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Inflammation and immunosuppression could persist for some patients up to a year after a hospitalization for sepsis, and these patients were more likely to experience worsened long-term outcomes, readmission after discharge, and mortality, according to a study published in JAMA Network Open.

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“Individuals with persistent biomarkers of inflammation and immunosuppression had a higher risk of readmission and death due to cardiovascular disease and cancer compared with those with normal circulating biomarkers,” Sachin Yende, MD, of the VA Pittsburgh Healthcare System and the University of Pittsburgh and colleagues wrote in their study. “Our findings suggest that long-term immunomodulation strategies should be explored in patients hospitalized with sepsis.”

Dr. Yende and colleagues performed a multicenter, prospective cohort study of 483 patients who were hospitalized for sepsis at 12 different sites between January 2012 and May 2017. They measured inflammation using interleukin-6, high-sensitivity C-reactive protein (hs-CRP), and soluble programmed death-ligand 1 (sPD-L1); hemostasis using plasminogen activator inhibitor 1 and D-dimer; and endothelial dysfunction using intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. The patients included were mean age 60.5 years, 54.9% were male, the mean Sequential Organ Failure Assessment score was 4.2, and a total of 376 patients (77.8%) had one or more chronic diseases.

Overall, there were 485 readmissions in 205 patients (42.5%). The mortality rate was 43 patients (8.9%) at 3 months, 56 patients (11.6%) at 6 months, and 85 patients (17.6%) at 12 months. At 3 months, 23 patients (25.8%) had elevated hs-CRP levels, which increased to 26 patients (30.2%) at 6 months and 40 patients (44.9%) at 12 months. sPD-L1 levels were elevated in 45 patients (46.4%) at 3 months, but the number of patients with elevated sPD-L1 did not appear to significantly increase at 6 months (40 patients; 44.9%) or 12 months (44 patients; 49.4%).

From these results, researchers developed a phenotype of hyperinflammation and immunosuppression that consisted of 326 of 477 (68.3%) patients with high hs-CRP and elevated sPD-L1 levels. Patients with this phenotype of hyperinflammation and immunosuppression had more than eight times the risk of 1-year mortality (odds ratio, 8.26; 95% confidence interval, 3.45-21.69; P less than .001) and more than five times the risk of readmission or mortality at 6 months related to cardiovascular disease (hazard ratio, 5.07; 95% CI, 1.18-21.84; P = .02) or cancer (hazard ratio, 5.15; 95% CI, 1.25-21.18; P = .02), compared with patients who had normal hs-CRP and sPD-L1 levels. This hyperinflammation and immunosuppression phenotype also was associated with greater risk of 6-month all-cause readmission or mortality (HR, 1.53; 95% CI, 1.10-2.13; P = .01), compared with patients who had the normal phenotype.

“The persistence of hyperinflammation in a large number of sepsis survivors and the increased risk of cardiovascular events among these patients may explain the association between infection and cardiovascular disease in a prior study,” the authors said. “Although prior trials tested immunomodulation strategies during only the early phase of hospitalization for sepsis, immunomodulation may be needed after hospital discharge,” and suggest points of future study for patients who survive sepsis and develop long-term sequelae.

This study was funded by grants from National Institutes of Health and resources from the VA Pittsburgh Healthcare System. The authors reported personal and institutional relationships in the form of personal fees, grants, and patents for Alung Technologies, Atox Bio, Bayer AG, Beckman Coulter, BristolMyers Squibb, Ferring, NIH, Roche, Selepressin, and the University of Pittsburgh.

SOURCE: Yende S et al. JAMA Netw Open. 2019 Aug 7. doi: 10.1001/jamanetworkopen.2019.8686.

Inflammation and immunosuppression could persist for some patients up to a year after a hospitalization for sepsis, and these patients were more likely to experience worsened long-term outcomes, readmission after discharge, and mortality, according to a study published in JAMA Network Open.

141820

“Individuals with persistent biomarkers of inflammation and immunosuppression had a higher risk of readmission and death due to cardiovascular disease and cancer compared with those with normal circulating biomarkers,” Sachin Yende, MD, of the VA Pittsburgh Healthcare System and the University of Pittsburgh and colleagues wrote in their study. “Our findings suggest that long-term immunomodulation strategies should be explored in patients hospitalized with sepsis.”

Dr. Yende and colleagues performed a multicenter, prospective cohort study of 483 patients who were hospitalized for sepsis at 12 different sites between January 2012 and May 2017. They measured inflammation using interleukin-6, high-sensitivity C-reactive protein (hs-CRP), and soluble programmed death-ligand 1 (sPD-L1); hemostasis using plasminogen activator inhibitor 1 and D-dimer; and endothelial dysfunction using intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. The patients included were mean age 60.5 years, 54.9% were male, the mean Sequential Organ Failure Assessment score was 4.2, and a total of 376 patients (77.8%) had one or more chronic diseases.

Overall, there were 485 readmissions in 205 patients (42.5%). The mortality rate was 43 patients (8.9%) at 3 months, 56 patients (11.6%) at 6 months, and 85 patients (17.6%) at 12 months. At 3 months, 23 patients (25.8%) had elevated hs-CRP levels, which increased to 26 patients (30.2%) at 6 months and 40 patients (44.9%) at 12 months. sPD-L1 levels were elevated in 45 patients (46.4%) at 3 months, but the number of patients with elevated sPD-L1 did not appear to significantly increase at 6 months (40 patients; 44.9%) or 12 months (44 patients; 49.4%).

From these results, researchers developed a phenotype of hyperinflammation and immunosuppression that consisted of 326 of 477 (68.3%) patients with high hs-CRP and elevated sPD-L1 levels. Patients with this phenotype of hyperinflammation and immunosuppression had more than eight times the risk of 1-year mortality (odds ratio, 8.26; 95% confidence interval, 3.45-21.69; P less than .001) and more than five times the risk of readmission or mortality at 6 months related to cardiovascular disease (hazard ratio, 5.07; 95% CI, 1.18-21.84; P = .02) or cancer (hazard ratio, 5.15; 95% CI, 1.25-21.18; P = .02), compared with patients who had normal hs-CRP and sPD-L1 levels. This hyperinflammation and immunosuppression phenotype also was associated with greater risk of 6-month all-cause readmission or mortality (HR, 1.53; 95% CI, 1.10-2.13; P = .01), compared with patients who had the normal phenotype.

“The persistence of hyperinflammation in a large number of sepsis survivors and the increased risk of cardiovascular events among these patients may explain the association between infection and cardiovascular disease in a prior study,” the authors said. “Although prior trials tested immunomodulation strategies during only the early phase of hospitalization for sepsis, immunomodulation may be needed after hospital discharge,” and suggest points of future study for patients who survive sepsis and develop long-term sequelae.

This study was funded by grants from National Institutes of Health and resources from the VA Pittsburgh Healthcare System. The authors reported personal and institutional relationships in the form of personal fees, grants, and patents for Alung Technologies, Atox Bio, Bayer AG, Beckman Coulter, BristolMyers Squibb, Ferring, NIH, Roche, Selepressin, and the University of Pittsburgh.

SOURCE: Yende S et al. JAMA Netw Open. 2019 Aug 7. doi: 10.1001/jamanetworkopen.2019.8686.

