Pediatrics

Obesity and hypoxia at the time of hospital admission predicted more severe disease in children diagnosed with COVID-19, based on data from 281 patients at 8 locations.

Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
 

Independent predictors of disease severity in children found

After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 10⁹ cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).

“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.

Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.

During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.

“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.

“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.

The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.

“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
 

Findings confirm other clinical experience

The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.

Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”

Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.

The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.

SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.

Obesity and hypoxia at the time of hospital admission predicted more severe disease in children diagnosed with COVID-19, based on data from 281 patients at 8 locations.

Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
 

Independent predictors of disease severity in children found

After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 10⁹ cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).

“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.

Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.

During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.

“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.

“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.

The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.

“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
 

Findings confirm other clinical experience

The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.

Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”

Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.

The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.

SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.

Obesity and hypoxia at the time of hospital admission predicted more severe disease in children diagnosed with COVID-19, based on data from 281 patients at 8 locations.

Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
 

Independent predictors of disease severity in children found

After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 10⁹ cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).

“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.

Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.

During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.

“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.

“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.

The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.

“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
 

Findings confirm other clinical experience

The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.

Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”

Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.

The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.

SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.

Additional blood cultures are not needed after two negative follow-up blood culture results in well-appearing patients with Staphylococcus aureus bacteremia, reported Caitlin Cardenas-Comfort, MD, of the section of pediatric infectious diseases at Baylor College of Medicine, Houston, and colleagues.

CDC/Janice Haney Carr

In a retrospective cohort study of 122 pediatric patients with documented Staphylococcus aureus bacteremia (SAB) that were hospitalized at one of three hospitals in the Texas Children’s Hospital network in Houston, Dr. Cardenas-Comfort and colleagues sought to determine whether specific recommendations can be made on the number of follow-up blood cultures (FUBC) needed to document clearance of SAB. Patients included in the study were under 18 years of age and had confirmed diagnosis of SAB between Jan. 1, and Dec. 31, 2018.
 

Most cases of bacteremia resolve in under 48 hours

In the majority of cases, patients had bacteremia for less than 48 hours and few to no complications. Only 16% of patients experienced bacteremia lasting 3 or more days, and they had either central line-associated bloodstream infection, endocarditis, or osteomyelitis. In such cases, “patients with endovascular and closed-space infections are at an increased risk of persistent bacteremia,” warranting more conservative monitoring and follow-up, cautioned the researchers.

Although Dr. Cardenas-Comfort and colleagues did note an association between the duration of bacteremia and a diagnosis of infectious disease, increased risk for persistent SAB did not appear to be tied to an underlying medical condition, including immunosuppression.

Fewer than 5% of patients with SAB had intermittent positive cultures and fewer than 1% had repeat positive cultures following two negative FUBC results. For those patients with intermittent positive cultures, the risk of being diagnosed with endocarditis or osteomyelitis is more than double. The authors suggested that “source control could be a critical variable” increasing the risk for intermittent positive cultures, noting that surgical debridement occurred more than 24 hours following initial blood draw for every patient in the osteomyelitis group. In contrast, of those who had consistently negative FUBC results, only 2 of 33 (6%) had debridement in the same period, and only 6 of 33 (18%) required more than one debridement.
 

Children are less likely to have intermittent positive cultures

Dr. Cardenas-Comfort and colleagues also observed that intermittent positive cultures may appear less frequently in children than adults, consistent with a recent study of adults in which intermittent cultures were found in 13% of 1.071 SAB cases. In just 4% of the cases in that study, more than 2 days of negative blood cultures preceded a repeat positive culture.

The researchers noted several study limitations in their own research. Because more than half (61%) of patients had two or less FUBCs collected, and 21% one or less, they acknowledged that their conclusions are based on the presumption that the 61% of patients would not have any further positive cultures if they had been drawn. Relying on provider documentation also suggested that cases of bacteremia without an identified source also likely were overrepresented. The retrospective nature of the study only allowed for limited collection of standardized follow-up metrics with the limited patient sample available. Patient characteristics also may have affected the quality of study results because a large number of patients had underlying medical conditions or were premature infants.
 

Look for ongoing hemodynamic instability before third FUBC

Dr. Cardenas-Comfort and colleagues only recommend a third FUBC in cases where patients demonstrate ongoing hemodynamic instability. Applying this to their study population, in retrospect, the authors noted that unnecessary FUBCs could have been prevented in 26% of patients included in the study. They further recommend a thorough clinical evaluation for any patients with SAB lasting 3 or more days with an unidentified infection source. Further research could be beneficial in evaluating cost savings that come from eliminating unnecessary cultures. Additionally, performing a powered analysis would help to determine the probability of an increase in complications based on implementation of these recommendations.

