The year 2020 was unlike any in recent history, particularly for those working in health care. With the onset of the SARs-CoV-2 pandemic, many physicians were met with increasing clinical demands, and hospitalists served an instrumental role in providing medical care as the world faced an unprecedented need for health care resources.

In addition, 2020 was a year in which many of us reflected on inequities both inside and outside of medicine. Many in health care witnessed the disproportionate burden that the SARs-CoV-2 pandemic placed on communities of color and inequities pertaining to vaccine distribution.

In spite of the challenges of 2020, the field of pediatric hospital medicine (PHM) has continued to grow and evolve, with an incredible amount of new literature published in 2020.

In this article, we identify the top 10 articles published in 2020, 5 of which are summarized below. These articles were presented at the Pediatric Update at SHM Converge 2021.
 

The top 5 articles

Association between parent comfort with English and adverse events among hospitalized children

Khan A et al. JAMA Pediatrics. December 2020.¹

Background: Hospitalized children experience similar rates of medical errors compared to adult patients, but higher rates in areas that could cause harm.¹ A major contributor to medical errors is communication failure, which language barriers frequently contribute to. Single-center data suggest that pediatric patients of families with limited comfort with English experience increased adverse events,² but multicenter data are lacking.

Findings: This prospective cohort study observed adverse event rates among 2,148 patients from seven teaching hospitals from December 2014 to January 2017. Survey data revealed 147 of 1,666 (9%) parents of patient families expressed limited comfort in English, and Spanish was the predominant language in this group (71%). There were 217 adverse events reported, 142 (65%) of which were deemed preventable by study personnel. Nearly twice as many children of parents with limited comfort with English experienced an adverse event when compared to their English-speaking counterparts (26 of 147 [17.7%] vs. 146 of 1,519 [9.6%]; adjusted odds ratio, 2.1; 95% confidence interval, 1.2-3.7). Interpreter use was not measured.

Impact to practice: Children of parents with limited comfort with English are nearly twice as likely to experience adverse events when hospitalized. Hospitals should reflect on current practice and make efforts to improve their ability to identify and communicate with this vulnerable cohort.
 

Saline-lock versus continuous infusion: Maintaining peripheral intravenous catheter access in children

Yeung F et al. Hospital Pediatrics. December 2020.³

Background: Peripheral intravenous catheter (PIV) insertion is performed on most hospitalized children. Unfortunately, PIVs frequently fail and need to be replaced. There is a widespread perception that infusing a crystalloid solution at a low rate through a PIV, a strategy known as “to keep vein open” (TKO) prolongs the patency of PIVs, however there is a lack of evidence to support this practice.⁴Findings: In this prospective, time-allocated study, 172 children were allocated to either a TKO strategy or a saline-lock strategy with a primary outcome of duration of PIV patency.³ Secondary outcomes included PIV–related complication rates and patient and caregiver satisfaction. The mean duration of PIV patency was 41.68 hours in the TKO group and 44.05 hours in the saline-lock group, which did not meet the prespecified definition of a clinically significant difference. There was no significant difference in prevalence of PIV-associated complications and patient satisfaction was similar between the two groups.

Impact to practice: Running fluid “to keep vein open” does not increase the duration of PIV patency compared to intermittent saline locks. Given that a TKO strategy limits a patient’s mobility, this low-value practice can be discontinued without increasing the risk of PIV failure.
 

Intensive care unit utilization after adoption of a ward-based high flow nasal cannula protocol

Coon ER et al. Journal of Hospital Medicine. June 2020.⁵

Background: High Flow Nasal Cannula (HFNC) has been widely adopted for escalation of respiratory support in patients with bronchiolitis; however, its use is dictated by highly variant local protocols.⁶ Small-scale randomized control trials and systematic reviews show that early HFNC initiation in mild to moderate disease does not change patient outcomes.⁷Findings: In this retrospective cohort study of ward-based HFNC, the authors used the Pediatric Health Information System database to identify 12 hospitals that had adopted ward-based HFNC protocols. The study used an interrupted time series analysis to compare outcomes for patients ages 3-24 months hospitalized with bronchiolitis (n = 32,809) in the three seasons before and after protocol adoption. Ward-based HFNC adoption paradoxically increased ICU admission (absolute increase 3.1%, 95% confidence interval, 2.8-3.4%) and ICU length of stay (absolute difference 9.1 days/100 patients, 95% CI, 5.1-13.2). Total length of stay and rates of mechanical ventilation were similar between groups.⁵Impact to practice: Ward-based HFNC protocols are associated with increased ICU utilization. As bronchiolitis is the leading diagnosis in pediatrics, pediatric hospitals can lead ward-based quality efforts to decrease HFNC overutilization focused on decreased initiation or deimplementation.
 

Lower versus traditional treatment threshold for neonatal hypoglycemia

Van Kempen AAMW et al. New England Journal of Medicine. February 2020.⁸

Background: Hypoglycemia is the most common metabolic abnormality in newborns, and up to 30% of newborns are routinely monitored for hypoglycemia. There is no consensus regarding the appropriate threshold at which hypoglycemia should be treated in order to prevent neurologic injury. Prior studies of neonatal hypoglycemia have largely been observation and have yielded conflicting results.⁸Findings: In this multicenter, randomized, noninferiority trial, 689 infants born at 35 weeks gestational age or later with risk factors for hypoglycemia and a measured blood glucose of 36-46 mg/dL were randomized to either a lower glucose treatment threshold (36 mg/dL) or traditional glucose treatment threshold (47 mg/dL). The primary outcome was psychomotor development at 18 months, assessed via the Bayley Scale of Infant and Toddler Development, third edition. There was no significant difference in cognitive or motor scores at 18 months. The lower treatment threshold group had a higher frequency of severe hypoglycemia (< 36 mg/dL) and were more likely to have four or more episodes of hypoglycemia. The traditional treatment threshold group had more supplemental feeding and more IV glucose administration. Length of stay for the mother and baby did not differ between groups.⁸

Impact to practice: This prospective, randomized study suggests that reducing the treatment threshold for neonatal hypoglycemia did not affect neurodevelopmental at 18 months of age. In contrast, a recent meta-analysis by Shah et al. suggested that neonatal hypoglycemia was not associated with adverse neurodevelopmental outcomes in early childhood; however, differences in rates of neurodevelopmental impairment, low literacy, and low numeracy were detectable by age five.⁹
 

Factors associated with family experience in pediatric inpatient care

Feng JY et al. Pediatrics. March 2020 Mar.¹⁰

Background: Positive patient experience is associated with better health care outcomes and reduced health care use.¹¹ Consequently, patient experience surveys have played a larger role in public reporting, financial risk sharing arrangements, and pay for performance programs. While adult studies have examined the importance of specific care dimensions for patient experience, data are lacking for inpatient pediatric populations.

Findings: A retrospective study collected Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys from 17,727 patients in 69 hospitals within the United States over a 14-month period.¹⁰ Of the 10 care dimensions analyzed, child comfort (aOR 1.50; 95% CI, 1.41-1.60) and nurse-parent communication (aOR 1.50; 95% CI, 1.42-1.58) were most strongly associated with a family’s willingness to recommend a hospital. Additional associated indices included preparing to leave the hospital (aOR 1.34; 95% CI, 1.27-1.41), doctor-parent communication (aOR 1.28; 95% CI, 1.21–1.35), and keeping parents informed (aOR 1.25; 95% CI, 1.18-1.33). Privacy and quietness, which are associated with positive patient experience in adult studies, were not significantly associated with willingness to recommend in this cohort.

Impact to practice: Hospitals seeking to improve patient experience will benefit most by focusing on improving patient comfort and nurse-parent communication. Factors that increase adult patient satisfaction may not be as important to the pediatric population and their families.



The other five articles that comprised the top 10 are listed below:
 

Comparison of as-needed and scheduled posthospitalization follow-up for children hospitalized for bronchiolitis

Coon ER et al. JAMA Pediatrics. September 2020.¹²

Clinical prediction rule for distinguishing bacterial from aseptic meningitis

Mintegi S et al. Pediatrics. September 2020.¹³

The Michigan Appropriateness Guide for Intravenous Catheters in Pediatrics: miniMAGIC Ullman AJ et al. Pediatrics. June 2020.¹⁴

A structured neonatal parenting elective: An approach for parenting leave during residency

Cree-Green M et al. Academic Pediatrics. Aug 2020.¹⁵

The KidzMed project: Teaching children to swallow tablet medication

Tse Y et al. Archives of Disease in Childhood. November 2020.¹⁶

Dr. Steed is an internal medicine and pediatrics hospitalist at Northwestern Memorial Hospital and Ann and Robert H. Lurie’s Children’s Hospital of Chicago. Dr. Fisher is a current fellow in hospice and palliative medicine and a clinical assistant professor at Michigan State University. Dr. Money is an assistant professor of pediatrics at the University of Utah and a fellowship-trained pediatric hospitalist at Utah Valley Hospital and Primary Children’s Hospital.

References

1. Khan A et al. Association between parent comfort with english and adverse events among hospitalized children. JAMA Pediatr. 2020 Dec 1;174(12):e203215. doi: 10.1001/jamapediatrics.2020.3215.

2. Wasserman M et al. Identifying and preventing medical errors in patients with limited English proficiency: Key findings and tools for the field. J Healthc Qual. May-Jun 2014;36(3):5-16. doi: 10.1111/jhq.12065.

3. Yeung F et al. Saline-lock versus continuous infusion: Maintaining peripheral intravenous catheter access in children. Hosp Pediatr. 2020 Dec;10(12):1038-43. doi: 10.1542/hpeds.2020-0137.

4. Mok E et al. A randomized controlled trial for maintaining peripheral intravenous lock in children. Int J Nurs Pract. 2007 Feb;13(1):33-45. doi: 10.1111/j.1440-172X.2006.00607.x.

5. Coon ER et al. Intensive care unit utilization after adoption of a ward-based high-flow nasal cannula protocol. J Hosp Med. 2020 Jun;15(6):325-30. doi: 10.12788/jhm.3417.

6. Kalburgi S and Halley T. High-flow nasal cannula use outside of the ICU setting. Pediatrics. 2020;146(5):e20194083. doi: 10.1542/peds.2019-4083.

7. Leyenaar JK and Ralston SL. Widespread adoption of low-value therapy: The case of bronchiolitis and high-flow oxygen. Pediatrics. 2020 Nov;146(5):e2020021188. doi: 10.1542/peds.2020-021188.

8. Van Kempen AAMW et al. Lower versus traditional treatment threshold for neonatal hypoglycemia. N Engl J Med. 2020 Feb 6;382(6):534-44. doi: 10.1056/NEJMoa1905593.

9. Shah R et al. Neonatal glycaemia and neurodevelopmental outcomes: A systematic review and meta-analysis. Neonatology. 2019;115(2):116-26. doi: 10.1159/000492859.

10. Feng JY et al. Factors associated with family experience in pediatric inpatient care. Pediatrics. 2020 Mar;145(3):e20191264. doi: 10.1542/peds.2019-1264.

11. Anhang Price R et al. Examining the role of patient experience surveys in measuring health care quality. Med Care Res Rev. 2014 Oct;71(5):522-54. doi: 10.1177/1077558714541480.

12. Coon ER et al. Comparison of as-needed and scheduled posthospitalization follow-up for children hospitalized for bronchiolitis: The Bronchiolitis Follow-up Intervention Trial (BeneFIT) randomized clinical trial. JAMA Pediatr. 2020 Sep 1;174(9):e201937. doi: 10.1001/jamapediatrics.2020.1937.