Inflammation and immunosuppression could persist for some patients up to a year after a hospitalization for sepsis, and these patients were more likely to experience worsened long-term outcomes, readmission after discharge, and mortality, according to a study published in JAMA Network Open.

141820

“Individuals with persistent biomarkers of inflammation and immunosuppression had a higher risk of readmission and death due to cardiovascular disease and cancer compared with those with normal circulating biomarkers,” Sachin Yende, MD, of the VA Pittsburgh Healthcare System and the University of Pittsburgh and colleagues wrote in their study. “Our findings suggest that long-term immunomodulation strategies should be explored in patients hospitalized with sepsis.”

Dr. Yende and colleagues performed a multicenter, prospective cohort study of 483 patients who were hospitalized for sepsis at 12 different sites between January 2012 and May 2017. They measured inflammation using interleukin-6, high-sensitivity C-reactive protein (hs-CRP), and soluble programmed death-ligand 1 (sPD-L1); hemostasis using plasminogen activator inhibitor 1 and D-dimer; and endothelial dysfunction using intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. The patients included were mean age 60.5 years, 54.9% were male, the mean Sequential Organ Failure Assessment score was 4.2, and a total of 376 patients (77.8%) had one or more chronic diseases.

Overall, there were 485 readmissions in 205 patients (42.5%). The mortality rate was 43 patients (8.9%) at 3 months, 56 patients (11.6%) at 6 months, and 85 patients (17.6%) at 12 months. At 3 months, 23 patients (25.8%) had elevated hs-CRP levels, which increased to 26 patients (30.2%) at 6 months and 40 patients (44.9%) at 12 months. sPD-L1 levels were elevated in 45 patients (46.4%) at 3 months, but the number of patients with elevated sPD-L1 did not appear to significantly increase at 6 months (40 patients; 44.9%) or 12 months (44 patients; 49.4%).

From these results, researchers developed a phenotype of hyperinflammation and immunosuppression that consisted of 326 of 477 (68.3%) patients with high hs-CRP and elevated sPD-L1 levels. Patients with this phenotype of hyperinflammation and immunosuppression had more than eight times the risk of 1-year mortality (odds ratio, 8.26; 95% confidence interval, 3.45-21.69; P less than .001) and more than five times the risk of readmission or mortality at 6 months related to cardiovascular disease (hazard ratio, 5.07; 95% CI, 1.18-21.84; P = .02) or cancer (hazard ratio, 5.15; 95% CI, 1.25-21.18; P = .02), compared with patients who had normal hs-CRP and sPD-L1 levels. This hyperinflammation and immunosuppression phenotype also was associated with greater risk of 6-month all-cause readmission or mortality (HR, 1.53; 95% CI, 1.10-2.13; P = .01), compared with patients who had the normal phenotype.

“The persistence of hyperinflammation in a large number of sepsis survivors and the increased risk of cardiovascular events among these patients may explain the association between infection and cardiovascular disease in a prior study,” the authors said. “Although prior trials tested immunomodulation strategies during only the early phase of hospitalization for sepsis, immunomodulation may be needed after hospital discharge,” and suggest points of future study for patients who survive sepsis and develop long-term sequelae.

This study was funded by grants from National Institutes of Health and resources from the VA Pittsburgh Healthcare System. The authors reported personal and institutional relationships in the form of personal fees, grants, and patents for Alung Technologies, Atox Bio, Bayer AG, Beckman Coulter, BristolMyers Squibb, Ferring, NIH, Roche, Selepressin, and the University of Pittsburgh.

SOURCE: Yende S et al. JAMA Netw Open. 2019 Aug 7. doi: 10.1001/jamanetworkopen.2019.8686.

LJUBLJANA, SLOVENIA – Encouraging safety and immunogenicity results reported from phase 1 studies of the first mRNA vaccines against the potentially pandemic H10N8 avian influenza and H7N9 influenza viruses suggest a bright future for what appears to be a breakthrough technology in vaccine development.

Bruce Jancin/MDedge News

“We have developed an mRNA platform that has the potential to be quite applicable to the vaccine space. It’s an agile platform with the potential for relatively rapid development of vaccine antigen without the use of dedicated facilities, or growth in eggs, or insects, or mammalian cells,” Lori Panther, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

“We now have a platform that is relatively plug and play. If one has the mRNA sequence that you’re after to produce the protein that you’re after, it is a relatively repetitive process somewhat irrespective of the goal of the protein that you’re going to manufacture. We’re introducing an mRNA into our cellular machinery – the destination is the cellular ribosome – where it hopefully is able to be translated with fidelity into the target protein. Essentially it’s like the biological equivalent of a software hack for our own cells,” explained Dr. Panther, who is director of clinical development for infectious diseases at Moderna, in Cambridge, Mass.

Indeed, Moderna has numerous ongoing or recently completed phase 1 clinical trials of mRNA vaccines developed to protect against a raft of viral infections: respiratory syncytial virus, cytomegalovirus (NCT03382405), zika, chikungunya (NCT03829384), human metapneumovirus, and parainfluenza virus 3, as well as the aforementioned H10N8 and H7N9 influenza viruses. And an mRNA varicella zoster virus vaccine is in preclinical studies.

The mRNA vaccines closely mimic native viral infections, eliciting both B- and T-cell responses.

Moreover, the company also has ongoing phase 1 studies of mRNA-based cancer vaccines – therapies targeting solid tumors and lymphomas – as well as mRNA-directed increased production of relaxin as a treatment for heart failure and of vascular endothelial growth factor to treat myocardial ischemia.

“For the purposes of my company, the desired protein at this juncture could be an antibody, it could be a tumor antigen, it could be an enzyme that will replace an enzyme that’s lacking in somebody with an inborn error of metabolism. Or it could be a vaccine antigen target,” Dr. Panther said.

In addition to highlighting the results of the two phase 1 proof-of-concept studies of mRNA vaccines targeting the feared H10N8 and H7N9 influenza viruses, she presented interim results of an ongoing 1-year study of an mRNA vaccine that contains two antigens simultaneously targeting human metapneumovirus (hMPV) and parainfluenza virus 3 (PIV3).

“The rationale behind this study is that, taken together, these are two viruses that are responsible for a fair bit of disease burden in terms of lower respiratory tract infections and hospitalizations in children [younger] than 12 months of age, which will be the target population,” the infectious disease specialist noted.

The early positive results of the mRNA influenza vaccine studies were of particular interest to her audience of pediatric infectious disease specialists. Since the first human H7N9 infections were reported in China in 2013, five outbreaks have occurred involving more than 1,500 documented infections, resulting in more than 600 deaths. And ever since the virulent H10N8 avian influenza virus popped up on the radar in 2013, infectious disease physicians the world over have been waiting for the other shoe to drop.

There is obvious appeal to a novel, precise, and rapidly scalable technology such as that promised by intracellular delivery of mRNA in order to ramp up high-volume production of effective vaccines in the face of a looming pandemic threat. Elsewhere at the meeting, it was noted that, during the H1N1 pandemic of 2009, it took 6 months for the first vaccine doses to become available using current antiquated egg-based production methods. Another 2 months elapsed before the necessary millions of doses were produced.