In a separate interview, Tina Q. Tan, MD, infectious disease specialist at Ann & Robert H. Lurie Children’s Hospital of Chicago noted: “This study provides some importance evidence-based guidance on deciding how many blood cultures are needed to demonstrate clearance of S. aureus bacteremia, even in children who have intermittent positive cultures after having negative FUBCs. The recommendation that additional blood cultures to document sterility are not needed after 2 FUBC results are negative in well-appearing children is one that has the potential to decrease cost and unnecessary discomfort in patients. The recommendation currently is for well-appearing children; children who are ill appearing may require further blood cultures to document sterility. Even though this is a single-center study with a relatively small number of patients (n = 122), the information provided is a very useful guide to all clinicians who deal with this issue. Further studies are needed to determine the impact on cost reduction by the elimination of unnecessary blood cultures and whether the rate of complications would increase as a result of not obtaining further cultures in well-appearing children who have two negative follow up blood cultures.”

Dr. Cardenas-Comfort and colleagues as well as Dr. Tan had no conflicts of interest and no relevant financial disclosures. There was no external funding for the study.

SOURCE: Cardenas-Comfort C et al. Pediatrics. 2020. doi: 10.1542/peds.2020-1821.

Additional blood cultures are not needed after two negative follow-up blood culture results in well-appearing patients with Staphylococcus aureus bacteremia, reported Caitlin Cardenas-Comfort, MD, of the section of pediatric infectious diseases at Baylor College of Medicine, Houston, and colleagues.

CDC/Janice Haney Carr

In a retrospective cohort study of 122 pediatric patients with documented Staphylococcus aureus bacteremia (SAB) that were hospitalized at one of three hospitals in the Texas Children’s Hospital network in Houston, Dr. Cardenas-Comfort and colleagues sought to determine whether specific recommendations can be made on the number of follow-up blood cultures (FUBC) needed to document clearance of SAB. Patients included in the study were under 18 years of age and had confirmed diagnosis of SAB between Jan. 1, and Dec. 31, 2018.
 

Most cases of bacteremia resolve in under 48 hours

In the majority of cases, patients had bacteremia for less than 48 hours and few to no complications. Only 16% of patients experienced bacteremia lasting 3 or more days, and they had either central line-associated bloodstream infection, endocarditis, or osteomyelitis. In such cases, “patients with endovascular and closed-space infections are at an increased risk of persistent bacteremia,” warranting more conservative monitoring and follow-up, cautioned the researchers.

Although Dr. Cardenas-Comfort and colleagues did note an association between the duration of bacteremia and a diagnosis of infectious disease, increased risk for persistent SAB did not appear to be tied to an underlying medical condition, including immunosuppression.

Fewer than 5% of patients with SAB had intermittent positive cultures and fewer than 1% had repeat positive cultures following two negative FUBC results. For those patients with intermittent positive cultures, the risk of being diagnosed with endocarditis or osteomyelitis is more than double. The authors suggested that “source control could be a critical variable” increasing the risk for intermittent positive cultures, noting that surgical debridement occurred more than 24 hours following initial blood draw for every patient in the osteomyelitis group. In contrast, of those who had consistently negative FUBC results, only 2 of 33 (6%) had debridement in the same period, and only 6 of 33 (18%) required more than one debridement.
 

Children are less likely to have intermittent positive cultures

Dr. Cardenas-Comfort and colleagues also observed that intermittent positive cultures may appear less frequently in children than adults, consistent with a recent study of adults in which intermittent cultures were found in 13% of 1.071 SAB cases. In just 4% of the cases in that study, more than 2 days of negative blood cultures preceded a repeat positive culture.

The researchers noted several study limitations in their own research. Because more than half (61%) of patients had two or less FUBCs collected, and 21% one or less, they acknowledged that their conclusions are based on the presumption that the 61% of patients would not have any further positive cultures if they had been drawn. Relying on provider documentation also suggested that cases of bacteremia without an identified source also likely were overrepresented. The retrospective nature of the study only allowed for limited collection of standardized follow-up metrics with the limited patient sample available. Patient characteristics also may have affected the quality of study results because a large number of patients had underlying medical conditions or were premature infants.
 

Look for ongoing hemodynamic instability before third FUBC

Dr. Cardenas-Comfort and colleagues only recommend a third FUBC in cases where patients demonstrate ongoing hemodynamic instability. Applying this to their study population, in retrospect, the authors noted that unnecessary FUBCs could have been prevented in 26% of patients included in the study. They further recommend a thorough clinical evaluation for any patients with SAB lasting 3 or more days with an unidentified infection source. Further research could be beneficial in evaluating cost savings that come from eliminating unnecessary cultures. Additionally, performing a powered analysis would help to determine the probability of an increase in complications based on implementation of these recommendations.

In a separate interview, Tina Q. Tan, MD, infectious disease specialist at Ann & Robert H. Lurie Children’s Hospital of Chicago noted: “This study provides some importance evidence-based guidance on deciding how many blood cultures are needed to demonstrate clearance of S. aureus bacteremia, even in children who have intermittent positive cultures after having negative FUBCs. The recommendation that additional blood cultures to document sterility are not needed after 2 FUBC results are negative in well-appearing children is one that has the potential to decrease cost and unnecessary discomfort in patients. The recommendation currently is for well-appearing children; children who are ill appearing may require further blood cultures to document sterility. Even though this is a single-center study with a relatively small number of patients (n = 122), the information provided is a very useful guide to all clinicians who deal with this issue. Further studies are needed to determine the impact on cost reduction by the elimination of unnecessary blood cultures and whether the rate of complications would increase as a result of not obtaining further cultures in well-appearing children who have two negative follow up blood cultures.”

