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One monoclonal dose gives preterm neonates season-long RSV protection
WASHINGTON – A single dose of a novel monoclonal antibody against a respiratory syncytial virus surface protein safely protected preterm infants against severe infections for 150 days during their first winter season in a randomized trial with more than 1,400 children.
One intramuscular injection of nirsevimab (also known as MEDI8897) administered to infants born at 29-35 weeks’ gestation at the start of the local respiratory syncytial virus (RSV) season (November in the Northern hemisphere) led to a 70% relative reduction in the rate of medically attended lower respiratory tract infections with RSV during the subsequent 150 days, compared with placebo, the study’s primary efficacy outcome, M. Pamela Griffin, MD, said at an annual scientific meeting on infectious diseases.
In a secondary efficacy measure, the rate of hospitalizations for RSV-caused lower respiratory tract infections, a single injection of nirsevimab dropped the incidence by 78%, relative to placebo. Both effects were statistically significant. The rate of total adverse events and serious adverse events was similar in the two treatment arms, reported Dr. Griffin, a clinical development lead with AstraZeneca.
These positive results for a single intramuscular injection of nirsevimab are the first findings from a series of studies aimed at getting the monoclonal antibody onto the U.S. market as a superior alternative to palivizumab (Synagis), which acts in a similar way to block RSV infection (albeit by targeting a different viral surface protein) but which requires administration every 30 days. This need for serial dosing of palivizumab in children younger than 1 year old for complete seasonal protection against RSV is probably a reason why the American Academy of Pediatrics, as well as other medical societies, have targeted using palivizumab only on certain types of high-risk infants: those born before 29 weeks’ gestational age, with chronic lung disease of prematurity, or with hemodynamically significant congenital heart disease (Pediatrics. 2014 Aug;134[2]:415-20). “It’s not feasible for most infants to come for five treatments during RSV season,” Dr. Griffin noted. A tweak in the structure of nirsevimab gives it a much longer blood half-life than palivizumab and allows a single dose to maintain efficacy for 5 months, the duration of RSV season.
“The big advantage of nirsevimab is one dose instead of five,” she said in an interview.
The study randomized 969 preterm infants to nirsevimab and 484 to placebo when the children averaged 3 months old and 4.5 kg. The incidence of the primary endpoint was 2.6% in the nirsevimab-treated infants and 9.5% in those who received placebo. The incidence of hospitalizations associated with an RSV lower respiratory tract infection was 0.8% in the nirsevimab group and 4.1% on placebo. Nirsevimab was equally effective regardless of RSV subtype, infant age, or sex. The rate of hypersensitivity reactions was low, less than 1%, and similar in the two treatment arms, as was the rate of detection of antidrug antibody, 3.8% with placebo and 5.6% with nirsevimab.
Two other large trials are underway to document the performance of nirsevimab in other types of infants. One study is examining the drug’s performance compared with placebo in term infants with a gestational age of at least 36 weeks, while another is comparing nirsevimab against a five-dose regimen of palivizumab in high-risk infants who are recommended to receive palivizumab by local medical societies. In the United States, this would be infants born at less than 29 weeks’ gestation, and those with either hemodynamically significant congenital heart disease or chronic lung disease of prematurity. In these studies, the researchers also will assess the cost effectiveness of nirsevimab relative to the costs for medical care needed by infants who receive comparator treatments, Dr. Griffin said.
The study was funded by AstraZeneca, the company developing nirsevimab. Dr. Griffin is an employee of and shareholder in AstraZeneca.
SOURCE: ClinicalTrials.gov identifier: NCT02878330.
WASHINGTON – A single dose of a novel monoclonal antibody against a respiratory syncytial virus surface protein safely protected preterm infants against severe infections for 150 days during their first winter season in a randomized trial with more than 1,400 children.
One intramuscular injection of nirsevimab (also known as MEDI8897) administered to infants born at 29-35 weeks’ gestation at the start of the local respiratory syncytial virus (RSV) season (November in the Northern hemisphere) led to a 70% relative reduction in the rate of medically attended lower respiratory tract infections with RSV during the subsequent 150 days, compared with placebo, the study’s primary efficacy outcome, M. Pamela Griffin, MD, said at an annual scientific meeting on infectious diseases.
In a secondary efficacy measure, the rate of hospitalizations for RSV-caused lower respiratory tract infections, a single injection of nirsevimab dropped the incidence by 78%, relative to placebo. Both effects were statistically significant. The rate of total adverse events and serious adverse events was similar in the two treatment arms, reported Dr. Griffin, a clinical development lead with AstraZeneca.
These positive results for a single intramuscular injection of nirsevimab are the first findings from a series of studies aimed at getting the monoclonal antibody onto the U.S. market as a superior alternative to palivizumab (Synagis), which acts in a similar way to block RSV infection (albeit by targeting a different viral surface protein) but which requires administration every 30 days. This need for serial dosing of palivizumab in children younger than 1 year old for complete seasonal protection against RSV is probably a reason why the American Academy of Pediatrics, as well as other medical societies, have targeted using palivizumab only on certain types of high-risk infants: those born before 29 weeks’ gestational age, with chronic lung disease of prematurity, or with hemodynamically significant congenital heart disease (Pediatrics. 2014 Aug;134[2]:415-20). “It’s not feasible for most infants to come for five treatments during RSV season,” Dr. Griffin noted. A tweak in the structure of nirsevimab gives it a much longer blood half-life than palivizumab and allows a single dose to maintain efficacy for 5 months, the duration of RSV season.
“The big advantage of nirsevimab is one dose instead of five,” she said in an interview.
The study randomized 969 preterm infants to nirsevimab and 484 to placebo when the children averaged 3 months old and 4.5 kg. The incidence of the primary endpoint was 2.6% in the nirsevimab-treated infants and 9.5% in those who received placebo. The incidence of hospitalizations associated with an RSV lower respiratory tract infection was 0.8% in the nirsevimab group and 4.1% on placebo. Nirsevimab was equally effective regardless of RSV subtype, infant age, or sex. The rate of hypersensitivity reactions was low, less than 1%, and similar in the two treatment arms, as was the rate of detection of antidrug antibody, 3.8% with placebo and 5.6% with nirsevimab.
Two other large trials are underway to document the performance of nirsevimab in other types of infants. One study is examining the drug’s performance compared with placebo in term infants with a gestational age of at least 36 weeks, while another is comparing nirsevimab against a five-dose regimen of palivizumab in high-risk infants who are recommended to receive palivizumab by local medical societies. In the United States, this would be infants born at less than 29 weeks’ gestation, and those with either hemodynamically significant congenital heart disease or chronic lung disease of prematurity. In these studies, the researchers also will assess the cost effectiveness of nirsevimab relative to the costs for medical care needed by infants who receive comparator treatments, Dr. Griffin said.
The study was funded by AstraZeneca, the company developing nirsevimab. Dr. Griffin is an employee of and shareholder in AstraZeneca.
SOURCE: ClinicalTrials.gov identifier: NCT02878330.
WASHINGTON – A single dose of a novel monoclonal antibody against a respiratory syncytial virus surface protein safely protected preterm infants against severe infections for 150 days during their first winter season in a randomized trial with more than 1,400 children.
One intramuscular injection of nirsevimab (also known as MEDI8897) administered to infants born at 29-35 weeks’ gestation at the start of the local respiratory syncytial virus (RSV) season (November in the Northern hemisphere) led to a 70% relative reduction in the rate of medically attended lower respiratory tract infections with RSV during the subsequent 150 days, compared with placebo, the study’s primary efficacy outcome, M. Pamela Griffin, MD, said at an annual scientific meeting on infectious diseases.
In a secondary efficacy measure, the rate of hospitalizations for RSV-caused lower respiratory tract infections, a single injection of nirsevimab dropped the incidence by 78%, relative to placebo. Both effects were statistically significant. The rate of total adverse events and serious adverse events was similar in the two treatment arms, reported Dr. Griffin, a clinical development lead with AstraZeneca.
These positive results for a single intramuscular injection of nirsevimab are the first findings from a series of studies aimed at getting the monoclonal antibody onto the U.S. market as a superior alternative to palivizumab (Synagis), which acts in a similar way to block RSV infection (albeit by targeting a different viral surface protein) but which requires administration every 30 days. This need for serial dosing of palivizumab in children younger than 1 year old for complete seasonal protection against RSV is probably a reason why the American Academy of Pediatrics, as well as other medical societies, have targeted using palivizumab only on certain types of high-risk infants: those born before 29 weeks’ gestational age, with chronic lung disease of prematurity, or with hemodynamically significant congenital heart disease (Pediatrics. 2014 Aug;134[2]:415-20). “It’s not feasible for most infants to come for five treatments during RSV season,” Dr. Griffin noted. A tweak in the structure of nirsevimab gives it a much longer blood half-life than palivizumab and allows a single dose to maintain efficacy for 5 months, the duration of RSV season.
“The big advantage of nirsevimab is one dose instead of five,” she said in an interview.
The study randomized 969 preterm infants to nirsevimab and 484 to placebo when the children averaged 3 months old and 4.5 kg. The incidence of the primary endpoint was 2.6% in the nirsevimab-treated infants and 9.5% in those who received placebo. The incidence of hospitalizations associated with an RSV lower respiratory tract infection was 0.8% in the nirsevimab group and 4.1% on placebo. Nirsevimab was equally effective regardless of RSV subtype, infant age, or sex. The rate of hypersensitivity reactions was low, less than 1%, and similar in the two treatment arms, as was the rate of detection of antidrug antibody, 3.8% with placebo and 5.6% with nirsevimab.
Two other large trials are underway to document the performance of nirsevimab in other types of infants. One study is examining the drug’s performance compared with placebo in term infants with a gestational age of at least 36 weeks, while another is comparing nirsevimab against a five-dose regimen of palivizumab in high-risk infants who are recommended to receive palivizumab by local medical societies. In the United States, this would be infants born at less than 29 weeks’ gestation, and those with either hemodynamically significant congenital heart disease or chronic lung disease of prematurity. In these studies, the researchers also will assess the cost effectiveness of nirsevimab relative to the costs for medical care needed by infants who receive comparator treatments, Dr. Griffin said.
The study was funded by AstraZeneca, the company developing nirsevimab. Dr. Griffin is an employee of and shareholder in AstraZeneca.
SOURCE: ClinicalTrials.gov identifier: NCT02878330.
REPORTING FROM ID WEEK 2019
Guidelines updated for treating community-acquired pneumonia
An update to the 2007 guidelines on the treatment of community-acquired pneumonia (CAP) was published by two medical societies, based upon the work of a multidisciplinary panel that “conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.”
The panel addressed 16 questions in the areas including diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Some of their recommendations remained unchanged from the 2007 guideline, but others were updated based upon more-recent clinical trials and epidemiological studies, according to Joshua P. Metlay, MD, of Massachusetts General Hospital, Boston, and colleagues on behalf of the Infectious Diseases Society of America and the American Thoracic Society.
Among the key recommendations differing from the previous guidelines, the 2019 guidelines include the following:
- Sputum and blood culture samples are recommended in patients with severe disease, as well as in all inpatients empirically treated for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa.