The details of the two phase 1 studies of the mRNA vaccines against H7N9 and H10N8 influenza have recently been published (Vaccine. 2019 May 31;37[25]:3326-34). The vaccines, delivered in the conventional manner via injection into the deltoid muscle, were well tolerated, with the most common adverse events being the familiar ones: injection site pain, erythema, headache, fatigue, and myalgia. The immune response was robust and durable.

In response to an audience question, Dr. Panther said the mRNA vaccines are amenable to development as intranasal formulations.

The ongoing 12-month, phase 1, dose-ranging study of the mRNA hMPV/PIV3 virus vaccine includes 124 healthy adults at three U.S. sites who received two vaccinations on days 1 and 28. One month after a single vaccination, hMPV neutralizing antibody titers were 6.2-6.4 times those in the placebo arm; PIV3 neutralization titers were increased 3.3-fold. The second injection didn’t further boost antibody titers, suggesting that, at least in this study population of preexposed adults, a single vaccination is sufficient.

The use of mRNA technology has been a long time in coming. Dr. Panther explained why: “It’s a big trick to take an mRNA that by its own nature is a pretty fragile molecule and to get it past the degrading enzymes, like RNAses, that are out to chew it up immediately, and then to sneak it across the cellular membrane and into the cytoplasm, all the while avoiding the innate immune responses that exist solely to recognize RNA that looks foreign and chew it up.”

Moderna has accomplished this using a proprietary lipid nanoparticle delivery system.

“Essentially it’s a lipid shield that surrounds the mRNAs and ushers them past those enzymes and past the innate immune response that would otherwise destroy them,” according to Dr. Panther.

She and her colleagues believe they may eventually be able to change the nucleotide sequence of their manufactured mRNAs in order to expand the immunogenicity epitope and achieve a stronger immune response than would result from natural infection.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Encouraging safety and immunogenicity results reported from phase 1 studies of the first mRNA vaccines against the potentially pandemic H10N8 avian influenza and H7N9 influenza viruses suggest a bright future for what appears to be a breakthrough technology in vaccine development.

Bruce Jancin/MDedge News

“We have developed an mRNA platform that has the potential to be quite applicable to the vaccine space. It’s an agile platform with the potential for relatively rapid development of vaccine antigen without the use of dedicated facilities, or growth in eggs, or insects, or mammalian cells,” Lori Panther, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

“We now have a platform that is relatively plug and play. If one has the mRNA sequence that you’re after to produce the protein that you’re after, it is a relatively repetitive process somewhat irrespective of the goal of the protein that you’re going to manufacture. We’re introducing an mRNA into our cellular machinery – the destination is the cellular ribosome – where it hopefully is able to be translated with fidelity into the target protein. Essentially it’s like the biological equivalent of a software hack for our own cells,” explained Dr. Panther, who is director of clinical development for infectious diseases at Moderna, in Cambridge, Mass.

Indeed, Moderna has numerous ongoing or recently completed phase 1 clinical trials of mRNA vaccines developed to protect against a raft of viral infections: respiratory syncytial virus, cytomegalovirus (NCT03382405), zika, chikungunya (NCT03829384), human metapneumovirus, and parainfluenza virus 3, as well as the aforementioned H10N8 and H7N9 influenza viruses. And an mRNA varicella zoster virus vaccine is in preclinical studies.

The mRNA vaccines closely mimic native viral infections, eliciting both B- and T-cell responses.

Moreover, the company also has ongoing phase 1 studies of mRNA-based cancer vaccines – therapies targeting solid tumors and lymphomas – as well as mRNA-directed increased production of relaxin as a treatment for heart failure and of vascular endothelial growth factor to treat myocardial ischemia.

“For the purposes of my company, the desired protein at this juncture could be an antibody, it could be a tumor antigen, it could be an enzyme that will replace an enzyme that’s lacking in somebody with an inborn error of metabolism. Or it could be a vaccine antigen target,” Dr. Panther said.

In addition to highlighting the results of the two phase 1 proof-of-concept studies of mRNA vaccines targeting the feared H10N8 and H7N9 influenza viruses, she presented interim results of an ongoing 1-year study of an mRNA vaccine that contains two antigens simultaneously targeting human metapneumovirus (hMPV) and parainfluenza virus 3 (PIV3).

“The rationale behind this study is that, taken together, these are two viruses that are responsible for a fair bit of disease burden in terms of lower respiratory tract infections and hospitalizations in children [younger] than 12 months of age, which will be the target population,” the infectious disease specialist noted.

The early positive results of the mRNA influenza vaccine studies were of particular interest to her audience of pediatric infectious disease specialists. Since the first human H7N9 infections were reported in China in 2013, five outbreaks have occurred involving more than 1,500 documented infections, resulting in more than 600 deaths. And ever since the virulent H10N8 avian influenza virus popped up on the radar in 2013, infectious disease physicians the world over have been waiting for the other shoe to drop.

There is obvious appeal to a novel, precise, and rapidly scalable technology such as that promised by intracellular delivery of mRNA in order to ramp up high-volume production of effective vaccines in the face of a looming pandemic threat. Elsewhere at the meeting, it was noted that, during the H1N1 pandemic of 2009, it took 6 months for the first vaccine doses to become available using current antiquated egg-based production methods. Another 2 months elapsed before the necessary millions of doses were produced.

The details of the two phase 1 studies of the mRNA vaccines against H7N9 and H10N8 influenza have recently been published (Vaccine. 2019 May 31;37[25]:3326-34). The vaccines, delivered in the conventional manner via injection into the deltoid muscle, were well tolerated, with the most common adverse events being the familiar ones: injection site pain, erythema, headache, fatigue, and myalgia. The immune response was robust and durable.

In response to an audience question, Dr. Panther said the mRNA vaccines are amenable to development as intranasal formulations.

The ongoing 12-month, phase 1, dose-ranging study of the mRNA hMPV/PIV3 virus vaccine includes 124 healthy adults at three U.S. sites who received two vaccinations on days 1 and 28. One month after a single vaccination, hMPV neutralizing antibody titers were 6.2-6.4 times those in the placebo arm; PIV3 neutralization titers were increased 3.3-fold. The second injection didn’t further boost antibody titers, suggesting that, at least in this study population of preexposed adults, a single vaccination is sufficient.

The use of mRNA technology has been a long time in coming. Dr. Panther explained why: “It’s a big trick to take an mRNA that by its own nature is a pretty fragile molecule and to get it past the degrading enzymes, like RNAses, that are out to chew it up immediately, and then to sneak it across the cellular membrane and into the cytoplasm, all the while avoiding the innate immune responses that exist solely to recognize RNA that looks foreign and chew it up.”

Moderna has accomplished this using a proprietary lipid nanoparticle delivery system.

“Essentially it’s a lipid shield that surrounds the mRNAs and ushers them past those enzymes and past the innate immune response that would otherwise destroy them,” according to Dr. Panther.

She and her colleagues believe they may eventually be able to change the nucleotide sequence of their manufactured mRNAs in order to expand the immunogenicity epitope and achieve a stronger immune response than would result from natural infection.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Encouraging safety and immunogenicity results reported from phase 1 studies of the first mRNA vaccines against the potentially pandemic H10N8 avian influenza and H7N9 influenza viruses suggest a bright future for what appears to be a breakthrough technology in vaccine development.

