the 9,565 surveys sent, 5,287 responses were collected and used in the final analysis, for a response rate of 55%. The mean age of respondents was 43, 73% were female, 85% were White, 6% were Asian, 5% were Black/African American, and the rest were Native American, Native Hawaiian/Pacific Islander, or from other races. More than half of respondents (59%) reported that they provided direct patient care, and 32% said they provided care for patients with COVID-19.

Of all survey respondents, 58% expressed their intent to receive a COVID-19 vaccine, but this varied by their role in the health care system. For example, in response to the statement, “If a vaccine were offered free of charge, I would take it,” 80% of scientists and physicians agreed that they would, while colleagues in other roles were unsure whether they would take the vaccine, including 34% of registered nurses, 32% of allied health professionals, and 32% of master’s-level clinicians. These differences across roles were significant (P less than .001).

The researchers also found that direct patient care or care for COVID-19 patients was associated with lower vaccination intent. For example, 54% of direct care providers and 62% of non-care providers indicated they would take the vaccine if offered, compared with 52% of those who had provided care for COVID-19 patients vs. 61% of those who had not (P less than .001).

“This was a really surprising finding,” said Dr. Shaw, who is a pediatric infectious diseases physician at SUNY Upstate. “In general, one would expect that perceived severity of disease would lead to a greater desire to get vaccinated. Because our question did not address severity of disease, it is possible that we oversampled respondents who took care of patients with mild disease (i.e., in an outpatient setting). This could have led to an underestimation of disease severity and resulted in lower vaccination intent.”
 

A focus on rebuilding trust

Survey respondents who agreed or strongly agreed that they would accept a vaccine were older (a mean age of 44 years), compared with those who were not sure or who disagreed (a mean age of 42 vs. 38 years, respectively; P less than .001). In addition, fewer females agreed or strongly agreed that they would accept a vaccine (54% vs. 73% of males), whereas those who self-identified as Black/African American were least likely to want to get vaccinated, compared with those from other ethnic groups (31%, compared with 74% of Asians, 58% of Whites, and 39% of American Indians or Alaska Natives).

“We are deeply aware of the poor decisions scientists made in the past, which led to a prevailing skepticism and ‘feeling like guinea pigs’ among people of color, especially Black adults,” Dr. Shaw said. “Black adults are less likely, compared [with] White adults, to have confidence that scientists act in the public interest. Rebuilding trust will take time and has to start with addressing health care disparities. In addition, we need to acknowledge contributions of Black researchers to science. For example, until recently very few knew that the Moderna vaccine was developed [with the help of] Dr. Kizzmekia Corbett, who is Black.”

The top five main areas of unease that all respondents expressed about a COVID-19 vaccine were concern about adverse events/side effects (47%), efficacy (15%), rushed release (11%), safety (11%), and the research and authorization process (3%).

“I think it is important that fellow clinicians recognize that, in order to boost vaccine confidence we will need careful, individually tailored communication strategies,” Dr. Shaw said. “A consideration should be given to those [strategies] that utilize interpersonal channels that deliver leadership by example and leverage influencers in the institution to encourage wider adoption of vaccination.”

Aaron M. Milstone, MD, MHS, asked to comment on the research, recommended that health care workers advocate for the vaccine and encourage their patients, friends, and loved ones to get vaccinated. “Soon, COVID-19 will have taken more than half a million lives in the U.S.,” said Dr. Milstone, a pediatric epidemiologist at Johns Hopkins University, Baltimore. “Although vaccines can have side effects like fever and muscle aches, and very, very rare more serious side effects, the risks of dying from COVID are much greater than the risk of a serious vaccine reaction. The study’s authors shed light on the ongoing need for leaders of all communities to support the COVID vaccines, not just the scientific community, but religious leaders, political leaders, and community leaders.”
 

Addressing vaccine hesitancy

Informed by their own survey, Dr. Shaw and her colleagues have developed a plan to address vaccine hesitancy to ensure high vaccine uptake at SUNY Upstate. Those strategies include, but aren’t limited to, institution-wide forums for all employees on COVID-19 vaccine safety, risks, and benefits followed by Q&A sessions, grand rounds for providers summarizing clinical trial data on mRNA vaccines, development of an Ask COVID email line for staff to ask vaccine-related questions, and a detailed vaccine-specific FAQ document.

In addition, SUNY Upstate experts have engaged in numerous media interviews to provide education and updates on the benefits of vaccination to public and staff, stationary vaccine locations, and mobile COVID-19 vaccine carts. “To date, the COVID-19 vaccination process has been well received, and we anticipate strong vaccine uptake,” she said.

Dr. Shaw acknowledged certain limitations of the survey, including its cross-sectional design and the fact that it was conducted in a single health care system in the northeastern United States. “Thus, generalizability to other regions of the U.S. and other countries may be limited,” Dr. Shaw said. “The study was also conducted before EUA [emergency use authorization] was granted to either the Moderna or Pfizer-BioNTech vaccines. It is therefore likely that vaccine acceptance will change over time as more people get vaccinated.”

The authors have disclosed no relevant financial relationships. Dr. Milstone disclosed that he has received a research grant from Merck, but it is not related to vaccines.

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

Nearly 60% of those working in a large health care system expressed their intent to roll up their sleeves to receive the COVID-19 vaccine, but about one-third were unsure of doing so.

