A real-world analysis of bulevirtide found a safety and efficacy profile similar to what was seen in earlier clinical trials in the treatment of hepatitis delta virus (HDV) infection.

HDV can only infect patients already carrying hepatitis B virus (HBV), but it causes the most severe form of viral hepatitis as it can progress to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years.

Bulevirtide is a first-in-class medication that mimics the hepatitis B surface antigen, binding to its receptor on hepatocytes and preventing HDV viral particles from binding to it. The drug received conditional marketing approval by the European Medicines Agency in 2020 and has received a breakthrough therapy designation from the U.S. Food and Drug Administration.

The study was presented at the annual meeting of the American Association for the Study of Liver Diseases by Victor De Ledinghen, PhD, who is a professor of hepatology and head of the hepatology and liver transplantation unit at Bordeaux (France) University Hospital.

The early-access program launched after the French National Agency for Medicines and Health Products approved bulevirtide in 2019. It was made available to patients with compensated cirrhosis or severe liver fibrosis (F3) or patients with F2 fibrosis and alanine amino transferase levels more than twice the upper limit of normal for 6 months or more. Patients received bulevirtide alone (n = 77) or in combination with peg-interferon (n = 68), as determined by their physician.

The researchers defined virologic efficacy as HDV RNA levels being undetectable, or decreased by at least 2 log₁₀ from baseline. They defined biochemical efficacy as ALT levels below 40 IU/L.

A per-protocol analysis included all patients in the bulevirtide group, but excluded 12 from the combination group who discontinued peg-interferon (n = 56). Nineteen patients in bulevirtide group had a treatment modification, and seven discontinued treatment. Five in the combination group had a treatment modification, and 14 stopped treatment. At 12 months, there was a greater decline in median log10 IU/mL in the combination group (–5.65 versus –3.64), though the study was not powered to compare the two. At 12 months, the combination group had 93.9% virologic efficacy, compared with 68.3% in the bulevirtide group.

The two groups had similar mean ALT levels at 12 months (48.91 and 48.03 IU/mL, respectively), with more patients in the bulevirtide group having normal ALT levels (<40 IU/L; 48.8% versus 36.4%). At 12 months, 39.0% of the bulevirtide group and 30.3% of the combination group had a combined response, defined as either undetectable HDV RNA or ≥2 log10 from baseline plus normal ALT levels.

Twenty-nine patients in the bulevirtide group had an adverse event, compared with 43 in the combination group. The two groups were similar in the frequency of grade 3-4 adverse events (7 versus 6), discontinuation due to adverse events (2 versus 3), deaths (0 in both), injection-site reactions (2 in both), liver-related adverse events (4 versus 2), and elevated bile acid (76 versus 68).

During the Q&A period following the presentation, Dr. De Ledinghen was asked if he has a preferred regimen for HDV patients. “I think it depends on the tolerance of peg-interferon because of all the side effects with this drug. I think we need to have predictive factors of virological response with or without interferon. At this time, I don’t have a preference, but I think at this time we need to work on predictive factors associated with virologic response,” he said.

The EMA’s conditional bulevirtide approval hinged on results from phase 2 clinical trials, while the phase 3 clinical studies are ongoing. “This was a very unusual step for the EMA to provide what is similar to emergency use approval while the phase 3 clinical trials are still ongoing,” said Anna Lok, MD, who was asked to comment on the study. Dr. Lok is a professor of internal medicine, director of clinical hepatology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

She noted that the phase 2 studies indicated that the combination with peg-interferon seems to have an additive effect on HDV suppression, while monotherapy with bulevirtide has a greater effect on normalizing ALT levels. The real-world experience confirms these findings.

But the real-world data revealed some concerns. “What really worried me is the large number of patients who required dose modifications or discontinuations, and that seems to be the case in both treatment groups. They didn’t really go into a lot of details [about] why patients needed treatment modifications, but one has to assume that this is due to side effects,” said Dr. Lok.

