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Can this patient get IV contrast?

Article Type
Changed
Mon, 03/02/2020 - 21:52

A 59-year-old man is admitted with abdominal pain. He has a history of pancreatitis. A contrast CT scan is ordered. He reports a history of severe shellfish allergy when the radiology tech checks him in for the procedure. You are paged regarding what to do:

A) Continue with scan as ordered.

B) Switch to MRI scan.

C) Switch to MRI scan with gadolinium.

D) Continue with CT with contrast, give dose of Solu-Medrol.

E) Continue with CT with contrast give IV diphenhydramine.
 

The correct answer here is A, This patient can receive his scan and receive contrast as ordered.

For many years, patients have been asked about shellfish allergy as a proxy for having increased risk when receiving iodine containing contrast. The mistaken thought was that shellfish contains iodine, so allergy to shellfish was likely to portend allergy to iodine.

Dr. Douglas S. Paauw

Allergy to shellfish is caused by individual proteins that are definitely not in iodine-containing contrast.1 Beaty et al. studied the prevalence of the belief that allergy to shellfish is tied to iodine allergy in a survey given to 231 faculty radiologists and interventional cardiologists.2 Almost 70% responded that they inquire about seafood allergy before procedures that require iodine contrast, and 37% reported they would withhold the contrast or premedicate patients if they had a seafood allergy.

In a more recent study, Westermann-Clark and colleagues surveyed 252 health professionals before and after an educational intervention to dispel the myth of shellfish allergy and iodinated contrast reactions.3 Before the intervention, 66% of participants felt it was important to ask about shellfish allergies and 93% felt it was important to ask about iodine allergies; 26% responded that they would withhold iodinated contrast material in patients with a shellfish allergy, and 56% would withhold in patients with an iodine allergy. A total of 62% reported they would premedicate patients with a shellfish allergy and 75% would premedicate patients with an iodine allergy. The numbers declined dramatically after the educational intervention.

Patients who have seafood allergy have a higher rate of reactions to iodinated contrast, but not at a higher rate than do patients with other food allergies or asthma.4 Most radiology departments do not screen for other food allergies despite the fact these allergies have the same increased risk as for patients with a seafood/shellfish allergy. These patients are more allergic, and in general, are more likely to have reactions. The American Academy of Allergy, Asthma, and Immunology recommends not routinely ordering low- or iso-osmolar radiocontrast media or pretreating with either antihistamines or steroids in patients with a history of seafood allergy.5



There is no evidence that iodine causes allergic reactions. It makes sense that iodine does not cause allergic reactions, as it is an essential component in the human body, in thyroid hormone and in amino acids.6 Patients with dermatitis following topical application of iodine preparations such as povidone-iodide are not reacting to the iodine.

Van Ketel and van den Berg patch-tested patients with a history of dermatitis after exposure to povidone-iodine.7 All patients reacted to patch testing with povidone-iodine, but none reacted to direct testing to iodine (0/5 with patch testing of potassium iodide and 0/3 with testing with iodine tincture).


Take home points:

  • It is unnecessary and unhelpful to ask patients about seafood allergies before ordering radiologic studies involving contrast.
  • Iodine allergy does not exist.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Narayan AK et al. Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. J Hosp Med. 2016 Jun;11(6):435-7.

2. Beaty AD et al. Seafood allergy and radiocontrast media: Are physicians propagating a myth? Am J Med. 2008 Feb;121(2):158.e1-4.

3. Westermann-Clark E et al. Debunking myths about “allergy” to radiocontrast media in an academic institution. Postgrad Med. 2015 Apr;127(3):295-300.

4. Coakley FV and DM Panicek. Iodine allergy: An oyster without a pearl? AJR Am J Roentgenol. 1997 Oct;169(4):951-2.

5. American Academy of Allergy, Asthma & Immunology recommendations on low- or iso-osmolar radiocontrast media.

6. Schabelman E and M Witting. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-7.

7. van Ketel WG and WH van den Berg. Sensitization to povidone-iodine. Dermatol Clin. 1990 Jan;8(1):107-9.

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A 59-year-old man is admitted with abdominal pain. He has a history of pancreatitis. A contrast CT scan is ordered. He reports a history of severe shellfish allergy when the radiology tech checks him in for the procedure. You are paged regarding what to do:

A) Continue with scan as ordered.

B) Switch to MRI scan.

C) Switch to MRI scan with gadolinium.

D) Continue with CT with contrast, give dose of Solu-Medrol.

E) Continue with CT with contrast give IV diphenhydramine.
 

The correct answer here is A, This patient can receive his scan and receive contrast as ordered.

For many years, patients have been asked about shellfish allergy as a proxy for having increased risk when receiving iodine containing contrast. The mistaken thought was that shellfish contains iodine, so allergy to shellfish was likely to portend allergy to iodine.

Dr. Douglas S. Paauw

Allergy to shellfish is caused by individual proteins that are definitely not in iodine-containing contrast.1 Beaty et al. studied the prevalence of the belief that allergy to shellfish is tied to iodine allergy in a survey given to 231 faculty radiologists and interventional cardiologists.2 Almost 70% responded that they inquire about seafood allergy before procedures that require iodine contrast, and 37% reported they would withhold the contrast or premedicate patients if they had a seafood allergy.

In a more recent study, Westermann-Clark and colleagues surveyed 252 health professionals before and after an educational intervention to dispel the myth of shellfish allergy and iodinated contrast reactions.3 Before the intervention, 66% of participants felt it was important to ask about shellfish allergies and 93% felt it was important to ask about iodine allergies; 26% responded that they would withhold iodinated contrast material in patients with a shellfish allergy, and 56% would withhold in patients with an iodine allergy. A total of 62% reported they would premedicate patients with a shellfish allergy and 75% would premedicate patients with an iodine allergy. The numbers declined dramatically after the educational intervention.

