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Congenital CMV linked to pediatric hyperdiploid ALL
Children with hyperdiploid acute lymphoblastic leukemia (ALL) are much more likely to also have congenital cytomegalovirus (CMV) infection, according to an analysis published in JAMA Network Open.
Although researchers found no association between ALL and congenital CMV infection overall, pediatric patients diagnosed with hyperdiploid ALL had sixfold greater odds of being positive for congenital CMV than cancer-free controls.
“These findings suggest mixed evidence for an association between congenital CMV infection and ALL” and that “a CMV-ALL association may be specific to hyperdiploid ALL,” said investigators, led by Jennifer Geris, PhD, a postdoctoral associate at Baylor College of Medicine, Houston.
A growing body of evidence suggests that CMV, a member of the herpesvirus family, may be a risk factor for ALL. Although the mechanism remains unclear, congenital CMV may encourage proliferation of CD34+ hematopoietic progenitor cells in bone marrow that are vulnerable to oncogenic transformation.
Two prior independent studies have suggested that prenatal CMV infection is associated with an increased risk of childhood ALL. However, given how common CMV infection is (more than 80% seropositivity worldwide) and the relatively rarity of pediatric ALL, Joseph Wiemels, PhD, argued in an accompanying editorial that CMV can’t be a direct cause of leukemia.
“Instead, CMV may play a supportive role” with infection in some infants altering immune function in a way that increases vulnerability to more direct causes of ALL, explained Dr. Wiemels, professor of population and public health sciences at the University of Southern California, Los Angeles. In other words, “exposure to CMV early rather than fulminant infection” at birth “may be the key epidemiologic feature.”
In the current study, Dr. Geris and colleagues tested dried newborn blood spots from 1189 children with ALL and 4,756 controls matched on age, sex, and mother’s race and ethnicity for the presence of cytomegalovirus at birth. Children were born in Michigan on or after Oct. 1, 1987.
Across the entire study population, congenital CMV was detected in 6 ALL cases (0.5%) and 21 controls (0.4%), with no difference in the odds of congenital CMV infection between the two groups. Among subjects positive for congenital CMV, it was not clear who had fulminant, clinically recognized disease and who did not.
Overall, 2 of 74 cases (2.7%) of hyperdiploid ALL were positive for congenital CMV. Compared with all controls in an unmatched analysis, those with hyperdiploid ALL were 6.26 times more likely to be CMV positive.
Overall, the investigators concluded that the current findings, in combination with previous evidence showing a similar connection, “strongly suggest CMV is associated specifically to hyperdiploid ALL.”
Although “the evidence supporting an association between CMV and ALL is tantalizing and mounting rapidly,” Dr. Wiemels noted that “much additional research attention is required to mechanistically describe pathways by which CMV may influence leukemia before the virus could be considered a potential target for prevention or clinical management of ALL.”
“We are still in the early chapters of the book describing the role of CMV and ALL,” but the virus might emerge as a clinical target “with much future promise for the health and well-being of our children,” he said.
The work was funded by the National Institutes of Health, the University of Minnesota, and the Department of Defense. The investigators and editorialist have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Children with hyperdiploid acute lymphoblastic leukemia (ALL) are much more likely to also have congenital cytomegalovirus (CMV) infection, according to an analysis published in JAMA Network Open.
Although researchers found no association between ALL and congenital CMV infection overall, pediatric patients diagnosed with hyperdiploid ALL had sixfold greater odds of being positive for congenital CMV than cancer-free controls.
“These findings suggest mixed evidence for an association between congenital CMV infection and ALL” and that “a CMV-ALL association may be specific to hyperdiploid ALL,” said investigators, led by Jennifer Geris, PhD, a postdoctoral associate at Baylor College of Medicine, Houston.
A growing body of evidence suggests that CMV, a member of the herpesvirus family, may be a risk factor for ALL. Although the mechanism remains unclear, congenital CMV may encourage proliferation of CD34+ hematopoietic progenitor cells in bone marrow that are vulnerable to oncogenic transformation.
Two prior independent studies have suggested that prenatal CMV infection is associated with an increased risk of childhood ALL. However, given how common CMV infection is (more than 80% seropositivity worldwide) and the relatively rarity of pediatric ALL, Joseph Wiemels, PhD, argued in an accompanying editorial that CMV can’t be a direct cause of leukemia.
