Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A four-year-old girl, with a history of one wheezing episode, presents to the emergency department (ED) with wheezing, tachypnea, and respiratory distress. She receives three successive treatments of short-acting bronchodilators and is given one dose of dexamethasone, after which she improves significantly. Because of persistent tachypnea and wheezing, she is admitted for further management. By the next day she is much improved, now requiring bronchodilator treatment every four hours. She receives a second dose of dexamethasone to complete her steroid burst. Was the trajectory of this patient’s illness altered by treatment with systemic corticosteroids (SCS)? Is there any benefit to SCS treatment in a wheezing preschool-aged patient?

Wheezing is common in preschool-aged children (ages 2-5 years), with up to half in this age group having experienced a wheezing episode and up to one-third, recurrent wheezing.^1,2 Young children with wheezing require ED visits and hospitalizations at much higher rates than older children and adults.³ Several studies have also demonstrated that children in this age group have higher rates of SCS prescriptions compared with older children.^4,5 Despite the high prevalence of wheezing in this age group, there is great heterogeneity in the etiology and clinical progression of early childhood wheezing, with up to six described phenotypes each with varying levels of association with the development of asthma.⁶ Given the high frequency of asthma, preschool-aged children admitted with wheezing are often treated with SCS, as this is the standard of care for an acute asthma exacerbation.⁷

The benefit of SCS in school-aged children and adolescents with multitrigger asthma exacerbation is well established and includes shorter time to resolution of acute illness and reduction in relapses.⁸ Because of these benefits, expert panels and regulatory agencies often include preschool-aged children in treatment recommendations for the older age groups.^7,9,10 Consequently, apart from infants diagnosed with bronchiolitis, SCS remain a common and accepted treatment for young children presenting with asthma-like symptoms.^4,5

Some data suggest that there may be clinical benefit from treatment with SCS in preschool children who wheeze. A recent trial by Foster et al. included 605 children, aged 24-72 months, presenting to a pediatric ED with wheeze plus viral upper respiratory symptoms.¹¹ Patients were randomized to receive a three-day course of prednisolone (1 mg/kg) or placebo. The primary outcome was length of hospital stay until ready for discharge, which they found was significantly longer for placebo-treated patients (540 minutes) versus prednisolone (370 minutes).

There are few randomized controlled trials evaluating the efficacy of SCS in preschool-aged children with viral-induced wheezing, and these children are often grouped with younger or older children in studies. While limited in number, these studies have evaluated SCS efficacy with acute wheezing in preschool-aged children in outpatient, ED, and inpatient settings (Appendix Table).^12-16 The majority of trials of SCS in this age group have shown mixed or negative results.

Admission rates for preschoolers with viral wheezing were not statistically different in those receiving oral prednisolone versus placebo in a study conducted by Oomen et al. evaluating outpatient, parent-initiated prednisolone.¹⁴ Tal et al. found overall benefit with reduced admission rate for patients treated in the ED with methylprednisolone versus placebo; however, this finding was not statistically significant in patients 24-54 months old.¹⁶

For those requiring hospitalization, length of hospital stay and time until readiness to discharge were the primary outcomes assessed by Panickar et al. and Jartti et al. Neither study found a statistically significant difference between groups who received oral prednisolone versus placebo for 3 or 5 days. Secondary outcomes such as symptom scores, symptom duration, albuterol use, and 60-day relapse rate were also not improved in those taking oral prednisolone compared with placebo.^14,15

The mixed results of studies assessing the efficacy of SCS in preschool-aged wheezing children may be attributed to the fact that wheezing in this age group likely represents multiple underlying processes. Most acute wheezing at this age is not associated with atopy and is often triggered by viral respiratory tract infections.¹⁷ Furthermore, 90% of wheezing in children under the age of five years does not persist to the asthma phenotype (recurrent episodes with multiple triggers, airway obstruction, and hyper-responsiveness) once they reach school age.¹⁸

While SCS are generally not expensive, their use is not without cost. Studies of oral corticosteroid use in children with asthma have shown adverse effects including vomiting, hypertension, and impaired growth.¹⁹ Children with recurrent wheeze receiving SCS may demonstrate biochemical hypothalamic-pituitary-axis dysfunction.²⁰ Given the high utilization and SCS prescription rates in this age group, reducing the use of SCS with wheezing episodes could have a large clinical and financial impact.^3,4 These medications should be used judiciously in order to balance benefit with potential risks.

Given that there is diversity in the phenotype of preschool-aged children who wheeze, it is possible that a subset of these children would benefit from SCS. Some studies have shown that certain groups of patients derive benefit, including those with rhinovirus infection, eczema, and children at higher risk for multitrigger asthma.^11,13 Children who have atopic wheeze are more likely to have persistent symptoms that may eventually be diagnosed as asthma.¹⁸ These children will have airway inflammation secondary to eosinophilic infiltration and may be responsive to SCS at times of exacerbation. However, attempts to classify preschool children based on risk of asthma have not shown consistent results.

The Asthma Predictive Index (API), a tool developed as a part of the Tucson Children’s Respiratory Study, uses clinical factors including history of wheeze, atopic dermatitis, and allergic rhinitis to determine a young child’s risk of having asthma symptoms after age six years.²¹ Jartti et al. and Panickar et al. used the API to stratify patients based on future asthma risk.^13,15 The high risk group in the Jartti et al. study showed the benefit of SCS, while there was no benefit in the Panickar et al. study. When Oommen et al. also attempted to stratify asthma risk using levels of blood eosinophil proteins, which when elevated, are predictive of persistent wheeze.¹⁴ There was no difference in drug efficacy between patients with high and low blood eosinophil proteins. Although Foster et al. demonstrated shorter length of stay (LOS) with SCS overall, this was only seen in the subgroup with a previous diagnosis of asthma.

Patients presenting with severe disease (including those requiring critical care or with the highest symptom scores) have mostly been excluded from these studies. Although patients with severe disease often receive steroids, there is insufficient evidence of the efficacy of SCS in this population.^12,13,15,22 Foster et al. did include patients with high symptom scores (although they excluded patients with “critical wheeze”) and found that the efficacy of SCS was clearest for those with severe presentations.¹¹

Finally, some studies have demonstrated a virus-specific effect, with a reduction in time to readiness for discharge and reduction in recurrent wheeze in children treated with prednisolone who were positive for rhinovirus.^12,23 Rhinovirus infection has also been associated with allergic sensitization and recurrent wheezing.^23,24 However, rhinovirus-specific steroid responsiveness has not been consistently replicated by other investigators.¹¹

The majority of preschool-aged children presenting with wheeze in the care of hospitalists have mild to moderate symptoms, triggered by viral infections.²² It can be helpful to categorize the wheezing child as atopic or nonatopic. Laboratory studies such as allergen-specific IgE, peripheral eosinophil count, and exhaled nitric oxide can aid in predicting response to asthma medications and progression to the classic asthma phenotype.²⁵ In the absence of these diagnostic studies, which are often costly and challenging to obtain in young children, a clinical score such as the API, or the recently validated Pediatric Asthma Risk Score (PARS), can help to assess future risk of developing multitrigger asthma.^21,26 A positive API requires a history of more than three episodes of wheeze over the past year as well as one major (physician-diagnosed atopic dermatitis or parental asthma) or two minor (peripheral blood eosinophilia, physician-diagnosed allergic rhinitis, or wheezing apart from colds) criteria.¹⁷ It has a sensitivity of 57% and specificity of 81%.²⁶ The PARS uses the presence of parental asthma, eczema, early wheezing, wheezing apart from colds, African-American race, and ≥2 positive skin prick tests to predict asthma. The sensitivity and specificity of PARS are similar to the API at 68% and 79%, respectively.²⁶

Given the mixed results from studies evaluating the benefit of SCS in preschoolers with atopic symptoms and/or a positive API, evidence is lacking to guide decision-making in these children.^13-15 However, it is reasonable to treat those at higher risk for future multitrigger asthma with SCS. There is also insufficient evidence to determine whether those with more severe disease or those infected with particular viral pathogens may benefit. Therefore, for the majority of children presenting with viral-induced wheezing, with a negative API or low PARS, there is no evidence that treatment with an SCS provides benefit in the form of reduced LOS, reduction in clinical symptoms, treatment failure, or relapse rate.

• Do not routinely treat with SCS preschool-aged children who have episodic wheezing triggered by viral respiratory tract infections and who do not have risk factors for persistent asthma.
• For preschool-aged children with a history of atopy, a positive API, or elevated PARS, SCS can be considered during admissions for respiratory distress and wheezing.
• Preschool-aged children presenting with severe disease or requiring intensive care may benefit from SCS, but there is insufficient evidence to conclude whether this practice provides benefit.

Current evidence does not support the routine use of SCS for preschool-aged children admitted for mild to moderate wheezing episodes. The majority of these children have viral episodic wheeze that does not develop into the asthma phenotype. For children with severe disease or at higher risk for asthma, SCS may be considered, although there remains insufficient evidence as to their efficacy. The patient in the introductory case lacks risk factors that would suggest SCS responsiveness (eg, positive API, previous asthma diagnosis, inhaled corticosteroid use, or severe disease) and would likely receive no clinical benefit from dexamethasone treatment.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason?” Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailing TWDFNR@hospitalmedicine.org.

Disclosures

Dr. Jennifer O’Toole consulted with and received honoraria payment from the I-PASS Patient Safety Institute. She also holds stock options in the I-PASS Patient Safety Institute, a nonpublicly traded company. Drs. Jones and Hubbell have nothing to disclose.

Funding

Dr. Thomson was supported by the Agency for Healthcare Research and Quality under award number K08HS025138.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A four-year-old girl, with a history of one wheezing episode, presents to the emergency department (ED) with wheezing, tachypnea, and respiratory distress. She receives three successive treatments of short-acting bronchodilators and is given one dose of dexamethasone, after which she improves significantly. Because of persistent tachypnea and wheezing, she is admitted for further management. By the next day she is much improved, now requiring bronchodilator treatment every four hours. She receives a second dose of dexamethasone to complete her steroid burst. Was the trajectory of this patient’s illness altered by treatment with systemic corticosteroids (SCS)? Is there any benefit to SCS treatment in a wheezing preschool-aged patient?