13. Mintegi S et al. Clinical prediction rule for distinguishing bacterial from aseptic meningitis. Pediatrics. 2020 Sept;146(3): e20201126. doi: 10.1542/peds.2020-1126.

14. Ullman AJ et al. The Michigan Appropriateness Guide for Intravenous Catheters in pediatrics: miniMAGIC. Pediatrics. 2020 Jun;145(Suppl 3):S269-S284. doi: 10.1542/peds.2019-3474I.

15. Cree-Green M et al. A structured neonatal parenting elective: an approach for parenting leave during residency. Acad Pediatr. 2021 Jan-Feb;21(1):16-18. doi: 10.1016/j.acap.2020.02.008.

16. Tse Y et al. The KidzMed project: Teaching children to swallow tablet medication. Arch Dis Child. 2020 Nov;105(11):1105-7. doi: 10.1136/archdischild-2019-317512.

The year 2020 was unlike any in recent history, particularly for those working in health care. With the onset of the SARs-CoV-2 pandemic, many physicians were met with increasing clinical demands, and hospitalists served an instrumental role in providing medical care as the world faced an unprecedented need for health care resources.

In addition, 2020 was a year in which many of us reflected on inequities both inside and outside of medicine. Many in health care witnessed the disproportionate burden that the SARs-CoV-2 pandemic placed on communities of color and inequities pertaining to vaccine distribution.

In spite of the challenges of 2020, the field of pediatric hospital medicine (PHM) has continued to grow and evolve, with an incredible amount of new literature published in 2020.

In this article, we identify the top 10 articles published in 2020, 5 of which are summarized below. These articles were presented at the Pediatric Update at SHM Converge 2021.
 

The top 5 articles

Association between parent comfort with English and adverse events among hospitalized children

Khan A et al. JAMA Pediatrics. December 2020.¹

Background: Hospitalized children experience similar rates of medical errors compared to adult patients, but higher rates in areas that could cause harm.¹ A major contributor to medical errors is communication failure, which language barriers frequently contribute to. Single-center data suggest that pediatric patients of families with limited comfort with English experience increased adverse events,² but multicenter data are lacking.

Findings: This prospective cohort study observed adverse event rates among 2,148 patients from seven teaching hospitals from December 2014 to January 2017. Survey data revealed 147 of 1,666 (9%) parents of patient families expressed limited comfort in English, and Spanish was the predominant language in this group (71%). There were 217 adverse events reported, 142 (65%) of which were deemed preventable by study personnel. Nearly twice as many children of parents with limited comfort with English experienced an adverse event when compared to their English-speaking counterparts (26 of 147 [17.7%] vs. 146 of 1,519 [9.6%]; adjusted odds ratio, 2.1; 95% confidence interval, 1.2-3.7). Interpreter use was not measured.

Impact to practice: Children of parents with limited comfort with English are nearly twice as likely to experience adverse events when hospitalized. Hospitals should reflect on current practice and make efforts to improve their ability to identify and communicate with this vulnerable cohort.
 

Saline-lock versus continuous infusion: Maintaining peripheral intravenous catheter access in children

Yeung F et al. Hospital Pediatrics. December 2020.³

Background: Peripheral intravenous catheter (PIV) insertion is performed on most hospitalized children. Unfortunately, PIVs frequently fail and need to be replaced. There is a widespread perception that infusing a crystalloid solution at a low rate through a PIV, a strategy known as “to keep vein open” (TKO) prolongs the patency of PIVs, however there is a lack of evidence to support this practice.⁴Findings: In this prospective, time-allocated study, 172 children were allocated to either a TKO strategy or a saline-lock strategy with a primary outcome of duration of PIV patency.³ Secondary outcomes included PIV–related complication rates and patient and caregiver satisfaction. The mean duration of PIV patency was 41.68 hours in the TKO group and 44.05 hours in the saline-lock group, which did not meet the prespecified definition of a clinically significant difference. There was no significant difference in prevalence of PIV-associated complications and patient satisfaction was similar between the two groups.

Impact to practice: Running fluid “to keep vein open” does not increase the duration of PIV patency compared to intermittent saline locks. Given that a TKO strategy limits a patient’s mobility, this low-value practice can be discontinued without increasing the risk of PIV failure.
 

Intensive care unit utilization after adoption of a ward-based high flow nasal cannula protocol

Coon ER et al. Journal of Hospital Medicine. June 2020.⁵

Background: High Flow Nasal Cannula (HFNC) has been widely adopted for escalation of respiratory support in patients with bronchiolitis; however, its use is dictated by highly variant local protocols.⁶ Small-scale randomized control trials and systematic reviews show that early HFNC initiation in mild to moderate disease does not change patient outcomes.⁷Findings: In this retrospective cohort study of ward-based HFNC, the authors used the Pediatric Health Information System database to identify 12 hospitals that had adopted ward-based HFNC protocols. The study used an interrupted time series analysis to compare outcomes for patients ages 3-24 months hospitalized with bronchiolitis (n = 32,809) in the three seasons before and after protocol adoption. Ward-based HFNC adoption paradoxically increased ICU admission (absolute increase 3.1%, 95% confidence interval, 2.8-3.4%) and ICU length of stay (absolute difference 9.1 days/100 patients, 95% CI, 5.1-13.2). Total length of stay and rates of mechanical ventilation were similar between groups.⁵Impact to practice: Ward-based HFNC protocols are associated with increased ICU utilization. As bronchiolitis is the leading diagnosis in pediatrics, pediatric hospitals can lead ward-based quality efforts to decrease HFNC overutilization focused on decreased initiation or deimplementation.
 

Lower versus traditional treatment threshold for neonatal hypoglycemia

Van Kempen AAMW et al. New England Journal of Medicine. February 2020.⁸

Background: Hypoglycemia is the most common metabolic abnormality in newborns, and up to 30% of newborns are routinely monitored for hypoglycemia. There is no consensus regarding the appropriate threshold at which hypoglycemia should be treated in order to prevent neurologic injury. Prior studies of neonatal hypoglycemia have largely been observation and have yielded conflicting results.⁸Findings: In this multicenter, randomized, noninferiority trial, 689 infants born at 35 weeks gestational age or later with risk factors for hypoglycemia and a measured blood glucose of 36-46 mg/dL were randomized to either a lower glucose treatment threshold (36 mg/dL) or traditional glucose treatment threshold (47 mg/dL). The primary outcome was psychomotor development at 18 months, assessed via the Bayley Scale of Infant and Toddler Development, third edition. There was no significant difference in cognitive or motor scores at 18 months. The lower treatment threshold group had a higher frequency of severe hypoglycemia (< 36 mg/dL) and were more likely to have four or more episodes of hypoglycemia. The traditional treatment threshold group had more supplemental feeding and more IV glucose administration. Length of stay for the mother and baby did not differ between groups.⁸

Impact to practice: This prospective, randomized study suggests that reducing the treatment threshold for neonatal hypoglycemia did not affect neurodevelopmental at 18 months of age. In contrast, a recent meta-analysis by Shah et al. suggested that neonatal hypoglycemia was not associated with adverse neurodevelopmental outcomes in early childhood; however, differences in rates of neurodevelopmental impairment, low literacy, and low numeracy were detectable by age five.⁹
 

Factors associated with family experience in pediatric inpatient care

Feng JY et al. Pediatrics. March 2020 Mar.¹⁰

Background: Positive patient experience is associated with better health care outcomes and reduced health care use.¹¹ Consequently, patient experience surveys have played a larger role in public reporting, financial risk sharing arrangements, and pay for performance programs. While adult studies have examined the importance of specific care dimensions for patient experience, data are lacking for inpatient pediatric populations.

Findings: A retrospective study collected Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys from 17,727 patients in 69 hospitals within the United States over a 14-month period.¹⁰ Of the 10 care dimensions analyzed, child comfort (aOR 1.50; 95% CI, 1.41-1.60) and nurse-parent communication (aOR 1.50; 95% CI, 1.42-1.58) were most strongly associated with a family’s willingness to recommend a hospital. Additional associated indices included preparing to leave the hospital (aOR 1.34; 95% CI, 1.27-1.41), doctor-parent communication (aOR 1.28; 95% CI, 1.21–1.35), and keeping parents informed (aOR 1.25; 95% CI, 1.18-1.33). Privacy and quietness, which are associated with positive patient experience in adult studies, were not significantly associated with willingness to recommend in this cohort.

Impact to practice: Hospitals seeking to improve patient experience will benefit most by focusing on improving patient comfort and nurse-parent communication. Factors that increase adult patient satisfaction may not be as important to the pediatric population and their families.



The other five articles that comprised the top 10 are listed below:
 

Comparison of as-needed and scheduled posthospitalization follow-up for children hospitalized for bronchiolitis

Coon ER et al. JAMA Pediatrics. September 2020.¹²

Clinical prediction rule for distinguishing bacterial from aseptic meningitis

Mintegi S et al. Pediatrics. September 2020.¹³

The Michigan Appropriateness Guide for Intravenous Catheters in Pediatrics: miniMAGIC Ullman AJ et al. Pediatrics. June 2020.¹⁴

A structured neonatal parenting elective: An approach for parenting leave during residency

Cree-Green M et al. Academic Pediatrics. Aug 2020.¹⁵

The KidzMed project: Teaching children to swallow tablet medication

Tse Y et al. Archives of Disease in Childhood. November 2020.¹⁶

Dr. Steed is an internal medicine and pediatrics hospitalist at Northwestern Memorial Hospital and Ann and Robert H. Lurie’s Children’s Hospital of Chicago. Dr. Fisher is a current fellow in hospice and palliative medicine and a clinical assistant professor at Michigan State University. Dr. Money is an assistant professor of pediatrics at the University of Utah and a fellowship-trained pediatric hospitalist at Utah Valley Hospital and Primary Children’s Hospital.

References

1. Khan A et al. Association between parent comfort with english and adverse events among hospitalized children. JAMA Pediatr. 2020 Dec 1;174(12):e203215. doi: 10.1001/jamapediatrics.2020.3215.

2. Wasserman M et al. Identifying and preventing medical errors in patients with limited English proficiency: Key findings and tools for the field. J Healthc Qual. May-Jun 2014;36(3):5-16. doi: 10.1111/jhq.12065.

3. Yeung F et al. Saline-lock versus continuous infusion: Maintaining peripheral intravenous catheter access in children. Hosp Pediatr. 2020 Dec;10(12):1038-43. doi: 10.1542/hpeds.2020-0137.

4. Mok E et al. A randomized controlled trial for maintaining peripheral intravenous lock in children. Int J Nurs Pract. 2007 Feb;13(1):33-45. doi: 10.1111/j.1440-172X.2006.00607.x.

5. Coon ER et al. Intensive care unit utilization after adoption of a ward-based high-flow nasal cannula protocol. J Hosp Med. 2020 Jun;15(6):325-30. doi: 10.12788/jhm.3417.

6. Kalburgi S and Halley T. High-flow nasal cannula use outside of the ICU setting. Pediatrics. 2020;146(5):e20194083. doi: 10.1542/peds.2019-4083.

7. Leyenaar JK and Ralston SL. Widespread adoption of low-value therapy: The case of bronchiolitis and high-flow oxygen. Pediatrics. 2020 Nov;146(5):e2020021188. doi: 10.1542/peds.2020-021188.

8. Van Kempen AAMW et al. Lower versus traditional treatment threshold for neonatal hypoglycemia. N Engl J Med. 2020 Feb 6;382(6):534-44. doi: 10.1056/NEJMoa1905593.

9. Shah R et al. Neonatal glycaemia and neurodevelopmental outcomes: A systematic review and meta-analysis. Neonatology. 2019;115(2):116-26. doi: 10.1159/000492859.

