Pulmonology

SEATTLE – There were no cases of aspiration with enteric feeds of 60 children aged up to 2 years on high flow nasal cannula (HFNC) for bronchiolitis at the University of Oklahoma Children’s Hospital, Oklahoma City, according to research presented at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

HFNC has become common for bronchiolitis management; it often saves infants from intubation. However, many providers opt for total parenteral nutrition during therapy instead of enteral feeding because of concerns about aspiration pneumonia.

Pediatricians at the children’s hospital began to wonder if the concern was really necessary. There have been reports of safe feeding during HFNC, and “clinical care literature has shown that feeding the gut throughout illness improves outcomes,” said lead investigator, Sarah Walter, MD, a third-year pediatrics resident at the hospital.

So her team took a leap of faith. They consulted the HFNC literature, asked their fellow providers what they would be comfortable with, and instituted a pediatric HFNC enteral feeding protocol at the children’s hospital for use on inpatient floors, pediatric ICUs, and elsewhere.

Feedings – formula or breast milk – are triggered by stable respiratory Tal scores over 8 hours, meaning that respiratory rates, breath sounds, and accessory muscle use were stable or improving. Children on a flow of 6 L/min or less, with a respiratory rate below 60 breaths per minute, are started on oral feeds, and those on higher flows on nasogastric (NG) tube feeds.

Feeds are started at 1 mL/kg per hour and advanced by the same amount every 3 hours until volume goals are reached; IV fluids are tapered accordingly. It’s a standing order, so nurses are able to initiate and advance feeding as indicated, any time of day.

Feeding was temporarily suspended in only 17 children: 6 for emesis, 6 for worsening respiratory scores, and the rest for dislodged NG tubes, procedures, or other issues. Enteric feeds were restarted with two stable scores below 7 points, at half the rate at which they were stopped.

NG tubes were used in over half of the 478 nursing shifts during which the 60 children – the majority aged 4-24 months – were fed; oral feeds in more than a third; and gastric tubes and other options in the rest. IV nutrition was used during just 1.8% of the shifts.

Enteric feeds were given up to a flow rate of 3.5 L/kg. There were no aspirations, even when children vomited. “We have seen good results so far that feeding is safe in these children,” Dr. Walters said.

“Our hospitalist team has been very receptive; they have been using the order set pretty continuously.” Parents also feel better when they know their children were “getting food in their belly,” even if by NG tube. “It’s important for family satisfaction,” she said.

The next step is to assess impact on length of stay, and education efforts to encourage broader use of the order set.

There was no external funding, and Dr. Walter had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

aotto@mdedge.com

SEATTLE – There were no cases of aspiration with enteric feeds of 60 children aged up to 2 years on high flow nasal cannula (HFNC) for bronchiolitis at the University of Oklahoma Children’s Hospital, Oklahoma City, according to research presented at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

HFNC has become common for bronchiolitis management; it often saves infants from intubation. However, many providers opt for total parenteral nutrition during therapy instead of enteral feeding because of concerns about aspiration pneumonia.

Pediatricians at the children’s hospital began to wonder if the concern was really necessary. There have been reports of safe feeding during HFNC, and “clinical care literature has shown that feeding the gut throughout illness improves outcomes,” said lead investigator, Sarah Walter, MD, a third-year pediatrics resident at the hospital.

So her team took a leap of faith. They consulted the HFNC literature, asked their fellow providers what they would be comfortable with, and instituted a pediatric HFNC enteral feeding protocol at the children’s hospital for use on inpatient floors, pediatric ICUs, and elsewhere.

Feedings – formula or breast milk – are triggered by stable respiratory Tal scores over 8 hours, meaning that respiratory rates, breath sounds, and accessory muscle use were stable or improving. Children on a flow of 6 L/min or less, with a respiratory rate below 60 breaths per minute, are started on oral feeds, and those on higher flows on nasogastric (NG) tube feeds.

Feeds are started at 1 mL/kg per hour and advanced by the same amount every 3 hours until volume goals are reached; IV fluids are tapered accordingly. It’s a standing order, so nurses are able to initiate and advance feeding as indicated, any time of day.

Feeding was temporarily suspended in only 17 children: 6 for emesis, 6 for worsening respiratory scores, and the rest for dislodged NG tubes, procedures, or other issues. Enteric feeds were restarted with two stable scores below 7 points, at half the rate at which they were stopped.

NG tubes were used in over half of the 478 nursing shifts during which the 60 children – the majority aged 4-24 months – were fed; oral feeds in more than a third; and gastric tubes and other options in the rest. IV nutrition was used during just 1.8% of the shifts.

Enteric feeds were given up to a flow rate of 3.5 L/kg. There were no aspirations, even when children vomited. “We have seen good results so far that feeding is safe in these children,” Dr. Walters said.

“Our hospitalist team has been very receptive; they have been using the order set pretty continuously.” Parents also feel better when they know their children were “getting food in their belly,” even if by NG tube. “It’s important for family satisfaction,” she said.

The next step is to assess impact on length of stay, and education efforts to encourage broader use of the order set.

There was no external funding, and Dr. Walter had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

aotto@mdedge.com

SEATTLE – There were no cases of aspiration with enteric feeds of 60 children aged up to 2 years on high flow nasal cannula (HFNC) for bronchiolitis at the University of Oklahoma Children’s Hospital, Oklahoma City, according to research presented at the 2019 Pediatric Hospital Medicine Conference.

M. Alexander Otto/MDedge News

HFNC has become common for bronchiolitis management; it often saves infants from intubation. However, many providers opt for total parenteral nutrition during therapy instead of enteral feeding because of concerns about aspiration pneumonia.

Pediatricians at the children’s hospital began to wonder if the concern was really necessary. There have been reports of safe feeding during HFNC, and “clinical care literature has shown that feeding the gut throughout illness improves outcomes,” said lead investigator, Sarah Walter, MD, a third-year pediatrics resident at the hospital.

So her team took a leap of faith. They consulted the HFNC literature, asked their fellow providers what they would be comfortable with, and instituted a pediatric HFNC enteral feeding protocol at the children’s hospital for use on inpatient floors, pediatric ICUs, and elsewhere.

Feedings – formula or breast milk – are triggered by stable respiratory Tal scores over 8 hours, meaning that respiratory rates, breath sounds, and accessory muscle use were stable or improving. Children on a flow of 6 L/min or less, with a respiratory rate below 60 breaths per minute, are started on oral feeds, and those on higher flows on nasogastric (NG) tube feeds.

Feeds are started at 1 mL/kg per hour and advanced by the same amount every 3 hours until volume goals are reached; IV fluids are tapered accordingly. It’s a standing order, so nurses are able to initiate and advance feeding as indicated, any time of day.

Feeding was temporarily suspended in only 17 children: 6 for emesis, 6 for worsening respiratory scores, and the rest for dislodged NG tubes, procedures, or other issues. Enteric feeds were restarted with two stable scores below 7 points, at half the rate at which they were stopped.

NG tubes were used in over half of the 478 nursing shifts during which the 60 children – the majority aged 4-24 months – were fed; oral feeds in more than a third; and gastric tubes and other options in the rest. IV nutrition was used during just 1.8% of the shifts.

Enteric feeds were given up to a flow rate of 3.5 L/kg. There were no aspirations, even when children vomited. “We have seen good results so far that feeding is safe in these children,” Dr. Walters said.

“Our hospitalist team has been very receptive; they have been using the order set pretty continuously.” Parents also feel better when they know their children were “getting food in their belly,” even if by NG tube. “It’s important for family satisfaction,” she said.

The next step is to assess impact on length of stay, and education efforts to encourage broader use of the order set.

There was no external funding, and Dr. Walter had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

aotto@mdedge.com

ORLANDO – Sinusitis is a complicated, multifactorial disease that should be treated based on the patient’s predisposing factors, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

The major signs and symptoms of sinusitis are pressure and pain on the anterior side of the face or in a localized headache, nasal obstruction, and pus observed at exam that is clouded or colored. Patients may also present with a feeling of facial congestion or fullness, nasal discharge, and fever, noted Brian Bizik, MS, PA-C, from Asthma & Allergy of Idaho and Nevada. The condition can present as acute (up to 4 weeks), subacute (4-12 weeks, with resolution of symptoms), chronic (12 weeks or more), and recurrent acute chronic sinusitis. Most cases of sinusitis are accompanied with contiguous nasal mucosa inflammation, and therefore the term rhinosinusitis is preferred.

To diagnose sinusitis, “you want patients to tell you where they’re hurting, and where their pressure is,” Mr. Bizik said, noting that he instructs patients to “point with one finger and tell me how you feel without using the word ‘sinus.’ ” Clinicians should ask whether a patient’s pain is continuous or cyclic, if they have bad breath even after brushing their teeth, if they have a chronic cough as opposed to postnasal drip, whether they have pain when they chew or walk, and if they feel like they are always tired.

