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Influenza: U.S. activity was low this summer
Influenza activity in the United States was typically low over the summer months, with influenza A(H3N2) viruses predominating, according to the Centers for Disease Control and Prevention.
From May 19 to Sept. 28, 2019, weekly flu activity – measured by the percentage of outpatient visits to health care professionals for influenza-like illness (ILI) – was below the national baseline of 2.2%, ranging from 0.7% to 1.4%. Since mid-August, however, when the rate was last 0.7%, it has been climbing slowly but steadily and was up to 1.3% for the week ending Sept. 28, CDC data show.
The various public health laboratories of the U.S. Influenza Surveillance System tested over 7,600 respiratory samples from May 19 to Sept. 28, and 22.7% were positive for influenza viruses, Scott Epperson, DVM, and associates at the CDC’s influenza division said Oct. 10 in the MMWR.
Of the 1,737 samples found to be positive, 69.8% were influenza A and 30.2% were influenza B. The subtype split among specimens positive for Influenza A was 71.9% A(H3N2) and 28.1% A(H1N1)pdm09, while the samples positive for influenza B went 93.9% B/Victoria and 6.1% B/Yamagata, they reported.
Over the same time period in the Southern Hemisphere, “seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries,” the CDC investigators noted.
They also reported the World Health Organization recommendations for the Southern Hemisphere’s 2020 flu vaccines. Components of the egg-based trivalent vaccine are an A/Brisbane/02/2018(H1N1)pdm09-like virus, an A/South Australia/34/2019(H3N2)-like virus, and a B/Washington/02/2019-like virus(B/Victoria lineage). The recommended quadrivalent vaccine adds a B/Phuket/3073/2013-like virus(B/Yamagata lineage), they wrote.
“It is too early in the season to know which viruses will circulate in the United States later this fall and winter or how severe the season might be; however, regardless of what is circulating, the best protection against influenza is an influenza vaccination,” Dr. Epperson and associates wrote.
SOURCE: Epperson S et al. MMWR. 2019 Oct 11;68(40):880-4.
Influenza activity in the United States was typically low over the summer months, with influenza A(H3N2) viruses predominating, according to the Centers for Disease Control and Prevention.
From May 19 to Sept. 28, 2019, weekly flu activity – measured by the percentage of outpatient visits to health care professionals for influenza-like illness (ILI) – was below the national baseline of 2.2%, ranging from 0.7% to 1.4%. Since mid-August, however, when the rate was last 0.7%, it has been climbing slowly but steadily and was up to 1.3% for the week ending Sept. 28, CDC data show.
The various public health laboratories of the U.S. Influenza Surveillance System tested over 7,600 respiratory samples from May 19 to Sept. 28, and 22.7% were positive for influenza viruses, Scott Epperson, DVM, and associates at the CDC’s influenza division said Oct. 10 in the MMWR.
Of the 1,737 samples found to be positive, 69.8% were influenza A and 30.2% were influenza B. The subtype split among specimens positive for Influenza A was 71.9% A(H3N2) and 28.1% A(H1N1)pdm09, while the samples positive for influenza B went 93.9% B/Victoria and 6.1% B/Yamagata, they reported.
Over the same time period in the Southern Hemisphere, “seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries,” the CDC investigators noted.
They also reported the World Health Organization recommendations for the Southern Hemisphere’s 2020 flu vaccines. Components of the egg-based trivalent vaccine are an A/Brisbane/02/2018(H1N1)pdm09-like virus, an A/South Australia/34/2019(H3N2)-like virus, and a B/Washington/02/2019-like virus(B/Victoria lineage). The recommended quadrivalent vaccine adds a B/Phuket/3073/2013-like virus(B/Yamagata lineage), they wrote.
“It is too early in the season to know which viruses will circulate in the United States later this fall and winter or how severe the season might be; however, regardless of what is circulating, the best protection against influenza is an influenza vaccination,” Dr. Epperson and associates wrote.
SOURCE: Epperson S et al. MMWR. 2019 Oct 11;68(40):880-4.
Influenza activity in the United States was typically low over the summer months, with influenza A(H3N2) viruses predominating, according to the Centers for Disease Control and Prevention.
From May 19 to Sept. 28, 2019, weekly flu activity – measured by the percentage of outpatient visits to health care professionals for influenza-like illness (ILI) – was below the national baseline of 2.2%, ranging from 0.7% to 1.4%. Since mid-August, however, when the rate was last 0.7%, it has been climbing slowly but steadily and was up to 1.3% for the week ending Sept. 28, CDC data show.
The various public health laboratories of the U.S. Influenza Surveillance System tested over 7,600 respiratory samples from May 19 to Sept. 28, and 22.7% were positive for influenza viruses, Scott Epperson, DVM, and associates at the CDC’s influenza division said Oct. 10 in the MMWR.
Of the 1,737 samples found to be positive, 69.8% were influenza A and 30.2% were influenza B. The subtype split among specimens positive for Influenza A was 71.9% A(H3N2) and 28.1% A(H1N1)pdm09, while the samples positive for influenza B went 93.9% B/Victoria and 6.1% B/Yamagata, they reported.
Over the same time period in the Southern Hemisphere, “seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries,” the CDC investigators noted.
They also reported the World Health Organization recommendations for the Southern Hemisphere’s 2020 flu vaccines. Components of the egg-based trivalent vaccine are an A/Brisbane/02/2018(H1N1)pdm09-like virus, an A/South Australia/34/2019(H3N2)-like virus, and a B/Washington/02/2019-like virus(B/Victoria lineage). The recommended quadrivalent vaccine adds a B/Phuket/3073/2013-like virus(B/Yamagata lineage), they wrote.
“It is too early in the season to know which viruses will circulate in the United States later this fall and winter or how severe the season might be; however, regardless of what is circulating, the best protection against influenza is an influenza vaccination,” Dr. Epperson and associates wrote.
SOURCE: Epperson S et al. MMWR. 2019 Oct 11;68(40):880-4.
FROM MMWR
Tape strips useful to identify biomarkers in skin of young children with atopic dermatitis
Adhesive according to a study published online on October 9 in JAMA Dermatology.
“Minimally invasive approaches that accurately capture key immune and barrier biomarkers in the skin of patients with early-onset pediatric AD are needed,” wrote Emma Guttman-Yassky, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Because tissue biopsies are considered the criterion standard for evaluating dysregulation in AD lesional and nonlesional skin, it is crucial to understand whether tape-strip profiling can accurately yield key AD-related biomarkers.”
In their cross-sectional study, researchers used large D-Squame tape strips to collect skin samples from 51 children under the age of 5 years (mean, 1.7-1.8 years), including 21 with moderate to severe AD and 30 controls who did not have AD. Samples were collected from lesional skin inside the crook of the elbow and nonlesional skin, on the same arm, then subjected to gene- and protein-expression analysis to identify skin biomarkers of disease.
The participants tolerated the tape stripping well, and there were no clinical effects of the procedure. The authors were able to detect mRNA in 70 of 71 samples.
They then analyzed a panel of 15 cellular markers that assessed markers of monocytes and macrophages, T cells, activated TH2 cells, dendritic cells and dendritic-cell subsets, and Langerhans cells. They found that most showed significant differences between lesional AD skin and normal skin.
They also found that levels of OX40 ligand receptor, a marker associated with atopic dendritic cells, the inducible T-cell costimulatory activation marker, CD209, CD123, and langerin protein, were also significantly higher in nonlesional AD skin.
When comparing lesional and nonlesional skin samples in the AD patients, the authors saw significant differences only in levels of colony-stimulating factor 1 and 2.
The authors noted that some of the mediators detected from the tape-strip samples had not been detected or evaluated in previous studies of the use of tape strips in AD. These included measures of cellular infiltrates, atopic dendritic cells, and key inflammatory markers.
“The novel epidermal cytokines IL [interleukin]–33 and IL-17C, which are currently targeted in clinical trials of patients with AD, were also highlighted as novel tape-strip biomarkers and demonstrated significant correlations with AD severity,” they wrote.
“Because tape stripping is painless, nonscarring, and allows repeated sampling, it may be associated with benefits for longitudinal pediatric studies and clinical trials, in which serial measures are needed to identify predictors of response, course, and comorbidities,” the authors concluded.
The study was supported by the Northwestern University Skin Disease Research Center and the Northwestern University Clinical and Translational Sciences Institute, and partly by a grant to two authors from Regeneron and Sanofi. Dr. Guttman-Yassky reported receiving grants from Regeneron during the study, and had other disclosures related to multiple pharmaceutical companies. Another author also received grants from Regeneron during the study, and another author had disclosures related to various manufacturers; no disclosures were reported for the remaining authors.
SOURCE: Guttman-Yassky E et al. JAMA Dermatol. 2019 Oct 9. doi: 10.1001/jamadermatol.2019.2983.
Skin biomarkers of atopic dermatitis (AD) are not well studied in children despite the fact that the disease largely affects this age group. Part of the challenge is the difficulty obtaining samples from children because phlebotomy and skin biopsies can cause trauma and anxiety both in children and their guardians. Better, noninvasive sampling techniques are needed.
This and another recent study show that tape stripping achieves skin samples that can provide clinically relevant AD DNA-expression levels and biomarkers that have been shown in multiple other studies – including some AD biomarkers not previously reported. Importantly, these biomarkers distinguish between children with AD and those without, and even between lesional and nonlesional skin.
While it remains to be seen if these biomarkers can predict disease outcomes or response to medication, this study shows that tape stripping in children with AD is a viable and useful method for future studies.
Leslie Castelo-Soccio, MD, PhD, is with the department of dermatology at the Children’s Hospital of Philadelphia. These comments are adapted from an accompanying editorial (JAMA Dermatol. 2019 Oct 9. doi: 10.1001/jamadermatol.2019.2792). No conflicts of interest were reported.
Skin biomarkers of atopic dermatitis (AD) are not well studied in children despite the fact that the disease largely affects this age group. Part of the challenge is the difficulty obtaining samples from children because phlebotomy and skin biopsies can cause trauma and anxiety both in children and their guardians. Better, noninvasive sampling techniques are needed.
This and another recent study show that tape stripping achieves skin samples that can provide clinically relevant AD DNA-expression levels and biomarkers that have been shown in multiple other studies – including some AD biomarkers not previously reported. Importantly, these biomarkers distinguish between children with AD and those without, and even between lesional and nonlesional skin.
While it remains to be seen if these biomarkers can predict disease outcomes or response to medication, this study shows that tape stripping in children with AD is a viable and useful method for future studies.
Leslie Castelo-Soccio, MD, PhD, is with the department of dermatology at the Children’s Hospital of Philadelphia. These comments are adapted from an accompanying editorial (JAMA Dermatol. 2019 Oct 9. doi: 10.1001/jamadermatol.2019.2792). No conflicts of interest were reported.
Skin biomarkers of atopic dermatitis (AD) are not well studied in children despite the fact that the disease largely affects this age group. Part of the challenge is the difficulty obtaining samples from children because phlebotomy and skin biopsies can cause trauma and anxiety both in children and their guardians. Better, noninvasive sampling techniques are needed.
This and another recent study show that tape stripping achieves skin samples that can provide clinically relevant AD DNA-expression levels and biomarkers that have been shown in multiple other studies – including some AD biomarkers not previously reported. Importantly, these biomarkers distinguish between children with AD and those without, and even between lesional and nonlesional skin.
While it remains to be seen if these biomarkers can predict disease outcomes or response to medication, this study shows that tape stripping in children with AD is a viable and useful method for future studies.
Leslie Castelo-Soccio, MD, PhD, is with the department of dermatology at the Children’s Hospital of Philadelphia. These comments are adapted from an accompanying editorial (JAMA Dermatol. 2019 Oct 9. doi: 10.1001/jamadermatol.2019.2792). No conflicts of interest were reported.
Adhesive according to a study published online on October 9 in JAMA Dermatology.
“Minimally invasive approaches that accurately capture key immune and barrier biomarkers in the skin of patients with early-onset pediatric AD are needed,” wrote Emma Guttman-Yassky, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Because tissue biopsies are considered the criterion standard for evaluating dysregulation in AD lesional and nonlesional skin, it is crucial to understand whether tape-strip profiling can accurately yield key AD-related biomarkers.”
In their cross-sectional study, researchers used large D-Squame tape strips to collect skin samples from 51 children under the age of 5 years (mean, 1.7-1.8 years), including 21 with moderate to severe AD and 30 controls who did not have AD. Samples were collected from lesional skin inside the crook of the elbow and nonlesional skin, on the same arm, then subjected to gene- and protein-expression analysis to identify skin biomarkers of disease.
The participants tolerated the tape stripping well, and there were no clinical effects of the procedure. The authors were able to detect mRNA in 70 of 71 samples.
They then analyzed a panel of 15 cellular markers that assessed markers of monocytes and macrophages, T cells, activated TH2 cells, dendritic cells and dendritic-cell subsets, and Langerhans cells. They found that most showed significant differences between lesional AD skin and normal skin.
They also found that levels of OX40 ligand receptor, a marker associated with atopic dendritic cells, the inducible T-cell costimulatory activation marker, CD209, CD123, and langerin protein, were also significantly higher in nonlesional AD skin.
When comparing lesional and nonlesional skin samples in the AD patients, the authors saw significant differences only in levels of colony-stimulating factor 1 and 2.
The authors noted that some of the mediators detected from the tape-strip samples had not been detected or evaluated in previous studies of the use of tape strips in AD. These included measures of cellular infiltrates, atopic dendritic cells, and key inflammatory markers.
“The novel epidermal cytokines IL [interleukin]–33 and IL-17C, which are currently targeted in clinical trials of patients with AD, were also highlighted as novel tape-strip biomarkers and demonstrated significant correlations with AD severity,” they wrote.
“Because tape stripping is painless, nonscarring, and allows repeated sampling, it may be associated with benefits for longitudinal pediatric studies and clinical trials, in which serial measures are needed to identify predictors of response, course, and comorbidities,” the authors concluded.
The study was supported by the Northwestern University Skin Disease Research Center and the Northwestern University Clinical and Translational Sciences Institute, and partly by a grant to two authors from Regeneron and Sanofi. Dr. Guttman-Yassky reported receiving grants from Regeneron during the study, and had other disclosures related to multiple pharmaceutical companies. Another author also received grants from Regeneron during the study, and another author had disclosures related to various manufacturers; no disclosures were reported for the remaining authors.
SOURCE: Guttman-Yassky E et al. JAMA Dermatol. 2019 Oct 9. doi: 10.1001/jamadermatol.2019.2983.
