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Antibiotic resistance rises among pneumococcus strains in kids
Antibiotic resistance in strains of Streptococcus pneumoniae has been rising since 2013 because of changing susceptibility profiles, based on data from 1,201 isolates collected from 448 children in primary care settings.
“New strains expressing capsular serotypes not included in the 13-valent pneumococcal conjugate vaccine are emerging to cause disease, and strains that acquire antibiotic resistance are increasing in frequency due to their survival of the fittest advantage,” wrote Ravinder Kaur, PhD, of Rochester (N.Y.) General Hospital Research Institute, and colleagues.
Similar Darwinian principles occurred after the introduction of PCV-7, the study authors added.
In a prospective cohort study published in Clinical Infectious Diseases, the researchers reviewed 1,201 isolates collected from the nasopharynx during healthy periods, and from the nasopharynx and middle ear fluid (MEF) during episodes of acute otitis media, in children aged 6-36 months who were seen in primary care settings.
The isolates were collected during 2006-2016 to reflect the pre- and post-PCV13 era. Children received PCV-7 from 2006 until April 2010, and received PCV-13 after April 2010.
Overall, the number of acute otitis media (AOM) cases caused by S. pneumoniae was not significantly different between the PCV-7 and PCV-13 eras, nor was the frequency of pneumococci identified in the nasopharynx during healthy visits and visits at the start of an AOM infection.
The researchers examined susceptibility using minimum inhibitory concentrations (MIC). During healthy visits, the MIC50 of isolated pneumococci was low (no greater than 0.06 mcg/mL) for all four beta-lactam drugs tested. And it didn’t change significantly over the study years.
In contrast, among the nasopharyngeal and MEF isolates during AOM, the MIC50 to penicillin, amoxicillin, ceftriaxone, and meropenem during 2013-2016 rose significantly, the investigators said.
A change in antibiotic susceptibility within a subtype also contributed to the development of PCV-13 resistance.
The study authors identified three serotypes that affected the changes in susceptibility in their study population. Serotypes 35B and 35F increased their beta-lactam resistance during 2013-2016, and serotype 11A had a higher MIC to quinolones and became more prevalent during 2013-2016. Those three serotypes accounted for most of the change in antibiotic susceptibility, the researchers said.
In addition, “the frequency of strains resistant to penicillin and amoxicillin decreased with the introduction of PCV-13, but rebounded to levels similar to those before PCV-13 introduction by 2015-2016,” the investigators noted.
The study findings were limited by several factors, including the homogeneous study population and potential lack of generalizability to other settings. In addition, the researchers did not study antibiotic consumption or antibiotic treatment failure, and they could not account for potential AOM cases that may have been treated in settings other than primary care.
However, the investigators said the results support the need for additional studies and attention to the development of the next generation of PCVs, the PCV-15 and PCV-20. Both include serotypes 22F and 33F, but neither includes 35B or 35F. The PCV-20 also includes 11A and 15B.
The study was supported in part by the National Institutes of Health and Sanofi Pasteur. Some isolates collected during the 2010-2013 time period were part of a study supported by Pfizer. The researchers had no relevant financial conflicts to disclose.
SOURCE: Kaur R et al. Clin Inf Dis. 2020 Feb 18. doi: 10.1093/cid/ciaa157.
Dr. Kaur and colleagues report their analysis of pneumococcal resistance among nasopharyngeal and middle ear isolates (90% nasopharyngeal and 10% middle ear) collected between 2008 and 2016. They demonstrate the dominant role that nonvaccine serotypes play in carriage and acute otitis media (AOM) in children, and by extension potentially the entire spectrum of pneumococcal disease in the 13-valent pneumococcal conjugate vaccine (PCV13) era. Nonsusceptibility to beta-lactams was reported for one-third of isolates with the increase in the most recent reported years (2013-2016).
What are the implications for treatment of pneumococcal infections? For AOM, amoxicillin minimum inhibitory concentrations (MIC) were all less than 4 mcg/mL, which is the pharmacodynamic breakpoint for high-dose (90 mg/kg per day) AOM regimens; these data support continued use of high-dose amoxicillin for children with AOM that requires antimicrobial treatment. Resistance to macrolides (erythromycin and likely azithromycin) occurred in approximately one-third of isolates; however, in contrast to beta-lactams (amoxicillin), higher macrolide doses do not overcome resistance. Thus macrolide use for AOM appears limited to those with beta-lactam allergy and no better alternative drug, i.e., expect failure in one-third of AOM patients if macrolides are used. For ceftriaxone, no 2013-2016 isolate had a MIC over 0.5 mcg/mL, implying that ceftriaxone remains appropriate first-line therapy for serious pneumococcal disease and effective for pneumococcal AOM when oral drugs have failed or are not an option because of repeated emesis. Interestingly, trimethoprim/sulfamethoxazole (T/S) had lower resistance rates against the nonvaccine “bad boy” serogroup 35 (8%-15%), compared with cephalosporins (32%-57%). Perhaps we are back to the future and T/S will again have a role against pneumococcal AOM. Of note, no isolate was resistant to levofloxacin or linezolid. Linezolid or macrolide use alone must be considered with the caveat that nontypeable Haemophilus influenzae now likely surpasses pneumococcus as an AOM pathogen, and neither drug class is active against nontypeable H. influenzae.
What are the implications for prevention? This is one of many studies in the post-PCV era reporting serotype replacement with nonvaccine serotypes. But most prior studies reported reduced overall disease burden; in other words, the absolute number of pneumococcal infections was reduced, but residual AOM nonvaccine types dominated as the etiology. The current study, however, suggests that the overall number of AOM episodes may not be less because increases in AOM caused by nonvaccine serotypes may be offsetting declines in AOM caused by vaccine serotypes. This concept contrasts to multiple large epidemiologic studies demonstrating a decline in overall incidence of AOM office visits/episodes and several Israeli studies reporting a decline in pneumococcal AOM in children who warrant tympanocentesis. These new data are food for thought, but antibiotic resistance can vary regionally, so confirmation based on data from other regions seems warranted.
Next-generation vaccines will need to consider which serotypes are prevalent in pneumococcal disease, including AOM, as we continue into the PCV13 era. However, serotypes causing invasive pneumococcal disease and pneumonia would be higher priorities than AOM. Indeed, several candidate PCV vaccines are currently in clinical trials adding up to seven serotypes, including most of the newly emerging invasive disease serotypes. One downside to the newer PCVs is lack of serogroup 35, a prominent culprit in AOM resistance in the current report.
Stephen I. Pelton, MD, is professor of pediatrics and epidemiology at Boston University and senior attending physician at Boston Medical Center. Christopher J. Harrison, MD, is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospital–Kansas City, Mo. Dr. Pelton has received honorarium from Merck Vaccines, Pfizer, and Sanofi for participation in advisory board meeting on pneumococcal vaccine and/or membership on the Data and Safety Monitoring Board. Boston Medical Center has received investigator-initiated research grants from Merck Vaccines and Pfizer.
Children’s Mercy Hospital – Kansas City Boston Medical Center has received funding from GlaxoSmithKline, Merck, and Pfizer for research vaccine studies, and from Pfizer and Merck for investigator-initiated research grants for in vitro pneumococcal investigations on which Dr. Harrison is an investigator.
Dr. Kaur and colleagues report their analysis of pneumococcal resistance among nasopharyngeal and middle ear isolates (90% nasopharyngeal and 10% middle ear) collected between 2008 and 2016. They demonstrate the dominant role that nonvaccine serotypes play in carriage and acute otitis media (AOM) in children, and by extension potentially the entire spectrum of pneumococcal disease in the 13-valent pneumococcal conjugate vaccine (PCV13) era. Nonsusceptibility to beta-lactams was reported for one-third of isolates with the increase in the most recent reported years (2013-2016).
What are the implications for treatment of pneumococcal infections? For AOM, amoxicillin minimum inhibitory concentrations (MIC) were all less than 4 mcg/mL, which is the pharmacodynamic breakpoint for high-dose (90 mg/kg per day) AOM regimens; these data support continued use of high-dose amoxicillin for children with AOM that requires antimicrobial treatment. Resistance to macrolides (erythromycin and likely azithromycin) occurred in approximately one-third of isolates; however, in contrast to beta-lactams (amoxicillin), higher macrolide doses do not overcome resistance. Thus macrolide use for AOM appears limited to those with beta-lactam allergy and no better alternative drug, i.e., expect failure in one-third of AOM patients if macrolides are used. For ceftriaxone, no 2013-2016 isolate had a MIC over 0.5 mcg/mL, implying that ceftriaxone remains appropriate first-line therapy for serious pneumococcal disease and effective for pneumococcal AOM when oral drugs have failed or are not an option because of repeated emesis. Interestingly, trimethoprim/sulfamethoxazole (T/S) had lower resistance rates against the nonvaccine “bad boy” serogroup 35 (8%-15%), compared with cephalosporins (32%-57%). Perhaps we are back to the future and T/S will again have a role against pneumococcal AOM. Of note, no isolate was resistant to levofloxacin or linezolid. Linezolid or macrolide use alone must be considered with the caveat that nontypeable Haemophilus influenzae now likely surpasses pneumococcus as an AOM pathogen, and neither drug class is active against nontypeable H. influenzae.
What are the implications for prevention? This is one of many studies in the post-PCV era reporting serotype replacement with nonvaccine serotypes. But most prior studies reported reduced overall disease burden; in other words, the absolute number of pneumococcal infections was reduced, but residual AOM nonvaccine types dominated as the etiology. The current study, however, suggests that the overall number of AOM episodes may not be less because increases in AOM caused by nonvaccine serotypes may be offsetting declines in AOM caused by vaccine serotypes. This concept contrasts to multiple large epidemiologic studies demonstrating a decline in overall incidence of AOM office visits/episodes and several Israeli studies reporting a decline in pneumococcal AOM in children who warrant tympanocentesis. These new data are food for thought, but antibiotic resistance can vary regionally, so confirmation based on data from other regions seems warranted.
Next-generation vaccines will need to consider which serotypes are prevalent in pneumococcal disease, including AOM, as we continue into the PCV13 era. However, serotypes causing invasive pneumococcal disease and pneumonia would be higher priorities than AOM. Indeed, several candidate PCV vaccines are currently in clinical trials adding up to seven serotypes, including most of the newly emerging invasive disease serotypes. One downside to the newer PCVs is lack of serogroup 35, a prominent culprit in AOM resistance in the current report.
Stephen I. Pelton, MD, is professor of pediatrics and epidemiology at Boston University and senior attending physician at Boston Medical Center. Christopher J. Harrison, MD, is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospital–Kansas City, Mo. Dr. Pelton has received honorarium from Merck Vaccines, Pfizer, and Sanofi for participation in advisory board meeting on pneumococcal vaccine and/or membership on the Data and Safety Monitoring Board. Boston Medical Center has received investigator-initiated research grants from Merck Vaccines and Pfizer.