“Instead, CMV may play a supportive role” with infection in some infants altering immune function in a way that increases vulnerability to more direct causes of ALL, explained Dr. Wiemels, professor of population and public health sciences at the University of Southern California, Los Angeles. In other words, “exposure to CMV early rather than fulminant infection” at birth “may be the key epidemiologic feature.”
In the current study, Dr. Geris and colleagues tested dried newborn blood spots from 1189 children with ALL and 4,756 controls matched on age, sex, and mother’s race and ethnicity for the presence of cytomegalovirus at birth. Children were born in Michigan on or after Oct. 1, 1987.
Across the entire study population, congenital CMV was detected in 6 ALL cases (0.5%) and 21 controls (0.4%), with no difference in the odds of congenital CMV infection between the two groups. Among subjects positive for congenital CMV, it was not clear who had fulminant, clinically recognized disease and who did not.
Overall, 2 of 74 cases (2.7%) of hyperdiploid ALL were positive for congenital CMV. Compared with all controls in an unmatched analysis, those with hyperdiploid ALL were 6.26 times more likely to be CMV positive.
Overall, the investigators concluded that the current findings, in combination with previous evidence showing a similar connection, “strongly suggest CMV is associated specifically to hyperdiploid ALL.”
Although “the evidence supporting an association between CMV and ALL is tantalizing and mounting rapidly,” Dr. Wiemels noted that “much additional research attention is required to mechanistically describe pathways by which CMV may influence leukemia before the virus could be considered a potential target for prevention or clinical management of ALL.”
“We are still in the early chapters of the book describing the role of CMV and ALL,” but the virus might emerge as a clinical target “with much future promise for the health and well-being of our children,” he said.
The work was funded by the National Institutes of Health, the University of Minnesota, and the Department of Defense. The investigators and editorialist have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Children with hyperdiploid acute lymphoblastic leukemia (ALL) are much more likely to also have congenital cytomegalovirus (CMV) infection, according to an analysis published in JAMA Network Open.
Although researchers found no association between ALL and congenital CMV infection overall, pediatric patients diagnosed with hyperdiploid ALL had sixfold greater odds of being positive for congenital CMV than cancer-free controls.
“These findings suggest mixed evidence for an association between congenital CMV infection and ALL” and that “a CMV-ALL association may be specific to hyperdiploid ALL,” said investigators, led by Jennifer Geris, PhD, a postdoctoral associate at Baylor College of Medicine, Houston.
A growing body of evidence suggests that CMV, a member of the herpesvirus family, may be a risk factor for ALL. Although the mechanism remains unclear, congenital CMV may encourage proliferation of CD34+ hematopoietic progenitor cells in bone marrow that are vulnerable to oncogenic transformation.
Two prior independent studies have suggested that prenatal CMV infection is associated with an increased risk of childhood ALL. However, given how common CMV infection is (more than 80% seropositivity worldwide) and the relatively rarity of pediatric ALL, Joseph Wiemels, PhD, argued in an accompanying editorial that CMV can’t be a direct cause of leukemia.
“Instead, CMV may play a supportive role” with infection in some infants altering immune function in a way that increases vulnerability to more direct causes of ALL, explained Dr. Wiemels, professor of population and public health sciences at the University of Southern California, Los Angeles. In other words, “exposure to CMV early rather than fulminant infection” at birth “may be the key epidemiologic feature.”
In the current study, Dr. Geris and colleagues tested dried newborn blood spots from 1189 children with ALL and 4,756 controls matched on age, sex, and mother’s race and ethnicity for the presence of cytomegalovirus at birth. Children were born in Michigan on or after Oct. 1, 1987.
Across the entire study population, congenital CMV was detected in 6 ALL cases (0.5%) and 21 controls (0.4%), with no difference in the odds of congenital CMV infection between the two groups. Among subjects positive for congenital CMV, it was not clear who had fulminant, clinically recognized disease and who did not.
Overall, 2 of 74 cases (2.7%) of hyperdiploid ALL were positive for congenital CMV. Compared with all controls in an unmatched analysis, those with hyperdiploid ALL were 6.26 times more likely to be CMV positive.
Overall, the investigators concluded that the current findings, in combination with previous evidence showing a similar connection, “strongly suggest CMV is associated specifically to hyperdiploid ALL.”
Although “the evidence supporting an association between CMV and ALL is tantalizing and mounting rapidly,” Dr. Wiemels noted that “much additional research attention is required to mechanistically describe pathways by which CMV may influence leukemia before the virus could be considered a potential target for prevention or clinical management of ALL.”