Adhesive according to a study published online on October 9 in JAMA Dermatology.
“Minimally invasive approaches that accurately capture key immune and barrier biomarkers in the skin of patients with early-onset pediatric AD are needed,” wrote Emma Guttman-Yassky, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Because tissue biopsies are considered the criterion standard for evaluating dysregulation in AD lesional and nonlesional skin, it is crucial to understand whether tape-strip profiling can accurately yield key AD-related biomarkers.”
In their cross-sectional study, researchers used large D-Squame tape strips to collect skin samples from 51 children under the age of 5 years (mean, 1.7-1.8 years), including 21 with moderate to severe AD and 30 controls who did not have AD. Samples were collected from lesional skin inside the crook of the elbow and nonlesional skin, on the same arm, then subjected to gene- and protein-expression analysis to identify skin biomarkers of disease.
The participants tolerated the tape stripping well, and there were no clinical effects of the procedure. The authors were able to detect mRNA in 70 of 71 samples.
They then analyzed a panel of 15 cellular markers that assessed markers of monocytes and macrophages, T cells, activated TH2 cells, dendritic cells and dendritic-cell subsets, and Langerhans cells. They found that most showed significant differences between lesional AD skin and normal skin.
They also found that levels of OX40 ligand receptor, a marker associated with atopic dendritic cells, the inducible T-cell costimulatory activation marker, CD209, CD123, and langerin protein, were also significantly higher in nonlesional AD skin.
When comparing lesional and nonlesional skin samples in the AD patients, the authors saw significant differences only in levels of colony-stimulating factor 1 and 2.
The authors noted that some of the mediators detected from the tape-strip samples had not been detected or evaluated in previous studies of the use of tape strips in AD. These included measures of cellular infiltrates, atopic dendritic cells, and key inflammatory markers.
“The novel epidermal cytokines IL [interleukin]–33 and IL-17C, which are currently targeted in clinical trials of patients with AD, were also highlighted as novel tape-strip biomarkers and demonstrated significant correlations with AD severity,” they wrote.
“Because tape stripping is painless, nonscarring, and allows repeated sampling, it may be associated with benefits for longitudinal pediatric studies and clinical trials, in which serial measures are needed to identify predictors of response, course, and comorbidities,” the authors concluded.
The study was supported by the Northwestern University Skin Disease Research Center and the Northwestern University Clinical and Translational Sciences Institute, and partly by a grant to two authors from Regeneron and Sanofi. Dr. Guttman-Yassky reported receiving grants from Regeneron during the study, and had other disclosures related to multiple pharmaceutical companies. Another author also received grants from Regeneron during the study, and another author had disclosures related to various manufacturers; no disclosures were reported for the remaining authors.
SOURCE: Guttman-Yassky E et al. JAMA Dermatol. 2019 Oct 9. doi: 10.1001/jamadermatol.2019.2983.
FROM JAMA DERMATOLOGY
Much work to be done in optimizing treatment for transgender children
ORLANDO – Janet Y. Lee, MD, MPH, said at the annual meeting of the American Society for Bone and Mineral Research.
According to a report from The Williams Institute in 2017, there were approximately 150,000 youth in the United States who identified as transgender, and among studies that measured transgender identity among youth, the percentage who identified as transgender ranged between 1.3% and 3.2% (Herman J et al. “Age of Individuals who Identify as Transgender in the United States.” Los Angeles: The Williams Institute, January 2017).
“If you’ve not seen one of these patients yet, you probably will in your career,” said Dr. Lee of the University of California, San Francisco.
At UCSF, Dr. Lee said the focus of care for transgender youth in early childhood to late childhood is on school resources and social transition, with puberty blockers such as gonadotropin-releasing hormone agents (GnRHa) beginning in late childhood and early puberty at Tanner stage 2. When patients reach early puberty and move to late puberty and adulthood, they usually begin gender-affirming sex hormones such as testosterone for masculinizing hormone therapy or estrogen and spironolactone or bicalutamide for feminizing hormone therapy in transgender women, and consideration of fertility preservation is undertaken. In adulthood, patients can begin gender-affirming surgery.
Dr. Lee said the specific timing of gender-affirming sex hormones is controversial and “seems to be a moving target in our field.” The average age to begin gender-affirming sex hormones at UCSF is 14 years old, but sometimes younger, said Dr. Lee. There also is a question of when to start gender-affirming sex hormones in gender diverse youth. “[They] may not want full adult doses of testosterone or full adult doses of estradiol,” said Dr. Lee. “It’s been very challenging to figure out [appropriate] treatment for these youth.”
In Europe, some studies have shown transwomen have lower bone mineral density (BMD) scores at baseline even after 2.5 years to 5 years of treatment with estradiol, compared with male reference standards. A study by Vlot et al. found transwomen had lower bone turnover markers and bone mineral apparent density in cohorts younger than 15 years old, compared with cohorts 15 years or older (Bone. 2017 Feb. doi: 10.1016/j.bone.2016.11.008).
As in the case of when to start gender-affirming sex hormones, how to approach treatment for gender diverse youth who have a low baseline BMD but are eligible for puberty blockers is debated. “We could go into a whole other talk about this because we have many [patients] who present with low baseline BMD,” said Dr. Lee. “We have to figure out a way to apply treatment without impairing their bone.”
Other questions that have yet to be answered are what dual x-ray absorptiometry standards to be used for transgender individuals and how body composition and height growth are affected by gender-affirming medical therapy, which is currently “really modeled after hypergonadic children,” said Dr. Lee.
Results from a National Institutes of Health–funded longitudinal observational study of transgender youth at UCSF, Children’s Hospital Los Angeles, Boston Children’s Hospital, and Ann & Robert H. Lurie Children’s Hospital of Chicago is currently examining the effect of using gender-affirming medical treatment for patients in early and late puberty and assessing factors such as mental health, psychological well-being, and bone health measures such as dual x-ray absorptiometry and quantitative computed tomography, as well as investigating dietary intake, physical activity and exercise, and vitamin D status. Preliminary findings from the study have shown low BMD z-scores in designated males at birth when compared with designated females at birth, with suboptimal dietary calcium intake in both designated males and designated females.
Dr. Lee reported no relevant conflicts of interest.
ORLANDO – Janet Y. Lee, MD, MPH, said at the annual meeting of the American Society for Bone and Mineral Research.
According to a report from The Williams Institute in 2017, there were approximately 150,000 youth in the United States who identified as transgender, and among studies that measured transgender identity among youth, the percentage who identified as transgender ranged between 1.3% and 3.2% (Herman J et al. “Age of Individuals who Identify as Transgender in the United States.” Los Angeles: The Williams Institute, January 2017).
“If you’ve not seen one of these patients yet, you probably will in your career,” said Dr. Lee of the University of California, San Francisco.
At UCSF, Dr. Lee said the focus of care for transgender youth in early childhood to late childhood is on school resources and social transition, with puberty blockers such as gonadotropin-releasing hormone agents (GnRHa) beginning in late childhood and early puberty at Tanner stage 2. When patients reach early puberty and move to late puberty and adulthood, they usually begin gender-affirming sex hormones such as testosterone for masculinizing hormone therapy or estrogen and spironolactone or bicalutamide for feminizing hormone therapy in transgender women, and consideration of fertility preservation is undertaken. In adulthood, patients can begin gender-affirming surgery.
Dr. Lee said the specific timing of gender-affirming sex hormones is controversial and “seems to be a moving target in our field.” The average age to begin gender-affirming sex hormones at UCSF is 14 years old, but sometimes younger, said Dr. Lee. There also is a question of when to start gender-affirming sex hormones in gender diverse youth. “[They] may not want full adult doses of testosterone or full adult doses of estradiol,” said Dr. Lee. “It’s been very challenging to figure out [appropriate] treatment for these youth.”
In Europe, some studies have shown transwomen have lower bone mineral density (BMD) scores at baseline even after 2.5 years to 5 years of treatment with estradiol, compared with male reference standards. A study by Vlot et al. found transwomen had lower bone turnover markers and bone mineral apparent density in cohorts younger than 15 years old, compared with cohorts 15 years or older (Bone. 2017 Feb. doi: 10.1016/j.bone.2016.11.008).
As in the case of when to start gender-affirming sex hormones, how to approach treatment for gender diverse youth who have a low baseline BMD but are eligible for puberty blockers is debated. “We could go into a whole other talk about this because we have many [patients] who present with low baseline BMD,” said Dr. Lee. “We have to figure out a way to apply treatment without impairing their bone.”
Other questions that have yet to be answered are what dual x-ray absorptiometry standards to be used for transgender individuals and how body composition and height growth are affected by gender-affirming medical therapy, which is currently “really modeled after hypergonadic children,” said Dr. Lee.
Results from a National Institutes of Health–funded longitudinal observational study of transgender youth at UCSF, Children’s Hospital Los Angeles, Boston Children’s Hospital, and Ann & Robert H. Lurie Children’s Hospital of Chicago is currently examining the effect of using gender-affirming medical treatment for patients in early and late puberty and assessing factors such as mental health, psychological well-being, and bone health measures such as dual x-ray absorptiometry and quantitative computed tomography, as well as investigating dietary intake, physical activity and exercise, and vitamin D status. Preliminary findings from the study have shown low BMD z-scores in designated males at birth when compared with designated females at birth, with suboptimal dietary calcium intake in both designated males and designated females.
Dr. Lee reported no relevant conflicts of interest.
ORLANDO – Janet Y. Lee, MD, MPH, said at the annual meeting of the American Society for Bone and Mineral Research.
According to a report from The Williams Institute in 2017, there were approximately 150,000 youth in the United States who identified as transgender, and among studies that measured transgender identity among youth, the percentage who identified as transgender ranged between 1.3% and 3.2% (Herman J et al. “Age of Individuals who Identify as Transgender in the United States.” Los Angeles: The Williams Institute, January 2017).
“If you’ve not seen one of these patients yet, you probably will in your career,” said Dr. Lee of the University of California, San Francisco.
At UCSF, Dr. Lee said the focus of care for transgender youth in early childhood to late childhood is on school resources and social transition, with puberty blockers such as gonadotropin-releasing hormone agents (GnRHa) beginning in late childhood and early puberty at Tanner stage 2. When patients reach early puberty and move to late puberty and adulthood, they usually begin gender-affirming sex hormones such as testosterone for masculinizing hormone therapy or estrogen and spironolactone or bicalutamide for feminizing hormone therapy in transgender women, and consideration of fertility preservation is undertaken. In adulthood, patients can begin gender-affirming surgery.
Dr. Lee said the specific timing of gender-affirming sex hormones is controversial and “seems to be a moving target in our field.” The average age to begin gender-affirming sex hormones at UCSF is 14 years old, but sometimes younger, said Dr. Lee. There also is a question of when to start gender-affirming sex hormones in gender diverse youth. “[They] may not want full adult doses of testosterone or full adult doses of estradiol,” said Dr. Lee. “It’s been very challenging to figure out [appropriate] treatment for these youth.”
In Europe, some studies have shown transwomen have lower bone mineral density (BMD) scores at baseline even after 2.5 years to 5 years of treatment with estradiol, compared with male reference standards. A study by Vlot et al. found transwomen had lower bone turnover markers and bone mineral apparent density in cohorts younger than 15 years old, compared with cohorts 15 years or older (Bone. 2017 Feb. doi: 10.1016/j.bone.2016.11.008).
As in the case of when to start gender-affirming sex hormones, how to approach treatment for gender diverse youth who have a low baseline BMD but are eligible for puberty blockers is debated. “We could go into a whole other talk about this because we have many [patients] who present with low baseline BMD,” said Dr. Lee. “We have to figure out a way to apply treatment without impairing their bone.”
Other questions that have yet to be answered are what dual x-ray absorptiometry standards to be used for transgender individuals and how body composition and height growth are affected by gender-affirming medical therapy, which is currently “really modeled after hypergonadic children,” said Dr. Lee.
Results from a National Institutes of Health–funded longitudinal observational study of transgender youth at UCSF, Children’s Hospital Los Angeles, Boston Children’s Hospital, and Ann & Robert H. Lurie Children’s Hospital of Chicago is currently examining the effect of using gender-affirming medical treatment for patients in early and late puberty and assessing factors such as mental health, psychological well-being, and bone health measures such as dual x-ray absorptiometry and quantitative computed tomography, as well as investigating dietary intake, physical activity and exercise, and vitamin D status. Preliminary findings from the study have shown low BMD z-scores in designated males at birth when compared with designated females at birth, with suboptimal dietary calcium intake in both designated males and designated females.
Dr. Lee reported no relevant conflicts of interest.
EXPERT ANALYSIS FROM ASBMR 2019
Newly described lung disorder strikes children with systemic juvenile idiopathic arthritis
An uncommon but potentially deadly inflammatory lung disease is emerging among children with systemic juvenile idiopathic arthritis, and its history appears to coincide with the rise of powerful biologics as first-line therapy for children with the disease.
Most confirmed cases of systemic juvenile idiopathic arthritis with lung disease (sJIA-LD) are in the United States. But it’s popping up in other places that have adopted early biologic treatment for sJIA – including Canada, South America, Europe, and the Middle East.
The respiratory symptoms are relatively subtle, so by the time of lung disease detection, the amount of affected lung can be extensive, said Elizabeth Mellins, MD, a Stanford (Calif.) University researcher who, along with first author Vivian Saper, MD, recently published the largest case series comprising reports from 37 institutions (Ann Rheum Dis. 2019 Sep 27. doi: 10.1136/annrheumdis-2019-216040). By the end of follow-up, 22 of the 61 children in her cohort had died, including all 12 patients who demonstrated excessively high neutrophil levels in bronchoalveolar lavage samples.
Another recent report, authored by Grant Schulert, MD, PhD, and colleagues of the Cincinnati Children’s Hospital Medical Center, described 18 patients, 9 of whom were also included in the Stanford cohort (Arthritis Rheumatol. 2019 Aug 5. doi: 10.1002/art.41073).
Both investigators have now identified new patients.
“We are aware of 60 additional cases beyond what were included in our series,” Dr. Mellins said in an interview, bringing her entire cohort to 121. Dr. Schulert also continues to expand his group, detailing nine new cases at a recent private meeting.
“We are up to 27 now,” he said. “The features of these new patients are all very similar: The children are very young, all have had macrophage activation syndrome in the past and very-difficult-to-control JIA. Reactions to tocilizumab [Actemra] were also not uncommon in this group.”
