Pulmonology

TOPLINE: 

There were few cases of SARS-CoV-2 infections among emergency department (ED) healthcare personnel and no substantial changes in the delivery of emergency medical care during the initial phase of the COVID-19 pandemic.

METHODOLOGY:

• This multicenter prospective cohort study of US ED healthcare personnel called Project COVERED was conducted from May to December 2020 to evaluate the following outcomes:
• The possibility of infected ED personnel reporting to work
• The burden of COVID-19 symptoms on an ED personnel’s work status
• The association between SARS-CoV-2 infection levels and ED staffing
• Project COVERED enrolled 1673 ED healthcare personnel with 29,825 person weeks of observational data from 25 geographically diverse EDs.
• The presence of any SARS-CoV-2 infection was determined using reverse transcription polymerase chain reaction or IgG antibody testing at baseline, week 2, week 4, and every four subsequent weeks through week 20.
• Investigators also collected weekly data on ED staffing and the incidence of SARS-CoV-2 infections in healthcare facilities.

TAKEAWAY:

• Despite the absence of widespread natural immunity or COVID-19 vaccine availability during the time of this study, only 4.5% of ED healthcare personnel tested positive for SARS-CoV-2 infections, with more than half (57.3%) not experiencing any symptoms.
• Most personnel (83%) who experienced symptoms associated with COVID-19 reported working at least one shift in the ED and nearly all of them continued to work until they received laboratory confirmation of their infection.
• The working time lost as a result of COVID-19 and related concerns was minimal, as 89 healthcare personnel reported 90 person weeks of missed work (0.3% of all weeks).
• During this study, physician-staffing levels ranged from 98.7% to 102.0% of normal staffing, with similar values noted for nursing and nonclinical staffs. Reduced staffing was rare, even during COVID-19 surges.

IN PRACTICE:

“Our findings suggest that the cumulative interaction between infected healthcare personnel and others resulted in a negligible risk of transmission on the scale of public health emergencies,” the authors wrote.

SOURCE:

This study was led by Kurt D. Weber, MD, Department of Emergency Medicine, Orlando Health, Orlando, Florida, and published online in Annals of Emergency Medicine.

LIMITATIONS:

Data regarding the Delta variant surges that occurred toward the end of December and the ED status after the advent of the COVID-19 vaccine were not recorded. There may also have been a selection bias risk in this study because the volunteer participants may have exhibited behaviors like social distancing and use of protective equipment, which may have decreased their risk for infections.

DISCLOSURES:

This study was funded by a cooperative agreement from the Centers for Disease Control and Prevention and the Institute for Clinical and Translational Science at the University of Iowa through a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

There were few cases of SARS-CoV-2 infections among emergency department (ED) healthcare personnel and no substantial changes in the delivery of emergency medical care during the initial phase of the COVID-19 pandemic.

METHODOLOGY:

• This multicenter prospective cohort study of US ED healthcare personnel called Project COVERED was conducted from May to December 2020 to evaluate the following outcomes:
• The possibility of infected ED personnel reporting to work
• The burden of COVID-19 symptoms on an ED personnel’s work status
• The association between SARS-CoV-2 infection levels and ED staffing
• Project COVERED enrolled 1673 ED healthcare personnel with 29,825 person weeks of observational data from 25 geographically diverse EDs.
• The presence of any SARS-CoV-2 infection was determined using reverse transcription polymerase chain reaction or IgG antibody testing at baseline, week 2, week 4, and every four subsequent weeks through week 20.
• Investigators also collected weekly data on ED staffing and the incidence of SARS-CoV-2 infections in healthcare facilities.

TAKEAWAY:

• Despite the absence of widespread natural immunity or COVID-19 vaccine availability during the time of this study, only 4.5% of ED healthcare personnel tested positive for SARS-CoV-2 infections, with more than half (57.3%) not experiencing any symptoms.
• Most personnel (83%) who experienced symptoms associated with COVID-19 reported working at least one shift in the ED and nearly all of them continued to work until they received laboratory confirmation of their infection.
• The working time lost as a result of COVID-19 and related concerns was minimal, as 89 healthcare personnel reported 90 person weeks of missed work (0.3% of all weeks).
• During this study, physician-staffing levels ranged from 98.7% to 102.0% of normal staffing, with similar values noted for nursing and nonclinical staffs. Reduced staffing was rare, even during COVID-19 surges.

IN PRACTICE:

“Our findings suggest that the cumulative interaction between infected healthcare personnel and others resulted in a negligible risk of transmission on the scale of public health emergencies,” the authors wrote.

SOURCE:

This study was led by Kurt D. Weber, MD, Department of Emergency Medicine, Orlando Health, Orlando, Florida, and published online in Annals of Emergency Medicine.

LIMITATIONS:

Data regarding the Delta variant surges that occurred toward the end of December and the ED status after the advent of the COVID-19 vaccine were not recorded. There may also have been a selection bias risk in this study because the volunteer participants may have exhibited behaviors like social distancing and use of protective equipment, which may have decreased their risk for infections.

DISCLOSURES:

This study was funded by a cooperative agreement from the Centers for Disease Control and Prevention and the Institute for Clinical and Translational Science at the University of Iowa through a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

There were few cases of SARS-CoV-2 infections among emergency department (ED) healthcare personnel and no substantial changes in the delivery of emergency medical care during the initial phase of the COVID-19 pandemic.

METHODOLOGY:

• This multicenter prospective cohort study of US ED healthcare personnel called Project COVERED was conducted from May to December 2020 to evaluate the following outcomes:
• The possibility of infected ED personnel reporting to work
• The burden of COVID-19 symptoms on an ED personnel’s work status
• The association between SARS-CoV-2 infection levels and ED staffing
• Project COVERED enrolled 1673 ED healthcare personnel with 29,825 person weeks of observational data from 25 geographically diverse EDs.
• The presence of any SARS-CoV-2 infection was determined using reverse transcription polymerase chain reaction or IgG antibody testing at baseline, week 2, week 4, and every four subsequent weeks through week 20.
• Investigators also collected weekly data on ED staffing and the incidence of SARS-CoV-2 infections in healthcare facilities.

TAKEAWAY:

• Despite the absence of widespread natural immunity or COVID-19 vaccine availability during the time of this study, only 4.5% of ED healthcare personnel tested positive for SARS-CoV-2 infections, with more than half (57.3%) not experiencing any symptoms.
• Most personnel (83%) who experienced symptoms associated with COVID-19 reported working at least one shift in the ED and nearly all of them continued to work until they received laboratory confirmation of their infection.
• The working time lost as a result of COVID-19 and related concerns was minimal, as 89 healthcare personnel reported 90 person weeks of missed work (0.3% of all weeks).
• During this study, physician-staffing levels ranged from 98.7% to 102.0% of normal staffing, with similar values noted for nursing and nonclinical staffs. Reduced staffing was rare, even during COVID-19 surges.

IN PRACTICE:

“Our findings suggest that the cumulative interaction between infected healthcare personnel and others resulted in a negligible risk of transmission on the scale of public health emergencies,” the authors wrote.

SOURCE:

This study was led by Kurt D. Weber, MD, Department of Emergency Medicine, Orlando Health, Orlando, Florida, and published online in Annals of Emergency Medicine.

LIMITATIONS:

Data regarding the Delta variant surges that occurred toward the end of December and the ED status after the advent of the COVID-19 vaccine were not recorded. There may also have been a selection bias risk in this study because the volunteer participants may have exhibited behaviors like social distancing and use of protective equipment, which may have decreased their risk for infections.

DISCLOSURES:

This study was funded by a cooperative agreement from the Centers for Disease Control and Prevention and the Institute for Clinical and Translational Science at the University of Iowa through a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

C-reactive protein (CRP) levels and eosinophil-to-platelet ratio (EPR) are significant independent predictors of adverse events in patients with chronic obstructive pulmonary disease (COPD) hospitalized with acute exacerbations.

METHODOLOGY:

• Known risk factors for COPD exacerbations do not fully explain the variation in susceptibility among patients; data on potential biomarkers as predictors of COPD exacerbations are limited.
• In a prospective, observational study at a single center, the researchers examined clinical and lab data including serum CRP levels, EPR, sarcopenia, lung function, nutrition, and frailty.
• The study population included 200 adults older than 40 years with COPD who were hospitalized for acute exacerbations; 50 experienced adverse events.

TAKEAWAY:

• Both elevated CRP and low EPR were significant predictors of adverse events in adjusted analysis in patients with COPD exacerbations (area under the curve, 0.71 and 0.76, respectively).
• In a multivariate analysis, EPR and CRP, as well as sarcopenia, were significantly associated with adverse events (adjusted odds ratios, 2.33, 2.09, and 1.97, respectively).
• COPD symptom scores, frailty, and malnutrition showed predictive value in bivariate but not multivariate analysis.

IN PRACTICE:

“Screening for these biomarkers [EPR and CRP] on admission could help identify high-risk patients who need more aggressive monitoring and treatment,” the researchers wrote in their discussion.

SOURCE:

The lead author on the study was Rohankumar Gandhi, MD, of Guru Gobind Singh Government Hospital, Jamnagar, India. The study was published online in Cureus.

LIMITATIONS:

The use of data from a single center, lack of information on nutritional interventions and counseling, and lack of data on outpatient outcomes limited the study findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

C-reactive protein (CRP) levels and eosinophil-to-platelet ratio (EPR) are significant independent predictors of adverse events in patients with chronic obstructive pulmonary disease (COPD) hospitalized with acute exacerbations.

METHODOLOGY:

• Known risk factors for COPD exacerbations do not fully explain the variation in susceptibility among patients; data on potential biomarkers as predictors of COPD exacerbations are limited.
• In a prospective, observational study at a single center, the researchers examined clinical and lab data including serum CRP levels, EPR, sarcopenia, lung function, nutrition, and frailty.
• The study population included 200 adults older than 40 years with COPD who were hospitalized for acute exacerbations; 50 experienced adverse events.