10. Feng JY et al. Factors associated with family experience in pediatric inpatient care. Pediatrics. 2020 Mar;145(3):e20191264. doi: 10.1542/peds.2019-1264.

11. Anhang Price R et al. Examining the role of patient experience surveys in measuring health care quality. Med Care Res Rev. 2014 Oct;71(5):522-54. doi: 10.1177/1077558714541480.

12. Coon ER et al. Comparison of as-needed and scheduled posthospitalization follow-up for children hospitalized for bronchiolitis: The Bronchiolitis Follow-up Intervention Trial (BeneFIT) randomized clinical trial. JAMA Pediatr. 2020 Sep 1;174(9):e201937. doi: 10.1001/jamapediatrics.2020.1937.

13. Mintegi S et al. Clinical prediction rule for distinguishing bacterial from aseptic meningitis. Pediatrics. 2020 Sept;146(3): e20201126. doi: 10.1542/peds.2020-1126.

14. Ullman AJ et al. The Michigan Appropriateness Guide for Intravenous Catheters in pediatrics: miniMAGIC. Pediatrics. 2020 Jun;145(Suppl 3):S269-S284. doi: 10.1542/peds.2019-3474I.

15. Cree-Green M et al. A structured neonatal parenting elective: an approach for parenting leave during residency. Acad Pediatr. 2021 Jan-Feb;21(1):16-18. doi: 10.1016/j.acap.2020.02.008.

16. Tse Y et al. The KidzMed project: Teaching children to swallow tablet medication. Arch Dis Child. 2020 Nov;105(11):1105-7. doi: 10.1136/archdischild-2019-317512.

The year 2020 was unlike any in recent history, particularly for those working in health care. With the onset of the SARs-CoV-2 pandemic, many physicians were met with increasing clinical demands, and hospitalists served an instrumental role in providing medical care as the world faced an unprecedented need for health care resources.

In addition, 2020 was a year in which many of us reflected on inequities both inside and outside of medicine. Many in health care witnessed the disproportionate burden that the SARs-CoV-2 pandemic placed on communities of color and inequities pertaining to vaccine distribution.

In spite of the challenges of 2020, the field of pediatric hospital medicine (PHM) has continued to grow and evolve, with an incredible amount of new literature published in 2020.

In this article, we identify the top 10 articles published in 2020, 5 of which are summarized below. These articles were presented at the Pediatric Update at SHM Converge 2021.
 

The top 5 articles

Association between parent comfort with English and adverse events among hospitalized children

Khan A et al. JAMA Pediatrics. December 2020.¹

Background: Hospitalized children experience similar rates of medical errors compared to adult patients, but higher rates in areas that could cause harm.¹ A major contributor to medical errors is communication failure, which language barriers frequently contribute to. Single-center data suggest that pediatric patients of families with limited comfort with English experience increased adverse events,² but multicenter data are lacking.

Findings: This prospective cohort study observed adverse event rates among 2,148 patients from seven teaching hospitals from December 2014 to January 2017. Survey data revealed 147 of 1,666 (9%) parents of patient families expressed limited comfort in English, and Spanish was the predominant language in this group (71%). There were 217 adverse events reported, 142 (65%) of which were deemed preventable by study personnel. Nearly twice as many children of parents with limited comfort with English experienced an adverse event when compared to their English-speaking counterparts (26 of 147 [17.7%] vs. 146 of 1,519 [9.6%]; adjusted odds ratio, 2.1; 95% confidence interval, 1.2-3.7). Interpreter use was not measured.

Impact to practice: Children of parents with limited comfort with English are nearly twice as likely to experience adverse events when hospitalized. Hospitals should reflect on current practice and make efforts to improve their ability to identify and communicate with this vulnerable cohort.
 

Saline-lock versus continuous infusion: Maintaining peripheral intravenous catheter access in children

Yeung F et al. Hospital Pediatrics. December 2020.³

Background: Peripheral intravenous catheter (PIV) insertion is performed on most hospitalized children. Unfortunately, PIVs frequently fail and need to be replaced. There is a widespread perception that infusing a crystalloid solution at a low rate through a PIV, a strategy known as “to keep vein open” (TKO) prolongs the patency of PIVs, however there is a lack of evidence to support this practice.⁴Findings: In this prospective, time-allocated study, 172 children were allocated to either a TKO strategy or a saline-lock strategy with a primary outcome of duration of PIV patency.³ Secondary outcomes included PIV–related complication rates and patient and caregiver satisfaction. The mean duration of PIV patency was 41.68 hours in the TKO group and 44.05 hours in the saline-lock group, which did not meet the prespecified definition of a clinically significant difference. There was no significant difference in prevalence of PIV-associated complications and patient satisfaction was similar between the two groups.

Impact to practice: Running fluid “to keep vein open” does not increase the duration of PIV patency compared to intermittent saline locks. Given that a TKO strategy limits a patient’s mobility, this low-value practice can be discontinued without increasing the risk of PIV failure.
 

Intensive care unit utilization after adoption of a ward-based high flow nasal cannula protocol

Coon ER et al. Journal of Hospital Medicine. June 2020.⁵

Background: High Flow Nasal Cannula (HFNC) has been widely adopted for escalation of respiratory support in patients with bronchiolitis; however, its use is dictated by highly variant local protocols.⁶ Small-scale randomized control trials and systematic reviews show that early HFNC initiation in mild to moderate disease does not change patient outcomes.⁷Findings: In this retrospective cohort study of ward-based HFNC, the authors used the Pediatric Health Information System database to identify 12 hospitals that had adopted ward-based HFNC protocols. The study used an interrupted time series analysis to compare outcomes for patients ages 3-24 months hospitalized with bronchiolitis (n = 32,809) in the three seasons before and after protocol adoption. Ward-based HFNC adoption paradoxically increased ICU admission (absolute increase 3.1%, 95% confidence interval, 2.8-3.4%) and ICU length of stay (absolute difference 9.1 days/100 patients, 95% CI, 5.1-13.2). Total length of stay and rates of mechanical ventilation were similar between groups.⁵Impact to practice: Ward-based HFNC protocols are associated with increased ICU utilization. As bronchiolitis is the leading diagnosis in pediatrics, pediatric hospitals can lead ward-based quality efforts to decrease HFNC overutilization focused on decreased initiation or deimplementation.
 

Lower versus traditional treatment threshold for neonatal hypoglycemia

Van Kempen AAMW et al. New England Journal of Medicine. February 2020.⁸

Background: Hypoglycemia is the most common metabolic abnormality in newborns, and up to 30% of newborns are routinely monitored for hypoglycemia. There is no consensus regarding the appropriate threshold at which hypoglycemia should be treated in order to prevent neurologic injury. Prior studies of neonatal hypoglycemia have largely been observation and have yielded conflicting results.⁸Findings: In this multicenter, randomized, noninferiority trial, 689 infants born at 35 weeks gestational age or later with risk factors for hypoglycemia and a measured blood glucose of 36-46 mg/dL were randomized to either a lower glucose treatment threshold (36 mg/dL) or traditional glucose treatment threshold (47 mg/dL). The primary outcome was psychomotor development at 18 months, assessed via the Bayley Scale of Infant and Toddler Development, third edition. There was no significant difference in cognitive or motor scores at 18 months. The lower treatment threshold group had a higher frequency of severe hypoglycemia (< 36 mg/dL) and were more likely to have four or more episodes of hypoglycemia. The traditional treatment threshold group had more supplemental feeding and more IV glucose administration. Length of stay for the mother and baby did not differ between groups.⁸

Impact to practice: This prospective, randomized study suggests that reducing the treatment threshold for neonatal hypoglycemia did not affect neurodevelopmental at 18 months of age. In contrast, a recent meta-analysis by Shah et al. suggested that neonatal hypoglycemia was not associated with adverse neurodevelopmental outcomes in early childhood; however, differences in rates of neurodevelopmental impairment, low literacy, and low numeracy were detectable by age five.⁹
 

Factors associated with family experience in pediatric inpatient care

Feng JY et al. Pediatrics. March 2020 Mar.¹⁰

Background: Positive patient experience is associated with better health care outcomes and reduced health care use.¹¹ Consequently, patient experience surveys have played a larger role in public reporting, financial risk sharing arrangements, and pay for performance programs. While adult studies have examined the importance of specific care dimensions for patient experience, data are lacking for inpatient pediatric populations.

Findings: A retrospective study collected Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys from 17,727 patients in 69 hospitals within the United States over a 14-month period.¹⁰ Of the 10 care dimensions analyzed, child comfort (aOR 1.50; 95% CI, 1.41-1.60) and nurse-parent communication (aOR 1.50; 95% CI, 1.42-1.58) were most strongly associated with a family’s willingness to recommend a hospital. Additional associated indices included preparing to leave the hospital (aOR 1.34; 95% CI, 1.27-1.41), doctor-parent communication (aOR 1.28; 95% CI, 1.21–1.35), and keeping parents informed (aOR 1.25; 95% CI, 1.18-1.33). Privacy and quietness, which are associated with positive patient experience in adult studies, were not significantly associated with willingness to recommend in this cohort.

Impact to practice: Hospitals seeking to improve patient experience will benefit most by focusing on improving patient comfort and nurse-parent communication. Factors that increase adult patient satisfaction may not be as important to the pediatric population and their families.



The other five articles that comprised the top 10 are listed below:
 

Comparison of as-needed and scheduled posthospitalization follow-up for children hospitalized for bronchiolitis

Coon ER et al. JAMA Pediatrics. September 2020.¹²

Clinical prediction rule for distinguishing bacterial from aseptic meningitis

Mintegi S et al. Pediatrics. September 2020.¹³

The Michigan Appropriateness Guide for Intravenous Catheters in Pediatrics: miniMAGIC Ullman AJ et al. Pediatrics. June 2020.¹⁴

A structured neonatal parenting elective: An approach for parenting leave during residency

Cree-Green M et al. Academic Pediatrics. Aug 2020.¹⁵

The KidzMed project: Teaching children to swallow tablet medication

Tse Y et al. Archives of Disease in Childhood. November 2020.¹⁶

Dr. Steed is an internal medicine and pediatrics hospitalist at Northwestern Memorial Hospital and Ann and Robert H. Lurie’s Children’s Hospital of Chicago. Dr. Fisher is a current fellow in hospice and palliative medicine and a clinical assistant professor at Michigan State University. Dr. Money is an assistant professor of pediatrics at the University of Utah and a fellowship-trained pediatric hospitalist at Utah Valley Hospital and Primary Children’s Hospital.

References

1. Khan A et al. Association between parent comfort with english and adverse events among hospitalized children. JAMA Pediatr. 2020 Dec 1;174(12):e203215. doi: 10.1001/jamapediatrics.2020.3215.

2. Wasserman M et al. Identifying and preventing medical errors in patients with limited English proficiency: Key findings and tools for the field. J Healthc Qual. May-Jun 2014;36(3):5-16. doi: 10.1111/jhq.12065.

3. Yeung F et al. Saline-lock versus continuous infusion: Maintaining peripheral intravenous catheter access in children. Hosp Pediatr. 2020 Dec;10(12):1038-43. doi: 10.1542/hpeds.2020-0137.

4. Mok E et al. A randomized controlled trial for maintaining peripheral intravenous lock in children. Int J Nurs Pract. 2007 Feb;13(1):33-45. doi: 10.1111/j.1440-172X.2006.00607.x.

5. Coon ER et al. Intensive care unit utilization after adoption of a ward-based high-flow nasal cannula protocol. J Hosp Med. 2020 Jun;15(6):325-30. doi: 10.12788/jhm.3417.