Children’s Mercy Hospital – Kansas City Boston Medical Center has received funding from GlaxoSmithKline, Merck, and Pfizer for research vaccine studies, and from Pfizer and Merck for investigator-initiated research grants for in vitro pneumococcal investigations on which Dr. Harrison is an investigator.
Dr. Kaur and colleagues report their analysis of pneumococcal resistance among nasopharyngeal and middle ear isolates (90% nasopharyngeal and 10% middle ear) collected between 2008 and 2016. They demonstrate the dominant role that nonvaccine serotypes play in carriage and acute otitis media (AOM) in children, and by extension potentially the entire spectrum of pneumococcal disease in the 13-valent pneumococcal conjugate vaccine (PCV13) era. Nonsusceptibility to beta-lactams was reported for one-third of isolates with the increase in the most recent reported years (2013-2016).
What are the implications for treatment of pneumococcal infections? For AOM, amoxicillin minimum inhibitory concentrations (MIC) were all less than 4 mcg/mL, which is the pharmacodynamic breakpoint for high-dose (90 mg/kg per day) AOM regimens; these data support continued use of high-dose amoxicillin for children with AOM that requires antimicrobial treatment. Resistance to macrolides (erythromycin and likely azithromycin) occurred in approximately one-third of isolates; however, in contrast to beta-lactams (amoxicillin), higher macrolide doses do not overcome resistance. Thus macrolide use for AOM appears limited to those with beta-lactam allergy and no better alternative drug, i.e., expect failure in one-third of AOM patients if macrolides are used. For ceftriaxone, no 2013-2016 isolate had a MIC over 0.5 mcg/mL, implying that ceftriaxone remains appropriate first-line therapy for serious pneumococcal disease and effective for pneumococcal AOM when oral drugs have failed or are not an option because of repeated emesis. Interestingly, trimethoprim/sulfamethoxazole (T/S) had lower resistance rates against the nonvaccine “bad boy” serogroup 35 (8%-15%), compared with cephalosporins (32%-57%). Perhaps we are back to the future and T/S will again have a role against pneumococcal AOM. Of note, no isolate was resistant to levofloxacin or linezolid. Linezolid or macrolide use alone must be considered with the caveat that nontypeable Haemophilus influenzae now likely surpasses pneumococcus as an AOM pathogen, and neither drug class is active against nontypeable H. influenzae.
What are the implications for prevention? This is one of many studies in the post-PCV era reporting serotype replacement with nonvaccine serotypes. But most prior studies reported reduced overall disease burden; in other words, the absolute number of pneumococcal infections was reduced, but residual AOM nonvaccine types dominated as the etiology. The current study, however, suggests that the overall number of AOM episodes may not be less because increases in AOM caused by nonvaccine serotypes may be offsetting declines in AOM caused by vaccine serotypes. This concept contrasts to multiple large epidemiologic studies demonstrating a decline in overall incidence of AOM office visits/episodes and several Israeli studies reporting a decline in pneumococcal AOM in children who warrant tympanocentesis. These new data are food for thought, but antibiotic resistance can vary regionally, so confirmation based on data from other regions seems warranted.
Next-generation vaccines will need to consider which serotypes are prevalent in pneumococcal disease, including AOM, as we continue into the PCV13 era. However, serotypes causing invasive pneumococcal disease and pneumonia would be higher priorities than AOM. Indeed, several candidate PCV vaccines are currently in clinical trials adding up to seven serotypes, including most of the newly emerging invasive disease serotypes. One downside to the newer PCVs is lack of serogroup 35, a prominent culprit in AOM resistance in the current report.
Stephen I. Pelton, MD, is professor of pediatrics and epidemiology at Boston University and senior attending physician at Boston Medical Center. Christopher J. Harrison, MD, is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospital–Kansas City, Mo. Dr. Pelton has received honorarium from Merck Vaccines, Pfizer, and Sanofi for participation in advisory board meeting on pneumococcal vaccine and/or membership on the Data and Safety Monitoring Board. Boston Medical Center has received investigator-initiated research grants from Merck Vaccines and Pfizer.
Children’s Mercy Hospital – Kansas City Boston Medical Center has received funding from GlaxoSmithKline, Merck, and Pfizer for research vaccine studies, and from Pfizer and Merck for investigator-initiated research grants for in vitro pneumococcal investigations on which Dr. Harrison is an investigator.
Antibiotic resistance in strains of Streptococcus pneumoniae has been rising since 2013 because of changing susceptibility profiles, based on data from 1,201 isolates collected from 448 children in primary care settings.
“New strains expressing capsular serotypes not included in the 13-valent pneumococcal conjugate vaccine are emerging to cause disease, and strains that acquire antibiotic resistance are increasing in frequency due to their survival of the fittest advantage,” wrote Ravinder Kaur, PhD, of Rochester (N.Y.) General Hospital Research Institute, and colleagues.
Similar Darwinian principles occurred after the introduction of PCV-7, the study authors added.
In a prospective cohort study published in Clinical Infectious Diseases, the researchers reviewed 1,201 isolates collected from the nasopharynx during healthy periods, and from the nasopharynx and middle ear fluid (MEF) during episodes of acute otitis media, in children aged 6-36 months who were seen in primary care settings.
The isolates were collected during 2006-2016 to reflect the pre- and post-PCV13 era. Children received PCV-7 from 2006 until April 2010, and received PCV-13 after April 2010.
Overall, the number of acute otitis media (AOM) cases caused by S. pneumoniae was not significantly different between the PCV-7 and PCV-13 eras, nor was the frequency of pneumococci identified in the nasopharynx during healthy visits and visits at the start of an AOM infection.
The researchers examined susceptibility using minimum inhibitory concentrations (MIC). During healthy visits, the MIC50 of isolated pneumococci was low (no greater than 0.06 mcg/mL) for all four beta-lactam drugs tested. And it didn’t change significantly over the study years.
In contrast, among the nasopharyngeal and MEF isolates during AOM, the MIC50 to penicillin, amoxicillin, ceftriaxone, and meropenem during 2013-2016 rose significantly, the investigators said.
A change in antibiotic susceptibility within a subtype also contributed to the development of PCV-13 resistance.
The study authors identified three serotypes that affected the changes in susceptibility in their study population. Serotypes 35B and 35F increased their beta-lactam resistance during 2013-2016, and serotype 11A had a higher MIC to quinolones and became more prevalent during 2013-2016. Those three serotypes accounted for most of the change in antibiotic susceptibility, the researchers said.
In addition, “the frequency of strains resistant to penicillin and amoxicillin decreased with the introduction of PCV-13, but rebounded to levels similar to those before PCV-13 introduction by 2015-2016,” the investigators noted.
The study findings were limited by several factors, including the homogeneous study population and potential lack of generalizability to other settings. In addition, the researchers did not study antibiotic consumption or antibiotic treatment failure, and they could not account for potential AOM cases that may have been treated in settings other than primary care.
However, the investigators said the results support the need for additional studies and attention to the development of the next generation of PCVs, the PCV-15 and PCV-20. Both include serotypes 22F and 33F, but neither includes 35B or 35F. The PCV-20 also includes 11A and 15B.
The study was supported in part by the National Institutes of Health and Sanofi Pasteur. Some isolates collected during the 2010-2013 time period were part of a study supported by Pfizer. The researchers had no relevant financial conflicts to disclose.
SOURCE: Kaur R et al. Clin Inf Dis. 2020 Feb 18. doi: 10.1093/cid/ciaa157.
Antibiotic resistance in strains of Streptococcus pneumoniae has been rising since 2013 because of changing susceptibility profiles, based on data from 1,201 isolates collected from 448 children in primary care settings.
“New strains expressing capsular serotypes not included in the 13-valent pneumococcal conjugate vaccine are emerging to cause disease, and strains that acquire antibiotic resistance are increasing in frequency due to their survival of the fittest advantage,” wrote Ravinder Kaur, PhD, of Rochester (N.Y.) General Hospital Research Institute, and colleagues.
Similar Darwinian principles occurred after the introduction of PCV-7, the study authors added.
In a prospective cohort study published in Clinical Infectious Diseases, the researchers reviewed 1,201 isolates collected from the nasopharynx during healthy periods, and from the nasopharynx and middle ear fluid (MEF) during episodes of acute otitis media, in children aged 6-36 months who were seen in primary care settings.
The isolates were collected during 2006-2016 to reflect the pre- and post-PCV13 era. Children received PCV-7 from 2006 until April 2010, and received PCV-13 after April 2010.
Overall, the number of acute otitis media (AOM) cases caused by S. pneumoniae was not significantly different between the PCV-7 and PCV-13 eras, nor was the frequency of pneumococci identified in the nasopharynx during healthy visits and visits at the start of an AOM infection.
The researchers examined susceptibility using minimum inhibitory concentrations (MIC). During healthy visits, the MIC50 of isolated pneumococci was low (no greater than 0.06 mcg/mL) for all four beta-lactam drugs tested. And it didn’t change significantly over the study years.
In contrast, among the nasopharyngeal and MEF isolates during AOM, the MIC50 to penicillin, amoxicillin, ceftriaxone, and meropenem during 2013-2016 rose significantly, the investigators said.
A change in antibiotic susceptibility within a subtype also contributed to the development of PCV-13 resistance.
The study authors identified three serotypes that affected the changes in susceptibility in their study population. Serotypes 35B and 35F increased their beta-lactam resistance during 2013-2016, and serotype 11A had a higher MIC to quinolones and became more prevalent during 2013-2016. Those three serotypes accounted for most of the change in antibiotic susceptibility, the researchers said.
In addition, “the frequency of strains resistant to penicillin and amoxicillin decreased with the introduction of PCV-13, but rebounded to levels similar to those before PCV-13 introduction by 2015-2016,” the investigators noted.
The study findings were limited by several factors, including the homogeneous study population and potential lack of generalizability to other settings. In addition, the researchers did not study antibiotic consumption or antibiotic treatment failure, and they could not account for potential AOM cases that may have been treated in settings other than primary care.
However, the investigators said the results support the need for additional studies and attention to the development of the next generation of PCVs, the PCV-15 and PCV-20. Both include serotypes 22F and 33F, but neither includes 35B or 35F. The PCV-20 also includes 11A and 15B.
The study was supported in part by the National Institutes of Health and Sanofi Pasteur. Some isolates collected during the 2010-2013 time period were part of a study supported by Pfizer. The researchers had no relevant financial conflicts to disclose.
SOURCE: Kaur R et al. Clin Inf Dis. 2020 Feb 18. doi: 10.1093/cid/ciaa157.