“We are still in the early chapters of the book describing the role of CMV and ALL,” but the virus might emerge as a clinical target “with much future promise for the health and well-being of our children,” he said.
The work was funded by the National Institutes of Health, the University of Minnesota, and the Department of Defense. The investigators and editorialist have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
A toddler presents with a dark line on a fingernail
Given the over 1-year history of an unchanging longitudinal band of pigment without extension to the proximal or lateral nailfolds or any other nail findings, the most likely diagnosis is benign longitudinal melanonychia.
Longitudinal melanonychia, also known as melanonychia striata, describes a brown to black streak of pigment extending from the nail matrix to the free edge of the nail.1,2
This disorder can occur secondary to a wide variety of benign and pathologic causes including lentigines, nevi, melanoma, chronic trauma, inflammatory skin diseases, systemic diseases, iatrogenic causes, and genetic syndromes.3 In melanocytic causes of longitudinal melanonychia, either melanocytic activation or hyperplasia drive pigmentary development leading to the brown to black band seen in the nail.4 Benign causes of longitudinal melanonychia include benign melanocyte activation, lentigo, and benign nevus.1
What’s the differential diagnosis?
The differential diagnosis for longitudinal melanonychia can include a wide variety of local and systemic causes. For our discussion, we will limit our differential to other locally involved disorders of the nail including subungual melanoma, subungual hematoma, onychomycosis, and glomus tumor.
Subungual melanoma is a rare subtype of acral lentiginous melanoma that most often presents as longitudinal melanonychia. Subungual melanoma is more common in those aged 50-70 years, individuals with personal or family history of melanoma or dysplastic nevus syndrome, and persons with African American, Native American, and Asian descent. Longitudinal melanonychia features that can be concerning for subungual melanoma include the presence of multiple colors, width greater than or equal to 3 mm, blurry borders, rapid increase in size, and extension to the proximal or lateral nailfolds (Hutchinson’s sign). Biopsy is required to make the diagnosis of subungual melanoma but is not necessary for melanonychia without atypical features.
Treatment of subungual melanoma depends on disease stage and can range from wide local excision of the nail apparatus to amputation of the affected digit and management with a medical oncologist. Given the absence of concerning neoplastic findings or personal or family history of melanoma, subungual melanoma is unlikely in this patient.
Subungual hematoma is an accumulation of blood underneath the nail plate that is typically the result of acute or chronic trauma to the distal phalanx. It can present as purple, red, pink, brown, or black discoloration under the nail plate and is most commonly found on the first toe. With acute trauma, pain is usually present upon initial injury. Subungual hematomas typically resolve on their own with normal nail growth. The absence of a history of trauma or pain, and the linear appearance of the lesion in our patient are inconsistent with a subungual hematoma.
Onychomycosis is a fungal infection of the nail caused by dermatophytes, nondermatophytes, or yeasts. It may present with longitudinal melanonychia; however, it more often presents with other nail abnormalities such as nail thickening, yellow discoloration, onycholysis, splitting, subungual hyperkeratosis, and nail plate destruction, which are not present in this patient. Furthermore, onychomycosis is more common in adults than children. Diagnosis is usually made with potassium hydroxide (KOH) preparations, histopathologic examination of nail clippings with a periodic acid-Schiff stain, fungal culture, or PCR.
Glomus tumor is a rare, benign neoplasm originating from cells of the glomus body. It is often found in the subungual region, in addition to other areas rich in glomus bodies such as the fingertips, palms, wrists, and forearms. Subungual glomus tumors present as a red, purple, or blueish lesions under the nail plate. Distal notching or an overlying longitudinal fissure may be present. Subungual glomus tumors are typically associated with pinpoint tenderness, paroxysmal pain, and cold sensitivity, features that are not present in our patient. The history and examination of our patient are much more consistent with benign longitudinal melanonychia.
It appears that melanoma associated with longitudinal melanonychia is very rare in children. According to one review published in 2020, only 12 cases of pediatric subungual melanoma have been reported.5 Recent series have observed longitudinal melanonychia in large sets of children, with findings that demonstrate that the vast majority of longitudinal melanonychia either stops progressing or regresses. These investigations therefore recommend serial observation of longitudinal melanonychia except in rare circumstances.6,7
Given the lack of troubling findings or concerning history, our patient was managed with observation. On follow-up 6 months later, he was found to have no change in his nail pigmentation.