She also noted that the per-protocol analysis, instead of an intention-to-treat analysis, is a weakness of the study. Additionally, over time, the number of patients analyzed decreased – as many as 40% of patients didn’t have test results at month 12. “It makes you wonder what happened to those patients. Many probably didn’t respond, in which case your overall response rate will be far lower,” said Dr. Lok.

The study was funded by Gilead. Dr. De Ledinghen has financial relationships with Gilead, AbbVie, Echosens, Hologic, Intercept Pharma, Tillotts, Orphalan, Alfasigma, Bristol Myers Squibb, and Siemens Healthineers. Dr. Lok has no relevant financial disclosures.

A real-world analysis of bulevirtide found a safety and efficacy profile similar to what was seen in earlier clinical trials in the treatment of hepatitis delta virus (HDV) infection.

HDV can only infect patients already carrying hepatitis B virus (HBV), but it causes the most severe form of viral hepatitis as it can progress to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years.

Bulevirtide is a first-in-class medication that mimics the hepatitis B surface antigen, binding to its receptor on hepatocytes and preventing HDV viral particles from binding to it. The drug received conditional marketing approval by the European Medicines Agency in 2020 and has received a breakthrough therapy designation from the U.S. Food and Drug Administration.

The study was presented at the annual meeting of the American Association for the Study of Liver Diseases by Victor De Ledinghen, PhD, who is a professor of hepatology and head of the hepatology and liver transplantation unit at Bordeaux (France) University Hospital.

The early-access program launched after the French National Agency for Medicines and Health Products approved bulevirtide in 2019. It was made available to patients with compensated cirrhosis or severe liver fibrosis (F3) or patients with F2 fibrosis and alanine amino transferase levels more than twice the upper limit of normal for 6 months or more. Patients received bulevirtide alone (n = 77) or in combination with peg-interferon (n = 68), as determined by their physician.

The researchers defined virologic efficacy as HDV RNA levels being undetectable, or decreased by at least 2 log₁₀ from baseline. They defined biochemical efficacy as ALT levels below 40 IU/L.

A per-protocol analysis included all patients in the bulevirtide group, but excluded 12 from the combination group who discontinued peg-interferon (n = 56). Nineteen patients in bulevirtide group had a treatment modification, and seven discontinued treatment. Five in the combination group had a treatment modification, and 14 stopped treatment. At 12 months, there was a greater decline in median log10 IU/mL in the combination group (–5.65 versus –3.64), though the study was not powered to compare the two. At 12 months, the combination group had 93.9% virologic efficacy, compared with 68.3% in the bulevirtide group.

The two groups had similar mean ALT levels at 12 months (48.91 and 48.03 IU/mL, respectively), with more patients in the bulevirtide group having normal ALT levels (<40 IU/L; 48.8% versus 36.4%). At 12 months, 39.0% of the bulevirtide group and 30.3% of the combination group had a combined response, defined as either undetectable HDV RNA or ≥2 log10 from baseline plus normal ALT levels.

Twenty-nine patients in the bulevirtide group had an adverse event, compared with 43 in the combination group. The two groups were similar in the frequency of grade 3-4 adverse events (7 versus 6), discontinuation due to adverse events (2 versus 3), deaths (0 in both), injection-site reactions (2 in both), liver-related adverse events (4 versus 2), and elevated bile acid (76 versus 68).

During the Q&A period following the presentation, Dr. De Ledinghen was asked if he has a preferred regimen for HDV patients. “I think it depends on the tolerance of peg-interferon because of all the side effects with this drug. I think we need to have predictive factors of virological response with or without interferon. At this time, I don’t have a preference, but I think at this time we need to work on predictive factors associated with virologic response,” he said.

The EMA’s conditional bulevirtide approval hinged on results from phase 2 clinical trials, while the phase 3 clinical studies are ongoing. “This was a very unusual step for the EMA to provide what is similar to emergency use approval while the phase 3 clinical trials are still ongoing,” said Anna Lok, MD, who was asked to comment on the study. Dr. Lok is a professor of internal medicine, director of clinical hepatology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

She noted that the phase 2 studies indicated that the combination with peg-interferon seems to have an additive effect on HDV suppression, while monotherapy with bulevirtide has a greater effect on normalizing ALT levels. The real-world experience confirms these findings.