Moreover, 54% of direct care providers indicated that they would take the vaccine if offered, compared with 60% of noncare providers.

The findings come from what is believed to be the largest survey of health care provider attitudes toward COVID-19 vaccination, published online Jan. 25 in Clinical Infectious Diseases.

“We have shown that self-reported willingness to receive vaccination against COVID-19 differs by age, gender, race and hospital role, with physicians and research scientists showing the highest acceptance,” Jana Shaw, MD, MPH, State University of New York, Syracuse, N.Y, the study’s corresponding author, told this news organization. “Building trust in authorities and confidence in vaccines is a complex and time-consuming process that requires commitment and resources. We have to make those investments as hesitancy can severely undermine vaccination coverage. Because health care providers are members of our communities, it is possible that their views are shared by the public at large. Our findings can assist public health professionals as a starting point of discussion and engagement with communities to ensure that we vaccinate at least 80% of the public to end the pandemic.”

For the study, Dr. Shaw and her colleagues emailed an anonymous survey to 9,565 employees of State University of New York Upstate Medical University, Syracuse, an academic medical center that cares for an estimated 1.8 million people. The survey, which contained questions intended to evaluate attitudes, belief, and willingness to get vaccinated, took place between Nov. 23 and Dec. 5, about a week before the U.S. Food and Drug Administration granted the first emergency use authorization for the Pfizer-BioNTech BNT162b2 mRNA vaccine.

Survey recipients included physicians, nurse practitioners, physician assistants, nurses, pharmacists, medical and nursing students, allied health professionals, and nonclinical ancillary staff.

Of the 9,565 surveys sent, 5,287 responses were collected and used in the final analysis, for a response rate of 55%. The mean age of respondents was 43, 73% were female, 85% were White, 6% were Asian, 5% were Black/African American, and the rest were Native American, Native Hawaiian/Pacific Islander, or from other races. More than half of respondents (59%) reported that they provided direct patient care, and 32% said they provided care for patients with COVID-19.

Of all survey respondents, 58% expressed their intent to receive a COVID-19 vaccine, but this varied by their role in the health care system. For example, in response to the statement, “If a vaccine were offered free of charge, I would take it,” 80% of scientists and physicians agreed that they would, while colleagues in other roles were unsure whether they would take the vaccine, including 34% of registered nurses, 32% of allied health professionals, and 32% of master’s-level clinicians. These differences across roles were significant (P less than .001).

The researchers also found that direct patient care or care for COVID-19 patients was associated with lower vaccination intent. For example, 54% of direct care providers and 62% of non-care providers indicated they would take the vaccine if offered, compared with 52% of those who had provided care for COVID-19 patients vs. 61% of those who had not (P less than .001).

“This was a really surprising finding,” said Dr. Shaw, who is a pediatric infectious diseases physician at SUNY Upstate. “In general, one would expect that perceived severity of disease would lead to a greater desire to get vaccinated. Because our question did not address severity of disease, it is possible that we oversampled respondents who took care of patients with mild disease (i.e., in an outpatient setting). This could have led to an underestimation of disease severity and resulted in lower vaccination intent.”
 

A focus on rebuilding trust

Survey respondents who agreed or strongly agreed that they would accept a vaccine were older (a mean age of 44 years), compared with those who were not sure or who disagreed (a mean age of 42 vs. 38 years, respectively; P less than .001). In addition, fewer females agreed or strongly agreed that they would accept a vaccine (54% vs. 73% of males), whereas those who self-identified as Black/African American were least likely to want to get vaccinated, compared with those from other ethnic groups (31%, compared with 74% of Asians, 58% of Whites, and 39% of American Indians or Alaska Natives).

“We are deeply aware of the poor decisions scientists made in the past, which led to a prevailing skepticism and ‘feeling like guinea pigs’ among people of color, especially Black adults,” Dr. Shaw said. “Black adults are less likely, compared [with] White adults, to have confidence that scientists act in the public interest. Rebuilding trust will take time and has to start with addressing health care disparities. In addition, we need to acknowledge contributions of Black researchers to science. For example, until recently very few knew that the Moderna vaccine was developed [with the help of] Dr. Kizzmekia Corbett, who is Black.”

The top five main areas of unease that all respondents expressed about a COVID-19 vaccine were concern about adverse events/side effects (47%), efficacy (15%), rushed release (11%), safety (11%), and the research and authorization process (3%).

“I think it is important that fellow clinicians recognize that, in order to boost vaccine confidence we will need careful, individually tailored communication strategies,” Dr. Shaw said. “A consideration should be given to those [strategies] that utilize interpersonal channels that deliver leadership by example and leverage influencers in the institution to encourage wider adoption of vaccination.”

Aaron M. Milstone, MD, MHS, asked to comment on the research, recommended that health care workers advocate for the vaccine and encourage their patients, friends, and loved ones to get vaccinated. “Soon, COVID-19 will have taken more than half a million lives in the U.S.,” said Dr. Milstone, a pediatric epidemiologist at Johns Hopkins University, Baltimore. “Although vaccines can have side effects like fever and muscle aches, and very, very rare more serious side effects, the risks of dying from COVID are much greater than the risk of a serious vaccine reaction. The study’s authors shed light on the ongoing need for leaders of all communities to support the COVID vaccines, not just the scientific community, but religious leaders, political leaders, and community leaders.”
 