Wheezing is common in preschool-aged children (ages 2-5 years), with up to half in this age group having experienced a wheezing episode and up to one-third, recurrent wheezing.^1,2 Young children with wheezing require ED visits and hospitalizations at much higher rates than older children and adults.³ Several studies have also demonstrated that children in this age group have higher rates of SCS prescriptions compared with older children.^4,5 Despite the high prevalence of wheezing in this age group, there is great heterogeneity in the etiology and clinical progression of early childhood wheezing, with up to six described phenotypes each with varying levels of association with the development of asthma.⁶ Given the high frequency of asthma, preschool-aged children admitted with wheezing are often treated with SCS, as this is the standard of care for an acute asthma exacerbation.⁷

The benefit of SCS in school-aged children and adolescents with multitrigger asthma exacerbation is well established and includes shorter time to resolution of acute illness and reduction in relapses.⁸ Because of these benefits, expert panels and regulatory agencies often include preschool-aged children in treatment recommendations for the older age groups.^7,9,10 Consequently, apart from infants diagnosed with bronchiolitis, SCS remain a common and accepted treatment for young children presenting with asthma-like symptoms.^4,5

Some data suggest that there may be clinical benefit from treatment with SCS in preschool children who wheeze. A recent trial by Foster et al. included 605 children, aged 24-72 months, presenting to a pediatric ED with wheeze plus viral upper respiratory symptoms.¹¹ Patients were randomized to receive a three-day course of prednisolone (1 mg/kg) or placebo. The primary outcome was length of hospital stay until ready for discharge, which they found was significantly longer for placebo-treated patients (540 minutes) versus prednisolone (370 minutes).

There are few randomized controlled trials evaluating the efficacy of SCS in preschool-aged children with viral-induced wheezing, and these children are often grouped with younger or older children in studies. While limited in number, these studies have evaluated SCS efficacy with acute wheezing in preschool-aged children in outpatient, ED, and inpatient settings (Appendix Table).^12-16 The majority of trials of SCS in this age group have shown mixed or negative results.

Admission rates for preschoolers with viral wheezing were not statistically different in those receiving oral prednisolone versus placebo in a study conducted by Oomen et al. evaluating outpatient, parent-initiated prednisolone.¹⁴ Tal et al. found overall benefit with reduced admission rate for patients treated in the ED with methylprednisolone versus placebo; however, this finding was not statistically significant in patients 24-54 months old.¹⁶

For those requiring hospitalization, length of hospital stay and time until readiness to discharge were the primary outcomes assessed by Panickar et al. and Jartti et al. Neither study found a statistically significant difference between groups who received oral prednisolone versus placebo for 3 or 5 days. Secondary outcomes such as symptom scores, symptom duration, albuterol use, and 60-day relapse rate were also not improved in those taking oral prednisolone compared with placebo.^14,15

The mixed results of studies assessing the efficacy of SCS in preschool-aged wheezing children may be attributed to the fact that wheezing in this age group likely represents multiple underlying processes. Most acute wheezing at this age is not associated with atopy and is often triggered by viral respiratory tract infections.¹⁷ Furthermore, 90% of wheezing in children under the age of five years does not persist to the asthma phenotype (recurrent episodes with multiple triggers, airway obstruction, and hyper-responsiveness) once they reach school age.¹⁸

While SCS are generally not expensive, their use is not without cost. Studies of oral corticosteroid use in children with asthma have shown adverse effects including vomiting, hypertension, and impaired growth.¹⁹ Children with recurrent wheeze receiving SCS may demonstrate biochemical hypothalamic-pituitary-axis dysfunction.²⁰ Given the high utilization and SCS prescription rates in this age group, reducing the use of SCS with wheezing episodes could have a large clinical and financial impact.^3,4 These medications should be used judiciously in order to balance benefit with potential risks.

Given that there is diversity in the phenotype of preschool-aged children who wheeze, it is possible that a subset of these children would benefit from SCS. Some studies have shown that certain groups of patients derive benefit, including those with rhinovirus infection, eczema, and children at higher risk for multitrigger asthma.^11,13 Children who have atopic wheeze are more likely to have persistent symptoms that may eventually be diagnosed as asthma.¹⁸ These children will have airway inflammation secondary to eosinophilic infiltration and may be responsive to SCS at times of exacerbation. However, attempts to classify preschool children based on risk of asthma have not shown consistent results.

The Asthma Predictive Index (API), a tool developed as a part of the Tucson Children’s Respiratory Study, uses clinical factors including history of wheeze, atopic dermatitis, and allergic rhinitis to determine a young child’s risk of having asthma symptoms after age six years.²¹ Jartti et al. and Panickar et al. used the API to stratify patients based on future asthma risk.^13,15 The high risk group in the Jartti et al. study showed the benefit of SCS, while there was no benefit in the Panickar et al. study. When Oommen et al. also attempted to stratify asthma risk using levels of blood eosinophil proteins, which when elevated, are predictive of persistent wheeze.¹⁴ There was no difference in drug efficacy between patients with high and low blood eosinophil proteins. Although Foster et al. demonstrated shorter length of stay (LOS) with SCS overall, this was only seen in the subgroup with a previous diagnosis of asthma.

Patients presenting with severe disease (including those requiring critical care or with the highest symptom scores) have mostly been excluded from these studies. Although patients with severe disease often receive steroids, there is insufficient evidence of the efficacy of SCS in this population.^12,13,15,22 Foster et al. did include patients with high symptom scores (although they excluded patients with “critical wheeze”) and found that the efficacy of SCS was clearest for those with severe presentations.¹¹

Finally, some studies have demonstrated a virus-specific effect, with a reduction in time to readiness for discharge and reduction in recurrent wheeze in children treated with prednisolone who were positive for rhinovirus.^12,23 Rhinovirus infection has also been associated with allergic sensitization and recurrent wheezing.^23,24 However, rhinovirus-specific steroid responsiveness has not been consistently replicated by other investigators.¹¹

The majority of preschool-aged children presenting with wheeze in the care of hospitalists have mild to moderate symptoms, triggered by viral infections.²² It can be helpful to categorize the wheezing child as atopic or nonatopic. Laboratory studies such as allergen-specific IgE, peripheral eosinophil count, and exhaled nitric oxide can aid in predicting response to asthma medications and progression to the classic asthma phenotype.²⁵ In the absence of these diagnostic studies, which are often costly and challenging to obtain in young children, a clinical score such as the API, or the recently validated Pediatric Asthma Risk Score (PARS), can help to assess future risk of developing multitrigger asthma.^21,26 A positive API requires a history of more than three episodes of wheeze over the past year as well as one major (physician-diagnosed atopic dermatitis or parental asthma) or two minor (peripheral blood eosinophilia, physician-diagnosed allergic rhinitis, or wheezing apart from colds) criteria.¹⁷ It has a sensitivity of 57% and specificity of 81%.²⁶ The PARS uses the presence of parental asthma, eczema, early wheezing, wheezing apart from colds, African-American race, and ≥2 positive skin prick tests to predict asthma. The sensitivity and specificity of PARS are similar to the API at 68% and 79%, respectively.²⁶

Given the mixed results from studies evaluating the benefit of SCS in preschoolers with atopic symptoms and/or a positive API, evidence is lacking to guide decision-making in these children.^13-15 However, it is reasonable to treat those at higher risk for future multitrigger asthma with SCS. There is also insufficient evidence to determine whether those with more severe disease or those infected with particular viral pathogens may benefit. Therefore, for the majority of children presenting with viral-induced wheezing, with a negative API or low PARS, there is no evidence that treatment with an SCS provides benefit in the form of reduced LOS, reduction in clinical symptoms, treatment failure, or relapse rate.

• Do not routinely treat with SCS preschool-aged children who have episodic wheezing triggered by viral respiratory tract infections and who do not have risk factors for persistent asthma.
• For preschool-aged children with a history of atopy, a positive API, or elevated PARS, SCS can be considered during admissions for respiratory distress and wheezing.
• Preschool-aged children presenting with severe disease or requiring intensive care may benefit from SCS, but there is insufficient evidence to conclude whether this practice provides benefit.

Current evidence does not support the routine use of SCS for preschool-aged children admitted for mild to moderate wheezing episodes. The majority of these children have viral episodic wheeze that does not develop into the asthma phenotype. For children with severe disease or at higher risk for asthma, SCS may be considered, although there remains insufficient evidence as to their efficacy. The patient in the introductory case lacks risk factors that would suggest SCS responsiveness (eg, positive API, previous asthma diagnosis, inhaled corticosteroid use, or severe disease) and would likely receive no clinical benefit from dexamethasone treatment.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason?” Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailing TWDFNR@hospitalmedicine.org.

Disclosures

Dr. Jennifer O’Toole consulted with and received honoraria payment from the I-PASS Patient Safety Institute. She also holds stock options in the I-PASS Patient Safety Institute, a nonpublicly traded company. Drs. Jones and Hubbell have nothing to disclose.

Funding

Dr. Thomson was supported by the Agency for Healthcare Research and Quality under award number K08HS025138.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A four-year-old girl, with a history of one wheezing episode, presents to the emergency department (ED) with wheezing, tachypnea, and respiratory distress. She receives three successive treatments of short-acting bronchodilators and is given one dose of dexamethasone, after which she improves significantly. Because of persistent tachypnea and wheezing, she is admitted for further management. By the next day she is much improved, now requiring bronchodilator treatment every four hours. She receives a second dose of dexamethasone to complete her steroid burst. Was the trajectory of this patient’s illness altered by treatment with systemic corticosteroids (SCS)? Is there any benefit to SCS treatment in a wheezing preschool-aged patient?

Wheezing is common in preschool-aged children (ages 2-5 years), with up to half in this age group having experienced a wheezing episode and up to one-third, recurrent wheezing.^1,2 Young children with wheezing require ED visits and hospitalizations at much higher rates than older children and adults.³ Several studies have also demonstrated that children in this age group have higher rates of SCS prescriptions compared with older children.^4,5 Despite the high prevalence of wheezing in this age group, there is great heterogeneity in the etiology and clinical progression of early childhood wheezing, with up to six described phenotypes each with varying levels of association with the development of asthma.⁶ Given the high frequency of asthma, preschool-aged children admitted with wheezing are often treated with SCS, as this is the standard of care for an acute asthma exacerbation.⁷

The benefit of SCS in school-aged children and adolescents with multitrigger asthma exacerbation is well established and includes shorter time to resolution of acute illness and reduction in relapses.⁸ Because of these benefits, expert panels and regulatory agencies often include preschool-aged children in treatment recommendations for the older age groups.^7,9,10 Consequently, apart from infants diagnosed with bronchiolitis, SCS remain a common and accepted treatment for young children presenting with asthma-like symptoms.^4,5

Some data suggest that there may be clinical benefit from treatment with SCS in preschool children who wheeze. A recent trial by Foster et al. included 605 children, aged 24-72 months, presenting to a pediatric ED with wheeze plus viral upper respiratory symptoms.¹¹ Patients were randomized to receive a three-day course of prednisolone (1 mg/kg) or placebo. The primary outcome was length of hospital stay until ready for discharge, which they found was significantly longer for placebo-treated patients (540 minutes) versus prednisolone (370 minutes).