Dr. Mellins also saw this association with allergic-type tocilizumab reactions, severe delayed hypersensitivity reactions to anakinra (Kineret) or canakinumab (Ilaris). Although serious lung disease in sJIA patients is not unheard of, this phenotype was virtually unknown until about a decade ago. Both investigators said that it’s been rising steadily since 2010 – just about the time that powerful cytokine-inhibiting biologics were changing these patients’ world for the better. After decades of relying almost solely on steroids and methotrexate, with rather poor results and significant long-term side effects, children were not only improving, but thriving. Gone was the life-changing glucocorticoid-related growth inhibition. Biologics could halt fevers, rash, and joint destruction in their tracks.
“For the first time in history, these kids could look forward to a more or less normal life,” Dr. Schulert said.
But the emergence of this particular type of lung disease could throw a pall over that success story, he said. If sJIA-LD is temporally associated with increasing reliance on long-term interleukin-1/IL-6 inhibition in children with early-onset disease, could these drugs actually be the causative agent? The picture remains unclear.
Some of the 18 in his initial series have improved, while 36% of those in the Stanford series died. Most who do recover stay on their IL-1 or IL-6 blocking therapy with good disease control without further lung problems. Both investigators found compelling genetic hints, but nothing conclusive. Children with trisomy 21 appear especially vulnerable. Most patients are very young – around 2 years old – but others are school aged. Some had a history of macrophage activation syndrome. Some had hard-to-control disease and some were clinically well controlled when the lung disease presented.
There are simply no answers yet.
With so many potential links, all unproven, clinicians may question the wisdom of embarking on long-term biologic therapy for their children with sJIA. Peter Nigrovic, MD, of Boston Children’s Hospital, addressed this in an accompanying editorial (Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41071).
“My take on this is that it’s a very worrisome trend,” he said in an interview. “We’ve been going full bore toward early biologic therapy in sJIA and at the same time we are seeing more of this lung disease. Is it guilt by association? Or is there something more? The challenge for us is not to jump too soon to that conclusion.”
Although the association is there, he said, association does not equal causation. And there’s no doubt that biologics have vastly improved the lives of sJIA patients. “The drugs might be causal, and I worry about that and think we need to study it. But we absolutely need stronger evidence before we change practice.”
“This is a new manifestation of the disease, and it’s coming at the same time we are changing the treatment paradigm,” Dr. Nigrovic continued. “It could be because of interleukin-1 or interleukin-6 blockade. There is biological plausibility for such a link. It could also be related to the fact that we are using less steroids and methotrexate, which might have been preventing this. The appearance of sJIA lung disease could also be that a distinct secular trend unrelated to treatment, just as we saw amyloid come and go in this population in Europe. These other therapies were actually preventing this. We just don’t know.”
Clinical characteristics
Children presented with similar symptoms. Respiratory symptoms are usually subtle and mild. These can include tachypnea, hypoxia (43% in the Stanford series), and pulmonary hypertension (30% in the Stanford series).
Digital clubbing, often with erythema, was a common finding. Some children showed pruritic, nonevanescent rashes. Eosinophilia occurred in 37% of the Stanford series and severe abdominal pain in 16%, although Dr. Mellins noted that belly pain may be underestimated, as it was only volunteered, not queried, information.
“There are some red flags that should raise suspicion even without obvious respiratory symptoms,” Dr. Mellins said. These include lymphopenia, unexplained abdominal pain, eosinophilia, an unusual rash, and finger clubbing with or without erythema.
Findings on imaging were consistent in both series. Several key clinic features emerged: pleural thickening, septal thickening, bronchial wall or peribronchovascular thickening, “tree-in-bud” opacities, “ground-glass” opacities, peripheral consolidation, and lymphadenopathy.
“The imaging findings correspond to two things,” Dr. Schulert said. “The first is inflammation in the interstitium, which is evidence of chronic and ongoing inflammation. The other thing is that the alveoli are filled with a lipoproteinaceous material which is actually surfactant that’s not being normally recycled by the lung macrophages. You can see these features in other conditions where there’s a problem with lung macrophages, like pulmonary alveolar proteinosis, genetic and autoimmune disorders, infections, or inhalants.”
Pathology showed alveolar filling – a location in the lung that hides usual symptoms until the lung disease is advanced. Prior drug reactions were common. Tocilizumab anaphylaxis occurred in close to 40% of the Stanford series – a surprising finding given the 0.6% reaction incidence in the drug’s sJIA trials. Dr. Schulert saw a similar story.
“In our cohort we also observed a striking number of adverse events to cytokine-targeted biologics exposure,” Dr. Schulert said. “Most of these reactions were to tocilizumab, and were described variously from pain and feeling unwell, to difficulty breathing, to anaphylaxis.”
In a risk analysis, Dr. Schulert determined that adverse events to cytokine-targeting biologics increased the likelihood of lung disease more than 13 times (odds ratio, 13.6).
“We also identified a statistically significant association with history of macrophage activation syndrome when compared to controls (OR, 14.5),” Dr. Schulert and associates wrote.
Genetics
Both the Cincinnati and Stanford teams conducted genetic analyses on some of their patients.
Among eight lung biopsy samples, Dr. Schulert found 37 differentially expressed genes: 36 with increased expression and 1 with decreased expression. Many of the up-regulated genes are involved in interferon-gamma response. Two (CXCL10 and CXCL9) are interferon-induced chemokines associated with macrophage activation syndrome. The down-regulated gene, PADI4, modulates immune response in lupus, and has been associated with the risk of interstitial lung disease in RA.
Dr. Mellins and her team analyzed whole-exome sequencing data from 20 patients and found some rare protein-altering gene variants in genes related to pulmonary alveolar proteinosis, all of which were heterozygous and shared with a healthy parent. But none of them could be directly tied to the disorder.
Another genetic puzzle demands attention, she said. About 10% of the children had trisomy 21 – a stark contrast to the typical 0.2% prevalence among a control group of sJIA patients without any known lung disease in the Childhood Arthritis and Rheumatology Research Alliance Registry cohort, similar to the background population rate. There were suggestions of more aggressive lung disease in all six of these children. Four presented with hypoxia, and two showed advanced interstitial fibrosis. Children with trisomy 21 also seemed more susceptible to infections; 83% had a viral or fungal lung infection at diagnosis, compared with 29% of those without trisomy 21.
Prior exposure to cytokine inhibitors
Parenchymal lung disease and pulmonary hypertension complicating sJIA was first highlighted in a series of 25 cases reported by Kimura et al. in 2013. These authors raised the question of the possible relationship of this and the increasing use of anti–IL-1 and anti–IL-6 biologics in sJIA treatment.
Following this lead, Dr. Mellins started looking into this new clinical entity in 2015. By then, she was identifying some past cases by autopsy records and current cases by clinical presentation. She saw a dramatic shift over time. From 2002 to 2011, she identified four cases, half of which had been exposed to IL-1/IL-6 inhibitors. From 2012 to 2014, eight new cases came to light, and seven had been exposed to those drugs. The crescendo continued from 2015 to 2017. During those years, Dr. Mellins and associates identified 10 new patients, 7 of whom had taken interleukin-inhibiting biologics. The mean time from initial drug exposure to diagnosis was a little more than 1 year.
An adjusted analysis comparing sJIA-LD patients and sJIA patients without lung disease didn’t find any significant difference in drug exposure. However, children with lung disease were more likely to have taken anakinra before the symptoms developed. Additionally, the symptoms of clubbing, abdominal pain, eosinophilia, hyperenhancing lymph nodes, and pulmonary alveolar proteinosis were much more common in children who’d taken the drugs.
The authors pointed out that this association does not prove causality and is confounded by the concomitant reduction in glucocorticoids with IL-1/IL-6 inhibitor use. And the vast majority of children with sJIA take cytokine inhibitors with no problems.
“Possibly, drug exposure may promote lung disease in a subset of children with sJIA, among the substantially larger group of patients who derive striking benefit from these drugs,” Dr. Mellins said, “Importantly, our results argue strongly for more investigation into a possible connection.”
Survival
After a mean follow-up of 1.7 years, the Stanford group saw high mortality. The 5-year survival rate translated to a mortality incidence of 159 deaths per 1,000 person-years, compared with 3.9 per 1,000 person-years in a historical cohort of sJIA patients who required biologic therapy.
Diffuse lung disease was the cause of 12 deaths; 5 of these patients also had macrophage activation syndrome at the time of death. Factors significantly associated with shortened survival included male sex, hypoxia at presentation, and neutrophilic bronchoalveolar lavage with more than 10 times the normal count. In an adjusted analysis, all of these variables fell out. However, none of the children with excessively high neutrophilic bronchoalveolar lavage survived.
Does it affect adults?
Could adults be experiencing the same disorder? There is some evidence to support it: The Food and Drug Administration adverse event website shows alveolar disease or pulmonary hypertension in 39 adults who have been exposed to IL-1 or IL-6 inhibition. Of these, 23 had RA, 11 adult-onset Still’s disease, and 5 unclassified rheumatic disorders.
The research groups were supported by grants from the sJIA Foundation, the Lucile Packard Foundation for Children’s Health, Stanford graduate fellowships, the Life Sciences Research Foundation, the Bill & Melinda Gates Foundation, Cincinnati Children’s Research Foundation, the Childhood Arthritis and Rheumatology Research Alliance, the Arthritis Foundation, and the National Institutes of Health. Many authors on both papers reported financial ties to Genentech, which markets tocilizumab, and other pharmaceutical companies*. Dr. Nigrovic reported receiving consulting fees and research support from Novartis and other companies.
SOURCES: Saper V et al. Ann Rheum Dis. 2019 Sep 27. doi: 10.1136/annrheumdis-2019-216040; Schulert GS et al. Arthritis Rheumatol. 2019 Aug 5. doi: 10.1002/art.41073; Nigrovic PA. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41071.
*Correction, 10/12/19: An earlier version of this article misstated the manufacturer of Actemra (tocilizumab).
This article was updated 10/14/19.
An uncommon but potentially deadly inflammatory lung disease is emerging among children with systemic juvenile idiopathic arthritis, and its history appears to coincide with the rise of powerful biologics as first-line therapy for children with the disease.
Most confirmed cases of systemic juvenile idiopathic arthritis with lung disease (sJIA-LD) are in the United States. But it’s popping up in other places that have adopted early biologic treatment for sJIA – including Canada, South America, Europe, and the Middle East.
The respiratory symptoms are relatively subtle, so by the time of lung disease detection, the amount of affected lung can be extensive, said Elizabeth Mellins, MD, a Stanford (Calif.) University researcher who, along with first author Vivian Saper, MD, recently published the largest case series comprising reports from 37 institutions (Ann Rheum Dis. 2019 Sep 27. doi: 10.1136/annrheumdis-2019-216040). By the end of follow-up, 22 of the 61 children in her cohort had died, including all 12 patients who demonstrated excessively high neutrophil levels in bronchoalveolar lavage samples.
Another recent report, authored by Grant Schulert, MD, PhD, and colleagues of the Cincinnati Children’s Hospital Medical Center, described 18 patients, 9 of whom were also included in the Stanford cohort (Arthritis Rheumatol. 2019 Aug 5. doi: 10.1002/art.41073).
Both investigators have now identified new patients.
“We are aware of 60 additional cases beyond what were included in our series,” Dr. Mellins said in an interview, bringing her entire cohort to 121. Dr. Schulert also continues to expand his group, detailing nine new cases at a recent private meeting.
“We are up to 27 now,” he said. “The features of these new patients are all very similar: The children are very young, all have had macrophage activation syndrome in the past and very-difficult-to-control JIA. Reactions to tocilizumab [Actemra] were also not uncommon in this group.”
Dr. Mellins also saw this association with allergic-type tocilizumab reactions, severe delayed hypersensitivity reactions to anakinra (Kineret) or canakinumab (Ilaris). Although serious lung disease in sJIA patients is not unheard of, this phenotype was virtually unknown until about a decade ago. Both investigators said that it’s been rising steadily since 2010 – just about the time that powerful cytokine-inhibiting biologics were changing these patients’ world for the better. After decades of relying almost solely on steroids and methotrexate, with rather poor results and significant long-term side effects, children were not only improving, but thriving. Gone was the life-changing glucocorticoid-related growth inhibition. Biologics could halt fevers, rash, and joint destruction in their tracks.
“For the first time in history, these kids could look forward to a more or less normal life,” Dr. Schulert said.
But the emergence of this particular type of lung disease could throw a pall over that success story, he said. If sJIA-LD is temporally associated with increasing reliance on long-term interleukin-1/IL-6 inhibition in children with early-onset disease, could these drugs actually be the causative agent? The picture remains unclear.
Some of the 18 in his initial series have improved, while 36% of those in the Stanford series died. Most who do recover stay on their IL-1 or IL-6 blocking therapy with good disease control without further lung problems. Both investigators found compelling genetic hints, but nothing conclusive. Children with trisomy 21 appear especially vulnerable. Most patients are very young – around 2 years old – but others are school aged. Some had a history of macrophage activation syndrome. Some had hard-to-control disease and some were clinically well controlled when the lung disease presented.
There are simply no answers yet.
With so many potential links, all unproven, clinicians may question the wisdom of embarking on long-term biologic therapy for their children with sJIA. Peter Nigrovic, MD, of Boston Children’s Hospital, addressed this in an accompanying editorial (Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41071).
“My take on this is that it’s a very worrisome trend,” he said in an interview. “We’ve been going full bore toward early biologic therapy in sJIA and at the same time we are seeing more of this lung disease. Is it guilt by association? Or is there something more? The challenge for us is not to jump too soon to that conclusion.”
Although the association is there, he said, association does not equal causation. And there’s no doubt that biologics have vastly improved the lives of sJIA patients. “The drugs might be causal, and I worry about that and think we need to study it. But we absolutely need stronger evidence before we change practice.”
“This is a new manifestation of the disease, and it’s coming at the same time we are changing the treatment paradigm,” Dr. Nigrovic continued. “It could be because of interleukin-1 or interleukin-6 blockade. There is biological plausibility for such a link. It could also be related to the fact that we are using less steroids and methotrexate, which might have been preventing this. The appearance of sJIA lung disease could also be that a distinct secular trend unrelated to treatment, just as we saw amyloid come and go in this population in Europe. These other therapies were actually preventing this. We just don’t know.”
Clinical characteristics
Children presented with similar symptoms. Respiratory symptoms are usually subtle and mild. These can include tachypnea, hypoxia (43% in the Stanford series), and pulmonary hypertension (30% in the Stanford series).