Bruce Jancin/MDedge News

“We have developed an mRNA platform that has the potential to be quite applicable to the vaccine space. It’s an agile platform with the potential for relatively rapid development of vaccine antigen without the use of dedicated facilities, or growth in eggs, or insects, or mammalian cells,” Lori Panther, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

“We now have a platform that is relatively plug and play. If one has the mRNA sequence that you’re after to produce the protein that you’re after, it is a relatively repetitive process somewhat irrespective of the goal of the protein that you’re going to manufacture. We’re introducing an mRNA into our cellular machinery – the destination is the cellular ribosome – where it hopefully is able to be translated with fidelity into the target protein. Essentially it’s like the biological equivalent of a software hack for our own cells,” explained Dr. Panther, who is director of clinical development for infectious diseases at Moderna, in Cambridge, Mass.

Indeed, Moderna has numerous ongoing or recently completed phase 1 clinical trials of mRNA vaccines developed to protect against a raft of viral infections: respiratory syncytial virus, cytomegalovirus (NCT03382405), zika, chikungunya (NCT03829384), human metapneumovirus, and parainfluenza virus 3, as well as the aforementioned H10N8 and H7N9 influenza viruses. And an mRNA varicella zoster virus vaccine is in preclinical studies.

The mRNA vaccines closely mimic native viral infections, eliciting both B- and T-cell responses.

Moreover, the company also has ongoing phase 1 studies of mRNA-based cancer vaccines – therapies targeting solid tumors and lymphomas – as well as mRNA-directed increased production of relaxin as a treatment for heart failure and of vascular endothelial growth factor to treat myocardial ischemia.

“For the purposes of my company, the desired protein at this juncture could be an antibody, it could be a tumor antigen, it could be an enzyme that will replace an enzyme that’s lacking in somebody with an inborn error of metabolism. Or it could be a vaccine antigen target,” Dr. Panther said.

In addition to highlighting the results of the two phase 1 proof-of-concept studies of mRNA vaccines targeting the feared H10N8 and H7N9 influenza viruses, she presented interim results of an ongoing 1-year study of an mRNA vaccine that contains two antigens simultaneously targeting human metapneumovirus (hMPV) and parainfluenza virus 3 (PIV3).

“The rationale behind this study is that, taken together, these are two viruses that are responsible for a fair bit of disease burden in terms of lower respiratory tract infections and hospitalizations in children [younger] than 12 months of age, which will be the target population,” the infectious disease specialist noted.

The early positive results of the mRNA influenza vaccine studies were of particular interest to her audience of pediatric infectious disease specialists. Since the first human H7N9 infections were reported in China in 2013, five outbreaks have occurred involving more than 1,500 documented infections, resulting in more than 600 deaths. And ever since the virulent H10N8 avian influenza virus popped up on the radar in 2013, infectious disease physicians the world over have been waiting for the other shoe to drop.

There is obvious appeal to a novel, precise, and rapidly scalable technology such as that promised by intracellular delivery of mRNA in order to ramp up high-volume production of effective vaccines in the face of a looming pandemic threat. Elsewhere at the meeting, it was noted that, during the H1N1 pandemic of 2009, it took 6 months for the first vaccine doses to become available using current antiquated egg-based production methods. Another 2 months elapsed before the necessary millions of doses were produced.

The details of the two phase 1 studies of the mRNA vaccines against H7N9 and H10N8 influenza have recently been published (Vaccine. 2019 May 31;37[25]:3326-34). The vaccines, delivered in the conventional manner via injection into the deltoid muscle, were well tolerated, with the most common adverse events being the familiar ones: injection site pain, erythema, headache, fatigue, and myalgia. The immune response was robust and durable.

In response to an audience question, Dr. Panther said the mRNA vaccines are amenable to development as intranasal formulations.

The ongoing 12-month, phase 1, dose-ranging study of the mRNA hMPV/PIV3 virus vaccine includes 124 healthy adults at three U.S. sites who received two vaccinations on days 1 and 28. One month after a single vaccination, hMPV neutralizing antibody titers were 6.2-6.4 times those in the placebo arm; PIV3 neutralization titers were increased 3.3-fold. The second injection didn’t further boost antibody titers, suggesting that, at least in this study population of preexposed adults, a single vaccination is sufficient.

The use of mRNA technology has been a long time in coming. Dr. Panther explained why: “It’s a big trick to take an mRNA that by its own nature is a pretty fragile molecule and to get it past the degrading enzymes, like RNAses, that are out to chew it up immediately, and then to sneak it across the cellular membrane and into the cytoplasm, all the while avoiding the innate immune responses that exist solely to recognize RNA that looks foreign and chew it up.”

Moderna has accomplished this using a proprietary lipid nanoparticle delivery system.

“Essentially it’s a lipid shield that surrounds the mRNAs and ushers them past those enzymes and past the innate immune response that would otherwise destroy them,” according to Dr. Panther.

She and her colleagues believe they may eventually be able to change the nucleotide sequence of their manufactured mRNAs in order to expand the immunogenicity epitope and achieve a stronger immune response than would result from natural infection.

bjancin@mdedge.com

ORLANDO – Regular education of patients with asthma and their loved ones about how to manage the disease is critical to successful treatment, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

“Every contact with them is a teachable moment,” Mary Lou Hayden, RN, MS, FNP-BC, AE-C, a board-certified nurse practitioner and asthma educator, said in her presentation. “You want to make sure you’re involving the important people in their lives to help them.”

Education for asthma includes teaching patients and their families the difference between long-term control and reliever medications; the proper timing and technique with the medications, as well as the importance of adherence; how to recognize and avoid triggers for asthma; how to self-monitor their asthma and control the disease; and when to seek medication care, she said.

“We review their inhaler technique every time they come in,” she added.

According to the American Lung Association, patients learn in visual, auditory, and kinesthetic styles. Teaching patients in a kinesthetic style by actually showing the patient how to take the medication through example will help the patient learn through feeling, or muscle memory. This also method works even if patients do not have the medication with them at the time, said Ms. Hayden.

“Let’s say, you don’t have [the medication], but you prescribe it,” she said. “When they come back, tell them to bring their bag of medications and make sure you go back through because if they can kinesthetically use it correctly, they’ve already mastered the visual and the auditory piece.

Written action plans are also important to successful asthma management. The plan should be tailored to the patient’s disease severity, loss of control, and include information like the peak expiratory flow and medication types, dosages, and frequencies. The action plan should also be available at home, daycare, and school. “You want them to know how to recognize their symptoms, what to do about their symptoms, and when to contact you or go to urgent care or [the emergency room],” said Ms. Hayden.

To simplify the plan, Ms. Hayden recommended zoning actions based on color, like the asthma action plan provided by the American Academy of Allergy, Asthma & Immunology. The AAAAI plan uses traffic colors to signify how well controlled a patient’s asthma is, with green indicating well-controlled disease, yellow denoting worsening asthma, and red indicating that the asthma needs to be treated right away.

Action plans should also address a patient’s health literacy level and culture. “Think about who’s going to be using it,” said Ms. Hayden.

The goal of asthma therapy is to prevent chronic or problematic symptoms, lower use of short-acting beta-agonists, maintain good pulmonary function, normalize activity levels at school and work, prevent exacerbations and hospitalizations, and meet the patient’s expectations, as well as those of their family. “If you’re thinking only severe patients have exacerbations that are near fatal or fatal, that’s not true,” she said. It’s “very common for somebody with a very mild and intermittent asthma to go to severe in a very short period of time.”