- Macrolide monotherapy is only conditionally recommended for outpatients based on resistance levels.
- Procalcitonin assessment, not covered in the 2007 guidelines, is not recommended in order to determine initial antibiotic therapy.
- Corticosteroid use, not covered in the 2007 guidelines, is not recommended, though it may be considered in patients with refractory septic shock.
- The use of health care–associated pneumonia (HCAP) as a category should be dropped, with a switch to an emphasis on local epidemiology and validated risk factors to determine the need for MRSA or P. aeruginosa treatment.
- Standard empiric therapy for severe CAP should be beta-lactam/macrolide and beta-lactam/fluoroquinolone combinations, but with stronger evidence in favor of the beta-lactam/macrolide combination.
The updated guidelines also include a number of other recommendations, such as those dealing with the management of patients with comorbidities, and were published in the American Journal of Respiratory and Critical Care Medicine.
“A difference between this guideline and previous ones is that we have significantly increased the proportion of patients in whom we recommend routinely obtaining respiratory tract samples for microbiologic studies. This decision is largely based on a desire to correct the overuse of anti-MRSA and antipseudomonal therapy that has occurred since the introduction of the HCAP classification (which we recommend abandoning) rather than high-quality evidence,” the authors stated in their conclusions. They added that they “expect our move against endorsing monotherapy with macrolides, which is based on population resistance data rather than high-quality clinical studies, will generate future outcomes studies comparing different treatment strategies.”
Many of the authors reported relationships with a variety of pharmaceutical companies; full disclosures are detailed at the end of the guideline publication.
SOURCE: Metlay JP et al. Am J Respir Crit Med. 2019;200(7):e45-67.
“Ever since we wrote the first CAP [community-acquired pneumonia] guidelines in 1993, we’ve heard good and bad things, and I agree with both,” Michael S. Niederman, MD, FCCP, said in a presentation at IDWeek 2019. “For good or for bad, [guidelines] are a standard against which care can be evaluated.” He discussed how, as guidelines have become more evidence based, they have often become “more wishy washy,” that when the evidence is weak, the recommendation is weak, and the guidelines merely advise doctors: “You figure it out.”
However, he pointed out that, since CAP guidelines were developed, there have been overall improvements in patient care and antibiotic stewardship. But he saw several weaknesses in the new guidelines, including the fact that they did not update minor criteria for determining severe CAP from the 2007 guidelines, despite several studies indicating that there were other criteria to consider. In addition, the updated guidelines held a negative view of the use of serum procalcitonin to guide site-of-care decisions, which Dr. Niederman argued went against an analysis of the Etiology of Pneumonia in the Community (EPIC) study (CHEST. 2016; 150[4]:819-28) and other studies that showed its utility. He referred to his own editorial, in which he discussed the subject extensively (Lancet Resp Med. 2016;4[12]:956).
“Similarly, to me, the macrolide issue is not resolved,” he added, citing several studies that, in contrast to the guideline recommendations, used outpatient macrolide monotherapy to good results, and one study showed that “there was a much better patient outcome for patients who got macrolide monotherapy than for those who got quinolones” (Resp Med. 2012;106[3]:451-8).
Dr. Niederman is clinical director of the division of pulmonary and critical care medicine at New York Presbyterian Hospital/Weill Cornell Medical Center, and professor of clinical medicine at Weill Cornell Medical College, New York. He disclosed that he is a consultant for and has received grants from a variety of pharmaceutical companies, including Bayer and Merck.
“Ever since we wrote the first CAP [community-acquired pneumonia] guidelines in 1993, we’ve heard good and bad things, and I agree with both,” Michael S. Niederman, MD, FCCP, said in a presentation at IDWeek 2019. “For good or for bad, [guidelines] are a standard against which care can be evaluated.” He discussed how, as guidelines have become more evidence based, they have often become “more wishy washy,” that when the evidence is weak, the recommendation is weak, and the guidelines merely advise doctors: “You figure it out.”
However, he pointed out that, since CAP guidelines were developed, there have been overall improvements in patient care and antibiotic stewardship. But he saw several weaknesses in the new guidelines, including the fact that they did not update minor criteria for determining severe CAP from the 2007 guidelines, despite several studies indicating that there were other criteria to consider. In addition, the updated guidelines held a negative view of the use of serum procalcitonin to guide site-of-care decisions, which Dr. Niederman argued went against an analysis of the Etiology of Pneumonia in the Community (EPIC) study (CHEST. 2016; 150[4]:819-28) and other studies that showed its utility. He referred to his own editorial, in which he discussed the subject extensively (Lancet Resp Med. 2016;4[12]:956).
“Similarly, to me, the macrolide issue is not resolved,” he added, citing several studies that, in contrast to the guideline recommendations, used outpatient macrolide monotherapy to good results, and one study showed that “there was a much better patient outcome for patients who got macrolide monotherapy than for those who got quinolones” (Resp Med. 2012;106[3]:451-8).
Dr. Niederman is clinical director of the division of pulmonary and critical care medicine at New York Presbyterian Hospital/Weill Cornell Medical Center, and professor of clinical medicine at Weill Cornell Medical College, New York. He disclosed that he is a consultant for and has received grants from a variety of pharmaceutical companies, including Bayer and Merck.
“Ever since we wrote the first CAP [community-acquired pneumonia] guidelines in 1993, we’ve heard good and bad things, and I agree with both,” Michael S. Niederman, MD, FCCP, said in a presentation at IDWeek 2019. “For good or for bad, [guidelines] are a standard against which care can be evaluated.” He discussed how, as guidelines have become more evidence based, they have often become “more wishy washy,” that when the evidence is weak, the recommendation is weak, and the guidelines merely advise doctors: “You figure it out.”
However, he pointed out that, since CAP guidelines were developed, there have been overall improvements in patient care and antibiotic stewardship. But he saw several weaknesses in the new guidelines, including the fact that they did not update minor criteria for determining severe CAP from the 2007 guidelines, despite several studies indicating that there were other criteria to consider. In addition, the updated guidelines held a negative view of the use of serum procalcitonin to guide site-of-care decisions, which Dr. Niederman argued went against an analysis of the Etiology of Pneumonia in the Community (EPIC) study (CHEST. 2016; 150[4]:819-28) and other studies that showed its utility. He referred to his own editorial, in which he discussed the subject extensively (Lancet Resp Med. 2016;4[12]:956).
“Similarly, to me, the macrolide issue is not resolved,” he added, citing several studies that, in contrast to the guideline recommendations, used outpatient macrolide monotherapy to good results, and one study showed that “there was a much better patient outcome for patients who got macrolide monotherapy than for those who got quinolones” (Resp Med. 2012;106[3]:451-8).
Dr. Niederman is clinical director of the division of pulmonary and critical care medicine at New York Presbyterian Hospital/Weill Cornell Medical Center, and professor of clinical medicine at Weill Cornell Medical College, New York. He disclosed that he is a consultant for and has received grants from a variety of pharmaceutical companies, including Bayer and Merck.
An update to the 2007 guidelines on the treatment of community-acquired pneumonia (CAP) was published by two medical societies, based upon the work of a multidisciplinary panel that “conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.”
The panel addressed 16 questions in the areas including diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Some of their recommendations remained unchanged from the 2007 guideline, but others were updated based upon more-recent clinical trials and epidemiological studies, according to Joshua P. Metlay, MD, of Massachusetts General Hospital, Boston, and colleagues on behalf of the Infectious Diseases Society of America and the American Thoracic Society.
Among the key recommendations differing from the previous guidelines, the 2019 guidelines include the following:
- Sputum and blood culture samples are recommended in patients with severe disease, as well as in all inpatients empirically treated for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa.
- Macrolide monotherapy is only conditionally recommended for outpatients based on resistance levels.
- Procalcitonin assessment, not covered in the 2007 guidelines, is not recommended in order to determine initial antibiotic therapy.
- Corticosteroid use, not covered in the 2007 guidelines, is not recommended, though it may be considered in patients with refractory septic shock.
- The use of health care–associated pneumonia (HCAP) as a category should be dropped, with a switch to an emphasis on local epidemiology and validated risk factors to determine the need for MRSA or P. aeruginosa treatment.
- Standard empiric therapy for severe CAP should be beta-lactam/macrolide and beta-lactam/fluoroquinolone combinations, but with stronger evidence in favor of the beta-lactam/macrolide combination.
The updated guidelines also include a number of other recommendations, such as those dealing with the management of patients with comorbidities, and were published in the American Journal of Respiratory and Critical Care Medicine.
“A difference between this guideline and previous ones is that we have significantly increased the proportion of patients in whom we recommend routinely obtaining respiratory tract samples for microbiologic studies. This decision is largely based on a desire to correct the overuse of anti-MRSA and antipseudomonal therapy that has occurred since the introduction of the HCAP classification (which we recommend abandoning) rather than high-quality evidence,” the authors stated in their conclusions. They added that they “expect our move against endorsing monotherapy with macrolides, which is based on population resistance data rather than high-quality clinical studies, will generate future outcomes studies comparing different treatment strategies.”
Many of the authors reported relationships with a variety of pharmaceutical companies; full disclosures are detailed at the end of the guideline publication.
SOURCE: Metlay JP et al. Am J Respir Crit Med. 2019;200(7):e45-67.
An update to the 2007 guidelines on the treatment of community-acquired pneumonia (CAP) was published by two medical societies, based upon the work of a multidisciplinary panel that “conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.”
The panel addressed 16 questions in the areas including diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Some of their recommendations remained unchanged from the 2007 guideline, but others were updated based upon more-recent clinical trials and epidemiological studies, according to Joshua P. Metlay, MD, of Massachusetts General Hospital, Boston, and colleagues on behalf of the Infectious Diseases Society of America and the American Thoracic Society.
Among the key recommendations differing from the previous guidelines, the 2019 guidelines include the following:
- Sputum and blood culture samples are recommended in patients with severe disease, as well as in all inpatients empirically treated for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa.
- Macrolide monotherapy is only conditionally recommended for outpatients based on resistance levels.
- Procalcitonin assessment, not covered in the 2007 guidelines, is not recommended in order to determine initial antibiotic therapy.
- Corticosteroid use, not covered in the 2007 guidelines, is not recommended, though it may be considered in patients with refractory septic shock.
- The use of health care–associated pneumonia (HCAP) as a category should be dropped, with a switch to an emphasis on local epidemiology and validated risk factors to determine the need for MRSA or P. aeruginosa treatment.
- Standard empiric therapy for severe CAP should be beta-lactam/macrolide and beta-lactam/fluoroquinolone combinations, but with stronger evidence in favor of the beta-lactam/macrolide combination.
The updated guidelines also include a number of other recommendations, such as those dealing with the management of patients with comorbidities, and were published in the American Journal of Respiratory and Critical Care Medicine.