Digital clubbing, often with erythema, was a common finding. Some children showed pruritic, nonevanescent rashes. Eosinophilia occurred in 37% of the Stanford series and severe abdominal pain in 16%, although Dr. Mellins noted that belly pain may be underestimated, as it was only volunteered, not queried, information.
“There are some red flags that should raise suspicion even without obvious respiratory symptoms,” Dr. Mellins said. These include lymphopenia, unexplained abdominal pain, eosinophilia, an unusual rash, and finger clubbing with or without erythema.
Findings on imaging were consistent in both series. Several key clinic features emerged: pleural thickening, septal thickening, bronchial wall or peribronchovascular thickening, “tree-in-bud” opacities, “ground-glass” opacities, peripheral consolidation, and lymphadenopathy.
“The imaging findings correspond to two things,” Dr. Schulert said. “The first is inflammation in the interstitium, which is evidence of chronic and ongoing inflammation. The other thing is that the alveoli are filled with a lipoproteinaceous material which is actually surfactant that’s not being normally recycled by the lung macrophages. You can see these features in other conditions where there’s a problem with lung macrophages, like pulmonary alveolar proteinosis, genetic and autoimmune disorders, infections, or inhalants.”
Pathology showed alveolar filling – a location in the lung that hides usual symptoms until the lung disease is advanced. Prior drug reactions were common. Tocilizumab anaphylaxis occurred in close to 40% of the Stanford series – a surprising finding given the 0.6% reaction incidence in the drug’s sJIA trials. Dr. Schulert saw a similar story.
“In our cohort we also observed a striking number of adverse events to cytokine-targeted biologics exposure,” Dr. Schulert said. “Most of these reactions were to tocilizumab, and were described variously from pain and feeling unwell, to difficulty breathing, to anaphylaxis.”
In a risk analysis, Dr. Schulert determined that adverse events to cytokine-targeting biologics increased the likelihood of lung disease more than 13 times (odds ratio, 13.6).
“We also identified a statistically significant association with history of macrophage activation syndrome when compared to controls (OR, 14.5),” Dr. Schulert and associates wrote.
Genetics
Both the Cincinnati and Stanford teams conducted genetic analyses on some of their patients.
Among eight lung biopsy samples, Dr. Schulert found 37 differentially expressed genes: 36 with increased expression and 1 with decreased expression. Many of the up-regulated genes are involved in interferon-gamma response. Two (CXCL10 and CXCL9) are interferon-induced chemokines associated with macrophage activation syndrome. The down-regulated gene, PADI4, modulates immune response in lupus, and has been associated with the risk of interstitial lung disease in RA.
Dr. Mellins and her team analyzed whole-exome sequencing data from 20 patients and found some rare protein-altering gene variants in genes related to pulmonary alveolar proteinosis, all of which were heterozygous and shared with a healthy parent. But none of them could be directly tied to the disorder.
Another genetic puzzle demands attention, she said. About 10% of the children had trisomy 21 – a stark contrast to the typical 0.2% prevalence among a control group of sJIA patients without any known lung disease in the Childhood Arthritis and Rheumatology Research Alliance Registry cohort, similar to the background population rate. There were suggestions of more aggressive lung disease in all six of these children. Four presented with hypoxia, and two showed advanced interstitial fibrosis. Children with trisomy 21 also seemed more susceptible to infections; 83% had a viral or fungal lung infection at diagnosis, compared with 29% of those without trisomy 21.
Prior exposure to cytokine inhibitors
Parenchymal lung disease and pulmonary hypertension complicating sJIA was first highlighted in a series of 25 cases reported by Kimura et al. in 2013. These authors raised the question of the possible relationship of this and the increasing use of anti–IL-1 and anti–IL-6 biologics in sJIA treatment.
Following this lead, Dr. Mellins started looking into this new clinical entity in 2015. By then, she was identifying some past cases by autopsy records and current cases by clinical presentation. She saw a dramatic shift over time. From 2002 to 2011, she identified four cases, half of which had been exposed to IL-1/IL-6 inhibitors. From 2012 to 2014, eight new cases came to light, and seven had been exposed to those drugs. The crescendo continued from 2015 to 2017. During those years, Dr. Mellins and associates identified 10 new patients, 7 of whom had taken interleukin-inhibiting biologics. The mean time from initial drug exposure to diagnosis was a little more than 1 year.
An adjusted analysis comparing sJIA-LD patients and sJIA patients without lung disease didn’t find any significant difference in drug exposure. However, children with lung disease were more likely to have taken anakinra before the symptoms developed. Additionally, the symptoms of clubbing, abdominal pain, eosinophilia, hyperenhancing lymph nodes, and pulmonary alveolar proteinosis were much more common in children who’d taken the drugs.
The authors pointed out that this association does not prove causality and is confounded by the concomitant reduction in glucocorticoids with IL-1/IL-6 inhibitor use. And the vast majority of children with sJIA take cytokine inhibitors with no problems.
“Possibly, drug exposure may promote lung disease in a subset of children with sJIA, among the substantially larger group of patients who derive striking benefit from these drugs,” Dr. Mellins said, “Importantly, our results argue strongly for more investigation into a possible connection.”
Survival
After a mean follow-up of 1.7 years, the Stanford group saw high mortality. The 5-year survival rate translated to a mortality incidence of 159 deaths per 1,000 person-years, compared with 3.9 per 1,000 person-years in a historical cohort of sJIA patients who required biologic therapy.
Diffuse lung disease was the cause of 12 deaths; 5 of these patients also had macrophage activation syndrome at the time of death. Factors significantly associated with shortened survival included male sex, hypoxia at presentation, and neutrophilic bronchoalveolar lavage with more than 10 times the normal count. In an adjusted analysis, all of these variables fell out. However, none of the children with excessively high neutrophilic bronchoalveolar lavage survived.
Does it affect adults?
Could adults be experiencing the same disorder? There is some evidence to support it: The Food and Drug Administration adverse event website shows alveolar disease or pulmonary hypertension in 39 adults who have been exposed to IL-1 or IL-6 inhibition. Of these, 23 had RA, 11 adult-onset Still’s disease, and 5 unclassified rheumatic disorders.
The research groups were supported by grants from the sJIA Foundation, the Lucile Packard Foundation for Children’s Health, Stanford graduate fellowships, the Life Sciences Research Foundation, the Bill & Melinda Gates Foundation, Cincinnati Children’s Research Foundation, the Childhood Arthritis and Rheumatology Research Alliance, the Arthritis Foundation, and the National Institutes of Health. Many authors on both papers reported financial ties to Genentech, which markets tocilizumab, and other pharmaceutical companies*. Dr. Nigrovic reported receiving consulting fees and research support from Novartis and other companies.
SOURCES: Saper V et al. Ann Rheum Dis. 2019 Sep 27. doi: 10.1136/annrheumdis-2019-216040; Schulert GS et al. Arthritis Rheumatol. 2019 Aug 5. doi: 10.1002/art.41073; Nigrovic PA. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41071.
*Correction, 10/12/19: An earlier version of this article misstated the manufacturer of Actemra (tocilizumab).
This article was updated 10/14/19.
An uncommon but potentially deadly inflammatory lung disease is emerging among children with systemic juvenile idiopathic arthritis, and its history appears to coincide with the rise of powerful biologics as first-line therapy for children with the disease.
Most confirmed cases of systemic juvenile idiopathic arthritis with lung disease (sJIA-LD) are in the United States. But it’s popping up in other places that have adopted early biologic treatment for sJIA – including Canada, South America, Europe, and the Middle East.
The respiratory symptoms are relatively subtle, so by the time of lung disease detection, the amount of affected lung can be extensive, said Elizabeth Mellins, MD, a Stanford (Calif.) University researcher who, along with first author Vivian Saper, MD, recently published the largest case series comprising reports from 37 institutions (Ann Rheum Dis. 2019 Sep 27. doi: 10.1136/annrheumdis-2019-216040). By the end of follow-up, 22 of the 61 children in her cohort had died, including all 12 patients who demonstrated excessively high neutrophil levels in bronchoalveolar lavage samples.
Another recent report, authored by Grant Schulert, MD, PhD, and colleagues of the Cincinnati Children’s Hospital Medical Center, described 18 patients, 9 of whom were also included in the Stanford cohort (Arthritis Rheumatol. 2019 Aug 5. doi: 10.1002/art.41073).
Both investigators have now identified new patients.
“We are aware of 60 additional cases beyond what were included in our series,” Dr. Mellins said in an interview, bringing her entire cohort to 121. Dr. Schulert also continues to expand his group, detailing nine new cases at a recent private meeting.
“We are up to 27 now,” he said. “The features of these new patients are all very similar: The children are very young, all have had macrophage activation syndrome in the past and very-difficult-to-control JIA. Reactions to tocilizumab [Actemra] were also not uncommon in this group.”
Dr. Mellins also saw this association with allergic-type tocilizumab reactions, severe delayed hypersensitivity reactions to anakinra (Kineret) or canakinumab (Ilaris). Although serious lung disease in sJIA patients is not unheard of, this phenotype was virtually unknown until about a decade ago. Both investigators said that it’s been rising steadily since 2010 – just about the time that powerful cytokine-inhibiting biologics were changing these patients’ world for the better. After decades of relying almost solely on steroids and methotrexate, with rather poor results and significant long-term side effects, children were not only improving, but thriving. Gone was the life-changing glucocorticoid-related growth inhibition. Biologics could halt fevers, rash, and joint destruction in their tracks.
“For the first time in history, these kids could look forward to a more or less normal life,” Dr. Schulert said.
But the emergence of this particular type of lung disease could throw a pall over that success story, he said. If sJIA-LD is temporally associated with increasing reliance on long-term interleukin-1/IL-6 inhibition in children with early-onset disease, could these drugs actually be the causative agent? The picture remains unclear.
Some of the 18 in his initial series have improved, while 36% of those in the Stanford series died. Most who do recover stay on their IL-1 or IL-6 blocking therapy with good disease control without further lung problems. Both investigators found compelling genetic hints, but nothing conclusive. Children with trisomy 21 appear especially vulnerable. Most patients are very young – around 2 years old – but others are school aged. Some had a history of macrophage activation syndrome. Some had hard-to-control disease and some were clinically well controlled when the lung disease presented.
There are simply no answers yet.
With so many potential links, all unproven, clinicians may question the wisdom of embarking on long-term biologic therapy for their children with sJIA. Peter Nigrovic, MD, of Boston Children’s Hospital, addressed this in an accompanying editorial (Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41071).
“My take on this is that it’s a very worrisome trend,” he said in an interview. “We’ve been going full bore toward early biologic therapy in sJIA and at the same time we are seeing more of this lung disease. Is it guilt by association? Or is there something more? The challenge for us is not to jump too soon to that conclusion.”
Although the association is there, he said, association does not equal causation. And there’s no doubt that biologics have vastly improved the lives of sJIA patients. “The drugs might be causal, and I worry about that and think we need to study it. But we absolutely need stronger evidence before we change practice.”
“This is a new manifestation of the disease, and it’s coming at the same time we are changing the treatment paradigm,” Dr. Nigrovic continued. “It could be because of interleukin-1 or interleukin-6 blockade. There is biological plausibility for such a link. It could also be related to the fact that we are using less steroids and methotrexate, which might have been preventing this. The appearance of sJIA lung disease could also be that a distinct secular trend unrelated to treatment, just as we saw amyloid come and go in this population in Europe. These other therapies were actually preventing this. We just don’t know.”
Clinical characteristics
Children presented with similar symptoms. Respiratory symptoms are usually subtle and mild. These can include tachypnea, hypoxia (43% in the Stanford series), and pulmonary hypertension (30% in the Stanford series).
Digital clubbing, often with erythema, was a common finding. Some children showed pruritic, nonevanescent rashes. Eosinophilia occurred in 37% of the Stanford series and severe abdominal pain in 16%, although Dr. Mellins noted that belly pain may be underestimated, as it was only volunteered, not queried, information.
“There are some red flags that should raise suspicion even without obvious respiratory symptoms,” Dr. Mellins said. These include lymphopenia, unexplained abdominal pain, eosinophilia, an unusual rash, and finger clubbing with or without erythema.
Findings on imaging were consistent in both series. Several key clinic features emerged: pleural thickening, septal thickening, bronchial wall or peribronchovascular thickening, “tree-in-bud” opacities, “ground-glass” opacities, peripheral consolidation, and lymphadenopathy.
“The imaging findings correspond to two things,” Dr. Schulert said. “The first is inflammation in the interstitium, which is evidence of chronic and ongoing inflammation. The other thing is that the alveoli are filled with a lipoproteinaceous material which is actually surfactant that’s not being normally recycled by the lung macrophages. You can see these features in other conditions where there’s a problem with lung macrophages, like pulmonary alveolar proteinosis, genetic and autoimmune disorders, infections, or inhalants.”
Pathology showed alveolar filling – a location in the lung that hides usual symptoms until the lung disease is advanced. Prior drug reactions were common. Tocilizumab anaphylaxis occurred in close to 40% of the Stanford series – a surprising finding given the 0.6% reaction incidence in the drug’s sJIA trials. Dr. Schulert saw a similar story.
“In our cohort we also observed a striking number of adverse events to cytokine-targeted biologics exposure,” Dr. Schulert said. “Most of these reactions were to tocilizumab, and were described variously from pain and feeling unwell, to difficulty breathing, to anaphylaxis.”
In a risk analysis, Dr. Schulert determined that adverse events to cytokine-targeting biologics increased the likelihood of lung disease more than 13 times (odds ratio, 13.6).
“We also identified a statistically significant association with history of macrophage activation syndrome when compared to controls (OR, 14.5),” Dr. Schulert and associates wrote.
Genetics
Both the Cincinnati and Stanford teams conducted genetic analyses on some of their patients.
Among eight lung biopsy samples, Dr. Schulert found 37 differentially expressed genes: 36 with increased expression and 1 with decreased expression. Many of the up-regulated genes are involved in interferon-gamma response. Two (CXCL10 and CXCL9) are interferon-induced chemokines associated with macrophage activation syndrome. The down-regulated gene, PADI4, modulates immune response in lupus, and has been associated with the risk of interstitial lung disease in RA.
Dr. Mellins and her team analyzed whole-exome sequencing data from 20 patients and found some rare protein-altering gene variants in genes related to pulmonary alveolar proteinosis, all of which were heterozygous and shared with a healthy parent. But none of them could be directly tied to the disorder.