TAKEAWAY:

• Both elevated CRP and low EPR were significant predictors of adverse events in adjusted analysis in patients with COPD exacerbations (area under the curve, 0.71 and 0.76, respectively).
• In a multivariate analysis, EPR and CRP, as well as sarcopenia, were significantly associated with adverse events (adjusted odds ratios, 2.33, 2.09, and 1.97, respectively).
• COPD symptom scores, frailty, and malnutrition showed predictive value in bivariate but not multivariate analysis.

IN PRACTICE:

“Screening for these biomarkers [EPR and CRP] on admission could help identify high-risk patients who need more aggressive monitoring and treatment,” the researchers wrote in their discussion.

SOURCE:

The lead author on the study was Rohankumar Gandhi, MD, of Guru Gobind Singh Government Hospital, Jamnagar, India. The study was published online in Cureus.

LIMITATIONS:

The use of data from a single center, lack of information on nutritional interventions and counseling, and lack of data on outpatient outcomes limited the study findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

C-reactive protein (CRP) levels and eosinophil-to-platelet ratio (EPR) are significant independent predictors of adverse events in patients with chronic obstructive pulmonary disease (COPD) hospitalized with acute exacerbations.

METHODOLOGY:

• Known risk factors for COPD exacerbations do not fully explain the variation in susceptibility among patients; data on potential biomarkers as predictors of COPD exacerbations are limited.
• In a prospective, observational study at a single center, the researchers examined clinical and lab data including serum CRP levels, EPR, sarcopenia, lung function, nutrition, and frailty.
• The study population included 200 adults older than 40 years with COPD who were hospitalized for acute exacerbations; 50 experienced adverse events.

TAKEAWAY:

• Both elevated CRP and low EPR were significant predictors of adverse events in adjusted analysis in patients with COPD exacerbations (area under the curve, 0.71 and 0.76, respectively).
• In a multivariate analysis, EPR and CRP, as well as sarcopenia, were significantly associated with adverse events (adjusted odds ratios, 2.33, 2.09, and 1.97, respectively).
• COPD symptom scores, frailty, and malnutrition showed predictive value in bivariate but not multivariate analysis.

IN PRACTICE:

“Screening for these biomarkers [EPR and CRP] on admission could help identify high-risk patients who need more aggressive monitoring and treatment,” the researchers wrote in their discussion.

SOURCE:

The lead author on the study was Rohankumar Gandhi, MD, of Guru Gobind Singh Government Hospital, Jamnagar, India. The study was published online in Cureus.

LIMITATIONS:

The use of data from a single center, lack of information on nutritional interventions and counseling, and lack of data on outpatient outcomes limited the study findings.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

CHEST

Evidence-based medicine (EBM) stems from making the best patient-centered decision from the highest-quality data available that comports with our understanding of pathophysiology. In some situations, clinicians are forced to draw conclusions from data that are imperfect and apply it to patients who are complex and dynamic. For most pathologies, available data provides some direction. There is, however, one pathophysiologic state that remains understudied, precarious, and common.

The Centers for Disease Control and Prevention (CDC) estimates that about 7.7% of the United States population has asthma. There were about 1 million ED visits in 2020, with asthma listed as the primary diagnosis, and only 94,000 required hospitalization.¹ There are many tools we employ that have greatly decreased inpatient admissions for asthma. The uptake of inhaled corticosteroids (ICS) has significantly reduced asthma-related morbidity and mortality and reduced exacerbations that require admission to a hospital. This treatment strategy is supported by the Global Initiative for Asthma (GINA) and National Asthma Education and Prevention Program (NAEPP) guidelines.^2,3 While we should celebrate the impact that EBM and ICS have had on asthma outcomes, we continue to struggle to control severe asthma.

Bronchodilator therapy in the hospital is ubiquitous. House staff and hospitalists click the bronchodilator order set early and often. However, the optimal frequency, dose, and duration of inhaled bronchodilator therapy for acute asthma exacerbation are unknown. Do frequency, dose, and duration change with exacerbation severity? Nothing gets ED, inpatient, or ICU physicians more jittery than the phrase “exacerbation of asthma on BiPap” or “intubated for asthma.” With its enormous clinical impact and notoriously difficult hospital and ICU course, the lack of evidence we have for managing these patients outside of the initial 24- to 48-hour visit is concerning. Neither NAEPP nor GINA provide management recommendations for the patient with severe asthma exacerbation that necessitates admission.

Albuterol is a commonly used medication for asthma and chronic obstructive airway disease. It is rapid acting and effective—few medications give patients (or clinicians) such instant satisfaction. As an internal medicine resident and pulmonary fellow, I ordered it countless times without ever looking at the dose. Sometimes, patients would come up from the emergency department after receiving a “continuous dose.” I would often wonder exactly what that meant. After some investigation, I found that in my hospital at the time, one dose of albuterol was 2.5 mg in 2 mL, and a continuous nebulization was four doses for a total of 10 mg.

Shrestha et al. found that high-dose albuterol (7.5 mg) administered continuously was superior to 2.5 mg albuterol delivered three times over 1.5 hours. There were demonstrable improvements in FEV₁ and no ICU admissions.⁴ This study is one of many that compared intermittent to continuous and high-dose vs low-dose albuterol in the emergency department. Most are small and occur over the first 24 hours of presentation to the hospital. They often use short-term changes in spirometry as their primary outcome measure. Being a pulmonary and critical care doctor, I see patients who require advanced rescue maneuvers such as noninvasive positive pressure ventilation (NIPPV) or other pharmacologic adjuncts, for which the current evidence is limited.

Because studies of inhaled bronchodilators in acute asthma exacerbation use spirometry as their primary outcome, those with more severe disease and higher acuity are excluded. Patients on NIPPV can’t perform spirometry. There is essentially no literature to guide treatment for a patient with asthma in the adult ICU. In pediatric intensive care units, there are some data to support either continuous or intermittent inhaled bronchodilator that extends beyond the initial ED visit up to about 60 hours.⁵ Much of the pediatric data revolve about the amount of albuterol given, which can be as high as 75 mg/hr though is typically closer to 10-20 mg/hr.⁶ This rate is continued until respiratory improvement occurs.

With poor evidence to guide us and no specific direction from major guidelines, how should providers manage severe asthma exacerbation? The amount of drug deposited in the lung varies by the device used to deliver it. For nebulization, only about 10% of the nebulized amount reaches the lungs for effect; this is a smaller amount compared with all other devices one could use, such as MDI or DPI.⁷ Once a patient with asthma reaches the emergency department, that person is usually placed on some form of nebulizer treatment. But based on local hospital protocols, the amount and duration can vary widely. Sometimes, in patients with severe exacerbation, there is trepidation to continuing albuterol therapy due to ongoing tachycardia. This seems reasonable given increased albuterol administration could beget an ongoing cycle of dyspnea and anxiety. It could also lead to choosing therapies that are less evidence based.

In closing, this seemingly mundane topic takes on new meaning when a patient is in severe exacerbation. Fortunately, providers are not often faced with the decision to wade into the evidence-free territory of severe asthma exacerbation that is unresponsive to first-line treatments. This narrative should serve as a general alert that this pathophysiologic state is understudied. When encountered, thoughtful consideration of pathology, physiology, and pharmacology is required to reverse it.

References

1. Centers for Disease Control and Prevention. (2023, May 10). Most recent national asthma data. Centers for Disease Control and Prevention. https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm

2. Global Initiative for Asthma - GINA. (2023, August 15). 2023 GINA Main Report - Global Initiative for Asthma - GINA. https://ginasthma.org/2023-gina-main-report/

3. Kiley J, Mensah GA, Boyce CA, et al (A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group). 2020 Focused updates to the: Asthma Management Guidelines. US Department of Health and Human Services, NIH, NHLBI 2020.

4. Shrestha M, Bidadi K, Gourlay S, Hayes J. Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults. Chest. 1996 Jul;110(1):42-7. doi: 10.1378/chest.110.1.42. PMID: 8681661.

5. Kulalert P, Phinyo P, Patumanond J, Smathakanee C, Chuenjit W, Nanthapisal S. Continuous versus intermittent short-acting β2-agonists nebulization as first-line therapy in hospitalized children with severe asthma exacerbation: a propensity score matching analysis. Asthma Res Pract. 2020 Jul 2;6:6. doi: 10.1186/s40733-020-00059-5. PMID: 32632352; PMCID: PMC7329360.

6. Phumeetham S, Bahk TJ, Abd-Allah S, Mathur M. Effect of high-dose continuous albuterol nebulization on clinical variables in children with status asthmaticus. Pediatr Crit Care Med. 2015 Feb;16(2):e41-6. doi: 10.1097/PCC.0000000000000314. PMID: 25560428.

7. Gardenhire DS, Burnett D, Strickland S, Myers, TR. A guide to aerosol delivery devices for respiratory therapists. American Association for Respiratory Care, Dallas, Texas 2017.

CHEST

Evidence-based medicine (EBM) stems from making the best patient-centered decision from the highest-quality data available that comports with our understanding of pathophysiology. In some situations, clinicians are forced to draw conclusions from data that are imperfect and apply it to patients who are complex and dynamic. For most pathologies, available data provides some direction. There is, however, one pathophysiologic state that remains understudied, precarious, and common.

The Centers for Disease Control and Prevention (CDC) estimates that about 7.7% of the United States population has asthma. There were about 1 million ED visits in 2020, with asthma listed as the primary diagnosis, and only 94,000 required hospitalization.¹ There are many tools we employ that have greatly decreased inpatient admissions for asthma. The uptake of inhaled corticosteroids (ICS) has significantly reduced asthma-related morbidity and mortality and reduced exacerbations that require admission to a hospital. This treatment strategy is supported by the Global Initiative for Asthma (GINA) and National Asthma Education and Prevention Program (NAEPP) guidelines.^2,3 While we should celebrate the impact that EBM and ICS have had on asthma outcomes, we continue to struggle to control severe asthma.