“A difference between this guideline and previous ones is that we have significantly increased the proportion of patients in whom we recommend routinely obtaining respiratory tract samples for microbiologic studies. This decision is largely based on a desire to correct the overuse of anti-MRSA and antipseudomonal therapy that has occurred since the introduction of the HCAP classification (which we recommend abandoning) rather than high-quality evidence,” the authors stated in their conclusions. They added that they “expect our move against endorsing monotherapy with macrolides, which is based on population resistance data rather than high-quality clinical studies, will generate future outcomes studies comparing different treatment strategies.”
Many of the authors reported relationships with a variety of pharmaceutical companies; full disclosures are detailed at the end of the guideline publication.
SOURCE: Metlay JP et al. Am J Respir Crit Med. 2019;200(7):e45-67.
FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Amoxicillin/clavulanate emerges as best antibiotic for childhood bronchiectasis
MADRID – A placebo-controlled trial has confirmed that amoxicillin/clavulanate is beneficial for resolution of acute exacerbations in nonsevere bronchiectasis while also demonstrating a greater relative effect than azithromycin, based on data presented at the annual congress of the European Respiratory Society.
“We now have robust data with which to support our guidelines,” reported Vikas Goyal, MD, of the Children’s Health Clinical Unit, University of Queensland, Brisbane, Australia.
The study addresses a knowledge gap. Antibiotics are already recommended by many guidelines for treatment of acute exacerbations in children with bronchiectasis, but Dr. Goyal said that no controlled trials have ever been performed in this age group to confirm superiority to placebo.
In this multicenter study, called BEST-1, 197 children with bronchiectasis were randomized at the start of an exacerbation to placebo, 45 mg/kg per day of amoxicillin/clavulanate, or 5 mg/kg per day of azithromycin. To maintain blinding, patients in the active treatment groups received a dummy for the opposite antibiotic while patients on placebo received dummies for both active agents.
For the primary outcome, 65% of children randomized to amoxicillin/clavulanate had resolution of their exacerbation by day 14 versus 61% of those randomized to azithromycin and 43% of those randomized to placebo. On the basis of relative risk for reaching this end point, the outcome was superior to placebo for amoxicillin/clavulanate (RR, 1.5; P = .015).
Although the relative risk for azithromycin (RR, 1.4; P = .042) was only slightly lower, it did not reach a prespecified level of significance set at P = .025. Dr. Goyal did report that the resolution rate at 14 days in the placebo group was “higher than expected.”
In this trial, 53% of the 154 children who were tested for respiratory viruses with nasal swabs on day 1 of the exacerbation were found to have respiratory viruses. Of these viruses, rhinovirus was the most common, according to Dr. Goyal, whose data were published just prior to his presentation (Lancet Respir Med. 2019;7:791-801).
The median durations of the exacerbations were 7 days, 8 days, and 10 days for those treated with amoxicillin/clavulanate, azithromycin, and placebo, respectively. The difference between amoxicillin/clavulanate and placebo, but not that between azithromycin and placebo, reached statistical significance, Dr. Goyal said.
There were no between group differences in the time to next exacerbation.
In discussing limitations of this study, Dr. Goyal pointed out that the optimal doses of amoxicillin/clavulanate or azithromycin have never been established for the treatment of exacerbations in children with bronchiectasis. He noted that some infectious disease specialists have advocated higher doses of both than those employed in this trial, but dose-ranging studies have never been conducted in this age group.
In this study, adverse events were less common on azithromycin than amoxicillin/clavulanate (21% vs. 30%), but none were severe, according to Dr. Goyal. He said treatment with azithromycin was associated with increased macrolide-resistant bacteria.
On the basis of these data, Dr. Goyal concluded that amoxicillin/clavulanate should remain, as already specified in some guidelines, the standard first-line therapy for nonsevere exacerbations in nonhospitalized children with bronchiectasis. He recommended reserving azithromycin as an alternative therapy.
Dr. Goyal reports no potential conflicts of interest.
SOURCE: Goyal V et al. Lancet Respir Med. 2019;7:791-801.
MADRID – A placebo-controlled trial has confirmed that amoxicillin/clavulanate is beneficial for resolution of acute exacerbations in nonsevere bronchiectasis while also demonstrating a greater relative effect than azithromycin, based on data presented at the annual congress of the European Respiratory Society.
“We now have robust data with which to support our guidelines,” reported Vikas Goyal, MD, of the Children’s Health Clinical Unit, University of Queensland, Brisbane, Australia.
The study addresses a knowledge gap. Antibiotics are already recommended by many guidelines for treatment of acute exacerbations in children with bronchiectasis, but Dr. Goyal said that no controlled trials have ever been performed in this age group to confirm superiority to placebo.
In this multicenter study, called BEST-1, 197 children with bronchiectasis were randomized at the start of an exacerbation to placebo, 45 mg/kg per day of amoxicillin/clavulanate, or 5 mg/kg per day of azithromycin. To maintain blinding, patients in the active treatment groups received a dummy for the opposite antibiotic while patients on placebo received dummies for both active agents.
For the primary outcome, 65% of children randomized to amoxicillin/clavulanate had resolution of their exacerbation by day 14 versus 61% of those randomized to azithromycin and 43% of those randomized to placebo. On the basis of relative risk for reaching this end point, the outcome was superior to placebo for amoxicillin/clavulanate (RR, 1.5; P = .015).
Although the relative risk for azithromycin (RR, 1.4; P = .042) was only slightly lower, it did not reach a prespecified level of significance set at P = .025. Dr. Goyal did report that the resolution rate at 14 days in the placebo group was “higher than expected.”
In this trial, 53% of the 154 children who were tested for respiratory viruses with nasal swabs on day 1 of the exacerbation were found to have respiratory viruses. Of these viruses, rhinovirus was the most common, according to Dr. Goyal, whose data were published just prior to his presentation (Lancet Respir Med. 2019;7:791-801).
The median durations of the exacerbations were 7 days, 8 days, and 10 days for those treated with amoxicillin/clavulanate, azithromycin, and placebo, respectively. The difference between amoxicillin/clavulanate and placebo, but not that between azithromycin and placebo, reached statistical significance, Dr. Goyal said.
There were no between group differences in the time to next exacerbation.
In discussing limitations of this study, Dr. Goyal pointed out that the optimal doses of amoxicillin/clavulanate or azithromycin have never been established for the treatment of exacerbations in children with bronchiectasis. He noted that some infectious disease specialists have advocated higher doses of both than those employed in this trial, but dose-ranging studies have never been conducted in this age group.
In this study, adverse events were less common on azithromycin than amoxicillin/clavulanate (21% vs. 30%), but none were severe, according to Dr. Goyal. He said treatment with azithromycin was associated with increased macrolide-resistant bacteria.
On the basis of these data, Dr. Goyal concluded that amoxicillin/clavulanate should remain, as already specified in some guidelines, the standard first-line therapy for nonsevere exacerbations in nonhospitalized children with bronchiectasis. He recommended reserving azithromycin as an alternative therapy.
Dr. Goyal reports no potential conflicts of interest.
SOURCE: Goyal V et al. Lancet Respir Med. 2019;7:791-801.
MADRID – A placebo-controlled trial has confirmed that amoxicillin/clavulanate is beneficial for resolution of acute exacerbations in nonsevere bronchiectasis while also demonstrating a greater relative effect than azithromycin, based on data presented at the annual congress of the European Respiratory Society.
“We now have robust data with which to support our guidelines,” reported Vikas Goyal, MD, of the Children’s Health Clinical Unit, University of Queensland, Brisbane, Australia.
The study addresses a knowledge gap. Antibiotics are already recommended by many guidelines for treatment of acute exacerbations in children with bronchiectasis, but Dr. Goyal said that no controlled trials have ever been performed in this age group to confirm superiority to placebo.
In this multicenter study, called BEST-1, 197 children with bronchiectasis were randomized at the start of an exacerbation to placebo, 45 mg/kg per day of amoxicillin/clavulanate, or 5 mg/kg per day of azithromycin. To maintain blinding, patients in the active treatment groups received a dummy for the opposite antibiotic while patients on placebo received dummies for both active agents.
For the primary outcome, 65% of children randomized to amoxicillin/clavulanate had resolution of their exacerbation by day 14 versus 61% of those randomized to azithromycin and 43% of those randomized to placebo. On the basis of relative risk for reaching this end point, the outcome was superior to placebo for amoxicillin/clavulanate (RR, 1.5; P = .015).
Although the relative risk for azithromycin (RR, 1.4; P = .042) was only slightly lower, it did not reach a prespecified level of significance set at P = .025. Dr. Goyal did report that the resolution rate at 14 days in the placebo group was “higher than expected.”
In this trial, 53% of the 154 children who were tested for respiratory viruses with nasal swabs on day 1 of the exacerbation were found to have respiratory viruses. Of these viruses, rhinovirus was the most common, according to Dr. Goyal, whose data were published just prior to his presentation (Lancet Respir Med. 2019;7:791-801).
The median durations of the exacerbations were 7 days, 8 days, and 10 days for those treated with amoxicillin/clavulanate, azithromycin, and placebo, respectively. The difference between amoxicillin/clavulanate and placebo, but not that between azithromycin and placebo, reached statistical significance, Dr. Goyal said.
There were no between group differences in the time to next exacerbation.
In discussing limitations of this study, Dr. Goyal pointed out that the optimal doses of amoxicillin/clavulanate or azithromycin have never been established for the treatment of exacerbations in children with bronchiectasis. He noted that some infectious disease specialists have advocated higher doses of both than those employed in this trial, but dose-ranging studies have never been conducted in this age group.
In this study, adverse events were less common on azithromycin than amoxicillin/clavulanate (21% vs. 30%), but none were severe, according to Dr. Goyal. He said treatment with azithromycin was associated with increased macrolide-resistant bacteria.
On the basis of these data, Dr. Goyal concluded that amoxicillin/clavulanate should remain, as already specified in some guidelines, the standard first-line therapy for nonsevere exacerbations in nonhospitalized children with bronchiectasis. He recommended reserving azithromycin as an alternative therapy.
Dr. Goyal reports no potential conflicts of interest.
SOURCE: Goyal V et al. Lancet Respir Med. 2019;7:791-801.
REPORTING FROM ERS 2019
‘Forward-Oriented’ Vector Holds Potential for Sickle Cell Cure
About 100,000 people in America have sickle cell disease. Of those, an estimated 27 people have undergone experimental gene therapy using conventional vectors—virus-based vehicles for delivering “therapeutic genes.” Now National Institutes of Health researchers have taken the vector idea and revved it up, bringing the possibility of curing sickle cell disease a bit closer.
With gene therapy, doctors add a normal copy of the β-globin gene to the patient’s hematopoietic stem cells, then reinfuse the modified stem cells into the patient to produce normal disc-shaped red blood cells. In animal studies, the new vector was up to 10 times more efficient at incorporating corrective genes into bone marrow stem cells with a carrying capacity of up to 6 times greater viral load than current vectors. The new vectors also can be produced in much higher amounts, saving time and lowering costs.
The researchers call it a “forward-oriented” vector because it changes the usual direction of how gene sequences in globin-containing vectors are read: from right to left. That backward orientation—globin-containing vectors are the only therapeutic vectors in clinical development that use it—the researchers say, “has remained unchallenged for decades despite its negative impacts on efficiency.”