Addressing vaccine hesitancy

Informed by their own survey, Dr. Shaw and her colleagues have developed a plan to address vaccine hesitancy to ensure high vaccine uptake at SUNY Upstate. Those strategies include, but aren’t limited to, institution-wide forums for all employees on COVID-19 vaccine safety, risks, and benefits followed by Q&A sessions, grand rounds for providers summarizing clinical trial data on mRNA vaccines, development of an Ask COVID email line for staff to ask vaccine-related questions, and a detailed vaccine-specific FAQ document.

In addition, SUNY Upstate experts have engaged in numerous media interviews to provide education and updates on the benefits of vaccination to public and staff, stationary vaccine locations, and mobile COVID-19 vaccine carts. “To date, the COVID-19 vaccination process has been well received, and we anticipate strong vaccine uptake,” she said.

Dr. Shaw acknowledged certain limitations of the survey, including its cross-sectional design and the fact that it was conducted in a single health care system in the northeastern United States. “Thus, generalizability to other regions of the U.S. and other countries may be limited,” Dr. Shaw said. “The study was also conducted before EUA [emergency use authorization] was granted to either the Moderna or Pfizer-BioNTech vaccines. It is therefore likely that vaccine acceptance will change over time as more people get vaccinated.”

The authors have disclosed no relevant financial relationships. Dr. Milstone disclosed that he has received a research grant from Merck, but it is not related to vaccines.

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

Nearly 60% of those working in a large health care system expressed their intent to roll up their sleeves to receive the COVID-19 vaccine, but about one-third were unsure of doing so.

Moreover, 54% of direct care providers indicated that they would take the vaccine if offered, compared with 60% of noncare providers.

The findings come from what is believed to be the largest survey of health care provider attitudes toward COVID-19 vaccination, published online Jan. 25 in Clinical Infectious Diseases.

“We have shown that self-reported willingness to receive vaccination against COVID-19 differs by age, gender, race and hospital role, with physicians and research scientists showing the highest acceptance,” Jana Shaw, MD, MPH, State University of New York, Syracuse, N.Y, the study’s corresponding author, told this news organization. “Building trust in authorities and confidence in vaccines is a complex and time-consuming process that requires commitment and resources. We have to make those investments as hesitancy can severely undermine vaccination coverage. Because health care providers are members of our communities, it is possible that their views are shared by the public at large. Our findings can assist public health professionals as a starting point of discussion and engagement with communities to ensure that we vaccinate at least 80% of the public to end the pandemic.”

For the study, Dr. Shaw and her colleagues emailed an anonymous survey to 9,565 employees of State University of New York Upstate Medical University, Syracuse, an academic medical center that cares for an estimated 1.8 million people. The survey, which contained questions intended to evaluate attitudes, belief, and willingness to get vaccinated, took place between Nov. 23 and Dec. 5, about a week before the U.S. Food and Drug Administration granted the first emergency use authorization for the Pfizer-BioNTech BNT162b2 mRNA vaccine.

Survey recipients included physicians, nurse practitioners, physician assistants, nurses, pharmacists, medical and nursing students, allied health professionals, and nonclinical ancillary staff.

Of the 9,565 surveys sent, 5,287 responses were collected and used in the final analysis, for a response rate of 55%. The mean age of respondents was 43, 73% were female, 85% were White, 6% were Asian, 5% were Black/African American, and the rest were Native American, Native Hawaiian/Pacific Islander, or from other races. More than half of respondents (59%) reported that they provided direct patient care, and 32% said they provided care for patients with COVID-19.

Of all survey respondents, 58% expressed their intent to receive a COVID-19 vaccine, but this varied by their role in the health care system. For example, in response to the statement, “If a vaccine were offered free of charge, I would take it,” 80% of scientists and physicians agreed that they would, while colleagues in other roles were unsure whether they would take the vaccine, including 34% of registered nurses, 32% of allied health professionals, and 32% of master’s-level clinicians. These differences across roles were significant (P less than .001).

The researchers also found that direct patient care or care for COVID-19 patients was associated with lower vaccination intent. For example, 54% of direct care providers and 62% of non-care providers indicated they would take the vaccine if offered, compared with 52% of those who had provided care for COVID-19 patients vs. 61% of those who had not (P less than .001).

“This was a really surprising finding,” said Dr. Shaw, who is a pediatric infectious diseases physician at SUNY Upstate. “In general, one would expect that perceived severity of disease would lead to a greater desire to get vaccinated. Because our question did not address severity of disease, it is possible that we oversampled respondents who took care of patients with mild disease (i.e., in an outpatient setting). This could have led to an underestimation of disease severity and resulted in lower vaccination intent.”
 

A focus on rebuilding trust

Survey respondents who agreed or strongly agreed that they would accept a vaccine were older (a mean age of 44 years), compared with those who were not sure or who disagreed (a mean age of 42 vs. 38 years, respectively; P less than .001). In addition, fewer females agreed or strongly agreed that they would accept a vaccine (54% vs. 73% of males), whereas those who self-identified as Black/African American were least likely to want to get vaccinated, compared with those from other ethnic groups (31%, compared with 74% of Asians, 58% of Whites, and 39% of American Indians or Alaska Natives).