6. Kalburgi S and Halley T. High-flow nasal cannula use outside of the ICU setting. Pediatrics. 2020;146(5):e20194083. doi: 10.1542/peds.2019-4083.

7. Leyenaar JK and Ralston SL. Widespread adoption of low-value therapy: The case of bronchiolitis and high-flow oxygen. Pediatrics. 2020 Nov;146(5):e2020021188. doi: 10.1542/peds.2020-021188.

8. Van Kempen AAMW et al. Lower versus traditional treatment threshold for neonatal hypoglycemia. N Engl J Med. 2020 Feb 6;382(6):534-44. doi: 10.1056/NEJMoa1905593.

9. Shah R et al. Neonatal glycaemia and neurodevelopmental outcomes: A systematic review and meta-analysis. Neonatology. 2019;115(2):116-26. doi: 10.1159/000492859.

10. Feng JY et al. Factors associated with family experience in pediatric inpatient care. Pediatrics. 2020 Mar;145(3):e20191264. doi: 10.1542/peds.2019-1264.

11. Anhang Price R et al. Examining the role of patient experience surveys in measuring health care quality. Med Care Res Rev. 2014 Oct;71(5):522-54. doi: 10.1177/1077558714541480.

12. Coon ER et al. Comparison of as-needed and scheduled posthospitalization follow-up for children hospitalized for bronchiolitis: The Bronchiolitis Follow-up Intervention Trial (BeneFIT) randomized clinical trial. JAMA Pediatr. 2020 Sep 1;174(9):e201937. doi: 10.1001/jamapediatrics.2020.1937.

13. Mintegi S et al. Clinical prediction rule for distinguishing bacterial from aseptic meningitis. Pediatrics. 2020 Sept;146(3): e20201126. doi: 10.1542/peds.2020-1126.

14. Ullman AJ et al. The Michigan Appropriateness Guide for Intravenous Catheters in pediatrics: miniMAGIC. Pediatrics. 2020 Jun;145(Suppl 3):S269-S284. doi: 10.1542/peds.2019-3474I.

15. Cree-Green M et al. A structured neonatal parenting elective: an approach for parenting leave during residency. Acad Pediatr. 2021 Jan-Feb;21(1):16-18. doi: 10.1016/j.acap.2020.02.008.

16. Tse Y et al. The KidzMed project: Teaching children to swallow tablet medication. Arch Dis Child. 2020 Nov;105(11):1105-7. doi: 10.1136/archdischild-2019-317512.

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the adjuvant treatment of stage IIB and IIC melanoma after complete resection in adults and children over age 12 years. The FDA also extended the approval to those with stage III disease.

The FDA approval on Dec. 3 was based on first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease. 

Since the anti-PD-1 therapy was approved in metastatic melanoma 7 years ago, “we have built on this foundation in melanoma and have expanded the use of KEYTRUDA into earlier stages of this disease,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “With today’s approval, we can now offer health care providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC, and stage III melanoma.”

In KEYNOTE-716, patients with completely resected stage IIB or IIC melanoma were randomly assigned to receive 200 mg of intravenous pembrolizumab, the pediatric dose 2 mg/kg (up to a maximum of 200 mg) every 3 weeks, or placebo for up to 1 year until disease recurrence or unacceptable toxicity.

After a median follow-up of 14.4 months, investigators reported a statistically significant 35% improvement in recurrence-free survival (RFS) in those treated with pembrolizumab, compared with those who received placebo (hazard ratio, 0.65).

The most common adverse reactions reported in patients receiving pembrolizumab in KEYNOTE-716 were fatigue, diarrhea, pruritus, and arthralgia, each occurring in at least 20% of patients.

“Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda,” according to Merck.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the adjuvant treatment of stage IIB and IIC melanoma after complete resection in adults and children over age 12 years. The FDA also extended the approval to those with stage III disease.

The FDA approval on Dec. 3 was based on first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease. 

Since the anti-PD-1 therapy was approved in metastatic melanoma 7 years ago, “we have built on this foundation in melanoma and have expanded the use of KEYTRUDA into earlier stages of this disease,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “With today’s approval, we can now offer health care providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC, and stage III melanoma.”

In KEYNOTE-716, patients with completely resected stage IIB or IIC melanoma were randomly assigned to receive 200 mg of intravenous pembrolizumab, the pediatric dose 2 mg/kg (up to a maximum of 200 mg) every 3 weeks, or placebo for up to 1 year until disease recurrence or unacceptable toxicity.

After a median follow-up of 14.4 months, investigators reported a statistically significant 35% improvement in recurrence-free survival (RFS) in those treated with pembrolizumab, compared with those who received placebo (hazard ratio, 0.65).

The most common adverse reactions reported in patients receiving pembrolizumab in KEYNOTE-716 were fatigue, diarrhea, pruritus, and arthralgia, each occurring in at least 20% of patients.

“Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda,” according to Merck.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the adjuvant treatment of stage IIB and IIC melanoma after complete resection in adults and children over age 12 years. The FDA also extended the approval to those with stage III disease.

The FDA approval on Dec. 3 was based on first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease. 

Since the anti-PD-1 therapy was approved in metastatic melanoma 7 years ago, “we have built on this foundation in melanoma and have expanded the use of KEYTRUDA into earlier stages of this disease,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “With today’s approval, we can now offer health care providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC, and stage III melanoma.”

In KEYNOTE-716, patients with completely resected stage IIB or IIC melanoma were randomly assigned to receive 200 mg of intravenous pembrolizumab, the pediatric dose 2 mg/kg (up to a maximum of 200 mg) every 3 weeks, or placebo for up to 1 year until disease recurrence or unacceptable toxicity.

After a median follow-up of 14.4 months, investigators reported a statistically significant 35% improvement in recurrence-free survival (RFS) in those treated with pembrolizumab, compared with those who received placebo (hazard ratio, 0.65).

The most common adverse reactions reported in patients receiving pembrolizumab in KEYNOTE-716 were fatigue, diarrhea, pruritus, and arthralgia, each occurring in at least 20% of patients.

“Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda,” according to Merck.

A version of this article first appeared on Medscape.com.

An abstract and poster presentation questioning the safety of mRNA-based COVID-19 vaccines, embraced by some and lambasted by others, has drawn an “expression of concern” from the American Heart Association, along with a bid for correction.

The abstract in question concludes that COVID vaccines “dramatically increase” levels of certain inflammatory biomarkers, and therefore, the 5-year risk of acute coronary syndromes (ACS), based on pre- and post-vaccination results of an obscure blood panel called the PULS Cardiac Test (GD Biosciences). The findings were presented at the AHA’s 2021 Scientific Sessionsas, an uncontrolled observational study of 566 patients in a preventive cardiology practice.

Some on social media have seized on the abstract as evidence of serious potential harm from the two available mRNA-based SARS-CoV-2 vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). But others contend that the study’s described design and findings are specious and its conclusions overstated.

They also point to the notoriety of its one listed author, Steven R. Gundry, MD, who promotes his diet books and supplements as well as fringe, highly criticized theories about diet and disease on several websites, including drgundry.com. Dr. Gundry has not responded to requests for an interview.

Dr. Gundry’s abstract from the AHA Scientific Sessions 2021, available on the meeting’s program planner, was marked with an “expression of concern” by the AHA that is to stand “until a suitable correction is published, to indicate that the abstract in its current version may not be reliable.”

The expression of concern statement, also published online Nov. 24 in Circulation, says “potential errors in the abstract” were brought to the attention of the meeting planners. “Specifically, there are several typographical errors, there is no data in the abstract regarding myocardial T-cell infiltration, there are no statistical analyses for significance provided, and the author is not clear that only anecdotal data was used.”

The biomarker elevations on which the abstract’s conclusions are based included hepatocyte growth factor, “which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue,” it states.

“The expression of concern about the abstract will remain in place until a correction is accepted and published” in Circulation, AHA spokesperson Suzanne Grant told this news organization by email.

“The specific data needed will be up to the abstract author to determine and supply,” she said, noting that Dr. Gundry “has been in communication with the journal throughout this process.”

Submitting researchers “must always attest to the validity of the abstract,” Ms. Grant said. “Abstracts are then curated by independent review panels, blinded to the identities of the abstract authors, and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting.”

Regarding the AHA’s system for vetting abstracts vying for acceptance to the scientific sessions, she said it is not primarily intended to “evaluate scientific validity” and that the organization is “currently reviewing its existing abstract submission processes.”

A recent Reuters report reviews the controversy and provides links to criticisms of the study on social media.

A version of this article first appeared on Medscape.com.

An abstract and poster presentation questioning the safety of mRNA-based COVID-19 vaccines, embraced by some and lambasted by others, has drawn an “expression of concern” from the American Heart Association, along with a bid for correction.

The abstract in question concludes that COVID vaccines “dramatically increase” levels of certain inflammatory biomarkers, and therefore, the 5-year risk of acute coronary syndromes (ACS), based on pre- and post-vaccination results of an obscure blood panel called the PULS Cardiac Test (GD Biosciences). The findings were presented at the AHA’s 2021 Scientific Sessionsas, an uncontrolled observational study of 566 patients in a preventive cardiology practice.

Some on social media have seized on the abstract as evidence of serious potential harm from the two available mRNA-based SARS-CoV-2 vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). But others contend that the study’s described design and findings are specious and its conclusions overstated.

They also point to the notoriety of its one listed author, Steven R. Gundry, MD, who promotes his diet books and supplements as well as fringe, highly criticized theories about diet and disease on several websites, including drgundry.com. Dr. Gundry has not responded to requests for an interview.

Dr. Gundry’s abstract from the AHA Scientific Sessions 2021, available on the meeting’s program planner, was marked with an “expression of concern” by the AHA that is to stand “until a suitable correction is published, to indicate that the abstract in its current version may not be reliable.”

The expression of concern statement, also published online Nov. 24 in Circulation, says “potential errors in the abstract” were brought to the attention of the meeting planners. “Specifically, there are several typographical errors, there is no data in the abstract regarding myocardial T-cell infiltration, there are no statistical analyses for significance provided, and the author is not clear that only anecdotal data was used.”

The biomarker elevations on which the abstract’s conclusions are based included hepatocyte growth factor, “which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue,” it states.

“The expression of concern about the abstract will remain in place until a correction is accepted and published” in Circulation, AHA spokesperson Suzanne Grant told this news organization by email.

“The specific data needed will be up to the abstract author to determine and supply,” she said, noting that Dr. Gundry “has been in communication with the journal throughout this process.”

Submitting researchers “must always attest to the validity of the abstract,” Ms. Grant said. “Abstracts are then curated by independent review panels, blinded to the identities of the abstract authors, and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting.”

Regarding the AHA’s system for vetting abstracts vying for acceptance to the scientific sessions, she said it is not primarily intended to “evaluate scientific validity” and that the organization is “currently reviewing its existing abstract submission processes.”

A recent Reuters report reviews the controversy and provides links to criticisms of the study on social media.

A version of this article first appeared on Medscape.com.

An abstract and poster presentation questioning the safety of mRNA-based COVID-19 vaccines, embraced by some and lambasted by others, has drawn an “expression of concern” from the American Heart Association, along with a bid for correction.

The abstract in question concludes that COVID vaccines “dramatically increase” levels of certain inflammatory biomarkers, and therefore, the 5-year risk of acute coronary syndromes (ACS), based on pre- and post-vaccination results of an obscure blood panel called the PULS Cardiac Test (GD Biosciences). The findings were presented at the AHA’s 2021 Scientific Sessionsas, an uncontrolled observational study of 566 patients in a preventive cardiology practice.

Some on social media have seized on the abstract as evidence of serious potential harm from the two available mRNA-based SARS-CoV-2 vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). But others contend that the study’s described design and findings are specious and its conclusions overstated.