Patients who have seafood allergy have a higher rate of reactions to iodinated contrast, but not at a higher rate than do patients with other food allergies or asthma.4 Most radiology departments do not screen for other food allergies despite the fact these allergies have the same increased risk as for patients with a seafood/shellfish allergy. These patients are more allergic, and in general, are more likely to have reactions. The American Academy of Allergy, Asthma, and Immunology recommends not routinely ordering low- or iso-osmolar radiocontrast media or pretreating with either antihistamines or steroids in patients with a history of seafood allergy.5



There is no evidence that iodine causes allergic reactions. It makes sense that iodine does not cause allergic reactions, as it is an essential component in the human body, in thyroid hormone and in amino acids.6 Patients with dermatitis following topical application of iodine preparations such as povidone-iodide are not reacting to the iodine.

Van Ketel and van den Berg patch-tested patients with a history of dermatitis after exposure to povidone-iodine.7 All patients reacted to patch testing with povidone-iodine, but none reacted to direct testing to iodine (0/5 with patch testing of potassium iodide and 0/3 with testing with iodine tincture).


Take home points:

  • It is unnecessary and unhelpful to ask patients about seafood allergies before ordering radiologic studies involving contrast.
  • Iodine allergy does not exist.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Narayan AK et al. Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. J Hosp Med. 2016 Jun;11(6):435-7.

2. Beaty AD et al. Seafood allergy and radiocontrast media: Are physicians propagating a myth? Am J Med. 2008 Feb;121(2):158.e1-4.

3. Westermann-Clark E et al. Debunking myths about “allergy” to radiocontrast media in an academic institution. Postgrad Med. 2015 Apr;127(3):295-300.

4. Coakley FV and DM Panicek. Iodine allergy: An oyster without a pearl? AJR Am J Roentgenol. 1997 Oct;169(4):951-2.

5. American Academy of Allergy, Asthma & Immunology recommendations on low- or iso-osmolar radiocontrast media.

6. Schabelman E and M Witting. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-7.

7. van Ketel WG and WH van den Berg. Sensitization to povidone-iodine. Dermatol Clin. 1990 Jan;8(1):107-9.

A 59-year-old man is admitted with abdominal pain. He has a history of pancreatitis. A contrast CT scan is ordered. He reports a history of severe shellfish allergy when the radiology tech checks him in for the procedure. You are paged regarding what to do:

A) Continue with scan as ordered.

B) Switch to MRI scan.

C) Switch to MRI scan with gadolinium.

D) Continue with CT with contrast, give dose of Solu-Medrol.

E) Continue with CT with contrast give IV diphenhydramine.
 

The correct answer here is A, This patient can receive his scan and receive contrast as ordered.

For many years, patients have been asked about shellfish allergy as a proxy for having increased risk when receiving iodine containing contrast. The mistaken thought was that shellfish contains iodine, so allergy to shellfish was likely to portend allergy to iodine.

Dr. Douglas S. Paauw

Allergy to shellfish is caused by individual proteins that are definitely not in iodine-containing contrast.1 Beaty et al. studied the prevalence of the belief that allergy to shellfish is tied to iodine allergy in a survey given to 231 faculty radiologists and interventional cardiologists.2 Almost 70% responded that they inquire about seafood allergy before procedures that require iodine contrast, and 37% reported they would withhold the contrast or premedicate patients if they had a seafood allergy.

In a more recent study, Westermann-Clark and colleagues surveyed 252 health professionals before and after an educational intervention to dispel the myth of shellfish allergy and iodinated contrast reactions.3 Before the intervention, 66% of participants felt it was important to ask about shellfish allergies and 93% felt it was important to ask about iodine allergies; 26% responded that they would withhold iodinated contrast material in patients with a shellfish allergy, and 56% would withhold in patients with an iodine allergy. A total of 62% reported they would premedicate patients with a shellfish allergy and 75% would premedicate patients with an iodine allergy. The numbers declined dramatically after the educational intervention.

Patients who have seafood allergy have a higher rate of reactions to iodinated contrast, but not at a higher rate than do patients with other food allergies or asthma.4 Most radiology departments do not screen for other food allergies despite the fact these allergies have the same increased risk as for patients with a seafood/shellfish allergy. These patients are more allergic, and in general, are more likely to have reactions. The American Academy of Allergy, Asthma, and Immunology recommends not routinely ordering low- or iso-osmolar radiocontrast media or pretreating with either antihistamines or steroids in patients with a history of seafood allergy.5



There is no evidence that iodine causes allergic reactions. It makes sense that iodine does not cause allergic reactions, as it is an essential component in the human body, in thyroid hormone and in amino acids.6 Patients with dermatitis following topical application of iodine preparations such as povidone-iodide are not reacting to the iodine.

Van Ketel and van den Berg patch-tested patients with a history of dermatitis after exposure to povidone-iodine.7 All patients reacted to patch testing with povidone-iodine, but none reacted to direct testing to iodine (0/5 with patch testing of potassium iodide and 0/3 with testing with iodine tincture).


Take home points:

  • It is unnecessary and unhelpful to ask patients about seafood allergies before ordering radiologic studies involving contrast.
  • Iodine allergy does not exist.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Narayan AK et al. Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. J Hosp Med. 2016 Jun;11(6):435-7.

2. Beaty AD et al. Seafood allergy and radiocontrast media: Are physicians propagating a myth? Am J Med. 2008 Feb;121(2):158.e1-4.

3. Westermann-Clark E et al. Debunking myths about “allergy” to radiocontrast media in an academic institution. Postgrad Med. 2015 Apr;127(3):295-300.

4. Coakley FV and DM Panicek. Iodine allergy: An oyster without a pearl? AJR Am J Roentgenol. 1997 Oct;169(4):951-2.

5. American Academy of Allergy, Asthma & Immunology recommendations on low- or iso-osmolar radiocontrast media.

6. Schabelman E and M Witting. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-7.

7. van Ketel WG and WH van den Berg. Sensitization to povidone-iodine. Dermatol Clin. 1990 Jan;8(1):107-9.