Dr. Cardenas-Comfort and colleagues as well as Dr. Tan had no conflicts of interest and no relevant financial disclosures. There was no external funding for the study.

SOURCE: Cardenas-Comfort C et al. Pediatrics. 2020. doi: 10.1542/peds.2020-1821.

Additional blood cultures are not needed after two negative follow-up blood culture results in well-appearing patients with Staphylococcus aureus bacteremia, reported Caitlin Cardenas-Comfort, MD, of the section of pediatric infectious diseases at Baylor College of Medicine, Houston, and colleagues.

CDC/Janice Haney Carr

In a retrospective cohort study of 122 pediatric patients with documented Staphylococcus aureus bacteremia (SAB) that were hospitalized at one of three hospitals in the Texas Children’s Hospital network in Houston, Dr. Cardenas-Comfort and colleagues sought to determine whether specific recommendations can be made on the number of follow-up blood cultures (FUBC) needed to document clearance of SAB. Patients included in the study were under 18 years of age and had confirmed diagnosis of SAB between Jan. 1, and Dec. 31, 2018.
 

Most cases of bacteremia resolve in under 48 hours

In the majority of cases, patients had bacteremia for less than 48 hours and few to no complications. Only 16% of patients experienced bacteremia lasting 3 or more days, and they had either central line-associated bloodstream infection, endocarditis, or osteomyelitis. In such cases, “patients with endovascular and closed-space infections are at an increased risk of persistent bacteremia,” warranting more conservative monitoring and follow-up, cautioned the researchers.

Although Dr. Cardenas-Comfort and colleagues did note an association between the duration of bacteremia and a diagnosis of infectious disease, increased risk for persistent SAB did not appear to be tied to an underlying medical condition, including immunosuppression.

Fewer than 5% of patients with SAB had intermittent positive cultures and fewer than 1% had repeat positive cultures following two negative FUBC results. For those patients with intermittent positive cultures, the risk of being diagnosed with endocarditis or osteomyelitis is more than double. The authors suggested that “source control could be a critical variable” increasing the risk for intermittent positive cultures, noting that surgical debridement occurred more than 24 hours following initial blood draw for every patient in the osteomyelitis group. In contrast, of those who had consistently negative FUBC results, only 2 of 33 (6%) had debridement in the same period, and only 6 of 33 (18%) required more than one debridement.
 

Children are less likely to have intermittent positive cultures

Dr. Cardenas-Comfort and colleagues also observed that intermittent positive cultures may appear less frequently in children than adults, consistent with a recent study of adults in which intermittent cultures were found in 13% of 1.071 SAB cases. In just 4% of the cases in that study, more than 2 days of negative blood cultures preceded a repeat positive culture.

The researchers noted several study limitations in their own research. Because more than half (61%) of patients had two or less FUBCs collected, and 21% one or less, they acknowledged that their conclusions are based on the presumption that the 61% of patients would not have any further positive cultures if they had been drawn. Relying on provider documentation also suggested that cases of bacteremia without an identified source also likely were overrepresented. The retrospective nature of the study only allowed for limited collection of standardized follow-up metrics with the limited patient sample available. Patient characteristics also may have affected the quality of study results because a large number of patients had underlying medical conditions or were premature infants.
 

Look for ongoing hemodynamic instability before third FUBC

Dr. Cardenas-Comfort and colleagues only recommend a third FUBC in cases where patients demonstrate ongoing hemodynamic instability. Applying this to their study population, in retrospect, the authors noted that unnecessary FUBCs could have been prevented in 26% of patients included in the study. They further recommend a thorough clinical evaluation for any patients with SAB lasting 3 or more days with an unidentified infection source. Further research could be beneficial in evaluating cost savings that come from eliminating unnecessary cultures. Additionally, performing a powered analysis would help to determine the probability of an increase in complications based on implementation of these recommendations.

In a separate interview, Tina Q. Tan, MD, infectious disease specialist at Ann & Robert H. Lurie Children’s Hospital of Chicago noted: “This study provides some importance evidence-based guidance on deciding how many blood cultures are needed to demonstrate clearance of S. aureus bacteremia, even in children who have intermittent positive cultures after having negative FUBCs. The recommendation that additional blood cultures to document sterility are not needed after 2 FUBC results are negative in well-appearing children is one that has the potential to decrease cost and unnecessary discomfort in patients. The recommendation currently is for well-appearing children; children who are ill appearing may require further blood cultures to document sterility. Even though this is a single-center study with a relatively small number of patients (n = 122), the information provided is a very useful guide to all clinicians who deal with this issue. Further studies are needed to determine the impact on cost reduction by the elimination of unnecessary blood cultures and whether the rate of complications would increase as a result of not obtaining further cultures in well-appearing children who have two negative follow up blood cultures.”