The right-to-left orientation was dictated by the need to prevent the loss of a key molecular component, intron 2, by RNA splicing during the vector preparation. The redesigned forward-reading method crucially leaves intron 2 intact and makes the gene-translation approach less complicated, says John Tisdale, MD, chief of the Cellular and Molecular Therapeutic Branch at the National Heart, Lung, and Blood Institute, who, with Naoya Uchida, MD, PhD, came up with the idea.
In testing, the new vectors also proved longer lasting, remaining in place 4 years after transplantation.
National Institutes of Health is working to accelerate research and development through the Cure Sickle Cell Initiative, launched by NHLBI in 2018 to identify and support the most promising genetic therapies for the more than 20 million people worldwide who have sickle cell disease. NIH holds the patent for the new vector, which still will need clinical testing in humans. Clinical trials are actively enrolling.
About 100,000 people in America have sickle cell disease. Of those, an estimated 27 people have undergone experimental gene therapy using conventional vectors—virus-based vehicles for delivering “therapeutic genes.” Now National Institutes of Health researchers have taken the vector idea and revved it up, bringing the possibility of curing sickle cell disease a bit closer.
With gene therapy, doctors add a normal copy of the β-globin gene to the patient’s hematopoietic stem cells, then reinfuse the modified stem cells into the patient to produce normal disc-shaped red blood cells. In animal studies, the new vector was up to 10 times more efficient at incorporating corrective genes into bone marrow stem cells with a carrying capacity of up to 6 times greater viral load than current vectors. The new vectors also can be produced in much higher amounts, saving time and lowering costs.
The researchers call it a “forward-oriented” vector because it changes the usual direction of how gene sequences in globin-containing vectors are read: from right to left. That backward orientation—globin-containing vectors are the only therapeutic vectors in clinical development that use it—the researchers say, “has remained unchallenged for decades despite its negative impacts on efficiency.”
The right-to-left orientation was dictated by the need to prevent the loss of a key molecular component, intron 2, by RNA splicing during the vector preparation. The redesigned forward-reading method crucially leaves intron 2 intact and makes the gene-translation approach less complicated, says John Tisdale, MD, chief of the Cellular and Molecular Therapeutic Branch at the National Heart, Lung, and Blood Institute, who, with Naoya Uchida, MD, PhD, came up with the idea.
In testing, the new vectors also proved longer lasting, remaining in place 4 years after transplantation.
National Institutes of Health is working to accelerate research and development through the Cure Sickle Cell Initiative, launched by NHLBI in 2018 to identify and support the most promising genetic therapies for the more than 20 million people worldwide who have sickle cell disease. NIH holds the patent for the new vector, which still will need clinical testing in humans. Clinical trials are actively enrolling.
About 100,000 people in America have sickle cell disease. Of those, an estimated 27 people have undergone experimental gene therapy using conventional vectors—virus-based vehicles for delivering “therapeutic genes.” Now National Institutes of Health researchers have taken the vector idea and revved it up, bringing the possibility of curing sickle cell disease a bit closer.
With gene therapy, doctors add a normal copy of the β-globin gene to the patient’s hematopoietic stem cells, then reinfuse the modified stem cells into the patient to produce normal disc-shaped red blood cells. In animal studies, the new vector was up to 10 times more efficient at incorporating corrective genes into bone marrow stem cells with a carrying capacity of up to 6 times greater viral load than current vectors. The new vectors also can be produced in much higher amounts, saving time and lowering costs.
The researchers call it a “forward-oriented” vector because it changes the usual direction of how gene sequences in globin-containing vectors are read: from right to left. That backward orientation—globin-containing vectors are the only therapeutic vectors in clinical development that use it—the researchers say, “has remained unchallenged for decades despite its negative impacts on efficiency.”
The right-to-left orientation was dictated by the need to prevent the loss of a key molecular component, intron 2, by RNA splicing during the vector preparation. The redesigned forward-reading method crucially leaves intron 2 intact and makes the gene-translation approach less complicated, says John Tisdale, MD, chief of the Cellular and Molecular Therapeutic Branch at the National Heart, Lung, and Blood Institute, who, with Naoya Uchida, MD, PhD, came up with the idea.
In testing, the new vectors also proved longer lasting, remaining in place 4 years after transplantation.
National Institutes of Health is working to accelerate research and development through the Cure Sickle Cell Initiative, launched by NHLBI in 2018 to identify and support the most promising genetic therapies for the more than 20 million people worldwide who have sickle cell disease. NIH holds the patent for the new vector, which still will need clinical testing in humans. Clinical trials are actively enrolling.
Physician: The nicotine, not the flavors, needs regulation
While most of the recent legislative action on e-cigarettes and other electronic nicotine delivery systems are focusing on the flavors that are appealing, especially to children,
Michael B. Siegel, MD, MPH, a physician and professor at Boston University School of Public Health, said the turning point in the spike in youth e-cigarettes occurred when products like Juul, Sourin, Smok, and Phix were introduced into the market.
Prior to that, he noted that, in 2014, citing that year’s National Youth Tobacco Survey from the Centers for Disease Control and Prevention, 74% of nonsmoking youth e-cigarette users reported using e-cigarettes no more than once per week, while only 4% reported daily use. By 2018, 12% of nonsmoking youth e-cigarette users were using e-cigarettes daily, while 42% of nonsmoking e-cigarette use was no more than once a week, according to that year’s CDC survey.
“All of these brands use a different nicotine formulation from virtually all other e-cigarettes,” Dr. Siegel testified Oct. 16 at a House Energy and Commerce Health Subcommittee hearing. “They use a nicotine salt at very high concentrations.”
His written testimony notes that Juul and similar products use nicotine salt at concentrations of 50 mg/mL, whereas most other e-cigarette products have nicotine concentrations that are less than 25 mg/mL.
“The use of nicotine salts allows nicotine to be absorbed into the bloodstream much more quickly, simulating the pattern you get with a real cigarette,” he continued. “That is why so many youth are now addicted to vaping. It is not the flavors. It’s the nicotine.”
Susanne Tanski, MD, testifying on behalf of the American Academy of Pediatrics agreed with Dr. Siegel that the Food and Drug Administration needs to be doing more to regulate the amount of nicotine that these products are releasing and that the introduction of nicotine salt was a significant cause of addiction.
However, she also targeted flavors as a key issue.
“There is reasonable concern that flavors may also modify the addictiveness of e-cigarettes, but with the thousands of flavor combinations on the market, there has not been specific research yet to test this hypothesis,” Dr. Tanksi, a pediatrician at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., noted in her written testimony. “We know that flavors unto themselves are pleasurable. If you link a pleasurable flavor with a buzz of nicotine from a powerful nicotine delivery system such as the newer e-cigarettes, perhaps this is even more behaviorally and biologically reinforcing to drive the addictiveness of this new generation of products.”
Other panelists also expressed concern about the flavoring of e-cigarettes.
Subcommittee Chair Anna Eshoo (D-Calif.) noted that “flavor is very attractive. It really drives our eating habits and other habits.” She then asked whether “e-cigarettes’ sweet flavors have contributed to youth tobacco use.”
Matthew L. Myers, president of the Campaign for Tobacco-Free Kids, responded by saying that all “of the evidence is that they are the driving force of that and that it has gotten worse over the last 4 years.”
He also noted that while youth use of flavored products has spiked in the last 4 years, there really has not been any growth in adult usage of flavored tobacco.
“What it shows is the introduction of all these flavors has fueled a youth epidemic, but it has had no impact whatsoever” on adults. “Indeed, before Juul was introduced, the most popular e-cigarette flavor was tobacco. So, for smokers who want to quit, that was a viable option until Juul changed the market.”
The subcommittee hearing was held to solicit opinions on H.R. 2339, the “Reversing the Youth Tobacco Epidemic Act of 2019.” Among the provisions in the bill are raising the minimum age of purchasing all tobacco and nicotine products to age 21 years, requiring health warning labels on e-cigarette products, placing restrictions on advertising that are similar to those on smoking products, and prohibiting Internet sales of e-cigarettes.
Dr. Siegel voiced his approval for the bill, providing the provision that bans all flavored tobacco products was removed.
He noted that the current epidemic of vaping illness and deaths recently has not been caused primarily from legit e-cigarette and other vaping products, but rather from black market, THC-laced vaping cartridges.
“A ban on flavored e-cigarettes would create a public health disaster because it would create a new black market for flavored e-liquids,” he testified. “It is nearly certain that we would see more outbreaks similar to what we are seeing now with these tainted THC vape cartridges.”
He continued: “Banning flavored e-liquids is not going to do anything to curtail this respiratory disease outbreak, but it may make the outbreak worse. Why? Because the supply of e-liquids that youth are vaping is going to transition from one dominated by nicotine products to one dominated by THC products, exactly the products that are causing this outbreak.”
Dr. Siegel also spoke to the potential effect it might have on adult smokers who have abandoned combustible tobacco products in favor of e-cigarettes.
“More than 2 million adult smokers in the U.S. have quit smoking completely by switching to flavored electronic cigarettes,” he said. “If these products are banned, many of these ex-smokers will return to cigarette smoking. Most of those who don’t will turn to a new potentially dangerous black market that will be created by this legislation.”
Dr. Tanski, on the other hand, called the provision banning all flavored tobacco products, including menthol, “the single most important policy that Congress can pass to address the youth tobacco epidemic, and a step that Congress took years ago for other flavored cigarettes.”
While most of the recent legislative action on e-cigarettes and other electronic nicotine delivery systems are focusing on the flavors that are appealing, especially to children,
Michael B. Siegel, MD, MPH, a physician and professor at Boston University School of Public Health, said the turning point in the spike in youth e-cigarettes occurred when products like Juul, Sourin, Smok, and Phix were introduced into the market.
Prior to that, he noted that, in 2014, citing that year’s National Youth Tobacco Survey from the Centers for Disease Control and Prevention, 74% of nonsmoking youth e-cigarette users reported using e-cigarettes no more than once per week, while only 4% reported daily use. By 2018, 12% of nonsmoking youth e-cigarette users were using e-cigarettes daily, while 42% of nonsmoking e-cigarette use was no more than once a week, according to that year’s CDC survey.
“All of these brands use a different nicotine formulation from virtually all other e-cigarettes,” Dr. Siegel testified Oct. 16 at a House Energy and Commerce Health Subcommittee hearing. “They use a nicotine salt at very high concentrations.”
His written testimony notes that Juul and similar products use nicotine salt at concentrations of 50 mg/mL, whereas most other e-cigarette products have nicotine concentrations that are less than 25 mg/mL.
“The use of nicotine salts allows nicotine to be absorbed into the bloodstream much more quickly, simulating the pattern you get with a real cigarette,” he continued. “That is why so many youth are now addicted to vaping. It is not the flavors. It’s the nicotine.”
Susanne Tanski, MD, testifying on behalf of the American Academy of Pediatrics agreed with Dr. Siegel that the Food and Drug Administration needs to be doing more to regulate the amount of nicotine that these products are releasing and that the introduction of nicotine salt was a significant cause of addiction.
However, she also targeted flavors as a key issue.