“We are deeply aware of the poor decisions scientists made in the past, which led to a prevailing skepticism and ‘feeling like guinea pigs’ among people of color, especially Black adults,” Dr. Shaw said. “Black adults are less likely, compared [with] White adults, to have confidence that scientists act in the public interest. Rebuilding trust will take time and has to start with addressing health care disparities. In addition, we need to acknowledge contributions of Black researchers to science. For example, until recently very few knew that the Moderna vaccine was developed [with the help of] Dr. Kizzmekia Corbett, who is Black.”

The top five main areas of unease that all respondents expressed about a COVID-19 vaccine were concern about adverse events/side effects (47%), efficacy (15%), rushed release (11%), safety (11%), and the research and authorization process (3%).

“I think it is important that fellow clinicians recognize that, in order to boost vaccine confidence we will need careful, individually tailored communication strategies,” Dr. Shaw said. “A consideration should be given to those [strategies] that utilize interpersonal channels that deliver leadership by example and leverage influencers in the institution to encourage wider adoption of vaccination.”

Aaron M. Milstone, MD, MHS, asked to comment on the research, recommended that health care workers advocate for the vaccine and encourage their patients, friends, and loved ones to get vaccinated. “Soon, COVID-19 will have taken more than half a million lives in the U.S.,” said Dr. Milstone, a pediatric epidemiologist at Johns Hopkins University, Baltimore. “Although vaccines can have side effects like fever and muscle aches, and very, very rare more serious side effects, the risks of dying from COVID are much greater than the risk of a serious vaccine reaction. The study’s authors shed light on the ongoing need for leaders of all communities to support the COVID vaccines, not just the scientific community, but religious leaders, political leaders, and community leaders.”
 

Addressing vaccine hesitancy

Informed by their own survey, Dr. Shaw and her colleagues have developed a plan to address vaccine hesitancy to ensure high vaccine uptake at SUNY Upstate. Those strategies include, but aren’t limited to, institution-wide forums for all employees on COVID-19 vaccine safety, risks, and benefits followed by Q&A sessions, grand rounds for providers summarizing clinical trial data on mRNA vaccines, development of an Ask COVID email line for staff to ask vaccine-related questions, and a detailed vaccine-specific FAQ document.

In addition, SUNY Upstate experts have engaged in numerous media interviews to provide education and updates on the benefits of vaccination to public and staff, stationary vaccine locations, and mobile COVID-19 vaccine carts. “To date, the COVID-19 vaccination process has been well received, and we anticipate strong vaccine uptake,” she said.

Dr. Shaw acknowledged certain limitations of the survey, including its cross-sectional design and the fact that it was conducted in a single health care system in the northeastern United States. “Thus, generalizability to other regions of the U.S. and other countries may be limited,” Dr. Shaw said. “The study was also conducted before EUA [emergency use authorization] was granted to either the Moderna or Pfizer-BioNTech vaccines. It is therefore likely that vaccine acceptance will change over time as more people get vaccinated.”

The authors have disclosed no relevant financial relationships. Dr. Milstone disclosed that he has received a research grant from Merck, but it is not related to vaccines.

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

For pediatric patients with respiratory tract infections (RTIs), immediately prescribing antibiotics may do more harm than good, based on prospective data from 436 children treated by primary care pediatricians in Spain.

In the largest trial of its kind to date, children who were immediately prescribed antibiotics showed no significant difference in symptom severity or duration from those who received a delayed prescription for antibiotics, or no prescription at all; yet those in the immediate-prescription group had a higher rate of gastrointestinal adverse events, reported lead author Gemma Mas-Dalmau, MD, of the Sant Pau Institute for Biomedical Research, Barcelona, and colleagues.

“Most RTIs are self-limiting, and antibiotics hardly alter the course of the condition, yet antibiotics are frequently prescribed for these conditions,” the investigators wrote in Pediatrics. “Antibiotic prescription for RTIs in children is especially considered to be inappropriately high.”

This clinical behavior is driven by several factors, according to Dr. Mas-Dalmau and colleagues, including limited diagnostics in primary care, pressure to meet parental expectations, and concern for possible complications if antibiotics are withheld or delayed.

In an accompanying editorial, Jeffrey S. Gerber, MD, PhD and Bonnie F. Offit, MD, of Children’s Hospital of Philadelphia, noted that “children in the United States receive more than one antibiotic prescription per year, driven largely by acute RTIs.”

Dr. Gerber and Dr. Offit noted that some RTIs are indeed caused by bacteria, and therefore benefit from antibiotics, but it’s “not always easy” to identify these cases.

“Primary care, urgent care, and emergency medicine clinicians have a hard job,” they wrote.

According to the Centers for Disease Control and Prevention, delayed prescription of antibiotics, in which a prescription is filled upon persistence or worsening of symptoms, can balance clinical caution and antibiotic stewardship.

“An example of this approach is acute otitis media, in which delayed prescribing has been shown to safely reduce antibiotic exposure,” wrote Dr. Gerber and Dr. Offit.

In a 2017 Cochrane systematic review of both adults and children with RTIs, antibiotic prescriptions, whether immediate, delayed, or not given at all, had no significant effect on most symptoms or complications. Although several randomized trials have evaluated delayed antibiotic prescriptions in children, Dr. Mas-Dalmau and colleagues described the current body of evidence as “scant.”