Dr. Cardenas-Comfort and colleagues as well as Dr. Tan had no conflicts of interest and no relevant financial disclosures. There was no external funding for the study.

SOURCE: Cardenas-Comfort C et al. Pediatrics. 2020. doi: 10.1542/peds.2020-1821.

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The news on children and COVID-19 for Thanksgiving week does not provide a lot of room for thankfulness.

“The number of new child COVID-19 cases reported this week, nearly 154,000, is the highest weekly increase since the pandemic began,” the American Academy of Pediatrics and the Children’s Hospital Association said in their latest weekly report.

For those not counting, the week ending Nov. 26 was the fifth in a row to show “the highest weekly increase since the pandemic began,” based on data the AAP and CHA have been collecting from 49 state health departments (New York does not report ages), as well as the District of Columbia, New York City, Puerto Rico, and Guam.

The 153,608 new cases bring the total number of COVID-19 cases in children to almost 1.34 million in those jurisdictions, which is 12% of the total number of cases (11.2 million) among all ages. For just the week ending Nov. 26, children represented 13.7% of all new cases in the United States, down from 14.1% the previous week, according to the AAP/CHA data.

Among the states reporting child cases, Florida has the lowest cumulative proportion of child cases, 6.4%, but the state is using an age range of 0-14 years (no other state goes lower than 17 years). New Jersey and Texas are next at 6.9%, although Texas “reported age for only 6% of total confirmed cases,” the AAP and CHA noted.

There are 35 states above the national number of 12.0%, the highest being Wyoming at 23.3%, followed by Tennessee at 18.3% and South Carolina at 18.2%. The two southern states are the only ones to use an age range of 0-20 years for child cases, the two groups said in this week’s report, which did not include the usual data on testing, hospitalization, and mortality because of the holiday.

[email protected]

The news on children and COVID-19 for Thanksgiving week does not provide a lot of room for thankfulness.

“The number of new child COVID-19 cases reported this week, nearly 154,000, is the highest weekly increase since the pandemic began,” the American Academy of Pediatrics and the Children’s Hospital Association said in their latest weekly report.

For those not counting, the week ending Nov. 26 was the fifth in a row to show “the highest weekly increase since the pandemic began,” based on data the AAP and CHA have been collecting from 49 state health departments (New York does not report ages), as well as the District of Columbia, New York City, Puerto Rico, and Guam.

The 153,608 new cases bring the total number of COVID-19 cases in children to almost 1.34 million in those jurisdictions, which is 12% of the total number of cases (11.2 million) among all ages. For just the week ending Nov. 26, children represented 13.7% of all new cases in the United States, down from 14.1% the previous week, according to the AAP/CHA data.

Among the states reporting child cases, Florida has the lowest cumulative proportion of child cases, 6.4%, but the state is using an age range of 0-14 years (no other state goes lower than 17 years). New Jersey and Texas are next at 6.9%, although Texas “reported age for only 6% of total confirmed cases,” the AAP and CHA noted.

There are 35 states above the national number of 12.0%, the highest being Wyoming at 23.3%, followed by Tennessee at 18.3% and South Carolina at 18.2%. The two southern states are the only ones to use an age range of 0-20 years for child cases, the two groups said in this week’s report, which did not include the usual data on testing, hospitalization, and mortality because of the holiday.

[email protected]

The news on children and COVID-19 for Thanksgiving week does not provide a lot of room for thankfulness.

“The number of new child COVID-19 cases reported this week, nearly 154,000, is the highest weekly increase since the pandemic began,” the American Academy of Pediatrics and the Children’s Hospital Association said in their latest weekly report.

For those not counting, the week ending Nov. 26 was the fifth in a row to show “the highest weekly increase since the pandemic began,” based on data the AAP and CHA have been collecting from 49 state health departments (New York does not report ages), as well as the District of Columbia, New York City, Puerto Rico, and Guam.

The 153,608 new cases bring the total number of COVID-19 cases in children to almost 1.34 million in those jurisdictions, which is 12% of the total number of cases (11.2 million) among all ages. For just the week ending Nov. 26, children represented 13.7% of all new cases in the United States, down from 14.1% the previous week, according to the AAP/CHA data.

Among the states reporting child cases, Florida has the lowest cumulative proportion of child cases, 6.4%, but the state is using an age range of 0-14 years (no other state goes lower than 17 years). New Jersey and Texas are next at 6.9%, although Texas “reported age for only 6% of total confirmed cases,” the AAP and CHA noted.

There are 35 states above the national number of 12.0%, the highest being Wyoming at 23.3%, followed by Tennessee at 18.3% and South Carolina at 18.2%. The two southern states are the only ones to use an age range of 0-20 years for child cases, the two groups said in this week’s report, which did not include the usual data on testing, hospitalization, and mortality because of the holiday.