Dr. Haft is an inflammatory skin disease fellow in the division of pediatric and adolescent dermatology; Ms. Sui is a research associate in the department of dermatology, division of pediatric and adolescent dermatology; and Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics, all at the University of California and Rady Children’s Hospital, San Diego. They have no relevant disclosures.
References
1. Mannava KA et al. Hand Surg. 2013;18(1):133-9.
2. Leung AKC et al. Int J Dermatol. 2019;58(11):1239-45.
3. Andre J and Lateur N. Dermatol Clin. 2006;24(3):329-39.
4. Lee DK and Lipner SR. Ann Med. 2022;54(1):694-712.
5. Smith RJ and Rubin AI. Curr Opin Pediatr. 2020;32(4):506-15. .
6. Matsui Y et al. J Am Acad Dermatol. 2022;86(4):946-8.
7. Lee JS et al. J Am Acad Dermatol. 2022;87(2):366-72.
Given the over 1-year history of an unchanging longitudinal band of pigment without extension to the proximal or lateral nailfolds or any other nail findings, the most likely diagnosis is benign longitudinal melanonychia.
Longitudinal melanonychia, also known as melanonychia striata, describes a brown to black streak of pigment extending from the nail matrix to the free edge of the nail.1,2
This disorder can occur secondary to a wide variety of benign and pathologic causes including lentigines, nevi, melanoma, chronic trauma, inflammatory skin diseases, systemic diseases, iatrogenic causes, and genetic syndromes.3 In melanocytic causes of longitudinal melanonychia, either melanocytic activation or hyperplasia drive pigmentary development leading to the brown to black band seen in the nail.4 Benign causes of longitudinal melanonychia include benign melanocyte activation, lentigo, and benign nevus.1
What’s the differential diagnosis?
The differential diagnosis for longitudinal melanonychia can include a wide variety of local and systemic causes. For our discussion, we will limit our differential to other locally involved disorders of the nail including subungual melanoma, subungual hematoma, onychomycosis, and glomus tumor.
Subungual melanoma is a rare subtype of acral lentiginous melanoma that most often presents as longitudinal melanonychia. Subungual melanoma is more common in those aged 50-70 years, individuals with personal or family history of melanoma or dysplastic nevus syndrome, and persons with African American, Native American, and Asian descent. Longitudinal melanonychia features that can be concerning for subungual melanoma include the presence of multiple colors, width greater than or equal to 3 mm, blurry borders, rapid increase in size, and extension to the proximal or lateral nailfolds (Hutchinson’s sign). Biopsy is required to make the diagnosis of subungual melanoma but is not necessary for melanonychia without atypical features.
Treatment of subungual melanoma depends on disease stage and can range from wide local excision of the nail apparatus to amputation of the affected digit and management with a medical oncologist. Given the absence of concerning neoplastic findings or personal or family history of melanoma, subungual melanoma is unlikely in this patient.
Subungual hematoma is an accumulation of blood underneath the nail plate that is typically the result of acute or chronic trauma to the distal phalanx. It can present as purple, red, pink, brown, or black discoloration under the nail plate and is most commonly found on the first toe. With acute trauma, pain is usually present upon initial injury. Subungual hematomas typically resolve on their own with normal nail growth. The absence of a history of trauma or pain, and the linear appearance of the lesion in our patient are inconsistent with a subungual hematoma.
Onychomycosis is a fungal infection of the nail caused by dermatophytes, nondermatophytes, or yeasts. It may present with longitudinal melanonychia; however, it more often presents with other nail abnormalities such as nail thickening, yellow discoloration, onycholysis, splitting, subungual hyperkeratosis, and nail plate destruction, which are not present in this patient. Furthermore, onychomycosis is more common in adults than children. Diagnosis is usually made with potassium hydroxide (KOH) preparations, histopathologic examination of nail clippings with a periodic acid-Schiff stain, fungal culture, or PCR.
Glomus tumor is a rare, benign neoplasm originating from cells of the glomus body. It is often found in the subungual region, in addition to other areas rich in glomus bodies such as the fingertips, palms, wrists, and forearms. Subungual glomus tumors present as a red, purple, or blueish lesions under the nail plate. Distal notching or an overlying longitudinal fissure may be present. Subungual glomus tumors are typically associated with pinpoint tenderness, paroxysmal pain, and cold sensitivity, features that are not present in our patient. The history and examination of our patient are much more consistent with benign longitudinal melanonychia.