When properly implemented, patient education is performed at the time of diagnosis, is done according to a plan, is integrated into care, reinforces important information, improves adherence, is individualized to the patient and addresses their needs, and builds a partnership between provider and patient.

“We really are thinking of the team concept: us, the patient and the important people the patient’s lives, and other clinicians that might be involved with other diseases to care for the patient,” said Ms. Hayden.

Ms. Hayden reports no relevant conflicts of interest. Global Academy for Medical Education and this news organization are owned by the same parent company.

ORLANDO – Regular education of patients with asthma and their loved ones about how to manage the disease is critical to successful treatment, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

“Every contact with them is a teachable moment,” Mary Lou Hayden, RN, MS, FNP-BC, AE-C, a board-certified nurse practitioner and asthma educator, said in her presentation. “You want to make sure you’re involving the important people in their lives to help them.”

Education for asthma includes teaching patients and their families the difference between long-term control and reliever medications; the proper timing and technique with the medications, as well as the importance of adherence; how to recognize and avoid triggers for asthma; how to self-monitor their asthma and control the disease; and when to seek medication care, she said.

“We review their inhaler technique every time they come in,” she added.

According to the American Lung Association, patients learn in visual, auditory, and kinesthetic styles. Teaching patients in a kinesthetic style by actually showing the patient how to take the medication through example will help the patient learn through feeling, or muscle memory. This also method works even if patients do not have the medication with them at the time, said Ms. Hayden.

“Let’s say, you don’t have [the medication], but you prescribe it,” she said. “When they come back, tell them to bring their bag of medications and make sure you go back through because if they can kinesthetically use it correctly, they’ve already mastered the visual and the auditory piece.

Written action plans are also important to successful asthma management. The plan should be tailored to the patient’s disease severity, loss of control, and include information like the peak expiratory flow and medication types, dosages, and frequencies. The action plan should also be available at home, daycare, and school. “You want them to know how to recognize their symptoms, what to do about their symptoms, and when to contact you or go to urgent care or [the emergency room],” said Ms. Hayden.

To simplify the plan, Ms. Hayden recommended zoning actions based on color, like the asthma action plan provided by the American Academy of Allergy, Asthma & Immunology. The AAAAI plan uses traffic colors to signify how well controlled a patient’s asthma is, with green indicating well-controlled disease, yellow denoting worsening asthma, and red indicating that the asthma needs to be treated right away.

Action plans should also address a patient’s health literacy level and culture. “Think about who’s going to be using it,” said Ms. Hayden.

The goal of asthma therapy is to prevent chronic or problematic symptoms, lower use of short-acting beta-agonists, maintain good pulmonary function, normalize activity levels at school and work, prevent exacerbations and hospitalizations, and meet the patient’s expectations, as well as those of their family. “If you’re thinking only severe patients have exacerbations that are near fatal or fatal, that’s not true,” she said. It’s “very common for somebody with a very mild and intermittent asthma to go to severe in a very short period of time.”

When properly implemented, patient education is performed at the time of diagnosis, is done according to a plan, is integrated into care, reinforces important information, improves adherence, is individualized to the patient and addresses their needs, and builds a partnership between provider and patient.

“We really are thinking of the team concept: us, the patient and the important people the patient’s lives, and other clinicians that might be involved with other diseases to care for the patient,” said Ms. Hayden.

Ms. Hayden reports no relevant conflicts of interest. Global Academy for Medical Education and this news organization are owned by the same parent company.

ORLANDO – Regular education of patients with asthma and their loved ones about how to manage the disease is critical to successful treatment, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.

“Every contact with them is a teachable moment,” Mary Lou Hayden, RN, MS, FNP-BC, AE-C, a board-certified nurse practitioner and asthma educator, said in her presentation. “You want to make sure you’re involving the important people in their lives to help them.”

Education for asthma includes teaching patients and their families the difference between long-term control and reliever medications; the proper timing and technique with the medications, as well as the importance of adherence; how to recognize and avoid triggers for asthma; how to self-monitor their asthma and control the disease; and when to seek medication care, she said.

“We review their inhaler technique every time they come in,” she added.

According to the American Lung Association, patients learn in visual, auditory, and kinesthetic styles. Teaching patients in a kinesthetic style by actually showing the patient how to take the medication through example will help the patient learn through feeling, or muscle memory. This also method works even if patients do not have the medication with them at the time, said Ms. Hayden.

“Let’s say, you don’t have [the medication], but you prescribe it,” she said. “When they come back, tell them to bring their bag of medications and make sure you go back through because if they can kinesthetically use it correctly, they’ve already mastered the visual and the auditory piece.

Written action plans are also important to successful asthma management. The plan should be tailored to the patient’s disease severity, loss of control, and include information like the peak expiratory flow and medication types, dosages, and frequencies. The action plan should also be available at home, daycare, and school. “You want them to know how to recognize their symptoms, what to do about their symptoms, and when to contact you or go to urgent care or [the emergency room],” said Ms. Hayden.

To simplify the plan, Ms. Hayden recommended zoning actions based on color, like the asthma action plan provided by the American Academy of Allergy, Asthma & Immunology. The AAAAI plan uses traffic colors to signify how well controlled a patient’s asthma is, with green indicating well-controlled disease, yellow denoting worsening asthma, and red indicating that the asthma needs to be treated right away.

Action plans should also address a patient’s health literacy level and culture. “Think about who’s going to be using it,” said Ms. Hayden.

The goal of asthma therapy is to prevent chronic or problematic symptoms, lower use of short-acting beta-agonists, maintain good pulmonary function, normalize activity levels at school and work, prevent exacerbations and hospitalizations, and meet the patient’s expectations, as well as those of their family. “If you’re thinking only severe patients have exacerbations that are near fatal or fatal, that’s not true,” she said. It’s “very common for somebody with a very mild and intermittent asthma to go to severe in a very short period of time.”

When properly implemented, patient education is performed at the time of diagnosis, is done according to a plan, is integrated into care, reinforces important information, improves adherence, is individualized to the patient and addresses their needs, and builds a partnership between provider and patient.

“We really are thinking of the team concept: us, the patient and the important people the patient’s lives, and other clinicians that might be involved with other diseases to care for the patient,” said Ms. Hayden.

Ms. Hayden reports no relevant conflicts of interest. Global Academy for Medical Education and this news organization are owned by the same parent company.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

Shared decision making around low-dose computed tomography screening for lung cancer should include risk and benefit information for baseline conditions such as chronic obstructive pulmonary disease (COPD), research suggests.

picsfive/Fotolia.com

Jonathan M. Iaccarino, MD, of the pulmonary center at the Boston University, and coauthors reported the results of a secondary analysis of patient-level outcomes from 75,138 low-dose CT (LDCT) scans in 26,453 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016).

Currently, LDCT screening is recommended annually for high-risk smokers aged 55-80 years. The National Lung Screening Trial showed that this screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in this group. The guidelines stress the importance of shared decision making, with discussion of the risks and benefits of screening.

Dr. Iaccarino and colleagues point out that decision aids for shared decision making need to include important baseline characteristics, such as the presence of COPD, as these can complicate the risk and benefit analysis.