There are few randomized controlled trials evaluating the efficacy of SCS in preschool-aged children with viral-induced wheezing, and these children are often grouped with younger or older children in studies. While limited in number, these studies have evaluated SCS efficacy with acute wheezing in preschool-aged children in outpatient, ED, and inpatient settings (Appendix Table).^12-16 The majority of trials of SCS in this age group have shown mixed or negative results.

Admission rates for preschoolers with viral wheezing were not statistically different in those receiving oral prednisolone versus placebo in a study conducted by Oomen et al. evaluating outpatient, parent-initiated prednisolone.¹⁴ Tal et al. found overall benefit with reduced admission rate for patients treated in the ED with methylprednisolone versus placebo; however, this finding was not statistically significant in patients 24-54 months old.¹⁶

For those requiring hospitalization, length of hospital stay and time until readiness to discharge were the primary outcomes assessed by Panickar et al. and Jartti et al. Neither study found a statistically significant difference between groups who received oral prednisolone versus placebo for 3 or 5 days. Secondary outcomes such as symptom scores, symptom duration, albuterol use, and 60-day relapse rate were also not improved in those taking oral prednisolone compared with placebo.^14,15

The mixed results of studies assessing the efficacy of SCS in preschool-aged wheezing children may be attributed to the fact that wheezing in this age group likely represents multiple underlying processes. Most acute wheezing at this age is not associated with atopy and is often triggered by viral respiratory tract infections.¹⁷ Furthermore, 90% of wheezing in children under the age of five years does not persist to the asthma phenotype (recurrent episodes with multiple triggers, airway obstruction, and hyper-responsiveness) once they reach school age.¹⁸

While SCS are generally not expensive, their use is not without cost. Studies of oral corticosteroid use in children with asthma have shown adverse effects including vomiting, hypertension, and impaired growth.¹⁹ Children with recurrent wheeze receiving SCS may demonstrate biochemical hypothalamic-pituitary-axis dysfunction.²⁰ Given the high utilization and SCS prescription rates in this age group, reducing the use of SCS with wheezing episodes could have a large clinical and financial impact.^3,4 These medications should be used judiciously in order to balance benefit with potential risks.

Given that there is diversity in the phenotype of preschool-aged children who wheeze, it is possible that a subset of these children would benefit from SCS. Some studies have shown that certain groups of patients derive benefit, including those with rhinovirus infection, eczema, and children at higher risk for multitrigger asthma.^11,13 Children who have atopic wheeze are more likely to have persistent symptoms that may eventually be diagnosed as asthma.¹⁸ These children will have airway inflammation secondary to eosinophilic infiltration and may be responsive to SCS at times of exacerbation. However, attempts to classify preschool children based on risk of asthma have not shown consistent results.

The Asthma Predictive Index (API), a tool developed as a part of the Tucson Children’s Respiratory Study, uses clinical factors including history of wheeze, atopic dermatitis, and allergic rhinitis to determine a young child’s risk of having asthma symptoms after age six years.²¹ Jartti et al. and Panickar et al. used the API to stratify patients based on future asthma risk.^13,15 The high risk group in the Jartti et al. study showed the benefit of SCS, while there was no benefit in the Panickar et al. study. When Oommen et al. also attempted to stratify asthma risk using levels of blood eosinophil proteins, which when elevated, are predictive of persistent wheeze.¹⁴ There was no difference in drug efficacy between patients with high and low blood eosinophil proteins. Although Foster et al. demonstrated shorter length of stay (LOS) with SCS overall, this was only seen in the subgroup with a previous diagnosis of asthma.

Patients presenting with severe disease (including those requiring critical care or with the highest symptom scores) have mostly been excluded from these studies. Although patients with severe disease often receive steroids, there is insufficient evidence of the efficacy of SCS in this population.^12,13,15,22 Foster et al. did include patients with high symptom scores (although they excluded patients with “critical wheeze”) and found that the efficacy of SCS was clearest for those with severe presentations.¹¹

Finally, some studies have demonstrated a virus-specific effect, with a reduction in time to readiness for discharge and reduction in recurrent wheeze in children treated with prednisolone who were positive for rhinovirus.^12,23 Rhinovirus infection has also been associated with allergic sensitization and recurrent wheezing.^23,24 However, rhinovirus-specific steroid responsiveness has not been consistently replicated by other investigators.¹¹

The majority of preschool-aged children presenting with wheeze in the care of hospitalists have mild to moderate symptoms, triggered by viral infections.²² It can be helpful to categorize the wheezing child as atopic or nonatopic. Laboratory studies such as allergen-specific IgE, peripheral eosinophil count, and exhaled nitric oxide can aid in predicting response to asthma medications and progression to the classic asthma phenotype.²⁵ In the absence of these diagnostic studies, which are often costly and challenging to obtain in young children, a clinical score such as the API, or the recently validated Pediatric Asthma Risk Score (PARS), can help to assess future risk of developing multitrigger asthma.^21,26 A positive API requires a history of more than three episodes of wheeze over the past year as well as one major (physician-diagnosed atopic dermatitis or parental asthma) or two minor (peripheral blood eosinophilia, physician-diagnosed allergic rhinitis, or wheezing apart from colds) criteria.¹⁷ It has a sensitivity of 57% and specificity of 81%.²⁶ The PARS uses the presence of parental asthma, eczema, early wheezing, wheezing apart from colds, African-American race, and ≥2 positive skin prick tests to predict asthma. The sensitivity and specificity of PARS are similar to the API at 68% and 79%, respectively.²⁶

Given the mixed results from studies evaluating the benefit of SCS in preschoolers with atopic symptoms and/or a positive API, evidence is lacking to guide decision-making in these children.^13-15 However, it is reasonable to treat those at higher risk for future multitrigger asthma with SCS. There is also insufficient evidence to determine whether those with more severe disease or those infected with particular viral pathogens may benefit. Therefore, for the majority of children presenting with viral-induced wheezing, with a negative API or low PARS, there is no evidence that treatment with an SCS provides benefit in the form of reduced LOS, reduction in clinical symptoms, treatment failure, or relapse rate.

• Do not routinely treat with SCS preschool-aged children who have episodic wheezing triggered by viral respiratory tract infections and who do not have risk factors for persistent asthma.
• For preschool-aged children with a history of atopy, a positive API, or elevated PARS, SCS can be considered during admissions for respiratory distress and wheezing.
• Preschool-aged children presenting with severe disease or requiring intensive care may benefit from SCS, but there is insufficient evidence to conclude whether this practice provides benefit.

Current evidence does not support the routine use of SCS for preschool-aged children admitted for mild to moderate wheezing episodes. The majority of these children have viral episodic wheeze that does not develop into the asthma phenotype. For children with severe disease or at higher risk for asthma, SCS may be considered, although there remains insufficient evidence as to their efficacy. The patient in the introductory case lacks risk factors that would suggest SCS responsiveness (eg, positive API, previous asthma diagnosis, inhaled corticosteroid use, or severe disease) and would likely receive no clinical benefit from dexamethasone treatment.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason?” Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailing TWDFNR@hospitalmedicine.org.

Disclosures

Dr. Jennifer O’Toole consulted with and received honoraria payment from the I-PASS Patient Safety Institute. She also holds stock options in the I-PASS Patient Safety Institute, a nonpublicly traded company. Drs. Jones and Hubbell have nothing to disclose.

Funding

Dr. Thomson was supported by the Agency for Healthcare Research and Quality under award number K08HS025138.

Electrolyte imbalances, per se, predispose to ventricular ectopy and, in extreme cases, sudden cardiac death.¹ As these outcomes are more common in the presence of intrinsic heart disease, serum electrolytes—particularly potassium and magnesium—are routinely monitored and made replete in patients with myocardial infarction (MI) or acute decompensated heart failure (ADHF).

Patients hospitalized with ADHF often present with metabolic derangements and varying degrees of chronic adaptations in their renin–angiotensin–aldosterone system.^1,2 In addition, during an ADHF hospitalization, they are subjected to guideline-directed medical therapy (GDMT), commonly in escalating doses, that exhibit well-established effects on serum potassium levels, including diuretics, angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, beta blockers, and mineralocorticoid receptor antagonists. Thus, there are myriad ways patients hospitalized for ADHF might experience electrolyte abnormalities.

In this issue of the Journal of Hospital Medicine, O’Sullivan et al. explore the associations between mean 72-hour serum potassium and important clinical outcomes—in-hospital mortality, transfer to an intensive care unit (ICU), and length of stay (LOS)—among patients with normal admission serum potassium hospitalized for ADHF.³ Through a retrospective review of electronic records from 116 hospitals, the authors identified 4,995 initially normokalemic heart failure (HF; identified by ICD-9 codes) patients and grouped them into low-normal (3.5-4.0 mEq/L), normal (4.0-4.5 mEq/L), and high-normal (4.5-5.0 mEq/L) potassium groups.³ Adjustments were made for composite scores encapsulating other lab abnormalities and comorbidities.

Over the 72-hour exposure window, the authors observed no statistically significant difference in mortality, ICU transfer, or LOS between the low-normal and normal potassium groups.³ Moreover, in a sensitivity analysis of patients who did not receive potassium supplementation, there remained statistically similar rates of mortality, ICU transfer, and LOS.³ Together, these findings suggest that maintenance of potassium >4 mEq/L may not be efficacious for preventing in-hospital complications of ADHF.³ In fact, they observed more frequent mortality and ICU transfer in patients who had high-normal potassium. This group, however, had a higher burden of chronic kidney disease and illness severity on presentation and was less likely to receive supplemental potassium.³

ADHF accounts for more than one million hospital admissions annually with one in four patients readmitted within 30 days; estimated costs surpass $30 billion.² Reducing unnecessary expenditures in the management of HF through evidence-based guidelines is paramount. Electrolyte repletion in the setting of ADHF may represent one such opportunity by reducing excess phlebotomy, laboratory services, and potassium supplementation. Patient experience may also improve from curbing these cumbersome practices. While society guidelines endorse potassium repletion in MI to reduce the risk of ventricular arrhythmia,⁴ there is no uniform consensus in ADHF. As the authors cite, existing data regarding ideal potassium levels in patients with ADHF is lacking, with current evidence drawn from small observational studies. The present study, being much larger in size and being linked with observed rates of active potassium supplementation, provides some of the strongest evidence to date that a potassium goal of >4 mEq/L may not be efficacious at reducing ADHF-related complications in the generalized HF population.