According to guidelines from the Infectious Diseases Society of America, if symptoms last longer than 10 days and patients have a fever above 39° C (102.2° F), it is more likely bacterial rather than viral. Another sign of bacterial infection is when patients get better after a few days before worsening again later, said Mr. Bizik. In patients where clinicians suspect bacterial infection, the IDSA recommends amoxicillin/clavulanate over amoxicillin alone because some acute bacterial rhinosinusitis could be Haemophilus influenzae, and up to 30% of these infections can produce beta-lactamase. Patients with an amoxicillin allergy should take doxycycline, which is the only currently recommended antibiotic for patients with acute bacterial rhinosinusitis.

In general, clinicians should treat acute bacterial rhinosinusitis based on whether the patient has the most severe disease, said Mr. Bizik. “Use those three criteria: fever, symptoms longer than 10 days, purulence, and feeling lousy. If you find these people are in the high-risk group, [the guidelines] recommend antibiotic treatment.”

In addition to antibiotics, patients can likely benefit from use of topical corticosteroids such as mometasone, fluticasone, flunisolide, and beclomethasone. “It comes down to simply what you like and what works well for you,” he said. With regard to oral steroids, patients with severe pain can benefit from medication like prednisone. Finally, decongestants and relief with sinus irrigation treatments like Neti pots can help relieve symptoms and promote healthy mucosal function.

On the other hand, sinusitis with a viral origin tends to have “light” flu symptoms that do not worsen over time and almost always resolve within 10 days. “If they fit the viral mold, we’re going to do everything the same [as bacterial sinusitis]; just skip the antibiotics,” he said.

In patients with chronic rhinosinusitis (CRS), the symptoms persist over a longer period of time. CRS has a large number of associated conditions, such as allergic rhinitis and gastroesophageal reflux, as well as environmental factors like cigarette smoke, viral illness, and rebound rhinitis. If a patient’s CRS is caused by allergies, treating the allergies aggressively will improve CRS symptoms. “If they have an allergic component, you really have to have a reason not to put them on montelukast. I would encourage you to do that,” said Mr. Bizik. “Cetirizine and montelukast at bedtime works very well. They’re cheap, effective, generic, and nonsteroidal.”

Other methods for treating symptoms of CRS include saline irrigation to increase mucociliary flow rates, high doses of mucolytics, and first- and second-generation antihistamines, which can take up to 10 days to see the full effect. “I have a 10-day reminder, and I call them on day 11,” said Mr. Bizik. “If they stick with it, they say it really did help. It’s a great way to avoid antibiotics.”

Intranasal corticosteroids are also effective first-line therapies for CRS. However, technique is important when using these medications. In his presentation, Mr. Bizik described the “opposite-hand” technique he teaches to patients to reduce some of the side effects patients experience when using intranasal corticosteroids, including nosebleeds.

“You insert it in the nose, you go in all the way until you just feel your fingers touching your nose, and you point it towards the earlobe so the left nostril goes to the left earlobe [and vice versa], and you just spray,” once or twice a day depending on indication, he said. “Using those consistently, when you do this, the flower smell is less, it doesn’t bother you, less goes down your throat, and it’s very effective.”

Dr. Bizik reports being a speaking and consultant for Grifols, Boehringer Ingelheim, Meda Pharmaceuticals, and an advisory board member for Circassia Pharmaceuticals.

Global Academy for Medical Education and this news organization are owned by the same parent company.

ORLANDO – Sinusitis is a complicated, multifactorial disease that should be treated based on the patient’s predisposing factors, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

The major signs and symptoms of sinusitis are pressure and pain on the anterior side of the face or in a localized headache, nasal obstruction, and pus observed at exam that is clouded or colored. Patients may also present with a feeling of facial congestion or fullness, nasal discharge, and fever, noted Brian Bizik, MS, PA-C, from Asthma & Allergy of Idaho and Nevada. The condition can present as acute (up to 4 weeks), subacute (4-12 weeks, with resolution of symptoms), chronic (12 weeks or more), and recurrent acute chronic sinusitis. Most cases of sinusitis are accompanied with contiguous nasal mucosa inflammation, and therefore the term rhinosinusitis is preferred.

To diagnose sinusitis, “you want patients to tell you where they’re hurting, and where their pressure is,” Mr. Bizik said, noting that he instructs patients to “point with one finger and tell me how you feel without using the word ‘sinus.’ ” Clinicians should ask whether a patient’s pain is continuous or cyclic, if they have bad breath even after brushing their teeth, if they have a chronic cough as opposed to postnasal drip, whether they have pain when they chew or walk, and if they feel like they are always tired.

According to guidelines from the Infectious Diseases Society of America, if symptoms last longer than 10 days and patients have a fever above 39° C (102.2° F), it is more likely bacterial rather than viral. Another sign of bacterial infection is when patients get better after a few days before worsening again later, said Mr. Bizik. In patients where clinicians suspect bacterial infection, the IDSA recommends amoxicillin/clavulanate over amoxicillin alone because some acute bacterial rhinosinusitis could be Haemophilus influenzae, and up to 30% of these infections can produce beta-lactamase. Patients with an amoxicillin allergy should take doxycycline, which is the only currently recommended antibiotic for patients with acute bacterial rhinosinusitis.

In general, clinicians should treat acute bacterial rhinosinusitis based on whether the patient has the most severe disease, said Mr. Bizik. “Use those three criteria: fever, symptoms longer than 10 days, purulence, and feeling lousy. If you find these people are in the high-risk group, [the guidelines] recommend antibiotic treatment.”

In addition to antibiotics, patients can likely benefit from use of topical corticosteroids such as mometasone, fluticasone, flunisolide, and beclomethasone. “It comes down to simply what you like and what works well for you,” he said. With regard to oral steroids, patients with severe pain can benefit from medication like prednisone. Finally, decongestants and relief with sinus irrigation treatments like Neti pots can help relieve symptoms and promote healthy mucosal function.

On the other hand, sinusitis with a viral origin tends to have “light” flu symptoms that do not worsen over time and almost always resolve within 10 days. “If they fit the viral mold, we’re going to do everything the same [as bacterial sinusitis]; just skip the antibiotics,” he said.

In patients with chronic rhinosinusitis (CRS), the symptoms persist over a longer period of time. CRS has a large number of associated conditions, such as allergic rhinitis and gastroesophageal reflux, as well as environmental factors like cigarette smoke, viral illness, and rebound rhinitis. If a patient’s CRS is caused by allergies, treating the allergies aggressively will improve CRS symptoms. “If they have an allergic component, you really have to have a reason not to put them on montelukast. I would encourage you to do that,” said Mr. Bizik. “Cetirizine and montelukast at bedtime works very well. They’re cheap, effective, generic, and nonsteroidal.”

Other methods for treating symptoms of CRS include saline irrigation to increase mucociliary flow rates, high doses of mucolytics, and first- and second-generation antihistamines, which can take up to 10 days to see the full effect. “I have a 10-day reminder, and I call them on day 11,” said Mr. Bizik. “If they stick with it, they say it really did help. It’s a great way to avoid antibiotics.”

Intranasal corticosteroids are also effective first-line therapies for CRS. However, technique is important when using these medications. In his presentation, Mr. Bizik described the “opposite-hand” technique he teaches to patients to reduce some of the side effects patients experience when using intranasal corticosteroids, including nosebleeds.

“You insert it in the nose, you go in all the way until you just feel your fingers touching your nose, and you point it towards the earlobe so the left nostril goes to the left earlobe [and vice versa], and you just spray,” once or twice a day depending on indication, he said. “Using those consistently, when you do this, the flower smell is less, it doesn’t bother you, less goes down your throat, and it’s very effective.”

Dr. Bizik reports being a speaking and consultant for Grifols, Boehringer Ingelheim, Meda Pharmaceuticals, and an advisory board member for Circassia Pharmaceuticals.

Global Academy for Medical Education and this news organization are owned by the same parent company.

ORLANDO – Sinusitis is a complicated, multifactorial disease that should be treated based on the patient’s predisposing factors, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

The major signs and symptoms of sinusitis are pressure and pain on the anterior side of the face or in a localized headache, nasal obstruction, and pus observed at exam that is clouded or colored. Patients may also present with a feeling of facial congestion or fullness, nasal discharge, and fever, noted Brian Bizik, MS, PA-C, from Asthma & Allergy of Idaho and Nevada. The condition can present as acute (up to 4 weeks), subacute (4-12 weeks, with resolution of symptoms), chronic (12 weeks or more), and recurrent acute chronic sinusitis. Most cases of sinusitis are accompanied with contiguous nasal mucosa inflammation, and therefore the term rhinosinusitis is preferred.