[email protected]

Autism spectrum disorder (ASD) is characterized by impairments in communication and social interactions, along with repetitive and perseverant behaviors.¹ It has a prevalence of 0.75% to 1.1% among the general population.¹ The presentation of ASD can vary, and patients may have a wide range of comorbidities, such as attention-deficit/hyperactivity disorder (ADHD), neurologic disorders, and genetic disorders.¹ Therefore, a comprehensive evaluation needs to include a multidisciplinary assessment by clinicians from several specialties, including primary care, psychiatry, psychology, and neurology. Here I offer psychiatrists 3 Ps and the mnemonic SONG to describe a multidisciplinary approach to assessing a patient with suspected or confirmed ASD.

Primary care evaluation of patients with ASD is important for the diagnosis and treatment of any co-existing medical conditions. Primary care physicians are often the source of referrals to psychiatry, although the reason for the referral may not always be suspicion of autism. In my clinical practice, almost all referrals from primary care involve a chief complaint of anger or behavioral problems, or even obsessive-compulsive behaviors.

Psychiatric evaluation should include obtaining a detailed history of the patient’s conception, birth, development, and social life, and his/her family history of genetic conditions. In my practice, ADHD and elimination disorders are common comorbidities in patients with ASD. Consider communicating with daycare staff or teachers and auxiliary staff, such as guidance counselors, because doing so can help elucidate the diagnosis. Also, ask adult family members, preferably a parent, for collateral information to help establish an accurate diagnosis in your adult patients.

Psychological evaluation should include testing to rule out intellectual disability and learning disorders, which are common in patients with ASD.² Tests commonly used for evaluation of ASD include the Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), and Autism Diagnostic Interview-Revised (ADI-R).

Speech evaluation. Deficits in language and communication are commonly observed in patients with ASD, especially in younger patients.³ A study of the relationship between early language skills (age of first word production) and later functioning in children with ASD indicated that earlier age of first word acquisition was associated with higher cognitive ability and adaptive skills when measured later in childhood.³ Therefore, timely intervention following speech evaluation can result in favorable outcomes.

Occupational evaluation. Approximately 69% to 93% of children and adults with ASD exhibit sensory symptoms (hyperresponsive, hyporesponsive, and sensory-seeking behaviors).⁴ Patients with sensory symptoms often experience limitations in multiple areas of their life. Early intervention by an occupational therapist can help improve long-term outcomes.⁴

Neurologic evaluation is important because ASD is a neurodevelopmental disorder. Patients with ASD often have comorbid seizure disorders.¹ The estimated prevalence of epilepsy in these patients ranges from 2.7% to 44.4%.¹ A baseline EEG and neuroimaging can help improve your understanding of the relationship between ASD and seizure disorders, and guide treatment.

Genetic testing. Between 10% to 15% of individuals with ASD have a medical condition, such as cytogenetic or single-gene disorder, that causes ASD.⁵ Fragile X syndrome, tuberous sclerosis, and Prader-Willi syndrome are a few common examples of genetic disorders associated with ASD.⁵ Autism spectrum disorder has also been known to have a strong genetic basis with high probability of heritability in families.⁵ Genetic testing can help to detect any underlying genetic disorders in your patients as well as their family members. Chromosomal microarray analysis has become more accessible due to improved insurance coverage, and is convenient to perform by collection of a buccal mucosa sample in the office setting.

Autism spectrum disorder (ASD) is characterized by impairments in communication and social interactions, along with repetitive and perseverant behaviors.¹ It has a prevalence of 0.75% to 1.1% among the general population.¹ The presentation of ASD can vary, and patients may have a wide range of comorbidities, such as attention-deficit/hyperactivity disorder (ADHD), neurologic disorders, and genetic disorders.¹ Therefore, a comprehensive evaluation needs to include a multidisciplinary assessment by clinicians from several specialties, including primary care, psychiatry, psychology, and neurology. Here I offer psychiatrists 3 Ps and the mnemonic SONG to describe a multidisciplinary approach to assessing a patient with suspected or confirmed ASD.

Primary care evaluation of patients with ASD is important for the diagnosis and treatment of any co-existing medical conditions. Primary care physicians are often the source of referrals to psychiatry, although the reason for the referral may not always be suspicion of autism. In my clinical practice, almost all referrals from primary care involve a chief complaint of anger or behavioral problems, or even obsessive-compulsive behaviors.

Psychiatric evaluation should include obtaining a detailed history of the patient’s conception, birth, development, and social life, and his/her family history of genetic conditions. In my practice, ADHD and elimination disorders are common comorbidities in patients with ASD. Consider communicating with daycare staff or teachers and auxiliary staff, such as guidance counselors, because doing so can help elucidate the diagnosis. Also, ask adult family members, preferably a parent, for collateral information to help establish an accurate diagnosis in your adult patients.

Psychological evaluation should include testing to rule out intellectual disability and learning disorders, which are common in patients with ASD.² Tests commonly used for evaluation of ASD include the Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), and Autism Diagnostic Interview-Revised (ADI-R).