FROM CLINICAL INFECTIOUS DISEASES
Abbreviated MRI bests digital breast tomosynthesis in finding cancer in dense breasts
For women with dense breasts, abbreviated magnetic resonance imaging was more effective than was digital breast tomosynthesis for detecting invasive breast cancer in a cross-sectional study of 1,444 women who underwent both procedures.
Dense breasts are a common reason for failed early diagnosis of breast cancer, wrote Christopher E. Comstock, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Digital breast tomosynthesis (DBT) and abbreviated breast magnetic resonance imaging (MRI) are becoming more popular as safe and cost-effective breast cancer screening options, but their effectiveness in women with dense breasts and average breast cancer risk has not been compared.
The researchers reviewed data from 1,444 women aged 40-75 years at 47 institutions in the United States and 1 in Germany. The women underwent both DBT and MRI. The primary endpoint was the detection of invasive cancers, of which 17 were identified at baseline screening. Abbreviated breast MRI detected all 17 cases of invasive cancer, compared with 7 detected by DBT. In addition, MRI detected six of seven women with ductal carcinoma in situ, while DBT identified two of the seven cases, according to the study, which was published in JAMA.
Overall, the invasive cancer detection rate was 11.8 per 1,000 women for MRI compared with 4.8 per 1,000 women for DBT. Sensitivity for MRI and DBT was 96% vs. 39%, and specificity was 87% vs. 97%.
The rate of recommendation for further screening was not significantly different between the procedures (8% for MRI and 10% for DBT). The most common adverse events were three cases of mild allergic reactions and two cases of anxiety.
The study findings were limited by several factors including the inability to show an association between abbreviated breast MRI and breast cancer mortality and the lack of cost-effectiveness comparisons for the two procedures. Because eligibility criteria required a prior breast mammogram to see if the breasts were dense, the study compared an incidence DBT screen to a prevalence abbreviated MRI screen, Dr. Comstock and associates noted.
However, the results show a significantly increased breast cancer detection rate with abbreviated MRI, which merits additional research to examine the relationship between screening strategies and clinical outcomes for women with dense breasts, they said.
The study was supported in part by the National Cancer Institute of the National Institutes of Health, and by Bracco Diagnostics through funding to the ECOG-ACRIN Cancer Research Group. Dr. Comstock disclosed financial relationships with Bracco Diagnostics and Bayer, and three coauthors disclosed financial relationships with other imaging companies. The remaining coauthors had no relevant financial disclosures.
SOURCE: Comstock CK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0572.
For women with dense breasts, abbreviated magnetic resonance imaging was more effective than was digital breast tomosynthesis for detecting invasive breast cancer in a cross-sectional study of 1,444 women who underwent both procedures.
Dense breasts are a common reason for failed early diagnosis of breast cancer, wrote Christopher E. Comstock, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Digital breast tomosynthesis (DBT) and abbreviated breast magnetic resonance imaging (MRI) are becoming more popular as safe and cost-effective breast cancer screening options, but their effectiveness in women with dense breasts and average breast cancer risk has not been compared.
The researchers reviewed data from 1,444 women aged 40-75 years at 47 institutions in the United States and 1 in Germany. The women underwent both DBT and MRI. The primary endpoint was the detection of invasive cancers, of which 17 were identified at baseline screening. Abbreviated breast MRI detected all 17 cases of invasive cancer, compared with 7 detected by DBT. In addition, MRI detected six of seven women with ductal carcinoma in situ, while DBT identified two of the seven cases, according to the study, which was published in JAMA.
Overall, the invasive cancer detection rate was 11.8 per 1,000 women for MRI compared with 4.8 per 1,000 women for DBT. Sensitivity for MRI and DBT was 96% vs. 39%, and specificity was 87% vs. 97%.
The rate of recommendation for further screening was not significantly different between the procedures (8% for MRI and 10% for DBT). The most common adverse events were three cases of mild allergic reactions and two cases of anxiety.
The study findings were limited by several factors including the inability to show an association between abbreviated breast MRI and breast cancer mortality and the lack of cost-effectiveness comparisons for the two procedures. Because eligibility criteria required a prior breast mammogram to see if the breasts were dense, the study compared an incidence DBT screen to a prevalence abbreviated MRI screen, Dr. Comstock and associates noted.
However, the results show a significantly increased breast cancer detection rate with abbreviated MRI, which merits additional research to examine the relationship between screening strategies and clinical outcomes for women with dense breasts, they said.
The study was supported in part by the National Cancer Institute of the National Institutes of Health, and by Bracco Diagnostics through funding to the ECOG-ACRIN Cancer Research Group. Dr. Comstock disclosed financial relationships with Bracco Diagnostics and Bayer, and three coauthors disclosed financial relationships with other imaging companies. The remaining coauthors had no relevant financial disclosures.
SOURCE: Comstock CK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0572.
For women with dense breasts, abbreviated magnetic resonance imaging was more effective than was digital breast tomosynthesis for detecting invasive breast cancer in a cross-sectional study of 1,444 women who underwent both procedures.
Dense breasts are a common reason for failed early diagnosis of breast cancer, wrote Christopher E. Comstock, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Digital breast tomosynthesis (DBT) and abbreviated breast magnetic resonance imaging (MRI) are becoming more popular as safe and cost-effective breast cancer screening options, but their effectiveness in women with dense breasts and average breast cancer risk has not been compared.
The researchers reviewed data from 1,444 women aged 40-75 years at 47 institutions in the United States and 1 in Germany. The women underwent both DBT and MRI. The primary endpoint was the detection of invasive cancers, of which 17 were identified at baseline screening. Abbreviated breast MRI detected all 17 cases of invasive cancer, compared with 7 detected by DBT. In addition, MRI detected six of seven women with ductal carcinoma in situ, while DBT identified two of the seven cases, according to the study, which was published in JAMA.
Overall, the invasive cancer detection rate was 11.8 per 1,000 women for MRI compared with 4.8 per 1,000 women for DBT. Sensitivity for MRI and DBT was 96% vs. 39%, and specificity was 87% vs. 97%.
The rate of recommendation for further screening was not significantly different between the procedures (8% for MRI and 10% for DBT). The most common adverse events were three cases of mild allergic reactions and two cases of anxiety.
The study findings were limited by several factors including the inability to show an association between abbreviated breast MRI and breast cancer mortality and the lack of cost-effectiveness comparisons for the two procedures. Because eligibility criteria required a prior breast mammogram to see if the breasts were dense, the study compared an incidence DBT screen to a prevalence abbreviated MRI screen, Dr. Comstock and associates noted.
However, the results show a significantly increased breast cancer detection rate with abbreviated MRI, which merits additional research to examine the relationship between screening strategies and clinical outcomes for women with dense breasts, they said.
The study was supported in part by the National Cancer Institute of the National Institutes of Health, and by Bracco Diagnostics through funding to the ECOG-ACRIN Cancer Research Group. Dr. Comstock disclosed financial relationships with Bracco Diagnostics and Bayer, and three coauthors disclosed financial relationships with other imaging companies. The remaining coauthors had no relevant financial disclosures.
SOURCE: Comstock CK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0572.
FROM JAMA
ACIP: Flu vaccines for older adults show similar safety profiles
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) recommends that age-appropriate vaccines be used when possible, said Kenneth E. Schmader, MD, professor of medicine at Duke University, Durham, N.C. However, no study to date had directly compared the safety of the trivalent high dose (HD-IIV3) and adjuvanted (aIIV3) vaccines or their impact on health-related quality of life. Dr. Schmader presented findings from a randomized trial at the February ACIP meeting.
To compare the safety of the vaccines, the researchers recruited community-dwelling volunteers aged 65 years and older who were cognitively intact, not immunosuppressed, and had no contraindications for influenza vaccination. A total of 378 individuals were randomized to aIIV3 and 379 to HD-IIV3. The average age was 72 years; 80 individuals in the aIIV3 group and 83 in the HDIIV3 group were 80 years and older. The primary outcome was moderate or severe injection site pain.
Overall, the proportion of participants with moderate or severe injection site pain was not significantly different after aIIV3 vs. HD-IIV3 (3.2% vs. 5.8%).
Nine participants in the aIIV3 group and three participants in the HD-IIV3 group experienced at least one serious adverse event, but no serious adverse events were deemed vaccine related, and the occurrence of serious adverse events was not significantly different between groups.
In addition, measures of short-term, postvaccination health-related quality of life were not significantly different between the groups. Changes in scores from day 1 prevaccination to day 3 postvaccination on the EuroQOL-5 dimensions-5 levels (EQ-5D-5L) were –0.05 for both groups.
The findings were limited in part by the lack of inclusion of older adults in nursing homes or similar settings, Dr. Schmader noted. However, the results suggest that “from the standpoint of safety, either vaccine is an acceptable option for the prevention of influenza in older adults.”
Studies comparing the immunogenicity of the vaccines are ongoing, and the data should be available within the next few months, he noted.
Dr. Schmader had no financial conflicts to disclose.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) recommends that age-appropriate vaccines be used when possible, said Kenneth E. Schmader, MD, professor of medicine at Duke University, Durham, N.C. However, no study to date had directly compared the safety of the trivalent high dose (HD-IIV3) and adjuvanted (aIIV3) vaccines or their impact on health-related quality of life. Dr. Schmader presented findings from a randomized trial at the February ACIP meeting.
To compare the safety of the vaccines, the researchers recruited community-dwelling volunteers aged 65 years and older who were cognitively intact, not immunosuppressed, and had no contraindications for influenza vaccination. A total of 378 individuals were randomized to aIIV3 and 379 to HD-IIV3. The average age was 72 years; 80 individuals in the aIIV3 group and 83 in the HDIIV3 group were 80 years and older. The primary outcome was moderate or severe injection site pain.
Overall, the proportion of participants with moderate or severe injection site pain was not significantly different after aIIV3 vs. HD-IIV3 (3.2% vs. 5.8%).
Nine participants in the aIIV3 group and three participants in the HD-IIV3 group experienced at least one serious adverse event, but no serious adverse events were deemed vaccine related, and the occurrence of serious adverse events was not significantly different between groups.
In addition, measures of short-term, postvaccination health-related quality of life were not significantly different between the groups. Changes in scores from day 1 prevaccination to day 3 postvaccination on the EuroQOL-5 dimensions-5 levels (EQ-5D-5L) were –0.05 for both groups.
The findings were limited in part by the lack of inclusion of older adults in nursing homes or similar settings, Dr. Schmader noted. However, the results suggest that “from the standpoint of safety, either vaccine is an acceptable option for the prevention of influenza in older adults.”
Studies comparing the immunogenicity of the vaccines are ongoing, and the data should be available within the next few months, he noted.