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No sedation fails to improve mortality in mechanically ventilated patients

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Changed
Tue, 03/03/2020 - 10:59

– For critically ill, mechanically ventilated patients, a strategy of no sedation resulted in a mortality rate that was not significantly different from a strategy of light sedation with interruption, according to results of a multicenter, randomized trial.

Dr. Palle Toft

The lack of sedation did significantly improve certain secondary endpoints, including a reduced number of thromboembolic events and preservation of physical function, according to Palle Toft, PhD, DMSc, of Odense (Denmark) University Hospital.

However, the 90-day mortality rate was 42.4% in the no-sedation group versus 37.0% in the sedation group in the NONSEDA study, which was intended to test the hypothesis that mortality would be lower in the no-sedation group.

That 5.4 percentage point difference between arms in NONSEDA was not statistically significant (P = .65) in results of the study, presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine and concurrently published in the New England Journal of Medicine.

Yet that mortality trend is in the “opposite direction” of an earlier, single-center trial by Dr. Toft and colleagues, noted Claude Guérin, MD, PhD, in a related editorial that also appeared in the journal. In that earlier study, the reported hospital mortality rates were 36% for no sedation and 47% for sedation with daily interruption.

“The results from this trial [NONSEDA] are important because they arouse concern about omitting sedation in mechanically ventilated patients and reinforce the need to monitor sedation clinically, with the aim of discontinuing it as early as possible or at least interrupting it daily,” Dr. Guérin wrote in his editorial.

That said, the earlier, single-center trial was not statistically powered to show between-group differences in mortality, Dr. Toft and coauthors wrote in their journal article.

In his presentation, Dr. Toft emphasized that light sedation with a wake-up trial was “comparable” with no sedation with regard to mortality.

“I think my main message is that we have to individualize patient treatment,” Dr. Toft told attendees at a late-breaking literature session. “Many patients would benefit from nonsedation, and some would benefit by light sedation with a daily wake-up trial. We have to respect patient autonomy, and try to establish a two-way communication with patients in 2020.”

Sandra L. Kane-Gill, PharmD, treasurer of SCCM and assistant professor of pharmacy and therapeutics at the University of Pittsburgh, said that current SCCM guidelines recommend using light sedation in critically ill, mechanically ventilated adults.

“I think we should stay consistent with what the guidelines are saying,” Dr. Kane-Gill said in an interview. “How you do that may vary, but targeting light sedation is consistent with what the evidence is suggesting in those guidelines.”

The depth of sedation between the no-sedation group in the light sedation group in the present study was not as great as the investigators had anticipated, which may explain the lack of statistically significant difference in mortality, according to Dr. Kane-Gill.

According to the report, 38.4% of patients in the no-sedation group received medication for sedation during their ICU stay, while Richmond Agitation and Sedation Scores increased in both groups, indicating a more alert state in both groups.

The multicenter NONSEDA trial included 700 mechanically ventilated ICU patients randomized either to no sedation or to light sedation, such that the patient was arousable, with daily interruption.

Previous studies have shown that daily interruption of sedation reduced mechanical ventilation duration, ICU stay length, and mortality in comparison with no interruption, the investigators noted.

While mortality at 90 days did not differ significantly between the no-sedation and light-sedation approaches, no sedation reduced thromboembolic events, Dr. Toft said at the meeting. The number of thrombolic events within 90 days was 10 (5%) in the sedation group and 1 (0.5%) in the no-sedation group (P less than .05), according to the reported data.

Likewise, several measures of physical function significantly improved in an a prior defined subgroup of 200 patients, he said. Those measures included hand grip at extubation and ICU discharge, as well as scores on the Barthel Index for Activities of Daily Living.

Nonsedation might improve kidney function, based on other reported outcomes of the study, Dr. Toft said. The number of coma- and delirium-free days was 3.0 in the no-sedation group versus 1.0 in the sedation group (P less than .01), he added.

The benefits of no sedation may extend beyond objective changes in health outcomes, according to Dr. Toft. “The patients are able to communicate with the staff, they might be able to enjoy food, in the evening they can look at the television instead of being sedated – and they can be mobilized and they can write their opinion about the treatments to the doctor, and in this way, you have two-way communication,” he explained in his presentation.

Dr. Toft reported that he had no financial relationships to disclose.

SOURCE: Toft P et al. N Engl J Med. 2019 Feb 16. doi: 10.1056/NEJMoa1906759.

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– For critically ill, mechanically ventilated patients, a strategy of no sedation resulted in a mortality rate that was not significantly different from a strategy of light sedation with interruption, according to results of a multicenter, randomized trial.

Dr. Palle Toft

The lack of sedation did significantly improve certain secondary endpoints, including a reduced number of thromboembolic events and preservation of physical function, according to Palle Toft, PhD, DMSc, of Odense (Denmark) University Hospital.

However, the 90-day mortality rate was 42.4% in the no-sedation group versus 37.0% in the sedation group in the NONSEDA study, which was intended to test the hypothesis that mortality would be lower in the no-sedation group.

That 5.4 percentage point difference between arms in NONSEDA was not statistically significant (P = .65) in results of the study, presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine and concurrently published in the New England Journal of Medicine.

Yet that mortality trend is in the “opposite direction” of an earlier, single-center trial by Dr. Toft and colleagues, noted Claude Guérin, MD, PhD, in a related editorial that also appeared in the journal. In that earlier study, the reported hospital mortality rates were 36% for no sedation and 47% for sedation with daily interruption.

“The results from this trial [NONSEDA] are important because they arouse concern about omitting sedation in mechanically ventilated patients and reinforce the need to monitor sedation clinically, with the aim of discontinuing it as early as possible or at least interrupting it daily,” Dr. Guérin wrote in his editorial.

That said, the earlier, single-center trial was not statistically powered to show between-group differences in mortality, Dr. Toft and coauthors wrote in their journal article.

In his presentation, Dr. Toft emphasized that light sedation with a wake-up trial was “comparable” with no sedation with regard to mortality.

“I think my main message is that we have to individualize patient treatment,” Dr. Toft told attendees at a late-breaking literature session. “Many patients would benefit from nonsedation, and some would benefit by light sedation with a daily wake-up trial. We have to respect patient autonomy, and try to establish a two-way communication with patients in 2020.”