While it remains uncertain if avoiding low-normal potassium levels in ADHF is beneficial, over the long term, intermediate-range potassium levels are clearly associated with the lowest HF-related mortality. In a study of over 2,000 HF patients who underwent longitudinal potassium monitoring, mortality was distributed along a U-shaped curve with highest mortality at the extremes of kalemia and a nadir at a level of 4.3 mEq/L.⁵

A major limitation of the present study is that it does not account for variability within the ADHF population. Firstly, knowledge regarding the use of GDMT, which not only affects serum potassium (all GDMTs) but also reduces the likelihood of arrhythmias (beta blockers), would have been informative. Moreover, the authors do not have access to data regarding incident arrhythmia and instead use ICU admission as a surrogate. In addition, ADHF patients in this study varied greatly in illness severity, ranging from those receiving initial therapy with loop diuretics alone to those requiring augmentation with thiazides and even the use of temporary mechanical circulatory support.³ Escalating loop diuretic or metolazone use not only is associated with increased mortality⁶ but often results in impressive natriuresis and, potentially dangerous, kaliuresis secondary to the sequential nephron blockade.⁷ Those who underwent extensive potassium swings in the study may not be appropriately captured using 72-hour serum potassium averages. Additionally, this study did not assess for quantity of diuresis, which is known to affect serum potassium values. It is possible that those with low-normal potassium represent patients who underwent more effective diuresis and therefore were discharged sooner. Adding to the variability, ADHF in this study encompassed both systolic (HF with a reduced ejection fraction) and diastolic (HF with a preserved ejection fraction) HF although, perhaps not surprisingly, there were marked differences in the HF subtype by potassium group—the proportions with only diastolic dysfunction were 37.1%, 39.0%, and 45.8% in the low-normal, normal, and high-normal groups, respectively (P = .0174).³ Given the known heterogeneity between these two HF subtypes,⁸ particularly with respect to their response to mortality-reducing GDMT,^2,8 the results may be significantly confounded.

Relatedly, by excluding initially hypokalemic patients, the authors have lost considerable power and broad generalizability as these patients likely represent those at greatest risk of recurrent hypokalemia and its attendant complications during admission.

This study should be lauded for critically appraising the ubiquitous practice of electrolyte repletion. The authors present compelling preliminary data suggesting that maintenance of potassium >4 mEq/L in the general ADHF population is not efficacious at preventing ADHF complications and, as a corollary, is likely not cost-effective. However, we agree with the authors that a randomized controlled trial will be needed to change clinical practice. Ideally, such a study would account for HF subtype and GDMT use and could compare rates of arrhythmia, AHDF-related death, and all-cause mortality in patients maintained to goal normokalemia (>3.5 mEq/L) versus “high goal” (>4 mEq/L) with repletion. Only these types of studies will provide the strength of evidence needed to end a practice as well engrained in modern medicine as “high-goal ‘lytes”.

Disclosures

Dr. Blaha reports grants from NIH, grants from FDA, grants from AHA, grants and personal fees from Amgen Foundation, grants from Aetna Foundation, personal fees from Sanofi, personal fees from Regeneron, and personal fees from Novartis, from Novo Nordisk, and from Bayer, outside the submitted work. Dr. Dudum and Dr. Lahti have nothing to disclose.

Electrolyte imbalances, per se, predispose to ventricular ectopy and, in extreme cases, sudden cardiac death.¹ As these outcomes are more common in the presence of intrinsic heart disease, serum electrolytes—particularly potassium and magnesium—are routinely monitored and made replete in patients with myocardial infarction (MI) or acute decompensated heart failure (ADHF).

Patients hospitalized with ADHF often present with metabolic derangements and varying degrees of chronic adaptations in their renin–angiotensin–aldosterone system.^1,2 In addition, during an ADHF hospitalization, they are subjected to guideline-directed medical therapy (GDMT), commonly in escalating doses, that exhibit well-established effects on serum potassium levels, including diuretics, angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, beta blockers, and mineralocorticoid receptor antagonists. Thus, there are myriad ways patients hospitalized for ADHF might experience electrolyte abnormalities.

In this issue of the Journal of Hospital Medicine, O’Sullivan et al. explore the associations between mean 72-hour serum potassium and important clinical outcomes—in-hospital mortality, transfer to an intensive care unit (ICU), and length of stay (LOS)—among patients with normal admission serum potassium hospitalized for ADHF.³ Through a retrospective review of electronic records from 116 hospitals, the authors identified 4,995 initially normokalemic heart failure (HF; identified by ICD-9 codes) patients and grouped them into low-normal (3.5-4.0 mEq/L), normal (4.0-4.5 mEq/L), and high-normal (4.5-5.0 mEq/L) potassium groups.³ Adjustments were made for composite scores encapsulating other lab abnormalities and comorbidities.

Over the 72-hour exposure window, the authors observed no statistically significant difference in mortality, ICU transfer, or LOS between the low-normal and normal potassium groups.³ Moreover, in a sensitivity analysis of patients who did not receive potassium supplementation, there remained statistically similar rates of mortality, ICU transfer, and LOS.³ Together, these findings suggest that maintenance of potassium >4 mEq/L may not be efficacious for preventing in-hospital complications of ADHF.³ In fact, they observed more frequent mortality and ICU transfer in patients who had high-normal potassium. This group, however, had a higher burden of chronic kidney disease and illness severity on presentation and was less likely to receive supplemental potassium.³

ADHF accounts for more than one million hospital admissions annually with one in four patients readmitted within 30 days; estimated costs surpass $30 billion.² Reducing unnecessary expenditures in the management of HF through evidence-based guidelines is paramount. Electrolyte repletion in the setting of ADHF may represent one such opportunity by reducing excess phlebotomy, laboratory services, and potassium supplementation. Patient experience may also improve from curbing these cumbersome practices. While society guidelines endorse potassium repletion in MI to reduce the risk of ventricular arrhythmia,⁴ there is no uniform consensus in ADHF. As the authors cite, existing data regarding ideal potassium levels in patients with ADHF is lacking, with current evidence drawn from small observational studies. The present study, being much larger in size and being linked with observed rates of active potassium supplementation, provides some of the strongest evidence to date that a potassium goal of >4 mEq/L may not be efficacious at reducing ADHF-related complications in the generalized HF population.

While it remains uncertain if avoiding low-normal potassium levels in ADHF is beneficial, over the long term, intermediate-range potassium levels are clearly associated with the lowest HF-related mortality. In a study of over 2,000 HF patients who underwent longitudinal potassium monitoring, mortality was distributed along a U-shaped curve with highest mortality at the extremes of kalemia and a nadir at a level of 4.3 mEq/L.⁵

A major limitation of the present study is that it does not account for variability within the ADHF population. Firstly, knowledge regarding the use of GDMT, which not only affects serum potassium (all GDMTs) but also reduces the likelihood of arrhythmias (beta blockers), would have been informative. Moreover, the authors do not have access to data regarding incident arrhythmia and instead use ICU admission as a surrogate. In addition, ADHF patients in this study varied greatly in illness severity, ranging from those receiving initial therapy with loop diuretics alone to those requiring augmentation with thiazides and even the use of temporary mechanical circulatory support.³ Escalating loop diuretic or metolazone use not only is associated with increased mortality⁶ but often results in impressive natriuresis and, potentially dangerous, kaliuresis secondary to the sequential nephron blockade.⁷ Those who underwent extensive potassium swings in the study may not be appropriately captured using 72-hour serum potassium averages. Additionally, this study did not assess for quantity of diuresis, which is known to affect serum potassium values. It is possible that those with low-normal potassium represent patients who underwent more effective diuresis and therefore were discharged sooner. Adding to the variability, ADHF in this study encompassed both systolic (HF with a reduced ejection fraction) and diastolic (HF with a preserved ejection fraction) HF although, perhaps not surprisingly, there were marked differences in the HF subtype by potassium group—the proportions with only diastolic dysfunction were 37.1%, 39.0%, and 45.8% in the low-normal, normal, and high-normal groups, respectively (P = .0174).³ Given the known heterogeneity between these two HF subtypes,⁸ particularly with respect to their response to mortality-reducing GDMT,^2,8 the results may be significantly confounded.

Relatedly, by excluding initially hypokalemic patients, the authors have lost considerable power and broad generalizability as these patients likely represent those at greatest risk of recurrent hypokalemia and its attendant complications during admission.

This study should be lauded for critically appraising the ubiquitous practice of electrolyte repletion. The authors present compelling preliminary data suggesting that maintenance of potassium >4 mEq/L in the general ADHF population is not efficacious at preventing ADHF complications and, as a corollary, is likely not cost-effective. However, we agree with the authors that a randomized controlled trial will be needed to change clinical practice. Ideally, such a study would account for HF subtype and GDMT use and could compare rates of arrhythmia, AHDF-related death, and all-cause mortality in patients maintained to goal normokalemia (>3.5 mEq/L) versus “high goal” (>4 mEq/L) with repletion. Only these types of studies will provide the strength of evidence needed to end a practice as well engrained in modern medicine as “high-goal ‘lytes”.

Disclosures

Dr. Blaha reports grants from NIH, grants from FDA, grants from AHA, grants and personal fees from Amgen Foundation, grants from Aetna Foundation, personal fees from Sanofi, personal fees from Regeneron, and personal fees from Novartis, from Novo Nordisk, and from Bayer, outside the submitted work. Dr. Dudum and Dr. Lahti have nothing to disclose.

Electrolyte imbalances, per se, predispose to ventricular ectopy and, in extreme cases, sudden cardiac death.¹ As these outcomes are more common in the presence of intrinsic heart disease, serum electrolytes—particularly potassium and magnesium—are routinely monitored and made replete in patients with myocardial infarction (MI) or acute decompensated heart failure (ADHF).

Patients hospitalized with ADHF often present with metabolic derangements and varying degrees of chronic adaptations in their renin–angiotensin–aldosterone system.^1,2 In addition, during an ADHF hospitalization, they are subjected to guideline-directed medical therapy (GDMT), commonly in escalating doses, that exhibit well-established effects on serum potassium levels, including diuretics, angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, beta blockers, and mineralocorticoid receptor antagonists. Thus, there are myriad ways patients hospitalized for ADHF might experience electrolyte abnormalities.

In this issue of the Journal of Hospital Medicine, O’Sullivan et al. explore the associations between mean 72-hour serum potassium and important clinical outcomes—in-hospital mortality, transfer to an intensive care unit (ICU), and length of stay (LOS)—among patients with normal admission serum potassium hospitalized for ADHF.³ Through a retrospective review of electronic records from 116 hospitals, the authors identified 4,995 initially normokalemic heart failure (HF; identified by ICD-9 codes) patients and grouped them into low-normal (3.5-4.0 mEq/L), normal (4.0-4.5 mEq/L), and high-normal (4.5-5.0 mEq/L) potassium groups.³ Adjustments were made for composite scores encapsulating other lab abnormalities and comorbidities.