It appears that melanoma associated with longitudinal melanonychia is very rare in children. According to one review published in 2020, only 12 cases of pediatric subungual melanoma have been reported.5 Recent series have observed longitudinal melanonychia in large sets of children, with findings that demonstrate that the vast majority of longitudinal melanonychia either stops progressing or regresses. These investigations therefore recommend serial observation of longitudinal melanonychia except in rare circumstances.6,7
Given the lack of troubling findings or concerning history, our patient was managed with observation. On follow-up 6 months later, he was found to have no change in his nail pigmentation.
Dr. Haft is an inflammatory skin disease fellow in the division of pediatric and adolescent dermatology; Ms. Sui is a research associate in the department of dermatology, division of pediatric and adolescent dermatology; and Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics, all at the University of California and Rady Children’s Hospital, San Diego. They have no relevant disclosures.
References
1. Mannava KA et al. Hand Surg. 2013;18(1):133-9.
2. Leung AKC et al. Int J Dermatol. 2019;58(11):1239-45.
3. Andre J and Lateur N. Dermatol Clin. 2006;24(3):329-39.
4. Lee DK and Lipner SR. Ann Med. 2022;54(1):694-712.
5. Smith RJ and Rubin AI. Curr Opin Pediatr. 2020;32(4):506-15. .
6. Matsui Y et al. J Am Acad Dermatol. 2022;86(4):946-8.
7. Lee JS et al. J Am Acad Dermatol. 2022;87(2):366-72.
Given the over 1-year history of an unchanging longitudinal band of pigment without extension to the proximal or lateral nailfolds or any other nail findings, the most likely diagnosis is benign longitudinal melanonychia.
Longitudinal melanonychia, also known as melanonychia striata, describes a brown to black streak of pigment extending from the nail matrix to the free edge of the nail.1,2
This disorder can occur secondary to a wide variety of benign and pathologic causes including lentigines, nevi, melanoma, chronic trauma, inflammatory skin diseases, systemic diseases, iatrogenic causes, and genetic syndromes.3 In melanocytic causes of longitudinal melanonychia, either melanocytic activation or hyperplasia drive pigmentary development leading to the brown to black band seen in the nail.4 Benign causes of longitudinal melanonychia include benign melanocyte activation, lentigo, and benign nevus.1
What’s the differential diagnosis?
The differential diagnosis for longitudinal melanonychia can include a wide variety of local and systemic causes. For our discussion, we will limit our differential to other locally involved disorders of the nail including subungual melanoma, subungual hematoma, onychomycosis, and glomus tumor.
Subungual melanoma is a rare subtype of acral lentiginous melanoma that most often presents as longitudinal melanonychia. Subungual melanoma is more common in those aged 50-70 years, individuals with personal or family history of melanoma or dysplastic nevus syndrome, and persons with African American, Native American, and Asian descent. Longitudinal melanonychia features that can be concerning for subungual melanoma include the presence of multiple colors, width greater than or equal to 3 mm, blurry borders, rapid increase in size, and extension to the proximal or lateral nailfolds (Hutchinson’s sign). Biopsy is required to make the diagnosis of subungual melanoma but is not necessary for melanonychia without atypical features.
Treatment of subungual melanoma depends on disease stage and can range from wide local excision of the nail apparatus to amputation of the affected digit and management with a medical oncologist. Given the absence of concerning neoplastic findings or personal or family history of melanoma, subungual melanoma is unlikely in this patient.
Subungual hematoma is an accumulation of blood underneath the nail plate that is typically the result of acute or chronic trauma to the distal phalanx. It can present as purple, red, pink, brown, or black discoloration under the nail plate and is most commonly found on the first toe. With acute trauma, pain is usually present upon initial injury. Subungual hematomas typically resolve on their own with normal nail growth. The absence of a history of trauma or pain, and the linear appearance of the lesion in our patient are inconsistent with a subungual hematoma.
Onychomycosis is a fungal infection of the nail caused by dermatophytes, nondermatophytes, or yeasts. It may present with longitudinal melanonychia; however, it more often presents with other nail abnormalities such as nail thickening, yellow discoloration, onycholysis, splitting, subungual hyperkeratosis, and nail plate destruction, which are not present in this patient. Furthermore, onychomycosis is more common in adults than children. Diagnosis is usually made with potassium hydroxide (KOH) preparations, histopathologic examination of nail clippings with a periodic acid-Schiff stain, fungal culture, or PCR.