Bronchodilator therapy in the hospital is ubiquitous. House staff and hospitalists click the bronchodilator order set early and often. However, the optimal frequency, dose, and duration of inhaled bronchodilator therapy for acute asthma exacerbation are unknown. Do frequency, dose, and duration change with exacerbation severity? Nothing gets ED, inpatient, or ICU physicians more jittery than the phrase “exacerbation of asthma on BiPap” or “intubated for asthma.” With its enormous clinical impact and notoriously difficult hospital and ICU course, the lack of evidence we have for managing these patients outside of the initial 24- to 48-hour visit is concerning. Neither NAEPP nor GINA provide management recommendations for the patient with severe asthma exacerbation that necessitates admission.

Albuterol is a commonly used medication for asthma and chronic obstructive airway disease. It is rapid acting and effective—few medications give patients (or clinicians) such instant satisfaction. As an internal medicine resident and pulmonary fellow, I ordered it countless times without ever looking at the dose. Sometimes, patients would come up from the emergency department after receiving a “continuous dose.” I would often wonder exactly what that meant. After some investigation, I found that in my hospital at the time, one dose of albuterol was 2.5 mg in 2 mL, and a continuous nebulization was four doses for a total of 10 mg.

Shrestha et al. found that high-dose albuterol (7.5 mg) administered continuously was superior to 2.5 mg albuterol delivered three times over 1.5 hours. There were demonstrable improvements in FEV₁ and no ICU admissions.⁴ This study is one of many that compared intermittent to continuous and high-dose vs low-dose albuterol in the emergency department. Most are small and occur over the first 24 hours of presentation to the hospital. They often use short-term changes in spirometry as their primary outcome measure. Being a pulmonary and critical care doctor, I see patients who require advanced rescue maneuvers such as noninvasive positive pressure ventilation (NIPPV) or other pharmacologic adjuncts, for which the current evidence is limited.

Because studies of inhaled bronchodilators in acute asthma exacerbation use spirometry as their primary outcome, those with more severe disease and higher acuity are excluded. Patients on NIPPV can’t perform spirometry. There is essentially no literature to guide treatment for a patient with asthma in the adult ICU. In pediatric intensive care units, there are some data to support either continuous or intermittent inhaled bronchodilator that extends beyond the initial ED visit up to about 60 hours.⁵ Much of the pediatric data revolve about the amount of albuterol given, which can be as high as 75 mg/hr though is typically closer to 10-20 mg/hr.⁶ This rate is continued until respiratory improvement occurs.

With poor evidence to guide us and no specific direction from major guidelines, how should providers manage severe asthma exacerbation? The amount of drug deposited in the lung varies by the device used to deliver it. For nebulization, only about 10% of the nebulized amount reaches the lungs for effect; this is a smaller amount compared with all other devices one could use, such as MDI or DPI.⁷ Once a patient with asthma reaches the emergency department, that person is usually placed on some form of nebulizer treatment. But based on local hospital protocols, the amount and duration can vary widely. Sometimes, in patients with severe exacerbation, there is trepidation to continuing albuterol therapy due to ongoing tachycardia. This seems reasonable given increased albuterol administration could beget an ongoing cycle of dyspnea and anxiety. It could also lead to choosing therapies that are less evidence based.

In closing, this seemingly mundane topic takes on new meaning when a patient is in severe exacerbation. Fortunately, providers are not often faced with the decision to wade into the evidence-free territory of severe asthma exacerbation that is unresponsive to first-line treatments. This narrative should serve as a general alert that this pathophysiologic state is understudied. When encountered, thoughtful consideration of pathology, physiology, and pharmacology is required to reverse it.

References

1. Centers for Disease Control and Prevention. (2023, May 10). Most recent national asthma data. Centers for Disease Control and Prevention. https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm

2. Global Initiative for Asthma - GINA. (2023, August 15). 2023 GINA Main Report - Global Initiative for Asthma - GINA. https://ginasthma.org/2023-gina-main-report/

3. Kiley J, Mensah GA, Boyce CA, et al (A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group). 2020 Focused updates to the: Asthma Management Guidelines. US Department of Health and Human Services, NIH, NHLBI 2020.

4. Shrestha M, Bidadi K, Gourlay S, Hayes J. Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults. Chest. 1996 Jul;110(1):42-7. doi: 10.1378/chest.110.1.42. PMID: 8681661.

5. Kulalert P, Phinyo P, Patumanond J, Smathakanee C, Chuenjit W, Nanthapisal S. Continuous versus intermittent short-acting β2-agonists nebulization as first-line therapy in hospitalized children with severe asthma exacerbation: a propensity score matching analysis. Asthma Res Pract. 2020 Jul 2;6:6. doi: 10.1186/s40733-020-00059-5. PMID: 32632352; PMCID: PMC7329360.

6. Phumeetham S, Bahk TJ, Abd-Allah S, Mathur M. Effect of high-dose continuous albuterol nebulization on clinical variables in children with status asthmaticus. Pediatr Crit Care Med. 2015 Feb;16(2):e41-6. doi: 10.1097/PCC.0000000000000314. PMID: 25560428.

7. Gardenhire DS, Burnett D, Strickland S, Myers, TR. A guide to aerosol delivery devices for respiratory therapists. American Association for Respiratory Care, Dallas, Texas 2017.

CHEST

Evidence-based medicine (EBM) stems from making the best patient-centered decision from the highest-quality data available that comports with our understanding of pathophysiology. In some situations, clinicians are forced to draw conclusions from data that are imperfect and apply it to patients who are complex and dynamic. For most pathologies, available data provides some direction. There is, however, one pathophysiologic state that remains understudied, precarious, and common.

The Centers for Disease Control and Prevention (CDC) estimates that about 7.7% of the United States population has asthma. There were about 1 million ED visits in 2020, with asthma listed as the primary diagnosis, and only 94,000 required hospitalization.¹ There are many tools we employ that have greatly decreased inpatient admissions for asthma. The uptake of inhaled corticosteroids (ICS) has significantly reduced asthma-related morbidity and mortality and reduced exacerbations that require admission to a hospital. This treatment strategy is supported by the Global Initiative for Asthma (GINA) and National Asthma Education and Prevention Program (NAEPP) guidelines.^2,3 While we should celebrate the impact that EBM and ICS have had on asthma outcomes, we continue to struggle to control severe asthma.

Bronchodilator therapy in the hospital is ubiquitous. House staff and hospitalists click the bronchodilator order set early and often. However, the optimal frequency, dose, and duration of inhaled bronchodilator therapy for acute asthma exacerbation are unknown. Do frequency, dose, and duration change with exacerbation severity? Nothing gets ED, inpatient, or ICU physicians more jittery than the phrase “exacerbation of asthma on BiPap” or “intubated for asthma.” With its enormous clinical impact and notoriously difficult hospital and ICU course, the lack of evidence we have for managing these patients outside of the initial 24- to 48-hour visit is concerning. Neither NAEPP nor GINA provide management recommendations for the patient with severe asthma exacerbation that necessitates admission.

Albuterol is a commonly used medication for asthma and chronic obstructive airway disease. It is rapid acting and effective—few medications give patients (or clinicians) such instant satisfaction. As an internal medicine resident and pulmonary fellow, I ordered it countless times without ever looking at the dose. Sometimes, patients would come up from the emergency department after receiving a “continuous dose.” I would often wonder exactly what that meant. After some investigation, I found that in my hospital at the time, one dose of albuterol was 2.5 mg in 2 mL, and a continuous nebulization was four doses for a total of 10 mg.

Shrestha et al. found that high-dose albuterol (7.5 mg) administered continuously was superior to 2.5 mg albuterol delivered three times over 1.5 hours. There were demonstrable improvements in FEV₁ and no ICU admissions.⁴ This study is one of many that compared intermittent to continuous and high-dose vs low-dose albuterol in the emergency department. Most are small and occur over the first 24 hours of presentation to the hospital. They often use short-term changes in spirometry as their primary outcome measure. Being a pulmonary and critical care doctor, I see patients who require advanced rescue maneuvers such as noninvasive positive pressure ventilation (NIPPV) or other pharmacologic adjuncts, for which the current evidence is limited.

Because studies of inhaled bronchodilators in acute asthma exacerbation use spirometry as their primary outcome, those with more severe disease and higher acuity are excluded. Patients on NIPPV can’t perform spirometry. There is essentially no literature to guide treatment for a patient with asthma in the adult ICU. In pediatric intensive care units, there are some data to support either continuous or intermittent inhaled bronchodilator that extends beyond the initial ED visit up to about 60 hours.⁵ Much of the pediatric data revolve about the amount of albuterol given, which can be as high as 75 mg/hr though is typically closer to 10-20 mg/hr.⁶ This rate is continued until respiratory improvement occurs.

With poor evidence to guide us and no specific direction from major guidelines, how should providers manage severe asthma exacerbation? The amount of drug deposited in the lung varies by the device used to deliver it. For nebulization, only about 10% of the nebulized amount reaches the lungs for effect; this is a smaller amount compared with all other devices one could use, such as MDI or DPI.⁷ Once a patient with asthma reaches the emergency department, that person is usually placed on some form of nebulizer treatment. But based on local hospital protocols, the amount and duration can vary widely. Sometimes, in patients with severe exacerbation, there is trepidation to continuing albuterol therapy due to ongoing tachycardia. This seems reasonable given increased albuterol administration could beget an ongoing cycle of dyspnea and anxiety. It could also lead to choosing therapies that are less evidence based.

In closing, this seemingly mundane topic takes on new meaning when a patient is in severe exacerbation. Fortunately, providers are not often faced with the decision to wade into the evidence-free territory of severe asthma exacerbation that is unresponsive to first-line treatments. This narrative should serve as a general alert that this pathophysiologic state is understudied. When encountered, thoughtful consideration of pathology, physiology, and pharmacology is required to reverse it.