The present study built upon this knowledge base by prospectively following 436 children treated at 39 primary care centers in Spain from 2012 to 2016. Patients were between 2 and 14 years of age and presented for rhinosinusitis, pharyngitis, acute otitis media, or acute bronchitis. Inclusion in the study required the pediatrician to have “reasonable doubts about the need to prescribe an antibiotic.” Clinics with access to rapid streptococcal testing did not enroll patients with pharyngitis.

Patients were randomized in approximately equal groups to receive either immediate prescription of antibiotics, delayed prescription, or no prescription. In the delayed group, caregivers were advised to fill prescriptions if any of following three events occurred:

• No symptom improvement after a certain amount of days, depending on presenting complaint (acute otitis media, 4 days; pharyngitis, 7 days; acute rhinosinusitis, 15 days; acute bronchitis, 20 days).
• Temperature of at least 39° C after 24 hours, or at least 38° C but less than 39° C after 48 hours.
• Patient feeling “much worse.”

Primary outcomes were severity and duration of symptoms over 30 days, while secondary outcomes included antibiotic use over 30 days, additional unscheduled visits to primary care over 30 days, and parental satisfaction and beliefs regarding antibiotic efficacy.

In the final dataset, 148 patients received immediate antibiotic prescriptions, while 146 received delayed prescriptions, and 142 received no prescription. Rate of antibiotic use was highest in the immediate prescription group, at 96%, versus 25.3% in the delayed group and 12% among those who received no prescription upon first presentation (P < .001).

Although the mean duration of severe symptoms was longest in the delayed-prescription group, at 12.4 days, versus 10.9 days in the no-prescription group and 10.1 days in the immediate-prescription group, these differences were not statistically significant (P = .539). Median score for greatest severity of any symptom was also similar across groups. Secondary outcomes echoed this pattern, in which reconsultation rates and caregiver satisfaction were statistically similar regardless of treatment type.

In contrast, patients who received immediate antibiotic prescriptions had a significantly higher rate of gastrointestinal adverse events (8.8%) than those who received a delayed prescription (3.4%) or no prescription (2.8%; P = .037).

“Delayed antibiotic prescription is an efficacious and safe strategy for reducing inappropriate antibiotic treatment of uncomplicated RTIs in children when the doctor has reasonable doubts regarding the indication,” the investigators concluded. “[It] is therefore a useful tool for addressing the public health issue of bacterial resistance. However, no antibiotic prescription remains the recommended strategy when it is clear that antibiotics are not indicated, like in most cases of acute bronchitis.”

“These data are reassuring,” wrote Dr. Gerber and Dr. Offit; however, they went on to suggest that the data “might not substantially move the needle.”

“With rare exceptions, children with acute pharyngitis should first receive a group A streptococcal test,” they wrote. “If results are positive, all patients should get antibiotics; if results are negative, no one gets them. Acute bronchitis (whatever that is in children) is viral. Acute sinusitis with persistent symptoms (the most commonly diagnosed variety) already has a delayed option, and the current study ... was not powered for this outcome. We are left with acute otitis media, which dominated enrollment but already has an evidence-based guideline.”

Still, Dr. Gerber and Dr. Offit suggested that the findings should further encourage pediatricians to prescribe antibiotics judiciously, and when elected, to choose the shortest duration and narrowest spectrum possible.

In a joint comment, Rana El Feghaly, MD, MSCI, director of outpatient antibiotic stewardship at Children’s Mercy, Kansas City, and her colleague, Mary Anne Jackson, MD, noted that the findings are “in accordance” with the 2017 Cochrane review.

Dr. Feghaly and Dr. Jackson said that these new data provide greater support for conservative use of antibiotics, which is badly needed, considering approximately 50% of outpatient prescriptions are unnecessary or inappropriate .

Delayed antibiotic prescription is part of a multifaceted approach to the issue, they said, joining “communication skills training, antibiotic justification documentation, audit and feedback reporting with peer comparison, diagnostic stewardship, [and] the use of clinician education on practice-based guidelines.”

“Leveraging delayed antibiotic prescription may be an excellent way to combat antibiotic overuse in the outpatient setting, while avoiding provider and parental fear of the ‘no antibiotic’ approach,” Dr. Feghaly and Dr. Jackson said.

Karlyn Kinsella, MD, of Pediatric Associates of Cheshire, Conn., suggested that clinicians discuss these findings with parents who request antibiotics for “otitis, pharyngitis, bronchitis, or sinusitis.”

“We can cite this study that antibiotics have no effect on symptom duration or severity for these illnesses,” Dr. Kinsella said. “Of course, our clinical opinion in each case takes precedent.”

According to Dr. Kinsella, conversations with parents also need to cover reasonable expectations, as the study did, with clear time frames for each condition in which children should start to get better.

“I think this is really key in our anticipatory guidance so that patients know what to expect,” she said.

The study was funded by Instituto de Salud Carlos III, the European Union, and the Spanish Ministry of Health, Social Services, and Equality. The investigators and interviewees reported no conflicts of interest.

For pediatric patients with respiratory tract infections (RTIs), immediately prescribing antibiotics may do more harm than good, based on prospective data from 436 children treated by primary care pediatricians in Spain.