Glomus tumor is a rare, benign neoplasm originating from cells of the glomus body. It is often found in the subungual region, in addition to other areas rich in glomus bodies such as the fingertips, palms, wrists, and forearms. Subungual glomus tumors present as a red, purple, or blueish lesions under the nail plate. Distal notching or an overlying longitudinal fissure may be present. Subungual glomus tumors are typically associated with pinpoint tenderness, paroxysmal pain, and cold sensitivity, features that are not present in our patient. The history and examination of our patient are much more consistent with benign longitudinal melanonychia.
It appears that melanoma associated with longitudinal melanonychia is very rare in children. According to one review published in 2020, only 12 cases of pediatric subungual melanoma have been reported.5 Recent series have observed longitudinal melanonychia in large sets of children, with findings that demonstrate that the vast majority of longitudinal melanonychia either stops progressing or regresses. These investigations therefore recommend serial observation of longitudinal melanonychia except in rare circumstances.6,7
Given the lack of troubling findings or concerning history, our patient was managed with observation. On follow-up 6 months later, he was found to have no change in his nail pigmentation.
Dr. Haft is an inflammatory skin disease fellow in the division of pediatric and adolescent dermatology; Ms. Sui is a research associate in the department of dermatology, division of pediatric and adolescent dermatology; and Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics, all at the University of California and Rady Children’s Hospital, San Diego. They have no relevant disclosures.
References
1. Mannava KA et al. Hand Surg. 2013;18(1):133-9.
2. Leung AKC et al. Int J Dermatol. 2019;58(11):1239-45.
3. Andre J and Lateur N. Dermatol Clin. 2006;24(3):329-39.
4. Lee DK and Lipner SR. Ann Med. 2022;54(1):694-712.
5. Smith RJ and Rubin AI. Curr Opin Pediatr. 2020;32(4):506-15. .
6. Matsui Y et al. J Am Acad Dermatol. 2022;86(4):946-8.
7. Lee JS et al. J Am Acad Dermatol. 2022;87(2):366-72.
Examination findings reveal a 2-mm brown longitudinal band on the radial aspect of the right thumbnail that does not extend into the proximal or lateral nailfolds. The rest of the skin and nail exam is unremarkable.
CDC frets over further dip in kindergarten vaccination rates
The percentage of kindergarteners in the United States who have received routine vaccines to protect against illnesses such as measles, whooping cough, and polio has declined for 2 straight years, a new study has found.
Drops in vaccine coverage leave communities more susceptible to outbreaks of vaccine-preventable diseases, such as those that occurred in 2022, public health officials said.
Coverage for four vaccines – against measles, mumps, and rubella (MMR); diphtheria, tetanus, and acellular pertussis (DTaP); poliovirus; and varicella – among kindergarten students was about 95% in 2019-2020.
The rate fell to 94% the following year.
For the 2021-2022 school year, coverage dropped another point, to 93%, according to the report, published online in Morbidity and Mortality Weekly Report.
The rate of vaccination overall remains high, but about 250,000 kindergarten students may not be protected against measles, the researchers estimate. Measles, which is highly infectious, can lead to serious illness and even death in children who have not been vaccinated against the virus.
“In 2022, two communities in the United States responded to outbreaks of measles where children have been hospitalized,” Georgina Peacock, MD, MPH, director of the immunization services division of the Centers for Disease Control and Prevention, said in a media briefing about the report. “One community reported a case of paralytic polio in an unvaccinated person. These outbreaks were preventable. The best way to prevent these diseases and their devastating impact on children is through vaccination.”
Exemptions steady
For the new study, Ranee Seither, MPH, with the CDC’s National Center for Immunization and Respiratory Diseases and her colleagues analyzed data reported by states to estimate nationwide coverage for the four routine vaccines.
The number of students with exemptions remained low, at 2.6%, but another 3.9% who were without exemptions were not up to date with the MMR vaccine, the investigators report.
In a separate study, researchers found that vaccination coverage for 2-year-olds has increased. Approximately 70% of children were up to date with a seven-vaccine series by age 24 months. The coverage rate was higher for children born during 2018-2019 than for those born during 2016-2017.
Although the COVID-19 pandemic was not associated with decreased vaccination rates in this younger age group overall, coverage fell by 4-5 percentage points for children living below the poverty level or in rural areas, according to the study.
In addition, uninsured children were eight times more likely than those with private insurance to not be vaccinated by their second birthday, the researchers found.