Over the 72-hour exposure window, the authors observed no statistically significant difference in mortality, ICU transfer, or LOS between the low-normal and normal potassium groups.³ Moreover, in a sensitivity analysis of patients who did not receive potassium supplementation, there remained statistically similar rates of mortality, ICU transfer, and LOS.³ Together, these findings suggest that maintenance of potassium >4 mEq/L may not be efficacious for preventing in-hospital complications of ADHF.³ In fact, they observed more frequent mortality and ICU transfer in patients who had high-normal potassium. This group, however, had a higher burden of chronic kidney disease and illness severity on presentation and was less likely to receive supplemental potassium.³

ADHF accounts for more than one million hospital admissions annually with one in four patients readmitted within 30 days; estimated costs surpass $30 billion.² Reducing unnecessary expenditures in the management of HF through evidence-based guidelines is paramount. Electrolyte repletion in the setting of ADHF may represent one such opportunity by reducing excess phlebotomy, laboratory services, and potassium supplementation. Patient experience may also improve from curbing these cumbersome practices. While society guidelines endorse potassium repletion in MI to reduce the risk of ventricular arrhythmia,⁴ there is no uniform consensus in ADHF. As the authors cite, existing data regarding ideal potassium levels in patients with ADHF is lacking, with current evidence drawn from small observational studies. The present study, being much larger in size and being linked with observed rates of active potassium supplementation, provides some of the strongest evidence to date that a potassium goal of >4 mEq/L may not be efficacious at reducing ADHF-related complications in the generalized HF population.

While it remains uncertain if avoiding low-normal potassium levels in ADHF is beneficial, over the long term, intermediate-range potassium levels are clearly associated with the lowest HF-related mortality. In a study of over 2,000 HF patients who underwent longitudinal potassium monitoring, mortality was distributed along a U-shaped curve with highest mortality at the extremes of kalemia and a nadir at a level of 4.3 mEq/L.⁵

A major limitation of the present study is that it does not account for variability within the ADHF population. Firstly, knowledge regarding the use of GDMT, which not only affects serum potassium (all GDMTs) but also reduces the likelihood of arrhythmias (beta blockers), would have been informative. Moreover, the authors do not have access to data regarding incident arrhythmia and instead use ICU admission as a surrogate. In addition, ADHF patients in this study varied greatly in illness severity, ranging from those receiving initial therapy with loop diuretics alone to those requiring augmentation with thiazides and even the use of temporary mechanical circulatory support.³ Escalating loop diuretic or metolazone use not only is associated with increased mortality⁶ but often results in impressive natriuresis and, potentially dangerous, kaliuresis secondary to the sequential nephron blockade.⁷ Those who underwent extensive potassium swings in the study may not be appropriately captured using 72-hour serum potassium averages. Additionally, this study did not assess for quantity of diuresis, which is known to affect serum potassium values. It is possible that those with low-normal potassium represent patients who underwent more effective diuresis and therefore were discharged sooner. Adding to the variability, ADHF in this study encompassed both systolic (HF with a reduced ejection fraction) and diastolic (HF with a preserved ejection fraction) HF although, perhaps not surprisingly, there were marked differences in the HF subtype by potassium group—the proportions with only diastolic dysfunction were 37.1%, 39.0%, and 45.8% in the low-normal, normal, and high-normal groups, respectively (P = .0174).³ Given the known heterogeneity between these two HF subtypes,⁸ particularly with respect to their response to mortality-reducing GDMT,^2,8 the results may be significantly confounded.

Relatedly, by excluding initially hypokalemic patients, the authors have lost considerable power and broad generalizability as these patients likely represent those at greatest risk of recurrent hypokalemia and its attendant complications during admission.

This study should be lauded for critically appraising the ubiquitous practice of electrolyte repletion. The authors present compelling preliminary data suggesting that maintenance of potassium >4 mEq/L in the general ADHF population is not efficacious at preventing ADHF complications and, as a corollary, is likely not cost-effective. However, we agree with the authors that a randomized controlled trial will be needed to change clinical practice. Ideally, such a study would account for HF subtype and GDMT use and could compare rates of arrhythmia, AHDF-related death, and all-cause mortality in patients maintained to goal normokalemia (>3.5 mEq/L) versus “high goal” (>4 mEq/L) with repletion. Only these types of studies will provide the strength of evidence needed to end a practice as well engrained in modern medicine as “high-goal ‘lytes”.

Disclosures

Dr. Blaha reports grants from NIH, grants from FDA, grants from AHA, grants and personal fees from Amgen Foundation, grants from Aetna Foundation, personal fees from Sanofi, personal fees from Regeneron, and personal fees from Novartis, from Novo Nordisk, and from Bayer, outside the submitted work. Dr. Dudum and Dr. Lahti have nothing to disclose.

The Food and Drug Administration has approved the Humira biosimilar Hadlima (adalimumab-bwwd), making it the fourth adalimumab biosimilar approved in the United States, the agency announced.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Hadlima is approved for seven of the reference product’s indications, which include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis.

The product will launch in the United States on June 30, 2023. Other FDA-approved adalimumab biosimilars – Amjevita (adalimunab-atto), Cyltezo (adalimumab-adbm), Hyrimoz (adalimumab-adaz) – similarly will not reach the U.S. market until 2023.

Hadlima is developed by Samsung Bioepis and commercialized by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.

*This article was updated on July 24, 2019.

jevans@mdedge.com

The Food and Drug Administration has approved the Humira biosimilar Hadlima (adalimumab-bwwd), making it the fourth adalimumab biosimilar approved in the United States, the agency announced.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Hadlima is approved for seven of the reference product’s indications, which include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis.

The product will launch in the United States on June 30, 2023. Other FDA-approved adalimumab biosimilars – Amjevita (adalimunab-atto), Cyltezo (adalimumab-adbm), Hyrimoz (adalimumab-adaz) – similarly will not reach the U.S. market until 2023.

Hadlima is developed by Samsung Bioepis and commercialized by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.

*This article was updated on July 24, 2019.

jevans@mdedge.com

The Food and Drug Administration has approved the Humira biosimilar Hadlima (adalimumab-bwwd), making it the fourth adalimumab biosimilar approved in the United States, the agency announced.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Hadlima is approved for seven of the reference product’s indications, which include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis.

The product will launch in the United States on June 30, 2023. Other FDA-approved adalimumab biosimilars – Amjevita (adalimunab-atto), Cyltezo (adalimumab-adbm), Hyrimoz (adalimumab-adaz) – similarly will not reach the U.S. market until 2023.

Hadlima is developed by Samsung Bioepis and commercialized by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.

*This article was updated on July 24, 2019.

jevans@mdedge.com

Individuals with undiagnosed autism spectrum disorders and those with a formal diagnosis employ similar compensation behaviors to manage social and cognitive difficulties, and undiagnosed individuals may go unrecognized, data from an online survey of 136 adults suggest.

Unlike other adaptive behaviors in psychiatry, “autistic compensators, despite apparent lack of observable autistic behavior, continue being autistic at the neurocognitive level,” wrote Lucy Anne Livingston of Kings College London, and colleagues. “Because autism spectrum disorder is diagnosed by behavior alone, compensators might not receive a diagnosis and support until later in life, if at all. “

The researchers compared compensation behaviors in adults with and without an autism diagnosis. They recruited adults aged 18 years and older through an online advertisement distributed through social media and the U.K. National Autistic Society. Participants completed an online survey during Oct. 19, 2017–Jan. 2, 2018. The study was published in the Lancet Psychiatry.

“Compensation involved using intellectual and executive functions to regulate social behavior, such as intellectually conceived patterns about social norms (e.g., making eye contact), preplanning social niceties (e.g., asking others questions about themselves), and switching between social rules,” the researchers wrote.

The study population included 58 individuals with a clinical diagnosis of autism, 19 of whom self-identified as autistic but were not formally diagnosed, and 59 of whom reported social difficulties but had no formal diagnosis and did not self-identify as autistic. The average age of the three groups was 36 years, 40 years, and 34 years, respectively, and the average age at diagnosis for the diagnosed group was 30 years. Most of the individuals in each group were women (64%, 47%, and 86%, respectively). Responses were examined using a thematic analysis and thematic map.

In general, participants reported that compensation was a cognitively taxing process that served as a secondary route for social interaction because the primary route was unavailable, but that compensation strategies fell short in certain situations, such as unexpected turns of conversation. Overall, 38% of the respondents said their compensation strategies were “extremely successful” and 56% reported “somewhat successful.” However, 12% also reported their strategies were “extremely tiring,” and 36% reported “somewhat tiring.”

Factors affecting the participants’ abilities to compensate included environmental and sensory factors such as bright lights, loud noise, and large groups with unstructured social settings, such as parties. Also, transition to living independently as an adult led to problems, because compensation had allowed individuals to grow up appearing normal but lacking in additional support and strategies, the researchers noted.

Factors that contributed to successful interactions included similar interests with an interaction partner, and motivation to develop meaningful relationships. Participants also said they viewed compensation as a way to avoid ostracism and bullying. In addition, “fitting neurotypical peoples’ interaction style (e.g., eye contact or small talk) was viewed as vital for achieving life goals (e.g., independence and employment),” the researchers wrote.

In an accompanying editorial, Julia Parish-Morris, PhD, suggested the observation made by Ms. Livingston, a researcher at the Institute of Psychiatry, Psychology and Neuroscience at the college, and associates that compensation also occurs in people who do not have autism suggests that compensation might be a “general social lubricant that facilitates community living and is therefore a potentially useful tool.”

“In other words, perhaps raising awareness about compensation in autism spectrum disorder is an important first step toward eliminating the need for it,” wrote Dr. Parish-Morris, of the Center for Autism Research at Children’s Hospital of Philadelphia (Lancet Psychiatry. 2019 Jul 23. doi: 10.1016/S2215-0366[19]30294-9).

The study data were limited by the prevalence of female, well-educated, late-diagnosed individuals in the study population, which might limit the generalizability of the findings, and the lack of data on subconscious compensation because of the use of self-reports, the researchers noted.

However, “Given the individual differences found in this study, we tentatively suggest that clinicians take an individualized approach when assessing and discussing compensatory strategies with people with autism,” they said. “It will be important to establish which compensatory strategies are most beneficial, and how their success might be maximized with changes to external environments irrespective of clinical intervention.”

The researchers had no financial interests to disclose.

SOURCE: Livingston LA et al. Lancet Psychiatry. 2019 Jul 23. doi. org/10.1016/S2215-0366(19)30224-X.

Individuals with undiagnosed autism spectrum disorders and those with a formal diagnosis employ similar compensation behaviors to manage social and cognitive difficulties, and undiagnosed individuals may go unrecognized, data from an online survey of 136 adults suggest.