“There is reasonable concern that flavors may also modify the addictiveness of e-cigarettes, but with the thousands of flavor combinations on the market, there has not been specific research yet to test this hypothesis,” Dr. Tanksi, a pediatrician at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., noted in her written testimony. “We know that flavors unto themselves are pleasurable. If you link a pleasurable flavor with a buzz of nicotine from a powerful nicotine delivery system such as the newer e-cigarettes, perhaps this is even more behaviorally and biologically reinforcing to drive the addictiveness of this new generation of products.”
Other panelists also expressed concern about the flavoring of e-cigarettes.
Subcommittee Chair Anna Eshoo (D-Calif.) noted that “flavor is very attractive. It really drives our eating habits and other habits.” She then asked whether “e-cigarettes’ sweet flavors have contributed to youth tobacco use.”
Matthew L. Myers, president of the Campaign for Tobacco-Free Kids, responded by saying that all “of the evidence is that they are the driving force of that and that it has gotten worse over the last 4 years.”
He also noted that while youth use of flavored products has spiked in the last 4 years, there really has not been any growth in adult usage of flavored tobacco.
“What it shows is the introduction of all these flavors has fueled a youth epidemic, but it has had no impact whatsoever” on adults. “Indeed, before Juul was introduced, the most popular e-cigarette flavor was tobacco. So, for smokers who want to quit, that was a viable option until Juul changed the market.”
The subcommittee hearing was held to solicit opinions on H.R. 2339, the “Reversing the Youth Tobacco Epidemic Act of 2019.” Among the provisions in the bill are raising the minimum age of purchasing all tobacco and nicotine products to age 21 years, requiring health warning labels on e-cigarette products, placing restrictions on advertising that are similar to those on smoking products, and prohibiting Internet sales of e-cigarettes.
Dr. Siegel voiced his approval for the bill, providing the provision that bans all flavored tobacco products was removed.
He noted that the current epidemic of vaping illness and deaths recently has not been caused primarily from legit e-cigarette and other vaping products, but rather from black market, THC-laced vaping cartridges.
“A ban on flavored e-cigarettes would create a public health disaster because it would create a new black market for flavored e-liquids,” he testified. “It is nearly certain that we would see more outbreaks similar to what we are seeing now with these tainted THC vape cartridges.”
He continued: “Banning flavored e-liquids is not going to do anything to curtail this respiratory disease outbreak, but it may make the outbreak worse. Why? Because the supply of e-liquids that youth are vaping is going to transition from one dominated by nicotine products to one dominated by THC products, exactly the products that are causing this outbreak.”
Dr. Siegel also spoke to the potential effect it might have on adult smokers who have abandoned combustible tobacco products in favor of e-cigarettes.
“More than 2 million adult smokers in the U.S. have quit smoking completely by switching to flavored electronic cigarettes,” he said. “If these products are banned, many of these ex-smokers will return to cigarette smoking. Most of those who don’t will turn to a new potentially dangerous black market that will be created by this legislation.”
Dr. Tanski, on the other hand, called the provision banning all flavored tobacco products, including menthol, “the single most important policy that Congress can pass to address the youth tobacco epidemic, and a step that Congress took years ago for other flavored cigarettes.”
While most of the recent legislative action on e-cigarettes and other electronic nicotine delivery systems are focusing on the flavors that are appealing, especially to children,
Michael B. Siegel, MD, MPH, a physician and professor at Boston University School of Public Health, said the turning point in the spike in youth e-cigarettes occurred when products like Juul, Sourin, Smok, and Phix were introduced into the market.
Prior to that, he noted that, in 2014, citing that year’s National Youth Tobacco Survey from the Centers for Disease Control and Prevention, 74% of nonsmoking youth e-cigarette users reported using e-cigarettes no more than once per week, while only 4% reported daily use. By 2018, 12% of nonsmoking youth e-cigarette users were using e-cigarettes daily, while 42% of nonsmoking e-cigarette use was no more than once a week, according to that year’s CDC survey.
“All of these brands use a different nicotine formulation from virtually all other e-cigarettes,” Dr. Siegel testified Oct. 16 at a House Energy and Commerce Health Subcommittee hearing. “They use a nicotine salt at very high concentrations.”
His written testimony notes that Juul and similar products use nicotine salt at concentrations of 50 mg/mL, whereas most other e-cigarette products have nicotine concentrations that are less than 25 mg/mL.
“The use of nicotine salts allows nicotine to be absorbed into the bloodstream much more quickly, simulating the pattern you get with a real cigarette,” he continued. “That is why so many youth are now addicted to vaping. It is not the flavors. It’s the nicotine.”
Susanne Tanski, MD, testifying on behalf of the American Academy of Pediatrics agreed with Dr. Siegel that the Food and Drug Administration needs to be doing more to regulate the amount of nicotine that these products are releasing and that the introduction of nicotine salt was a significant cause of addiction.
However, she also targeted flavors as a key issue.
“There is reasonable concern that flavors may also modify the addictiveness of e-cigarettes, but with the thousands of flavor combinations on the market, there has not been specific research yet to test this hypothesis,” Dr. Tanksi, a pediatrician at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., noted in her written testimony. “We know that flavors unto themselves are pleasurable. If you link a pleasurable flavor with a buzz of nicotine from a powerful nicotine delivery system such as the newer e-cigarettes, perhaps this is even more behaviorally and biologically reinforcing to drive the addictiveness of this new generation of products.”
Other panelists also expressed concern about the flavoring of e-cigarettes.
Subcommittee Chair Anna Eshoo (D-Calif.) noted that “flavor is very attractive. It really drives our eating habits and other habits.” She then asked whether “e-cigarettes’ sweet flavors have contributed to youth tobacco use.”
Matthew L. Myers, president of the Campaign for Tobacco-Free Kids, responded by saying that all “of the evidence is that they are the driving force of that and that it has gotten worse over the last 4 years.”
He also noted that while youth use of flavored products has spiked in the last 4 years, there really has not been any growth in adult usage of flavored tobacco.
“What it shows is the introduction of all these flavors has fueled a youth epidemic, but it has had no impact whatsoever” on adults. “Indeed, before Juul was introduced, the most popular e-cigarette flavor was tobacco. So, for smokers who want to quit, that was a viable option until Juul changed the market.”
The subcommittee hearing was held to solicit opinions on H.R. 2339, the “Reversing the Youth Tobacco Epidemic Act of 2019.” Among the provisions in the bill are raising the minimum age of purchasing all tobacco and nicotine products to age 21 years, requiring health warning labels on e-cigarette products, placing restrictions on advertising that are similar to those on smoking products, and prohibiting Internet sales of e-cigarettes.
Dr. Siegel voiced his approval for the bill, providing the provision that bans all flavored tobacco products was removed.
He noted that the current epidemic of vaping illness and deaths recently has not been caused primarily from legit e-cigarette and other vaping products, but rather from black market, THC-laced vaping cartridges.
“A ban on flavored e-cigarettes would create a public health disaster because it would create a new black market for flavored e-liquids,” he testified. “It is nearly certain that we would see more outbreaks similar to what we are seeing now with these tainted THC vape cartridges.”
He continued: “Banning flavored e-liquids is not going to do anything to curtail this respiratory disease outbreak, but it may make the outbreak worse. Why? Because the supply of e-liquids that youth are vaping is going to transition from one dominated by nicotine products to one dominated by THC products, exactly the products that are causing this outbreak.”
Dr. Siegel also spoke to the potential effect it might have on adult smokers who have abandoned combustible tobacco products in favor of e-cigarettes.
“More than 2 million adult smokers in the U.S. have quit smoking completely by switching to flavored electronic cigarettes,” he said. “If these products are banned, many of these ex-smokers will return to cigarette smoking. Most of those who don’t will turn to a new potentially dangerous black market that will be created by this legislation.”
Dr. Tanski, on the other hand, called the provision banning all flavored tobacco products, including menthol, “the single most important policy that Congress can pass to address the youth tobacco epidemic, and a step that Congress took years ago for other flavored cigarettes.”
REPORTING FROM A HOUSE ENERGY AND COMMERCE HEALTH SUBCOMMITTEE HEARING
Vaping-linked lung injuries near 1,500
according to the latest update provided by the Centers for Disease Control and Prevention. Thirty-three deaths have been confirmed.
E-cigarette–linked lung injuries, now called EVALI, occurred in all U.S. states (except Alaska), the District of Columbia, and the U.S. Virgin Islands. Seventy percent of patients are male, and 79% are under age 35 years.
Information on the substances used over the previous 3 months before symptom onset was available for 849 patients and included the following:
- 78% reported using THC-containing products, with or without nicotine-containing products;
- 31% reported exclusive use of THC-containing products;
- 58% reported using nicotine-containing products, with or without THC-containing products; and
- 10% reported exclusive use of nicotine-containing products.
CDC is now doing additional testing on available samples for chemical in the bronchoalveolar lavage fluid, blood, or urine, as well as lung biopsy or autopsy specimens. CDC is also validating methods for aerosol emission testing of case-associated product samples from vaping products and e-liquids.
In a related development, JUUL, maker of e-cigarette products, has announced that it will suspend the sale of nontobacco, nonmenthol flavors (mango, creme, fruit, and cucumber) in the United States, pending review by the Food and Drug Administration. The JUUL announcement comes in advance of an expected FDA ban on flavored e-cigarettes.
The CDC continues its investigation into EVALI but stated, “Since the specific cause or causes of lung injury are not yet known, the only way to assure that you are not at risk while the investigation continues is to consider refraining from use of all e-cigarette, or vaping, products.”
For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.
according to the latest update provided by the Centers for Disease Control and Prevention. Thirty-three deaths have been confirmed.
E-cigarette–linked lung injuries, now called EVALI, occurred in all U.S. states (except Alaska), the District of Columbia, and the U.S. Virgin Islands. Seventy percent of patients are male, and 79% are under age 35 years.
Information on the substances used over the previous 3 months before symptom onset was available for 849 patients and included the following:
- 78% reported using THC-containing products, with or without nicotine-containing products;
- 31% reported exclusive use of THC-containing products;
- 58% reported using nicotine-containing products, with or without THC-containing products; and
- 10% reported exclusive use of nicotine-containing products.
CDC is now doing additional testing on available samples for chemical in the bronchoalveolar lavage fluid, blood, or urine, as well as lung biopsy or autopsy specimens. CDC is also validating methods for aerosol emission testing of case-associated product samples from vaping products and e-liquids.
In a related development, JUUL, maker of e-cigarette products, has announced that it will suspend the sale of nontobacco, nonmenthol flavors (mango, creme, fruit, and cucumber) in the United States, pending review by the Food and Drug Administration. The JUUL announcement comes in advance of an expected FDA ban on flavored e-cigarettes.
The CDC continues its investigation into EVALI but stated, “Since the specific cause or causes of lung injury are not yet known, the only way to assure that you are not at risk while the investigation continues is to consider refraining from use of all e-cigarette, or vaping, products.”
For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.
according to the latest update provided by the Centers for Disease Control and Prevention. Thirty-three deaths have been confirmed.