Sandra L. Kane-Gill, PharmD, treasurer of SCCM and assistant professor of pharmacy and therapeutics at the University of Pittsburgh, said that current SCCM guidelines recommend using light sedation in critically ill, mechanically ventilated adults.

“I think we should stay consistent with what the guidelines are saying,” Dr. Kane-Gill said in an interview. “How you do that may vary, but targeting light sedation is consistent with what the evidence is suggesting in those guidelines.”

The depth of sedation between the no-sedation group in the light sedation group in the present study was not as great as the investigators had anticipated, which may explain the lack of statistically significant difference in mortality, according to Dr. Kane-Gill.

According to the report, 38.4% of patients in the no-sedation group received medication for sedation during their ICU stay, while Richmond Agitation and Sedation Scores increased in both groups, indicating a more alert state in both groups.

The multicenter NONSEDA trial included 700 mechanically ventilated ICU patients randomized either to no sedation or to light sedation, such that the patient was arousable, with daily interruption.

Previous studies have shown that daily interruption of sedation reduced mechanical ventilation duration, ICU stay length, and mortality in comparison with no interruption, the investigators noted.

While mortality at 90 days did not differ significantly between the no-sedation and light-sedation approaches, no sedation reduced thromboembolic events, Dr. Toft said at the meeting. The number of thrombolic events within 90 days was 10 (5%) in the sedation group and 1 (0.5%) in the no-sedation group (P less than .05), according to the reported data.

Likewise, several measures of physical function significantly improved in an a prior defined subgroup of 200 patients, he said. Those measures included hand grip at extubation and ICU discharge, as well as scores on the Barthel Index for Activities of Daily Living.

Nonsedation might improve kidney function, based on other reported outcomes of the study, Dr. Toft said. The number of coma- and delirium-free days was 3.0 in the no-sedation group versus 1.0 in the sedation group (P less than .01), he added.

The benefits of no sedation may extend beyond objective changes in health outcomes, according to Dr. Toft. “The patients are able to communicate with the staff, they might be able to enjoy food, in the evening they can look at the television instead of being sedated – and they can be mobilized and they can write their opinion about the treatments to the doctor, and in this way, you have two-way communication,” he explained in his presentation.

Dr. Toft reported that he had no financial relationships to disclose.

SOURCE: Toft P et al. N Engl J Med. 2019 Feb 16. doi: 10.1056/NEJMoa1906759.

– For critically ill, mechanically ventilated patients, a strategy of no sedation resulted in a mortality rate that was not significantly different from a strategy of light sedation with interruption, according to results of a multicenter, randomized trial.

Dr. Palle Toft

The lack of sedation did significantly improve certain secondary endpoints, including a reduced number of thromboembolic events and preservation of physical function, according to Palle Toft, PhD, DMSc, of Odense (Denmark) University Hospital.

However, the 90-day mortality rate was 42.4% in the no-sedation group versus 37.0% in the sedation group in the NONSEDA study, which was intended to test the hypothesis that mortality would be lower in the no-sedation group.

That 5.4 percentage point difference between arms in NONSEDA was not statistically significant (P = .65) in results of the study, presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine and concurrently published in the New England Journal of Medicine.

Yet that mortality trend is in the “opposite direction” of an earlier, single-center trial by Dr. Toft and colleagues, noted Claude Guérin, MD, PhD, in a related editorial that also appeared in the journal. In that earlier study, the reported hospital mortality rates were 36% for no sedation and 47% for sedation with daily interruption.

“The results from this trial [NONSEDA] are important because they arouse concern about omitting sedation in mechanically ventilated patients and reinforce the need to monitor sedation clinically, with the aim of discontinuing it as early as possible or at least interrupting it daily,” Dr. Guérin wrote in his editorial.

That said, the earlier, single-center trial was not statistically powered to show between-group differences in mortality, Dr. Toft and coauthors wrote in their journal article.

In his presentation, Dr. Toft emphasized that light sedation with a wake-up trial was “comparable” with no sedation with regard to mortality.

“I think my main message is that we have to individualize patient treatment,” Dr. Toft told attendees at a late-breaking literature session. “Many patients would benefit from nonsedation, and some would benefit by light sedation with a daily wake-up trial. We have to respect patient autonomy, and try to establish a two-way communication with patients in 2020.”

Sandra L. Kane-Gill, PharmD, treasurer of SCCM and assistant professor of pharmacy and therapeutics at the University of Pittsburgh, said that current SCCM guidelines recommend using light sedation in critically ill, mechanically ventilated adults.

“I think we should stay consistent with what the guidelines are saying,” Dr. Kane-Gill said in an interview. “How you do that may vary, but targeting light sedation is consistent with what the evidence is suggesting in those guidelines.”

The depth of sedation between the no-sedation group in the light sedation group in the present study was not as great as the investigators had anticipated, which may explain the lack of statistically significant difference in mortality, according to Dr. Kane-Gill.

According to the report, 38.4% of patients in the no-sedation group received medication for sedation during their ICU stay, while Richmond Agitation and Sedation Scores increased in both groups, indicating a more alert state in both groups.

The multicenter NONSEDA trial included 700 mechanically ventilated ICU patients randomized either to no sedation or to light sedation, such that the patient was arousable, with daily interruption.

Previous studies have shown that daily interruption of sedation reduced mechanical ventilation duration, ICU stay length, and mortality in comparison with no interruption, the investigators noted.

While mortality at 90 days did not differ significantly between the no-sedation and light-sedation approaches, no sedation reduced thromboembolic events, Dr. Toft said at the meeting. The number of thrombolic events within 90 days was 10 (5%) in the sedation group and 1 (0.5%) in the no-sedation group (P less than .05), according to the reported data.

Likewise, several measures of physical function significantly improved in an a prior defined subgroup of 200 patients, he said. Those measures included hand grip at extubation and ICU discharge, as well as scores on the Barthel Index for Activities of Daily Living.