Speech evaluation. Deficits in language and communication are commonly observed in patients with ASD, especially in younger patients.³ A study of the relationship between early language skills (age of first word production) and later functioning in children with ASD indicated that earlier age of first word acquisition was associated with higher cognitive ability and adaptive skills when measured later in childhood.³ Therefore, timely intervention following speech evaluation can result in favorable outcomes.

Occupational evaluation. Approximately 69% to 93% of children and adults with ASD exhibit sensory symptoms (hyperresponsive, hyporesponsive, and sensory-seeking behaviors).⁴ Patients with sensory symptoms often experience limitations in multiple areas of their life. Early intervention by an occupational therapist can help improve long-term outcomes.⁴

Neurologic evaluation is important because ASD is a neurodevelopmental disorder. Patients with ASD often have comorbid seizure disorders.¹ The estimated prevalence of epilepsy in these patients ranges from 2.7% to 44.4%.¹ A baseline EEG and neuroimaging can help improve your understanding of the relationship between ASD and seizure disorders, and guide treatment.

Genetic testing. Between 10% to 15% of individuals with ASD have a medical condition, such as cytogenetic or single-gene disorder, that causes ASD.⁵ Fragile X syndrome, tuberous sclerosis, and Prader-Willi syndrome are a few common examples of genetic disorders associated with ASD.⁵ Autism spectrum disorder has also been known to have a strong genetic basis with high probability of heritability in families.⁵ Genetic testing can help to detect any underlying genetic disorders in your patients as well as their family members. Chromosomal microarray analysis has become more accessible due to improved insurance coverage, and is convenient to perform by collection of a buccal mucosa sample in the office setting.

Autism spectrum disorder (ASD) is characterized by impairments in communication and social interactions, along with repetitive and perseverant behaviors.¹ It has a prevalence of 0.75% to 1.1% among the general population.¹ The presentation of ASD can vary, and patients may have a wide range of comorbidities, such as attention-deficit/hyperactivity disorder (ADHD), neurologic disorders, and genetic disorders.¹ Therefore, a comprehensive evaluation needs to include a multidisciplinary assessment by clinicians from several specialties, including primary care, psychiatry, psychology, and neurology. Here I offer psychiatrists 3 Ps and the mnemonic SONG to describe a multidisciplinary approach to assessing a patient with suspected or confirmed ASD.

Primary care evaluation of patients with ASD is important for the diagnosis and treatment of any co-existing medical conditions. Primary care physicians are often the source of referrals to psychiatry, although the reason for the referral may not always be suspicion of autism. In my clinical practice, almost all referrals from primary care involve a chief complaint of anger or behavioral problems, or even obsessive-compulsive behaviors.

Psychiatric evaluation should include obtaining a detailed history of the patient’s conception, birth, development, and social life, and his/her family history of genetic conditions. In my practice, ADHD and elimination disorders are common comorbidities in patients with ASD. Consider communicating with daycare staff or teachers and auxiliary staff, such as guidance counselors, because doing so can help elucidate the diagnosis. Also, ask adult family members, preferably a parent, for collateral information to help establish an accurate diagnosis in your adult patients.

Psychological evaluation should include testing to rule out intellectual disability and learning disorders, which are common in patients with ASD.² Tests commonly used for evaluation of ASD include the Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), and Autism Diagnostic Interview-Revised (ADI-R).

Speech evaluation. Deficits in language and communication are commonly observed in patients with ASD, especially in younger patients.³ A study of the relationship between early language skills (age of first word production) and later functioning in children with ASD indicated that earlier age of first word acquisition was associated with higher cognitive ability and adaptive skills when measured later in childhood.³ Therefore, timely intervention following speech evaluation can result in favorable outcomes.

Occupational evaluation. Approximately 69% to 93% of children and adults with ASD exhibit sensory symptoms (hyperresponsive, hyporesponsive, and sensory-seeking behaviors).⁴ Patients with sensory symptoms often experience limitations in multiple areas of their life. Early intervention by an occupational therapist can help improve long-term outcomes.⁴

Neurologic evaluation is important because ASD is a neurodevelopmental disorder. Patients with ASD often have comorbid seizure disorders.¹ The estimated prevalence of epilepsy in these patients ranges from 2.7% to 44.4%.¹ A baseline EEG and neuroimaging can help improve your understanding of the relationship between ASD and seizure disorders, and guide treatment.

Genetic testing. Between 10% to 15% of individuals with ASD have a medical condition, such as cytogenetic or single-gene disorder, that causes ASD.⁵ Fragile X syndrome, tuberous sclerosis, and Prader-Willi syndrome are a few common examples of genetic disorders associated with ASD.⁵ Autism spectrum disorder has also been known to have a strong genetic basis with high probability of heritability in families.⁵ Genetic testing can help to detect any underlying genetic disorders in your patients as well as their family members. Chromosomal microarray analysis has become more accessible due to improved insurance coverage, and is convenient to perform by collection of a buccal mucosa sample in the office setting.