In the largest trial of its kind to date, children who were immediately prescribed antibiotics showed no significant difference in symptom severity or duration from those who received a delayed prescription for antibiotics, or no prescription at all; yet those in the immediate-prescription group had a higher rate of gastrointestinal adverse events, reported lead author Gemma Mas-Dalmau, MD, of the Sant Pau Institute for Biomedical Research, Barcelona, and colleagues.

“Most RTIs are self-limiting, and antibiotics hardly alter the course of the condition, yet antibiotics are frequently prescribed for these conditions,” the investigators wrote in Pediatrics. “Antibiotic prescription for RTIs in children is especially considered to be inappropriately high.”

This clinical behavior is driven by several factors, according to Dr. Mas-Dalmau and colleagues, including limited diagnostics in primary care, pressure to meet parental expectations, and concern for possible complications if antibiotics are withheld or delayed.

In an accompanying editorial, Jeffrey S. Gerber, MD, PhD and Bonnie F. Offit, MD, of Children’s Hospital of Philadelphia, noted that “children in the United States receive more than one antibiotic prescription per year, driven largely by acute RTIs.”

Dr. Gerber and Dr. Offit noted that some RTIs are indeed caused by bacteria, and therefore benefit from antibiotics, but it’s “not always easy” to identify these cases.

“Primary care, urgent care, and emergency medicine clinicians have a hard job,” they wrote.

According to the Centers for Disease Control and Prevention, delayed prescription of antibiotics, in which a prescription is filled upon persistence or worsening of symptoms, can balance clinical caution and antibiotic stewardship.

“An example of this approach is acute otitis media, in which delayed prescribing has been shown to safely reduce antibiotic exposure,” wrote Dr. Gerber and Dr. Offit.

In a 2017 Cochrane systematic review of both adults and children with RTIs, antibiotic prescriptions, whether immediate, delayed, or not given at all, had no significant effect on most symptoms or complications. Although several randomized trials have evaluated delayed antibiotic prescriptions in children, Dr. Mas-Dalmau and colleagues described the current body of evidence as “scant.”

The present study built upon this knowledge base by prospectively following 436 children treated at 39 primary care centers in Spain from 2012 to 2016. Patients were between 2 and 14 years of age and presented for rhinosinusitis, pharyngitis, acute otitis media, or acute bronchitis. Inclusion in the study required the pediatrician to have “reasonable doubts about the need to prescribe an antibiotic.” Clinics with access to rapid streptococcal testing did not enroll patients with pharyngitis.

Patients were randomized in approximately equal groups to receive either immediate prescription of antibiotics, delayed prescription, or no prescription. In the delayed group, caregivers were advised to fill prescriptions if any of following three events occurred:

• No symptom improvement after a certain amount of days, depending on presenting complaint (acute otitis media, 4 days; pharyngitis, 7 days; acute rhinosinusitis, 15 days; acute bronchitis, 20 days).
• Temperature of at least 39° C after 24 hours, or at least 38° C but less than 39° C after 48 hours.
• Patient feeling “much worse.”

Primary outcomes were severity and duration of symptoms over 30 days, while secondary outcomes included antibiotic use over 30 days, additional unscheduled visits to primary care over 30 days, and parental satisfaction and beliefs regarding antibiotic efficacy.

In the final dataset, 148 patients received immediate antibiotic prescriptions, while 146 received delayed prescriptions, and 142 received no prescription. Rate of antibiotic use was highest in the immediate prescription group, at 96%, versus 25.3% in the delayed group and 12% among those who received no prescription upon first presentation (P < .001).

Although the mean duration of severe symptoms was longest in the delayed-prescription group, at 12.4 days, versus 10.9 days in the no-prescription group and 10.1 days in the immediate-prescription group, these differences were not statistically significant (P = .539). Median score for greatest severity of any symptom was also similar across groups. Secondary outcomes echoed this pattern, in which reconsultation rates and caregiver satisfaction were statistically similar regardless of treatment type.

In contrast, patients who received immediate antibiotic prescriptions had a significantly higher rate of gastrointestinal adverse events (8.8%) than those who received a delayed prescription (3.4%) or no prescription (2.8%; P = .037).

“Delayed antibiotic prescription is an efficacious and safe strategy for reducing inappropriate antibiotic treatment of uncomplicated RTIs in children when the doctor has reasonable doubts regarding the indication,” the investigators concluded. “[It] is therefore a useful tool for addressing the public health issue of bacterial resistance. However, no antibiotic prescription remains the recommended strategy when it is clear that antibiotics are not indicated, like in most cases of acute bronchitis.”

“These data are reassuring,” wrote Dr. Gerber and Dr. Offit; however, they went on to suggest that the data “might not substantially move the needle.”

“With rare exceptions, children with acute pharyngitis should first receive a group A streptococcal test,” they wrote. “If results are positive, all patients should get antibiotics; if results are negative, no one gets them. Acute bronchitis (whatever that is in children) is viral. Acute sinusitis with persistent symptoms (the most commonly diagnosed variety) already has a delayed option, and the current study ... was not powered for this outcome. We are left with acute otitis media, which dominated enrollment but already has an evidence-based guideline.”