Nonsedation might improve kidney function, based on other reported outcomes of the study, Dr. Toft said. The number of coma- and delirium-free days was 3.0 in the no-sedation group versus 1.0 in the sedation group (P less than .01), he added.

The benefits of no sedation may extend beyond objective changes in health outcomes, according to Dr. Toft. “The patients are able to communicate with the staff, they might be able to enjoy food, in the evening they can look at the television instead of being sedated – and they can be mobilized and they can write their opinion about the treatments to the doctor, and in this way, you have two-way communication,” he explained in his presentation.

Dr. Toft reported that he had no financial relationships to disclose.

SOURCE: Toft P et al. N Engl J Med. 2019 Feb 16. doi: 10.1056/NEJMoa1906759.

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Antibiotic resistance rises among pneumococcus strains in kids

What are the implications for treatment
Article Type
Changed
Wed, 03/04/2020 - 11:14

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.

 

 

Body

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. 

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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. 

Body

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. 

Title
What are the implications for treatment
What are the implications for treatment

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.

 

 

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U.S. reports first death from COVID-19, possible outbreak at long-term care facility

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The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov
(From left) NIAID Director Dr. Anthony S. Fauci, President Donald Trump, Vice President Mike Pence, and CDC Director Dr. Robert R. Redfield at a press conference Feb. 29, 2020, on COVID-19.

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

 

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

 

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The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov
(From left) NIAID Director Dr. Anthony S. Fauci, President Donald Trump, Vice President Mike Pence, and CDC Director Dr. Robert R. Redfield at a press conference Feb. 29, 2020, on COVID-19.

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

 

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

 

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov
(From left) NIAID Director Dr. Anthony S. Fauci, President Donald Trump, Vice President Mike Pence, and CDC Director Dr. Robert R. Redfield at a press conference Feb. 29, 2020, on COVID-19.

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

 

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

 

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CDC revises COVID-19 test kits, broadens ‘person under investigation’ definition

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Mon, 03/02/2020 - 14:18

In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention announced that the agency has updated the definition of “Person Under Investigation,” or PUI, for the disease.

The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.

Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”

The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”

The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.

Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.

Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.

These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.

As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.

While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.

She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.

[email protected]

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In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention announced that the agency has updated the definition of “Person Under Investigation,” or PUI, for the disease.

The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.

Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”

The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”

The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.

Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.

Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.

These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.

As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.

While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.

She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.

[email protected]

In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention announced that the agency has updated the definition of “Person Under Investigation,” or PUI, for the disease.

The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.

Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”

The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”

The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.

Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.

Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.

These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.

As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.

While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.

She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.

[email protected]

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REPORTING FROM A CDC BRIEFING

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Children bearing the brunt of declining flu activity

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Tue, 06/16/2020 - 14:42

National flu activity decreased for the second consecutive week, but pediatric mortality is heading in the opposite direction, according to the Centers for Disease Control and Prevention.

MDedge News

Influenza-like illness (ILI) represented 5.5% of all visits to outpatient health care providers during the week ending Feb. 22, compared with 6.1% the previous week, the CDC’s influenza division reported Feb. 28. The ILI visit rate had reached 6.6% in early February after dropping to 5.0% in mid-January, following a rise to a season-high 7.1% in the last week of December.

Another measure of ILI activity, the percentage of laboratory specimens testing positive, also declined for the second week in a row. The rate was 26.4% for the week ending Feb. 22, which is down from the season high of 30.3% reached 2 weeks before, the influenza division said.



ILI-related deaths among children, however, are not dropping. There were 20 pediatric deaths reported during the week, more than any other single week this season. The total for 2019-2020 is now up to 125, and that “number is higher for the same time period than in every season since reporting began in 2004-05, except for the 2009 pandemic,” the CDC noted.

Hospitalization rates, which have been fairly typical in the general population, also are elevated for young adults and school-aged children, the agency said, and “rates among children 0-4 years old are now the highest CDC has on record at this point in the season, surpassing rates reported during the second wave of the 2009 H1N1 pandemic.”

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National flu activity decreased for the second consecutive week, but pediatric mortality is heading in the opposite direction, according to the Centers for Disease Control and Prevention.

MDedge News

Influenza-like illness (ILI) represented 5.5% of all visits to outpatient health care providers during the week ending Feb. 22, compared with 6.1% the previous week, the CDC’s influenza division reported Feb. 28. The ILI visit rate had reached 6.6% in early February after dropping to 5.0% in mid-January, following a rise to a season-high 7.1% in the last week of December.

Another measure of ILI activity, the percentage of laboratory specimens testing positive, also declined for the second week in a row. The rate was 26.4% for the week ending Feb. 22, which is down from the season high of 30.3% reached 2 weeks before, the influenza division said.



ILI-related deaths among children, however, are not dropping. There were 20 pediatric deaths reported during the week, more than any other single week this season. The total for 2019-2020 is now up to 125, and that “number is higher for the same time period than in every season since reporting began in 2004-05, except for the 2009 pandemic,” the CDC noted.

Hospitalization rates, which have been fairly typical in the general population, also are elevated for young adults and school-aged children, the agency said, and “rates among children 0-4 years old are now the highest CDC has on record at this point in the season, surpassing rates reported during the second wave of the 2009 H1N1 pandemic.”

National flu activity decreased for the second consecutive week, but pediatric mortality is heading in the opposite direction, according to the Centers for Disease Control and Prevention.

MDedge News

Influenza-like illness (ILI) represented 5.5% of all visits to outpatient health care providers during the week ending Feb. 22, compared with 6.1% the previous week, the CDC’s influenza division reported Feb. 28. The ILI visit rate had reached 6.6% in early February after dropping to 5.0% in mid-January, following a rise to a season-high 7.1% in the last week of December.

Another measure of ILI activity, the percentage of laboratory specimens testing positive, also declined for the second week in a row. The rate was 26.4% for the week ending Feb. 22, which is down from the season high of 30.3% reached 2 weeks before, the influenza division said.