Dr. Schmader had no financial conflicts to disclose.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) recommends that age-appropriate vaccines be used when possible, said Kenneth E. Schmader, MD, professor of medicine at Duke University, Durham, N.C. However, no study to date had directly compared the safety of the trivalent high dose (HD-IIV3) and adjuvanted (aIIV3) vaccines or their impact on health-related quality of life. Dr. Schmader presented findings from a randomized trial at the February ACIP meeting.
To compare the safety of the vaccines, the researchers recruited community-dwelling volunteers aged 65 years and older who were cognitively intact, not immunosuppressed, and had no contraindications for influenza vaccination. A total of 378 individuals were randomized to aIIV3 and 379 to HD-IIV3. The average age was 72 years; 80 individuals in the aIIV3 group and 83 in the HDIIV3 group were 80 years and older. The primary outcome was moderate or severe injection site pain.
Overall, the proportion of participants with moderate or severe injection site pain was not significantly different after aIIV3 vs. HD-IIV3 (3.2% vs. 5.8%).
Nine participants in the aIIV3 group and three participants in the HD-IIV3 group experienced at least one serious adverse event, but no serious adverse events were deemed vaccine related, and the occurrence of serious adverse events was not significantly different between groups.
In addition, measures of short-term, postvaccination health-related quality of life were not significantly different between the groups. Changes in scores from day 1 prevaccination to day 3 postvaccination on the EuroQOL-5 dimensions-5 levels (EQ-5D-5L) were –0.05 for both groups.
The findings were limited in part by the lack of inclusion of older adults in nursing homes or similar settings, Dr. Schmader noted. However, the results suggest that “from the standpoint of safety, either vaccine is an acceptable option for the prevention of influenza in older adults.”
Studies comparing the immunogenicity of the vaccines are ongoing, and the data should be available within the next few months, he noted.
Dr. Schmader had no financial conflicts to disclose.
FROM AN ACIP MEETING
ACIP advocates pre-exposure Ebola vaccination for high-risk groups
Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).
The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:
- They are responding to an outbreak of Ebola virus disease.
- They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
- The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.
Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.
In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.
Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.
Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.
Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.
The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.
The ACIP members had no relevant financial conflicts to disclose.
Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).
The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:
- They are responding to an outbreak of Ebola virus disease.
- They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
- The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.
Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.
In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.
Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.
Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.
Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.
The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.
The ACIP members had no relevant financial conflicts to disclose.
Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).
The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:
- They are responding to an outbreak of Ebola virus disease.
- They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
- The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.
Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.
In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.
Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.
Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.
Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.
The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.
The ACIP members had no relevant financial conflicts to disclose.
Nemolizumab tames itching in prurigo nodularis patients in phase 2 study
compared with patients treated with placebo, according to data from a phase 2 trial of 70 patients.
Prurigo nodularis (PN) is a chronic skin condition distinguished by hyperkeratotic red nodules and extreme pruritus, which contributes to crusting and excoriation of the lesions. Lesions can range in size from a few millimeters to 3 centimeters in diameter, and number from a handful to hundreds.
“The pathogenesis of prurigo nodularis is not well understood, but it has been considered to include a form of neuronal sensitization of itch-processing neurons and the development of an itch–scratch cycle,” wrote Sonja Ständer, MD, of the department of dermatology and Center for Chronic Pruritus, University Hospital Münster, Germany, and coauthors. “Interleukin-31, when bound to its receptor complex, has been shown to be a mediator of pruritus, especially in atopic dermatitis and prurigo nodularis,” they noted.
In a study published in the New England Journal of Medicine, the researchers randomized 70 adults with PN to nemolizumab, a monoclonal antibody targeting the interleukin-31 receptor, or a placebo. Patients received 0.5 mg/kg of the drug or placebo subcutaneously at baseline and again at 4 and 8 weeks; safety data were assessed through 18 weeks.
At week 4, the primary outcome of average peak pruritus score based on the numerical rating scale (PP-NRS) decreased by 4.5 points in the nemolizumab group, compared with 1.7 points in the placebo group (reductions of 53% and 20%, respectively). At baseline, weekly peak scores on the PP-NRS were 8.4 for both groups.
In addition, 24% of the nemolizumab patients reported 75% or more healed lesions at week 4, compared with 11% of the placebo group, and at the week 18 final follow-up visit, “the least-squares mean change in the lesion count was −13.3 in the nemolizumab group and − 7.5 in the placebo group,” the researchers said.
Adverse events were similar in both nemolizumab and placebo groups (68% and 67%, respectively) with the most common being gastrointestinal symptoms and musculoskeletal pain. Four nemolizumab patients and three placebo patients experienced serious adverse events. The serious adverse events in the nemolizumab patients included one case each of psoriasiform rash, clavicular fracture, fibromyalgia, and bladder lithiasis. Two patients in each group discontinued the study because of adverse events.
The study findings were limited by the small sample size and short duration, the researchers noted. However, the Food and Drug Administration granted nemolizumab a Breakthrough Therapy Designation in 2019, according to Galderma, and the company is planning a phase 3 trial of nemolizumab in adults with PN to begin later in 2020.
Galderma sponsored and designed the study. Lead author Dr. Ständer disclosed ties with Galderma, Almirall, Beiersdorf, Bellus Health, Cara Therapeutics, Celgene, LEO Pharma, Sienna Biopharmaceuticals, and Vanda Pharmaceuticals. Several coauthors were Galderma employees.
SOURCE: Ständer S et al. N Engl J Med. 2020 Feb 20;382(8):706-16.
compared with patients treated with placebo, according to data from a phase 2 trial of 70 patients.
Prurigo nodularis (PN) is a chronic skin condition distinguished by hyperkeratotic red nodules and extreme pruritus, which contributes to crusting and excoriation of the lesions. Lesions can range in size from a few millimeters to 3 centimeters in diameter, and number from a handful to hundreds.
“The pathogenesis of prurigo nodularis is not well understood, but it has been considered to include a form of neuronal sensitization of itch-processing neurons and the development of an itch–scratch cycle,” wrote Sonja Ständer, MD, of the department of dermatology and Center for Chronic Pruritus, University Hospital Münster, Germany, and coauthors. “Interleukin-31, when bound to its receptor complex, has been shown to be a mediator of pruritus, especially in atopic dermatitis and prurigo nodularis,” they noted.
In a study published in the New England Journal of Medicine, the researchers randomized 70 adults with PN to nemolizumab, a monoclonal antibody targeting the interleukin-31 receptor, or a placebo. Patients received 0.5 mg/kg of the drug or placebo subcutaneously at baseline and again at 4 and 8 weeks; safety data were assessed through 18 weeks.
At week 4, the primary outcome of average peak pruritus score based on the numerical rating scale (PP-NRS) decreased by 4.5 points in the nemolizumab group, compared with 1.7 points in the placebo group (reductions of 53% and 20%, respectively). At baseline, weekly peak scores on the PP-NRS were 8.4 for both groups.
In addition, 24% of the nemolizumab patients reported 75% or more healed lesions at week 4, compared with 11% of the placebo group, and at the week 18 final follow-up visit, “the least-squares mean change in the lesion count was −13.3 in the nemolizumab group and − 7.5 in the placebo group,” the researchers said.
Adverse events were similar in both nemolizumab and placebo groups (68% and 67%, respectively) with the most common being gastrointestinal symptoms and musculoskeletal pain. Four nemolizumab patients and three placebo patients experienced serious adverse events. The serious adverse events in the nemolizumab patients included one case each of psoriasiform rash, clavicular fracture, fibromyalgia, and bladder lithiasis. Two patients in each group discontinued the study because of adverse events.
The study findings were limited by the small sample size and short duration, the researchers noted. However, the Food and Drug Administration granted nemolizumab a Breakthrough Therapy Designation in 2019, according to Galderma, and the company is planning a phase 3 trial of nemolizumab in adults with PN to begin later in 2020.
Galderma sponsored and designed the study. Lead author Dr. Ständer disclosed ties with Galderma, Almirall, Beiersdorf, Bellus Health, Cara Therapeutics, Celgene, LEO Pharma, Sienna Biopharmaceuticals, and Vanda Pharmaceuticals. Several coauthors were Galderma employees.
SOURCE: Ständer S et al. N Engl J Med. 2020 Feb 20;382(8):706-16.
compared with patients treated with placebo, according to data from a phase 2 trial of 70 patients.
Prurigo nodularis (PN) is a chronic skin condition distinguished by hyperkeratotic red nodules and extreme pruritus, which contributes to crusting and excoriation of the lesions. Lesions can range in size from a few millimeters to 3 centimeters in diameter, and number from a handful to hundreds.
“The pathogenesis of prurigo nodularis is not well understood, but it has been considered to include a form of neuronal sensitization of itch-processing neurons and the development of an itch–scratch cycle,” wrote Sonja Ständer, MD, of the department of dermatology and Center for Chronic Pruritus, University Hospital Münster, Germany, and coauthors. “Interleukin-31, when bound to its receptor complex, has been shown to be a mediator of pruritus, especially in atopic dermatitis and prurigo nodularis,” they noted.
In a study published in the New England Journal of Medicine, the researchers randomized 70 adults with PN to nemolizumab, a monoclonal antibody targeting the interleukin-31 receptor, or a placebo. Patients received 0.5 mg/kg of the drug or placebo subcutaneously at baseline and again at 4 and 8 weeks; safety data were assessed through 18 weeks.
At week 4, the primary outcome of average peak pruritus score based on the numerical rating scale (PP-NRS) decreased by 4.5 points in the nemolizumab group, compared with 1.7 points in the placebo group (reductions of 53% and 20%, respectively). At baseline, weekly peak scores on the PP-NRS were 8.4 for both groups.
In addition, 24% of the nemolizumab patients reported 75% or more healed lesions at week 4, compared with 11% of the placebo group, and at the week 18 final follow-up visit, “the least-squares mean change in the lesion count was −13.3 in the nemolizumab group and − 7.5 in the placebo group,” the researchers said.
Adverse events were similar in both nemolizumab and placebo groups (68% and 67%, respectively) with the most common being gastrointestinal symptoms and musculoskeletal pain. Four nemolizumab patients and three placebo patients experienced serious adverse events. The serious adverse events in the nemolizumab patients included one case each of psoriasiform rash, clavicular fracture, fibromyalgia, and bladder lithiasis. Two patients in each group discontinued the study because of adverse events.
The study findings were limited by the small sample size and short duration, the researchers noted. However, the Food and Drug Administration granted nemolizumab a Breakthrough Therapy Designation in 2019, according to Galderma, and the company is planning a phase 3 trial of nemolizumab in adults with PN to begin later in 2020.