Unlike other adaptive behaviors in psychiatry, “autistic compensators, despite apparent lack of observable autistic behavior, continue being autistic at the neurocognitive level,” wrote Lucy Anne Livingston of Kings College London, and colleagues. “Because autism spectrum disorder is diagnosed by behavior alone, compensators might not receive a diagnosis and support until later in life, if at all. “

The researchers compared compensation behaviors in adults with and without an autism diagnosis. They recruited adults aged 18 years and older through an online advertisement distributed through social media and the U.K. National Autistic Society. Participants completed an online survey during Oct. 19, 2017–Jan. 2, 2018. The study was published in the Lancet Psychiatry.

“Compensation involved using intellectual and executive functions to regulate social behavior, such as intellectually conceived patterns about social norms (e.g., making eye contact), preplanning social niceties (e.g., asking others questions about themselves), and switching between social rules,” the researchers wrote.

The study population included 58 individuals with a clinical diagnosis of autism, 19 of whom self-identified as autistic but were not formally diagnosed, and 59 of whom reported social difficulties but had no formal diagnosis and did not self-identify as autistic. The average age of the three groups was 36 years, 40 years, and 34 years, respectively, and the average age at diagnosis for the diagnosed group was 30 years. Most of the individuals in each group were women (64%, 47%, and 86%, respectively). Responses were examined using a thematic analysis and thematic map.

In general, participants reported that compensation was a cognitively taxing process that served as a secondary route for social interaction because the primary route was unavailable, but that compensation strategies fell short in certain situations, such as unexpected turns of conversation. Overall, 38% of the respondents said their compensation strategies were “extremely successful” and 56% reported “somewhat successful.” However, 12% also reported their strategies were “extremely tiring,” and 36% reported “somewhat tiring.”

Factors affecting the participants’ abilities to compensate included environmental and sensory factors such as bright lights, loud noise, and large groups with unstructured social settings, such as parties. Also, transition to living independently as an adult led to problems, because compensation had allowed individuals to grow up appearing normal but lacking in additional support and strategies, the researchers noted.

Factors that contributed to successful interactions included similar interests with an interaction partner, and motivation to develop meaningful relationships. Participants also said they viewed compensation as a way to avoid ostracism and bullying. In addition, “fitting neurotypical peoples’ interaction style (e.g., eye contact or small talk) was viewed as vital for achieving life goals (e.g., independence and employment),” the researchers wrote.

In an accompanying editorial, Julia Parish-Morris, PhD, suggested the observation made by Ms. Livingston, a researcher at the Institute of Psychiatry, Psychology and Neuroscience at the college, and associates that compensation also occurs in people who do not have autism suggests that compensation might be a “general social lubricant that facilitates community living and is therefore a potentially useful tool.”

“In other words, perhaps raising awareness about compensation in autism spectrum disorder is an important first step toward eliminating the need for it,” wrote Dr. Parish-Morris, of the Center for Autism Research at Children’s Hospital of Philadelphia (Lancet Psychiatry. 2019 Jul 23. doi: 10.1016/S2215-0366[19]30294-9).

The study data were limited by the prevalence of female, well-educated, late-diagnosed individuals in the study population, which might limit the generalizability of the findings, and the lack of data on subconscious compensation because of the use of self-reports, the researchers noted.

However, “Given the individual differences found in this study, we tentatively suggest that clinicians take an individualized approach when assessing and discussing compensatory strategies with people with autism,” they said. “It will be important to establish which compensatory strategies are most beneficial, and how their success might be maximized with changes to external environments irrespective of clinical intervention.”

The researchers had no financial interests to disclose.

SOURCE: Livingston LA et al. Lancet Psychiatry. 2019 Jul 23. doi. org/10.1016/S2215-0366(19)30224-X.

Individuals with undiagnosed autism spectrum disorders and those with a formal diagnosis employ similar compensation behaviors to manage social and cognitive difficulties, and undiagnosed individuals may go unrecognized, data from an online survey of 136 adults suggest.

Unlike other adaptive behaviors in psychiatry, “autistic compensators, despite apparent lack of observable autistic behavior, continue being autistic at the neurocognitive level,” wrote Lucy Anne Livingston of Kings College London, and colleagues. “Because autism spectrum disorder is diagnosed by behavior alone, compensators might not receive a diagnosis and support until later in life, if at all. “

The researchers compared compensation behaviors in adults with and without an autism diagnosis. They recruited adults aged 18 years and older through an online advertisement distributed through social media and the U.K. National Autistic Society. Participants completed an online survey during Oct. 19, 2017–Jan. 2, 2018. The study was published in the Lancet Psychiatry.

“Compensation involved using intellectual and executive functions to regulate social behavior, such as intellectually conceived patterns about social norms (e.g., making eye contact), preplanning social niceties (e.g., asking others questions about themselves), and switching between social rules,” the researchers wrote.

The study population included 58 individuals with a clinical diagnosis of autism, 19 of whom self-identified as autistic but were not formally diagnosed, and 59 of whom reported social difficulties but had no formal diagnosis and did not self-identify as autistic. The average age of the three groups was 36 years, 40 years, and 34 years, respectively, and the average age at diagnosis for the diagnosed group was 30 years. Most of the individuals in each group were women (64%, 47%, and 86%, respectively). Responses were examined using a thematic analysis and thematic map.

In general, participants reported that compensation was a cognitively taxing process that served as a secondary route for social interaction because the primary route was unavailable, but that compensation strategies fell short in certain situations, such as unexpected turns of conversation. Overall, 38% of the respondents said their compensation strategies were “extremely successful” and 56% reported “somewhat successful.” However, 12% also reported their strategies were “extremely tiring,” and 36% reported “somewhat tiring.”

Factors affecting the participants’ abilities to compensate included environmental and sensory factors such as bright lights, loud noise, and large groups with unstructured social settings, such as parties. Also, transition to living independently as an adult led to problems, because compensation had allowed individuals to grow up appearing normal but lacking in additional support and strategies, the researchers noted.

Factors that contributed to successful interactions included similar interests with an interaction partner, and motivation to develop meaningful relationships. Participants also said they viewed compensation as a way to avoid ostracism and bullying. In addition, “fitting neurotypical peoples’ interaction style (e.g., eye contact or small talk) was viewed as vital for achieving life goals (e.g., independence and employment),” the researchers wrote.

In an accompanying editorial, Julia Parish-Morris, PhD, suggested the observation made by Ms. Livingston, a researcher at the Institute of Psychiatry, Psychology and Neuroscience at the college, and associates that compensation also occurs in people who do not have autism suggests that compensation might be a “general social lubricant that facilitates community living and is therefore a potentially useful tool.”

“In other words, perhaps raising awareness about compensation in autism spectrum disorder is an important first step toward eliminating the need for it,” wrote Dr. Parish-Morris, of the Center for Autism Research at Children’s Hospital of Philadelphia (Lancet Psychiatry. 2019 Jul 23. doi: 10.1016/S2215-0366[19]30294-9).

The study data were limited by the prevalence of female, well-educated, late-diagnosed individuals in the study population, which might limit the generalizability of the findings, and the lack of data on subconscious compensation because of the use of self-reports, the researchers noted.

However, “Given the individual differences found in this study, we tentatively suggest that clinicians take an individualized approach when assessing and discussing compensatory strategies with people with autism,” they said. “It will be important to establish which compensatory strategies are most beneficial, and how their success might be maximized with changes to external environments irrespective of clinical intervention.”

The researchers had no financial interests to disclose.

SOURCE: Livingston LA et al. Lancet Psychiatry. 2019 Jul 23. doi. org/10.1016/S2215-0366(19)30224-X.

Are preschoolers with signs of ADHD ready for school? A new study suggests they’re far from prepared.

A small sample of children with symptoms of moderate to severe ADHD scored markedly lower than comparable children on 8 of 10 measures of readiness for primary education in a study published in Pediatrics.

patchareeporn_s/Getty Images

SOURCE: Perrin HT et al. Pediatrics. 2019 Aug. doi: 10.1542/peds.2019-0038.

Are preschoolers with signs of ADHD ready for school? A new study suggests they’re far from prepared.

A small sample of children with symptoms of moderate to severe ADHD scored markedly lower than comparable children on 8 of 10 measures of readiness for primary education in a study published in Pediatrics.

patchareeporn_s/Getty Images

SOURCE: Perrin HT et al. Pediatrics. 2019 Aug. doi: 10.1542/peds.2019-0038.

Are preschoolers with signs of ADHD ready for school? A new study suggests they’re far from prepared.

A small sample of children with symptoms of moderate to severe ADHD scored markedly lower than comparable children on 8 of 10 measures of readiness for primary education in a study published in Pediatrics.

patchareeporn_s/Getty Images

SOURCE: Perrin HT et al. Pediatrics. 2019 Aug. doi: 10.1542/peds.2019-0038.

The Food and Drug Administration has approved rituximab-pvvr (Ruxience) for adults with non-Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), and granulomatosis with polyangiitis and microscopic polyangiitis. It is the first biosimilar approved to treat these two rare autoimmune conditions.

Specifically, the biosimilar product is approved as single-agent therapy for relapsed or refractory, low grade or follicular, CD20-positive B-cell non-Hodgkin lymphoma; in combination with chemotherapy for other types of previously untreated CD20-positive B-cell non-Hodgkin lymphoma; and as a single agent for nonprogressing, low-grade, CD20-positive B-cell non-Hodgkin lymphoma after first-line chemotherapy treatment. It is also approved for both previously untreated and previously treated CD20-positive CLL in combination with chemotherapy. And it is approved for granulomatosis with polyangiitis and microscopic polyangiitis in combination with glucocorticoids.

The approval is based on demonstration that rituximab-pvvr had no clinically meaningful differences in safety or efficacy when compared with the reference drug, rituximab (Rituxan), according to a release from the biosimilar’s developer. As with rituximab, rituximab-pvvr’s label comes with an FDA boxed warning. In the biosimilar’s case, it warns against fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy. Other adverse reactions include fever, headache, neutropenia, and lymphopenia.

cpalmer@mdedge.com

The Food and Drug Administration has approved rituximab-pvvr (Ruxience) for adults with non-Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), and granulomatosis with polyangiitis and microscopic polyangiitis. It is the first biosimilar approved to treat these two rare autoimmune conditions.

Specifically, the biosimilar product is approved as single-agent therapy for relapsed or refractory, low grade or follicular, CD20-positive B-cell non-Hodgkin lymphoma; in combination with chemotherapy for other types of previously untreated CD20-positive B-cell non-Hodgkin lymphoma; and as a single agent for nonprogressing, low-grade, CD20-positive B-cell non-Hodgkin lymphoma after first-line chemotherapy treatment. It is also approved for both previously untreated and previously treated CD20-positive CLL in combination with chemotherapy. And it is approved for granulomatosis with polyangiitis and microscopic polyangiitis in combination with glucocorticoids.