They also point to the notoriety of its one listed author, Steven R. Gundry, MD, who promotes his diet books and supplements as well as fringe, highly criticized theories about diet and disease on several websites, including drgundry.com. Dr. Gundry has not responded to requests for an interview.

Dr. Gundry’s abstract from the AHA Scientific Sessions 2021, available on the meeting’s program planner, was marked with an “expression of concern” by the AHA that is to stand “until a suitable correction is published, to indicate that the abstract in its current version may not be reliable.”

The expression of concern statement, also published online Nov. 24 in Circulation, says “potential errors in the abstract” were brought to the attention of the meeting planners. “Specifically, there are several typographical errors, there is no data in the abstract regarding myocardial T-cell infiltration, there are no statistical analyses for significance provided, and the author is not clear that only anecdotal data was used.”

The biomarker elevations on which the abstract’s conclusions are based included hepatocyte growth factor, “which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue,” it states.

“The expression of concern about the abstract will remain in place until a correction is accepted and published” in Circulation, AHA spokesperson Suzanne Grant told this news organization by email.

“The specific data needed will be up to the abstract author to determine and supply,” she said, noting that Dr. Gundry “has been in communication with the journal throughout this process.”

Submitting researchers “must always attest to the validity of the abstract,” Ms. Grant said. “Abstracts are then curated by independent review panels, blinded to the identities of the abstract authors, and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting.”

Regarding the AHA’s system for vetting abstracts vying for acceptance to the scientific sessions, she said it is not primarily intended to “evaluate scientific validity” and that the organization is “currently reviewing its existing abstract submission processes.”

A recent Reuters report reviews the controversy and provides links to criticisms of the study on social media.

A version of this article first appeared on Medscape.com.

Louisiana Gov. John Bel Edwards says the state government plans to make the COVID-19 vaccine a required immunization for students 16 and older in the state’s public school system.

“I just think it’s really, really important to embrace the science and really it’s also important to not engage in misinformation,” said Gov. Edwards, a Democrat, according to The Advocate. “Absent some compelling reason, which I at present have not seen, I fully expect that we will be adding the vaccine to the schedule.”

Parents could opt out their children from the requirement with a letter from a medical provider or a simple signature in dissent, The Advocate reported. The new rule would go into effect at the start of the 2022 school year and at first would apply to students aged 16 and older.

Republican legislators voiced their opposition to the COVID-19 vaccine requirement at a hearing on Dec. 6, calling it unneeded and an example of governmental overreach.

“I believe the vaccine should be highly recommended but not mandated,” state Rep. Laurie Schlegel said, according to TV station WDSU.

State Sen. Cameron Henry of Metairie said he received “hundreds of emails” from parents asking him to prevent the rule from going into effect, WDSU said.

WDSU said the governor can overrule the committee if it rejects the proposed vaccine rule.

Louisiana State Health Officer Joseph Kanter, MD, testified on Dec. 6 that 18 children had died of COVID-19 in Louisiana and many others had become sick because of it.

“I can’t think of another disease on that childhood schedule that we’ve lost that many kids from. In my mind, it’s very much in the public interest. But it’s the family and the parents’ decision,” Dr. Kanter said.

The addition of the vaccine is being proposed by the Louisiana Department of Health, which has added other vaccines to the required list over the years. In 2015, the legislature added meningitis as a required shot with no controversy, The Advocate said.

A version of this article first appeared on WebMD.com.

Louisiana Gov. John Bel Edwards says the state government plans to make the COVID-19 vaccine a required immunization for students 16 and older in the state’s public school system.

“I just think it’s really, really important to embrace the science and really it’s also important to not engage in misinformation,” said Gov. Edwards, a Democrat, according to The Advocate. “Absent some compelling reason, which I at present have not seen, I fully expect that we will be adding the vaccine to the schedule.”

Parents could opt out their children from the requirement with a letter from a medical provider or a simple signature in dissent, The Advocate reported. The new rule would go into effect at the start of the 2022 school year and at first would apply to students aged 16 and older.

Republican legislators voiced their opposition to the COVID-19 vaccine requirement at a hearing on Dec. 6, calling it unneeded and an example of governmental overreach.

“I believe the vaccine should be highly recommended but not mandated,” state Rep. Laurie Schlegel said, according to TV station WDSU.

State Sen. Cameron Henry of Metairie said he received “hundreds of emails” from parents asking him to prevent the rule from going into effect, WDSU said.

WDSU said the governor can overrule the committee if it rejects the proposed vaccine rule.

Louisiana State Health Officer Joseph Kanter, MD, testified on Dec. 6 that 18 children had died of COVID-19 in Louisiana and many others had become sick because of it.

“I can’t think of another disease on that childhood schedule that we’ve lost that many kids from. In my mind, it’s very much in the public interest. But it’s the family and the parents’ decision,” Dr. Kanter said.

The addition of the vaccine is being proposed by the Louisiana Department of Health, which has added other vaccines to the required list over the years. In 2015, the legislature added meningitis as a required shot with no controversy, The Advocate said.

A version of this article first appeared on WebMD.com.

Louisiana Gov. John Bel Edwards says the state government plans to make the COVID-19 vaccine a required immunization for students 16 and older in the state’s public school system.

“I just think it’s really, really important to embrace the science and really it’s also important to not engage in misinformation,” said Gov. Edwards, a Democrat, according to The Advocate. “Absent some compelling reason, which I at present have not seen, I fully expect that we will be adding the vaccine to the schedule.”

Parents could opt out their children from the requirement with a letter from a medical provider or a simple signature in dissent, The Advocate reported. The new rule would go into effect at the start of the 2022 school year and at first would apply to students aged 16 and older.

Republican legislators voiced their opposition to the COVID-19 vaccine requirement at a hearing on Dec. 6, calling it unneeded and an example of governmental overreach.

“I believe the vaccine should be highly recommended but not mandated,” state Rep. Laurie Schlegel said, according to TV station WDSU.

State Sen. Cameron Henry of Metairie said he received “hundreds of emails” from parents asking him to prevent the rule from going into effect, WDSU said.

WDSU said the governor can overrule the committee if it rejects the proposed vaccine rule.

Louisiana State Health Officer Joseph Kanter, MD, testified on Dec. 6 that 18 children had died of COVID-19 in Louisiana and many others had become sick because of it.

“I can’t think of another disease on that childhood schedule that we’ve lost that many kids from. In my mind, it’s very much in the public interest. But it’s the family and the parents’ decision,” Dr. Kanter said.

The addition of the vaccine is being proposed by the Louisiana Department of Health, which has added other vaccines to the required list over the years. In 2015, the legislature added meningitis as a required shot with no controversy, The Advocate said.

A version of this article first appeared on WebMD.com.

The erectile dysfunction medication Viagra could potentially be used as a treatment for Alzheimer’s disease, according to a new study published in the journal Nature Aging.

Patients who used the drug sildenafil, the generic name for Viagra, were 69% less likely to develop the disease than were nonusers.

“Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate,” Feixiong Cheng, PhD, the lead study author in the Cleveland Clinic’s Genomic Medicine Institute, said in a statement.

“Notably, we found that sildenafil use reduced the likelihood of Alzheimer’s in individuals with coronary artery disease, hypertension, and type 2 diabetes, all of which are comorbidities significantly associated with risk of the disease, as well as in those without,” he said.

Alzheimer’s, which is the most common form of age-related dementia, affects hundreds of millions of people worldwide. The disease is expected to affect nearly 14 million Americans by 2050. There is no approved treatment for it.

Dr. Cheng and colleagues at the Cleveland Clinic used a large gene-mapping network to analyze whether more than 1,600 Food and Drug Administration–approved drugs could work against Alzheimer’s. They gave higher scores to drugs that target both amyloid and tau proteins in the brain, which are two hallmarks of the disease. Sildenafil appeared at the top of the list.

Then the researchers used a database of health insurance claims for more than 7 million people in the U.S. to understand the relationship between sildenafil and Alzheimer’s disease outcomes. They compared sildenafil users to nonusers and found that those who used the drug were 69% less likely to have the neurodegenerative disease, even after 6 years of follow-up.

After that, the research team came up with a lab model that showed the sildenafil increased brain cell growth and targeted tau proteins. The lab model could indicate how the drug influences disease-related brain changes.

But Dr. Cheng cautioned against drawing strong conclusions. The study doesn’t demonstrate a causal relationship between sildenafil and Alzheimer’s disease. Researchers will need to conduct clinical trials with a placebo control to see how well the drug works.

Other researchers said the findings offer a new avenue for research but don’t yet provide solid answers.

“Being able to repurpose a drug already licensed for health conditions could help speed up the drug discovery process and bring about life-changing dementia treatments sooner,” Susan Kohlhaas, PhD, director of research at Alzheimer’s Research UK, told the Science Media Centre.

“Importantly, this research doesn’t prove that sildenafil is responsible for reducing dementia risk, or that it slows or stops the disease,” she continued. “If you want to discuss any treatments you are receiving, the first port of call is to speak to your doctor.”

And doctors won’t likely recommend it as a treatment just yet either.

“While these data are interesting scientifically, based on this study, I would not rush out to start taking sildenafil as a prevention for Alzheimer’s disease,” Tara Spires-Jones, PhD, deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh, told the Science Media Centre.

A version of this article first appeared on WebMD.com.

The erectile dysfunction medication Viagra could potentially be used as a treatment for Alzheimer’s disease, according to a new study published in the journal Nature Aging.

Patients who used the drug sildenafil, the generic name for Viagra, were 69% less likely to develop the disease than were nonusers.

“Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate,” Feixiong Cheng, PhD, the lead study author in the Cleveland Clinic’s Genomic Medicine Institute, said in a statement.

“Notably, we found that sildenafil use reduced the likelihood of Alzheimer’s in individuals with coronary artery disease, hypertension, and type 2 diabetes, all of which are comorbidities significantly associated with risk of the disease, as well as in those without,” he said.

Alzheimer’s, which is the most common form of age-related dementia, affects hundreds of millions of people worldwide. The disease is expected to affect nearly 14 million Americans by 2050. There is no approved treatment for it.

Dr. Cheng and colleagues at the Cleveland Clinic used a large gene-mapping network to analyze whether more than 1,600 Food and Drug Administration–approved drugs could work against Alzheimer’s. They gave higher scores to drugs that target both amyloid and tau proteins in the brain, which are two hallmarks of the disease. Sildenafil appeared at the top of the list.

Then the researchers used a database of health insurance claims for more than 7 million people in the U.S. to understand the relationship between sildenafil and Alzheimer’s disease outcomes. They compared sildenafil users to nonusers and found that those who used the drug were 69% less likely to have the neurodegenerative disease, even after 6 years of follow-up.

After that, the research team came up with a lab model that showed the sildenafil increased brain cell growth and targeted tau proteins. The lab model could indicate how the drug influences disease-related brain changes.

But Dr. Cheng cautioned against drawing strong conclusions. The study doesn’t demonstrate a causal relationship between sildenafil and Alzheimer’s disease. Researchers will need to conduct clinical trials with a placebo control to see how well the drug works.

Other researchers said the findings offer a new avenue for research but don’t yet provide solid answers.

“Being able to repurpose a drug already licensed for health conditions could help speed up the drug discovery process and bring about life-changing dementia treatments sooner,” Susan Kohlhaas, PhD, director of research at Alzheimer’s Research UK, told the Science Media Centre.

“Importantly, this research doesn’t prove that sildenafil is responsible for reducing dementia risk, or that it slows or stops the disease,” she continued. “If you want to discuss any treatments you are receiving, the first port of call is to speak to your doctor.”