Galderma sponsored and designed the study. Lead author Dr. Ständer disclosed ties with Galderma, Almirall, Beiersdorf, Bellus Health, Cara Therapeutics, Celgene, LEO Pharma, Sienna Biopharmaceuticals, and Vanda Pharmaceuticals. Several coauthors were Galderma employees.
SOURCE: Ständer S et al. N Engl J Med. 2020 Feb 20;382(8):706-16.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Vitamin E acetate found in more vapers’ lung fluid
Analysis of additional lung fluid samples confirms the presence of vitamin E acetate in patients with electronic-cigarette, or vaping, product use–associated lung injury, according to a report on 51 patients in 16 states.
The average age of the patients was 23 years; 69% were male.
The report extends previous work by the Centers for Disease Control and Prevention to test for harmful substances in bronchoalveolar-lavage (BAL) fluid obtained from patients with electronic-cigarette, or vaping, product use–associated lung injury (EVALI) as part of a strategy to understand and manage the recent outbreak of EVALI cases in the United States, wrote Benjamin C. Blount, PhD, of the Division of Laboratory Sciences at the CDC’s National Center for Environmental Health, and colleagues.
“CDC was addressing a serious outbreak of lung injury that was sometimes lethal; but after the first 10 weeks of the outbreak investigation, the cause was still unknown,” Dr. Blount said in an interview. “Possible theories could not be evaluated unless the laboratory could develop tests that could confidently connect exposure to lung injury. Detection of toxicants in bronchoalveolar-lavage fluid from patients with EVALI can provide direct information on exposure within the lung.”
In a study published in the New England Journal of Medicine, the researchers examined the BAL of 51 cases of EVALI from 16 states. They analyzed the samples for multiple toxicants, including vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.
Overall, 77% of the patients reported using products containing THC, 67% reported using products containing nicotine, and 51% reported using both types.
Researchers found vitamin E acetate in 48 of the 51 patients (94%); no vitamin E acetate was found in the BAL of healthy controls. Coconut oil and limonene were found in one patient each, but none of the other toxicants was found in the samples from the patients or controls.
In addition, 47 of the 50 patients for whom data were available either had detectable tetrahydrocannabinol (THC) or its metabolites in their BAL fluid samples, or they reported vaping THC products within 90 days before they became ill. Nicotine or its metabolites were found in 30 of 47 patients (64%).
The study findings were limited by several factors, including the potential role of vitamin E acetate as a marker for exposure to other toxicants, the uncertainty of the role of aerosolized constituents formed when vitamin E acetate is heated, and the lack of data on the timing and burden of toxicant exposure, the investigators noted.
As for the next steps in research, “additional studies are needed to examine the respiratory effects of inhaling aerosolized vitamin E acetate and provide information on whether vitamin E acetate in isolation causes lung injury,” Dr. Blount explained. Analysis of the aerosol and gases generated by case-associated product fluids is ongoing.
“When CDC developed the BAL study for this response, we considered several possible toxicants in this investigation to find a possible cause of the outbreak,” Dr. Blount noted. “To accomplish the study, CDC’s Environmental Health Laboratory developed 12 analytical methods and validated them in less than 3 weeks because of the urgent nature of the emergency.”
Dr. Blount said he would advise clinicians to “continue to reference CDC guidance on treating suspected or EVALI patients.” In December, the CDC published updated guidance for clinicians on hospitalized EVALI patients. “Following this guidance and other recommendations could reduce EVALI-associated morbidity and mortality,” Dr. Blount said.
The study was supported in part by the National Cancer Institute, the FDA Center for Tobacco Products, and Ohio State University Pelotonia Intramural Research. The researchers had no financial conflicts to disclose.
SOURCE: Blount BC et al. N Engl J Med. 2020 Feb 20. doi: 10.1056/NEJMoa1916433.
Analysis of additional lung fluid samples confirms the presence of vitamin E acetate in patients with electronic-cigarette, or vaping, product use–associated lung injury, according to a report on 51 patients in 16 states.
The average age of the patients was 23 years; 69% were male.
The report extends previous work by the Centers for Disease Control and Prevention to test for harmful substances in bronchoalveolar-lavage (BAL) fluid obtained from patients with electronic-cigarette, or vaping, product use–associated lung injury (EVALI) as part of a strategy to understand and manage the recent outbreak of EVALI cases in the United States, wrote Benjamin C. Blount, PhD, of the Division of Laboratory Sciences at the CDC’s National Center for Environmental Health, and colleagues.
“CDC was addressing a serious outbreak of lung injury that was sometimes lethal; but after the first 10 weeks of the outbreak investigation, the cause was still unknown,” Dr. Blount said in an interview. “Possible theories could not be evaluated unless the laboratory could develop tests that could confidently connect exposure to lung injury. Detection of toxicants in bronchoalveolar-lavage fluid from patients with EVALI can provide direct information on exposure within the lung.”
In a study published in the New England Journal of Medicine, the researchers examined the BAL of 51 cases of EVALI from 16 states. They analyzed the samples for multiple toxicants, including vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.
Overall, 77% of the patients reported using products containing THC, 67% reported using products containing nicotine, and 51% reported using both types.
Researchers found vitamin E acetate in 48 of the 51 patients (94%); no vitamin E acetate was found in the BAL of healthy controls. Coconut oil and limonene were found in one patient each, but none of the other toxicants was found in the samples from the patients or controls.
In addition, 47 of the 50 patients for whom data were available either had detectable tetrahydrocannabinol (THC) or its metabolites in their BAL fluid samples, or they reported vaping THC products within 90 days before they became ill. Nicotine or its metabolites were found in 30 of 47 patients (64%).
The study findings were limited by several factors, including the potential role of vitamin E acetate as a marker for exposure to other toxicants, the uncertainty of the role of aerosolized constituents formed when vitamin E acetate is heated, and the lack of data on the timing and burden of toxicant exposure, the investigators noted.
As for the next steps in research, “additional studies are needed to examine the respiratory effects of inhaling aerosolized vitamin E acetate and provide information on whether vitamin E acetate in isolation causes lung injury,” Dr. Blount explained. Analysis of the aerosol and gases generated by case-associated product fluids is ongoing.
“When CDC developed the BAL study for this response, we considered several possible toxicants in this investigation to find a possible cause of the outbreak,” Dr. Blount noted. “To accomplish the study, CDC’s Environmental Health Laboratory developed 12 analytical methods and validated them in less than 3 weeks because of the urgent nature of the emergency.”
Dr. Blount said he would advise clinicians to “continue to reference CDC guidance on treating suspected or EVALI patients.” In December, the CDC published updated guidance for clinicians on hospitalized EVALI patients. “Following this guidance and other recommendations could reduce EVALI-associated morbidity and mortality,” Dr. Blount said.
The study was supported in part by the National Cancer Institute, the FDA Center for Tobacco Products, and Ohio State University Pelotonia Intramural Research. The researchers had no financial conflicts to disclose.
SOURCE: Blount BC et al. N Engl J Med. 2020 Feb 20. doi: 10.1056/NEJMoa1916433.
Analysis of additional lung fluid samples confirms the presence of vitamin E acetate in patients with electronic-cigarette, or vaping, product use–associated lung injury, according to a report on 51 patients in 16 states.
The average age of the patients was 23 years; 69% were male.
The report extends previous work by the Centers for Disease Control and Prevention to test for harmful substances in bronchoalveolar-lavage (BAL) fluid obtained from patients with electronic-cigarette, or vaping, product use–associated lung injury (EVALI) as part of a strategy to understand and manage the recent outbreak of EVALI cases in the United States, wrote Benjamin C. Blount, PhD, of the Division of Laboratory Sciences at the CDC’s National Center for Environmental Health, and colleagues.
“CDC was addressing a serious outbreak of lung injury that was sometimes lethal; but after the first 10 weeks of the outbreak investigation, the cause was still unknown,” Dr. Blount said in an interview. “Possible theories could not be evaluated unless the laboratory could develop tests that could confidently connect exposure to lung injury. Detection of toxicants in bronchoalveolar-lavage fluid from patients with EVALI can provide direct information on exposure within the lung.”
In a study published in the New England Journal of Medicine, the researchers examined the BAL of 51 cases of EVALI from 16 states. They analyzed the samples for multiple toxicants, including vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.
Overall, 77% of the patients reported using products containing THC, 67% reported using products containing nicotine, and 51% reported using both types.
Researchers found vitamin E acetate in 48 of the 51 patients (94%); no vitamin E acetate was found in the BAL of healthy controls. Coconut oil and limonene were found in one patient each, but none of the other toxicants was found in the samples from the patients or controls.
In addition, 47 of the 50 patients for whom data were available either had detectable tetrahydrocannabinol (THC) or its metabolites in their BAL fluid samples, or they reported vaping THC products within 90 days before they became ill. Nicotine or its metabolites were found in 30 of 47 patients (64%).
The study findings were limited by several factors, including the potential role of vitamin E acetate as a marker for exposure to other toxicants, the uncertainty of the role of aerosolized constituents formed when vitamin E acetate is heated, and the lack of data on the timing and burden of toxicant exposure, the investigators noted.
As for the next steps in research, “additional studies are needed to examine the respiratory effects of inhaling aerosolized vitamin E acetate and provide information on whether vitamin E acetate in isolation causes lung injury,” Dr. Blount explained. Analysis of the aerosol and gases generated by case-associated product fluids is ongoing.
“When CDC developed the BAL study for this response, we considered several possible toxicants in this investigation to find a possible cause of the outbreak,” Dr. Blount noted. “To accomplish the study, CDC’s Environmental Health Laboratory developed 12 analytical methods and validated them in less than 3 weeks because of the urgent nature of the emergency.”
Dr. Blount said he would advise clinicians to “continue to reference CDC guidance on treating suspected or EVALI patients.” In December, the CDC published updated guidance for clinicians on hospitalized EVALI patients. “Following this guidance and other recommendations could reduce EVALI-associated morbidity and mortality,” Dr. Blount said.
The study was supported in part by the National Cancer Institute, the FDA Center for Tobacco Products, and Ohio State University Pelotonia Intramural Research. The researchers had no financial conflicts to disclose.
SOURCE: Blount BC et al. N Engl J Med. 2020 Feb 20. doi: 10.1056/NEJMoa1916433.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Psoriasis elevates cancer risk
Psoriasis patients are at increased risk for several types of cancer, notably lymphoma and keratinocyte cancer, based on data from a systematic review and meta-analysis of more than 2 million patients.
Previous studies have identified an increased overall cancer risk in psoriasis patients, compared with the general population or controls without psoriasis, and both lymphomas and keratinocyte cancers occur more often in psoriasis patients, compared with controls, but additional larger studies have been conducted since the last meta-analysis was published in 2013, wrote Sofie Vaengebjerg, MD, of the University of Copenhagen and colleagues.