Strategies to increase vaccination coverage include enforcing school vaccination requirements and holding vaccination clinics at schools, the CDC said.
“Providers should review children’s histories and recommend needed vaccinations during every clinical encounter and address parental hesitancy to help reduce disparities and ensure that all children are protected from vaccine-preventable diseases,” the agency said.
To that end, the agency launched an initiative this week called Let’s RISE (Routine Immunizations on Schedule for Everyone) to provide clinicians with resources to help patients get on track with their immunizations.
Hundreds of thousands unprotected
MMR vaccination coverage for kindergartners is the lowest it has been in over a decade, Dr. Peacock noted. Decreased coverage for kindergarten students might be tied to pandemic-related disruptions in health care systems and schools, she said. School administrators and parents may have been less focused on routine vaccination paperwork amid the return to in-person learning, for instance.
Hesitancy about COVID vaccines could be affecting routine vaccinations. “That’s something that we are watching very closely,” Dr. Peacock said.
The 2-point decrease in vaccination coverage “translates to hundreds of thousands of children starting school without being fully protected” against preventable diseases that can spread easily in classrooms, Sean O’Leary, MD, chair of the American Academy of Pediatrics’ Committee on Infectious Diseases, said.
Despite the drop in coverage, Dr. O’Leary said he saw some encouraging signs in the data: Nonmedical exemptions for kindergarten students have not increased. And the vast majority of parents are still having their children vaccinated. At the same time, the reports highlight a need to address child poverty and improve vaccine access in rural areas, he said.
A version of this article first appeared on Medscape.com.
The percentage of kindergarteners in the United States who have received routine vaccines to protect against illnesses such as measles, whooping cough, and polio has declined for 2 straight years, a new study has found.
Drops in vaccine coverage leave communities more susceptible to outbreaks of vaccine-preventable diseases, such as those that occurred in 2022, public health officials said.
Coverage for four vaccines – against measles, mumps, and rubella (MMR); diphtheria, tetanus, and acellular pertussis (DTaP); poliovirus; and varicella – among kindergarten students was about 95% in 2019-2020.
The rate fell to 94% the following year.
For the 2021-2022 school year, coverage dropped another point, to 93%, according to the report, published online in Morbidity and Mortality Weekly Report.
The rate of vaccination overall remains high, but about 250,000 kindergarten students may not be protected against measles, the researchers estimate. Measles, which is highly infectious, can lead to serious illness and even death in children who have not been vaccinated against the virus.
“In 2022, two communities in the United States responded to outbreaks of measles where children have been hospitalized,” Georgina Peacock, MD, MPH, director of the immunization services division of the Centers for Disease Control and Prevention, said in a media briefing about the report. “One community reported a case of paralytic polio in an unvaccinated person. These outbreaks were preventable. The best way to prevent these diseases and their devastating impact on children is through vaccination.”
Exemptions steady
For the new study, Ranee Seither, MPH, with the CDC’s National Center for Immunization and Respiratory Diseases and her colleagues analyzed data reported by states to estimate nationwide coverage for the four routine vaccines.
The number of students with exemptions remained low, at 2.6%, but another 3.9% who were without exemptions were not up to date with the MMR vaccine, the investigators report.
In a separate study, researchers found that vaccination coverage for 2-year-olds has increased. Approximately 70% of children were up to date with a seven-vaccine series by age 24 months. The coverage rate was higher for children born during 2018-2019 than for those born during 2016-2017.
Although the COVID-19 pandemic was not associated with decreased vaccination rates in this younger age group overall, coverage fell by 4-5 percentage points for children living below the poverty level or in rural areas, according to the study.
In addition, uninsured children were eight times more likely than those with private insurance to not be vaccinated by their second birthday, the researchers found.
Strategies to increase vaccination coverage include enforcing school vaccination requirements and holding vaccination clinics at schools, the CDC said.
“Providers should review children’s histories and recommend needed vaccinations during every clinical encounter and address parental hesitancy to help reduce disparities and ensure that all children are protected from vaccine-preventable diseases,” the agency said.
To that end, the agency launched an initiative this week called Let’s RISE (Routine Immunizations on Schedule for Everyone) to provide clinicians with resources to help patients get on track with their immunizations.
Hundreds of thousands unprotected
MMR vaccination coverage for kindergartners is the lowest it has been in over a decade, Dr. Peacock noted. Decreased coverage for kindergarten students might be tied to pandemic-related disruptions in health care systems and schools, she said. School administrators and parents may have been less focused on routine vaccination paperwork amid the return to in-person learning, for instance.