But the real-world data revealed some concerns. “What really worried me is the large number of patients who required dose modifications or discontinuations, and that seems to be the case in both treatment groups. They didn’t really go into a lot of details [about] why patients needed treatment modifications, but one has to assume that this is due to side effects,” said Dr. Lok.

She also noted that the per-protocol analysis, instead of an intention-to-treat analysis, is a weakness of the study. Additionally, over time, the number of patients analyzed decreased – as many as 40% of patients didn’t have test results at month 12. “It makes you wonder what happened to those patients. Many probably didn’t respond, in which case your overall response rate will be far lower,” said Dr. Lok.

The study was funded by Gilead. Dr. De Ledinghen has financial relationships with Gilead, AbbVie, Echosens, Hologic, Intercept Pharma, Tillotts, Orphalan, Alfasigma, Bristol Myers Squibb, and Siemens Healthineers. Dr. Lok has no relevant financial disclosures.

A real-world analysis of bulevirtide found a safety and efficacy profile similar to what was seen in earlier clinical trials in the treatment of hepatitis delta virus (HDV) infection.

HDV can only infect patients already carrying hepatitis B virus (HBV), but it causes the most severe form of viral hepatitis as it can progress to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years.

Bulevirtide is a first-in-class medication that mimics the hepatitis B surface antigen, binding to its receptor on hepatocytes and preventing HDV viral particles from binding to it. The drug received conditional marketing approval by the European Medicines Agency in 2020 and has received a breakthrough therapy designation from the U.S. Food and Drug Administration.

The study was presented at the annual meeting of the American Association for the Study of Liver Diseases by Victor De Ledinghen, PhD, who is a professor of hepatology and head of the hepatology and liver transplantation unit at Bordeaux (France) University Hospital.

The early-access program launched after the French National Agency for Medicines and Health Products approved bulevirtide in 2019. It was made available to patients with compensated cirrhosis or severe liver fibrosis (F3) or patients with F2 fibrosis and alanine amino transferase levels more than twice the upper limit of normal for 6 months or more. Patients received bulevirtide alone (n = 77) or in combination with peg-interferon (n = 68), as determined by their physician.

The researchers defined virologic efficacy as HDV RNA levels being undetectable, or decreased by at least 2 log₁₀ from baseline. They defined biochemical efficacy as ALT levels below 40 IU/L.

A per-protocol analysis included all patients in the bulevirtide group, but excluded 12 from the combination group who discontinued peg-interferon (n = 56). Nineteen patients in bulevirtide group had a treatment modification, and seven discontinued treatment. Five in the combination group had a treatment modification, and 14 stopped treatment. At 12 months, there was a greater decline in median log10 IU/mL in the combination group (–5.65 versus –3.64), though the study was not powered to compare the two. At 12 months, the combination group had 93.9% virologic efficacy, compared with 68.3% in the bulevirtide group.

The two groups had similar mean ALT levels at 12 months (48.91 and 48.03 IU/mL, respectively), with more patients in the bulevirtide group having normal ALT levels (<40 IU/L; 48.8% versus 36.4%). At 12 months, 39.0% of the bulevirtide group and 30.3% of the combination group had a combined response, defined as either undetectable HDV RNA or ≥2 log10 from baseline plus normal ALT levels.

Twenty-nine patients in the bulevirtide group had an adverse event, compared with 43 in the combination group. The two groups were similar in the frequency of grade 3-4 adverse events (7 versus 6), discontinuation due to adverse events (2 versus 3), deaths (0 in both), injection-site reactions (2 in both), liver-related adverse events (4 versus 2), and elevated bile acid (76 versus 68).

During the Q&A period following the presentation, Dr. De Ledinghen was asked if he has a preferred regimen for HDV patients. “I think it depends on the tolerance of peg-interferon because of all the side effects with this drug. I think we need to have predictive factors of virological response with or without interferon. At this time, I don’t have a preference, but I think at this time we need to work on predictive factors associated with virologic response,” he said.