To diagnose sinusitis, “you want patients to tell you where they’re hurting, and where their pressure is,” Mr. Bizik said, noting that he instructs patients to “point with one finger and tell me how you feel without using the word ‘sinus.’ ” Clinicians should ask whether a patient’s pain is continuous or cyclic, if they have bad breath even after brushing their teeth, if they have a chronic cough as opposed to postnasal drip, whether they have pain when they chew or walk, and if they feel like they are always tired.

According to guidelines from the Infectious Diseases Society of America, if symptoms last longer than 10 days and patients have a fever above 39° C (102.2° F), it is more likely bacterial rather than viral. Another sign of bacterial infection is when patients get better after a few days before worsening again later, said Mr. Bizik. In patients where clinicians suspect bacterial infection, the IDSA recommends amoxicillin/clavulanate over amoxicillin alone because some acute bacterial rhinosinusitis could be Haemophilus influenzae, and up to 30% of these infections can produce beta-lactamase. Patients with an amoxicillin allergy should take doxycycline, which is the only currently recommended antibiotic for patients with acute bacterial rhinosinusitis.

In general, clinicians should treat acute bacterial rhinosinusitis based on whether the patient has the most severe disease, said Mr. Bizik. “Use those three criteria: fever, symptoms longer than 10 days, purulence, and feeling lousy. If you find these people are in the high-risk group, [the guidelines] recommend antibiotic treatment.”

In addition to antibiotics, patients can likely benefit from use of topical corticosteroids such as mometasone, fluticasone, flunisolide, and beclomethasone. “It comes down to simply what you like and what works well for you,” he said. With regard to oral steroids, patients with severe pain can benefit from medication like prednisone. Finally, decongestants and relief with sinus irrigation treatments like Neti pots can help relieve symptoms and promote healthy mucosal function.

On the other hand, sinusitis with a viral origin tends to have “light” flu symptoms that do not worsen over time and almost always resolve within 10 days. “If they fit the viral mold, we’re going to do everything the same [as bacterial sinusitis]; just skip the antibiotics,” he said.

In patients with chronic rhinosinusitis (CRS), the symptoms persist over a longer period of time. CRS has a large number of associated conditions, such as allergic rhinitis and gastroesophageal reflux, as well as environmental factors like cigarette smoke, viral illness, and rebound rhinitis. If a patient’s CRS is caused by allergies, treating the allergies aggressively will improve CRS symptoms. “If they have an allergic component, you really have to have a reason not to put them on montelukast. I would encourage you to do that,” said Mr. Bizik. “Cetirizine and montelukast at bedtime works very well. They’re cheap, effective, generic, and nonsteroidal.”

Other methods for treating symptoms of CRS include saline irrigation to increase mucociliary flow rates, high doses of mucolytics, and first- and second-generation antihistamines, which can take up to 10 days to see the full effect. “I have a 10-day reminder, and I call them on day 11,” said Mr. Bizik. “If they stick with it, they say it really did help. It’s a great way to avoid antibiotics.”

Intranasal corticosteroids are also effective first-line therapies for CRS. However, technique is important when using these medications. In his presentation, Mr. Bizik described the “opposite-hand” technique he teaches to patients to reduce some of the side effects patients experience when using intranasal corticosteroids, including nosebleeds.

“You insert it in the nose, you go in all the way until you just feel your fingers touching your nose, and you point it towards the earlobe so the left nostril goes to the left earlobe [and vice versa], and you just spray,” once or twice a day depending on indication, he said. “Using those consistently, when you do this, the flower smell is less, it doesn’t bother you, less goes down your throat, and it’s very effective.”

Dr. Bizik reports being a speaking and consultant for Grifols, Boehringer Ingelheim, Meda Pharmaceuticals, and an advisory board member for Circassia Pharmaceuticals.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SEATTLE – Adding a 3-day course of azithromycin to treatment regimens of children hospitalized with asthma did not shorten length of stay or bring other benefits in a randomized, blinded trial of more than 150 youngsters at The Children’s Hospital at Montefiore, New York.

M. Alexander Otto/MDedge News

In recent years, some pediatricians at Montefiore had begun giving short-course azithromycin to hospitalized children who were not recovering as quickly as they had hoped, spurred by outpatient reports of reduced exacerbations and other benefits with long-term azithromycin (e.g., Lancet. 2017 Aug 12;390(10095):659-68).

“We had no evidence for doing that at all” in the hospital, and it might be going on elsewhere, said senior investigator Alyssa Silver, MD, assistant professor of pediatrics at Montefiore and Albert Einstein College of Medicine, New York. She and her colleagues, including primary investigator Lindsey Douglas, MD, assistant professor of pediatrics at the Icahn School of Medicine at Mount Sinai, New York, took a closer look.

The negative results mean that “we can stop doing this, giving kids unnecessary things. Word is starting to get out” at Montefiore. “People are not using it as much,” she said at Pediatric Hospital Medicine, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The team had expected azithromycin to shorten length of stay (LOS) by about half a day, due to its anti-inflammatory effects, but that’s not what was found when they randomized 80 children aged 4-12 years with persistent asthma to oral azithromycin 10 mg/kg per day for 3 days within 12 hours of admission, and 79 to placebo.

LOS was 1.86 days in the placebo arm, and 1.69 days in the azithromycin group (P = .23). One placebo child was transferred to the pediatric ICU, versus none in the azithromycin arm (P = .50). The study was stopped short of its 214 subject enrollment goal because of futility, but even so, it was well powered to detect a difference in LOS, the primary outcome, Dr. Silver said.

At 1 week phone follow-up, 7 placebo children and 11 in the azithromycin arm had persistent asthma symptoms (P = .42), and 1 placebo child and 2 azithromycin children had been readmitted (P greater than .99). There were no differences in days of school missed, or work days missed among parents and guardians.

At one month, 23 placebo and 18 azithromycin children had persistent asthma symptoms (P = .5); 7 placebo and 6 azithromycin children had returned to the ED (P = .75).

In short, “we really found no difference” with short-course azithromycin. “Clinicians should consider [these] data before prescribing azithromycin [to] children hospitalized with asthma,” Dr. Silver and her team concluded.

Subjects were an average of about 7 years old, and about two-thirds were boys. They were not on azithromycin or other antibiotics prior to admission. About half had been admitted in the previous year, and about a quarter had at least one previous pediatric ICU admission. Over two-thirds had been on daily asthma medications. There were about 2 days of symptoms prior to admission.

There was no external funding, and Dr. Silver had no disclosures.

aotto@mdedge.com

SEATTLE – Adding a 3-day course of azithromycin to treatment regimens of children hospitalized with asthma did not shorten length of stay or bring other benefits in a randomized, blinded trial of more than 150 youngsters at The Children’s Hospital at Montefiore, New York.

M. Alexander Otto/MDedge News

In recent years, some pediatricians at Montefiore had begun giving short-course azithromycin to hospitalized children who were not recovering as quickly as they had hoped, spurred by outpatient reports of reduced exacerbations and other benefits with long-term azithromycin (e.g., Lancet. 2017 Aug 12;390(10095):659-68).

“We had no evidence for doing that at all” in the hospital, and it might be going on elsewhere, said senior investigator Alyssa Silver, MD, assistant professor of pediatrics at Montefiore and Albert Einstein College of Medicine, New York. She and her colleagues, including primary investigator Lindsey Douglas, MD, assistant professor of pediatrics at the Icahn School of Medicine at Mount Sinai, New York, took a closer look.

The negative results mean that “we can stop doing this, giving kids unnecessary things. Word is starting to get out” at Montefiore. “People are not using it as much,” she said at Pediatric Hospital Medicine, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The team had expected azithromycin to shorten length of stay (LOS) by about half a day, due to its anti-inflammatory effects, but that’s not what was found when they randomized 80 children aged 4-12 years with persistent asthma to oral azithromycin 10 mg/kg per day for 3 days within 12 hours of admission, and 79 to placebo.

LOS was 1.86 days in the placebo arm, and 1.69 days in the azithromycin group (P = .23). One placebo child was transferred to the pediatric ICU, versus none in the azithromycin arm (P = .50). The study was stopped short of its 214 subject enrollment goal because of futility, but even so, it was well powered to detect a difference in LOS, the primary outcome, Dr. Silver said.

At 1 week phone follow-up, 7 placebo children and 11 in the azithromycin arm had persistent asthma symptoms (P = .42), and 1 placebo child and 2 azithromycin children had been readmitted (P greater than .99). There were no differences in days of school missed, or work days missed among parents and guardians.

At one month, 23 placebo and 18 azithromycin children had persistent asthma symptoms (P = .5); 7 placebo and 6 azithromycin children had returned to the ED (P = .75).

In short, “we really found no difference” with short-course azithromycin. “Clinicians should consider [these] data before prescribing azithromycin [to] children hospitalized with asthma,” Dr. Silver and her team concluded.