In this study, they found that 14.2% of LDCT scans performed led to a subsequent diagnostic study and 1.5% resulted in an invasive procedure. In addition, 0.3% of scans resulted in a procedure-related complication, and in 89 cases (0.1%), this procedure-related complication was serious.

At the patient level, nearly one-third (30.5%) received a diagnostic study, 4.2% underwent an invasive procedure – 41% of whom ultimately were found not to have lung cancer – 0.9% had a procedure-related complication, and 0.3% had a serious procedure related complication. Furthermore, among those who experienced a serious complication, 12.5% were found not to have lung cancer.

“Our study analyzes cumulative outcomes at the level of the individual patient over the three years of LDCT screening during the NLST, showing higher rates of diagnostic procedures, invasive procedures, complications and serious complications than apparent when data is presented at the level of the individual test,” the authors wrote.

The 4,632 participants with COPD were significantly more likely to undergo diagnostic studies (36.2%), have an invasive procedure (6%), experience a procedure-related complication (1.5%) and experience a serious procedure-related complication (0.6%) than were participants without COPD. However, they also had a significantly higher incidence of lung cancer diagnosis than did participants without COPD (6.1% vs. 3.6%).

“While most decision aids note the risks of screening may be increased in those with COPD, our study helps quantify these increased risks as well as the increased likelihood of a lung cancer diagnosis, a critical advance given that providing personalized (rather than generic) information results in more accurate risk perception and more informed choices among individuals considering screening,” the authors wrote. “With the significant change in the balance of benefits and risks of screening in patients with COPD, it is critical to adjust the shared decision-making discussions accordingly.”

They also noted that other comorbidities, such as heart disease, vascular disease, and other lung diseases, would likely affect the balance of risk and benefit of LDCT screening, and that there was a need for further exploration of screening in these patients.

Noting the study’s limitations, the authors pointed that their analysis focused on outcomes that were not the primary outcomes of the National Lung Screening trial, and that they relied on self-reported COPD diagnoses.

The study was supported by the American Society of Clinical Oncology, the Charles A. King Trust, and Edith Nourse Rogers Memorial Veterans Hospital. No conflicts of interest were declared.

SOURCE: Iaccarino JM et al. CHEST 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016.

Shared decision making around low-dose computed tomography screening for lung cancer should include risk and benefit information for baseline conditions such as chronic obstructive pulmonary disease (COPD), research suggests.

picsfive/Fotolia.com

Jonathan M. Iaccarino, MD, of the pulmonary center at the Boston University, and coauthors reported the results of a secondary analysis of patient-level outcomes from 75,138 low-dose CT (LDCT) scans in 26,453 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016).

Currently, LDCT screening is recommended annually for high-risk smokers aged 55-80 years. The National Lung Screening Trial showed that this screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in this group. The guidelines stress the importance of shared decision making, with discussion of the risks and benefits of screening.

Dr. Iaccarino and colleagues point out that decision aids for shared decision making need to include important baseline characteristics, such as the presence of COPD, as these can complicate the risk and benefit analysis.

In this study, they found that 14.2% of LDCT scans performed led to a subsequent diagnostic study and 1.5% resulted in an invasive procedure. In addition, 0.3% of scans resulted in a procedure-related complication, and in 89 cases (0.1%), this procedure-related complication was serious.

At the patient level, nearly one-third (30.5%) received a diagnostic study, 4.2% underwent an invasive procedure – 41% of whom ultimately were found not to have lung cancer – 0.9% had a procedure-related complication, and 0.3% had a serious procedure related complication. Furthermore, among those who experienced a serious complication, 12.5% were found not to have lung cancer.

“Our study analyzes cumulative outcomes at the level of the individual patient over the three years of LDCT screening during the NLST, showing higher rates of diagnostic procedures, invasive procedures, complications and serious complications than apparent when data is presented at the level of the individual test,” the authors wrote.

The 4,632 participants with COPD were significantly more likely to undergo diagnostic studies (36.2%), have an invasive procedure (6%), experience a procedure-related complication (1.5%) and experience a serious procedure-related complication (0.6%) than were participants without COPD. However, they also had a significantly higher incidence of lung cancer diagnosis than did participants without COPD (6.1% vs. 3.6%).

“While most decision aids note the risks of screening may be increased in those with COPD, our study helps quantify these increased risks as well as the increased likelihood of a lung cancer diagnosis, a critical advance given that providing personalized (rather than generic) information results in more accurate risk perception and more informed choices among individuals considering screening,” the authors wrote. “With the significant change in the balance of benefits and risks of screening in patients with COPD, it is critical to adjust the shared decision-making discussions accordingly.”

They also noted that other comorbidities, such as heart disease, vascular disease, and other lung diseases, would likely affect the balance of risk and benefit of LDCT screening, and that there was a need for further exploration of screening in these patients.

Noting the study’s limitations, the authors pointed that their analysis focused on outcomes that were not the primary outcomes of the National Lung Screening trial, and that they relied on self-reported COPD diagnoses.

The study was supported by the American Society of Clinical Oncology, the Charles A. King Trust, and Edith Nourse Rogers Memorial Veterans Hospital. No conflicts of interest were declared.

SOURCE: Iaccarino JM et al. CHEST 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016.

Shared decision making around low-dose computed tomography screening for lung cancer should include risk and benefit information for baseline conditions such as chronic obstructive pulmonary disease (COPD), research suggests.

picsfive/Fotolia.com

Jonathan M. Iaccarino, MD, of the pulmonary center at the Boston University, and coauthors reported the results of a secondary analysis of patient-level outcomes from 75,138 low-dose CT (LDCT) scans in 26,453 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016).

Currently, LDCT screening is recommended annually for high-risk smokers aged 55-80 years. The National Lung Screening Trial showed that this screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in this group. The guidelines stress the importance of shared decision making, with discussion of the risks and benefits of screening.

Dr. Iaccarino and colleagues point out that decision aids for shared decision making need to include important baseline characteristics, such as the presence of COPD, as these can complicate the risk and benefit analysis.

In this study, they found that 14.2% of LDCT scans performed led to a subsequent diagnostic study and 1.5% resulted in an invasive procedure. In addition, 0.3% of scans resulted in a procedure-related complication, and in 89 cases (0.1%), this procedure-related complication was serious.

At the patient level, nearly one-third (30.5%) received a diagnostic study, 4.2% underwent an invasive procedure – 41% of whom ultimately were found not to have lung cancer – 0.9% had a procedure-related complication, and 0.3% had a serious procedure related complication. Furthermore, among those who experienced a serious complication, 12.5% were found not to have lung cancer.

“Our study analyzes cumulative outcomes at the level of the individual patient over the three years of LDCT screening during the NLST, showing higher rates of diagnostic procedures, invasive procedures, complications and serious complications than apparent when data is presented at the level of the individual test,” the authors wrote.

The 4,632 participants with COPD were significantly more likely to undergo diagnostic studies (36.2%), have an invasive procedure (6%), experience a procedure-related complication (1.5%) and experience a serious procedure-related complication (0.6%) than were participants without COPD. However, they also had a significantly higher incidence of lung cancer diagnosis than did participants without COPD (6.1% vs. 3.6%).

“While most decision aids note the risks of screening may be increased in those with COPD, our study helps quantify these increased risks as well as the increased likelihood of a lung cancer diagnosis, a critical advance given that providing personalized (rather than generic) information results in more accurate risk perception and more informed choices among individuals considering screening,” the authors wrote. “With the significant change in the balance of benefits and risks of screening in patients with COPD, it is critical to adjust the shared decision-making discussions accordingly.”