References

1. Centers for Disease Control and Prevention. (2023, May 10). Most recent national asthma data. Centers for Disease Control and Prevention. https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm

2. Global Initiative for Asthma - GINA. (2023, August 15). 2023 GINA Main Report - Global Initiative for Asthma - GINA. https://ginasthma.org/2023-gina-main-report/

3. Kiley J, Mensah GA, Boyce CA, et al (A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group). 2020 Focused updates to the: Asthma Management Guidelines. US Department of Health and Human Services, NIH, NHLBI 2020.

4. Shrestha M, Bidadi K, Gourlay S, Hayes J. Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults. Chest. 1996 Jul;110(1):42-7. doi: 10.1378/chest.110.1.42. PMID: 8681661.

5. Kulalert P, Phinyo P, Patumanond J, Smathakanee C, Chuenjit W, Nanthapisal S. Continuous versus intermittent short-acting β2-agonists nebulization as first-line therapy in hospitalized children with severe asthma exacerbation: a propensity score matching analysis. Asthma Res Pract. 2020 Jul 2;6:6. doi: 10.1186/s40733-020-00059-5. PMID: 32632352; PMCID: PMC7329360.

6. Phumeetham S, Bahk TJ, Abd-Allah S, Mathur M. Effect of high-dose continuous albuterol nebulization on clinical variables in children with status asthmaticus. Pediatr Crit Care Med. 2015 Feb;16(2):e41-6. doi: 10.1097/PCC.0000000000000314. PMID: 25560428.

7. Gardenhire DS, Burnett D, Strickland S, Myers, TR. A guide to aerosol delivery devices for respiratory therapists. American Association for Respiratory Care, Dallas, Texas 2017.

A few weeks ago I stumbled upon a two-sentence blurb in a pediatric newsletter summarizing the results of a study comparing the chemical profile of infant body odor with that of postpubertal adolescents. The investigators found that, not surprisingly, the smell of the chemical constituents wafting from babies was more appealing than that emanating from sweaty teenagers. I quickly moved on to the next blurb hoping to find something I hadn’t already experienced or figured out on my own.

But, as I navigated through the rest of my day filled with pickleball, bicycling, and the smell of home-cooked food, something about that study of body odor nagged at me. Who had funded that voyage into the obvious? Were my tax dollars involved? Had I been duped by some alleged nonprofit that had promised my donation would save lives or at least ameliorate suffering? Finally, as the sun dipped below the horizon, my curiosity got the best of me and I searched out the original study. Within minutes I fell down a rabbit hole into the cavernous world of odor science.

Having had zero experience in this niche field, I was amazed at the lengths to which these German odor investigators had gone to analyze the chemicals on and around their subjects. Just trying to ensure that materials and microclimates in the experimental environment were scent-free was a heroic effort. There was “Mono-trap sampling of volatiles, followed by thermodesorption-comprehensive gas chromatography, and time of flight-mass spectrometry analysis.” There were graphs and charts galore. This is serious science, folks. However, they still use the abbreviation “BO” freely, just as I learned to do in junior high. And, in some situations, the investigators relied on the observation of a panel of trained human sniffers to assess the detection threshold and the degree of pleasantness.

Ultimately, the authors’ conclusion was “sexual maturation coincides with changes in body odor chemical composition. Whether those changes explain differences in parental olfactory perception needs to be determined in future studies.” Again, no surprises here.

Exhausted by my venture into the realm of odor science, I finally found the answer to my burning question. The study was supported by the German Research Foundation and the European Union. Phew! Not on my nickel.

Lest you think that I believe any investigation into the potential role of smell in our health and well-being is pure bunk, let me make it clear that I think the role of odor detection is one of the least well-studied and potentially most valuable areas of medical research. Having had one family tell me that their black lab had twice successfully “diagnosed” their pre-verbal child’s ear infection (which I confirmed with an otoscope and the tympanic membrane was intact) I have been keenly interested in the role of animal-assisted diagnosis.

If you also have wondered whether you could write off your pedigreed Portuguese Water Dog as an office expense, I would direct you to an article titled “Canine olfactory detection and its relevance to medical detection.” The authors note that there is some evidence of dogs successfully alerting physicians to Parkinson’s disease, some cancers, malaria, and COVID-19, among others. However, they caution that the reliability is, in most cases, not of a quality that would be helpful on a larger scale.

I can understand the reasons for their caution. However, from my own personal experience, I am completely confident that I can diagnose strep throat by smell, sometimes simply on opening the examination room door. My false-positive rate over 40 years of practice is zero. Of course I still test and, not surprisingly, my false-negative rate is nothing to brag about. However, if a dog can produce even close to my zero false negative with a given disease, that information is valuable and suggests that we should be pointing the odor investigators and their tool box of skills in that direction. I’m pretty sure we don’t need them to dig much deeper into why babies smell better than teenagers.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

A few weeks ago I stumbled upon a two-sentence blurb in a pediatric newsletter summarizing the results of a study comparing the chemical profile of infant body odor with that of postpubertal adolescents. The investigators found that, not surprisingly, the smell of the chemical constituents wafting from babies was more appealing than that emanating from sweaty teenagers. I quickly moved on to the next blurb hoping to find something I hadn’t already experienced or figured out on my own.

But, as I navigated through the rest of my day filled with pickleball, bicycling, and the smell of home-cooked food, something about that study of body odor nagged at me. Who had funded that voyage into the obvious? Were my tax dollars involved? Had I been duped by some alleged nonprofit that had promised my donation would save lives or at least ameliorate suffering? Finally, as the sun dipped below the horizon, my curiosity got the best of me and I searched out the original study. Within minutes I fell down a rabbit hole into the cavernous world of odor science.

Having had zero experience in this niche field, I was amazed at the lengths to which these German odor investigators had gone to analyze the chemicals on and around their subjects. Just trying to ensure that materials and microclimates in the experimental environment were scent-free was a heroic effort. There was “Mono-trap sampling of volatiles, followed by thermodesorption-comprehensive gas chromatography, and time of flight-mass spectrometry analysis.” There were graphs and charts galore. This is serious science, folks. However, they still use the abbreviation “BO” freely, just as I learned to do in junior high. And, in some situations, the investigators relied on the observation of a panel of trained human sniffers to assess the detection threshold and the degree of pleasantness.

Ultimately, the authors’ conclusion was “sexual maturation coincides with changes in body odor chemical composition. Whether those changes explain differences in parental olfactory perception needs to be determined in future studies.” Again, no surprises here.

Exhausted by my venture into the realm of odor science, I finally found the answer to my burning question. The study was supported by the German Research Foundation and the European Union. Phew! Not on my nickel.

Lest you think that I believe any investigation into the potential role of smell in our health and well-being is pure bunk, let me make it clear that I think the role of odor detection is one of the least well-studied and potentially most valuable areas of medical research. Having had one family tell me that their black lab had twice successfully “diagnosed” their pre-verbal child’s ear infection (which I confirmed with an otoscope and the tympanic membrane was intact) I have been keenly interested in the role of animal-assisted diagnosis.

If you also have wondered whether you could write off your pedigreed Portuguese Water Dog as an office expense, I would direct you to an article titled “Canine olfactory detection and its relevance to medical detection.” The authors note that there is some evidence of dogs successfully alerting physicians to Parkinson’s disease, some cancers, malaria, and COVID-19, among others. However, they caution that the reliability is, in most cases, not of a quality that would be helpful on a larger scale.

I can understand the reasons for their caution. However, from my own personal experience, I am completely confident that I can diagnose strep throat by smell, sometimes simply on opening the examination room door. My false-positive rate over 40 years of practice is zero. Of course I still test and, not surprisingly, my false-negative rate is nothing to brag about. However, if a dog can produce even close to my zero false negative with a given disease, that information is valuable and suggests that we should be pointing the odor investigators and their tool box of skills in that direction. I’m pretty sure we don’t need them to dig much deeper into why babies smell better than teenagers.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

A few weeks ago I stumbled upon a two-sentence blurb in a pediatric newsletter summarizing the results of a study comparing the chemical profile of infant body odor with that of postpubertal adolescents. The investigators found that, not surprisingly, the smell of the chemical constituents wafting from babies was more appealing than that emanating from sweaty teenagers. I quickly moved on to the next blurb hoping to find something I hadn’t already experienced or figured out on my own.

But, as I navigated through the rest of my day filled with pickleball, bicycling, and the smell of home-cooked food, something about that study of body odor nagged at me. Who had funded that voyage into the obvious? Were my tax dollars involved? Had I been duped by some alleged nonprofit that had promised my donation would save lives or at least ameliorate suffering? Finally, as the sun dipped below the horizon, my curiosity got the best of me and I searched out the original study. Within minutes I fell down a rabbit hole into the cavernous world of odor science.

Having had zero experience in this niche field, I was amazed at the lengths to which these German odor investigators had gone to analyze the chemicals on and around their subjects. Just trying to ensure that materials and microclimates in the experimental environment were scent-free was a heroic effort. There was “Mono-trap sampling of volatiles, followed by thermodesorption-comprehensive gas chromatography, and time of flight-mass spectrometry analysis.” There were graphs and charts galore. This is serious science, folks. However, they still use the abbreviation “BO” freely, just as I learned to do in junior high. And, in some situations, the investigators relied on the observation of a panel of trained human sniffers to assess the detection threshold and the degree of pleasantness.

Ultimately, the authors’ conclusion was “sexual maturation coincides with changes in body odor chemical composition. Whether those changes explain differences in parental olfactory perception needs to be determined in future studies.” Again, no surprises here.

Exhausted by my venture into the realm of odor science, I finally found the answer to my burning question. The study was supported by the German Research Foundation and the European Union. Phew! Not on my nickel.