The EMA’s conditional bulevirtide approval hinged on results from phase 2 clinical trials, while the phase 3 clinical studies are ongoing. “This was a very unusual step for the EMA to provide what is similar to emergency use approval while the phase 3 clinical trials are still ongoing,” said Anna Lok, MD, who was asked to comment on the study. Dr. Lok is a professor of internal medicine, director of clinical hepatology, and assistant dean for clinical research at the University of Michigan, Ann Arbor.

She noted that the phase 2 studies indicated that the combination with peg-interferon seems to have an additive effect on HDV suppression, while monotherapy with bulevirtide has a greater effect on normalizing ALT levels. The real-world experience confirms these findings.

But the real-world data revealed some concerns. “What really worried me is the large number of patients who required dose modifications or discontinuations, and that seems to be the case in both treatment groups. They didn’t really go into a lot of details [about] why patients needed treatment modifications, but one has to assume that this is due to side effects,” said Dr. Lok.

She also noted that the per-protocol analysis, instead of an intention-to-treat analysis, is a weakness of the study. Additionally, over time, the number of patients analyzed decreased – as many as 40% of patients didn’t have test results at month 12. “It makes you wonder what happened to those patients. Many probably didn’t respond, in which case your overall response rate will be far lower,” said Dr. Lok.

The study was funded by Gilead. Dr. De Ledinghen has financial relationships with Gilead, AbbVie, Echosens, Hologic, Intercept Pharma, Tillotts, Orphalan, Alfasigma, Bristol Myers Squibb, and Siemens Healthineers. Dr. Lok has no relevant financial disclosures.

Adolescents and adults younger than age 21 who develop myocarditis after mRNA COVID-19 vaccination frequently have abnormal findings on cardiac MRI (cMRI) but most have a mild clinical course with rapid resolution of symptoms, a new study concludes.

• Most patients were male (90.6%), White (66.2%) and with a median age of 15.8 years.
• Suspected myocarditis occurred in 136 patients (97.8%) following mRNA vaccine, with 131 (94.2%) following the Pfizer-BioNTech vaccine; 128 cases (91.4%) occurred after the second dose.
• Symptoms started a median of 2 days (range 0 to 22 days) following vaccination administration.
• Chest pain was the most common symptom (99.3%), with fever present in 30.9% of patients and shortness of breath in 27.3%.
• Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%) or no anti-inflammatory therapies (8.6%).
• Twenty-six patients (18.7%) were admitted to the intensive care unit; 2 received inotropic/vasoactive support; none required extracorporeal membrane oxygenation or died.
• Median time spent in the hospital was 2 days.
• A total of 111 patients had elevated troponin I (8.12 ng/mL) and 28 had elevated troponin T (0.61 ng/mL).
• More than two-thirds (69.8%) had abnormal electrocardiograms and/or arrhythmias (7 with nonsustained ventricular tachycardia).
• Twenty-six patients (18.7%) had left ventricular ejection fraction (LVEF) less than 55% on echocardiogram; LVEF had returned to normal in the 25 who returned for follow-up.
• 75 of 97 patients (77.3%) who underwent cMRI at a median of 5 days from symptom onset had abnormal findings; 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria for myocarditis.

“These data suggest that most cases of suspected COVID-19 vaccine–related myocarditis in people younger than 21 are mild and resolve quickly,” corresponding author Dongngan Truong, MD, Division of Pediatric Cardiology, University of Utah and Primary Children’s Hospital, Salt Lake City, said in a statement.

“We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication,” Dr. Truong added.

Dr. Lloyd-Jones said these findings support the AHA’s position that COVID-19 vaccines are “safe, highly effective, and fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic.”

The study received no funding. Dr. Truong consults for Pfizer on vaccine-associated myocarditis. A complete list of author disclosures is available with the original article.

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

Adolescents and adults younger than age 21 who develop myocarditis after mRNA COVID-19 vaccination frequently have abnormal findings on cardiac MRI (cMRI) but most have a mild clinical course with rapid resolution of symptoms, a new study concludes.