E-cigarette–linked lung injuries, now called EVALI, occurred in all U.S. states (except Alaska), the District of Columbia, and the U.S. Virgin Islands. Seventy percent of patients are male, and 79% are under age 35 years.
Information on the substances used over the previous 3 months before symptom onset was available for 849 patients and included the following:
- 78% reported using THC-containing products, with or without nicotine-containing products;
- 31% reported exclusive use of THC-containing products;
- 58% reported using nicotine-containing products, with or without THC-containing products; and
- 10% reported exclusive use of nicotine-containing products.
CDC is now doing additional testing on available samples for chemical in the bronchoalveolar lavage fluid, blood, or urine, as well as lung biopsy or autopsy specimens. CDC is also validating methods for aerosol emission testing of case-associated product samples from vaping products and e-liquids.
In a related development, JUUL, maker of e-cigarette products, has announced that it will suspend the sale of nontobacco, nonmenthol flavors (mango, creme, fruit, and cucumber) in the United States, pending review by the Food and Drug Administration. The JUUL announcement comes in advance of an expected FDA ban on flavored e-cigarettes.
The CDC continues its investigation into EVALI but stated, “Since the specific cause or causes of lung injury are not yet known, the only way to assure that you are not at risk while the investigation continues is to consider refraining from use of all e-cigarette, or vaping, products.”
For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.
Eureka Challenge Winners Help Lighten the Load of Life With Alzheimer Disease
Mobile applications and other tech solutions that target the specific needs of patients with Alzheimer and their caregivers won the day in the first Eureka prize competition, sponsored by the National Institute on Aging.
The Improving Care for People with Alzheimer’s Disease and Related Dementias Using Technology (iCare-AD/ADRD) Challenge received 33 applications for mobile device applications or web-based methods to help users coordinate and navigate life with dementia. The judging was based on creativity and innovation, rationale and potential impact, value to relevant stakeholders, usability, and functionality and feasibility.
First place, with $250,000, went to MapHabit for mobile software that provides behavior prompts with customizable picture-and-keyword visual maps to help people with activities of daily living. The platform has different interfaces for users: people with impaired memory, caregiver, or long-term care community manager. Simple commands, such as “take a shower,” are scheduled, with feedback provided to caregivers. The system takes advantage of the brain’s habit (procedural) memory system, the researchers say, rather than the hippocampal (declarative) memory system that is damaged early in AD.
A team from University of California, Los Angeles, won second prize of $100,000 for their web-based Dementia Care Software system, which helps coordinate complex medical and social services. The software, which can be integrated into any of the leading electronic health record systems, has already been used in support of the UCLA Alzheimer’s and Dementia Care Program, a nurse-practitioner co-management approach that includes structured needs assessment, individualized dementia care plans, and round-the-clock access for assistance and advice. The researchers say more than 2,600 patients with dementia have participated in the program so far.
Caregiver411, developed by researchers from North Carolina Agricultural and Technical State University, won the third-place prize of $50,000. The mobile app helps people make informed decisions by, for instance, capturing the care recipient’s stage of AD in order to provide targeted recommendations. Dementia caregivers can obtain tailored resources related to mental, emotional, physical, social, legal, and financial concerns. The app also gives them a forum for social connections and family chat groups through a messaging center.
The Eureka Challenge is part of the 21st Century Cures Act, signed into law in 2016, designed to help accelerate medical product development with innovations incorporating the perspectives of patients. More detailed project descriptions are available at www.nia.nih.gov/challenge-prize.
Mobile applications and other tech solutions that target the specific needs of patients with Alzheimer and their caregivers won the day in the first Eureka prize competition, sponsored by the National Institute on Aging.
The Improving Care for People with Alzheimer’s Disease and Related Dementias Using Technology (iCare-AD/ADRD) Challenge received 33 applications for mobile device applications or web-based methods to help users coordinate and navigate life with dementia. The judging was based on creativity and innovation, rationale and potential impact, value to relevant stakeholders, usability, and functionality and feasibility.
First place, with $250,000, went to MapHabit for mobile software that provides behavior prompts with customizable picture-and-keyword visual maps to help people with activities of daily living. The platform has different interfaces for users: people with impaired memory, caregiver, or long-term care community manager. Simple commands, such as “take a shower,” are scheduled, with feedback provided to caregivers. The system takes advantage of the brain’s habit (procedural) memory system, the researchers say, rather than the hippocampal (declarative) memory system that is damaged early in AD.
A team from University of California, Los Angeles, won second prize of $100,000 for their web-based Dementia Care Software system, which helps coordinate complex medical and social services. The software, which can be integrated into any of the leading electronic health record systems, has already been used in support of the UCLA Alzheimer’s and Dementia Care Program, a nurse-practitioner co-management approach that includes structured needs assessment, individualized dementia care plans, and round-the-clock access for assistance and advice. The researchers say more than 2,600 patients with dementia have participated in the program so far.
Caregiver411, developed by researchers from North Carolina Agricultural and Technical State University, won the third-place prize of $50,000. The mobile app helps people make informed decisions by, for instance, capturing the care recipient’s stage of AD in order to provide targeted recommendations. Dementia caregivers can obtain tailored resources related to mental, emotional, physical, social, legal, and financial concerns. The app also gives them a forum for social connections and family chat groups through a messaging center.
The Eureka Challenge is part of the 21st Century Cures Act, signed into law in 2016, designed to help accelerate medical product development with innovations incorporating the perspectives of patients. More detailed project descriptions are available at www.nia.nih.gov/challenge-prize.
Mobile applications and other tech solutions that target the specific needs of patients with Alzheimer and their caregivers won the day in the first Eureka prize competition, sponsored by the National Institute on Aging.
The Improving Care for People with Alzheimer’s Disease and Related Dementias Using Technology (iCare-AD/ADRD) Challenge received 33 applications for mobile device applications or web-based methods to help users coordinate and navigate life with dementia. The judging was based on creativity and innovation, rationale and potential impact, value to relevant stakeholders, usability, and functionality and feasibility.
First place, with $250,000, went to MapHabit for mobile software that provides behavior prompts with customizable picture-and-keyword visual maps to help people with activities of daily living. The platform has different interfaces for users: people with impaired memory, caregiver, or long-term care community manager. Simple commands, such as “take a shower,” are scheduled, with feedback provided to caregivers. The system takes advantage of the brain’s habit (procedural) memory system, the researchers say, rather than the hippocampal (declarative) memory system that is damaged early in AD.
A team from University of California, Los Angeles, won second prize of $100,000 for their web-based Dementia Care Software system, which helps coordinate complex medical and social services. The software, which can be integrated into any of the leading electronic health record systems, has already been used in support of the UCLA Alzheimer’s and Dementia Care Program, a nurse-practitioner co-management approach that includes structured needs assessment, individualized dementia care plans, and round-the-clock access for assistance and advice. The researchers say more than 2,600 patients with dementia have participated in the program so far.
Caregiver411, developed by researchers from North Carolina Agricultural and Technical State University, won the third-place prize of $50,000. The mobile app helps people make informed decisions by, for instance, capturing the care recipient’s stage of AD in order to provide targeted recommendations. Dementia caregivers can obtain tailored resources related to mental, emotional, physical, social, legal, and financial concerns. The app also gives them a forum for social connections and family chat groups through a messaging center.
The Eureka Challenge is part of the 21st Century Cures Act, signed into law in 2016, designed to help accelerate medical product development with innovations incorporating the perspectives of patients. More detailed project descriptions are available at www.nia.nih.gov/challenge-prize.
The Health Impacts of Comorbid PTSD and MDD
It is well established, both in research and everyday real-world experience, that posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) independently can have a huge impact on physical health. There is evidence, for instance, that both are independent “robust risk factors” for the onset of chronic physical illnesses, including musculoskeletal, digestive, and circulatory, say researchers from VA San Diego; University of California, San Diego; VA Center of Excellence for Stress and Mental Health, San Diego; National Center for PTSD, Vermont; VA Connecticut Health Care System, and Yale. However, less is known about how the 2 conditions might synergistically affect physical health and well-being.
In this, the first population-based study of the burden of medical illness associated with PTSD, MDD, and their comorbidity, the researchers examined data from 2,732 participants in the National Health and Resilience in Veterans Study.
Of the participants, 40 had PTSD only, 141 had MDD only, and 60 had both. Among veterans who screened positive for probable PTSD, 47% also screened positive for probable MDD. Among veterans who screened positive for probable MDD, 83% screened positive for probable PTSD.
The participants with PTSD, MDD, or both had substantially greater burden of medical illness compared with that of those participants who had no lifetime history of either condition. Consistent with findings from previous studies, each group had a greater prevalence of a broad range of medical conditions, including cardiovascular, respiratory, neurologic, and chronic pain-related diseases.
However, the study results indicated that comorbid PTSD/MDD was associated with substantially greater medical comorbidity compared with either disorder alone. Veterans with co-occurring PTSD and MDD had higher odds of being diagnosed with migraine, fibromyalgia, and rheumatoid arthritis, for instance, relative to those with MDD alone.
Co-occurring PTSD/MDD was also associated with “markedly worse” cardiovascular health compared with either condition alone. Veterans with PTSD/MDD had more than twice the likelihood of being diagnosed with hypercholesterolemia and hypertension compared with those who had PTSD alone. They had more than double the odds of being diagnosed with heart disease compared with those who had only MDD.
Several factors may account for why PTSD seems to compound risk for pain-related conditions, the researchers say. People with PTSD may have increased attentional bias toward threatening internal stimuli (above and beyond MDD), which may heighten appraisal of pain; they also tend to have higher levels of anxiety sensitivity, which may amplify fear reactivity to pain. Some evidence suggests that the brain region involved in processing the affective component of pain is dysfunctional in PTSD, leading to an exaggerated response.
The associations between PTSD and pain, and PTSD/MDD and cardiovascular risks were noteworthy, the researchers say, because they were found even after “stringently controlling” for relevant covariates, including lifetime trauma exposure; combat veteran status; and alcohol, drug, and nicotine use disorder.
The finding that PTSD/MDD and PTSD were associated with higher levels of somatization is consistent with other research, the researchers note. But they say more research is needed to examine whether somatization increases vulnerability to the development of PTSD and MDD, or whether symptoms arise as a consequence of the disorders.
Further, they underscore the importance of integrating mental health services in primary care settings. Previous research has shown that older veterans tend to report mental health concerns to their primary care provider rather than seek specialty mental health treatment; they also underreport symptoms related to emotional difficulties and overreport somatic complaints.
Perhaps most important from a public health perspective, the researchers say, is that current findings suggest that veterans with co-occurring PTSD/MDD represent a “particularly high-risk group” for cardiovascular problems. The issue, they emphasize, “deserves careful attention” from the VA and other health care systems.
It is well established, both in research and everyday real-world experience, that posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) independently can have a huge impact on physical health. There is evidence, for instance, that both are independent “robust risk factors” for the onset of chronic physical illnesses, including musculoskeletal, digestive, and circulatory, say researchers from VA San Diego; University of California, San Diego; VA Center of Excellence for Stress and Mental Health, San Diego; National Center for PTSD, Vermont; VA Connecticut Health Care System, and Yale. However, less is known about how the 2 conditions might synergistically affect physical health and well-being.