The approval is based on demonstration that rituximab-pvvr had no clinically meaningful differences in safety or efficacy when compared with the reference drug, rituximab (Rituxan), according to a release from the biosimilar’s developer. As with rituximab, rituximab-pvvr’s label comes with an FDA boxed warning. In the biosimilar’s case, it warns against fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy. Other adverse reactions include fever, headache, neutropenia, and lymphopenia.

cpalmer@mdedge.com

The Food and Drug Administration has approved rituximab-pvvr (Ruxience) for adults with non-Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), and granulomatosis with polyangiitis and microscopic polyangiitis. It is the first biosimilar approved to treat these two rare autoimmune conditions.

Specifically, the biosimilar product is approved as single-agent therapy for relapsed or refractory, low grade or follicular, CD20-positive B-cell non-Hodgkin lymphoma; in combination with chemotherapy for other types of previously untreated CD20-positive B-cell non-Hodgkin lymphoma; and as a single agent for nonprogressing, low-grade, CD20-positive B-cell non-Hodgkin lymphoma after first-line chemotherapy treatment. It is also approved for both previously untreated and previously treated CD20-positive CLL in combination with chemotherapy. And it is approved for granulomatosis with polyangiitis and microscopic polyangiitis in combination with glucocorticoids.

The approval is based on demonstration that rituximab-pvvr had no clinically meaningful differences in safety or efficacy when compared with the reference drug, rituximab (Rituxan), according to a release from the biosimilar’s developer. As with rituximab, rituximab-pvvr’s label comes with an FDA boxed warning. In the biosimilar’s case, it warns against fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy. Other adverse reactions include fever, headache, neutropenia, and lymphopenia.

cpalmer@mdedge.com

The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.

©pixologicstudio/thinkstockphotos.com

Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.

The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.

They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).

“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.

The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.

mlesney@mdedge.com

SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.

The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.

©pixologicstudio/thinkstockphotos.com

Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.

The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.

They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).

“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.

The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.

mlesney@mdedge.com

SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.

The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.

©pixologicstudio/thinkstockphotos.com

Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.

The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.

They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).

“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.

The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.

mlesney@mdedge.com

SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.

AGA member Zobair Younossi, MD, MPH, and three other expert and patient panelists called upon Congress to help educate policymakers and the public on the increasing burden of NASH and to take steps to prevent its increase, including more funding for research.

Dr. Younossi provided congressional staffers with an informative presentation on the prevalence, adverse clinical outcomes, and economic outcomes of nonalcoholic steatohepatitis (NASH). He noted that 6.65 million adults have NASH – 688,000 have advanced NASH. Treatment of these patients carries an economic burden of $222.6 billion in direct costs and $95.4 billion in lifetime direct costs of advanced NASH.

Although NASH was discovered almost 40 years ago, the prevalence has doubled in the last 15 years and challenges to optimize disease diagnosis and management remain. The briefing was sponsored by the Global Liver Institute and its founder and CEO, Donna Cryer, JD, is a NASH patient and liver transplant recipient. Dr. Younossi noted that, between 2015 and 2030, the percentage of nonalcoholic fatty liver disease (NAFLD) that is related to NASH is projected to increase from 20% to 27%.

AGA thanks Dr. Younossi, the other panelists, and the Global Liver Institute for assembling this important educational forum and encouraging Congress to take action.
 

ginews@gastro.org

AGA member Zobair Younossi, MD, MPH, and three other expert and patient panelists called upon Congress to help educate policymakers and the public on the increasing burden of NASH and to take steps to prevent its increase, including more funding for research.

Dr. Younossi provided congressional staffers with an informative presentation on the prevalence, adverse clinical outcomes, and economic outcomes of nonalcoholic steatohepatitis (NASH). He noted that 6.65 million adults have NASH – 688,000 have advanced NASH. Treatment of these patients carries an economic burden of $222.6 billion in direct costs and $95.4 billion in lifetime direct costs of advanced NASH.

Although NASH was discovered almost 40 years ago, the prevalence has doubled in the last 15 years and challenges to optimize disease diagnosis and management remain. The briefing was sponsored by the Global Liver Institute and its founder and CEO, Donna Cryer, JD, is a NASH patient and liver transplant recipient. Dr. Younossi noted that, between 2015 and 2030, the percentage of nonalcoholic fatty liver disease (NAFLD) that is related to NASH is projected to increase from 20% to 27%.

AGA thanks Dr. Younossi, the other panelists, and the Global Liver Institute for assembling this important educational forum and encouraging Congress to take action.
 

ginews@gastro.org

AGA member Zobair Younossi, MD, MPH, and three other expert and patient panelists called upon Congress to help educate policymakers and the public on the increasing burden of NASH and to take steps to prevent its increase, including more funding for research.

Dr. Younossi provided congressional staffers with an informative presentation on the prevalence, adverse clinical outcomes, and economic outcomes of nonalcoholic steatohepatitis (NASH). He noted that 6.65 million adults have NASH – 688,000 have advanced NASH. Treatment of these patients carries an economic burden of $222.6 billion in direct costs and $95.4 billion in lifetime direct costs of advanced NASH.

Although NASH was discovered almost 40 years ago, the prevalence has doubled in the last 15 years and challenges to optimize disease diagnosis and management remain. The briefing was sponsored by the Global Liver Institute and its founder and CEO, Donna Cryer, JD, is a NASH patient and liver transplant recipient. Dr. Younossi noted that, between 2015 and 2030, the percentage of nonalcoholic fatty liver disease (NAFLD) that is related to NASH is projected to increase from 20% to 27%.

AGA thanks Dr. Younossi, the other panelists, and the Global Liver Institute for assembling this important educational forum and encouraging Congress to take action.
 

ginews@gastro.org

The AGA journals – Gastroenterology, Clinical Gastroenterology and Hepatology (CGH), and Cellular and Molecular Gastroenterology and Hepatology (CMGH) – are pleased to announce their 2019-2020 editorial fellows.


Gastroenterology
Feng Su, MD
University of Washington, Seattle
@FengSu_MD

Victoria Weis, PhD
Wake Forest School of Medicine, Winston-Salem, N.C.

CGH
Austin Chiang, MD, MPH
Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia
@AustinChiangMD

Jennifer Kolb, MD
University of Colorado Anschutz Medical Campus, Aurora

CMGH
Cambrian Liu, PhD
The Saban Research Institute, Children’s Hospital Los Angeles

Tirthadipa Pradhan-Sundd, PhD
University of Pittsburgh, Pennsylvania
@Tirthadipa

The editorial fellows will be mentored on their respective journals’ editorial processes, including peer review and the publication process from manuscript submission to acceptance. They will participate in discussions and conferences with the boards of editors and work closely with the AGA editorial staff. Additionally, the fellows will participate in AGA’s new reviewer education program and will also be offered the opportunity to contribute content to their respective journals. The newly expanded program builds on the success of the previous 2 years when Gastroenterology had an editorial fellow.

The journals’ board of editors and editorial staff congratulate the fellows and are excited to work with them over the next year.
 

ginews@gastro.org

The AGA journals – Gastroenterology, Clinical Gastroenterology and Hepatology (CGH), and Cellular and Molecular Gastroenterology and Hepatology (CMGH) – are pleased to announce their 2019-2020 editorial fellows.


Gastroenterology
Feng Su, MD
University of Washington, Seattle
@FengSu_MD

Victoria Weis, PhD
Wake Forest School of Medicine, Winston-Salem, N.C.

CGH
Austin Chiang, MD, MPH
Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia
@AustinChiangMD

Jennifer Kolb, MD
University of Colorado Anschutz Medical Campus, Aurora

CMGH
Cambrian Liu, PhD
The Saban Research Institute, Children’s Hospital Los Angeles

Tirthadipa Pradhan-Sundd, PhD
University of Pittsburgh, Pennsylvania
@Tirthadipa

The editorial fellows will be mentored on their respective journals’ editorial processes, including peer review and the publication process from manuscript submission to acceptance. They will participate in discussions and conferences with the boards of editors and work closely with the AGA editorial staff. Additionally, the fellows will participate in AGA’s new reviewer education program and will also be offered the opportunity to contribute content to their respective journals. The newly expanded program builds on the success of the previous 2 years when Gastroenterology had an editorial fellow.

The journals’ board of editors and editorial staff congratulate the fellows and are excited to work with them over the next year.
 

ginews@gastro.org

The AGA journals – Gastroenterology, Clinical Gastroenterology and Hepatology (CGH), and Cellular and Molecular Gastroenterology and Hepatology (CMGH) – are pleased to announce their 2019-2020 editorial fellows.


Gastroenterology
Feng Su, MD
University of Washington, Seattle
@FengSu_MD

Victoria Weis, PhD
Wake Forest School of Medicine, Winston-Salem, N.C.

CGH
Austin Chiang, MD, MPH
Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia
@AustinChiangMD

Jennifer Kolb, MD
University of Colorado Anschutz Medical Campus, Aurora

CMGH
Cambrian Liu, PhD
The Saban Research Institute, Children’s Hospital Los Angeles

Tirthadipa Pradhan-Sundd, PhD
University of Pittsburgh, Pennsylvania
@Tirthadipa

The editorial fellows will be mentored on their respective journals’ editorial processes, including peer review and the publication process from manuscript submission to acceptance. They will participate in discussions and conferences with the boards of editors and work closely with the AGA editorial staff. Additionally, the fellows will participate in AGA’s new reviewer education program and will also be offered the opportunity to contribute content to their respective journals. The newly expanded program builds on the success of the previous 2 years when Gastroenterology had an editorial fellow.

The journals’ board of editors and editorial staff congratulate the fellows and are excited to work with them over the next year.
 

ginews@gastro.org

AGA’s microbiome leaders recently met with representatives from FDA’s Center for Biologics Evaluation and Research (CBER) to share clinician and researcher perspectives on fecal microbiota transplantation (FMT) and understand CBER’s current thinking on the regulation of FMT for the treatment of Clostridioides difficile (C. difficile) infection. Here are the key takeaways from AGA’s discussion with CBER.

AGA made clear to FDA the needs and concerns of the clinical and research communities regarding FMT. AGA communicated clinician concerns about patient access to whole-stool FMT being restricted or perhaps eliminated once drugs containing live microbials are FDA approved. AGA’s representatives also shared concerns about the narrow inclusion criteria for current clinical trials and whether the new drugs will be as effective as whole-stool FMT for vulnerable populations such as the elderly or immunocompromised, who make up the majority of patients with C. difficile infection but are often excluded from current trials. Finally, AGA emphasized the need to encourage innovation in product development and the importance of performing controlled safety and efficacy studies on products that can be manufactured predictably and reproducibly.