To better identify the risk of cancer in psoriasis and psoriatic arthritis patients and to explore the impact of biologics, the researchers reviewed data from 112 studies totaling 2,053,932 patients in a study published in JAMA Dermatology.
Overall, the risk of any cancer was slightly higher in psoriasis patients (risk ratio, 1.21; 95% confidence interval, 1.11-1.33), compared with controls, with a prevalence of 4.78% and an incidence rate of 11.75 per 1,000 person-years. The most common cancer among psoriasis patients was keratinocyte cancer, with a risk ratio of 2.28 (95% CI, 1.73-3.01), a prevalence of 2.55%, and an incidence rate of 4.35 per 1,000 person-years.
Other cancers with significantly elevated risk among psoriasis patients were lymphomas (RR, 1.56; 95% CI, 1.37-1.78), lung cancer (RR, 1.26; 95% CI, 1.13-1.40), and bladder cancer (RR, 1.12; 95% CI, 1.04-1.19).
No increased risk of cancer was noted among psoriasis patients who were treated with biologics. “However, patients receiving biologic agents are selected and the results might be reliant on selection bias, and studies investigating long-term safety of these drugs are still limited,” the researchers wrote.
In addition, psoriatic arthritis was not associated with any overall increase in cancer risk, with the exception of three studies showing an increased risk for breast cancer, the researchers noted. The overall cancer prevalence for psoriatic arthritis patients was 5.74%, with an incidence rate of 6.44 per 1,000 person-years.
The study findings were limited by several factors, including the inconsistencies in study design and characteristics and the small amount of data on biologic agents and psoriatic arthritis, the researchers noted. However, the results were strengthened by the large number of patients, real-world study settings, inclusion of biologics, and analysis of cancer in psoriatic arthritis patients.
“Clinicians treating patients with psoriasis should be aware of this increased risk, especially for lymphomas, as immunogenic treatment might be associated with exacerbations,” and should be aware that more research is needed to assess cancer risk associated with biologics, they concluded.
The study received no outside funding. Lead author Dr. Vaengebjerg had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including AbbVie, Janssen, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi.
SOURCE: Vaengebjerg S et al. JAMA Dermatol. 2020 Feb 19. doi:10.1001/jamadermatol.2020.0024.
Psoriasis patients are at increased risk for several types of cancer, notably lymphoma and keratinocyte cancer, based on data from a systematic review and meta-analysis of more than 2 million patients.
Previous studies have identified an increased overall cancer risk in psoriasis patients, compared with the general population or controls without psoriasis, and both lymphomas and keratinocyte cancers occur more often in psoriasis patients, compared with controls, but additional larger studies have been conducted since the last meta-analysis was published in 2013, wrote Sofie Vaengebjerg, MD, of the University of Copenhagen and colleagues.
To better identify the risk of cancer in psoriasis and psoriatic arthritis patients and to explore the impact of biologics, the researchers reviewed data from 112 studies totaling 2,053,932 patients in a study published in JAMA Dermatology.
Overall, the risk of any cancer was slightly higher in psoriasis patients (risk ratio, 1.21; 95% confidence interval, 1.11-1.33), compared with controls, with a prevalence of 4.78% and an incidence rate of 11.75 per 1,000 person-years. The most common cancer among psoriasis patients was keratinocyte cancer, with a risk ratio of 2.28 (95% CI, 1.73-3.01), a prevalence of 2.55%, and an incidence rate of 4.35 per 1,000 person-years.
Other cancers with significantly elevated risk among psoriasis patients were lymphomas (RR, 1.56; 95% CI, 1.37-1.78), lung cancer (RR, 1.26; 95% CI, 1.13-1.40), and bladder cancer (RR, 1.12; 95% CI, 1.04-1.19).
No increased risk of cancer was noted among psoriasis patients who were treated with biologics. “However, patients receiving biologic agents are selected and the results might be reliant on selection bias, and studies investigating long-term safety of these drugs are still limited,” the researchers wrote.
In addition, psoriatic arthritis was not associated with any overall increase in cancer risk, with the exception of three studies showing an increased risk for breast cancer, the researchers noted. The overall cancer prevalence for psoriatic arthritis patients was 5.74%, with an incidence rate of 6.44 per 1,000 person-years.
The study findings were limited by several factors, including the inconsistencies in study design and characteristics and the small amount of data on biologic agents and psoriatic arthritis, the researchers noted. However, the results were strengthened by the large number of patients, real-world study settings, inclusion of biologics, and analysis of cancer in psoriatic arthritis patients.
“Clinicians treating patients with psoriasis should be aware of this increased risk, especially for lymphomas, as immunogenic treatment might be associated with exacerbations,” and should be aware that more research is needed to assess cancer risk associated with biologics, they concluded.
The study received no outside funding. Lead author Dr. Vaengebjerg had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including AbbVie, Janssen, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi.
SOURCE: Vaengebjerg S et al. JAMA Dermatol. 2020 Feb 19. doi:10.1001/jamadermatol.2020.0024.
Psoriasis patients are at increased risk for several types of cancer, notably lymphoma and keratinocyte cancer, based on data from a systematic review and meta-analysis of more than 2 million patients.
Previous studies have identified an increased overall cancer risk in psoriasis patients, compared with the general population or controls without psoriasis, and both lymphomas and keratinocyte cancers occur more often in psoriasis patients, compared with controls, but additional larger studies have been conducted since the last meta-analysis was published in 2013, wrote Sofie Vaengebjerg, MD, of the University of Copenhagen and colleagues.
To better identify the risk of cancer in psoriasis and psoriatic arthritis patients and to explore the impact of biologics, the researchers reviewed data from 112 studies totaling 2,053,932 patients in a study published in JAMA Dermatology.
Overall, the risk of any cancer was slightly higher in psoriasis patients (risk ratio, 1.21; 95% confidence interval, 1.11-1.33), compared with controls, with a prevalence of 4.78% and an incidence rate of 11.75 per 1,000 person-years. The most common cancer among psoriasis patients was keratinocyte cancer, with a risk ratio of 2.28 (95% CI, 1.73-3.01), a prevalence of 2.55%, and an incidence rate of 4.35 per 1,000 person-years.
Other cancers with significantly elevated risk among psoriasis patients were lymphomas (RR, 1.56; 95% CI, 1.37-1.78), lung cancer (RR, 1.26; 95% CI, 1.13-1.40), and bladder cancer (RR, 1.12; 95% CI, 1.04-1.19).
No increased risk of cancer was noted among psoriasis patients who were treated with biologics. “However, patients receiving biologic agents are selected and the results might be reliant on selection bias, and studies investigating long-term safety of these drugs are still limited,” the researchers wrote.
In addition, psoriatic arthritis was not associated with any overall increase in cancer risk, with the exception of three studies showing an increased risk for breast cancer, the researchers noted. The overall cancer prevalence for psoriatic arthritis patients was 5.74%, with an incidence rate of 6.44 per 1,000 person-years.
The study findings were limited by several factors, including the inconsistencies in study design and characteristics and the small amount of data on biologic agents and psoriatic arthritis, the researchers noted. However, the results were strengthened by the large number of patients, real-world study settings, inclusion of biologics, and analysis of cancer in psoriatic arthritis patients.
“Clinicians treating patients with psoriasis should be aware of this increased risk, especially for lymphomas, as immunogenic treatment might be associated with exacerbations,” and should be aware that more research is needed to assess cancer risk associated with biologics, they concluded.
The study received no outside funding. Lead author Dr. Vaengebjerg had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including AbbVie, Janssen, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi.
SOURCE: Vaengebjerg S et al. JAMA Dermatol. 2020 Feb 19. doi:10.1001/jamadermatol.2020.0024.
FROM JAMA DERMATOLOGY
Infection with 2019 novel coronavirus extends to infants
between Dec. 8, 2019, and Feb. 6, 2020, based on data from the Chinese central government and local health departments.
“As of February 6, 2020, China reported 31,211 confirmed cases of COVID-19 and 637 fatalities,” wrote Min Wei, MD, of Wuhan University, China, and colleagues. However, “few infections in children have been reported.”
In a research letter published in JAMA, the investigators reviewed data from nine infants aged 28 days to 1 year who were hospitalized with a diagnosis of COVID-19 between Dec. 8, 2019, and Feb. 6, 2020. The ages of the infants ranged from 1 month to 11 months, and seven were female. The patients included two children from Beijing, two from Hainan, and one each from the areas of Guangdong, Anhui, Shanghai, Zhejiang, and Guizhou.
All infected infants had at least one infected family member, and the infants’ infections occurred after the family members’ infections; seven infants lived in Wuhan or had family members who had visited Wuhan.
One of the infants had no symptoms but tested positive for the 2019 novel coronavirus, and two others had a diagnosis but missing information on any symptoms. Fever occurred in four patients, and mild upper respiratory tract symptoms occurred in two patients.
None of the infants died, and none reported severe complications or the need for intensive care or mechanical ventilation, the investigators said. The fact that most of the infants were female might suggest that they are more susceptible to the virus than males, although overall COVID-19 viral infections have been more common in adult men, especially those with chronic comorbidities, Dr. Wei and associates noted.
The study findings were limited by the small sample size and lack of symptom data for some patients, the researchers said. However, the results confirm that the COVID-19 virus is transmissible to infants younger than 1 year, and adult caregivers should exercise protective measures including wearing masks, washing hands before contact with infants, and routinely sterilizing toys and tableware, they emphasized.
The study was supported by the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities. The researchers had no financial conflicts to disclose.
SOURCE: Wei M et al. JAMA. 2020 Feb 14. doi:10.1001/jama.2020.2131.
between Dec. 8, 2019, and Feb. 6, 2020, based on data from the Chinese central government and local health departments.
“As of February 6, 2020, China reported 31,211 confirmed cases of COVID-19 and 637 fatalities,” wrote Min Wei, MD, of Wuhan University, China, and colleagues. However, “few infections in children have been reported.”
In a research letter published in JAMA, the investigators reviewed data from nine infants aged 28 days to 1 year who were hospitalized with a diagnosis of COVID-19 between Dec. 8, 2019, and Feb. 6, 2020. The ages of the infants ranged from 1 month to 11 months, and seven were female. The patients included two children from Beijing, two from Hainan, and one each from the areas of Guangdong, Anhui, Shanghai, Zhejiang, and Guizhou.
All infected infants had at least one infected family member, and the infants’ infections occurred after the family members’ infections; seven infants lived in Wuhan or had family members who had visited Wuhan.
One of the infants had no symptoms but tested positive for the 2019 novel coronavirus, and two others had a diagnosis but missing information on any symptoms. Fever occurred in four patients, and mild upper respiratory tract symptoms occurred in two patients.