In this, the first population-based study of the burden of medical illness associated with PTSD, MDD, and their comorbidity, the researchers examined data from 2,732 participants in the National Health and Resilience in Veterans Study.
Of the participants, 40 had PTSD only, 141 had MDD only, and 60 had both. Among veterans who screened positive for probable PTSD, 47% also screened positive for probable MDD. Among veterans who screened positive for probable MDD, 83% screened positive for probable PTSD.
The participants with PTSD, MDD, or both had substantially greater burden of medical illness compared with that of those participants who had no lifetime history of either condition. Consistent with findings from previous studies, each group had a greater prevalence of a broad range of medical conditions, including cardiovascular, respiratory, neurologic, and chronic pain-related diseases.
However, the study results indicated that comorbid PTSD/MDD was associated with substantially greater medical comorbidity compared with either disorder alone. Veterans with co-occurring PTSD and MDD had higher odds of being diagnosed with migraine, fibromyalgia, and rheumatoid arthritis, for instance, relative to those with MDD alone.
Co-occurring PTSD/MDD was also associated with “markedly worse” cardiovascular health compared with either condition alone. Veterans with PTSD/MDD had more than twice the likelihood of being diagnosed with hypercholesterolemia and hypertension compared with those who had PTSD alone. They had more than double the odds of being diagnosed with heart disease compared with those who had only MDD.
Several factors may account for why PTSD seems to compound risk for pain-related conditions, the researchers say. People with PTSD may have increased attentional bias toward threatening internal stimuli (above and beyond MDD), which may heighten appraisal of pain; they also tend to have higher levels of anxiety sensitivity, which may amplify fear reactivity to pain. Some evidence suggests that the brain region involved in processing the affective component of pain is dysfunctional in PTSD, leading to an exaggerated response.
The associations between PTSD and pain, and PTSD/MDD and cardiovascular risks were noteworthy, the researchers say, because they were found even after “stringently controlling” for relevant covariates, including lifetime trauma exposure; combat veteran status; and alcohol, drug, and nicotine use disorder.
The finding that PTSD/MDD and PTSD were associated with higher levels of somatization is consistent with other research, the researchers note. But they say more research is needed to examine whether somatization increases vulnerability to the development of PTSD and MDD, or whether symptoms arise as a consequence of the disorders.
Further, they underscore the importance of integrating mental health services in primary care settings. Previous research has shown that older veterans tend to report mental health concerns to their primary care provider rather than seek specialty mental health treatment; they also underreport symptoms related to emotional difficulties and overreport somatic complaints.
Perhaps most important from a public health perspective, the researchers say, is that current findings suggest that veterans with co-occurring PTSD/MDD represent a “particularly high-risk group” for cardiovascular problems. The issue, they emphasize, “deserves careful attention” from the VA and other health care systems.
It is well established, both in research and everyday real-world experience, that posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) independently can have a huge impact on physical health. There is evidence, for instance, that both are independent “robust risk factors” for the onset of chronic physical illnesses, including musculoskeletal, digestive, and circulatory, say researchers from VA San Diego; University of California, San Diego; VA Center of Excellence for Stress and Mental Health, San Diego; National Center for PTSD, Vermont; VA Connecticut Health Care System, and Yale. However, less is known about how the 2 conditions might synergistically affect physical health and well-being.
In this, the first population-based study of the burden of medical illness associated with PTSD, MDD, and their comorbidity, the researchers examined data from 2,732 participants in the National Health and Resilience in Veterans Study.
Of the participants, 40 had PTSD only, 141 had MDD only, and 60 had both. Among veterans who screened positive for probable PTSD, 47% also screened positive for probable MDD. Among veterans who screened positive for probable MDD, 83% screened positive for probable PTSD.
The participants with PTSD, MDD, or both had substantially greater burden of medical illness compared with that of those participants who had no lifetime history of either condition. Consistent with findings from previous studies, each group had a greater prevalence of a broad range of medical conditions, including cardiovascular, respiratory, neurologic, and chronic pain-related diseases.
However, the study results indicated that comorbid PTSD/MDD was associated with substantially greater medical comorbidity compared with either disorder alone. Veterans with co-occurring PTSD and MDD had higher odds of being diagnosed with migraine, fibromyalgia, and rheumatoid arthritis, for instance, relative to those with MDD alone.
Co-occurring PTSD/MDD was also associated with “markedly worse” cardiovascular health compared with either condition alone. Veterans with PTSD/MDD had more than twice the likelihood of being diagnosed with hypercholesterolemia and hypertension compared with those who had PTSD alone. They had more than double the odds of being diagnosed with heart disease compared with those who had only MDD.
Several factors may account for why PTSD seems to compound risk for pain-related conditions, the researchers say. People with PTSD may have increased attentional bias toward threatening internal stimuli (above and beyond MDD), which may heighten appraisal of pain; they also tend to have higher levels of anxiety sensitivity, which may amplify fear reactivity to pain. Some evidence suggests that the brain region involved in processing the affective component of pain is dysfunctional in PTSD, leading to an exaggerated response.
The associations between PTSD and pain, and PTSD/MDD and cardiovascular risks were noteworthy, the researchers say, because they were found even after “stringently controlling” for relevant covariates, including lifetime trauma exposure; combat veteran status; and alcohol, drug, and nicotine use disorder.
The finding that PTSD/MDD and PTSD were associated with higher levels of somatization is consistent with other research, the researchers note. But they say more research is needed to examine whether somatization increases vulnerability to the development of PTSD and MDD, or whether symptoms arise as a consequence of the disorders.
Further, they underscore the importance of integrating mental health services in primary care settings. Previous research has shown that older veterans tend to report mental health concerns to their primary care provider rather than seek specialty mental health treatment; they also underreport symptoms related to emotional difficulties and overreport somatic complaints.
Perhaps most important from a public health perspective, the researchers say, is that current findings suggest that veterans with co-occurring PTSD/MDD represent a “particularly high-risk group” for cardiovascular problems. The issue, they emphasize, “deserves careful attention” from the VA and other health care systems.
No clear benefit from conservative oxygen in mechanical ventilation
More conservative oxygen therapy during mechanical ventilation in intensive care does not appear to increase the number of ventilator-free days or reduce mortality, according to a study published online in the New England Journal of Medicine.
Diane Mackle of the Medical Research Institute of New Zealand and her co-authors wrote that hyperoxemia in adults undergoing mechanical ventilation has been associated with increased mortality, as well as fewer days free of ventilation, but there was a lack of data to guide oxygen administration.
In a parallel-group trial, 1,000 adults who were expected to require mechanical ventilation – with an intention-to-treat population of 965 – were randomized either to conservative oxygen therapy or usual therapy. For the conservative therapy, the upper limit of the pulse oximetry alarm would sound when levels reached 97% and the F102 was decreased to 0.21 if the pulse oximetry was above the acceptable lower limit, while usual therapy involved no specific limiting measures. In both groups, the default lower limit for oxygen saturation was 90%.
At day 28 after ventilation, there was no significant difference between the conservative and usual care groups in the number of ventilator-free days (21.3 days vs. 22.1 days). The patients in the conservative oxygen group spent a median of 29 hours receiving an F102 level of 0.21, compared with 1 hour in the usual care group.
The mortality rate at day 180 was 35.7% in the conservative oxygen group, and 34.5% in the usual-oxygen group (HR 1.05, 95% CI 0.85 – 1.30). Researchers also saw no differences between the two groups in paid employment and cognitive function.
In patients with suspected hypoxic-ischemic encephalopathy between-group differences were apparent; At day 28, those in the conservative-oxygen group had a median of 21.1 ventilator-free days, compared with none in the usual-oxygen group. The usual-oxygen group also had a higher 180-day mortality rate than those in the conservative-oxygen group (43% vs. 59%).
“Our data are suggestive of a possible benefit of conservative oxygen therapy in patients with suspected hypoxic-ischemic encephalopathy,” the authors wrote. “It is biologically plausible that conservative oxygen therapy reduces the incidence of secondary brain damage after resuscitation from cardiac arrest, and observational data suggest that exposure to hyperoxemia in such patients may be harmful.”
The authors noted that their trial did not rule out the possibility of benefit or harm had they used a more liberal oxygen regimen in their usual-care group, and that different conservative regimens might also have achieved different outcomes.
The study was funded by the New Zealand Health Research Council. Six authors declared research support for the trial from the study funder, and two declared unrelated research grants from private industry. No other conflicts of interest were declared.
SOURCE: Mackle D et al. NJEM 2019, October 14. DOI:10.1056/NEJMoa1903297.
More conservative oxygen therapy during mechanical ventilation in intensive care does not appear to increase the number of ventilator-free days or reduce mortality, according to a study published online in the New England Journal of Medicine.
Diane Mackle of the Medical Research Institute of New Zealand and her co-authors wrote that hyperoxemia in adults undergoing mechanical ventilation has been associated with increased mortality, as well as fewer days free of ventilation, but there was a lack of data to guide oxygen administration.
In a parallel-group trial, 1,000 adults who were expected to require mechanical ventilation – with an intention-to-treat population of 965 – were randomized either to conservative oxygen therapy or usual therapy. For the conservative therapy, the upper limit of the pulse oximetry alarm would sound when levels reached 97% and the F102 was decreased to 0.21 if the pulse oximetry was above the acceptable lower limit, while usual therapy involved no specific limiting measures. In both groups, the default lower limit for oxygen saturation was 90%.
At day 28 after ventilation, there was no significant difference between the conservative and usual care groups in the number of ventilator-free days (21.3 days vs. 22.1 days). The patients in the conservative oxygen group spent a median of 29 hours receiving an F102 level of 0.21, compared with 1 hour in the usual care group.
The mortality rate at day 180 was 35.7% in the conservative oxygen group, and 34.5% in the usual-oxygen group (HR 1.05, 95% CI 0.85 – 1.30). Researchers also saw no differences between the two groups in paid employment and cognitive function.
In patients with suspected hypoxic-ischemic encephalopathy between-group differences were apparent; At day 28, those in the conservative-oxygen group had a median of 21.1 ventilator-free days, compared with none in the usual-oxygen group. The usual-oxygen group also had a higher 180-day mortality rate than those in the conservative-oxygen group (43% vs. 59%).
“Our data are suggestive of a possible benefit of conservative oxygen therapy in patients with suspected hypoxic-ischemic encephalopathy,” the authors wrote. “It is biologically plausible that conservative oxygen therapy reduces the incidence of secondary brain damage after resuscitation from cardiac arrest, and observational data suggest that exposure to hyperoxemia in such patients may be harmful.”
The authors noted that their trial did not rule out the possibility of benefit or harm had they used a more liberal oxygen regimen in their usual-care group, and that different conservative regimens might also have achieved different outcomes.
The study was funded by the New Zealand Health Research Council. Six authors declared research support for the trial from the study funder, and two declared unrelated research grants from private industry. No other conflicts of interest were declared.