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The Food and Drug Administration has granted accelerated approval for naxitamab (Danyelza) to treat certain patients with neuroblastoma, based on response rates in two small trials.

Naxitamab is a humanized monoclonal antibody that targets GD2, a disialoganglioside highly expressed on neuroblastomas.

The FDA approved naxitamab for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in adults and children aged 1 year and older who have relapsed or refractory, high-risk neuroblastoma in the bone or bone marrow that demonstrated a partial response, minor response, or stable disease to prior therapy.

Naxitamab was originally developed at Memorial Sloan Kettering Cancer Center in New York, and licensed exclusively to Y-mAbs Therapeutics. As a result of the licensing arrangement, MSKCC has institutional financial interests in the product, the company noted.
 

Study results

The accelerated approval of naxitamab was based on the overall response rate (ORR) and duration of response in two single-arm, open-label trials: Study 201 (NCT03363373) in 22 patients and Study 12-230 (NCT01757626) in 38 patients.

In both studies, patients received naxitamab at 3 mg/kg administered as an intravenous infusion on days 1, 3, and 5 of each 4-week cycle in combination with GM-CSF subcutaneously at 250 mcg/m²/day on days -4 to 0 and at 500 mcg/m²/day on days 1-5.

Some patients also received radiotherapy. At the investigator’s discretion, patients were permitted to receive preplanned radiation to the primary disease site in Study 201 and radiation to nontarget bony lesions or soft tissue disease in Study 12-230.

The ORR was 45% in Study 201 and 34% in Study 12-230. Responses were observed in the bone and/or bone marrow, the FDA noted.

Less than a third of patients had a duration of response that lasted 6 months or more – 30% of responders in Study 201 and 23% of responders in Study 12-230.

The FDA noted that continued approval of naxitamab may be contingent upon verification and description of clinical benefit in confirmatory trials.

The agency also noted that naxitamab was granted priority review, breakthrough therapy, and orphan drug designation. In addition, a priority review voucher was issued for the rare pediatric disease product application.
 

Boxed warning and adverse events

Naxitamab has a boxed warning about serious infusion-related reactions and neurotoxicity.

The product information notes that, in clinical studies, naxitamab has been shown to cause serious infusion reactions, including anaphylaxis, cardiac arrest, bronchospasm, stridor, and hypotension. Infusion reactions generally occurred within 24 hours of completing an infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion in each cycle.

To mitigate these risks, Y-mAbs Therapeutics recommends premedication with an antihistamine, acetaminophen, an H2 antagonist, and corticosteroid, as well as close monitoring of patients during and for at least 2 hours after each infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.

Based on its mechanism of action, naxitamab can cause severe pain, according to Y-mAbs Therapeutics. The company recommends premedication with gabapentin and, for example, oral oxycodone, and recommends treating break-through pain with intravenous hydromorphone or an equivalent intervention.

In addition, naxitamab may cause severe hypertension. The onset of hypertension may be delayed, so blood pressure should be monitored both during and after infusion.

The product insert also notes that one case of transverse myelitis (grade 3) and two cases of posterior reversible encephalopathy syndrome have been reported.

The most common adverse reactions (incidence ≥ 25% in either trial) were infusion-related reactions, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability.

The most common grade 3 or 4 laboratory abnormalities (≥ 5% in either trial) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, and decreased phosphate.
 

A version of this article appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval for naxitamab (Danyelza) to treat certain patients with neuroblastoma, based on response rates in two small trials.

Naxitamab is a humanized monoclonal antibody that targets GD2, a disialoganglioside highly expressed on neuroblastomas.

The FDA approved naxitamab for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in adults and children aged 1 year and older who have relapsed or refractory, high-risk neuroblastoma in the bone or bone marrow that demonstrated a partial response, minor response, or stable disease to prior therapy.

Naxitamab was originally developed at Memorial Sloan Kettering Cancer Center in New York, and licensed exclusively to Y-mAbs Therapeutics. As a result of the licensing arrangement, MSKCC has institutional financial interests in the product, the company noted.
 

Study results

The accelerated approval of naxitamab was based on the overall response rate (ORR) and duration of response in two single-arm, open-label trials: Study 201 (NCT03363373) in 22 patients and Study 12-230 (NCT01757626) in 38 patients.

In both studies, patients received naxitamab at 3 mg/kg administered as an intravenous infusion on days 1, 3, and 5 of each 4-week cycle in combination with GM-CSF subcutaneously at 250 mcg/m²/day on days -4 to 0 and at 500 mcg/m²/day on days 1-5.

Some patients also received radiotherapy. At the investigator’s discretion, patients were permitted to receive preplanned radiation to the primary disease site in Study 201 and radiation to nontarget bony lesions or soft tissue disease in Study 12-230.

The ORR was 45% in Study 201 and 34% in Study 12-230. Responses were observed in the bone and/or bone marrow, the FDA noted.

Less than a third of patients had a duration of response that lasted 6 months or more – 30% of responders in Study 201 and 23% of responders in Study 12-230.