ILI-related deaths among children, however, are not dropping. There were 20 pediatric deaths reported during the week, more than any other single week this season. The total for 2019-2020 is now up to 125, and that “number is higher for the same time period than in every season since reporting began in 2004-05, except for the 2009 pandemic,” the CDC noted.

Hospitalization rates, which have been fairly typical in the general population, also are elevated for young adults and school-aged children, the agency said, and “rates among children 0-4 years old are now the highest CDC has on record at this point in the season, surpassing rates reported during the second wave of the 2009 H1N1 pandemic.”

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Pembrolizumab plus chemoradiotherapy shows early promise in NSCLC

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Thu, 02/27/2020 - 13:52

Combination pembrolizumab and chemoradiotherapy appears safe and active for patients with locally advanced non–small cell lung cancer (NSCLC), results from a phase 1 trial suggest.

Nearly 90% of evaluable patients responded to the combination, and the 12-month progression-free survival rate was 69.7%. Pneumonitis was common, but most patients responded to high-dose corticosteroids.

Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, in New Brunswick, and colleagues reported these results in JAMA Oncology.

The phase 1 study included 21 patients with locally advanced, unresectable, stage III NSCLC. Planned treatment consisted of pembrolizumab (Keytruda) at various dosing schedules, chemotherapy (weekly carboplatin and paclitaxel), and radiation (2 Gy/day, 60 Gy total).

The researchers used a standard 3 + 3 design to evaluate the safety and tolerability of pembrolizumab in five dosing cohorts.

In cohort 1, patients received pembrolizumab at 200 mg every 21 days within 2-6 weeks of completing chemoradiotherapy. In cohort 2, patients received pembrolizumab at 100 mg every 21 days, starting on day 29 of chemoradiotherapy. Cohort 3 received the 200 mg dose of pembrolizumab, starting on day 29.

Pembrolizumab was started on day 1 of chemoradiotherapy at the 100-mg dose in cohort 4 and at the 200-mg dose in cohort 5. An additional six-patient safety expansion cohort received the same treatment as cohort 5.

The median follow-up was 16 months. There was one dose-limiting toxicity – grade 5 pneumonitis, which occurred in the safety expansion cohort.

Grade 2 or higher immune-related toxicities were observed in 14 patients (67%), and grade 2 or higher pneumonitis occurred in 7 patients (33%).

“Although we observed an increased rate of pneumonitis, most patients had pneumonitis that responded to high-dose corticosteroid treatment,” the researchers noted.

There were 19 patients who received at least two cycles of pembrolizumab and were evaluable for response. The best response was complete response in 3 patients (16%), partial response in 14 patients (74%), and stable disease in 1 patient (5%).

The progression-free survival rate was 81.0% at 6 months and 69.7% at 12 months. The overall survival rate was 95.2% at 6 months and 85.2% at 12 months.

The researchers acknowledged that two key limitations of this study were the small sample size and short duration of follow-up.

“Pembrolizumab with concurrent chemoradiotherapy is tolerable for patients with locally advanced, unresectable NSCLC, although the risk of pneumonitis and long-term outcomes should be evaluated in additional studies,” commented Enriqueta Felip, MD, PhD, of Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in this study.

The study was funded by Merck. The authors and Dr. Felip disclosed relationships with Merck and other companies.

SOURCE: Jabbour SK et al. JAMA Oncol. 2020 Feb 20. doi: 10.1001/jamaoncol.2019.6731.

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Combination pembrolizumab and chemoradiotherapy appears safe and active for patients with locally advanced non–small cell lung cancer (NSCLC), results from a phase 1 trial suggest.

Nearly 90% of evaluable patients responded to the combination, and the 12-month progression-free survival rate was 69.7%. Pneumonitis was common, but most patients responded to high-dose corticosteroids.

Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, in New Brunswick, and colleagues reported these results in JAMA Oncology.

The phase 1 study included 21 patients with locally advanced, unresectable, stage III NSCLC. Planned treatment consisted of pembrolizumab (Keytruda) at various dosing schedules, chemotherapy (weekly carboplatin and paclitaxel), and radiation (2 Gy/day, 60 Gy total).

The researchers used a standard 3 + 3 design to evaluate the safety and tolerability of pembrolizumab in five dosing cohorts.

In cohort 1, patients received pembrolizumab at 200 mg every 21 days within 2-6 weeks of completing chemoradiotherapy. In cohort 2, patients received pembrolizumab at 100 mg every 21 days, starting on day 29 of chemoradiotherapy. Cohort 3 received the 200 mg dose of pembrolizumab, starting on day 29.

Pembrolizumab was started on day 1 of chemoradiotherapy at the 100-mg dose in cohort 4 and at the 200-mg dose in cohort 5. An additional six-patient safety expansion cohort received the same treatment as cohort 5.

The median follow-up was 16 months. There was one dose-limiting toxicity – grade 5 pneumonitis, which occurred in the safety expansion cohort.

Grade 2 or higher immune-related toxicities were observed in 14 patients (67%), and grade 2 or higher pneumonitis occurred in 7 patients (33%).

“Although we observed an increased rate of pneumonitis, most patients had pneumonitis that responded to high-dose corticosteroid treatment,” the researchers noted.

There were 19 patients who received at least two cycles of pembrolizumab and were evaluable for response. The best response was complete response in 3 patients (16%), partial response in 14 patients (74%), and stable disease in 1 patient (5%).

The progression-free survival rate was 81.0% at 6 months and 69.7% at 12 months. The overall survival rate was 95.2% at 6 months and 85.2% at 12 months.

The researchers acknowledged that two key limitations of this study were the small sample size and short duration of follow-up.

“Pembrolizumab with concurrent chemoradiotherapy is tolerable for patients with locally advanced, unresectable NSCLC, although the risk of pneumonitis and long-term outcomes should be evaluated in additional studies,” commented Enriqueta Felip, MD, PhD, of Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in this study.

The study was funded by Merck. The authors and Dr. Felip disclosed relationships with Merck and other companies.