And doctors won’t likely recommend it as a treatment just yet either.

“While these data are interesting scientifically, based on this study, I would not rush out to start taking sildenafil as a prevention for Alzheimer’s disease,” Tara Spires-Jones, PhD, deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh, told the Science Media Centre.

A version of this article first appeared on WebMD.com.

The erectile dysfunction medication Viagra could potentially be used as a treatment for Alzheimer’s disease, according to a new study published in the journal Nature Aging.

Patients who used the drug sildenafil, the generic name for Viagra, were 69% less likely to develop the disease than were nonusers.

“Sildenafil, which has been shown to significantly improve cognition and memory in preclinical models, presented as the best drug candidate,” Feixiong Cheng, PhD, the lead study author in the Cleveland Clinic’s Genomic Medicine Institute, said in a statement.

“Notably, we found that sildenafil use reduced the likelihood of Alzheimer’s in individuals with coronary artery disease, hypertension, and type 2 diabetes, all of which are comorbidities significantly associated with risk of the disease, as well as in those without,” he said.

Alzheimer’s, which is the most common form of age-related dementia, affects hundreds of millions of people worldwide. The disease is expected to affect nearly 14 million Americans by 2050. There is no approved treatment for it.

Dr. Cheng and colleagues at the Cleveland Clinic used a large gene-mapping network to analyze whether more than 1,600 Food and Drug Administration–approved drugs could work against Alzheimer’s. They gave higher scores to drugs that target both amyloid and tau proteins in the brain, which are two hallmarks of the disease. Sildenafil appeared at the top of the list.

Then the researchers used a database of health insurance claims for more than 7 million people in the U.S. to understand the relationship between sildenafil and Alzheimer’s disease outcomes. They compared sildenafil users to nonusers and found that those who used the drug were 69% less likely to have the neurodegenerative disease, even after 6 years of follow-up.

After that, the research team came up with a lab model that showed the sildenafil increased brain cell growth and targeted tau proteins. The lab model could indicate how the drug influences disease-related brain changes.

But Dr. Cheng cautioned against drawing strong conclusions. The study doesn’t demonstrate a causal relationship between sildenafil and Alzheimer’s disease. Researchers will need to conduct clinical trials with a placebo control to see how well the drug works.

Other researchers said the findings offer a new avenue for research but don’t yet provide solid answers.

“Being able to repurpose a drug already licensed for health conditions could help speed up the drug discovery process and bring about life-changing dementia treatments sooner,” Susan Kohlhaas, PhD, director of research at Alzheimer’s Research UK, told the Science Media Centre.

“Importantly, this research doesn’t prove that sildenafil is responsible for reducing dementia risk, or that it slows or stops the disease,” she continued. “If you want to discuss any treatments you are receiving, the first port of call is to speak to your doctor.”

And doctors won’t likely recommend it as a treatment just yet either.

“While these data are interesting scientifically, based on this study, I would not rush out to start taking sildenafil as a prevention for Alzheimer’s disease,” Tara Spires-Jones, PhD, deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh, told the Science Media Centre.

A version of this article first appeared on WebMD.com.

Retrospective data suggest that improvements over time in overall survival (OS) among COVID-19-infected patients with chronic lymphocytic leukemia (CLL) mirror those observed in COVID-19–infected patients in general, but the data also highlight areas for further investigation, according to the researchers.

MSKCC

Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.

The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.

“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”

“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
 

Trends in outcomes

The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.

Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).

Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).

The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).

“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”

“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.

Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).

“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).

The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”

Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.

They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”

The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.

Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
 

Changing the odds

In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”

“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”

The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.

Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.

In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.

Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”

“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”

Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.

The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.

The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.

sworcester@mdedge.com

Retrospective data suggest that improvements over time in overall survival (OS) among COVID-19-infected patients with chronic lymphocytic leukemia (CLL) mirror those observed in COVID-19–infected patients in general, but the data also highlight areas for further investigation, according to the researchers.

MSKCC

Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.

The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.

“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”

“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
 

Trends in outcomes

The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.

Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).

Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).

The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).

“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”

“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.

Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).

“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).

The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”

Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.

They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”

The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.

Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
 

Changing the odds

In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”

“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”

The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.

Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.

In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.

Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”

“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”

Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.

The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.

The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.

sworcester@mdedge.com

Retrospective data suggest that improvements over time in overall survival (OS) among COVID-19-infected patients with chronic lymphocytic leukemia (CLL) mirror those observed in COVID-19–infected patients in general, but the data also highlight areas for further investigation, according to the researchers.

MSKCC

Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.

The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.

“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”

“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
 

Trends in outcomes

The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.

Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).

Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).

The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).

“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”

“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.

Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).

“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).

The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”

Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.

They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”

The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.

Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
 

Changing the odds

In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”

“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”

The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.

Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.

In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.

Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”

“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”

Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.

The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.

The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.

sworcester@mdedge.com

Motivated, calm, and high-functioning. On the surface, you are the epitome of success. You arrive at work early. You are driven, meet all deadlines and, in fact, excel at tasks. Not only are you successful in your work, but also you appear well put-together – not a single hair out of place. You have a busy social life, always smiling, laughing, or generally in an uplifting mood. On the surface, you have everything together. 

Inside, you’re drowning. You’re in constant survival mode – always overthinking, ruminating, and fearful. Your need for self-preservation is in overdrive. You use your anxiety and fear as motivation. You are a people pleaser, need constant reassurance, and are unable to enjoy the present moment. You have an inability to say no regardless of your overloaded schedule. You are mentally and physically fatigued and overworked beyond the brink of exhaustion. You need to take time off but can’t bring yourself to do so. Others wouldn’t see you in this light because you always appear to be doing well.

The portraits I’ve painted here sound like two different people, but in fact are representative of one. High-functioning anxiety, while not a formal health diagnosis, is a term that broadly encapsulates individuals who experience anxiety but also function well in their day-to-day lives. On the surface, individuals with high-functioning anxiety appear to be “perfect” but in actuality are under constant stress and anxiety in fear of disappointing others. They are perceived as overachievers, but this perception fails to recognize and acknowledge the mental health toll required to achieve at such a high level.

I came across this concept when a friend sent me a post on social media. It was a completely new but oddly familiar concept when I first read about high-functioning anxiety. In fact, I related to this concept almost immediately based on interactions with friends and colleagues, and their recollection of stressors over the years in high-stress, high-functioning environments. 

In addition to personal interactions, I’ve seen anxiety and mental health at large become more “normalized” on various platforms (e.g., Instagram, TikTok) over the years. Interestingly, normalizing these concepts could be beneficial. For example, they increase awareness, encourage conversations (e.g., creating communities), and minimize the barriers toward understanding and respecting individuals who experience high-functioning anxiety. However, social media also has the potential to be harmful (e.g., “humorizing” the concept or turning it into memes, diminishing the experience).

However, the question that nagged at my mind even further was: What reasons are there, if any, for why high-functioning anxiety is not recognized as a formal diagnosis? Is this concept too new? Difficult to diagnose? Anecdotal evidence seems to suggest that high-functioning anxiety is debilitating and impairs one’s quality of life. There appears to be a need to formally recognize this subtype of anxiety and invest more time and research. Increasing the sphere of knowledge may bring more good than harm, as a way to let others know that it’s okay.

Ms. Lui is an MSc candidate at the University of Toronto and is with the mood disorders psychopharmacology unit, Toronto Western Hospital, University Health Network, also in Toronto. She reported receiving income from Braxia Scientific.

A version of this article first appeared on Medscape.com.

Motivated, calm, and high-functioning. On the surface, you are the epitome of success. You arrive at work early. You are driven, meet all deadlines and, in fact, excel at tasks. Not only are you successful in your work, but also you appear well put-together – not a single hair out of place. You have a busy social life, always smiling, laughing, or generally in an uplifting mood. On the surface, you have everything together. 

Inside, you’re drowning. You’re in constant survival mode – always overthinking, ruminating, and fearful. Your need for self-preservation is in overdrive. You use your anxiety and fear as motivation. You are a people pleaser, need constant reassurance, and are unable to enjoy the present moment. You have an inability to say no regardless of your overloaded schedule. You are mentally and physically fatigued and overworked beyond the brink of exhaustion. You need to take time off but can’t bring yourself to do so. Others wouldn’t see you in this light because you always appear to be doing well.

The portraits I’ve painted here sound like two different people, but in fact are representative of one. High-functioning anxiety, while not a formal health diagnosis, is a term that broadly encapsulates individuals who experience anxiety but also function well in their day-to-day lives. On the surface, individuals with high-functioning anxiety appear to be “perfect” but in actuality are under constant stress and anxiety in fear of disappointing others. They are perceived as overachievers, but this perception fails to recognize and acknowledge the mental health toll required to achieve at such a high level.

I came across this concept when a friend sent me a post on social media. It was a completely new but oddly familiar concept when I first read about high-functioning anxiety. In fact, I related to this concept almost immediately based on interactions with friends and colleagues, and their recollection of stressors over the years in high-stress, high-functioning environments. 

In addition to personal interactions, I’ve seen anxiety and mental health at large become more “normalized” on various platforms (e.g., Instagram, TikTok) over the years. Interestingly, normalizing these concepts could be beneficial. For example, they increase awareness, encourage conversations (e.g., creating communities), and minimize the barriers toward understanding and respecting individuals who experience high-functioning anxiety. However, social media also has the potential to be harmful (e.g., “humorizing” the concept or turning it into memes, diminishing the experience).

However, the question that nagged at my mind even further was: What reasons are there, if any, for why high-functioning anxiety is not recognized as a formal diagnosis? Is this concept too new? Difficult to diagnose? Anecdotal evidence seems to suggest that high-functioning anxiety is debilitating and impairs one’s quality of life. There appears to be a need to formally recognize this subtype of anxiety and invest more time and research. Increasing the sphere of knowledge may bring more good than harm, as a way to let others know that it’s okay.

Ms. Lui is an MSc candidate at the University of Toronto and is with the mood disorders psychopharmacology unit, Toronto Western Hospital, University Health Network, also in Toronto. She reported receiving income from Braxia Scientific.

A version of this article first appeared on Medscape.com.

Motivated, calm, and high-functioning. On the surface, you are the epitome of success. You arrive at work early. You are driven, meet all deadlines and, in fact, excel at tasks. Not only are you successful in your work, but also you appear well put-together – not a single hair out of place. You have a busy social life, always smiling, laughing, or generally in an uplifting mood. On the surface, you have everything together. 

Inside, you’re drowning. You’re in constant survival mode – always overthinking, ruminating, and fearful. Your need for self-preservation is in overdrive. You use your anxiety and fear as motivation. You are a people pleaser, need constant reassurance, and are unable to enjoy the present moment. You have an inability to say no regardless of your overloaded schedule. You are mentally and physically fatigued and overworked beyond the brink of exhaustion. You need to take time off but can’t bring yourself to do so. Others wouldn’t see you in this light because you always appear to be doing well.

The portraits I’ve painted here sound like two different people, but in fact are representative of one. High-functioning anxiety, while not a formal health diagnosis, is a term that broadly encapsulates individuals who experience anxiety but also function well in their day-to-day lives. On the surface, individuals with high-functioning anxiety appear to be “perfect” but in actuality are under constant stress and anxiety in fear of disappointing others. They are perceived as overachievers, but this perception fails to recognize and acknowledge the mental health toll required to achieve at such a high level.

I came across this concept when a friend sent me a post on social media. It was a completely new but oddly familiar concept when I first read about high-functioning anxiety. In fact, I related to this concept almost immediately based on interactions with friends and colleagues, and their recollection of stressors over the years in high-stress, high-functioning environments. 