They also noted that other comorbidities, such as heart disease, vascular disease, and other lung diseases, would likely affect the balance of risk and benefit of LDCT screening, and that there was a need for further exploration of screening in these patients.

Noting the study’s limitations, the authors pointed that their analysis focused on outcomes that were not the primary outcomes of the National Lung Screening trial, and that they relied on self-reported COPD diagnoses.

The study was supported by the American Society of Clinical Oncology, the Charles A. King Trust, and Edith Nourse Rogers Memorial Veterans Hospital. No conflicts of interest were declared.

SOURCE: Iaccarino JM et al. CHEST 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016.

During Operations Iraqi and Enduring Freedom, everything from old uniforms to plastic, aerosol cans, electronic equipment, human waste, tires, and batteries were thrown into open pits, often doused with jet fuel, and set on fire.

Many deployed soldiers were exposed to smoke from these open-air burn pits, putting them at risk for cancer, neurologic effects, reproductive effects, respiratory toxicity, and cardiovascular toxicity. Veterans who were close to burn pits have reported eye irritation, itching, rashes, and respiratory problems, such as bronchitis, asthma, and emphysema.

In May 2019, the VA redesignated the Airborne Hazards Center of Excellence (AHCE), established in 2013, as the Airborne Hazards and Burn Pits Center of Excellence (AHBPCE). The redesignation was a consequence of the Helping Veterans Exposed to Burn Pits Act, which stemmed from an 18-month bipartisan effort to prevent burn pits from becoming “the Agent Orange of this generation of soldiers.” Senator Amy Klobuchar (D-MN), who cosponsored the legislation with Thom Tillis (R-NC) said, “After the Vietnam War, it took the US government years to recognize that there was a link between Agent Orange and its devastating health effects on our soldiers. … [W]e can’t make that same tragic mistake again by failing to identify the devastating health effects associated with burn pits.”

The AHCE was responsible for assessing veterans’ cardiopulmonary function, military/ nonmilitary exposures, and health-related symptoms for those with airborne hazard concerns. The AHBPCE will specialize in clinical and transitional research, focusing on expanding understanding of health outcomes and treatments for burn pit–related issues.

VA providers can consult with the AHBPCE about assessment and treatment. When appropriate, veterans may be invited for a comprehensive, multiday health evaluation from a specialized team. The examination includes state-of-the-art assessments of lung function and exercise capacity. The findings are used to develop recommendations, which are shared with the veteran and referring provider for follow-up care. The findings also are used by researchers at the center and throughout the VA to develop research questions to investigate and potentially improve clinical practice.

Veterans (including those who receive VA-authorized care in the community) with complex clinical presentations who are unable to be diagnosed locally may be referred for consultation or examination.

AHBPCE, which is located at the New Jersey War Related Illness and Injury Study Center (WRIISC), also provides the AHBPCE-WRIISC Airborne hazards Registry (AWARE) program, designed for veterans who complete the Airborne Hazards and Open Burn Pit Registry online questionnaire, report chronic respiratory symptoms, and meet other eligibility criteria. AHBPCE’s mandate also includes analyzing registry data to monitor the VA’s overall clinical response to exposure concerns.

During Operations Iraqi and Enduring Freedom, everything from old uniforms to plastic, aerosol cans, electronic equipment, human waste, tires, and batteries were thrown into open pits, often doused with jet fuel, and set on fire.

Many deployed soldiers were exposed to smoke from these open-air burn pits, putting them at risk for cancer, neurologic effects, reproductive effects, respiratory toxicity, and cardiovascular toxicity. Veterans who were close to burn pits have reported eye irritation, itching, rashes, and respiratory problems, such as bronchitis, asthma, and emphysema.

In May 2019, the VA redesignated the Airborne Hazards Center of Excellence (AHCE), established in 2013, as the Airborne Hazards and Burn Pits Center of Excellence (AHBPCE). The redesignation was a consequence of the Helping Veterans Exposed to Burn Pits Act, which stemmed from an 18-month bipartisan effort to prevent burn pits from becoming “the Agent Orange of this generation of soldiers.” Senator Amy Klobuchar (D-MN), who cosponsored the legislation with Thom Tillis (R-NC) said, “After the Vietnam War, it took the US government years to recognize that there was a link between Agent Orange and its devastating health effects on our soldiers. … [W]e can’t make that same tragic mistake again by failing to identify the devastating health effects associated with burn pits.”

The AHCE was responsible for assessing veterans’ cardiopulmonary function, military/ nonmilitary exposures, and health-related symptoms for those with airborne hazard concerns. The AHBPCE will specialize in clinical and transitional research, focusing on expanding understanding of health outcomes and treatments for burn pit–related issues.

VA providers can consult with the AHBPCE about assessment and treatment. When appropriate, veterans may be invited for a comprehensive, multiday health evaluation from a specialized team. The examination includes state-of-the-art assessments of lung function and exercise capacity. The findings are used to develop recommendations, which are shared with the veteran and referring provider for follow-up care. The findings also are used by researchers at the center and throughout the VA to develop research questions to investigate and potentially improve clinical practice.

Veterans (including those who receive VA-authorized care in the community) with complex clinical presentations who are unable to be diagnosed locally may be referred for consultation or examination.

AHBPCE, which is located at the New Jersey War Related Illness and Injury Study Center (WRIISC), also provides the AHBPCE-WRIISC Airborne hazards Registry (AWARE) program, designed for veterans who complete the Airborne Hazards and Open Burn Pit Registry online questionnaire, report chronic respiratory symptoms, and meet other eligibility criteria. AHBPCE’s mandate also includes analyzing registry data to monitor the VA’s overall clinical response to exposure concerns.

During Operations Iraqi and Enduring Freedom, everything from old uniforms to plastic, aerosol cans, electronic equipment, human waste, tires, and batteries were thrown into open pits, often doused with jet fuel, and set on fire.

Many deployed soldiers were exposed to smoke from these open-air burn pits, putting them at risk for cancer, neurologic effects, reproductive effects, respiratory toxicity, and cardiovascular toxicity. Veterans who were close to burn pits have reported eye irritation, itching, rashes, and respiratory problems, such as bronchitis, asthma, and emphysema.

In May 2019, the VA redesignated the Airborne Hazards Center of Excellence (AHCE), established in 2013, as the Airborne Hazards and Burn Pits Center of Excellence (AHBPCE). The redesignation was a consequence of the Helping Veterans Exposed to Burn Pits Act, which stemmed from an 18-month bipartisan effort to prevent burn pits from becoming “the Agent Orange of this generation of soldiers.” Senator Amy Klobuchar (D-MN), who cosponsored the legislation with Thom Tillis (R-NC) said, “After the Vietnam War, it took the US government years to recognize that there was a link between Agent Orange and its devastating health effects on our soldiers. … [W]e can’t make that same tragic mistake again by failing to identify the devastating health effects associated with burn pits.”

The AHCE was responsible for assessing veterans’ cardiopulmonary function, military/ nonmilitary exposures, and health-related symptoms for those with airborne hazard concerns. The AHBPCE will specialize in clinical and transitional research, focusing on expanding understanding of health outcomes and treatments for burn pit–related issues.