None of the infants died, and none reported severe complications or the need for intensive care or mechanical ventilation, the investigators said. The fact that most of the infants were female might suggest that they are more susceptible to the virus than males, although overall COVID-19 viral infections have been more common in adult men, especially those with chronic comorbidities, Dr. Wei and associates noted.
The study findings were limited by the small sample size and lack of symptom data for some patients, the researchers said. However, the results confirm that the COVID-19 virus is transmissible to infants younger than 1 year, and adult caregivers should exercise protective measures including wearing masks, washing hands before contact with infants, and routinely sterilizing toys and tableware, they emphasized.
The study was supported by the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities. The researchers had no financial conflicts to disclose.
SOURCE: Wei M et al. JAMA. 2020 Feb 14. doi:10.1001/jama.2020.2131.
between Dec. 8, 2019, and Feb. 6, 2020, based on data from the Chinese central government and local health departments.
“As of February 6, 2020, China reported 31,211 confirmed cases of COVID-19 and 637 fatalities,” wrote Min Wei, MD, of Wuhan University, China, and colleagues. However, “few infections in children have been reported.”
In a research letter published in JAMA, the investigators reviewed data from nine infants aged 28 days to 1 year who were hospitalized with a diagnosis of COVID-19 between Dec. 8, 2019, and Feb. 6, 2020. The ages of the infants ranged from 1 month to 11 months, and seven were female. The patients included two children from Beijing, two from Hainan, and one each from the areas of Guangdong, Anhui, Shanghai, Zhejiang, and Guizhou.
All infected infants had at least one infected family member, and the infants’ infections occurred after the family members’ infections; seven infants lived in Wuhan or had family members who had visited Wuhan.
One of the infants had no symptoms but tested positive for the 2019 novel coronavirus, and two others had a diagnosis but missing information on any symptoms. Fever occurred in four patients, and mild upper respiratory tract symptoms occurred in two patients.
None of the infants died, and none reported severe complications or the need for intensive care or mechanical ventilation, the investigators said. The fact that most of the infants were female might suggest that they are more susceptible to the virus than males, although overall COVID-19 viral infections have been more common in adult men, especially those with chronic comorbidities, Dr. Wei and associates noted.
The study findings were limited by the small sample size and lack of symptom data for some patients, the researchers said. However, the results confirm that the COVID-19 virus is transmissible to infants younger than 1 year, and adult caregivers should exercise protective measures including wearing masks, washing hands before contact with infants, and routinely sterilizing toys and tableware, they emphasized.
The study was supported by the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities. The researchers had no financial conflicts to disclose.
SOURCE: Wei M et al. JAMA. 2020 Feb 14. doi:10.1001/jama.2020.2131.
FROM JAMA
Heart disease risk rises with gut metabolite linked to red meat
Changes in gut microbiota linked to red meat intake over time were significantly associated with increased risk of coronary heart disease, regardless of baseline microbiota measures, based on data from 760 participants in the Nurses’ Health Study.
“A gut microbiota–related metabolite, trimethylamine N-oxide (TMAO), has been related to risks of major adverse cardiovascular events including myocardial infarction and coronary heart disease (CHD) in epidemiological studies,” but previous studies have not examined the impact of long-term changes in TMAO on CHD risk, wrote Yoriko Heianza, RD, PhD, of Tulane University, New Orleans, and colleagues.
Red meat has been shown to increase TMAO levels, whereas discontinuation of red meat intake reduced plasma TMAO levels (Eur Heart J 2019;40:583-94), the investigators wrote.
In their study, published in the Journal of the American College of Cardiology, the researchers evaluated blood samples from 760 women who were participants in the Nurses’ Health Study. The samples were collected at two time points: 1989-1990 and 2000-2002. The researchers identified 360 incident cases of CHD over the study period and compared them with matched controls.
Over roughly 10 years, increases in TMAO over time were significantly associated with increased CHD risk, with a relative risk of 1.58 for the top tertile and a relative risk of 1.33 per each standard deviation.
Women with elevated levels of TMAO both at baseline and at the 10-year point had the highest CHD risk (relative risk 1.79), compared with women with low TMAO levels at baseline and 10 years later.
The researchers also found an impact of diet on the TMAO-CHD relationship. Individuals with unhealthy eating patterns based on the Alternate Healthy Eating Index showed greater increases in TMAO and greater CHD risk. By contrast, greater adherence to healthy eating habits attenuated the impact of TMAO and CHD.
The study findings were limited by several factors, including the inability to assess the timing of the changes in the metabolites that contributed to CHD, the reliance on self-reports for dietary patterns and other variables, and the inclusion only of women health professionals in the study population, the researchers noted. However, the results were strengthened by the availability of long-term blood samples and a patient population free of disease at baseline.
In addition, “adherence to healthy dietary patterns may modulate the adverse relationship between TMAO changes and CHD, suggesting that TMAO as a potential intermediate endpoint of interventions focusing on dietary modifications for CHD prevention,” the researchers wrote.
“The findings of the study provide further evidence for the role of TMAO as a predictive biomarker for atherosclerotic heart disease and strengthen the case for TMAO as a potential intervention target in CV [cardiovascular] disease prevention,” wrote Paul A. Heidenreich, MD, and Petra Mamic, MD, of Stanford (Calif.) University, in an accompanying editorial.
In addition, “It is increasingly clear that GMB [gut microbiota] metabolites have biological activity, and that dietary changes alter the GMB and its metabolic output, with subsequent modulation of downstream host effects,” they wrote.
“While acknowledging the limitations of self-reported dietary pattern assessment, this is an important finding because it suggests that healthy dietary patterns may in some ways neutralize TMAO’s harmful effects on the CV system, potentially through other identified and unidentified GMB-mediated pathways,” they added.
The study was sponsored in part by the National Institutes of Health, the Boston Obesity Nutrition Research Center, and the United States–Israel Binational Science Foundation. Neither the researchers nor the editorialists had any financial conflicts to disclose.
SOURCES: Heianza Y et al. J Am Coll Cardiol. 2020 Feb 17. doi: 0.1016/j.jacc.2019.11.060; Heidenreich PA, Mamic P. J Am Coll Cardiol. 2020 Feb 17. doi: 10.1016/j.jacc.2019.12.023.
Changes in gut microbiota linked to red meat intake over time were significantly associated with increased risk of coronary heart disease, regardless of baseline microbiota measures, based on data from 760 participants in the Nurses’ Health Study.
“A gut microbiota–related metabolite, trimethylamine N-oxide (TMAO), has been related to risks of major adverse cardiovascular events including myocardial infarction and coronary heart disease (CHD) in epidemiological studies,” but previous studies have not examined the impact of long-term changes in TMAO on CHD risk, wrote Yoriko Heianza, RD, PhD, of Tulane University, New Orleans, and colleagues.
Red meat has been shown to increase TMAO levels, whereas discontinuation of red meat intake reduced plasma TMAO levels (Eur Heart J 2019;40:583-94), the investigators wrote.
In their study, published in the Journal of the American College of Cardiology, the researchers evaluated blood samples from 760 women who were participants in the Nurses’ Health Study. The samples were collected at two time points: 1989-1990 and 2000-2002. The researchers identified 360 incident cases of CHD over the study period and compared them with matched controls.
Over roughly 10 years, increases in TMAO over time were significantly associated with increased CHD risk, with a relative risk of 1.58 for the top tertile and a relative risk of 1.33 per each standard deviation.
Women with elevated levels of TMAO both at baseline and at the 10-year point had the highest CHD risk (relative risk 1.79), compared with women with low TMAO levels at baseline and 10 years later.
The researchers also found an impact of diet on the TMAO-CHD relationship. Individuals with unhealthy eating patterns based on the Alternate Healthy Eating Index showed greater increases in TMAO and greater CHD risk. By contrast, greater adherence to healthy eating habits attenuated the impact of TMAO and CHD.
The study findings were limited by several factors, including the inability to assess the timing of the changes in the metabolites that contributed to CHD, the reliance on self-reports for dietary patterns and other variables, and the inclusion only of women health professionals in the study population, the researchers noted. However, the results were strengthened by the availability of long-term blood samples and a patient population free of disease at baseline.
In addition, “adherence to healthy dietary patterns may modulate the adverse relationship between TMAO changes and CHD, suggesting that TMAO as a potential intermediate endpoint of interventions focusing on dietary modifications for CHD prevention,” the researchers wrote.
“The findings of the study provide further evidence for the role of TMAO as a predictive biomarker for atherosclerotic heart disease and strengthen the case for TMAO as a potential intervention target in CV [cardiovascular] disease prevention,” wrote Paul A. Heidenreich, MD, and Petra Mamic, MD, of Stanford (Calif.) University, in an accompanying editorial.
In addition, “It is increasingly clear that GMB [gut microbiota] metabolites have biological activity, and that dietary changes alter the GMB and its metabolic output, with subsequent modulation of downstream host effects,” they wrote.
“While acknowledging the limitations of self-reported dietary pattern assessment, this is an important finding because it suggests that healthy dietary patterns may in some ways neutralize TMAO’s harmful effects on the CV system, potentially through other identified and unidentified GMB-mediated pathways,” they added.
The study was sponsored in part by the National Institutes of Health, the Boston Obesity Nutrition Research Center, and the United States–Israel Binational Science Foundation. Neither the researchers nor the editorialists had any financial conflicts to disclose.
SOURCES: Heianza Y et al. J Am Coll Cardiol. 2020 Feb 17. doi: 0.1016/j.jacc.2019.11.060; Heidenreich PA, Mamic P. J Am Coll Cardiol. 2020 Feb 17. doi: 10.1016/j.jacc.2019.12.023.
Changes in gut microbiota linked to red meat intake over time were significantly associated with increased risk of coronary heart disease, regardless of baseline microbiota measures, based on data from 760 participants in the Nurses’ Health Study.
“A gut microbiota–related metabolite, trimethylamine N-oxide (TMAO), has been related to risks of major adverse cardiovascular events including myocardial infarction and coronary heart disease (CHD) in epidemiological studies,” but previous studies have not examined the impact of long-term changes in TMAO on CHD risk, wrote Yoriko Heianza, RD, PhD, of Tulane University, New Orleans, and colleagues.
Red meat has been shown to increase TMAO levels, whereas discontinuation of red meat intake reduced plasma TMAO levels (Eur Heart J 2019;40:583-94), the investigators wrote.
In their study, published in the Journal of the American College of Cardiology, the researchers evaluated blood samples from 760 women who were participants in the Nurses’ Health Study. The samples were collected at two time points: 1989-1990 and 2000-2002. The researchers identified 360 incident cases of CHD over the study period and compared them with matched controls.