Another genetic puzzle demands attention, she said. About 10% of the children had trisomy 21 – a stark contrast to the typical 0.2% prevalence among a control group of sJIA patients without any known lung disease in the Childhood Arthritis and Rheumatology Research Alliance Registry cohort, similar to the background population rate. There were suggestions of more aggressive lung disease in all six of these children. Four presented with hypoxia, and two showed advanced interstitial fibrosis. Children with trisomy 21 also seemed more susceptible to infections; 83% had a viral or fungal lung infection at diagnosis, compared with 29% of those without trisomy 21.
Prior exposure to cytokine inhibitors
Parenchymal lung disease and pulmonary hypertension complicating sJIA was first highlighted in a series of 25 cases reported by Kimura et al. in 2013. These authors raised the question of the possible relationship of this and the increasing use of anti–IL-1 and anti–IL-6 biologics in sJIA treatment.
Following this lead, Dr. Mellins started looking into this new clinical entity in 2015. By then, she was identifying some past cases by autopsy records and current cases by clinical presentation. She saw a dramatic shift over time. From 2002 to 2011, she identified four cases, half of which had been exposed to IL-1/IL-6 inhibitors. From 2012 to 2014, eight new cases came to light, and seven had been exposed to those drugs. The crescendo continued from 2015 to 2017. During those years, Dr. Mellins and associates identified 10 new patients, 7 of whom had taken interleukin-inhibiting biologics. The mean time from initial drug exposure to diagnosis was a little more than 1 year.
An adjusted analysis comparing sJIA-LD patients and sJIA patients without lung disease didn’t find any significant difference in drug exposure. However, children with lung disease were more likely to have taken anakinra before the symptoms developed. Additionally, the symptoms of clubbing, abdominal pain, eosinophilia, hyperenhancing lymph nodes, and pulmonary alveolar proteinosis were much more common in children who’d taken the drugs.
The authors pointed out that this association does not prove causality and is confounded by the concomitant reduction in glucocorticoids with IL-1/IL-6 inhibitor use. And the vast majority of children with sJIA take cytokine inhibitors with no problems.
“Possibly, drug exposure may promote lung disease in a subset of children with sJIA, among the substantially larger group of patients who derive striking benefit from these drugs,” Dr. Mellins said, “Importantly, our results argue strongly for more investigation into a possible connection.”
Survival
After a mean follow-up of 1.7 years, the Stanford group saw high mortality. The 5-year survival rate translated to a mortality incidence of 159 deaths per 1,000 person-years, compared with 3.9 per 1,000 person-years in a historical cohort of sJIA patients who required biologic therapy.
Diffuse lung disease was the cause of 12 deaths; 5 of these patients also had macrophage activation syndrome at the time of death. Factors significantly associated with shortened survival included male sex, hypoxia at presentation, and neutrophilic bronchoalveolar lavage with more than 10 times the normal count. In an adjusted analysis, all of these variables fell out. However, none of the children with excessively high neutrophilic bronchoalveolar lavage survived.
Does it affect adults?
Could adults be experiencing the same disorder? There is some evidence to support it: The Food and Drug Administration adverse event website shows alveolar disease or pulmonary hypertension in 39 adults who have been exposed to IL-1 or IL-6 inhibition. Of these, 23 had RA, 11 adult-onset Still’s disease, and 5 unclassified rheumatic disorders.
The research groups were supported by grants from the sJIA Foundation, the Lucile Packard Foundation for Children’s Health, Stanford graduate fellowships, the Life Sciences Research Foundation, the Bill & Melinda Gates Foundation, Cincinnati Children’s Research Foundation, the Childhood Arthritis and Rheumatology Research Alliance, the Arthritis Foundation, and the National Institutes of Health. Many authors on both papers reported financial ties to Genentech, which markets tocilizumab, and other pharmaceutical companies*. Dr. Nigrovic reported receiving consulting fees and research support from Novartis and other companies.
SOURCES: Saper V et al. Ann Rheum Dis. 2019 Sep 27. doi: 10.1136/annrheumdis-2019-216040; Schulert GS et al. Arthritis Rheumatol. 2019 Aug 5. doi: 10.1002/art.41073; Nigrovic PA. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41071.
*Correction, 10/12/19: An earlier version of this article misstated the manufacturer of Actemra (tocilizumab).
This article was updated 10/14/19.
Congenital heart disease in children linked to increased autism risk
A new study of children who were born with congenital heart disease (CHD) has found that they have increased odds of developing autism spectrum disorder.
“To our knowledge, this is the only study in which there has been a comparison between [autism spectrum disorder] and multiple CHD subtypes,” wrote Eric R. Sigmon, MD, of Emory University, Atlanta, and coauthors. “Our findings are consistent with previous studies of CHD developmental outcomes, which have shown an increased risk of developmental and academic delay after CHD diagnosis and treatment.” The study was published in Pediatrics.
To further investigate the association between CHD and autism, the researchers performed a case-control study using the Military Health System administrative database. They uncovered 8,760 cases of children with autism spectrum disorder and matched each one with three controls (n = 26,280). From that sample size, they identified 1,063 children with CHD: 401 in the autism spectrum disorder group and 662 in the control group.
Before analysis, children with autism spectrum disorder had an odds ratio of 1.85 of having any form of CHD, compared with controls (95% confidence interval, 1.63-2.10). After adjustment for covariates – including genetic syndromes, maternal age and morbidity, perinatal morbidity, and neonatal complications – the OR was 1.33 (95% CI, 1.16-1.52).
In the sensitivity analysis – which included only 593 children with CHD – the OR was a similar 1.32 (95% CI, 1.10-1.59).
Left heart obstructive lesion was significantly associated with autism spectrum disorder after covariate adjustment (OR, 1.42; 95% CI, 1.04-1.93), but the finding was no longer significant in the sensitivity analysis.
The authors noted the potential limitations of their study, including the general weaknesses of administrative data, which they attempted to counter with the sensitive analysis. In addition, they recognized that children with either autism spectrum disorder or CHD “tend to present for care more frequently,” which could have created an ascertainment bias.
In an accompanying editorial, Johanna Calderon, PhD, David C. Bellinger, PhD, and Jane W. Newburger, MD, MPH, stated that more work needs to be done to further quantify the relationship between CHD and autism spectrum disorder (Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2019-2752). The three authors – all affiliated with Boston Children’s Hospital and Harvard Medical School, also in Boston – reiterated the acknowledgment from Dr. Sigmon and coauthors that the “etiologic pathways that might explain” the link between the two remains unknown. They also noted their surprise that autism spectrum disorder risk appears to be increased in children with modestly severe forms of CHD, stating that this finding required additional investigation.
“Despite the strengths of this study,” they wrote, “it raises more questions than answers.”
The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
SOURCE: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
A new study of children who were born with congenital heart disease (CHD) has found that they have increased odds of developing autism spectrum disorder.
“To our knowledge, this is the only study in which there has been a comparison between [autism spectrum disorder] and multiple CHD subtypes,” wrote Eric R. Sigmon, MD, of Emory University, Atlanta, and coauthors. “Our findings are consistent with previous studies of CHD developmental outcomes, which have shown an increased risk of developmental and academic delay after CHD diagnosis and treatment.” The study was published in Pediatrics.
To further investigate the association between CHD and autism, the researchers performed a case-control study using the Military Health System administrative database. They uncovered 8,760 cases of children with autism spectrum disorder and matched each one with three controls (n = 26,280). From that sample size, they identified 1,063 children with CHD: 401 in the autism spectrum disorder group and 662 in the control group.
Before analysis, children with autism spectrum disorder had an odds ratio of 1.85 of having any form of CHD, compared with controls (95% confidence interval, 1.63-2.10). After adjustment for covariates – including genetic syndromes, maternal age and morbidity, perinatal morbidity, and neonatal complications – the OR was 1.33 (95% CI, 1.16-1.52).
In the sensitivity analysis – which included only 593 children with CHD – the OR was a similar 1.32 (95% CI, 1.10-1.59).
Left heart obstructive lesion was significantly associated with autism spectrum disorder after covariate adjustment (OR, 1.42; 95% CI, 1.04-1.93), but the finding was no longer significant in the sensitivity analysis.
The authors noted the potential limitations of their study, including the general weaknesses of administrative data, which they attempted to counter with the sensitive analysis. In addition, they recognized that children with either autism spectrum disorder or CHD “tend to present for care more frequently,” which could have created an ascertainment bias.
In an accompanying editorial, Johanna Calderon, PhD, David C. Bellinger, PhD, and Jane W. Newburger, MD, MPH, stated that more work needs to be done to further quantify the relationship between CHD and autism spectrum disorder (Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2019-2752). The three authors – all affiliated with Boston Children’s Hospital and Harvard Medical School, also in Boston – reiterated the acknowledgment from Dr. Sigmon and coauthors that the “etiologic pathways that might explain” the link between the two remains unknown. They also noted their surprise that autism spectrum disorder risk appears to be increased in children with modestly severe forms of CHD, stating that this finding required additional investigation.
“Despite the strengths of this study,” they wrote, “it raises more questions than answers.”
The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
SOURCE: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
A new study of children who were born with congenital heart disease (CHD) has found that they have increased odds of developing autism spectrum disorder.
“To our knowledge, this is the only study in which there has been a comparison between [autism spectrum disorder] and multiple CHD subtypes,” wrote Eric R. Sigmon, MD, of Emory University, Atlanta, and coauthors. “Our findings are consistent with previous studies of CHD developmental outcomes, which have shown an increased risk of developmental and academic delay after CHD diagnosis and treatment.” The study was published in Pediatrics.
To further investigate the association between CHD and autism, the researchers performed a case-control study using the Military Health System administrative database. They uncovered 8,760 cases of children with autism spectrum disorder and matched each one with three controls (n = 26,280). From that sample size, they identified 1,063 children with CHD: 401 in the autism spectrum disorder group and 662 in the control group.
Before analysis, children with autism spectrum disorder had an odds ratio of 1.85 of having any form of CHD, compared with controls (95% confidence interval, 1.63-2.10). After adjustment for covariates – including genetic syndromes, maternal age and morbidity, perinatal morbidity, and neonatal complications – the OR was 1.33 (95% CI, 1.16-1.52).
In the sensitivity analysis – which included only 593 children with CHD – the OR was a similar 1.32 (95% CI, 1.10-1.59).
Left heart obstructive lesion was significantly associated with autism spectrum disorder after covariate adjustment (OR, 1.42; 95% CI, 1.04-1.93), but the finding was no longer significant in the sensitivity analysis.
The authors noted the potential limitations of their study, including the general weaknesses of administrative data, which they attempted to counter with the sensitive analysis. In addition, they recognized that children with either autism spectrum disorder or CHD “tend to present for care more frequently,” which could have created an ascertainment bias.
In an accompanying editorial, Johanna Calderon, PhD, David C. Bellinger, PhD, and Jane W. Newburger, MD, MPH, stated that more work needs to be done to further quantify the relationship between CHD and autism spectrum disorder (Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2019-2752). The three authors – all affiliated with Boston Children’s Hospital and Harvard Medical School, also in Boston – reiterated the acknowledgment from Dr. Sigmon and coauthors that the “etiologic pathways that might explain” the link between the two remains unknown. They also noted their surprise that autism spectrum disorder risk appears to be increased in children with modestly severe forms of CHD, stating that this finding required additional investigation.
“Despite the strengths of this study,” they wrote, “it raises more questions than answers.”
The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
SOURCE: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
FROM PEDIATRICS
Key clinical point: Children born with congenital heart disease have higher odds of developing autism, especially with certain forms of CHD, such as atrial and ventricular septal defects.
Major finding: After sensitivity analysis, children with congenital heart disease had increased odds of autism, compared with controls (odds ratio, 1.32; 95% confidence interval, 1.10-1.59).
Study details: A case-control study of children enrolled in the U.S. Military Health System from 2001 to 2013.
Disclosures: The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
Source: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
Faster enteral feeding does not up adverse outcomes risk in preterm infants
including moderate or severe neurodevelopmental disability and necrotizing enterocolitis, according to recent research published in the New England Journal of Medicine.
Although some data have shown rapidly increasing the speed of enteral-feeding volumes for preterm infants can raise the risk of necrotizing enterocolitis, these data are from observational case-control and uncontrolled studies, said Jon Dorling, MD, of the division of neonatal–perinatal medicine at Dalhousie University in Halifax, N.S., and colleagues in their study.
Dr. Doring and colleagues randomized 2,804 infants who were either very preterm or with a very low birth weight to receive daily milk increments at different volumes until the infants reached full feeding volume. Infants in the faster-increment group received daily milk at 30 mL per kg of body weight, while the slower-increment group received 18 mL per kg of body weight each day. The researchers analyzed infant survival without moderate or severe neurodevelopmental disability, with secondary outcomes of sepsis, necrotizing enterocolitis, and cerebral palsy at 24 months.
Overall, the researchers had information on the primary outcome for 87.4% of infants in the faster-increment group and 88.7% of infants in the slower-increment group. They found that 65.5% of infants in the faster-increment group and 68.1% of infants in the slower-increment group achieved an outcome of survival without moderate or severe neurodevelopmental disability at 24 months (adjusted risk ratio, 0.96; 95% confidence interval, 0.92-1.01; P equals .16). Secondary outcomes showed similar rates of adverse outcomes in the two groups, with 29.8% of infants in the faster-increment group and 31.1% of infants in the slower-increment group developing late-onset sepsis (aRR, 0.96; 95% CI, 0.86-1.07). Infants in the faster-increment group also had a similar rate of necrotizing enterocolitis (5.0%), compared with infants in the slower-increment group (5.6%) (aRR, 0.88; 95% CI, 0.68-1.16). Motor impairment was higher among infants in the faster-increment group (7.5%), compared with the slow-increment group (5.0%).
In the faster-increment group, the median number of days to reach full milk-feeding volumes was 7 vs. 10 in the slower-increment group.
“Although these feeding outcomes seem to favor faster increments, the risk of moderate or severe motor impairment was unexpectedly higher in the faster-increment group than in the slower-increment group,” the researchers said. “This observation is unexplained, and there were not more cases of late-onset sepsis or necrotizing enterocolitis in the faster-increment group.”
It is possible that it is a chance finding, since it was one of multiple secondary outcomes assessed, but biologically plausible explanations include increased cardiorespiratory events from pressure on the diaphragm or inability to absorb enteral nutrition,” they added.
The researchers said one potential limitation of the study was that it was unblinded.