In addition to personal interactions, I’ve seen anxiety and mental health at large become more “normalized” on various platforms (e.g., Instagram, TikTok) over the years. Interestingly, normalizing these concepts could be beneficial. For example, they increase awareness, encourage conversations (e.g., creating communities), and minimize the barriers toward understanding and respecting individuals who experience high-functioning anxiety. However, social media also has the potential to be harmful (e.g., “humorizing” the concept or turning it into memes, diminishing the experience).

However, the question that nagged at my mind even further was: What reasons are there, if any, for why high-functioning anxiety is not recognized as a formal diagnosis? Is this concept too new? Difficult to diagnose? Anecdotal evidence seems to suggest that high-functioning anxiety is debilitating and impairs one’s quality of life. There appears to be a need to formally recognize this subtype of anxiety and invest more time and research. Increasing the sphere of knowledge may bring more good than harm, as a way to let others know that it’s okay.

Ms. Lui is an MSc candidate at the University of Toronto and is with the mood disorders psychopharmacology unit, Toronto Western Hospital, University Health Network, also in Toronto. She reported receiving income from Braxia Scientific.

A version of this article first appeared on Medscape.com.

Background: Acute kidney injury (AKI) is a common complication that occurs in seriously ill patients admitted to the ICU, and many of these patients eventually require RRT. When complicated by major metabolic disorders, it is usually clear when therapy should be initiated. However, when these complications are absent, the most appropriate time to initiate RRT is unclear. There are potential advantages to performing early RRT in patients with severe AKI, such as restoring acid-base balance, preventing fluid accumulation, and preventing major electrolyte disturbances.

Dr. Kim is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: Acute kidney injury (AKI) is a common complication that occurs in seriously ill patients admitted to the ICU, and many of these patients eventually require RRT. When complicated by major metabolic disorders, it is usually clear when therapy should be initiated. However, when these complications are absent, the most appropriate time to initiate RRT is unclear. There are potential advantages to performing early RRT in patients with severe AKI, such as restoring acid-base balance, preventing fluid accumulation, and preventing major electrolyte disturbances.

Dr. Kim is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: Acute kidney injury (AKI) is a common complication that occurs in seriously ill patients admitted to the ICU, and many of these patients eventually require RRT. When complicated by major metabolic disorders, it is usually clear when therapy should be initiated. However, when these complications are absent, the most appropriate time to initiate RRT is unclear. There are potential advantages to performing early RRT in patients with severe AKI, such as restoring acid-base balance, preventing fluid accumulation, and preventing major electrolyte disturbances.

Dr. Kim is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Higher resting heart rate (RHR) is associated with increased risk for dementia and accelerated cognitive decline in older adults, independent of the presence of cardiovascular disease (CVD) risk factors, new research shows.

“RHR is easy to measure and might be used to identify older people potentially at high risk of dementia and cognitive decline for early interventions,” Yume Imahori, MD, PhD, with the Aging Research Center, Karolinska Institutet, Stockholm, said in an interview.

“Health care professionals should be aware of potential cognitive consequences associated with elevated RHR in older people and may advise older people with high RHR to have a follow-up assessment of cognitive function,” Dr. Imahori said.

The study was published online Dec. 3, 2021, in Alzheimer’s & Dementia.
 

Heart-brain connection

The findings are based on 2,147 adults (62% women) aged 60 years and older (mean age, 70.6 years) from the population-based Swedish National Aging and Care in Kungsholmen (SNAC-K) study. All were free of dementia at baseline and were followed regularly from 2001-2004 to 2013-2016.

The average RHR at baseline was 65.7 bpm. Individuals in higher RHR groups were older, less educated, and were more likely to be smokers and sedentary and to have hypertension. There were no differences among RHR groups in the prevalence of CVD at baseline.

During a median follow-up of 11.4 years, 289 participants were diagnosed with dementia.

In the fully adjusted model, participants with RHR of 80 bpm or higher had a 55% increased risk of developing dementia, compared with peers with lower RHR of 60 to 69 bpm (hazard ratio, 1.55; 95% CI, 1.06-2.27).

“This association was not due to underlying cardiovascular diseases such as atrial fibrillation and heart failure, which is important because elevated RHR is often related to heart disease,” Dr. Imahori said in an interview.

Regarding cognitive function, Mini-Mental State Examination scores declined over time during the follow-up period in all RHR groups, but participants with RHR 70-79 and 80+ bpm had a greater decline, compared with those with lower RHR of 60-69 bpm.

Dr. Imahori said these findings are in line with data from the U.S. Atherosclerosis Risk in Communities study linking elevated RHR of 80+ bpm in midlife to dementia and cognitive decline in late life.
 

Public health implications

Reached for comment, Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, said this study adds to the “growing body of research showing the health of the heart and brain are closely connected. However, this study only shows a correlation between resting heart rate and cognition, not causation. More research is needed.

“Evidence shows that other risk factors for cardiovascular disease and stroke – obesity, high blood pressure, and diabetes – negatively impact your cognitive health,” Dr. Sexton said in an interview.

“The Alzheimer’s Association believes the conversation about heart health management is something everyone should be having with their doctor,” she said.

“There are things you can do today to lower your risk for cardiovascular disease, including regular exercise and maintaining a healthy diet. Improving your heart health is an important step to maintaining your brain health as you age,” Dr. Sexton added.

SNAC-K is supported by the Swedish Ministry of Health and Social Affairs and the participating county councils and municipalities and in part by additional grants from the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare. Dr. Imahori and Dr. Sexton disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Higher resting heart rate (RHR) is associated with increased risk for dementia and accelerated cognitive decline in older adults, independent of the presence of cardiovascular disease (CVD) risk factors, new research shows.

“RHR is easy to measure and might be used to identify older people potentially at high risk of dementia and cognitive decline for early interventions,” Yume Imahori, MD, PhD, with the Aging Research Center, Karolinska Institutet, Stockholm, said in an interview.

“Health care professionals should be aware of potential cognitive consequences associated with elevated RHR in older people and may advise older people with high RHR to have a follow-up assessment of cognitive function,” Dr. Imahori said.

The study was published online Dec. 3, 2021, in Alzheimer’s & Dementia.
 

Heart-brain connection

The findings are based on 2,147 adults (62% women) aged 60 years and older (mean age, 70.6 years) from the population-based Swedish National Aging and Care in Kungsholmen (SNAC-K) study. All were free of dementia at baseline and were followed regularly from 2001-2004 to 2013-2016.

The average RHR at baseline was 65.7 bpm. Individuals in higher RHR groups were older, less educated, and were more likely to be smokers and sedentary and to have hypertension. There were no differences among RHR groups in the prevalence of CVD at baseline.

During a median follow-up of 11.4 years, 289 participants were diagnosed with dementia.

In the fully adjusted model, participants with RHR of 80 bpm or higher had a 55% increased risk of developing dementia, compared with peers with lower RHR of 60 to 69 bpm (hazard ratio, 1.55; 95% CI, 1.06-2.27).

“This association was not due to underlying cardiovascular diseases such as atrial fibrillation and heart failure, which is important because elevated RHR is often related to heart disease,” Dr. Imahori said in an interview.

Regarding cognitive function, Mini-Mental State Examination scores declined over time during the follow-up period in all RHR groups, but participants with RHR 70-79 and 80+ bpm had a greater decline, compared with those with lower RHR of 60-69 bpm.

Dr. Imahori said these findings are in line with data from the U.S. Atherosclerosis Risk in Communities study linking elevated RHR of 80+ bpm in midlife to dementia and cognitive decline in late life.
 

Public health implications

Reached for comment, Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, said this study adds to the “growing body of research showing the health of the heart and brain are closely connected. However, this study only shows a correlation between resting heart rate and cognition, not causation. More research is needed.

“Evidence shows that other risk factors for cardiovascular disease and stroke – obesity, high blood pressure, and diabetes – negatively impact your cognitive health,” Dr. Sexton said in an interview.

“The Alzheimer’s Association believes the conversation about heart health management is something everyone should be having with their doctor,” she said.

“There are things you can do today to lower your risk for cardiovascular disease, including regular exercise and maintaining a healthy diet. Improving your heart health is an important step to maintaining your brain health as you age,” Dr. Sexton added.

SNAC-K is supported by the Swedish Ministry of Health and Social Affairs and the participating county councils and municipalities and in part by additional grants from the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare. Dr. Imahori and Dr. Sexton disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Higher resting heart rate (RHR) is associated with increased risk for dementia and accelerated cognitive decline in older adults, independent of the presence of cardiovascular disease (CVD) risk factors, new research shows.

“RHR is easy to measure and might be used to identify older people potentially at high risk of dementia and cognitive decline for early interventions,” Yume Imahori, MD, PhD, with the Aging Research Center, Karolinska Institutet, Stockholm, said in an interview.

“Health care professionals should be aware of potential cognitive consequences associated with elevated RHR in older people and may advise older people with high RHR to have a follow-up assessment of cognitive function,” Dr. Imahori said.

The study was published online Dec. 3, 2021, in Alzheimer’s & Dementia.
 

Heart-brain connection

The findings are based on 2,147 adults (62% women) aged 60 years and older (mean age, 70.6 years) from the population-based Swedish National Aging and Care in Kungsholmen (SNAC-K) study. All were free of dementia at baseline and were followed regularly from 2001-2004 to 2013-2016.

The average RHR at baseline was 65.7 bpm. Individuals in higher RHR groups were older, less educated, and were more likely to be smokers and sedentary and to have hypertension. There were no differences among RHR groups in the prevalence of CVD at baseline.

During a median follow-up of 11.4 years, 289 participants were diagnosed with dementia.

In the fully adjusted model, participants with RHR of 80 bpm or higher had a 55% increased risk of developing dementia, compared with peers with lower RHR of 60 to 69 bpm (hazard ratio, 1.55; 95% CI, 1.06-2.27).

“This association was not due to underlying cardiovascular diseases such as atrial fibrillation and heart failure, which is important because elevated RHR is often related to heart disease,” Dr. Imahori said in an interview.

Regarding cognitive function, Mini-Mental State Examination scores declined over time during the follow-up period in all RHR groups, but participants with RHR 70-79 and 80+ bpm had a greater decline, compared with those with lower RHR of 60-69 bpm.

Dr. Imahori said these findings are in line with data from the U.S. Atherosclerosis Risk in Communities study linking elevated RHR of 80+ bpm in midlife to dementia and cognitive decline in late life.
 

Public health implications

Reached for comment, Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, said this study adds to the “growing body of research showing the health of the heart and brain are closely connected. However, this study only shows a correlation between resting heart rate and cognition, not causation. More research is needed.

“Evidence shows that other risk factors for cardiovascular disease and stroke – obesity, high blood pressure, and diabetes – negatively impact your cognitive health,” Dr. Sexton said in an interview.

“The Alzheimer’s Association believes the conversation about heart health management is something everyone should be having with their doctor,” she said.

“There are things you can do today to lower your risk for cardiovascular disease, including regular exercise and maintaining a healthy diet. Improving your heart health is an important step to maintaining your brain health as you age,” Dr. Sexton added.

SNAC-K is supported by the Swedish Ministry of Health and Social Affairs and the participating county councils and municipalities and in part by additional grants from the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare. Dr. Imahori and Dr. Sexton disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Younger patients with two genetic subtypes of diffuse large B cell lymphoma (DLBCL) – specifically MCD and N1 – show substantial improvements in survival with the addition of ibrutinib to standard R-CHOP chemotherapy, compared with R-CHOP alone, new research shows.