All stakeholders agreed that the AGA FMT National Registry is an important effort to collect short- and long-term data on the safety and efficacy of FMT. AGA will maintain dialogue with CBER regarding data from the registry and lessons learned. Clinicians practicing FMT are strongly encouraged to participate in the FMT National Registry, which will follow short- and long-term outcomes of patients receiving FMT for up to 10 years. The registry is funded by a grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (award number R24 AI118629) and is a partnership of AGA, the Crohn’s &nd Colitis Foundation, the Infectious Diseases Society of America and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

CBER is currently working on an update to the enforcement discretion policy on the use of FMT for C. difficile infection not responsive to standard therapies.Agency representatives noted that all comments will be considered as the agency finalizes the guidance. The current enforcement discretion policy has been in place since July 2013 and was most recently updated by CBER in a draft guidance in March 2016. The policy enables clinicians to use FMT for the treatment of C. difficile infection not responsive to standard therapies without having an investigational new drug (IND) application in place.

Human stool will continue to be regulated as a drug and biological product. The agency stated that human stool does not meet the definition of a tissue and FDA does not intend to change how it is currently classified.

CBER is interested in hearing ideas for novel trial designs that may help address the challenges of patient recruitment for clinical trials in C. difficile infection and other indications for FMT. AGA encourages members to share their thoughts on this topic through the AGA Community.

Following AGA’s meeting with CBER, FDA issued a safety alert because of the death of a patient who died from an FMT containing a multi-drug resistant organism. The agency has since issued additional requirements for IND holders on stool donor screening. AGA will continue to engage with FDA on this issue and share updates as they become available with all members.

Meeting participants from AGA membership included:

• Gail A. Hecht, MD, MS, AGAF, immediate past chair, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Colleen R. Kelly, MD, co-chair, AGA FMT National Registry Steering Committee

• Alexander Khoruts, MD, member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Gary D. Wu, MD, AGAF, basic research councilor, AGA Institute Governing Board, and member, AGA FMT National Registry Steering Committee


Meeting participants from FDA/CBER included:

• Peter Marks, MD, PhD, Director, CBER

• Celia Witten, PhD, MD, Deputy Director, CBER

• Diane Maloney, JD, Associate Director for Policy, CBER

• Julie Tierney, JD, Senior Policy Advisor for Strategic Planning & Legislation, CBER

• Marion Gruber, PhD, Director, Office of Vaccines Research and Review (OVRR), CBER

• Theresa Finn, PhD, Associate Director for Policy, OVRR, CBER

• Doran Fink, MD, PhD, Deputy Director, Clinical, Division of Vaccines and Related Products Applications, OVRR, CBER

• Paul Carlson, PhD, Senior Staff Fellow, OVRR

• Lorrie McNeill, Director, Office of Communication, Outreach and Development, CBER


This meeting took place on May 6, 2019, at the FDA headquarters in Silver Spring, Md.
 

ginews@gastro.org

AGA’s microbiome leaders recently met with representatives from FDA’s Center for Biologics Evaluation and Research (CBER) to share clinician and researcher perspectives on fecal microbiota transplantation (FMT) and understand CBER’s current thinking on the regulation of FMT for the treatment of Clostridioides difficile (C. difficile) infection. Here are the key takeaways from AGA’s discussion with CBER.

AGA made clear to FDA the needs and concerns of the clinical and research communities regarding FMT. AGA communicated clinician concerns about patient access to whole-stool FMT being restricted or perhaps eliminated once drugs containing live microbials are FDA approved. AGA’s representatives also shared concerns about the narrow inclusion criteria for current clinical trials and whether the new drugs will be as effective as whole-stool FMT for vulnerable populations such as the elderly or immunocompromised, who make up the majority of patients with C. difficile infection but are often excluded from current trials. Finally, AGA emphasized the need to encourage innovation in product development and the importance of performing controlled safety and efficacy studies on products that can be manufactured predictably and reproducibly.

All stakeholders agreed that the AGA FMT National Registry is an important effort to collect short- and long-term data on the safety and efficacy of FMT. AGA will maintain dialogue with CBER regarding data from the registry and lessons learned. Clinicians practicing FMT are strongly encouraged to participate in the FMT National Registry, which will follow short- and long-term outcomes of patients receiving FMT for up to 10 years. The registry is funded by a grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (award number R24 AI118629) and is a partnership of AGA, the Crohn’s &nd Colitis Foundation, the Infectious Diseases Society of America and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

CBER is currently working on an update to the enforcement discretion policy on the use of FMT for C. difficile infection not responsive to standard therapies.Agency representatives noted that all comments will be considered as the agency finalizes the guidance. The current enforcement discretion policy has been in place since July 2013 and was most recently updated by CBER in a draft guidance in March 2016. The policy enables clinicians to use FMT for the treatment of C. difficile infection not responsive to standard therapies without having an investigational new drug (IND) application in place.

Human stool will continue to be regulated as a drug and biological product. The agency stated that human stool does not meet the definition of a tissue and FDA does not intend to change how it is currently classified.

CBER is interested in hearing ideas for novel trial designs that may help address the challenges of patient recruitment for clinical trials in C. difficile infection and other indications for FMT. AGA encourages members to share their thoughts on this topic through the AGA Community.

Following AGA’s meeting with CBER, FDA issued a safety alert because of the death of a patient who died from an FMT containing a multi-drug resistant organism. The agency has since issued additional requirements for IND holders on stool donor screening. AGA will continue to engage with FDA on this issue and share updates as they become available with all members.

Meeting participants from AGA membership included:

• Gail A. Hecht, MD, MS, AGAF, immediate past chair, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Colleen R. Kelly, MD, co-chair, AGA FMT National Registry Steering Committee

• Alexander Khoruts, MD, member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Gary D. Wu, MD, AGAF, basic research councilor, AGA Institute Governing Board, and member, AGA FMT National Registry Steering Committee


Meeting participants from FDA/CBER included:

• Peter Marks, MD, PhD, Director, CBER

• Celia Witten, PhD, MD, Deputy Director, CBER

• Diane Maloney, JD, Associate Director for Policy, CBER

• Julie Tierney, JD, Senior Policy Advisor for Strategic Planning & Legislation, CBER

• Marion Gruber, PhD, Director, Office of Vaccines Research and Review (OVRR), CBER

• Theresa Finn, PhD, Associate Director for Policy, OVRR, CBER

• Doran Fink, MD, PhD, Deputy Director, Clinical, Division of Vaccines and Related Products Applications, OVRR, CBER

• Paul Carlson, PhD, Senior Staff Fellow, OVRR

• Lorrie McNeill, Director, Office of Communication, Outreach and Development, CBER


This meeting took place on May 6, 2019, at the FDA headquarters in Silver Spring, Md.
 

ginews@gastro.org

AGA’s microbiome leaders recently met with representatives from FDA’s Center for Biologics Evaluation and Research (CBER) to share clinician and researcher perspectives on fecal microbiota transplantation (FMT) and understand CBER’s current thinking on the regulation of FMT for the treatment of Clostridioides difficile (C. difficile) infection. Here are the key takeaways from AGA’s discussion with CBER.

AGA made clear to FDA the needs and concerns of the clinical and research communities regarding FMT. AGA communicated clinician concerns about patient access to whole-stool FMT being restricted or perhaps eliminated once drugs containing live microbials are FDA approved. AGA’s representatives also shared concerns about the narrow inclusion criteria for current clinical trials and whether the new drugs will be as effective as whole-stool FMT for vulnerable populations such as the elderly or immunocompromised, who make up the majority of patients with C. difficile infection but are often excluded from current trials. Finally, AGA emphasized the need to encourage innovation in product development and the importance of performing controlled safety and efficacy studies on products that can be manufactured predictably and reproducibly.

All stakeholders agreed that the AGA FMT National Registry is an important effort to collect short- and long-term data on the safety and efficacy of FMT. AGA will maintain dialogue with CBER regarding data from the registry and lessons learned. Clinicians practicing FMT are strongly encouraged to participate in the FMT National Registry, which will follow short- and long-term outcomes of patients receiving FMT for up to 10 years. The registry is funded by a grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (award number R24 AI118629) and is a partnership of AGA, the Crohn’s &nd Colitis Foundation, the Infectious Diseases Society of America and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

CBER is currently working on an update to the enforcement discretion policy on the use of FMT for C. difficile infection not responsive to standard therapies.Agency representatives noted that all comments will be considered as the agency finalizes the guidance. The current enforcement discretion policy has been in place since July 2013 and was most recently updated by CBER in a draft guidance in March 2016. The policy enables clinicians to use FMT for the treatment of C. difficile infection not responsive to standard therapies without having an investigational new drug (IND) application in place.

Human stool will continue to be regulated as a drug and biological product. The agency stated that human stool does not meet the definition of a tissue and FDA does not intend to change how it is currently classified.

CBER is interested in hearing ideas for novel trial designs that may help address the challenges of patient recruitment for clinical trials in C. difficile infection and other indications for FMT. AGA encourages members to share their thoughts on this topic through the AGA Community.

Following AGA’s meeting with CBER, FDA issued a safety alert because of the death of a patient who died from an FMT containing a multi-drug resistant organism. The agency has since issued additional requirements for IND holders on stool donor screening. AGA will continue to engage with FDA on this issue and share updates as they become available with all members.

Meeting participants from AGA membership included:

• Gail A. Hecht, MD, MS, AGAF, immediate past chair, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Colleen R. Kelly, MD, co-chair, AGA FMT National Registry Steering Committee

• Alexander Khoruts, MD, member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Gary D. Wu, MD, AGAF, basic research councilor, AGA Institute Governing Board, and member, AGA FMT National Registry Steering Committee


Meeting participants from FDA/CBER included:

• Peter Marks, MD, PhD, Director, CBER

• Celia Witten, PhD, MD, Deputy Director, CBER

• Diane Maloney, JD, Associate Director for Policy, CBER

• Julie Tierney, JD, Senior Policy Advisor for Strategic Planning & Legislation, CBER

• Marion Gruber, PhD, Director, Office of Vaccines Research and Review (OVRR), CBER

• Theresa Finn, PhD, Associate Director for Policy, OVRR, CBER

• Doran Fink, MD, PhD, Deputy Director, Clinical, Division of Vaccines and Related Products Applications, OVRR, CBER

• Paul Carlson, PhD, Senior Staff Fellow, OVRR

• Lorrie McNeill, Director, Office of Communication, Outreach and Development, CBER


This meeting took place on May 6, 2019, at the FDA headquarters in Silver Spring, Md.
 

ginews@gastro.org