Subjects were an average of about 7 years old, and about two-thirds were boys. They were not on azithromycin or other antibiotics prior to admission. About half had been admitted in the previous year, and about a quarter had at least one previous pediatric ICU admission. Over two-thirds had been on daily asthma medications. There were about 2 days of symptoms prior to admission.

There was no external funding, and Dr. Silver had no disclosures.

aotto@mdedge.com

SEATTLE – Adding a 3-day course of azithromycin to treatment regimens of children hospitalized with asthma did not shorten length of stay or bring other benefits in a randomized, blinded trial of more than 150 youngsters at The Children’s Hospital at Montefiore, New York.

M. Alexander Otto/MDedge News

In recent years, some pediatricians at Montefiore had begun giving short-course azithromycin to hospitalized children who were not recovering as quickly as they had hoped, spurred by outpatient reports of reduced exacerbations and other benefits with long-term azithromycin (e.g., Lancet. 2017 Aug 12;390(10095):659-68).

“We had no evidence for doing that at all” in the hospital, and it might be going on elsewhere, said senior investigator Alyssa Silver, MD, assistant professor of pediatrics at Montefiore and Albert Einstein College of Medicine, New York. She and her colleagues, including primary investigator Lindsey Douglas, MD, assistant professor of pediatrics at the Icahn School of Medicine at Mount Sinai, New York, took a closer look.

The negative results mean that “we can stop doing this, giving kids unnecessary things. Word is starting to get out” at Montefiore. “People are not using it as much,” she said at Pediatric Hospital Medicine, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The team had expected azithromycin to shorten length of stay (LOS) by about half a day, due to its anti-inflammatory effects, but that’s not what was found when they randomized 80 children aged 4-12 years with persistent asthma to oral azithromycin 10 mg/kg per day for 3 days within 12 hours of admission, and 79 to placebo.

LOS was 1.86 days in the placebo arm, and 1.69 days in the azithromycin group (P = .23). One placebo child was transferred to the pediatric ICU, versus none in the azithromycin arm (P = .50). The study was stopped short of its 214 subject enrollment goal because of futility, but even so, it was well powered to detect a difference in LOS, the primary outcome, Dr. Silver said.

At 1 week phone follow-up, 7 placebo children and 11 in the azithromycin arm had persistent asthma symptoms (P = .42), and 1 placebo child and 2 azithromycin children had been readmitted (P greater than .99). There were no differences in days of school missed, or work days missed among parents and guardians.

At one month, 23 placebo and 18 azithromycin children had persistent asthma symptoms (P = .5); 7 placebo and 6 azithromycin children had returned to the ED (P = .75).

In short, “we really found no difference” with short-course azithromycin. “Clinicians should consider [these] data before prescribing azithromycin [to] children hospitalized with asthma,” Dr. Silver and her team concluded.

Subjects were an average of about 7 years old, and about two-thirds were boys. They were not on azithromycin or other antibiotics prior to admission. About half had been admitted in the previous year, and about a quarter had at least one previous pediatric ICU admission. Over two-thirds had been on daily asthma medications. There were about 2 days of symptoms prior to admission.

There was no external funding, and Dr. Silver had no disclosures.

aotto@mdedge.com

Physician recommendations of cough and cold medicine for children have “declined substantially” since 2002, with evidence suggesting replacement by off-label antihistamines, according to analysis of two national databases.

Compared with older children, declines in both opioid and nonopioid cold and cough medicine (CCM) use “appeared to accelerate in children younger than 2 years … and among children younger than 6 years for opioid-containing CCM” after the Food and Drug Administration’s 2008 public health advisory on use of OTC forms of CCM, Daniel B. Horton, MD, of the Robert Wood Johnson Medical School, New Brunswick, N.J., and his associates wrote in JAMA Pediatrics.

Meanwhile, recommendations for single-agent antihistamines rose – for some age groups significantly – over the 14-year study period, which was divided into two eras: 2002-2008 and 2009-2015.

When the two eras were compared, trends for decreased use of CCM in children under 2 years of age (nonopioid) and under 4 years (opioid) approached – both were P = .05 – but did not quite reach the less than .05 considered statistically significant. Adjusted odds ratios for the other age groups were further off the mark. For antihistamines, the upward trend between the two eras was significant for children aged under 2 years, 2-3 years, and 6-11 years, Dr. Horton and associates reported.

The two youngest groups, under 2 years and 2-3, were combined for the opioid CCM analyses to avoid a population under 30, which would have yielded unreliable estimates. The investigators used data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, with the sample representing 3.1 billion pediatric visits from 2002 to 2015.

Dr. Horton is supported by an award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The investigators reported no disclosures relevant to this study.

rfranki@mdedge.com

SOURCE: Horton DB et al. JAMA Pediatr. 2019 Jul 29. doi: 10.1001/jamapediatrics.2019.2252.

Physician recommendations of cough and cold medicine for children have “declined substantially” since 2002, with evidence suggesting replacement by off-label antihistamines, according to analysis of two national databases.

Compared with older children, declines in both opioid and nonopioid cold and cough medicine (CCM) use “appeared to accelerate in children younger than 2 years … and among children younger than 6 years for opioid-containing CCM” after the Food and Drug Administration’s 2008 public health advisory on use of OTC forms of CCM, Daniel B. Horton, MD, of the Robert Wood Johnson Medical School, New Brunswick, N.J., and his associates wrote in JAMA Pediatrics.

Meanwhile, recommendations for single-agent antihistamines rose – for some age groups significantly – over the 14-year study period, which was divided into two eras: 2002-2008 and 2009-2015.

When the two eras were compared, trends for decreased use of CCM in children under 2 years of age (nonopioid) and under 4 years (opioid) approached – both were P = .05 – but did not quite reach the less than .05 considered statistically significant. Adjusted odds ratios for the other age groups were further off the mark. For antihistamines, the upward trend between the two eras was significant for children aged under 2 years, 2-3 years, and 6-11 years, Dr. Horton and associates reported.

The two youngest groups, under 2 years and 2-3, were combined for the opioid CCM analyses to avoid a population under 30, which would have yielded unreliable estimates. The investigators used data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, with the sample representing 3.1 billion pediatric visits from 2002 to 2015.

Dr. Horton is supported by an award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The investigators reported no disclosures relevant to this study.

rfranki@mdedge.com

SOURCE: Horton DB et al. JAMA Pediatr. 2019 Jul 29. doi: 10.1001/jamapediatrics.2019.2252.

Physician recommendations of cough and cold medicine for children have “declined substantially” since 2002, with evidence suggesting replacement by off-label antihistamines, according to analysis of two national databases.

Compared with older children, declines in both opioid and nonopioid cold and cough medicine (CCM) use “appeared to accelerate in children younger than 2 years … and among children younger than 6 years for opioid-containing CCM” after the Food and Drug Administration’s 2008 public health advisory on use of OTC forms of CCM, Daniel B. Horton, MD, of the Robert Wood Johnson Medical School, New Brunswick, N.J., and his associates wrote in JAMA Pediatrics.

Meanwhile, recommendations for single-agent antihistamines rose – for some age groups significantly – over the 14-year study period, which was divided into two eras: 2002-2008 and 2009-2015.

When the two eras were compared, trends for decreased use of CCM in children under 2 years of age (nonopioid) and under 4 years (opioid) approached – both were P = .05 – but did not quite reach the less than .05 considered statistically significant. Adjusted odds ratios for the other age groups were further off the mark. For antihistamines, the upward trend between the two eras was significant for children aged under 2 years, 2-3 years, and 6-11 years, Dr. Horton and associates reported.

The two youngest groups, under 2 years and 2-3, were combined for the opioid CCM analyses to avoid a population under 30, which would have yielded unreliable estimates. The investigators used data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, with the sample representing 3.1 billion pediatric visits from 2002 to 2015.

Dr. Horton is supported by an award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The investigators reported no disclosures relevant to this study.

rfranki@mdedge.com

SOURCE: Horton DB et al. JAMA Pediatr. 2019 Jul 29. doi: 10.1001/jamapediatrics.2019.2252.

ORLANDO – Inhaler choice for patients with chronic obstructive pulmonary disease (COPD) should be chosen on the basis of access, cost, prescriber, patient ability, and patient preference.

That’s according to Gabriel Ortiz, MPAS, PA-C, DFAAPA, a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

There are several treatment options available in inhaler form for patients with COPD, including short-acting and long-acting beta₂-agonists (SABA/LABA), short-acting and long-acting antimuscarinics (SAMA/LAMA), combination therapy, and triple therapy. But education and training on how to use an inhaler is also important, Mr. Ortiz said in his presentation.