This study was funded by the Health Technology Assessment Programme of the National Institute for Health Research. The authors reported various relationships with Baxter Bioscience, Chiesi Farmaceutici, Danone Early Life Nutrition, Fresenius Kabi USA LLC, National Institute for Health Research, Nestle Nutrition Institute, Nutrina, Medical Research Council, and Prolacta Biosciences in the form of consultancies, grants, travel reimbursement, board memberships, and editorial board appointments.
SOURCE: Doring J et al. N Eng J Med. 2019. doi: 10.1056/NEJMoa1816654.
including moderate or severe neurodevelopmental disability and necrotizing enterocolitis, according to recent research published in the New England Journal of Medicine.
Although some data have shown rapidly increasing the speed of enteral-feeding volumes for preterm infants can raise the risk of necrotizing enterocolitis, these data are from observational case-control and uncontrolled studies, said Jon Dorling, MD, of the division of neonatal–perinatal medicine at Dalhousie University in Halifax, N.S., and colleagues in their study.
Dr. Doring and colleagues randomized 2,804 infants who were either very preterm or with a very low birth weight to receive daily milk increments at different volumes until the infants reached full feeding volume. Infants in the faster-increment group received daily milk at 30 mL per kg of body weight, while the slower-increment group received 18 mL per kg of body weight each day. The researchers analyzed infant survival without moderate or severe neurodevelopmental disability, with secondary outcomes of sepsis, necrotizing enterocolitis, and cerebral palsy at 24 months.
Overall, the researchers had information on the primary outcome for 87.4% of infants in the faster-increment group and 88.7% of infants in the slower-increment group. They found that 65.5% of infants in the faster-increment group and 68.1% of infants in the slower-increment group achieved an outcome of survival without moderate or severe neurodevelopmental disability at 24 months (adjusted risk ratio, 0.96; 95% confidence interval, 0.92-1.01; P equals .16). Secondary outcomes showed similar rates of adverse outcomes in the two groups, with 29.8% of infants in the faster-increment group and 31.1% of infants in the slower-increment group developing late-onset sepsis (aRR, 0.96; 95% CI, 0.86-1.07). Infants in the faster-increment group also had a similar rate of necrotizing enterocolitis (5.0%), compared with infants in the slower-increment group (5.6%) (aRR, 0.88; 95% CI, 0.68-1.16). Motor impairment was higher among infants in the faster-increment group (7.5%), compared with the slow-increment group (5.0%).
In the faster-increment group, the median number of days to reach full milk-feeding volumes was 7 vs. 10 in the slower-increment group.
“Although these feeding outcomes seem to favor faster increments, the risk of moderate or severe motor impairment was unexpectedly higher in the faster-increment group than in the slower-increment group,” the researchers said. “This observation is unexplained, and there were not more cases of late-onset sepsis or necrotizing enterocolitis in the faster-increment group.”
It is possible that it is a chance finding, since it was one of multiple secondary outcomes assessed, but biologically plausible explanations include increased cardiorespiratory events from pressure on the diaphragm or inability to absorb enteral nutrition,” they added.
The researchers said one potential limitation of the study was that it was unblinded.
This study was funded by the Health Technology Assessment Programme of the National Institute for Health Research. The authors reported various relationships with Baxter Bioscience, Chiesi Farmaceutici, Danone Early Life Nutrition, Fresenius Kabi USA LLC, National Institute for Health Research, Nestle Nutrition Institute, Nutrina, Medical Research Council, and Prolacta Biosciences in the form of consultancies, grants, travel reimbursement, board memberships, and editorial board appointments.
SOURCE: Doring J et al. N Eng J Med. 2019. doi: 10.1056/NEJMoa1816654.
including moderate or severe neurodevelopmental disability and necrotizing enterocolitis, according to recent research published in the New England Journal of Medicine.
Although some data have shown rapidly increasing the speed of enteral-feeding volumes for preterm infants can raise the risk of necrotizing enterocolitis, these data are from observational case-control and uncontrolled studies, said Jon Dorling, MD, of the division of neonatal–perinatal medicine at Dalhousie University in Halifax, N.S., and colleagues in their study.
Dr. Doring and colleagues randomized 2,804 infants who were either very preterm or with a very low birth weight to receive daily milk increments at different volumes until the infants reached full feeding volume. Infants in the faster-increment group received daily milk at 30 mL per kg of body weight, while the slower-increment group received 18 mL per kg of body weight each day. The researchers analyzed infant survival without moderate or severe neurodevelopmental disability, with secondary outcomes of sepsis, necrotizing enterocolitis, and cerebral palsy at 24 months.
Overall, the researchers had information on the primary outcome for 87.4% of infants in the faster-increment group and 88.7% of infants in the slower-increment group. They found that 65.5% of infants in the faster-increment group and 68.1% of infants in the slower-increment group achieved an outcome of survival without moderate or severe neurodevelopmental disability at 24 months (adjusted risk ratio, 0.96; 95% confidence interval, 0.92-1.01; P equals .16). Secondary outcomes showed similar rates of adverse outcomes in the two groups, with 29.8% of infants in the faster-increment group and 31.1% of infants in the slower-increment group developing late-onset sepsis (aRR, 0.96; 95% CI, 0.86-1.07). Infants in the faster-increment group also had a similar rate of necrotizing enterocolitis (5.0%), compared with infants in the slower-increment group (5.6%) (aRR, 0.88; 95% CI, 0.68-1.16). Motor impairment was higher among infants in the faster-increment group (7.5%), compared with the slow-increment group (5.0%).
In the faster-increment group, the median number of days to reach full milk-feeding volumes was 7 vs. 10 in the slower-increment group.
“Although these feeding outcomes seem to favor faster increments, the risk of moderate or severe motor impairment was unexpectedly higher in the faster-increment group than in the slower-increment group,” the researchers said. “This observation is unexplained, and there were not more cases of late-onset sepsis or necrotizing enterocolitis in the faster-increment group.”
It is possible that it is a chance finding, since it was one of multiple secondary outcomes assessed, but biologically plausible explanations include increased cardiorespiratory events from pressure on the diaphragm or inability to absorb enteral nutrition,” they added.
The researchers said one potential limitation of the study was that it was unblinded.
This study was funded by the Health Technology Assessment Programme of the National Institute for Health Research. The authors reported various relationships with Baxter Bioscience, Chiesi Farmaceutici, Danone Early Life Nutrition, Fresenius Kabi USA LLC, National Institute for Health Research, Nestle Nutrition Institute, Nutrina, Medical Research Council, and Prolacta Biosciences in the form of consultancies, grants, travel reimbursement, board memberships, and editorial board appointments.
SOURCE: Doring J et al. N Eng J Med. 2019. doi: 10.1056/NEJMoa1816654.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Congenital syphilis continues to rise at an alarming rate
One of the nation’s most preventable diseases is killing newborns in ever-increasing numbers.
Seventy-eight of those babies were stillborn, and 16 died after birth.
In California, cases of congenital syphilis – the term used when a mother passes the infection to her baby during pregnancy – continued a stark 7-year climb, to 332 cases, an 18.1% increase from 2017, according to the federal data. Only Texas, Nevada, Louisiana, and Arizona had congenital syphilis rates higher than California’s. Those five states combined made up nearly two-thirds of total cases, although all but 17 states saw increases in their congenital syphilis rates.
The state-by-state numbers were released as part of a broader report from the Centers for Disease Control and Prevention tracking trends in sexually transmitted diseases. Cases of syphilis, gonorrhea, and chlamydia combined reached an all-time high in 2018. Cases of the most infectious stage of syphilis rose 14% to more than 35,000 cases; gonorrhea increased 5% to more than 580,000 cases; and chlamydia increased 3% to more than 1.7 million cases.
For veteran public health workers, the upward trend in congenital syphilis numbers is particularly disturbing because the condition is so easy to prevent. Blood tests can identify infection in pregnant women. The treatment is relatively simple and effective. When caught during pregnancy, transmission from mother to baby generally can be stopped.
“When we see a case of congenital syphilis, it is a hallmark of a health system and a health care failure,” said Virginia Bowen, PhD, an epidemiologist with the CDC and an author of the report.
It takes just a few shots of antibiotics to prevent a baby from getting syphilis from its mother. Left untreated, Treponema pallidum, the corkscrew-shaped organism that causes syphilis, can wiggle its way through a mother’s placenta and into a fetus. Once there, it can multiply furiously, invading every part of the body.
The effects on a newborn can be devastating. Philip Cheng, MD, is a neonatologist at St. Joseph’s Medical Center in Stockton, a city in San Joaquin County in California’s Central Valley. Twenty-six babies were infected last year in San Joaquin County, according to state data.
The brain of one of Cheng’s patients didn’t develop properly and the baby died shortly after birth. Other young patients survive but battle blood abnormalities, bone deformities, and organ damage. Congenital syphilis can cause blindness and excruciating pain.
Public health departments across the Central Valley, a largely rural expanse, report similar experiences. Following the release of the CDC report Tuesday, the California Department of Public Health released its county-by-county numbers for 2018. The report showed syphilis, gonorrhea, and chlamydia levels at their highest in 30 years, and attributed 22 stillbirths or neonatal deaths to congenital syphilis.
For the past several years, Fresno County, which had 63 cases of congenital syphilis in 2017, had the highest rate in California. In 2018, Fresno fell to fourth, behind Yuba, Kern, and San Joaquin counties. But the epidemic is far from under control. “I couldn’t even tell you how soon I think we’re going to see a decrease,” said Jena Adams, who oversees HIV and STD programs for Fresno County.
Syphilis was once a prolific and widely feared STD. But by the 1940s, penicillin was found to have a near-perfect cure rate for the disease. By 2000, syphilis rates were so low in the U.S. that the federal government launched a plan to eliminate the disease. Today, that goal is a distant memory.
Health departments once tracked down every person who tested positive for chlamydia, gonorrhea, or syphilis, to make sure they and their partners got treatment. With limited funds and climbing caseloads, many states now devote resources only to tracking syphilis. The caseloads are so high in some California counties that they track only women of childbearing age or just pregnant women.
“A lot of the funding for day-to-day public health work isn’t there,” said Jeffrey Klausner, MD, a professor at the University of California-Los Angeles who ran San Francisco’s STD program for more than a decade.
The bulk of STD prevention funding is appropriated by Congress to the CDC, which passes it on to states. That funding has been largely flat since 2003, according to data from the National Coalition of STD Directors, which represents health departments across the country. Take into account inflation and the growing caseloads, and the money is spread thinner. “It takes money, it takes training, it takes resources,” Dr. Klausner said, “and policymakers have just not prioritized that.”
A report this year by Trust for America’s Health, a public health policy research and advocacy group, estimated that 55,000 jobs were cut from local public health departments from 2008 to 2017. “We have our hands tied as much as [states] do,” said Dr. Bowen of the CDC. “We take what we’re given and try to distribute it as fairly as we can.”
San Joaquin County health officials have reorganized the department and applied for grants to increase the number of investigators available while congenital syphilis has spiked, said Hemal Parikh, county coordinator for STD control. But even with new hires and cutting back to tracking only women of childbearing age with syphilis, an investigator can have anywhere from 20 to 30 open cases at a time. In other counties, the caseload can be double that.
In 2018, Jennifer Wagman, PhD, a UCLA professor who studies infectious diseases and gender inequality, was part of a group that received CDC funding to look into what is causing the spike in congenital syphilis in California’s Central Valley.
Dr. Wagman said that, after years of studying health systems in other countries, she was shocked to see how much basic public health infrastructure has crumbled in California. In many parts of the Central Valley, county walk-in clinics that tested for and treated STDs were shuttered in the wake of the recession. That left few places for drop-in care, and investigators with no place to take someone for immediate treatment. Investigators or their patients must make appointments at one of the few providers who carry the right kind of treatment and hope the patients can keep the appointment when the time comes.
In focus groups, women told Dr. Wagman that working hourly jobs, or dealing with chaotic lives involving homelessness, abusive partners, and drug use, can make it all but impossible to stick to the appointments required at private clinics.
Dr. Wagman found that women in these high-risk groups were seeking care, though sometimes late in their pregnancy. They were just more likely to visit an emergency room, urgent care, or even a methadone clinic – places that take drop-ins but don’t necessarily routinely test for or treat syphilis.
“These people already have a million barriers,” said Jenny Malone, the public health nurse for San Joaquin County. “Now there are more.”
The most challenging cases in California are wrapped up with the state’s growing housing crisis and a methamphetamine epidemic with few treatment options. Women who are homeless often have unreliable contact information and are unlikely to have a primary care doctor. That makes them tough to track down to give a positive diagnosis or to follow up on a treatment plan.
Louisiana had the highest rate of congenital syphilis in the country for several years – until 2018. After a 22% drop in its rate, combined with increases in other states, Louisiana now ranks behind Texas and Nevada. That drop is the direct result of $550 million in temporary supplemental funding that the CDC gave the state to combat the epidemic, said Chaquetta Johnson, DNP, deputy director of operations for the state’s STD/HIV/hepatitis program. The money helped bolster the state’s lagging public health infrastructure. It was used to host two conferences for providers in the hardest-hit areas, hire two case managers and a nurse educator, create a program for in-home treatment, and improve data systems to track cases, among other things.
In California, more than 40% of pregnant women with syphilis passed it on to their baby in 2016, the most recent year for which data is available. Gov. Gavin Newsom (D) made additional funding available this year, but it’s a “drop in the bucket,” said Sergio Morales of Essential Access Health, a nonprofit that focuses on sexual and reproductive health and is working with Kern County on congenital syphilis. “We are seeing the results of years of inaction and a lack of prioritization of STD prevention, and we’re now paying the price.”
This KHN story first published on California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
[Update: This story was revised at 6:50 p.m. ET on Oct. 8 to reflect news developments.]
One of the nation’s most preventable diseases is killing newborns in ever-increasing numbers.
Seventy-eight of those babies were stillborn, and 16 died after birth.
In California, cases of congenital syphilis – the term used when a mother passes the infection to her baby during pregnancy – continued a stark 7-year climb, to 332 cases, an 18.1% increase from 2017, according to the federal data. Only Texas, Nevada, Louisiana, and Arizona had congenital syphilis rates higher than California’s. Those five states combined made up nearly two-thirds of total cases, although all but 17 states saw increases in their congenital syphilis rates.
The state-by-state numbers were released as part of a broader report from the Centers for Disease Control and Prevention tracking trends in sexually transmitted diseases. Cases of syphilis, gonorrhea, and chlamydia combined reached an all-time high in 2018. Cases of the most infectious stage of syphilis rose 14% to more than 35,000 cases; gonorrhea increased 5% to more than 580,000 cases; and chlamydia increased 3% to more than 1.7 million cases.