• Most patients were male (90.6%), White (66.2%) and with a median age of 15.8 years.
• Suspected myocarditis occurred in 136 patients (97.8%) following mRNA vaccine, with 131 (94.2%) following the Pfizer-BioNTech vaccine; 128 cases (91.4%) occurred after the second dose.
• Symptoms started a median of 2 days (range 0 to 22 days) following vaccination administration.
• Chest pain was the most common symptom (99.3%), with fever present in 30.9% of patients and shortness of breath in 27.3%.
• Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%) or no anti-inflammatory therapies (8.6%).
• Twenty-six patients (18.7%) were admitted to the intensive care unit; 2 received inotropic/vasoactive support; none required extracorporeal membrane oxygenation or died.
• Median time spent in the hospital was 2 days.
• A total of 111 patients had elevated troponin I (8.12 ng/mL) and 28 had elevated troponin T (0.61 ng/mL).
• More than two-thirds (69.8%) had abnormal electrocardiograms and/or arrhythmias (7 with nonsustained ventricular tachycardia).
• Twenty-six patients (18.7%) had left ventricular ejection fraction (LVEF) less than 55% on echocardiogram; LVEF had returned to normal in the 25 who returned for follow-up.
• 75 of 97 patients (77.3%) who underwent cMRI at a median of 5 days from symptom onset had abnormal findings; 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria for myocarditis.

“These data suggest that most cases of suspected COVID-19 vaccine–related myocarditis in people younger than 21 are mild and resolve quickly,” corresponding author Dongngan Truong, MD, Division of Pediatric Cardiology, University of Utah and Primary Children’s Hospital, Salt Lake City, said in a statement.

“We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication,” Dr. Truong added.

Dr. Lloyd-Jones said these findings support the AHA’s position that COVID-19 vaccines are “safe, highly effective, and fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic.”

The study received no funding. Dr. Truong consults for Pfizer on vaccine-associated myocarditis. A complete list of author disclosures is available with the original article.

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

Adolescents and adults younger than age 21 who develop myocarditis after mRNA COVID-19 vaccination frequently have abnormal findings on cardiac MRI (cMRI) but most have a mild clinical course with rapid resolution of symptoms, a new study concludes.

• Most patients were male (90.6%), White (66.2%) and with a median age of 15.8 years.
• Suspected myocarditis occurred in 136 patients (97.8%) following mRNA vaccine, with 131 (94.2%) following the Pfizer-BioNTech vaccine; 128 cases (91.4%) occurred after the second dose.
• Symptoms started a median of 2 days (range 0 to 22 days) following vaccination administration.
• Chest pain was the most common symptom (99.3%), with fever present in 30.9% of patients and shortness of breath in 27.3%.
• Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%) or no anti-inflammatory therapies (8.6%).
• Twenty-six patients (18.7%) were admitted to the intensive care unit; 2 received inotropic/vasoactive support; none required extracorporeal membrane oxygenation or died.
• Median time spent in the hospital was 2 days.
• A total of 111 patients had elevated troponin I (8.12 ng/mL) and 28 had elevated troponin T (0.61 ng/mL).
• More than two-thirds (69.8%) had abnormal electrocardiograms and/or arrhythmias (7 with nonsustained ventricular tachycardia).
• Twenty-six patients (18.7%) had left ventricular ejection fraction (LVEF) less than 55% on echocardiogram; LVEF had returned to normal in the 25 who returned for follow-up.
• 75 of 97 patients (77.3%) who underwent cMRI at a median of 5 days from symptom onset had abnormal findings; 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria for myocarditis.

“These data suggest that most cases of suspected COVID-19 vaccine–related myocarditis in people younger than 21 are mild and resolve quickly,” corresponding author Dongngan Truong, MD, Division of Pediatric Cardiology, University of Utah and Primary Children’s Hospital, Salt Lake City, said in a statement.

“We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication,” Dr. Truong added.

Dr. Lloyd-Jones said these findings support the AHA’s position that COVID-19 vaccines are “safe, highly effective, and fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic.”

The study received no funding. Dr. Truong consults for Pfizer on vaccine-associated myocarditis. A complete list of author disclosures is available with the original article.

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

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.