Providers should help a patient choose an inhaler they are most likely to use. “It’s difficult to actuate and inhale, so there’s a lot of education that goes into that,” said Mr. Ortiz, of Pediatric Pulmonary Services in El Paso, Texas. “What we do for our patients is, we educate them, we tell them to demonstrate it, then bring [the] inhaler back on the next visit and demonstrate to us every time.”

“Make sure that they demonstrate because, as patients get older, they may lose their ability to actuate and inhale,” he added.

Adherence to therapy should also be considered before changing from a current therapy, he added. Mr. Ortiz described a scenario in which a prescription was filled, but because of the cost, the patient reduced the dose by half to make the therapy last longer.

“We could be the best providers in the world, prescribing the best medication in the world. If the medication doesn’t get to where we need it, it’s not going to help anybody,” he said.

Providers should also use nonpharmacological treatments to prevent or keep COPD from progressing. Smoking cessation is key to reducing the risk of developing COPD, and it is not clear whether e-cigarettes aid in smoking cessation, despite companies that market these products making that claim. “We have a huge e-cigarette epidemic here,” he said.

Instead, Mr. Ortiz recommended identifying which patients are current tobacco users, encouraging them to quit, determining whether the patient is willing to make a commitment to cut down on tobacco use or stop entirely, helping draft a quit plan and obtaining intra- and extratreatment social support for smoking cessation, and scheduling follow-up. Providers should discuss smoking cessation at each visit, and it may take multiple visits before a patient is willing to consider quitting, he said.

Another measure providers can take is making sure patients with COPD have received influenza and pneumococcal vaccinations because this can lower the risk of respiratory tract infections. Physical activity, training in exercise, nutritional support, and pulmonary rehabilitation can improve their health status, dyspnea, and exercise tolerance. While C-level evidence shows education alone is not effective according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, providers working with patients through self-management interventions have been shown to improve health status and decrease COPD-related hospitalizations.

Oxygen therapy has been effective for patients with severe resting chronic hypoxia and improves survival, said Mr. Ortiz. For patients who gradually decline in health despite treatment, palliative, hospice, and end-of-life care may be an option. “Remember that as acute exacerbations continue, that increases the risk of death,” he said. “We want to try and prevent [those] exacerbations and improve quality of life.”

During follow-up visits, providers should continue performing spirometry tests annually to measure decline in forced expiratory volume in 1 second, information on symptoms that have presented since the previous visit, details of any exacerbations that occurred, and current smoking status. When making decisions to adjust therapy, providers should examine the effectiveness of the current regimen and consider the dose of prescribed medications, whether the patient is adhering to the regimen, inhaler technique, and any side effects.

Mr. Ortiz reports also being a paid employee for Thermo Fisher, a biotechnology product development company based in Waltham, Mass. Global Academy for Medical Education and this news organization are owned by the same parent company.


 

ORLANDO – Inhaler choice for patients with chronic obstructive pulmonary disease (COPD) should be chosen on the basis of access, cost, prescriber, patient ability, and patient preference.

That’s according to Gabriel Ortiz, MPAS, PA-C, DFAAPA, a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

There are several treatment options available in inhaler form for patients with COPD, including short-acting and long-acting beta₂-agonists (SABA/LABA), short-acting and long-acting antimuscarinics (SAMA/LAMA), combination therapy, and triple therapy. But education and training on how to use an inhaler is also important, Mr. Ortiz said in his presentation.

Providers should help a patient choose an inhaler they are most likely to use. “It’s difficult to actuate and inhale, so there’s a lot of education that goes into that,” said Mr. Ortiz, of Pediatric Pulmonary Services in El Paso, Texas. “What we do for our patients is, we educate them, we tell them to demonstrate it, then bring [the] inhaler back on the next visit and demonstrate to us every time.”

“Make sure that they demonstrate because, as patients get older, they may lose their ability to actuate and inhale,” he added.

Adherence to therapy should also be considered before changing from a current therapy, he added. Mr. Ortiz described a scenario in which a prescription was filled, but because of the cost, the patient reduced the dose by half to make the therapy last longer.

“We could be the best providers in the world, prescribing the best medication in the world. If the medication doesn’t get to where we need it, it’s not going to help anybody,” he said.

Providers should also use nonpharmacological treatments to prevent or keep COPD from progressing. Smoking cessation is key to reducing the risk of developing COPD, and it is not clear whether e-cigarettes aid in smoking cessation, despite companies that market these products making that claim. “We have a huge e-cigarette epidemic here,” he said.

Instead, Mr. Ortiz recommended identifying which patients are current tobacco users, encouraging them to quit, determining whether the patient is willing to make a commitment to cut down on tobacco use or stop entirely, helping draft a quit plan and obtaining intra- and extratreatment social support for smoking cessation, and scheduling follow-up. Providers should discuss smoking cessation at each visit, and it may take multiple visits before a patient is willing to consider quitting, he said.

Another measure providers can take is making sure patients with COPD have received influenza and pneumococcal vaccinations because this can lower the risk of respiratory tract infections. Physical activity, training in exercise, nutritional support, and pulmonary rehabilitation can improve their health status, dyspnea, and exercise tolerance. While C-level evidence shows education alone is not effective according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, providers working with patients through self-management interventions have been shown to improve health status and decrease COPD-related hospitalizations.

Oxygen therapy has been effective for patients with severe resting chronic hypoxia and improves survival, said Mr. Ortiz. For patients who gradually decline in health despite treatment, palliative, hospice, and end-of-life care may be an option. “Remember that as acute exacerbations continue, that increases the risk of death,” he said. “We want to try and prevent [those] exacerbations and improve quality of life.”

During follow-up visits, providers should continue performing spirometry tests annually to measure decline in forced expiratory volume in 1 second, information on symptoms that have presented since the previous visit, details of any exacerbations that occurred, and current smoking status. When making decisions to adjust therapy, providers should examine the effectiveness of the current regimen and consider the dose of prescribed medications, whether the patient is adhering to the regimen, inhaler technique, and any side effects.

Mr. Ortiz reports also being a paid employee for Thermo Fisher, a biotechnology product development company based in Waltham, Mass. Global Academy for Medical Education and this news organization are owned by the same parent company.


 

ORLANDO – Inhaler choice for patients with chronic obstructive pulmonary disease (COPD) should be chosen on the basis of access, cost, prescriber, patient ability, and patient preference.

That’s according to Gabriel Ortiz, MPAS, PA-C, DFAAPA, a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

There are several treatment options available in inhaler form for patients with COPD, including short-acting and long-acting beta₂-agonists (SABA/LABA), short-acting and long-acting antimuscarinics (SAMA/LAMA), combination therapy, and triple therapy. But education and training on how to use an inhaler is also important, Mr. Ortiz said in his presentation.

Providers should help a patient choose an inhaler they are most likely to use. “It’s difficult to actuate and inhale, so there’s a lot of education that goes into that,” said Mr. Ortiz, of Pediatric Pulmonary Services in El Paso, Texas. “What we do for our patients is, we educate them, we tell them to demonstrate it, then bring [the] inhaler back on the next visit and demonstrate to us every time.”

“Make sure that they demonstrate because, as patients get older, they may lose their ability to actuate and inhale,” he added.

Adherence to therapy should also be considered before changing from a current therapy, he added. Mr. Ortiz described a scenario in which a prescription was filled, but because of the cost, the patient reduced the dose by half to make the therapy last longer.

“We could be the best providers in the world, prescribing the best medication in the world. If the medication doesn’t get to where we need it, it’s not going to help anybody,” he said.

Providers should also use nonpharmacological treatments to prevent or keep COPD from progressing. Smoking cessation is key to reducing the risk of developing COPD, and it is not clear whether e-cigarettes aid in smoking cessation, despite companies that market these products making that claim. “We have a huge e-cigarette epidemic here,” he said.

Instead, Mr. Ortiz recommended identifying which patients are current tobacco users, encouraging them to quit, determining whether the patient is willing to make a commitment to cut down on tobacco use or stop entirely, helping draft a quit plan and obtaining intra- and extratreatment social support for smoking cessation, and scheduling follow-up. Providers should discuss smoking cessation at each visit, and it may take multiple visits before a patient is willing to consider quitting, he said.

Another measure providers can take is making sure patients with COPD have received influenza and pneumococcal vaccinations because this can lower the risk of respiratory tract infections. Physical activity, training in exercise, nutritional support, and pulmonary rehabilitation can improve their health status, dyspnea, and exercise tolerance. While C-level evidence shows education alone is not effective according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, providers working with patients through self-management interventions have been shown to improve health status and decrease COPD-related hospitalizations.

Oxygen therapy has been effective for patients with severe resting chronic hypoxia and improves survival, said Mr. Ortiz. For patients who gradually decline in health despite treatment, palliative, hospice, and end-of-life care may be an option. “Remember that as acute exacerbations continue, that increases the risk of death,” he said. “We want to try and prevent [those] exacerbations and improve quality of life.”