SOURCE: Jabbour SK et al. JAMA Oncol. 2020 Feb 20. doi: 10.1001/jamaoncol.2019.6731.

Combination pembrolizumab and chemoradiotherapy appears safe and active for patients with locally advanced non–small cell lung cancer (NSCLC), results from a phase 1 trial suggest.

Nearly 90% of evaluable patients responded to the combination, and the 12-month progression-free survival rate was 69.7%. Pneumonitis was common, but most patients responded to high-dose corticosteroids.

Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, in New Brunswick, and colleagues reported these results in JAMA Oncology.

The phase 1 study included 21 patients with locally advanced, unresectable, stage III NSCLC. Planned treatment consisted of pembrolizumab (Keytruda) at various dosing schedules, chemotherapy (weekly carboplatin and paclitaxel), and radiation (2 Gy/day, 60 Gy total).

The researchers used a standard 3 + 3 design to evaluate the safety and tolerability of pembrolizumab in five dosing cohorts.

In cohort 1, patients received pembrolizumab at 200 mg every 21 days within 2-6 weeks of completing chemoradiotherapy. In cohort 2, patients received pembrolizumab at 100 mg every 21 days, starting on day 29 of chemoradiotherapy. Cohort 3 received the 200 mg dose of pembrolizumab, starting on day 29.

Pembrolizumab was started on day 1 of chemoradiotherapy at the 100-mg dose in cohort 4 and at the 200-mg dose in cohort 5. An additional six-patient safety expansion cohort received the same treatment as cohort 5.

The median follow-up was 16 months. There was one dose-limiting toxicity – grade 5 pneumonitis, which occurred in the safety expansion cohort.

Grade 2 or higher immune-related toxicities were observed in 14 patients (67%), and grade 2 or higher pneumonitis occurred in 7 patients (33%).

“Although we observed an increased rate of pneumonitis, most patients had pneumonitis that responded to high-dose corticosteroid treatment,” the researchers noted.

There were 19 patients who received at least two cycles of pembrolizumab and were evaluable for response. The best response was complete response in 3 patients (16%), partial response in 14 patients (74%), and stable disease in 1 patient (5%).

The progression-free survival rate was 81.0% at 6 months and 69.7% at 12 months. The overall survival rate was 95.2% at 6 months and 85.2% at 12 months.

The researchers acknowledged that two key limitations of this study were the small sample size and short duration of follow-up.

“Pembrolizumab with concurrent chemoradiotherapy is tolerable for patients with locally advanced, unresectable NSCLC, although the risk of pneumonitis and long-term outcomes should be evaluated in additional studies,” commented Enriqueta Felip, MD, PhD, of Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in this study.

The study was funded by Merck. The authors and Dr. Felip disclosed relationships with Merck and other companies.

SOURCE: Jabbour SK et al. JAMA Oncol. 2020 Feb 20. doi: 10.1001/jamaoncol.2019.6731.

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FROM JAMA ONCOLOGY

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ACIP: Flu vaccines for older adults show similar safety profiles

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Mon, 06/08/2020 - 16:30

The two currently available flu vaccines specifically for older adults showed similar safety profiles, based on data from 757 individuals.

copyright Wavebreakmedia/Thinkstock

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.

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The two currently available flu vaccines specifically for older adults showed similar safety profiles, based on data from 757 individuals.

copyright Wavebreakmedia/Thinkstock

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 two currently available flu vaccines specifically for older adults showed similar safety profiles, based on data from 757 individuals.

copyright Wavebreakmedia/Thinkstock

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.

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FROM AN ACIP MEETING

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Pence named COVID-19 point person as CDC reports possible community spread

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Tue, 03/17/2020 - 09:57

Vice President Mike Pence will be the White House point person quarterbacking the administration’s response to COVID-19, although President Donald Trump was quick to dismiss the notion that he is a so-called coronavirus “czar.”

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President Trump and Vice President Pence at a press conference on COVID-19

President Trump introduced Vice President Pence in this role during a Feb. 26 press conference. The same night, officials at the Centers for Disease Control and Prevention announced the first case of possible community spread of the novel coronavirus in the United States.

“I am going to be putting our vice president, Mike Pence, in charge, and Mike will be working with the professionals, the doctors, and everybody else that is working” on this, President Trump said.

“Mike is going to be in charge and Mike will report back to me, but he’s got a certain talent for this,” President Trump continued, noting that while Vice President Pence was governor of Indiana, his was the first state to have a patient affected by the 2014 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, so he has experience in a similar situation.

“I know full well the importance of presidential leadership, the importance of administration leadership, and the vital role of partnerships of state and local governments and health authorities in responding to the potential threat of dangerous infectious diseases,” Vice President Pence said.

He said that his role will be to continue to meet with the Coronavirus Task Force and bring to the president “the best options for action and to see to the safety and well being and health of the American people. I will also be continuing to reach out to governors [and] state and local officials.”

Vice President Pence said he will also be working with Congress to ensure that resources are available.

It was noted during the press conference that some members of Congress consider the $2.5 billion in emergency appropriations requested by the White House to be inadequate and that the legislative branch is working to provide more funding.

Vice President Pence’s new role does not change the command structure of the Coronavirus Task Force, which is currently led by Department of Health & Human Services Secretary Alex Azar.

Speaking at the press conference, Secretary Azar noted that he is still chairman of the task force. “Having the vice president gives me the biggest stick one can have in the government on this whole-of-government approach.”

He emphatically stated, “not in the least,” in response to a question about whether he felt he was being replaced. “When this was mentioned to me, I said I was delighted that I get to have the vice president helping in this way. Delighted.”

The announcement came as President Trump continued to downplay the threat of the coronavirus to U.S. citizens, going so far as to contradict CDC officials who have stated that it is a matter of when, not if, there will be community spread in the United States.

“I don’t think it’s inevitable,” President Trump said. “I think that there’s a chance that it could get worse. There’s a chance it could get fairly substantially worse, but nothing’s inevitable.”