SOURCE: Mackle D et al. NJEM 2019, October 14. DOI:10.1056/NEJMoa1903297.
More conservative oxygen therapy during mechanical ventilation in intensive care does not appear to increase the number of ventilator-free days or reduce mortality, according to a study published online in the New England Journal of Medicine.
Diane Mackle of the Medical Research Institute of New Zealand and her co-authors wrote that hyperoxemia in adults undergoing mechanical ventilation has been associated with increased mortality, as well as fewer days free of ventilation, but there was a lack of data to guide oxygen administration.
In a parallel-group trial, 1,000 adults who were expected to require mechanical ventilation – with an intention-to-treat population of 965 – were randomized either to conservative oxygen therapy or usual therapy. For the conservative therapy, the upper limit of the pulse oximetry alarm would sound when levels reached 97% and the F102 was decreased to 0.21 if the pulse oximetry was above the acceptable lower limit, while usual therapy involved no specific limiting measures. In both groups, the default lower limit for oxygen saturation was 90%.
At day 28 after ventilation, there was no significant difference between the conservative and usual care groups in the number of ventilator-free days (21.3 days vs. 22.1 days). The patients in the conservative oxygen group spent a median of 29 hours receiving an F102 level of 0.21, compared with 1 hour in the usual care group.
The mortality rate at day 180 was 35.7% in the conservative oxygen group, and 34.5% in the usual-oxygen group (HR 1.05, 95% CI 0.85 – 1.30). Researchers also saw no differences between the two groups in paid employment and cognitive function.
In patients with suspected hypoxic-ischemic encephalopathy between-group differences were apparent; At day 28, those in the conservative-oxygen group had a median of 21.1 ventilator-free days, compared with none in the usual-oxygen group. The usual-oxygen group also had a higher 180-day mortality rate than those in the conservative-oxygen group (43% vs. 59%).
“Our data are suggestive of a possible benefit of conservative oxygen therapy in patients with suspected hypoxic-ischemic encephalopathy,” the authors wrote. “It is biologically plausible that conservative oxygen therapy reduces the incidence of secondary brain damage after resuscitation from cardiac arrest, and observational data suggest that exposure to hyperoxemia in such patients may be harmful.”
The authors noted that their trial did not rule out the possibility of benefit or harm had they used a more liberal oxygen regimen in their usual-care group, and that different conservative regimens might also have achieved different outcomes.
The study was funded by the New Zealand Health Research Council. Six authors declared research support for the trial from the study funder, and two declared unrelated research grants from private industry. No other conflicts of interest were declared.
SOURCE: Mackle D et al. NJEM 2019, October 14. DOI:10.1056/NEJMoa1903297.
FROM NEJM
Key clinical point: Conservative oxygen therapy during mechanical ventilation does not increase ventilation-free days.
Major finding: The number of ventilation-free days was similar in adults on conservative oxygen therapy and those on usual care.
Study details: Parallel-group randomized controlled trial in 965 adults undergoing mechanical ventilation.
Disclosures: The study was funded by the New Zealand Health Research Council. Six authors declared research support for the trial from the study funder, and two declared unrelated research grants from private industry. No other conflicts of interest were declared.
Source: Mackle D et al. NJEM 2019, October 14. DOI: 10.1056/NEJMoa1903297.
Retraining Working Memory to Reduce PTSD Symptoms
Working memory (WM)—the function that allows us to temporarily store information and use it for cognitive tasks like learning, reasoning, and comprehension—is thought to play an important role in managing anxiety and intrusive symptoms of posttraumatic stress disorder (PTSD). Researchers have found inefficient filtering of threatening material from WM and increased storage of task-irrelevant threat distractors are associated with elevated anxiety. Thus, veterans with high levels of anxiety may disproportionately allocate cognitive resources toward threatening stimuli, and have trouble keeping threatening thoughts from entering WM and staying there. People with PTSD also have been shown to have problems using WM in emotional contexts, making it hard for them to deal with stressful situations in work and personal life. Some research has suggested that WM training that incorporates affective stimuli may increase the ability to use WM in emotional contexts. In a pilot study, researchers from Medical College of Wisconsin and University of Wisconsin-Milwaukee expanded on that possibility by testing 2 kinds of WM training in 21 veterans with elevated PTSD symptoms.
Participants completed a pretest, 15 sessions of at-home computerized training, a posttest, and a 1-month follow-up session. The computerized tests included tasks to measure WM capacity, such as solving math questions while trying to remember a set of unrelated numbers. The participants were then assigned to active emotional WM training (n-back) or control emotional WM training (1-back). The n-back training involved constant updating of information stored in WM and shifting between visual and auditory stimuli using 8 different faces and 8 different negative words. The training sessions started at the 1-back level and increased in difficulty level by level with performance with > 95% accuracy, or were scaled back with performance with < 75% accuracy. The control training was the same but consisted only of 1 level.
Overall, the researchers say, contrary to their hypothesis, they did not find a significant difference in results from the 2 groups. But they did find that both trainings had an overall “significant and sizable” impact on PTSD symptoms in both groups: 73% of the n-back group and 60% of the 1-back group had a reduction of ≥ 10 points on the PTSD Checklist total scores, which the researchers say is considered a clinically meaningful change. Moreover, both groups showed a clinically meaningful reduction in symptoms at follow-up: 55% and 40%, respectively.
It was interesting, the researchers say, that both groups showed improvement, especially with the 1-back intervention, which they had used as a “minimally effective” control condition. They also note that, anecdotally, the participants found both interventions “quite challenging.” It may be that in this population even the 1-back intervention is enough to detectably reduce symptoms, the researchers say. They were also encouraged to see that the n-back condition (marginally) outperformed the 1-back condition in improving reexperiencing symptoms, theoretically the most relevant training target of WM-focused intervention. The researchers believe that their study yields useful pilot data, suggesting that n-back training can have a clinical impact primarily by reducing reexperiencing symptoms, which are highly likely to indicate the presence of impaired WM functioning.
Working memory (WM)—the function that allows us to temporarily store information and use it for cognitive tasks like learning, reasoning, and comprehension—is thought to play an important role in managing anxiety and intrusive symptoms of posttraumatic stress disorder (PTSD). Researchers have found inefficient filtering of threatening material from WM and increased storage of task-irrelevant threat distractors are associated with elevated anxiety. Thus, veterans with high levels of anxiety may disproportionately allocate cognitive resources toward threatening stimuli, and have trouble keeping threatening thoughts from entering WM and staying there. People with PTSD also have been shown to have problems using WM in emotional contexts, making it hard for them to deal with stressful situations in work and personal life. Some research has suggested that WM training that incorporates affective stimuli may increase the ability to use WM in emotional contexts. In a pilot study, researchers from Medical College of Wisconsin and University of Wisconsin-Milwaukee expanded on that possibility by testing 2 kinds of WM training in 21 veterans with elevated PTSD symptoms.
Participants completed a pretest, 15 sessions of at-home computerized training, a posttest, and a 1-month follow-up session. The computerized tests included tasks to measure WM capacity, such as solving math questions while trying to remember a set of unrelated numbers. The participants were then assigned to active emotional WM training (n-back) or control emotional WM training (1-back). The n-back training involved constant updating of information stored in WM and shifting between visual and auditory stimuli using 8 different faces and 8 different negative words. The training sessions started at the 1-back level and increased in difficulty level by level with performance with > 95% accuracy, or were scaled back with performance with < 75% accuracy. The control training was the same but consisted only of 1 level.
Overall, the researchers say, contrary to their hypothesis, they did not find a significant difference in results from the 2 groups. But they did find that both trainings had an overall “significant and sizable” impact on PTSD symptoms in both groups: 73% of the n-back group and 60% of the 1-back group had a reduction of ≥ 10 points on the PTSD Checklist total scores, which the researchers say is considered a clinically meaningful change. Moreover, both groups showed a clinically meaningful reduction in symptoms at follow-up: 55% and 40%, respectively.
It was interesting, the researchers say, that both groups showed improvement, especially with the 1-back intervention, which they had used as a “minimally effective” control condition. They also note that, anecdotally, the participants found both interventions “quite challenging.” It may be that in this population even the 1-back intervention is enough to detectably reduce symptoms, the researchers say. They were also encouraged to see that the n-back condition (marginally) outperformed the 1-back condition in improving reexperiencing symptoms, theoretically the most relevant training target of WM-focused intervention. The researchers believe that their study yields useful pilot data, suggesting that n-back training can have a clinical impact primarily by reducing reexperiencing symptoms, which are highly likely to indicate the presence of impaired WM functioning.
Working memory (WM)—the function that allows us to temporarily store information and use it for cognitive tasks like learning, reasoning, and comprehension—is thought to play an important role in managing anxiety and intrusive symptoms of posttraumatic stress disorder (PTSD). Researchers have found inefficient filtering of threatening material from WM and increased storage of task-irrelevant threat distractors are associated with elevated anxiety. Thus, veterans with high levels of anxiety may disproportionately allocate cognitive resources toward threatening stimuli, and have trouble keeping threatening thoughts from entering WM and staying there. People with PTSD also have been shown to have problems using WM in emotional contexts, making it hard for them to deal with stressful situations in work and personal life. Some research has suggested that WM training that incorporates affective stimuli may increase the ability to use WM in emotional contexts. In a pilot study, researchers from Medical College of Wisconsin and University of Wisconsin-Milwaukee expanded on that possibility by testing 2 kinds of WM training in 21 veterans with elevated PTSD symptoms.
Participants completed a pretest, 15 sessions of at-home computerized training, a posttest, and a 1-month follow-up session. The computerized tests included tasks to measure WM capacity, such as solving math questions while trying to remember a set of unrelated numbers. The participants were then assigned to active emotional WM training (n-back) or control emotional WM training (1-back). The n-back training involved constant updating of information stored in WM and shifting between visual and auditory stimuli using 8 different faces and 8 different negative words. The training sessions started at the 1-back level and increased in difficulty level by level with performance with > 95% accuracy, or were scaled back with performance with < 75% accuracy. The control training was the same but consisted only of 1 level.
Overall, the researchers say, contrary to their hypothesis, they did not find a significant difference in results from the 2 groups. But they did find that both trainings had an overall “significant and sizable” impact on PTSD symptoms in both groups: 73% of the n-back group and 60% of the 1-back group had a reduction of ≥ 10 points on the PTSD Checklist total scores, which the researchers say is considered a clinically meaningful change. Moreover, both groups showed a clinically meaningful reduction in symptoms at follow-up: 55% and 40%, respectively.
It was interesting, the researchers say, that both groups showed improvement, especially with the 1-back intervention, which they had used as a “minimally effective” control condition. They also note that, anecdotally, the participants found both interventions “quite challenging.” It may be that in this population even the 1-back intervention is enough to detectably reduce symptoms, the researchers say. They were also encouraged to see that the n-back condition (marginally) outperformed the 1-back condition in improving reexperiencing symptoms, theoretically the most relevant training target of WM-focused intervention. The researchers believe that their study yields useful pilot data, suggesting that n-back training can have a clinical impact primarily by reducing reexperiencing symptoms, which are highly likely to indicate the presence of impaired WM functioning.