During follow-up visits, providers should continue performing spirometry tests annually to measure decline in forced expiratory volume in 1 second, information on symptoms that have presented since the previous visit, details of any exacerbations that occurred, and current smoking status. When making decisions to adjust therapy, providers should examine the effectiveness of the current regimen and consider the dose of prescribed medications, whether the patient is adhering to the regimen, inhaler technique, and any side effects.

Mr. Ortiz reports also being a paid employee for Thermo Fisher, a biotechnology product development company based in Waltham, Mass. Global Academy for Medical Education and this news organization are owned by the same parent company.


 

The Food and Drug Administration Arthritis Advisory Committee recommended approval of nintedanib for the treatment of interstitial lung disease in patients with systemic sclerosis by a 10-7 vote on July 25, 2019. If the FDA acts in accord with the panel’s recommendation, it would make nintedanib (Ofev) the first drug to receive marketing approval for this indication.

Nintedanib has had FDA approval for treating idiopathic pulmonary fibrosis since 2014, and the manufacturer, Boehringer Ingelheim, designed the current pivotal trial with 576 patients to broaden the indication to patients with a different but similar fibrotic lung disease, interstitial lung disease (ILD), that is a common and eventually lethal complication of systemic sclerosis. The results of the pivotal study, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) trial, recently appeared in print and showed that patients randomized to receive 150 mg of nintedanib orally twice daily had an average 41-mL cut in the rate of loss of forced vital capacity (FVC) during 52 weeks on treatment, compared with those randomized to placebo. This was a 44% relative reduction in rate of FVC loss that was statistically significant for the study’s primary endpoint (N Engl J Med. 2019 June 27;380[26]:2518-28).

Votes in favor of FDA approval for many on the panel seemed to stem from a combination of the fact that nintedanib met the pivotal trial’s primary endpoint; which had been developed in consultation with the FDA, as well as the absence of any new safety signals when compared with prior experience using the drug; the lack of any treatment specifically recognized as beneficial to systemic sclerosis patients who develop the terminal complication of ILD; and the challenge of running a second trial in an orphan disease with an estimated U.S. prevalence of no more than 100,000 patients. Several committee members who voted in favor of nintedanib’s approval also voiced concern that the case in favor of its benefit/risk balance was not open and shut.

“I have a fair amount of apprehension,” admitted the committee’s chair, Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School, Boston. “I support the needs of patients, but we don’t want to give them false hope. We need to be able to say who will benefit, and the single study [SENSCIS] results don’t tell us how to use the drug. I want to understand which patient subgroups benefit.” He suggested that the FDA mandate further data collection through postmarketing studies.

Comments from panel members who voted against recommending approval generally focused on what was generally agreed to be a very modest treatment effect with a 41-mL average difference in FVC decline that has marginal clinical meaningfulness. Although the SENSCIS results met the study’s primary endpoint it was neutral for all prespecified secondary endpoints, including a measure of quality of life, although many on the panel agreed that a good measure of quality of life in the target patient population is lacking. Some sensitivity analyses run by FDA staffers also failed to confirm the primary result. Fewer questions arose about safety, although some panelists expressed concern about gastrointestinal effects, especially diarrhea, that seemed to link with treatment, as well as a signal for an increased incidence of pneumonia among patients on nintedanib. The data also showed a possible signal of reduced efficacy among patients who also received treatment with the immunosuppressive agent mycophenolate mofetil, often used off label to treat systemic sclerosis patients with ILD. However, a statistician involved in the discussion warned against overinterpreting this or other subgroup analyses.

Dr. Solomon has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer.

mzoler@mdedge.com

The Food and Drug Administration Arthritis Advisory Committee recommended approval of nintedanib for the treatment of interstitial lung disease in patients with systemic sclerosis by a 10-7 vote on July 25, 2019. If the FDA acts in accord with the panel’s recommendation, it would make nintedanib (Ofev) the first drug to receive marketing approval for this indication.

Nintedanib has had FDA approval for treating idiopathic pulmonary fibrosis since 2014, and the manufacturer, Boehringer Ingelheim, designed the current pivotal trial with 576 patients to broaden the indication to patients with a different but similar fibrotic lung disease, interstitial lung disease (ILD), that is a common and eventually lethal complication of systemic sclerosis. The results of the pivotal study, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) trial, recently appeared in print and showed that patients randomized to receive 150 mg of nintedanib orally twice daily had an average 41-mL cut in the rate of loss of forced vital capacity (FVC) during 52 weeks on treatment, compared with those randomized to placebo. This was a 44% relative reduction in rate of FVC loss that was statistically significant for the study’s primary endpoint (N Engl J Med. 2019 June 27;380[26]:2518-28).

Votes in favor of FDA approval for many on the panel seemed to stem from a combination of the fact that nintedanib met the pivotal trial’s primary endpoint; which had been developed in consultation with the FDA, as well as the absence of any new safety signals when compared with prior experience using the drug; the lack of any treatment specifically recognized as beneficial to systemic sclerosis patients who develop the terminal complication of ILD; and the challenge of running a second trial in an orphan disease with an estimated U.S. prevalence of no more than 100,000 patients. Several committee members who voted in favor of nintedanib’s approval also voiced concern that the case in favor of its benefit/risk balance was not open and shut.

“I have a fair amount of apprehension,” admitted the committee’s chair, Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School, Boston. “I support the needs of patients, but we don’t want to give them false hope. We need to be able to say who will benefit, and the single study [SENSCIS] results don’t tell us how to use the drug. I want to understand which patient subgroups benefit.” He suggested that the FDA mandate further data collection through postmarketing studies.

Comments from panel members who voted against recommending approval generally focused on what was generally agreed to be a very modest treatment effect with a 41-mL average difference in FVC decline that has marginal clinical meaningfulness. Although the SENSCIS results met the study’s primary endpoint it was neutral for all prespecified secondary endpoints, including a measure of quality of life, although many on the panel agreed that a good measure of quality of life in the target patient population is lacking. Some sensitivity analyses run by FDA staffers also failed to confirm the primary result. Fewer questions arose about safety, although some panelists expressed concern about gastrointestinal effects, especially diarrhea, that seemed to link with treatment, as well as a signal for an increased incidence of pneumonia among patients on nintedanib. The data also showed a possible signal of reduced efficacy among patients who also received treatment with the immunosuppressive agent mycophenolate mofetil, often used off label to treat systemic sclerosis patients with ILD. However, a statistician involved in the discussion warned against overinterpreting this or other subgroup analyses.

Dr. Solomon has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer.

mzoler@mdedge.com

The Food and Drug Administration Arthritis Advisory Committee recommended approval of nintedanib for the treatment of interstitial lung disease in patients with systemic sclerosis by a 10-7 vote on July 25, 2019. If the FDA acts in accord with the panel’s recommendation, it would make nintedanib (Ofev) the first drug to receive marketing approval for this indication.

Nintedanib has had FDA approval for treating idiopathic pulmonary fibrosis since 2014, and the manufacturer, Boehringer Ingelheim, designed the current pivotal trial with 576 patients to broaden the indication to patients with a different but similar fibrotic lung disease, interstitial lung disease (ILD), that is a common and eventually lethal complication of systemic sclerosis. The results of the pivotal study, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) trial, recently appeared in print and showed that patients randomized to receive 150 mg of nintedanib orally twice daily had an average 41-mL cut in the rate of loss of forced vital capacity (FVC) during 52 weeks on treatment, compared with those randomized to placebo. This was a 44% relative reduction in rate of FVC loss that was statistically significant for the study’s primary endpoint (N Engl J Med. 2019 June 27;380[26]:2518-28).

Votes in favor of FDA approval for many on the panel seemed to stem from a combination of the fact that nintedanib met the pivotal trial’s primary endpoint; which had been developed in consultation with the FDA, as well as the absence of any new safety signals when compared with prior experience using the drug; the lack of any treatment specifically recognized as beneficial to systemic sclerosis patients who develop the terminal complication of ILD; and the challenge of running a second trial in an orphan disease with an estimated U.S. prevalence of no more than 100,000 patients. Several committee members who voted in favor of nintedanib’s approval also voiced concern that the case in favor of its benefit/risk balance was not open and shut.

“I have a fair amount of apprehension,” admitted the committee’s chair, Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School, Boston. “I support the needs of patients, but we don’t want to give them false hope. We need to be able to say who will benefit, and the single study [SENSCIS] results don’t tell us how to use the drug. I want to understand which patient subgroups benefit.” He suggested that the FDA mandate further data collection through postmarketing studies.