The findings, published Nov. 4, 2021, in Cancer Cell, come from a subanalysis of the phase 3 Phoenix trial. They show that patients with DLBCL aged 60 and younger with either the MCD or N1 genetic subtype had 3-year event-free survival rates as high as 100% when treated with ibrutinib plus R-CHOP, whereas with R-CHOP chemotherapy alone, the survival rates were approximately half of that rate.

“A 100% 3-year event-free survival is almost unheard-of in DLBCL and speaks to the intense dependency of these subtypes to constitutive B cell receptor signaling and their vulnerability to ibrutinib,” first author Louis M. Staudt, MD, of the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., said in an interview.

“By contrast, in ABC DLBCL, the addition of ibrutinib to R-CHOP increased event-free survival by 12.4% to 76.9% in younger patients,” Dr. Staudt said.

ABC, along with GCB and unclassified, are among three key genetic classifications of DLBCL, which is the most common type of lymphoma. While previous studies have shown the Bruton kinase (BTK) inhibitor ibrutinib to induce very low responses among those with the GCB type, favorable responses are seen with the ABC type, of which MCD and N1 are genetic subtypes.

For the Phoenix trial, 838 previously untreated DLBCL patients of the ABC subtype were randomized to ibrutinib (560 mg per day, orally) or placebo plus R-CHOP, in a 21-day cycle for 6 or 8 cycles.

In the overall population, the study failed to achieve its primary survival endpoint of improved survival with ibrutinib. However, a subset analysis stratifying patients by age revealed significant event-free, progression-free, and overall survival benefits with ibrutinib among patients aged 60 and under, with manageable safety. Unexpectedly, this treatment was associated with a worsening of survival outcomes among patients over 60, due to toxicities.

In the new subanalysis, focusing on patients aged 60 and under, Dr. Staudt and his colleagues found that those with the MCD subtype of ABC DLBCL (n = 31) who were treated with ibrutinib had 3-year event-free survival and overall survival rates as high as 100% each, while these rates were significantly lower with R-CHOP alone (48%; P = .01, and 69.6%; P = .032, respectively).

Likewise, among younger patients with the N1 subtype (n = 13), the addition of ibrutinib was associated 3-year event-free and overall survival of 100%, while the R-CHOP alone patients had a significantly lower event-free- (50%; P = .0161) and overall survival (50%; P = .0134).

In the study in general, younger patients who were neither MCD nor N1 also showed better responses with ibrutinib versus placebo; however, the effects were not as strong as those with the MCD and N1 genetic subtypes.

Older patients over 60 showed no benefit from ibrutinib, regardless of their genetic subtype. And benefits were not observed in younger patients with BN2 DLBCL (n = 21), another ABC subtype.

The results are important – despite being secondary endpoints, Dr. Staudt emphasized.

“The automatic assumption regarding secondary endpoints is that any positive findings might have occurred by chance. In the present study, we show that this is not the case.”

“Rather, two previously defined genetic subtypes of DLBCL had an exceptional benefit from ibrutinib,” he said.

“Our study provides strong biological support for the view that the original Phoenix trial should be viewed as a positive trial for younger patients (under 60) with non-GCB DLBCL,” Dr. Staudt said.

While the responses to ibrutinib among younger ABC patients in general were not as robust as with the MCD and N1 subtypes, those improvements nevertheless suggest important benefit with the added treatment, he noted.

“Overall, MCD and N1 constitute roughly 10% of DLBCLs; however, our conclusion is that ibrutinib should be considered in younger patients with non-GCB DLBCL, which constitutes roughly 43% of all DLBCLs,” he said.

Dr. Staudt and other authors are inventors on NIH patent applications covering the LymphGen algorithm (a genetic predictor tool) and covering the use of BTK inhibitors in genetic subtypes of DLBCL. The Phoenix trial received support from Janssen Global Services.

Younger patients with two genetic subtypes of diffuse large B cell lymphoma (DLBCL) – specifically MCD and N1 – show substantial improvements in survival with the addition of ibrutinib to standard R-CHOP chemotherapy, compared with R-CHOP alone, new research shows.

The findings, published Nov. 4, 2021, in Cancer Cell, come from a subanalysis of the phase 3 Phoenix trial. They show that patients with DLBCL aged 60 and younger with either the MCD or N1 genetic subtype had 3-year event-free survival rates as high as 100% when treated with ibrutinib plus R-CHOP, whereas with R-CHOP chemotherapy alone, the survival rates were approximately half of that rate.

“A 100% 3-year event-free survival is almost unheard-of in DLBCL and speaks to the intense dependency of these subtypes to constitutive B cell receptor signaling and their vulnerability to ibrutinib,” first author Louis M. Staudt, MD, of the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., said in an interview.

“By contrast, in ABC DLBCL, the addition of ibrutinib to R-CHOP increased event-free survival by 12.4% to 76.9% in younger patients,” Dr. Staudt said.

ABC, along with GCB and unclassified, are among three key genetic classifications of DLBCL, which is the most common type of lymphoma. While previous studies have shown the Bruton kinase (BTK) inhibitor ibrutinib to induce very low responses among those with the GCB type, favorable responses are seen with the ABC type, of which MCD and N1 are genetic subtypes.

For the Phoenix trial, 838 previously untreated DLBCL patients of the ABC subtype were randomized to ibrutinib (560 mg per day, orally) or placebo plus R-CHOP, in a 21-day cycle for 6 or 8 cycles.

In the overall population, the study failed to achieve its primary survival endpoint of improved survival with ibrutinib. However, a subset analysis stratifying patients by age revealed significant event-free, progression-free, and overall survival benefits with ibrutinib among patients aged 60 and under, with manageable safety. Unexpectedly, this treatment was associated with a worsening of survival outcomes among patients over 60, due to toxicities.

In the new subanalysis, focusing on patients aged 60 and under, Dr. Staudt and his colleagues found that those with the MCD subtype of ABC DLBCL (n = 31) who were treated with ibrutinib had 3-year event-free survival and overall survival rates as high as 100% each, while these rates were significantly lower with R-CHOP alone (48%; P = .01, and 69.6%; P = .032, respectively).

Likewise, among younger patients with the N1 subtype (n = 13), the addition of ibrutinib was associated 3-year event-free and overall survival of 100%, while the R-CHOP alone patients had a significantly lower event-free- (50%; P = .0161) and overall survival (50%; P = .0134).

In the study in general, younger patients who were neither MCD nor N1 also showed better responses with ibrutinib versus placebo; however, the effects were not as strong as those with the MCD and N1 genetic subtypes.

Older patients over 60 showed no benefit from ibrutinib, regardless of their genetic subtype. And benefits were not observed in younger patients with BN2 DLBCL (n = 21), another ABC subtype.

The results are important – despite being secondary endpoints, Dr. Staudt emphasized.

“The automatic assumption regarding secondary endpoints is that any positive findings might have occurred by chance. In the present study, we show that this is not the case.”

“Rather, two previously defined genetic subtypes of DLBCL had an exceptional benefit from ibrutinib,” he said.

“Our study provides strong biological support for the view that the original Phoenix trial should be viewed as a positive trial for younger patients (under 60) with non-GCB DLBCL,” Dr. Staudt said.

While the responses to ibrutinib among younger ABC patients in general were not as robust as with the MCD and N1 subtypes, those improvements nevertheless suggest important benefit with the added treatment, he noted.

“Overall, MCD and N1 constitute roughly 10% of DLBCLs; however, our conclusion is that ibrutinib should be considered in younger patients with non-GCB DLBCL, which constitutes roughly 43% of all DLBCLs,” he said.

Dr. Staudt and other authors are inventors on NIH patent applications covering the LymphGen algorithm (a genetic predictor tool) and covering the use of BTK inhibitors in genetic subtypes of DLBCL. The Phoenix trial received support from Janssen Global Services.

Younger patients with two genetic subtypes of diffuse large B cell lymphoma (DLBCL) – specifically MCD and N1 – show substantial improvements in survival with the addition of ibrutinib to standard R-CHOP chemotherapy, compared with R-CHOP alone, new research shows.

The findings, published Nov. 4, 2021, in Cancer Cell, come from a subanalysis of the phase 3 Phoenix trial. They show that patients with DLBCL aged 60 and younger with either the MCD or N1 genetic subtype had 3-year event-free survival rates as high as 100% when treated with ibrutinib plus R-CHOP, whereas with R-CHOP chemotherapy alone, the survival rates were approximately half of that rate.

“A 100% 3-year event-free survival is almost unheard-of in DLBCL and speaks to the intense dependency of these subtypes to constitutive B cell receptor signaling and their vulnerability to ibrutinib,” first author Louis M. Staudt, MD, of the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., said in an interview.

“By contrast, in ABC DLBCL, the addition of ibrutinib to R-CHOP increased event-free survival by 12.4% to 76.9% in younger patients,” Dr. Staudt said.

ABC, along with GCB and unclassified, are among three key genetic classifications of DLBCL, which is the most common type of lymphoma. While previous studies have shown the Bruton kinase (BTK) inhibitor ibrutinib to induce very low responses among those with the GCB type, favorable responses are seen with the ABC type, of which MCD and N1 are genetic subtypes.

For the Phoenix trial, 838 previously untreated DLBCL patients of the ABC subtype were randomized to ibrutinib (560 mg per day, orally) or placebo plus R-CHOP, in a 21-day cycle for 6 or 8 cycles.

In the overall population, the study failed to achieve its primary survival endpoint of improved survival with ibrutinib. However, a subset analysis stratifying patients by age revealed significant event-free, progression-free, and overall survival benefits with ibrutinib among patients aged 60 and under, with manageable safety. Unexpectedly, this treatment was associated with a worsening of survival outcomes among patients over 60, due to toxicities.

In the new subanalysis, focusing on patients aged 60 and under, Dr. Staudt and his colleagues found that those with the MCD subtype of ABC DLBCL (n = 31) who were treated with ibrutinib had 3-year event-free survival and overall survival rates as high as 100% each, while these rates were significantly lower with R-CHOP alone (48%; P = .01, and 69.6%; P = .032, respectively).

Likewise, among younger patients with the N1 subtype (n = 13), the addition of ibrutinib was associated 3-year event-free and overall survival of 100%, while the R-CHOP alone patients had a significantly lower event-free- (50%; P = .0161) and overall survival (50%; P = .0134).

In the study in general, younger patients who were neither MCD nor N1 also showed better responses with ibrutinib versus placebo; however, the effects were not as strong as those with the MCD and N1 genetic subtypes.

Older patients over 60 showed no benefit from ibrutinib, regardless of their genetic subtype. And benefits were not observed in younger patients with BN2 DLBCL (n = 21), another ABC subtype.

The results are important – despite being secondary endpoints, Dr. Staudt emphasized.

“The automatic assumption regarding secondary endpoints is that any positive findings might have occurred by chance. In the present study, we show that this is not the case.”

“Rather, two previously defined genetic subtypes of DLBCL had an exceptional benefit from ibrutinib,” he said.

“Our study provides strong biological support for the view that the original Phoenix trial should be viewed as a positive trial for younger patients (under 60) with non-GCB DLBCL,” Dr. Staudt said.

While the responses to ibrutinib among younger ABC patients in general were not as robust as with the MCD and N1 subtypes, those improvements nevertheless suggest important benefit with the added treatment, he noted.

“Overall, MCD and N1 constitute roughly 10% of DLBCLs; however, our conclusion is that ibrutinib should be considered in younger patients with non-GCB DLBCL, which constitutes roughly 43% of all DLBCLs,” he said.

Dr. Staudt and other authors are inventors on NIH patent applications covering the LymphGen algorithm (a genetic predictor tool) and covering the use of BTK inhibitors in genetic subtypes of DLBCL. The Phoenix trial received support from Janssen Global Services.