For veteran public health workers, the upward trend in congenital syphilis numbers is particularly disturbing because the condition is so easy to prevent. Blood tests can identify infection in pregnant women. The treatment is relatively simple and effective. When caught during pregnancy, transmission from mother to baby generally can be stopped.
“When we see a case of congenital syphilis, it is a hallmark of a health system and a health care failure,” said Virginia Bowen, PhD, an epidemiologist with the CDC and an author of the report.
It takes just a few shots of antibiotics to prevent a baby from getting syphilis from its mother. Left untreated, Treponema pallidum, the corkscrew-shaped organism that causes syphilis, can wiggle its way through a mother’s placenta and into a fetus. Once there, it can multiply furiously, invading every part of the body.
The effects on a newborn can be devastating. Philip Cheng, MD, is a neonatologist at St. Joseph’s Medical Center in Stockton, a city in San Joaquin County in California’s Central Valley. Twenty-six babies were infected last year in San Joaquin County, according to state data.
The brain of one of Cheng’s patients didn’t develop properly and the baby died shortly after birth. Other young patients survive but battle blood abnormalities, bone deformities, and organ damage. Congenital syphilis can cause blindness and excruciating pain.
Public health departments across the Central Valley, a largely rural expanse, report similar experiences. Following the release of the CDC report Tuesday, the California Department of Public Health released its county-by-county numbers for 2018. The report showed syphilis, gonorrhea, and chlamydia levels at their highest in 30 years, and attributed 22 stillbirths or neonatal deaths to congenital syphilis.
For the past several years, Fresno County, which had 63 cases of congenital syphilis in 2017, had the highest rate in California. In 2018, Fresno fell to fourth, behind Yuba, Kern, and San Joaquin counties. But the epidemic is far from under control. “I couldn’t even tell you how soon I think we’re going to see a decrease,” said Jena Adams, who oversees HIV and STD programs for Fresno County.
Syphilis was once a prolific and widely feared STD. But by the 1940s, penicillin was found to have a near-perfect cure rate for the disease. By 2000, syphilis rates were so low in the U.S. that the federal government launched a plan to eliminate the disease. Today, that goal is a distant memory.
Health departments once tracked down every person who tested positive for chlamydia, gonorrhea, or syphilis, to make sure they and their partners got treatment. With limited funds and climbing caseloads, many states now devote resources only to tracking syphilis. The caseloads are so high in some California counties that they track only women of childbearing age or just pregnant women.
“A lot of the funding for day-to-day public health work isn’t there,” said Jeffrey Klausner, MD, a professor at the University of California-Los Angeles who ran San Francisco’s STD program for more than a decade.
The bulk of STD prevention funding is appropriated by Congress to the CDC, which passes it on to states. That funding has been largely flat since 2003, according to data from the National Coalition of STD Directors, which represents health departments across the country. Take into account inflation and the growing caseloads, and the money is spread thinner. “It takes money, it takes training, it takes resources,” Dr. Klausner said, “and policymakers have just not prioritized that.”
A report this year by Trust for America’s Health, a public health policy research and advocacy group, estimated that 55,000 jobs were cut from local public health departments from 2008 to 2017. “We have our hands tied as much as [states] do,” said Dr. Bowen of the CDC. “We take what we’re given and try to distribute it as fairly as we can.”
San Joaquin County health officials have reorganized the department and applied for grants to increase the number of investigators available while congenital syphilis has spiked, said Hemal Parikh, county coordinator for STD control. But even with new hires and cutting back to tracking only women of childbearing age with syphilis, an investigator can have anywhere from 20 to 30 open cases at a time. In other counties, the caseload can be double that.
In 2018, Jennifer Wagman, PhD, a UCLA professor who studies infectious diseases and gender inequality, was part of a group that received CDC funding to look into what is causing the spike in congenital syphilis in California’s Central Valley.
Dr. Wagman said that, after years of studying health systems in other countries, she was shocked to see how much basic public health infrastructure has crumbled in California. In many parts of the Central Valley, county walk-in clinics that tested for and treated STDs were shuttered in the wake of the recession. That left few places for drop-in care, and investigators with no place to take someone for immediate treatment. Investigators or their patients must make appointments at one of the few providers who carry the right kind of treatment and hope the patients can keep the appointment when the time comes.
In focus groups, women told Dr. Wagman that working hourly jobs, or dealing with chaotic lives involving homelessness, abusive partners, and drug use, can make it all but impossible to stick to the appointments required at private clinics.
Dr. Wagman found that women in these high-risk groups were seeking care, though sometimes late in their pregnancy. They were just more likely to visit an emergency room, urgent care, or even a methadone clinic – places that take drop-ins but don’t necessarily routinely test for or treat syphilis.
“These people already have a million barriers,” said Jenny Malone, the public health nurse for San Joaquin County. “Now there are more.”
The most challenging cases in California are wrapped up with the state’s growing housing crisis and a methamphetamine epidemic with few treatment options. Women who are homeless often have unreliable contact information and are unlikely to have a primary care doctor. That makes them tough to track down to give a positive diagnosis or to follow up on a treatment plan.
Louisiana had the highest rate of congenital syphilis in the country for several years – until 2018. After a 22% drop in its rate, combined with increases in other states, Louisiana now ranks behind Texas and Nevada. That drop is the direct result of $550 million in temporary supplemental funding that the CDC gave the state to combat the epidemic, said Chaquetta Johnson, DNP, deputy director of operations for the state’s STD/HIV/hepatitis program. The money helped bolster the state’s lagging public health infrastructure. It was used to host two conferences for providers in the hardest-hit areas, hire two case managers and a nurse educator, create a program for in-home treatment, and improve data systems to track cases, among other things.
In California, more than 40% of pregnant women with syphilis passed it on to their baby in 2016, the most recent year for which data is available. Gov. Gavin Newsom (D) made additional funding available this year, but it’s a “drop in the bucket,” said Sergio Morales of Essential Access Health, a nonprofit that focuses on sexual and reproductive health and is working with Kern County on congenital syphilis. “We are seeing the results of years of inaction and a lack of prioritization of STD prevention, and we’re now paying the price.”
This KHN story first published on California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
[Update: This story was revised at 6:50 p.m. ET on Oct. 8 to reflect news developments.]
One of the nation’s most preventable diseases is killing newborns in ever-increasing numbers.
Seventy-eight of those babies were stillborn, and 16 died after birth.
In California, cases of congenital syphilis – the term used when a mother passes the infection to her baby during pregnancy – continued a stark 7-year climb, to 332 cases, an 18.1% increase from 2017, according to the federal data. Only Texas, Nevada, Louisiana, and Arizona had congenital syphilis rates higher than California’s. Those five states combined made up nearly two-thirds of total cases, although all but 17 states saw increases in their congenital syphilis rates.
The state-by-state numbers were released as part of a broader report from the Centers for Disease Control and Prevention tracking trends in sexually transmitted diseases. Cases of syphilis, gonorrhea, and chlamydia combined reached an all-time high in 2018. Cases of the most infectious stage of syphilis rose 14% to more than 35,000 cases; gonorrhea increased 5% to more than 580,000 cases; and chlamydia increased 3% to more than 1.7 million cases.
For veteran public health workers, the upward trend in congenital syphilis numbers is particularly disturbing because the condition is so easy to prevent. Blood tests can identify infection in pregnant women. The treatment is relatively simple and effective. When caught during pregnancy, transmission from mother to baby generally can be stopped.
“When we see a case of congenital syphilis, it is a hallmark of a health system and a health care failure,” said Virginia Bowen, PhD, an epidemiologist with the CDC and an author of the report.
It takes just a few shots of antibiotics to prevent a baby from getting syphilis from its mother. Left untreated, Treponema pallidum, the corkscrew-shaped organism that causes syphilis, can wiggle its way through a mother’s placenta and into a fetus. Once there, it can multiply furiously, invading every part of the body.
The effects on a newborn can be devastating. Philip Cheng, MD, is a neonatologist at St. Joseph’s Medical Center in Stockton, a city in San Joaquin County in California’s Central Valley. Twenty-six babies were infected last year in San Joaquin County, according to state data.
The brain of one of Cheng’s patients didn’t develop properly and the baby died shortly after birth. Other young patients survive but battle blood abnormalities, bone deformities, and organ damage. Congenital syphilis can cause blindness and excruciating pain.
Public health departments across the Central Valley, a largely rural expanse, report similar experiences. Following the release of the CDC report Tuesday, the California Department of Public Health released its county-by-county numbers for 2018. The report showed syphilis, gonorrhea, and chlamydia levels at their highest in 30 years, and attributed 22 stillbirths or neonatal deaths to congenital syphilis.
For the past several years, Fresno County, which had 63 cases of congenital syphilis in 2017, had the highest rate in California. In 2018, Fresno fell to fourth, behind Yuba, Kern, and San Joaquin counties. But the epidemic is far from under control. “I couldn’t even tell you how soon I think we’re going to see a decrease,” said Jena Adams, who oversees HIV and STD programs for Fresno County.
Syphilis was once a prolific and widely feared STD. But by the 1940s, penicillin was found to have a near-perfect cure rate for the disease. By 2000, syphilis rates were so low in the U.S. that the federal government launched a plan to eliminate the disease. Today, that goal is a distant memory.
Health departments once tracked down every person who tested positive for chlamydia, gonorrhea, or syphilis, to make sure they and their partners got treatment. With limited funds and climbing caseloads, many states now devote resources only to tracking syphilis. The caseloads are so high in some California counties that they track only women of childbearing age or just pregnant women.
“A lot of the funding for day-to-day public health work isn’t there,” said Jeffrey Klausner, MD, a professor at the University of California-Los Angeles who ran San Francisco’s STD program for more than a decade.
The bulk of STD prevention funding is appropriated by Congress to the CDC, which passes it on to states. That funding has been largely flat since 2003, according to data from the National Coalition of STD Directors, which represents health departments across the country. Take into account inflation and the growing caseloads, and the money is spread thinner. “It takes money, it takes training, it takes resources,” Dr. Klausner said, “and policymakers have just not prioritized that.”
A report this year by Trust for America’s Health, a public health policy research and advocacy group, estimated that 55,000 jobs were cut from local public health departments from 2008 to 2017. “We have our hands tied as much as [states] do,” said Dr. Bowen of the CDC. “We take what we’re given and try to distribute it as fairly as we can.”
San Joaquin County health officials have reorganized the department and applied for grants to increase the number of investigators available while congenital syphilis has spiked, said Hemal Parikh, county coordinator for STD control. But even with new hires and cutting back to tracking only women of childbearing age with syphilis, an investigator can have anywhere from 20 to 30 open cases at a time. In other counties, the caseload can be double that.
In 2018, Jennifer Wagman, PhD, a UCLA professor who studies infectious diseases and gender inequality, was part of a group that received CDC funding to look into what is causing the spike in congenital syphilis in California’s Central Valley.
Dr. Wagman said that, after years of studying health systems in other countries, she was shocked to see how much basic public health infrastructure has crumbled in California. In many parts of the Central Valley, county walk-in clinics that tested for and treated STDs were shuttered in the wake of the recession. That left few places for drop-in care, and investigators with no place to take someone for immediate treatment. Investigators or their patients must make appointments at one of the few providers who carry the right kind of treatment and hope the patients can keep the appointment when the time comes.
In focus groups, women told Dr. Wagman that working hourly jobs, or dealing with chaotic lives involving homelessness, abusive partners, and drug use, can make it all but impossible to stick to the appointments required at private clinics.
Dr. Wagman found that women in these high-risk groups were seeking care, though sometimes late in their pregnancy. They were just more likely to visit an emergency room, urgent care, or even a methadone clinic – places that take drop-ins but don’t necessarily routinely test for or treat syphilis.
“These people already have a million barriers,” said Jenny Malone, the public health nurse for San Joaquin County. “Now there are more.”
The most challenging cases in California are wrapped up with the state’s growing housing crisis and a methamphetamine epidemic with few treatment options. Women who are homeless often have unreliable contact information and are unlikely to have a primary care doctor. That makes them tough to track down to give a positive diagnosis or to follow up on a treatment plan.
Louisiana had the highest rate of congenital syphilis in the country for several years – until 2018. After a 22% drop in its rate, combined with increases in other states, Louisiana now ranks behind Texas and Nevada. That drop is the direct result of $550 million in temporary supplemental funding that the CDC gave the state to combat the epidemic, said Chaquetta Johnson, DNP, deputy director of operations for the state’s STD/HIV/hepatitis program. The money helped bolster the state’s lagging public health infrastructure. It was used to host two conferences for providers in the hardest-hit areas, hire two case managers and a nurse educator, create a program for in-home treatment, and improve data systems to track cases, among other things.
In California, more than 40% of pregnant women with syphilis passed it on to their baby in 2016, the most recent year for which data is available. Gov. Gavin Newsom (D) made additional funding available this year, but it’s a “drop in the bucket,” said Sergio Morales of Essential Access Health, a nonprofit that focuses on sexual and reproductive health and is working with Kern County on congenital syphilis. “We are seeing the results of years of inaction and a lack of prioritization of STD prevention, and we’re now paying the price.”
This KHN story first published on California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
[Update: This story was revised at 6:50 p.m. ET on Oct. 8 to reflect news developments.]
One-year data support dupilumab’s efficacy and safety in adolescents with AD
A study of and continued evidence of efficacy for up to 52 weeks, reported the authors of the study, published online Oct. 9 in the British Journal of Dermatology.
The phase 2a open-label, ascending-dose cohort study of dupilumab in 40 adolescents with moderate to severe AD was followed by a 48-week phase 3 open-label extension study in 36 of those participants. Dupilumab is a monoclonal antibody that inhibits signaling of interleukin (IL)-4 and IL-13.
In the phase 2a study, participants were treated with a single subcutaneous dose of dupilumab – either 2 mg/kg or 4 mg/kg – and had 8 weeks of pharmacokinetic sampling. They subsequently received that same dose weekly for 4 weeks, with an 8-week-long safety follow-up period. Those who participated in the open-label extension continued their weekly dose to a maximum of 300 mg. per kg
The most common treatment-emergent adverse events (a primary endpoint) seen in both the phase 2a and phase 3 studies were nasopharyngitis and exacerbation of AD – in the phase 2a study, exacerbations were seen in the period when patients weren’t taking the treatment. In the 2-mg and 4-mg groups, the incidence of skin infections was 29% and 42%, respectively, and the incidence of injection site reactions – which were mostly mild – were 18% and 11%, respectively. Researchers also noted conjunctivitis in 18% and 16% of the patients in the 2-mg and 4-mg groups, respectively, but none of the cases were considered serious and all resolved over the course of the study. In the phase 2a study, 50% of patients on the 2-mg/kg dose and 65% of those on the 4-mg/kg dose experienced an adverse event, while in the open-label extension all reported at least one adverse event.