Comments from panel members who voted against recommending approval generally focused on what was generally agreed to be a very modest treatment effect with a 41-mL average difference in FVC decline that has marginal clinical meaningfulness. Although the SENSCIS results met the study’s primary endpoint it was neutral for all prespecified secondary endpoints, including a measure of quality of life, although many on the panel agreed that a good measure of quality of life in the target patient population is lacking. Some sensitivity analyses run by FDA staffers also failed to confirm the primary result. Fewer questions arose about safety, although some panelists expressed concern about gastrointestinal effects, especially diarrhea, that seemed to link with treatment, as well as a signal for an increased incidence of pneumonia among patients on nintedanib. The data also showed a possible signal of reduced efficacy among patients who also received treatment with the immunosuppressive agent mycophenolate mofetil, often used off label to treat systemic sclerosis patients with ILD. However, a statistician involved in the discussion warned against overinterpreting this or other subgroup analyses.

Dr. Solomon has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer.

mzoler@mdedge.com

Concomitant administration of pneumococcal and meningococcal vaccines is not only safe but also offers the potential to improve vaccine uptake and reduce the number of doctors’ visits required for routine vaccination, advised Marco Aurelio P. Safadi, MD, PhD, of Santa Casa de São Paulo School of Medical Sciences, Brazil, and associates.

MarianVejcik/Getty Images

In a post hoc analysis of a phase 3b open-label study, Dr. Safadi and associates sought to evaluate immune response in pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) administered concomitantly with either meningococcal serogroup B (4CMenB) vaccine and CRM-conjugated meningococcal serogroup C vaccine (MenC-CRM) or with MenC-CRM alone using reduced schedules in 213 healthy infants aged 83-104 days. Study participants were enrolled and randomized to one of two groups between April 2011 and December 2014 at four sites in Brazil (Vaccine. 2019 Jul 18. doi: 10.1016/j.vaccine.2019.07.021).

Similar immune response was seen with vaccine serotypes and vaccine-related pneumococcal serotypes 6A and 19A in children who had received concomitant administration of PHiD-CV, 4CMenB, and MenC-CRM without 4CMenB.

Dr. Safadi and associates pointed out that PHiD-CV was given in accordance with a 3+1 dosing schedule, while 4CMenB used a reduced 2+1 schedule, which was observed to produce an immune response and provide an acceptable safety profile.

The findings yielded valuable information for the 2+1 PHiD-CV vaccination schedule, which was recently introduced in Brazil, the researchers said. The post-booster results further reflect the “immunogenicity following 3-dose priming.”

The post hoc nature of this study design effectively demonstrated that “PHiD-CV was immunogenic for the 10 vaccine serotypes and vaccine-related serotypes 6A and 19A” when given at the same time with 4CMenB and MenC-CRM or with MenC-CRM alone, they explained.

The study was supported by GlaxoSmithKline (GSK) Biologicals. Three authors are employees of the GSK group of companies, and three others received a grant from the GSK companies, two of whom received compensation from other pharmaceutical companies. The institution of one of the authors received clinical trial fees from the GSK companies, and received personal fees/nonfinancial support/grants/other from the GSK companies and many other pharmaceutical companies.

Concomitant administration of pneumococcal and meningococcal vaccines is not only safe but also offers the potential to improve vaccine uptake and reduce the number of doctors’ visits required for routine vaccination, advised Marco Aurelio P. Safadi, MD, PhD, of Santa Casa de São Paulo School of Medical Sciences, Brazil, and associates.

MarianVejcik/Getty Images

In a post hoc analysis of a phase 3b open-label study, Dr. Safadi and associates sought to evaluate immune response in pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) administered concomitantly with either meningococcal serogroup B (4CMenB) vaccine and CRM-conjugated meningococcal serogroup C vaccine (MenC-CRM) or with MenC-CRM alone using reduced schedules in 213 healthy infants aged 83-104 days. Study participants were enrolled and randomized to one of two groups between April 2011 and December 2014 at four sites in Brazil (Vaccine. 2019 Jul 18. doi: 10.1016/j.vaccine.2019.07.021).

Similar immune response was seen with vaccine serotypes and vaccine-related pneumococcal serotypes 6A and 19A in children who had received concomitant administration of PHiD-CV, 4CMenB, and MenC-CRM without 4CMenB.

Dr. Safadi and associates pointed out that PHiD-CV was given in accordance with a 3+1 dosing schedule, while 4CMenB used a reduced 2+1 schedule, which was observed to produce an immune response and provide an acceptable safety profile.

The findings yielded valuable information for the 2+1 PHiD-CV vaccination schedule, which was recently introduced in Brazil, the researchers said. The post-booster results further reflect the “immunogenicity following 3-dose priming.”

The post hoc nature of this study design effectively demonstrated that “PHiD-CV was immunogenic for the 10 vaccine serotypes and vaccine-related serotypes 6A and 19A” when given at the same time with 4CMenB and MenC-CRM or with MenC-CRM alone, they explained.

The study was supported by GlaxoSmithKline (GSK) Biologicals. Three authors are employees of the GSK group of companies, and three others received a grant from the GSK companies, two of whom received compensation from other pharmaceutical companies. The institution of one of the authors received clinical trial fees from the GSK companies, and received personal fees/nonfinancial support/grants/other from the GSK companies and many other pharmaceutical companies.

Concomitant administration of pneumococcal and meningococcal vaccines is not only safe but also offers the potential to improve vaccine uptake and reduce the number of doctors’ visits required for routine vaccination, advised Marco Aurelio P. Safadi, MD, PhD, of Santa Casa de São Paulo School of Medical Sciences, Brazil, and associates.

MarianVejcik/Getty Images

In a post hoc analysis of a phase 3b open-label study, Dr. Safadi and associates sought to evaluate immune response in pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) administered concomitantly with either meningococcal serogroup B (4CMenB) vaccine and CRM-conjugated meningococcal serogroup C vaccine (MenC-CRM) or with MenC-CRM alone using reduced schedules in 213 healthy infants aged 83-104 days. Study participants were enrolled and randomized to one of two groups between April 2011 and December 2014 at four sites in Brazil (Vaccine. 2019 Jul 18. doi: 10.1016/j.vaccine.2019.07.021).

Similar immune response was seen with vaccine serotypes and vaccine-related pneumococcal serotypes 6A and 19A in children who had received concomitant administration of PHiD-CV, 4CMenB, and MenC-CRM without 4CMenB.

Dr. Safadi and associates pointed out that PHiD-CV was given in accordance with a 3+1 dosing schedule, while 4CMenB used a reduced 2+1 schedule, which was observed to produce an immune response and provide an acceptable safety profile.

The findings yielded valuable information for the 2+1 PHiD-CV vaccination schedule, which was recently introduced in Brazil, the researchers said. The post-booster results further reflect the “immunogenicity following 3-dose priming.”

The post hoc nature of this study design effectively demonstrated that “PHiD-CV was immunogenic for the 10 vaccine serotypes and vaccine-related serotypes 6A and 19A” when given at the same time with 4CMenB and MenC-CRM or with MenC-CRM alone, they explained.

The study was supported by GlaxoSmithKline (GSK) Biologicals. Three authors are employees of the GSK group of companies, and three others received a grant from the GSK companies, two of whom received compensation from other pharmaceutical companies. The institution of one of the authors received clinical trial fees from the GSK companies, and received personal fees/nonfinancial support/grants/other from the GSK companies and many other pharmaceutical companies.

Exposure to air pollution may contribute to significant reductions in life expectancy in the United States, particularly among lower-income populations, research suggests.

copyright Sergiy Serdyuk/istockphoto.com

A study published in PLOS Medicine used vital registration and population data from across the United States for 1999-2015 to estimate the number of deaths and loss of life expectancy associated with four different models of concentrations of fine particulate matter pollution, and examine how that has changed over time.

While the current national ambient air quality standard for particle pollution is 12 mcg/m³ in almost all counties, the study found that in 1999, 59% of the 1,339 county units had concentrations above this level. At that time, the population-weighted average fine particulate matter pollution concentration for the entire country was 13.6mcg/m³. The highest level was seen in Fresno county in California, which had a fine particulate pollution concentration of 22.1 mcg/m³.

By 2015, national concentrations had declined to 8.0 mcg/m³, and the lowest observed concentration was 2.8 mcg/m³.

The investigators wrote, “Each model was applied to county-level cardiorespiratory death rates separately by sex and age group (5-year age groups from birth to 85 years and 85 years and older) because death rates vary by age group and sex, as might their associations with air pollution. From each model we estimated age-specific proportional increases in death rates (i.e. rate ratios) for each 1 mcg/m³ of PM_2.5 [fine particulate matter].” The analysis revealed that fine particulate matter pollution above the lowest observed concentration of 2.8 mcg/m³ was associated with higher death rates from cardiorespiratory diseases.

Overall, researchers estimated that these higher levels contributed to 15,612 deaths from cardiorespiratory diseases in women and 14,757 deaths in men, representing 2.8% and 2.7% of all cardiorespiratory deaths, respectively. This amounted to 0.15 years of life expectancy lost in women and 0.13 years lost in men.