Lest you think that I believe any investigation into the potential role of smell in our health and well-being is pure bunk, let me make it clear that I think the role of odor detection is one of the least well-studied and potentially most valuable areas of medical research. Having had one family tell me that their black lab had twice successfully “diagnosed” their pre-verbal child’s ear infection (which I confirmed with an otoscope and the tympanic membrane was intact) I have been keenly interested in the role of animal-assisted diagnosis.

If you also have wondered whether you could write off your pedigreed Portuguese Water Dog as an office expense, I would direct you to an article titled “Canine olfactory detection and its relevance to medical detection.” The authors note that there is some evidence of dogs successfully alerting physicians to Parkinson’s disease, some cancers, malaria, and COVID-19, among others. However, they caution that the reliability is, in most cases, not of a quality that would be helpful on a larger scale.

I can understand the reasons for their caution. However, from my own personal experience, I am completely confident that I can diagnose strep throat by smell, sometimes simply on opening the examination room door. My false-positive rate over 40 years of practice is zero. Of course I still test and, not surprisingly, my false-negative rate is nothing to brag about. However, if a dog can produce even close to my zero false negative with a given disease, that information is valuable and suggests that we should be pointing the odor investigators and their tool box of skills in that direction. I’m pretty sure we don’t need them to dig much deeper into why babies smell better than teenagers.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.

Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

The research was presented at the European Lung Cancer Congress 2024 on March 22.

Tarlatamab targets cancer cells that express the delta-like ligand 3 (DLL3), which occurs infrequently on normal cells but on most SCLC cells. 

Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.

The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.

At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.

The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.

Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.

The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.

Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.

Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.

In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.

No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome. 

Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall. 

“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.

And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”

On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.

“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.

DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
 

A version of this article appeared on Medscape.com.

The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.

Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

The research was presented at the European Lung Cancer Congress 2024 on March 22.

Tarlatamab targets cancer cells that express the delta-like ligand 3 (DLL3), which occurs infrequently on normal cells but on most SCLC cells. 

Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.

The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.

At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.

The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.

Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.

The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.

Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.

Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.

In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.

No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome. 

Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall. 

“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.

And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”

On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.

“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.

DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
 

A version of this article appeared on Medscape.com.

The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.

Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

The research was presented at the European Lung Cancer Congress 2024 on March 22.

Tarlatamab targets cancer cells that express the delta-like ligand 3 (DLL3), which occurs infrequently on normal cells but on most SCLC cells. 

Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.

The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.

At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.

The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.

Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.

The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.

Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.

Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.

In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.

No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome. 

Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall. 

“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.

And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”

On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.

“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.

DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sotatercept (Winrevair, Merck), for the treatment of adults with pulmonary arterial hypertension (PAH), World Health Organization (WHO) Group 1, to increase exercise capacity, improve WHO functional class, and reduce the risk for clinical worsening events.

Sotatercept, which had breakthrough therapy designation, is a first-in-class activin signaling inhibitor that works by improving the balance between pro- and antiproliferative signaling to regulate the vascular cell proliferation that underlies PAH.

“Sotatercept added to background therapy has the potential to become a new standard-of-care option for patients with pulmonary arterial hypertension,” added coinvestigator Aaron B. Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, Boston.

The approval was based on results of the phase 3 STELLAR study, a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which, 323 patients with PAH (WHO Group 1, functional class II or III) were randomly assigned 1:1 to add sotatercept or placebo to stable background therapy.

The results showed that sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved average 6-minute walk distance from baseline by a significant and clinically meaningful 40.8 meters compared with placebo for the trial’s primary efficacy endpoint (P < .001).

Sotatercept also led to significant improvement in multiple secondary outcome measures, including:

• Reduction in the risk for death from any cause or PAH clinical worsening events by 84% vs background therapy alone (number of events: 9 vs 42; hazard ratio [HR], 0.16; P < .001) 
• Improvement in FC from baseline at 24 weeks in 29% of patients compared with 14% of patients treated with placebo (P < .001) 
• Improvement in pulmonary vascular resistance (PVR), with an average 235 dyn/sec/cm⁵ reduction in PVR from baseline (P < .001) 
• Improvement from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between sotatercept and placebo was -442 pg/mL (P < .001) 

The results were reported last year at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, with simultaneous publication in The New England Journal of Medicine. 

Sotatercept injection may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider. The recommended starting dose is 0.3 mg/kg. The recommended target dose is 0.7 mg/kg every 3 weeks.

Sotatercept may increase hemoglobin, may lead to erythrocytosis, and may decrease platelet count and lead to severe thrombocytopenia. Treatment should not be initiated if platelet count is < 50,000/mm³. 

Hemoglobin and platelets should be monitored before each dose of sotatercept for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. 

Full prescribing information is available online. 

Merck estimates that sotatercept will be available for dispensing by select specialty pharmacies in the United States by the end of April 2024.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sotatercept (Winrevair, Merck), for the treatment of adults with pulmonary arterial hypertension (PAH), World Health Organization (WHO) Group 1, to increase exercise capacity, improve WHO functional class, and reduce the risk for clinical worsening events.

Sotatercept, which had breakthrough therapy designation, is a first-in-class activin signaling inhibitor that works by improving the balance between pro- and antiproliferative signaling to regulate the vascular cell proliferation that underlies PAH.

“Sotatercept added to background therapy has the potential to become a new standard-of-care option for patients with pulmonary arterial hypertension,” added coinvestigator Aaron B. Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, Boston.

The approval was based on results of the phase 3 STELLAR study, a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which, 323 patients with PAH (WHO Group 1, functional class II or III) were randomly assigned 1:1 to add sotatercept or placebo to stable background therapy.

The results showed that sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved average 6-minute walk distance from baseline by a significant and clinically meaningful 40.8 meters compared with placebo for the trial’s primary efficacy endpoint (P < .001).

Sotatercept also led to significant improvement in multiple secondary outcome measures, including:

• Reduction in the risk for death from any cause or PAH clinical worsening events by 84% vs background therapy alone (number of events: 9 vs 42; hazard ratio [HR], 0.16; P < .001) 
• Improvement in FC from baseline at 24 weeks in 29% of patients compared with 14% of patients treated with placebo (P < .001) 
• Improvement in pulmonary vascular resistance (PVR), with an average 235 dyn/sec/cm⁵ reduction in PVR from baseline (P < .001) 
• Improvement from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between sotatercept and placebo was -442 pg/mL (P < .001) 

The results were reported last year at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, with simultaneous publication in The New England Journal of Medicine. 

Sotatercept injection may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider. The recommended starting dose is 0.3 mg/kg. The recommended target dose is 0.7 mg/kg every 3 weeks.

Sotatercept may increase hemoglobin, may lead to erythrocytosis, and may decrease platelet count and lead to severe thrombocytopenia. Treatment should not be initiated if platelet count is < 50,000/mm³. 

Hemoglobin and platelets should be monitored before each dose of sotatercept for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. 

Full prescribing information is available online. 

Merck estimates that sotatercept will be available for dispensing by select specialty pharmacies in the United States by the end of April 2024.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sotatercept (Winrevair, Merck), for the treatment of adults with pulmonary arterial hypertension (PAH), World Health Organization (WHO) Group 1, to increase exercise capacity, improve WHO functional class, and reduce the risk for clinical worsening events.

Sotatercept, which had breakthrough therapy designation, is a first-in-class activin signaling inhibitor that works by improving the balance between pro- and antiproliferative signaling to regulate the vascular cell proliferation that underlies PAH.

“Sotatercept added to background therapy has the potential to become a new standard-of-care option for patients with pulmonary arterial hypertension,” added coinvestigator Aaron B. Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, Boston.

The approval was based on results of the phase 3 STELLAR study, a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which, 323 patients with PAH (WHO Group 1, functional class II or III) were randomly assigned 1:1 to add sotatercept or placebo to stable background therapy.

The results showed that sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved average 6-minute walk distance from baseline by a significant and clinically meaningful 40.8 meters compared with placebo for the trial’s primary efficacy endpoint (P < .001).

Sotatercept also led to significant improvement in multiple secondary outcome measures, including:

• Reduction in the risk for death from any cause or PAH clinical worsening events by 84% vs background therapy alone (number of events: 9 vs 42; hazard ratio [HR], 0.16; P < .001) 
• Improvement in FC from baseline at 24 weeks in 29% of patients compared with 14% of patients treated with placebo (P < .001) 
• Improvement in pulmonary vascular resistance (PVR), with an average 235 dyn/sec/cm⁵ reduction in PVR from baseline (P < .001) 
• Improvement from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between sotatercept and placebo was -442 pg/mL (P < .001) 

The results were reported last year at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, with simultaneous publication in The New England Journal of Medicine. 

Sotatercept injection may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider. The recommended starting dose is 0.3 mg/kg. The recommended target dose is 0.7 mg/kg every 3 weeks.

Sotatercept may increase hemoglobin, may lead to erythrocytosis, and may decrease platelet count and lead to severe thrombocytopenia. Treatment should not be initiated if platelet count is < 50,000/mm³. 

Hemoglobin and platelets should be monitored before each dose of sotatercept for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. 

Full prescribing information is available online. 

Merck estimates that sotatercept will be available for dispensing by select specialty pharmacies in the United States by the end of April 2024.

A version of this article appeared on Medscape.com.

Screening for lung cancer can detect other health issues, as well.

The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.

In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.

With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.

Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.

The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.

Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.

The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.

It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.

At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.

To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.

Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.

Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.

The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.

The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.

The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.

4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.

Screening for lung cancer can detect other health issues, as well.

The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.

In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.

With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.

Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.

The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.

Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.

The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.

It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.

At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.

To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.

Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.

Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.

The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.

The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.

The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.

4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.

Screening for lung cancer can detect other health issues, as well.

The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.

In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.

With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.

Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.

The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.

Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.

The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.

It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.

At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.

To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.

Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.

Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.

The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.

The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.

The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.

4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.