Over roughly 10 years, increases in TMAO over time were significantly associated with increased CHD risk, with a relative risk of 1.58 for the top tertile and a relative risk of 1.33 per each standard deviation.
Women with elevated levels of TMAO both at baseline and at the 10-year point had the highest CHD risk (relative risk 1.79), compared with women with low TMAO levels at baseline and 10 years later.
The researchers also found an impact of diet on the TMAO-CHD relationship. Individuals with unhealthy eating patterns based on the Alternate Healthy Eating Index showed greater increases in TMAO and greater CHD risk. By contrast, greater adherence to healthy eating habits attenuated the impact of TMAO and CHD.
The study findings were limited by several factors, including the inability to assess the timing of the changes in the metabolites that contributed to CHD, the reliance on self-reports for dietary patterns and other variables, and the inclusion only of women health professionals in the study population, the researchers noted. However, the results were strengthened by the availability of long-term blood samples and a patient population free of disease at baseline.
In addition, “adherence to healthy dietary patterns may modulate the adverse relationship between TMAO changes and CHD, suggesting that TMAO as a potential intermediate endpoint of interventions focusing on dietary modifications for CHD prevention,” the researchers wrote.
“The findings of the study provide further evidence for the role of TMAO as a predictive biomarker for atherosclerotic heart disease and strengthen the case for TMAO as a potential intervention target in CV [cardiovascular] disease prevention,” wrote Paul A. Heidenreich, MD, and Petra Mamic, MD, of Stanford (Calif.) University, in an accompanying editorial.
In addition, “It is increasingly clear that GMB [gut microbiota] metabolites have biological activity, and that dietary changes alter the GMB and its metabolic output, with subsequent modulation of downstream host effects,” they wrote.
“While acknowledging the limitations of self-reported dietary pattern assessment, this is an important finding because it suggests that healthy dietary patterns may in some ways neutralize TMAO’s harmful effects on the CV system, potentially through other identified and unidentified GMB-mediated pathways,” they added.
The study was sponsored in part by the National Institutes of Health, the Boston Obesity Nutrition Research Center, and the United States–Israel Binational Science Foundation. Neither the researchers nor the editorialists had any financial conflicts to disclose.
SOURCES: Heianza Y et al. J Am Coll Cardiol. 2020 Feb 17. doi: 0.1016/j.jacc.2019.11.060; Heidenreich PA, Mamic P. J Am Coll Cardiol. 2020 Feb 17. doi: 10.1016/j.jacc.2019.12.023.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Acne treatment may vary based on race, gender, insurance
based on findings from a retrospective, cohort study of 29,928 individuals with acne.
“Our findings suggest the presence of racial/ethnic, sex, and insurance-based disparities in health care use and treatment for acne and raise particular concern for undertreatment among racial/ethnic minority and female patients,” John S. Barbieri, MD, a dermatology research fellow at the University of Pennsylvania, Philadelphia, and colleagues wrote in a study published in JAMA Dermatology.
Data from previous studies have suggested racial disparities in the management of several dermatologic conditions, including atopic dermatitis and psoriasis, but associations between social demographics and prescribing patterns have not been well studied for acne treatment, the authors noted.
For the current study, the researchers used deidentified data from the Optum electronic health record from Jan. 1, 2007 to June 30, 2017. In all, 29,928 patients aged 15-35 years and who were being treated for acne were included in the study. Of that total, 64% were women, 8% were non-Hispanic black and 68% were white, with the remaining patients grouped as non-Hispanic Asian, Hispanic, or other.
Non-Hispanic black patients were significantly more likely to be seen by a dermatologist, compared with non-Hispanic white patients, who were designated as the reference (odds ratio, 1.20). However, the black patients were less likely to receive prescriptions for any acne medication (incidence rate ratio, 0.89).
Non-Hispanic black patients were more likely than non-Hispanic white patients to be prescribed topical retinoids or topical antibiotics (OR, 1.25 and 1.35, respectively). They were also were less likely than their white counterparts to be prescribed oral antibiotics, spironolactone, and isotretinoin (OR, 0.80, 0.68, and 0.39, respectively).
Overall, men were more than twice as likely as women to receive prescriptions for isotretinoin (OR, 2.44). They were also more likely to receive prescriptions for the other treatments, but the differences were not as high as those for isotretinoin.
In addition, patients with Medicaid insurance were significantly less likely than those with commercial insurance (the reference) to see a dermatologist (OR, 0.46). Medicaid patients also were less likely to be prescribed topical retinoids, oral antibiotics, spironolactone, or isotretinoin (OR, 0.82, 0.87, 0.50, and 0.43, respectively).
The study findings were limited by several factors, among them, the use of automated pharmacy data without confirmation that patients had picked up the medications they had been prescribed, the researchers said. The study also lacked data on acne severity, clinical outcomes, and the use of over-the-counter acne treatments.
“Further study is needed to confirm our findings, provide understanding of the reasons for these potential disparities, and develop strategies to ensure equitable care for patients with acne,” the researchers concluded.
The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, and by a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Barbieri had no financial conflicts to disclose. One of the study coauthors disclosed relationships with Pfizer, Eli Lilly, and Novartis.
SOURCE: Barbieri JS et al. JAMA Dermatol. 2020 Feb 5. doi: 10.1001/jamadermatol.2019.4818.
based on findings from a retrospective, cohort study of 29,928 individuals with acne.
“Our findings suggest the presence of racial/ethnic, sex, and insurance-based disparities in health care use and treatment for acne and raise particular concern for undertreatment among racial/ethnic minority and female patients,” John S. Barbieri, MD, a dermatology research fellow at the University of Pennsylvania, Philadelphia, and colleagues wrote in a study published in JAMA Dermatology.
Data from previous studies have suggested racial disparities in the management of several dermatologic conditions, including atopic dermatitis and psoriasis, but associations between social demographics and prescribing patterns have not been well studied for acne treatment, the authors noted.
For the current study, the researchers used deidentified data from the Optum electronic health record from Jan. 1, 2007 to June 30, 2017. In all, 29,928 patients aged 15-35 years and who were being treated for acne were included in the study. Of that total, 64% were women, 8% were non-Hispanic black and 68% were white, with the remaining patients grouped as non-Hispanic Asian, Hispanic, or other.
Non-Hispanic black patients were significantly more likely to be seen by a dermatologist, compared with non-Hispanic white patients, who were designated as the reference (odds ratio, 1.20). However, the black patients were less likely to receive prescriptions for any acne medication (incidence rate ratio, 0.89).
Non-Hispanic black patients were more likely than non-Hispanic white patients to be prescribed topical retinoids or topical antibiotics (OR, 1.25 and 1.35, respectively). They were also were less likely than their white counterparts to be prescribed oral antibiotics, spironolactone, and isotretinoin (OR, 0.80, 0.68, and 0.39, respectively).
Overall, men were more than twice as likely as women to receive prescriptions for isotretinoin (OR, 2.44). They were also more likely to receive prescriptions for the other treatments, but the differences were not as high as those for isotretinoin.
In addition, patients with Medicaid insurance were significantly less likely than those with commercial insurance (the reference) to see a dermatologist (OR, 0.46). Medicaid patients also were less likely to be prescribed topical retinoids, oral antibiotics, spironolactone, or isotretinoin (OR, 0.82, 0.87, 0.50, and 0.43, respectively).
The study findings were limited by several factors, among them, the use of automated pharmacy data without confirmation that patients had picked up the medications they had been prescribed, the researchers said. The study also lacked data on acne severity, clinical outcomes, and the use of over-the-counter acne treatments.
“Further study is needed to confirm our findings, provide understanding of the reasons for these potential disparities, and develop strategies to ensure equitable care for patients with acne,” the researchers concluded.
The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, and by a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Barbieri had no financial conflicts to disclose. One of the study coauthors disclosed relationships with Pfizer, Eli Lilly, and Novartis.
SOURCE: Barbieri JS et al. JAMA Dermatol. 2020 Feb 5. doi: 10.1001/jamadermatol.2019.4818.
based on findings from a retrospective, cohort study of 29,928 individuals with acne.
“Our findings suggest the presence of racial/ethnic, sex, and insurance-based disparities in health care use and treatment for acne and raise particular concern for undertreatment among racial/ethnic minority and female patients,” John S. Barbieri, MD, a dermatology research fellow at the University of Pennsylvania, Philadelphia, and colleagues wrote in a study published in JAMA Dermatology.
Data from previous studies have suggested racial disparities in the management of several dermatologic conditions, including atopic dermatitis and psoriasis, but associations between social demographics and prescribing patterns have not been well studied for acne treatment, the authors noted.
For the current study, the researchers used deidentified data from the Optum electronic health record from Jan. 1, 2007 to June 30, 2017. In all, 29,928 patients aged 15-35 years and who were being treated for acne were included in the study. Of that total, 64% were women, 8% were non-Hispanic black and 68% were white, with the remaining patients grouped as non-Hispanic Asian, Hispanic, or other.
Non-Hispanic black patients were significantly more likely to be seen by a dermatologist, compared with non-Hispanic white patients, who were designated as the reference (odds ratio, 1.20). However, the black patients were less likely to receive prescriptions for any acne medication (incidence rate ratio, 0.89).
Non-Hispanic black patients were more likely than non-Hispanic white patients to be prescribed topical retinoids or topical antibiotics (OR, 1.25 and 1.35, respectively). They were also were less likely than their white counterparts to be prescribed oral antibiotics, spironolactone, and isotretinoin (OR, 0.80, 0.68, and 0.39, respectively).
Overall, men were more than twice as likely as women to receive prescriptions for isotretinoin (OR, 2.44). They were also more likely to receive prescriptions for the other treatments, but the differences were not as high as those for isotretinoin.
In addition, patients with Medicaid insurance were significantly less likely than those with commercial insurance (the reference) to see a dermatologist (OR, 0.46). Medicaid patients also were less likely to be prescribed topical retinoids, oral antibiotics, spironolactone, or isotretinoin (OR, 0.82, 0.87, 0.50, and 0.43, respectively).
The study findings were limited by several factors, among them, the use of automated pharmacy data without confirmation that patients had picked up the medications they had been prescribed, the researchers said. The study also lacked data on acne severity, clinical outcomes, and the use of over-the-counter acne treatments.
“Further study is needed to confirm our findings, provide understanding of the reasons for these potential disparities, and develop strategies to ensure equitable care for patients with acne,” the researchers concluded.
The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, and by a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Barbieri had no financial conflicts to disclose. One of the study coauthors disclosed relationships with Pfizer, Eli Lilly, and Novartis.
SOURCE: Barbieri JS et al. JAMA Dermatol. 2020 Feb 5. doi: 10.1001/jamadermatol.2019.4818.
FROM JAMA DERMATOLOGY