There was significant variation in the cost to life expectancy around the country. In the midwestern and Rocky Mountain counties in states such as New Mexico, Colorado, and Arizona, which had lower levels of air pollution, life expectancy loss was less than 0.05 years. But in southern states where the air pollution levels were highest, such as Arkansas, Oklahoma, Alabama, and around Los Angeles, the life expectancy loss was greater than 0.3 years.

“While current PM_2.5 pollution is responsible for a significant mortality burden and loss of longevity, reductions in pollution since the late 1990s have benefited virtually the entire country, with the exception of 14 counties where PM_2.5 increased slightly over this period,” wrote James E. Bennett, PhD, of the School of Public Health at Imperial College London and coauthors.

The primary limitation of the study is that this association between air pollution and cardiorespiratory health or life expectancy cannot be shown to be causal. Other pollutants and other environmental and behavioral factors that impact cardiorespiratory health may be significant. For example, including ozone and nitrogen dioxide levels in the models could result in different results in terms of the impact of PM2.5 on cardiorespiratory health.

The data highlighted that life expectancy loss associated with air pollution was larger in lower-income counties, those where a higher proportion of the population had a family income below the poverty line, and those where a higher proportion of the population were black or African American.

“This inequality in mortality burden occurs because lower-income counties, those with more poverty, with a greater proportion who are of black or African American race, or with a lower proportion who have graduated high school tend to have higher baseline death rates at any pollution level because of conditions associated with these covariates and hence experience a larger absolute number of deaths as a result of air pollution,” the authors wrote.

The study was funded by the U.S. Environmental Protection Agency and the Wellcome Trust. One author declared grants and personal fees from private industry, outside the submitted work.
 

SOURCE: Bennett JE et al. PLoS Med. 2019 Jul 23. doi: 10.1371/journal.pmed.1002856.

Exposure to air pollution may contribute to significant reductions in life expectancy in the United States, particularly among lower-income populations, research suggests.

copyright Sergiy Serdyuk/istockphoto.com

A study published in PLOS Medicine used vital registration and population data from across the United States for 1999-2015 to estimate the number of deaths and loss of life expectancy associated with four different models of concentrations of fine particulate matter pollution, and examine how that has changed over time.

While the current national ambient air quality standard for particle pollution is 12 mcg/m³ in almost all counties, the study found that in 1999, 59% of the 1,339 county units had concentrations above this level. At that time, the population-weighted average fine particulate matter pollution concentration for the entire country was 13.6mcg/m³. The highest level was seen in Fresno county in California, which had a fine particulate pollution concentration of 22.1 mcg/m³.

By 2015, national concentrations had declined to 8.0 mcg/m³, and the lowest observed concentration was 2.8 mcg/m³.

The investigators wrote, “Each model was applied to county-level cardiorespiratory death rates separately by sex and age group (5-year age groups from birth to 85 years and 85 years and older) because death rates vary by age group and sex, as might their associations with air pollution. From each model we estimated age-specific proportional increases in death rates (i.e. rate ratios) for each 1 mcg/m³ of PM_2.5 [fine particulate matter].” The analysis revealed that fine particulate matter pollution above the lowest observed concentration of 2.8 mcg/m³ was associated with higher death rates from cardiorespiratory diseases.

Overall, researchers estimated that these higher levels contributed to 15,612 deaths from cardiorespiratory diseases in women and 14,757 deaths in men, representing 2.8% and 2.7% of all cardiorespiratory deaths, respectively. This amounted to 0.15 years of life expectancy lost in women and 0.13 years lost in men.

There was significant variation in the cost to life expectancy around the country. In the midwestern and Rocky Mountain counties in states such as New Mexico, Colorado, and Arizona, which had lower levels of air pollution, life expectancy loss was less than 0.05 years. But in southern states where the air pollution levels were highest, such as Arkansas, Oklahoma, Alabama, and around Los Angeles, the life expectancy loss was greater than 0.3 years.

“While current PM_2.5 pollution is responsible for a significant mortality burden and loss of longevity, reductions in pollution since the late 1990s have benefited virtually the entire country, with the exception of 14 counties where PM_2.5 increased slightly over this period,” wrote James E. Bennett, PhD, of the School of Public Health at Imperial College London and coauthors.

The primary limitation of the study is that this association between air pollution and cardiorespiratory health or life expectancy cannot be shown to be causal. Other pollutants and other environmental and behavioral factors that impact cardiorespiratory health may be significant. For example, including ozone and nitrogen dioxide levels in the models could result in different results in terms of the impact of PM2.5 on cardiorespiratory health.

The data highlighted that life expectancy loss associated with air pollution was larger in lower-income counties, those where a higher proportion of the population had a family income below the poverty line, and those where a higher proportion of the population were black or African American.

“This inequality in mortality burden occurs because lower-income counties, those with more poverty, with a greater proportion who are of black or African American race, or with a lower proportion who have graduated high school tend to have higher baseline death rates at any pollution level because of conditions associated with these covariates and hence experience a larger absolute number of deaths as a result of air pollution,” the authors wrote.

The study was funded by the U.S. Environmental Protection Agency and the Wellcome Trust. One author declared grants and personal fees from private industry, outside the submitted work.
 

SOURCE: Bennett JE et al. PLoS Med. 2019 Jul 23. doi: 10.1371/journal.pmed.1002856.

Exposure to air pollution may contribute to significant reductions in life expectancy in the United States, particularly among lower-income populations, research suggests.

copyright Sergiy Serdyuk/istockphoto.com

A study published in PLOS Medicine used vital registration and population data from across the United States for 1999-2015 to estimate the number of deaths and loss of life expectancy associated with four different models of concentrations of fine particulate matter pollution, and examine how that has changed over time.

While the current national ambient air quality standard for particle pollution is 12 mcg/m³ in almost all counties, the study found that in 1999, 59% of the 1,339 county units had concentrations above this level. At that time, the population-weighted average fine particulate matter pollution concentration for the entire country was 13.6mcg/m³. The highest level was seen in Fresno county in California, which had a fine particulate pollution concentration of 22.1 mcg/m³.

By 2015, national concentrations had declined to 8.0 mcg/m³, and the lowest observed concentration was 2.8 mcg/m³.

The investigators wrote, “Each model was applied to county-level cardiorespiratory death rates separately by sex and age group (5-year age groups from birth to 85 years and 85 years and older) because death rates vary by age group and sex, as might their associations with air pollution. From each model we estimated age-specific proportional increases in death rates (i.e. rate ratios) for each 1 mcg/m³ of PM_2.5 [fine particulate matter].” The analysis revealed that fine particulate matter pollution above the lowest observed concentration of 2.8 mcg/m³ was associated with higher death rates from cardiorespiratory diseases.

Overall, researchers estimated that these higher levels contributed to 15,612 deaths from cardiorespiratory diseases in women and 14,757 deaths in men, representing 2.8% and 2.7% of all cardiorespiratory deaths, respectively. This amounted to 0.15 years of life expectancy lost in women and 0.13 years lost in men.

There was significant variation in the cost to life expectancy around the country. In the midwestern and Rocky Mountain counties in states such as New Mexico, Colorado, and Arizona, which had lower levels of air pollution, life expectancy loss was less than 0.05 years. But in southern states where the air pollution levels were highest, such as Arkansas, Oklahoma, Alabama, and around Los Angeles, the life expectancy loss was greater than 0.3 years.

“While current PM_2.5 pollution is responsible for a significant mortality burden and loss of longevity, reductions in pollution since the late 1990s have benefited virtually the entire country, with the exception of 14 counties where PM_2.5 increased slightly over this period,” wrote James E. Bennett, PhD, of the School of Public Health at Imperial College London and coauthors.

The primary limitation of the study is that this association between air pollution and cardiorespiratory health or life expectancy cannot be shown to be causal. Other pollutants and other environmental and behavioral factors that impact cardiorespiratory health may be significant. For example, including ozone and nitrogen dioxide levels in the models could result in different results in terms of the impact of PM2.5 on cardiorespiratory health.

The data highlighted that life expectancy loss associated with air pollution was larger in lower-income counties, those where a higher proportion of the population had a family income below the poverty line, and those where a higher proportion of the population were black or African American.

“This inequality in mortality burden occurs because lower-income counties, those with more poverty, with a greater proportion who are of black or African American race, or with a lower proportion who have graduated high school tend to have higher baseline death rates at any pollution level because of conditions associated with these covariates and hence experience a larger absolute number of deaths as a result of air pollution,” the authors wrote.

The study was funded by the U.S. Environmental Protection Agency and the Wellcome Trust. One author declared grants and personal fees from private industry, outside the submitted work.
 

SOURCE: Bennett JE et al. PLoS Med. 2019 Jul 23. doi: 10.1371/journal.pmed.1002856.