For Courtney Stinson, ensuring her daughter’s comfort is a constant battle against the challenges of congenital myopathy. At 9 years old, she relies on a ventilator to breathe, has multiple respiratory treatments daily, and is under the constant care of rotating skilled caregivers. Last year alone, she endured 36 doctor appointments.

To ease her daughter’s struggles with sleep, and after consulting a pediatrician, Ms. Stinson turned to melatonin, a hormone naturally produced by the body to manage sleep. She gave her daughter a low dose of melatonin and saw significant improvement in her ability to settle down, especially when her mind raced.

“She would have such a hard time sleeping when everything is swirling in her head,” said Ms. Stinson, a mother of two who lives in Milan, Michigan. “It’s really been helpful when her brain is moving 100 miles an hour.”

Melatonin is sold without a prescription as a sleep aid in the form of a supplement. For some parents, especially those whose children have complex needs, melatonin can be a valuable resource — but the rise in melatonin across otherwise healthy populations has had its consequences, too, according to pediatric sleep experts. 

Recent data from the CDC illustrates one of these drawbacks: a significant surge in accidental melatonin ingestion among young children over the past 2 decades.

Between 2012 and 2021, poison center calls related to pediatric melatonin exposures skyrocketed by 530%, while emergency department visits for unsupervised melatonin ingestion by infants and young children surged by 420% from 2009 to 2020, according to the CDC report.

Between 2019 and 2022, an estimated 10,930 emergency room visits were linked to 295 cases of children under the age of 6 ingesting melatonin. These incidents accounted for 7.1% of all emergency department visits for medication exposures in this age group, according to the report.

The share of U.S. adults using melatonin increased from 0.4% during 1999 to 2000 to 2.1% during 2017 to 2018.

Doctors say the escalating number of melatonin-related incidents underscores the need for increased awareness and safety measures to protect young children from unintentional overdose, which can cause nausea, vomiting, diarrhea, dizziness, and confusion.

“I do think there is a safe way to use it in certain children, but it should only be used under the guidance of a physician,” said Laura Sterni, MD, director of the Johns Hopkins Pediatric Sleep Center. “There are dangers to using it without that guidance.”
 

Almost 1 in 5 Children Use Melatonin 

Nearly 1 in 5 school-age children and preteens take melatonin for sleep, according to research published last year in JAMA Pediatrics, which also found that 18% of children between 5 and 9 take the supplement.

The American Academy of Sleep Medicine issued a warning in 2022 advising parents to approach the sleep aid with caution. 

“While melatonin can be useful in treating certain sleep-wake disorders, like jet lag, there is much less evidence it can help healthy children or adults fall asleep faster,” M. Adeel Rishi, MD, vice chair of the Academy of Sleep Medicine’s Public Safety Committee, warned on the academy’s site. “Instead of turning to melatonin, parents should work on encouraging their children to develop good sleep habits, like setting a regular bedtime and wake time, having a bedtime routine, and limiting screen time as bedtime approaches.”
 

What’s the Best Way to Give Kids Melatonin?

Melatonin has been found to work well for children with attention deficit hyperactive disorder (ADHD), autism spectrum disorder, or other conditions like blindness that can hinder the development of a normal circadian rhythm. 

But beyond consulting a pediatrician, caregivers whose children are otherwise healthy should consider trying other approaches to sleep disruption first, Dr. Sterni said, and things like proper sleep hygiene and anxiety should be addressed first. 

“Most sleep problems in children really should be managed with behavioral therapy alone,” she said. “To first pull out a medication to treat that I think is the wrong approach.”

Sterni also recommends starting with the lowest dose possible, which is 0.5 milligrams, with the help of pediatrician. It should be taken 1 to 2 hours before bedtime and 2 hours after their last meal, she said. 

But she notes that because melatonin is sold as a supplement and is not regulated by the FDA, it is impossible to know the exact amount in each dose.

According to JAMA, out of 25 supplements of melatonin, most of the products contained up to 50% more melatonin than what was listed.
 

Dangers of Keeping It Within Reach 

One of the biggest dangers for children is that melatonin is often sold in the form of gummies or chewable tablets — things that appeal to children, said Jenna Wheeler, MD, a pediatric critical care doctor at Orlando Health Arnold Palmer Hospital for Children. 

Because it is sold as a supplement, there are no child-safe packaging requirements. 

“From a critical care standpoint, just remember to keep it up high, not on the nightstand or in a drawer,” Dr. Wheeler said. “A child may eat the whole bottle, thinking, ‘This is just like fruits snacks.’ ”

She noted that the amount people need is often lower than what they buy at the store, and that regardless of whether it is used in proper amounts, it is not meant to be a long-term supplement — for adults or for children.

“Like with anything that’s out there, it’s all about how it’s used,” Dr. Wheeler said. “The problem is when kids get into it accidentally or when it’s not used appropriately.”
 

A version of this article appeared on WebMD.com.

For Courtney Stinson, ensuring her daughter’s comfort is a constant battle against the challenges of congenital myopathy. At 9 years old, she relies on a ventilator to breathe, has multiple respiratory treatments daily, and is under the constant care of rotating skilled caregivers. Last year alone, she endured 36 doctor appointments.

To ease her daughter’s struggles with sleep, and after consulting a pediatrician, Ms. Stinson turned to melatonin, a hormone naturally produced by the body to manage sleep. She gave her daughter a low dose of melatonin and saw significant improvement in her ability to settle down, especially when her mind raced.

“She would have such a hard time sleeping when everything is swirling in her head,” said Ms. Stinson, a mother of two who lives in Milan, Michigan. “It’s really been helpful when her brain is moving 100 miles an hour.”

Melatonin is sold without a prescription as a sleep aid in the form of a supplement. For some parents, especially those whose children have complex needs, melatonin can be a valuable resource — but the rise in melatonin across otherwise healthy populations has had its consequences, too, according to pediatric sleep experts. 

Recent data from the CDC illustrates one of these drawbacks: a significant surge in accidental melatonin ingestion among young children over the past 2 decades.

Between 2012 and 2021, poison center calls related to pediatric melatonin exposures skyrocketed by 530%, while emergency department visits for unsupervised melatonin ingestion by infants and young children surged by 420% from 2009 to 2020, according to the CDC report.

Between 2019 and 2022, an estimated 10,930 emergency room visits were linked to 295 cases of children under the age of 6 ingesting melatonin. These incidents accounted for 7.1% of all emergency department visits for medication exposures in this age group, according to the report.

The share of U.S. adults using melatonin increased from 0.4% during 1999 to 2000 to 2.1% during 2017 to 2018.

Doctors say the escalating number of melatonin-related incidents underscores the need for increased awareness and safety measures to protect young children from unintentional overdose, which can cause nausea, vomiting, diarrhea, dizziness, and confusion.

“I do think there is a safe way to use it in certain children, but it should only be used under the guidance of a physician,” said Laura Sterni, MD, director of the Johns Hopkins Pediatric Sleep Center. “There are dangers to using it without that guidance.”
 

Almost 1 in 5 Children Use Melatonin 

Nearly 1 in 5 school-age children and preteens take melatonin for sleep, according to research published last year in JAMA Pediatrics, which also found that 18% of children between 5 and 9 take the supplement.

The American Academy of Sleep Medicine issued a warning in 2022 advising parents to approach the sleep aid with caution. 

“While melatonin can be useful in treating certain sleep-wake disorders, like jet lag, there is much less evidence it can help healthy children or adults fall asleep faster,” M. Adeel Rishi, MD, vice chair of the Academy of Sleep Medicine’s Public Safety Committee, warned on the academy’s site. “Instead of turning to melatonin, parents should work on encouraging their children to develop good sleep habits, like setting a regular bedtime and wake time, having a bedtime routine, and limiting screen time as bedtime approaches.”
 

What’s the Best Way to Give Kids Melatonin?

Melatonin has been found to work well for children with attention deficit hyperactive disorder (ADHD), autism spectrum disorder, or other conditions like blindness that can hinder the development of a normal circadian rhythm. 

But beyond consulting a pediatrician, caregivers whose children are otherwise healthy should consider trying other approaches to sleep disruption first, Dr. Sterni said, and things like proper sleep hygiene and anxiety should be addressed first. 

“Most sleep problems in children really should be managed with behavioral therapy alone,” she said. “To first pull out a medication to treat that I think is the wrong approach.”

Sterni also recommends starting with the lowest dose possible, which is 0.5 milligrams, with the help of pediatrician. It should be taken 1 to 2 hours before bedtime and 2 hours after their last meal, she said. 

But she notes that because melatonin is sold as a supplement and is not regulated by the FDA, it is impossible to know the exact amount in each dose.

According to JAMA, out of 25 supplements of melatonin, most of the products contained up to 50% more melatonin than what was listed.
 

Dangers of Keeping It Within Reach 

One of the biggest dangers for children is that melatonin is often sold in the form of gummies or chewable tablets — things that appeal to children, said Jenna Wheeler, MD, a pediatric critical care doctor at Orlando Health Arnold Palmer Hospital for Children. 

Because it is sold as a supplement, there are no child-safe packaging requirements. 

“From a critical care standpoint, just remember to keep it up high, not on the nightstand or in a drawer,” Dr. Wheeler said. “A child may eat the whole bottle, thinking, ‘This is just like fruits snacks.’ ”

She noted that the amount people need is often lower than what they buy at the store, and that regardless of whether it is used in proper amounts, it is not meant to be a long-term supplement — for adults or for children.

“Like with anything that’s out there, it’s all about how it’s used,” Dr. Wheeler said. “The problem is when kids get into it accidentally or when it’s not used appropriately.”
 

A version of this article appeared on WebMD.com.

For Courtney Stinson, ensuring her daughter’s comfort is a constant battle against the challenges of congenital myopathy. At 9 years old, she relies on a ventilator to breathe, has multiple respiratory treatments daily, and is under the constant care of rotating skilled caregivers. Last year alone, she endured 36 doctor appointments.