The FDA noted that continued approval of naxitamab may be contingent upon verification and description of clinical benefit in confirmatory trials.

The agency also noted that naxitamab was granted priority review, breakthrough therapy, and orphan drug designation. In addition, a priority review voucher was issued for the rare pediatric disease product application.
 

Boxed warning and adverse events

Naxitamab has a boxed warning about serious infusion-related reactions and neurotoxicity.

The product information notes that, in clinical studies, naxitamab has been shown to cause serious infusion reactions, including anaphylaxis, cardiac arrest, bronchospasm, stridor, and hypotension. Infusion reactions generally occurred within 24 hours of completing an infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion in each cycle.

To mitigate these risks, Y-mAbs Therapeutics recommends premedication with an antihistamine, acetaminophen, an H2 antagonist, and corticosteroid, as well as close monitoring of patients during and for at least 2 hours after each infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.

Based on its mechanism of action, naxitamab can cause severe pain, according to Y-mAbs Therapeutics. The company recommends premedication with gabapentin and, for example, oral oxycodone, and recommends treating break-through pain with intravenous hydromorphone or an equivalent intervention.

In addition, naxitamab may cause severe hypertension. The onset of hypertension may be delayed, so blood pressure should be monitored both during and after infusion.

The product insert also notes that one case of transverse myelitis (grade 3) and two cases of posterior reversible encephalopathy syndrome have been reported.

The most common adverse reactions (incidence ≥ 25% in either trial) were infusion-related reactions, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability.

The most common grade 3 or 4 laboratory abnormalities (≥ 5% in either trial) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, and decreased phosphate.
 

A version of this article appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval for naxitamab (Danyelza) to treat certain patients with neuroblastoma, based on response rates in two small trials.

Naxitamab is a humanized monoclonal antibody that targets GD2, a disialoganglioside highly expressed on neuroblastomas.

The FDA approved naxitamab for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in adults and children aged 1 year and older who have relapsed or refractory, high-risk neuroblastoma in the bone or bone marrow that demonstrated a partial response, minor response, or stable disease to prior therapy.

Naxitamab was originally developed at Memorial Sloan Kettering Cancer Center in New York, and licensed exclusively to Y-mAbs Therapeutics. As a result of the licensing arrangement, MSKCC has institutional financial interests in the product, the company noted.
 

Study results

The accelerated approval of naxitamab was based on the overall response rate (ORR) and duration of response in two single-arm, open-label trials: Study 201 (NCT03363373) in 22 patients and Study 12-230 (NCT01757626) in 38 patients.

In both studies, patients received naxitamab at 3 mg/kg administered as an intravenous infusion on days 1, 3, and 5 of each 4-week cycle in combination with GM-CSF subcutaneously at 250 mcg/m²/day on days -4 to 0 and at 500 mcg/m²/day on days 1-5.

Some patients also received radiotherapy. At the investigator’s discretion, patients were permitted to receive preplanned radiation to the primary disease site in Study 201 and radiation to nontarget bony lesions or soft tissue disease in Study 12-230.

The ORR was 45% in Study 201 and 34% in Study 12-230. Responses were observed in the bone and/or bone marrow, the FDA noted.

Less than a third of patients had a duration of response that lasted 6 months or more – 30% of responders in Study 201 and 23% of responders in Study 12-230.

The FDA noted that continued approval of naxitamab may be contingent upon verification and description of clinical benefit in confirmatory trials.

The agency also noted that naxitamab was granted priority review, breakthrough therapy, and orphan drug designation. In addition, a priority review voucher was issued for the rare pediatric disease product application.
 

Boxed warning and adverse events

Naxitamab has a boxed warning about serious infusion-related reactions and neurotoxicity.

The product information notes that, in clinical studies, naxitamab has been shown to cause serious infusion reactions, including anaphylaxis, cardiac arrest, bronchospasm, stridor, and hypotension. Infusion reactions generally occurred within 24 hours of completing an infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion in each cycle.

To mitigate these risks, Y-mAbs Therapeutics recommends premedication with an antihistamine, acetaminophen, an H2 antagonist, and corticosteroid, as well as close monitoring of patients during and for at least 2 hours after each infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.

Based on its mechanism of action, naxitamab can cause severe pain, according to Y-mAbs Therapeutics. The company recommends premedication with gabapentin and, for example, oral oxycodone, and recommends treating break-through pain with intravenous hydromorphone or an equivalent intervention.

In addition, naxitamab may cause severe hypertension. The onset of hypertension may be delayed, so blood pressure should be monitored both during and after infusion.

The product insert also notes that one case of transverse myelitis (grade 3) and two cases of posterior reversible encephalopathy syndrome have been reported.

The most common adverse reactions (incidence ≥ 25% in either trial) were infusion-related reactions, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability.

The most common grade 3 or 4 laboratory abnormalities (≥ 5% in either trial) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, and decreased phosphate.
 

A version of this article appeared on Medscape.com.

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]