Still, Dr. Gerber and Dr. Offit suggested that the findings should further encourage pediatricians to prescribe antibiotics judiciously, and when elected, to choose the shortest duration and narrowest spectrum possible.

In a joint comment, Rana El Feghaly, MD, MSCI, director of outpatient antibiotic stewardship at Children’s Mercy, Kansas City, and her colleague, Mary Anne Jackson, MD, noted that the findings are “in accordance” with the 2017 Cochrane review.

Dr. Feghaly and Dr. Jackson said that these new data provide greater support for conservative use of antibiotics, which is badly needed, considering approximately 50% of outpatient prescriptions are unnecessary or inappropriate .

Delayed antibiotic prescription is part of a multifaceted approach to the issue, they said, joining “communication skills training, antibiotic justification documentation, audit and feedback reporting with peer comparison, diagnostic stewardship, [and] the use of clinician education on practice-based guidelines.”

“Leveraging delayed antibiotic prescription may be an excellent way to combat antibiotic overuse in the outpatient setting, while avoiding provider and parental fear of the ‘no antibiotic’ approach,” Dr. Feghaly and Dr. Jackson said.

Karlyn Kinsella, MD, of Pediatric Associates of Cheshire, Conn., suggested that clinicians discuss these findings with parents who request antibiotics for “otitis, pharyngitis, bronchitis, or sinusitis.”

“We can cite this study that antibiotics have no effect on symptom duration or severity for these illnesses,” Dr. Kinsella said. “Of course, our clinical opinion in each case takes precedent.”

According to Dr. Kinsella, conversations with parents also need to cover reasonable expectations, as the study did, with clear time frames for each condition in which children should start to get better.

“I think this is really key in our anticipatory guidance so that patients know what to expect,” she said.

The study was funded by Instituto de Salud Carlos III, the European Union, and the Spanish Ministry of Health, Social Services, and Equality. The investigators and interviewees reported no conflicts of interest.

For pediatric patients with respiratory tract infections (RTIs), immediately prescribing antibiotics may do more harm than good, based on prospective data from 436 children treated by primary care pediatricians in Spain.

In the largest trial of its kind to date, children who were immediately prescribed antibiotics showed no significant difference in symptom severity or duration from those who received a delayed prescription for antibiotics, or no prescription at all; yet those in the immediate-prescription group had a higher rate of gastrointestinal adverse events, reported lead author Gemma Mas-Dalmau, MD, of the Sant Pau Institute for Biomedical Research, Barcelona, and colleagues.

“Most RTIs are self-limiting, and antibiotics hardly alter the course of the condition, yet antibiotics are frequently prescribed for these conditions,” the investigators wrote in Pediatrics. “Antibiotic prescription for RTIs in children is especially considered to be inappropriately high.”

This clinical behavior is driven by several factors, according to Dr. Mas-Dalmau and colleagues, including limited diagnostics in primary care, pressure to meet parental expectations, and concern for possible complications if antibiotics are withheld or delayed.

In an accompanying editorial, Jeffrey S. Gerber, MD, PhD and Bonnie F. Offit, MD, of Children’s Hospital of Philadelphia, noted that “children in the United States receive more than one antibiotic prescription per year, driven largely by acute RTIs.”

Dr. Gerber and Dr. Offit noted that some RTIs are indeed caused by bacteria, and therefore benefit from antibiotics, but it’s “not always easy” to identify these cases.

“Primary care, urgent care, and emergency medicine clinicians have a hard job,” they wrote.

According to the Centers for Disease Control and Prevention, delayed prescription of antibiotics, in which a prescription is filled upon persistence or worsening of symptoms, can balance clinical caution and antibiotic stewardship.

“An example of this approach is acute otitis media, in which delayed prescribing has been shown to safely reduce antibiotic exposure,” wrote Dr. Gerber and Dr. Offit.

In a 2017 Cochrane systematic review of both adults and children with RTIs, antibiotic prescriptions, whether immediate, delayed, or not given at all, had no significant effect on most symptoms or complications. Although several randomized trials have evaluated delayed antibiotic prescriptions in children, Dr. Mas-Dalmau and colleagues described the current body of evidence as “scant.”

The present study built upon this knowledge base by prospectively following 436 children treated at 39 primary care centers in Spain from 2012 to 2016. Patients were between 2 and 14 years of age and presented for rhinosinusitis, pharyngitis, acute otitis media, or acute bronchitis. Inclusion in the study required the pediatrician to have “reasonable doubts about the need to prescribe an antibiotic.” Clinics with access to rapid streptococcal testing did not enroll patients with pharyngitis.

Patients were randomized in approximately equal groups to receive either immediate prescription of antibiotics, delayed prescription, or no prescription. In the delayed group, caregivers were advised to fill prescriptions if any of following three events occurred:

• No symptom improvement after a certain amount of days, depending on presenting complaint (acute otitis media, 4 days; pharyngitis, 7 days; acute rhinosinusitis, 15 days; acute bronchitis, 20 days).
• Temperature of at least 39° C after 24 hours, or at least 38° C but less than 39° C after 48 hours.
• Patient feeling “much worse.”

Primary outcomes were severity and duration of symptoms over 30 days, while secondary outcomes included antibiotic use over 30 days, additional unscheduled visits to primary care over 30 days, and parental satisfaction and beliefs regarding antibiotic efficacy.