To ease her daughter’s struggles with sleep, and after consulting a pediatrician, Ms. Stinson turned to melatonin, a hormone naturally produced by the body to manage sleep. She gave her daughter a low dose of melatonin and saw significant improvement in her ability to settle down, especially when her mind raced.

“She would have such a hard time sleeping when everything is swirling in her head,” said Ms. Stinson, a mother of two who lives in Milan, Michigan. “It’s really been helpful when her brain is moving 100 miles an hour.”

Melatonin is sold without a prescription as a sleep aid in the form of a supplement. For some parents, especially those whose children have complex needs, melatonin can be a valuable resource — but the rise in melatonin across otherwise healthy populations has had its consequences, too, according to pediatric sleep experts. 

Recent data from the CDC illustrates one of these drawbacks: a significant surge in accidental melatonin ingestion among young children over the past 2 decades.

Between 2012 and 2021, poison center calls related to pediatric melatonin exposures skyrocketed by 530%, while emergency department visits for unsupervised melatonin ingestion by infants and young children surged by 420% from 2009 to 2020, according to the CDC report.

Between 2019 and 2022, an estimated 10,930 emergency room visits were linked to 295 cases of children under the age of 6 ingesting melatonin. These incidents accounted for 7.1% of all emergency department visits for medication exposures in this age group, according to the report.

The share of U.S. adults using melatonin increased from 0.4% during 1999 to 2000 to 2.1% during 2017 to 2018.

Doctors say the escalating number of melatonin-related incidents underscores the need for increased awareness and safety measures to protect young children from unintentional overdose, which can cause nausea, vomiting, diarrhea, dizziness, and confusion.

“I do think there is a safe way to use it in certain children, but it should only be used under the guidance of a physician,” said Laura Sterni, MD, director of the Johns Hopkins Pediatric Sleep Center. “There are dangers to using it without that guidance.”
 

Almost 1 in 5 Children Use Melatonin 

Nearly 1 in 5 school-age children and preteens take melatonin for sleep, according to research published last year in JAMA Pediatrics, which also found that 18% of children between 5 and 9 take the supplement.

The American Academy of Sleep Medicine issued a warning in 2022 advising parents to approach the sleep aid with caution. 

“While melatonin can be useful in treating certain sleep-wake disorders, like jet lag, there is much less evidence it can help healthy children or adults fall asleep faster,” M. Adeel Rishi, MD, vice chair of the Academy of Sleep Medicine’s Public Safety Committee, warned on the academy’s site. “Instead of turning to melatonin, parents should work on encouraging their children to develop good sleep habits, like setting a regular bedtime and wake time, having a bedtime routine, and limiting screen time as bedtime approaches.”
 

What’s the Best Way to Give Kids Melatonin?

Melatonin has been found to work well for children with attention deficit hyperactive disorder (ADHD), autism spectrum disorder, or other conditions like blindness that can hinder the development of a normal circadian rhythm. 

But beyond consulting a pediatrician, caregivers whose children are otherwise healthy should consider trying other approaches to sleep disruption first, Dr. Sterni said, and things like proper sleep hygiene and anxiety should be addressed first. 

“Most sleep problems in children really should be managed with behavioral therapy alone,” she said. “To first pull out a medication to treat that I think is the wrong approach.”

Sterni also recommends starting with the lowest dose possible, which is 0.5 milligrams, with the help of pediatrician. It should be taken 1 to 2 hours before bedtime and 2 hours after their last meal, she said. 

But she notes that because melatonin is sold as a supplement and is not regulated by the FDA, it is impossible to know the exact amount in each dose.

According to JAMA, out of 25 supplements of melatonin, most of the products contained up to 50% more melatonin than what was listed.
 

Dangers of Keeping It Within Reach 

One of the biggest dangers for children is that melatonin is often sold in the form of gummies or chewable tablets — things that appeal to children, said Jenna Wheeler, MD, a pediatric critical care doctor at Orlando Health Arnold Palmer Hospital for Children. 

Because it is sold as a supplement, there are no child-safe packaging requirements. 

“From a critical care standpoint, just remember to keep it up high, not on the nightstand or in a drawer,” Dr. Wheeler said. “A child may eat the whole bottle, thinking, ‘This is just like fruits snacks.’ ”

She noted that the amount people need is often lower than what they buy at the store, and that regardless of whether it is used in proper amounts, it is not meant to be a long-term supplement — for adults or for children.

“Like with anything that’s out there, it’s all about how it’s used,” Dr. Wheeler said. “The problem is when kids get into it accidentally or when it’s not used appropriately.”
 

A version of this article appeared on WebMD.com.

Routine use of rapid respiratory virus testing in the emergency department (ED) appears to show limited benefit among patients with signs and symptoms of acute respiratory infection (ARI), according to a new study.

Rapid viral testing wasn’t associated with reduced antibiotic use, ED length of stay, or rates of ED return visits or hospitalization. However, testing was associated with a small increase in antiviral prescriptions and a small reduction in blood tests and chest x-rays.

“Our interest in studying the benefits of rapid viral testing in emergency departments comes from a commitment to diagnostic stewardship — ensuring that the right tests are administered to the right patients at the right time while also curbing overuse,” said lead author Tilmann Schober, MD, a resident in pediatric infectious disease at McGill University and Montreal Children’s Hospital.

“Following the SARS-CoV-2 pandemic, we have seen a surge in the availability of rapid viral testing, including molecular multiplex panels,” he said. “However, the actual impact of these advancements on patient care in the ED remains uncertain.”

The study was published online on March 4, 2024, in JAMA Internal Medicine).
 

Rapid Viral Testing

Dr. Schober and colleagues conducted a systematic review and meta-analysis of 11 randomized clinical trials to understand whether rapid testing for respiratory viruses was associated with patient treatment in the ED.

In particular, the research team looked at whether testing in patients with suspected ARI was associated with decreased antibiotic use, ancillary tests, ED length of stay, ED return visits, hospitalization, and increased influenza antiviral treatment.

Among the trials, seven studies included molecular testing, and eight used multiplex panels, including influenza and respiratory syncytial virus (RSV), influenza/RSV/adenovirus/parainfluenza, or a panel of 15 or more respiratory viruses. No study evaluated testing for SARS-CoV-2. The research team reported risk ratios (RRs) and risk difference estimates.

In general, routine rapid viral testing was associated with higher use of influenza antivirals (RR, 1.33) and lower use of chest radiography (RR, 0.88) and blood tests (RR, 0.81). However, the magnitude of these effects was small. For instance, to achieve one additional viral prescription, 70 patients would need to be tested, and to save one x-ray, 30 patients would need to be tested.

“This suggests that, while statistically significant, the practical impact of these secondary outcomes may not justify the extensive effort and resources involved in widespread testing,” Dr. Schober said.

In addition, there was no association between rapid testing and antibiotic use (RR, 0.99), urine testing (RR, 0.95), ED length of stay (0 h), return visits (RR, 0.93), or hospitalization (RR, 1.01).

Notably, there was no association between rapid viral testing and antibiotic use in any prespecified subgroup based on age, test method, publication date, number of viral targets, risk of bias, or industry funding, the authors said. They concluded that rapid virus testing should be reserved for patients for whom the testing will change treatment, such as high-risk patients or those with severe disease.

“It’s crucial to note that our study specifically evaluated the impact of systematic testing of patients with signs and symptoms of acute respiratory infection. Our findings do not advocate against rapid respiratory virus testing in general,” Dr. Schober said. “There is well-established evidence supporting the benefits of viral testing in certain contexts, such as hospitalized patients, to guide infection control practices or in specific high-risk populations.”
 

Future Research

Additional studies should look at testing among subgroups, particularly those with high-risk conditions, the study authors wrote. In addition, the research team would like to study the implementation of novel diagnostic stewardship programs as compared with well-established antibiotic stewardship programs.

“Acute respiratory tract illnesses represent one of the most common reasons for being evaluated in an acute care setting, especially in pediatrics, and these visits have traditionally resulted in excessive antibiotic prescribing, despite the etiology of the infection mostly being viral,” said Suchitra Rao, MBBS, associate professor of pediatrics at the University of Colorado School of Medicine and associate medical director of infection prevention and control at Children’s Hospital Colorado, Aurora.

Dr. Rao, who wasn’t involved with this study, has surveyed ED providers about respiratory viral testing and changes in clinical decision-making. She and colleagues found that providers most commonly changed clinical decision-making while prescribing an antiviral if influenza was detected or withholding antivirals if influenza wasn’t detected.

“Multiplex testing for respiratory viruses and atypical bacteria is becoming more widespread, with newer-generation platforms having shorter turnaround times, and offers the potential to impact point-of-care decision-making,” she said. “However, these tests are expensive, and more studies are needed to explore whether respiratory pathogen panel testing in the acute care setting has an impact in terms of reduced antibiotic use as well as other outcomes, including ED visits, health-seeking behaviors, and hospitalization.”

For instance, more recent studies around SARS-CoV-2 with newer-generation panels may make a difference, as well as multiplex panels that include numerous viral targets, she said.

“Further RCTs are required to evaluate the impact of influenza/RSV/SARS-CoV-2 panels, as well as respiratory pathogen panel testing in conjunction with antimicrobial and diagnostic stewardship efforts, which have been associated with improved outcomes for other rapid molecular platforms, such as blood culture identification panels,” Rao said.

The study was funded by the Research Institute of the McGill University Health Center. Dr. Schober reported no disclosures, and several study authors reported grants or personal fees from companies outside of this research. Dr. Rao disclosed no relevant relationships.

A version of this article appeared on Medscape.com .

Routine use of rapid respiratory virus testing in the emergency department (ED) appears to show limited benefit among patients with signs and symptoms of acute respiratory infection (ARI), according to a new study.