There was one case of suicidal behavior and one case of systemic or severe hypersensitivity reported in the 2-mg/kg groups, both of which were considered adverse events of special interest. There were no deaths.
However none of the serious adverse events – which included infected AD, palpitations, patent ductus arteriosus, and food allergy – were linked to the study treatment, and no adverse events led to study discontinuation, the authors reported.
By week 12, 70% of participants in the 2-mg/kg group and 75% in the 4-mg/kg group had achieved a 50% or greater improvement in their Eczema Area and Severity Index (EASI) scores, which was a secondary outcome. By week 52, that had increased to 100% and 89% respectively.
More than half the patients (55%) in the 2-mg/kg group, and 40% of those in the 4-mg/kg group achieved a 75% or more improvement in their EASI scores by week 12, which increased to 88% and 78%, respectively, by week 52 in the open label phase.
“The results from these studies support use of dupilumab for the long-term management of moderate to severe AD in adolescents,” wrote Michael J. Cork, MD, professor of dermatology, University of Sheffield, England, and coauthors. No new safety signals were identified, “compared with the known safety profile of dupilumab in adults with moderate to severe AD,” and “the PK profile was characterized by nonlinear, target-mediated kinetics, consistent with the profile in adults with moderate to severe AD,” they added.
Dupilumab was approved in the United States in March 2019 for adolescents with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
The study was sponsored by dupilumab manufacturers Sanofi and Regeneron Pharmaceuticals, which market dupilumab as Dupixent in the United States. Dr. Cork disclosures included those related to Sanofi Genzyme and Regeneron; other authors included employees of the companies.
SOURCE: Cork M et al. Br J Dermatol. 2019 Oct 9. doi: 10.1111/bjd.18476.
A study of and continued evidence of efficacy for up to 52 weeks, reported the authors of the study, published online Oct. 9 in the British Journal of Dermatology.
The phase 2a open-label, ascending-dose cohort study of dupilumab in 40 adolescents with moderate to severe AD was followed by a 48-week phase 3 open-label extension study in 36 of those participants. Dupilumab is a monoclonal antibody that inhibits signaling of interleukin (IL)-4 and IL-13.
In the phase 2a study, participants were treated with a single subcutaneous dose of dupilumab – either 2 mg/kg or 4 mg/kg – and had 8 weeks of pharmacokinetic sampling. They subsequently received that same dose weekly for 4 weeks, with an 8-week-long safety follow-up period. Those who participated in the open-label extension continued their weekly dose to a maximum of 300 mg. per kg
The most common treatment-emergent adverse events (a primary endpoint) seen in both the phase 2a and phase 3 studies were nasopharyngitis and exacerbation of AD – in the phase 2a study, exacerbations were seen in the period when patients weren’t taking the treatment. In the 2-mg and 4-mg groups, the incidence of skin infections was 29% and 42%, respectively, and the incidence of injection site reactions – which were mostly mild – were 18% and 11%, respectively. Researchers also noted conjunctivitis in 18% and 16% of the patients in the 2-mg and 4-mg groups, respectively, but none of the cases were considered serious and all resolved over the course of the study. In the phase 2a study, 50% of patients on the 2-mg/kg dose and 65% of those on the 4-mg/kg dose experienced an adverse event, while in the open-label extension all reported at least one adverse event.
There was one case of suicidal behavior and one case of systemic or severe hypersensitivity reported in the 2-mg/kg groups, both of which were considered adverse events of special interest. There were no deaths.
However none of the serious adverse events – which included infected AD, palpitations, patent ductus arteriosus, and food allergy – were linked to the study treatment, and no adverse events led to study discontinuation, the authors reported.
By week 12, 70% of participants in the 2-mg/kg group and 75% in the 4-mg/kg group had achieved a 50% or greater improvement in their Eczema Area and Severity Index (EASI) scores, which was a secondary outcome. By week 52, that had increased to 100% and 89% respectively.
More than half the patients (55%) in the 2-mg/kg group, and 40% of those in the 4-mg/kg group achieved a 75% or more improvement in their EASI scores by week 12, which increased to 88% and 78%, respectively, by week 52 in the open label phase.
“The results from these studies support use of dupilumab for the long-term management of moderate to severe AD in adolescents,” wrote Michael J. Cork, MD, professor of dermatology, University of Sheffield, England, and coauthors. No new safety signals were identified, “compared with the known safety profile of dupilumab in adults with moderate to severe AD,” and “the PK profile was characterized by nonlinear, target-mediated kinetics, consistent with the profile in adults with moderate to severe AD,” they added.
Dupilumab was approved in the United States in March 2019 for adolescents with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
The study was sponsored by dupilumab manufacturers Sanofi and Regeneron Pharmaceuticals, which market dupilumab as Dupixent in the United States. Dr. Cork disclosures included those related to Sanofi Genzyme and Regeneron; other authors included employees of the companies.
SOURCE: Cork M et al. Br J Dermatol. 2019 Oct 9. doi: 10.1111/bjd.18476.
A study of and continued evidence of efficacy for up to 52 weeks, reported the authors of the study, published online Oct. 9 in the British Journal of Dermatology.
The phase 2a open-label, ascending-dose cohort study of dupilumab in 40 adolescents with moderate to severe AD was followed by a 48-week phase 3 open-label extension study in 36 of those participants. Dupilumab is a monoclonal antibody that inhibits signaling of interleukin (IL)-4 and IL-13.
In the phase 2a study, participants were treated with a single subcutaneous dose of dupilumab – either 2 mg/kg or 4 mg/kg – and had 8 weeks of pharmacokinetic sampling. They subsequently received that same dose weekly for 4 weeks, with an 8-week-long safety follow-up period. Those who participated in the open-label extension continued their weekly dose to a maximum of 300 mg. per kg
The most common treatment-emergent adverse events (a primary endpoint) seen in both the phase 2a and phase 3 studies were nasopharyngitis and exacerbation of AD – in the phase 2a study, exacerbations were seen in the period when patients weren’t taking the treatment. In the 2-mg and 4-mg groups, the incidence of skin infections was 29% and 42%, respectively, and the incidence of injection site reactions – which were mostly mild – were 18% and 11%, respectively. Researchers also noted conjunctivitis in 18% and 16% of the patients in the 2-mg and 4-mg groups, respectively, but none of the cases were considered serious and all resolved over the course of the study. In the phase 2a study, 50% of patients on the 2-mg/kg dose and 65% of those on the 4-mg/kg dose experienced an adverse event, while in the open-label extension all reported at least one adverse event.
There was one case of suicidal behavior and one case of systemic or severe hypersensitivity reported in the 2-mg/kg groups, both of which were considered adverse events of special interest. There were no deaths.
However none of the serious adverse events – which included infected AD, palpitations, patent ductus arteriosus, and food allergy – were linked to the study treatment, and no adverse events led to study discontinuation, the authors reported.
By week 12, 70% of participants in the 2-mg/kg group and 75% in the 4-mg/kg group had achieved a 50% or greater improvement in their Eczema Area and Severity Index (EASI) scores, which was a secondary outcome. By week 52, that had increased to 100% and 89% respectively.
More than half the patients (55%) in the 2-mg/kg group, and 40% of those in the 4-mg/kg group achieved a 75% or more improvement in their EASI scores by week 12, which increased to 88% and 78%, respectively, by week 52 in the open label phase.
“The results from these studies support use of dupilumab for the long-term management of moderate to severe AD in adolescents,” wrote Michael J. Cork, MD, professor of dermatology, University of Sheffield, England, and coauthors. No new safety signals were identified, “compared with the known safety profile of dupilumab in adults with moderate to severe AD,” and “the PK profile was characterized by nonlinear, target-mediated kinetics, consistent with the profile in adults with moderate to severe AD,” they added.
Dupilumab was approved in the United States in March 2019 for adolescents with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
The study was sponsored by dupilumab manufacturers Sanofi and Regeneron Pharmaceuticals, which market dupilumab as Dupixent in the United States. Dr. Cork disclosures included those related to Sanofi Genzyme and Regeneron; other authors included employees of the companies.
SOURCE: Cork M et al. Br J Dermatol. 2019 Oct 9. doi: 10.1111/bjd.18476.
FROM THE BRITISH JOURNAL OF DERMATOLOGY
Dysregulated sleep is common in children with eosinophilic esophagitis
, Rasintra Siriwat, MD, and colleagues have ascertained.
Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.
The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m2. A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.
Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.
Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).
All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.
“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.
The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).
Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.
“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”
Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.
SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.
, Rasintra Siriwat, MD, and colleagues have ascertained.
Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.
The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m2. A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.
Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.
Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).
All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.
“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.
The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).
Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.
“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”
Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.
SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.
, Rasintra Siriwat, MD, and colleagues have ascertained.
Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.
The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m2. A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.
Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.
Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).
All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.
“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.
The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).
Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.
“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”
Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.
SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.
FROM SLEEP MEDICINE
Interventions significantly improve NICU immunization rates
according to a study in Pediatrics.
Investigators led by Raymond C. Stetson, MD, of the Mayo Clinic in Rochester, Minn., identified three root causes of underimmunization in a NICU at Mayo Clinic: providers’ lack of knowledge about recommended immunization schedules; immunizations not being ordered when they were due; and parental hesitancy toward vaccination. They addressed these causes with the following five phases of intervention: an intranet resource educating providers about vaccine schedules and dosing intervals; a spreadsheet-based checklist to track and flag immunization status; an intranet resource aimed at discussion with vaccine-hesitant parents; education about safety in providing immunization and review of material from the first three interventions; and education about documentation, including parental consent.
Over the project period, 1,242 infants were discharged or transferred from the NICU. The study included a 6-month “improve phase,” during which interventions were implemented, and a “control phase,” during which the ongoing effects after implementation were observed. At baseline, the rate of fully immunized infants in the NICU was only 56% by time of discharge or transfer, but during the combined improve and control phases, it was 93% with a P value of less than .001.
One of the limitations of the study is that the first three interventions were introduced simultaneously, which makes it hard to determine how much effect each might have had.
“Infants treated in NICUs represent a vulnerable population with the potential for high morbidity and mortality from vaccine-preventable infections,” the investigators wrote. “Our [quality improvement] effort, and others, demonstrate that this population is at risk for underimmunization and that immunization rates can be improved with a small number of interventions. Additionally, we were able to significantly decrease the number of days that immunizations were delayed compared to the routine infant vaccination schedule.”
There was no external funding for the study. One of the coauthors is on safety committees of vaccine studies for Merck. The other authors have no relevant financial disclosures.
SOURCE: Stetson R et al. Pediatr. 2019. doi: 10.1542/peds.2019-0337.
according to a study in Pediatrics.
Investigators led by Raymond C. Stetson, MD, of the Mayo Clinic in Rochester, Minn., identified three root causes of underimmunization in a NICU at Mayo Clinic: providers’ lack of knowledge about recommended immunization schedules; immunizations not being ordered when they were due; and parental hesitancy toward vaccination. They addressed these causes with the following five phases of intervention: an intranet resource educating providers about vaccine schedules and dosing intervals; a spreadsheet-based checklist to track and flag immunization status; an intranet resource aimed at discussion with vaccine-hesitant parents; education about safety in providing immunization and review of material from the first three interventions; and education about documentation, including parental consent.
Over the project period, 1,242 infants were discharged or transferred from the NICU. The study included a 6-month “improve phase,” during which interventions were implemented, and a “control phase,” during which the ongoing effects after implementation were observed. At baseline, the rate of fully immunized infants in the NICU was only 56% by time of discharge or transfer, but during the combined improve and control phases, it was 93% with a P value of less than .001.
One of the limitations of the study is that the first three interventions were introduced simultaneously, which makes it hard to determine how much effect each might have had.
“Infants treated in NICUs represent a vulnerable population with the potential for high morbidity and mortality from vaccine-preventable infections,” the investigators wrote. “Our [quality improvement] effort, and others, demonstrate that this population is at risk for underimmunization and that immunization rates can be improved with a small number of interventions. Additionally, we were able to significantly decrease the number of days that immunizations were delayed compared to the routine infant vaccination schedule.”
There was no external funding for the study. One of the coauthors is on safety committees of vaccine studies for Merck. The other authors have no relevant financial disclosures.
SOURCE: Stetson R et al. Pediatr. 2019. doi: 10.1542/peds.2019-0337.
according to a study in Pediatrics.
Investigators led by Raymond C. Stetson, MD, of the Mayo Clinic in Rochester, Minn., identified three root causes of underimmunization in a NICU at Mayo Clinic: providers’ lack of knowledge about recommended immunization schedules; immunizations not being ordered when they were due; and parental hesitancy toward vaccination. They addressed these causes with the following five phases of intervention: an intranet resource educating providers about vaccine schedules and dosing intervals; a spreadsheet-based checklist to track and flag immunization status; an intranet resource aimed at discussion with vaccine-hesitant parents; education about safety in providing immunization and review of material from the first three interventions; and education about documentation, including parental consent.
Over the project period, 1,242 infants were discharged or transferred from the NICU. The study included a 6-month “improve phase,” during which interventions were implemented, and a “control phase,” during which the ongoing effects after implementation were observed. At baseline, the rate of fully immunized infants in the NICU was only 56% by time of discharge or transfer, but during the combined improve and control phases, it was 93% with a P value of less than .001.
One of the limitations of the study is that the first three interventions were introduced simultaneously, which makes it hard to determine how much effect each might have had.
“Infants treated in NICUs represent a vulnerable population with the potential for high morbidity and mortality from vaccine-preventable infections,” the investigators wrote. “Our [quality improvement] effort, and others, demonstrate that this population is at risk for underimmunization and that immunization rates can be improved with a small number of interventions. Additionally, we were able to significantly decrease the number of days that immunizations were delayed compared to the routine infant vaccination schedule.”
There was no external funding for the study. One of the coauthors is on safety committees of vaccine studies for Merck. The other authors have no relevant financial disclosures.
SOURCE: Stetson R et al. Pediatr. 2019. doi: 10.1542/peds.2019-0337.
FROM PEDIATRICS