VA providers can consult with the AHBPCE about assessment and treatment. When appropriate, veterans may be invited for a comprehensive, multiday health evaluation from a specialized team. The examination includes state-of-the-art assessments of lung function and exercise capacity. The findings are used to develop recommendations, which are shared with the veteran and referring provider for follow-up care. The findings also are used by researchers at the center and throughout the VA to develop research questions to investigate and potentially improve clinical practice.

Veterans (including those who receive VA-authorized care in the community) with complex clinical presentations who are unable to be diagnosed locally may be referred for consultation or examination.

AHBPCE, which is located at the New Jersey War Related Illness and Injury Study Center (WRIISC), also provides the AHBPCE-WRIISC Airborne hazards Registry (AWARE) program, designed for veterans who complete the Airborne Hazards and Open Burn Pit Registry online questionnaire, report chronic respiratory symptoms, and meet other eligibility criteria. AHBPCE’s mandate also includes analyzing registry data to monitor the VA’s overall clinical response to exposure concerns.

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

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

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

When influenza season arrives, conventional morbidity and mortality statistics, health care encounters, and laboratory data might not “fully reflect the disruption caused to the social and economic life of the community,” say CDC researchers. That is the reason that the National Institute for Occupational Safety and Health (NIOSH) monitors health-related workplace absenteeism every month, and why the World Health Organization (WHO) uses those data to help determine the impact of influenza season worldwide.

The workplace is a prime area for transmission—people share workspace and equipment and interact with one another closely. Estimates of influenza attack rates for working-aged adults can be as high as 14.3% in a given influenza season, the CDC says.

According to NIOSH, absenteeism rose sharply in the 2017-2018 season, to a level significantly higher than that of the average during the previous 5 seasons. In October, 1.7% of workers were absent due to health issues. That figure began climbing in November, peaking in January at 3.0%, significantly exceeding the epidemic threshold. Absenteeism declined steadily after that to a low of 1.4%, then began rising again in August and September.

Male workers, people aged 45 to 64 years, and those working in certain occupations (including management, business, and repair services) were more likely to be out.

Regional absenteeism peaks corresponded to concurrent peaks in influenza-like illness (ILI) activity in those regions. The researchers say this is in line with a longtime recognition that health-related workplace absenteeism correlates well with the presence of ILI, which is why absenteeism data are used as a nonspecific indicator of ILI in the community. During the 2009-2010 influenza A (H1N1) pandemic, for instance, peak workplace absenteeism correlated with the highest occurrence of both ILI and influenza-positive laboratory tests, according to NIOSH.

The associations between ILI, absenteeism, and demographic characteristics are complex, the researchers say, and mediated by factors such as vaccination coverage and access to paid sick leave.

The usual recommendations—vaccination, covering coughs and sneezes, handwashing, and routinely cleaning frequently touched surfaces—are the most effective ways to prevent transmission, the researchers note. During a pandemic, other measures may be needed, such as “social distancing” in workplaces.

NIOSH makes absenteeism surveillance results available (https://www.cdc.gov/niosh/topics/absences/default.html). The researchers suggest that employers might wish to consult them when developing prevention messages.

When influenza season arrives, conventional morbidity and mortality statistics, health care encounters, and laboratory data might not “fully reflect the disruption caused to the social and economic life of the community,” say CDC researchers. That is the reason that the National Institute for Occupational Safety and Health (NIOSH) monitors health-related workplace absenteeism every month, and why the World Health Organization (WHO) uses those data to help determine the impact of influenza season worldwide.

The workplace is a prime area for transmission—people share workspace and equipment and interact with one another closely. Estimates of influenza attack rates for working-aged adults can be as high as 14.3% in a given influenza season, the CDC says.

According to NIOSH, absenteeism rose sharply in the 2017-2018 season, to a level significantly higher than that of the average during the previous 5 seasons. In October, 1.7% of workers were absent due to health issues. That figure began climbing in November, peaking in January at 3.0%, significantly exceeding the epidemic threshold. Absenteeism declined steadily after that to a low of 1.4%, then began rising again in August and September.

Male workers, people aged 45 to 64 years, and those working in certain occupations (including management, business, and repair services) were more likely to be out.

Regional absenteeism peaks corresponded to concurrent peaks in influenza-like illness (ILI) activity in those regions. The researchers say this is in line with a longtime recognition that health-related workplace absenteeism correlates well with the presence of ILI, which is why absenteeism data are used as a nonspecific indicator of ILI in the community. During the 2009-2010 influenza A (H1N1) pandemic, for instance, peak workplace absenteeism correlated with the highest occurrence of both ILI and influenza-positive laboratory tests, according to NIOSH.

The associations between ILI, absenteeism, and demographic characteristics are complex, the researchers say, and mediated by factors such as vaccination coverage and access to paid sick leave.

The usual recommendations—vaccination, covering coughs and sneezes, handwashing, and routinely cleaning frequently touched surfaces—are the most effective ways to prevent transmission, the researchers note. During a pandemic, other measures may be needed, such as “social distancing” in workplaces.

NIOSH makes absenteeism surveillance results available (https://www.cdc.gov/niosh/topics/absences/default.html). The researchers suggest that employers might wish to consult them when developing prevention messages.

When influenza season arrives, conventional morbidity and mortality statistics, health care encounters, and laboratory data might not “fully reflect the disruption caused to the social and economic life of the community,” say CDC researchers. That is the reason that the National Institute for Occupational Safety and Health (NIOSH) monitors health-related workplace absenteeism every month, and why the World Health Organization (WHO) uses those data to help determine the impact of influenza season worldwide.

The workplace is a prime area for transmission—people share workspace and equipment and interact with one another closely. Estimates of influenza attack rates for working-aged adults can be as high as 14.3% in a given influenza season, the CDC says.

According to NIOSH, absenteeism rose sharply in the 2017-2018 season, to a level significantly higher than that of the average during the previous 5 seasons. In October, 1.7% of workers were absent due to health issues. That figure began climbing in November, peaking in January at 3.0%, significantly exceeding the epidemic threshold. Absenteeism declined steadily after that to a low of 1.4%, then began rising again in August and September.

Male workers, people aged 45 to 64 years, and those working in certain occupations (including management, business, and repair services) were more likely to be out.

Regional absenteeism peaks corresponded to concurrent peaks in influenza-like illness (ILI) activity in those regions. The researchers say this is in line with a longtime recognition that health-related workplace absenteeism correlates well with the presence of ILI, which is why absenteeism data are used as a nonspecific indicator of ILI in the community. During the 2009-2010 influenza A (H1N1) pandemic, for instance, peak workplace absenteeism correlated with the highest occurrence of both ILI and influenza-positive laboratory tests, according to NIOSH.

The associations between ILI, absenteeism, and demographic characteristics are complex, the researchers say, and mediated by factors such as vaccination coverage and access to paid sick leave.

The usual recommendations—vaccination, covering coughs and sneezes, handwashing, and routinely cleaning frequently touched surfaces—are the most effective ways to prevent transmission, the researchers note. During a pandemic, other measures may be needed, such as “social distancing” in workplaces.

NIOSH makes absenteeism surveillance results available (https://www.cdc.gov/niosh/topics/absences/default.html). The researchers suggest that employers might wish to consult them when developing prevention messages.