Rapid viral testing wasn’t associated with reduced antibiotic use, ED length of stay, or rates of ED return visits or hospitalization. However, testing was associated with a small increase in antiviral prescriptions and a small reduction in blood tests and chest x-rays.

“Our interest in studying the benefits of rapid viral testing in emergency departments comes from a commitment to diagnostic stewardship — ensuring that the right tests are administered to the right patients at the right time while also curbing overuse,” said lead author Tilmann Schober, MD, a resident in pediatric infectious disease at McGill University and Montreal Children’s Hospital.

“Following the SARS-CoV-2 pandemic, we have seen a surge in the availability of rapid viral testing, including molecular multiplex panels,” he said. “However, the actual impact of these advancements on patient care in the ED remains uncertain.”

The study was published online on March 4, 2024, in JAMA Internal Medicine).
 

Rapid Viral Testing

Dr. Schober and colleagues conducted a systematic review and meta-analysis of 11 randomized clinical trials to understand whether rapid testing for respiratory viruses was associated with patient treatment in the ED.

In particular, the research team looked at whether testing in patients with suspected ARI was associated with decreased antibiotic use, ancillary tests, ED length of stay, ED return visits, hospitalization, and increased influenza antiviral treatment.

Among the trials, seven studies included molecular testing, and eight used multiplex panels, including influenza and respiratory syncytial virus (RSV), influenza/RSV/adenovirus/parainfluenza, or a panel of 15 or more respiratory viruses. No study evaluated testing for SARS-CoV-2. The research team reported risk ratios (RRs) and risk difference estimates.

In general, routine rapid viral testing was associated with higher use of influenza antivirals (RR, 1.33) and lower use of chest radiography (RR, 0.88) and blood tests (RR, 0.81). However, the magnitude of these effects was small. For instance, to achieve one additional viral prescription, 70 patients would need to be tested, and to save one x-ray, 30 patients would need to be tested.

“This suggests that, while statistically significant, the practical impact of these secondary outcomes may not justify the extensive effort and resources involved in widespread testing,” Dr. Schober said.

In addition, there was no association between rapid testing and antibiotic use (RR, 0.99), urine testing (RR, 0.95), ED length of stay (0 h), return visits (RR, 0.93), or hospitalization (RR, 1.01).

Notably, there was no association between rapid viral testing and antibiotic use in any prespecified subgroup based on age, test method, publication date, number of viral targets, risk of bias, or industry funding, the authors said. They concluded that rapid virus testing should be reserved for patients for whom the testing will change treatment, such as high-risk patients or those with severe disease.

“It’s crucial to note that our study specifically evaluated the impact of systematic testing of patients with signs and symptoms of acute respiratory infection. Our findings do not advocate against rapid respiratory virus testing in general,” Dr. Schober said. “There is well-established evidence supporting the benefits of viral testing in certain contexts, such as hospitalized patients, to guide infection control practices or in specific high-risk populations.”
 

Future Research

Additional studies should look at testing among subgroups, particularly those with high-risk conditions, the study authors wrote. In addition, the research team would like to study the implementation of novel diagnostic stewardship programs as compared with well-established antibiotic stewardship programs.

“Acute respiratory tract illnesses represent one of the most common reasons for being evaluated in an acute care setting, especially in pediatrics, and these visits have traditionally resulted in excessive antibiotic prescribing, despite the etiology of the infection mostly being viral,” said Suchitra Rao, MBBS, associate professor of pediatrics at the University of Colorado School of Medicine and associate medical director of infection prevention and control at Children’s Hospital Colorado, Aurora.

Dr. Rao, who wasn’t involved with this study, has surveyed ED providers about respiratory viral testing and changes in clinical decision-making. She and colleagues found that providers most commonly changed clinical decision-making while prescribing an antiviral if influenza was detected or withholding antivirals if influenza wasn’t detected.

“Multiplex testing for respiratory viruses and atypical bacteria is becoming more widespread, with newer-generation platforms having shorter turnaround times, and offers the potential to impact point-of-care decision-making,” she said. “However, these tests are expensive, and more studies are needed to explore whether respiratory pathogen panel testing in the acute care setting has an impact in terms of reduced antibiotic use as well as other outcomes, including ED visits, health-seeking behaviors, and hospitalization.”

For instance, more recent studies around SARS-CoV-2 with newer-generation panels may make a difference, as well as multiplex panels that include numerous viral targets, she said.

“Further RCTs are required to evaluate the impact of influenza/RSV/SARS-CoV-2 panels, as well as respiratory pathogen panel testing in conjunction with antimicrobial and diagnostic stewardship efforts, which have been associated with improved outcomes for other rapid molecular platforms, such as blood culture identification panels,” Rao said.

The study was funded by the Research Institute of the McGill University Health Center. Dr. Schober reported no disclosures, and several study authors reported grants or personal fees from companies outside of this research. Dr. Rao disclosed no relevant relationships.

A version of this article appeared on Medscape.com .

Routine use of rapid respiratory virus testing in the emergency department (ED) appears to show limited benefit among patients with signs and symptoms of acute respiratory infection (ARI), according to a new study.

Rapid viral testing wasn’t associated with reduced antibiotic use, ED length of stay, or rates of ED return visits or hospitalization. However, testing was associated with a small increase in antiviral prescriptions and a small reduction in blood tests and chest x-rays.

“Our interest in studying the benefits of rapid viral testing in emergency departments comes from a commitment to diagnostic stewardship — ensuring that the right tests are administered to the right patients at the right time while also curbing overuse,” said lead author Tilmann Schober, MD, a resident in pediatric infectious disease at McGill University and Montreal Children’s Hospital.

“Following the SARS-CoV-2 pandemic, we have seen a surge in the availability of rapid viral testing, including molecular multiplex panels,” he said. “However, the actual impact of these advancements on patient care in the ED remains uncertain.”

The study was published online on March 4, 2024, in JAMA Internal Medicine).
 

Rapid Viral Testing

Dr. Schober and colleagues conducted a systematic review and meta-analysis of 11 randomized clinical trials to understand whether rapid testing for respiratory viruses was associated with patient treatment in the ED.

In particular, the research team looked at whether testing in patients with suspected ARI was associated with decreased antibiotic use, ancillary tests, ED length of stay, ED return visits, hospitalization, and increased influenza antiviral treatment.

Among the trials, seven studies included molecular testing, and eight used multiplex panels, including influenza and respiratory syncytial virus (RSV), influenza/RSV/adenovirus/parainfluenza, or a panel of 15 or more respiratory viruses. No study evaluated testing for SARS-CoV-2. The research team reported risk ratios (RRs) and risk difference estimates.

In general, routine rapid viral testing was associated with higher use of influenza antivirals (RR, 1.33) and lower use of chest radiography (RR, 0.88) and blood tests (RR, 0.81). However, the magnitude of these effects was small. For instance, to achieve one additional viral prescription, 70 patients would need to be tested, and to save one x-ray, 30 patients would need to be tested.

“This suggests that, while statistically significant, the practical impact of these secondary outcomes may not justify the extensive effort and resources involved in widespread testing,” Dr. Schober said.

In addition, there was no association between rapid testing and antibiotic use (RR, 0.99), urine testing (RR, 0.95), ED length of stay (0 h), return visits (RR, 0.93), or hospitalization (RR, 1.01).

Notably, there was no association between rapid viral testing and antibiotic use in any prespecified subgroup based on age, test method, publication date, number of viral targets, risk of bias, or industry funding, the authors said. They concluded that rapid virus testing should be reserved for patients for whom the testing will change treatment, such as high-risk patients or those with severe disease.

“It’s crucial to note that our study specifically evaluated the impact of systematic testing of patients with signs and symptoms of acute respiratory infection. Our findings do not advocate against rapid respiratory virus testing in general,” Dr. Schober said. “There is well-established evidence supporting the benefits of viral testing in certain contexts, such as hospitalized patients, to guide infection control practices or in specific high-risk populations.”
 

Future Research

Additional studies should look at testing among subgroups, particularly those with high-risk conditions, the study authors wrote. In addition, the research team would like to study the implementation of novel diagnostic stewardship programs as compared with well-established antibiotic stewardship programs.

“Acute respiratory tract illnesses represent one of the most common reasons for being evaluated in an acute care setting, especially in pediatrics, and these visits have traditionally resulted in excessive antibiotic prescribing, despite the etiology of the infection mostly being viral,” said Suchitra Rao, MBBS, associate professor of pediatrics at the University of Colorado School of Medicine and associate medical director of infection prevention and control at Children’s Hospital Colorado, Aurora.

Dr. Rao, who wasn’t involved with this study, has surveyed ED providers about respiratory viral testing and changes in clinical decision-making. She and colleagues found that providers most commonly changed clinical decision-making while prescribing an antiviral if influenza was detected or withholding antivirals if influenza wasn’t detected.

“Multiplex testing for respiratory viruses and atypical bacteria is becoming more widespread, with newer-generation platforms having shorter turnaround times, and offers the potential to impact point-of-care decision-making,” she said. “However, these tests are expensive, and more studies are needed to explore whether respiratory pathogen panel testing in the acute care setting has an impact in terms of reduced antibiotic use as well as other outcomes, including ED visits, health-seeking behaviors, and hospitalization.”

For instance, more recent studies around SARS-CoV-2 with newer-generation panels may make a difference, as well as multiplex panels that include numerous viral targets, she said.

“Further RCTs are required to evaluate the impact of influenza/RSV/SARS-CoV-2 panels, as well as respiratory pathogen panel testing in conjunction with antimicrobial and diagnostic stewardship efforts, which have been associated with improved outcomes for other rapid molecular platforms, such as blood culture identification panels,” Rao said.

The study was funded by the Research Institute of the McGill University Health Center. Dr. Schober reported no disclosures, and several study authors reported grants or personal fees from companies outside of this research. Dr. Rao disclosed no relevant relationships.

A version of this article appeared on Medscape.com .