Immediately after President Trump wrapped up his statement, however, the CDC formally announced the first case of possible community spread of the coronavirus. In a statement issued to the press, the agency announced the 15th confirmed case in the United States, a person in California “who reportedly did not have relevant travel history or exposure to another known patient” with the coronavirus.

“This case was detected through the U.S. public health system – picked up by astute clinicians,” CDC added, noting it will continue to provide updates on the evolving situation.

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Vice President Mike Pence will be the White House point person quarterbacking the administration’s response to COVID-19, although President Donald Trump was quick to dismiss the notion that he is a so-called coronavirus “czar.”

WhiteHouse.gov
President Trump and Vice President Pence at a press conference on COVID-19

President Trump introduced Vice President Pence in this role during a Feb. 26 press conference. The same night, officials at the Centers for Disease Control and Prevention announced the first case of possible community spread of the novel coronavirus in the United States.

“I am going to be putting our vice president, Mike Pence, in charge, and Mike will be working with the professionals, the doctors, and everybody else that is working” on this, President Trump said.

“Mike is going to be in charge and Mike will report back to me, but he’s got a certain talent for this,” President Trump continued, noting that while Vice President Pence was governor of Indiana, his was the first state to have a patient affected by the 2014 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, so he has experience in a similar situation.

“I know full well the importance of presidential leadership, the importance of administration leadership, and the vital role of partnerships of state and local governments and health authorities in responding to the potential threat of dangerous infectious diseases,” Vice President Pence said.

He said that his role will be to continue to meet with the Coronavirus Task Force and bring to the president “the best options for action and to see to the safety and well being and health of the American people. I will also be continuing to reach out to governors [and] state and local officials.”

Vice President Pence said he will also be working with Congress to ensure that resources are available.

It was noted during the press conference that some members of Congress consider the $2.5 billion in emergency appropriations requested by the White House to be inadequate and that the legislative branch is working to provide more funding.

Vice President Pence’s new role does not change the command structure of the Coronavirus Task Force, which is currently led by Department of Health & Human Services Secretary Alex Azar.

Speaking at the press conference, Secretary Azar noted that he is still chairman of the task force. “Having the vice president gives me the biggest stick one can have in the government on this whole-of-government approach.”

He emphatically stated, “not in the least,” in response to a question about whether he felt he was being replaced. “When this was mentioned to me, I said I was delighted that I get to have the vice president helping in this way. Delighted.”

The announcement came as President Trump continued to downplay the threat of the coronavirus to U.S. citizens, going so far as to contradict CDC officials who have stated that it is a matter of when, not if, there will be community spread in the United States.

“I don’t think it’s inevitable,” President Trump said. “I think that there’s a chance that it could get worse. There’s a chance it could get fairly substantially worse, but nothing’s inevitable.”

Immediately after President Trump wrapped up his statement, however, the CDC formally announced the first case of possible community spread of the coronavirus. In a statement issued to the press, the agency announced the 15th confirmed case in the United States, a person in California “who reportedly did not have relevant travel history or exposure to another known patient” with the coronavirus.

“This case was detected through the U.S. public health system – picked up by astute clinicians,” CDC added, noting it will continue to provide updates on the evolving situation.

[email protected]

Vice President Mike Pence will be the White House point person quarterbacking the administration’s response to COVID-19, although President Donald Trump was quick to dismiss the notion that he is a so-called coronavirus “czar.”

WhiteHouse.gov
President Trump and Vice President Pence at a press conference on COVID-19

President Trump introduced Vice President Pence in this role during a Feb. 26 press conference. The same night, officials at the Centers for Disease Control and Prevention announced the first case of possible community spread of the novel coronavirus in the United States.

“I am going to be putting our vice president, Mike Pence, in charge, and Mike will be working with the professionals, the doctors, and everybody else that is working” on this, President Trump said.

“Mike is going to be in charge and Mike will report back to me, but he’s got a certain talent for this,” President Trump continued, noting that while Vice President Pence was governor of Indiana, his was the first state to have a patient affected by the 2014 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, so he has experience in a similar situation.

“I know full well the importance of presidential leadership, the importance of administration leadership, and the vital role of partnerships of state and local governments and health authorities in responding to the potential threat of dangerous infectious diseases,” Vice President Pence said.

He said that his role will be to continue to meet with the Coronavirus Task Force and bring to the president “the best options for action and to see to the safety and well being and health of the American people. I will also be continuing to reach out to governors [and] state and local officials.”

Vice President Pence said he will also be working with Congress to ensure that resources are available.

It was noted during the press conference that some members of Congress consider the $2.5 billion in emergency appropriations requested by the White House to be inadequate and that the legislative branch is working to provide more funding.

Vice President Pence’s new role does not change the command structure of the Coronavirus Task Force, which is currently led by Department of Health & Human Services Secretary Alex Azar.

Speaking at the press conference, Secretary Azar noted that he is still chairman of the task force. “Having the vice president gives me the biggest stick one can have in the government on this whole-of-government approach.”

He emphatically stated, “not in the least,” in response to a question about whether he felt he was being replaced. “When this was mentioned to me, I said I was delighted that I get to have the vice president helping in this way. Delighted.”

The announcement came as President Trump continued to downplay the threat of the coronavirus to U.S. citizens, going so far as to contradict CDC officials who have stated that it is a matter of when, not if, there will be community spread in the United States.

“I don’t think it’s inevitable,” President Trump said. “I think that there’s a chance that it could get worse. There’s a chance it could get fairly substantially worse, but nothing’s inevitable.”

Immediately after President Trump wrapped up his statement, however, the CDC formally announced the first case of possible community spread of the coronavirus. In a statement issued to the press, the agency announced the 15th confirmed case in the United States, a person in California “who reportedly did not have relevant travel history or exposure to another known patient” with the coronavirus.

“This case was detected through the U.S. public health system – picked up by astute clinicians,” CDC added, noting it will continue to provide updates on the evolving situation.

[email protected]

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ACIP advocates pre-exposure Ebola vaccination for high-risk groups

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Thu, 02/27/2020 - 10:24

 

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.

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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.

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