In the final dataset, 148 patients received immediate antibiotic prescriptions, while 146 received delayed prescriptions, and 142 received no prescription. Rate of antibiotic use was highest in the immediate prescription group, at 96%, versus 25.3% in the delayed group and 12% among those who received no prescription upon first presentation (P < .001).

Although the mean duration of severe symptoms was longest in the delayed-prescription group, at 12.4 days, versus 10.9 days in the no-prescription group and 10.1 days in the immediate-prescription group, these differences were not statistically significant (P = .539). Median score for greatest severity of any symptom was also similar across groups. Secondary outcomes echoed this pattern, in which reconsultation rates and caregiver satisfaction were statistically similar regardless of treatment type.

In contrast, patients who received immediate antibiotic prescriptions had a significantly higher rate of gastrointestinal adverse events (8.8%) than those who received a delayed prescription (3.4%) or no prescription (2.8%; P = .037).

“Delayed antibiotic prescription is an efficacious and safe strategy for reducing inappropriate antibiotic treatment of uncomplicated RTIs in children when the doctor has reasonable doubts regarding the indication,” the investigators concluded. “[It] is therefore a useful tool for addressing the public health issue of bacterial resistance. However, no antibiotic prescription remains the recommended strategy when it is clear that antibiotics are not indicated, like in most cases of acute bronchitis.”

“These data are reassuring,” wrote Dr. Gerber and Dr. Offit; however, they went on to suggest that the data “might not substantially move the needle.”

“With rare exceptions, children with acute pharyngitis should first receive a group A streptococcal test,” they wrote. “If results are positive, all patients should get antibiotics; if results are negative, no one gets them. Acute bronchitis (whatever that is in children) is viral. Acute sinusitis with persistent symptoms (the most commonly diagnosed variety) already has a delayed option, and the current study ... was not powered for this outcome. We are left with acute otitis media, which dominated enrollment but already has an evidence-based guideline.”

Still, Dr. Gerber and Dr. Offit suggested that the findings should further encourage pediatricians to prescribe antibiotics judiciously, and when elected, to choose the shortest duration and narrowest spectrum possible.

In a joint comment, Rana El Feghaly, MD, MSCI, director of outpatient antibiotic stewardship at Children’s Mercy, Kansas City, and her colleague, Mary Anne Jackson, MD, noted that the findings are “in accordance” with the 2017 Cochrane review.

Dr. Feghaly and Dr. Jackson said that these new data provide greater support for conservative use of antibiotics, which is badly needed, considering approximately 50% of outpatient prescriptions are unnecessary or inappropriate .

Delayed antibiotic prescription is part of a multifaceted approach to the issue, they said, joining “communication skills training, antibiotic justification documentation, audit and feedback reporting with peer comparison, diagnostic stewardship, [and] the use of clinician education on practice-based guidelines.”

“Leveraging delayed antibiotic prescription may be an excellent way to combat antibiotic overuse in the outpatient setting, while avoiding provider and parental fear of the ‘no antibiotic’ approach,” Dr. Feghaly and Dr. Jackson said.

Karlyn Kinsella, MD, of Pediatric Associates of Cheshire, Conn., suggested that clinicians discuss these findings with parents who request antibiotics for “otitis, pharyngitis, bronchitis, or sinusitis.”

“We can cite this study that antibiotics have no effect on symptom duration or severity for these illnesses,” Dr. Kinsella said. “Of course, our clinical opinion in each case takes precedent.”

According to Dr. Kinsella, conversations with parents also need to cover reasonable expectations, as the study did, with clear time frames for each condition in which children should start to get better.

“I think this is really key in our anticipatory guidance so that patients know what to expect,” she said.

The study was funded by Instituto de Salud Carlos III, the European Union, and the Spanish Ministry of Health, Social Services, and Equality. The investigators and interviewees reported no conflicts of interest.

Exposure to antibiotics in mid- to late pregnancy was associated with childhood asthma in vaginally born children, in a Danish birth cohort study.

The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.

Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
 

Antibiotic use in pregnancy likely to continue

Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.

The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.

“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”

Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.

To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
 

Children of mothers who took and did not take antibiotics compared

In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.

During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.

In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).

Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.

The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
 

Mode of delivery may matter

The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.

Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.

“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.

“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.

How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.

“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”

The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.

The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.

[email protected]

Exposure to antibiotics in mid- to late pregnancy was associated with childhood asthma in vaginally born children, in a Danish birth cohort study.

The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.

Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
 

Antibiotic use in pregnancy likely to continue

Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.

The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.

“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”

Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.

To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
 

Children of mothers who took and did not take antibiotics compared

In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.

During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.

In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).

Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.

The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
 

Mode of delivery may matter

The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.

Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.

“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.

“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.

How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.

“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”

The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.

The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.

[email protected]

Exposure to antibiotics in mid- to late pregnancy was associated with childhood asthma in vaginally born children, in a Danish birth cohort study.

The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.

Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
 

Antibiotic use in pregnancy likely to continue

Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.

The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.

“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”

Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.

To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
 

Children of mothers who took and did not take antibiotics compared

In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.

During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.

In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).

Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.

The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
 

Mode of delivery may matter

The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.

Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.

“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.

“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.

How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.

“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”

The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.

The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.

[email protected]