Hesitancy about COVID vaccines could be affecting routine vaccinations. “That’s something that we are watching very closely,” Dr. Peacock said.
The 2-point decrease in vaccination coverage “translates to hundreds of thousands of children starting school without being fully protected” against preventable diseases that can spread easily in classrooms, Sean O’Leary, MD, chair of the American Academy of Pediatrics’ Committee on Infectious Diseases, said.
Despite the drop in coverage, Dr. O’Leary said he saw some encouraging signs in the data: Nonmedical exemptions for kindergarten students have not increased. And the vast majority of parents are still having their children vaccinated. At the same time, the reports highlight a need to address child poverty and improve vaccine access in rural areas, he said.
A version of this article first appeared on Medscape.com.
The percentage of kindergarteners in the United States who have received routine vaccines to protect against illnesses such as measles, whooping cough, and polio has declined for 2 straight years, a new study has found.
Drops in vaccine coverage leave communities more susceptible to outbreaks of vaccine-preventable diseases, such as those that occurred in 2022, public health officials said.
Coverage for four vaccines – against measles, mumps, and rubella (MMR); diphtheria, tetanus, and acellular pertussis (DTaP); poliovirus; and varicella – among kindergarten students was about 95% in 2019-2020.
The rate fell to 94% the following year.
For the 2021-2022 school year, coverage dropped another point, to 93%, according to the report, published online in Morbidity and Mortality Weekly Report.
The rate of vaccination overall remains high, but about 250,000 kindergarten students may not be protected against measles, the researchers estimate. Measles, which is highly infectious, can lead to serious illness and even death in children who have not been vaccinated against the virus.
“In 2022, two communities in the United States responded to outbreaks of measles where children have been hospitalized,” Georgina Peacock, MD, MPH, director of the immunization services division of the Centers for Disease Control and Prevention, said in a media briefing about the report. “One community reported a case of paralytic polio in an unvaccinated person. These outbreaks were preventable. The best way to prevent these diseases and their devastating impact on children is through vaccination.”
Exemptions steady
For the new study, Ranee Seither, MPH, with the CDC’s National Center for Immunization and Respiratory Diseases and her colleagues analyzed data reported by states to estimate nationwide coverage for the four routine vaccines.
The number of students with exemptions remained low, at 2.6%, but another 3.9% who were without exemptions were not up to date with the MMR vaccine, the investigators report.
In a separate study, researchers found that vaccination coverage for 2-year-olds has increased. Approximately 70% of children were up to date with a seven-vaccine series by age 24 months. The coverage rate was higher for children born during 2018-2019 than for those born during 2016-2017.
Although the COVID-19 pandemic was not associated with decreased vaccination rates in this younger age group overall, coverage fell by 4-5 percentage points for children living below the poverty level or in rural areas, according to the study.
In addition, uninsured children were eight times more likely than those with private insurance to not be vaccinated by their second birthday, the researchers found.
Strategies to increase vaccination coverage include enforcing school vaccination requirements and holding vaccination clinics at schools, the CDC said.
“Providers should review children’s histories and recommend needed vaccinations during every clinical encounter and address parental hesitancy to help reduce disparities and ensure that all children are protected from vaccine-preventable diseases,” the agency said.
To that end, the agency launched an initiative this week called Let’s RISE (Routine Immunizations on Schedule for Everyone) to provide clinicians with resources to help patients get on track with their immunizations.
Hundreds of thousands unprotected
MMR vaccination coverage for kindergartners is the lowest it has been in over a decade, Dr. Peacock noted. Decreased coverage for kindergarten students might be tied to pandemic-related disruptions in health care systems and schools, she said. School administrators and parents may have been less focused on routine vaccination paperwork amid the return to in-person learning, for instance.
Hesitancy about COVID vaccines could be affecting routine vaccinations. “That’s something that we are watching very closely,” Dr. Peacock said.
The 2-point decrease in vaccination coverage “translates to hundreds of thousands of children starting school without being fully protected” against preventable diseases that can spread easily in classrooms, Sean O’Leary, MD, chair of the American Academy of Pediatrics’ Committee on Infectious Diseases, said.
Despite the drop in coverage, Dr. O’Leary said he saw some encouraging signs in the data: Nonmedical exemptions for kindergarten students have not increased. And the vast majority of parents are still having their children vaccinated. At the same time, the reports highlight a need to address child poverty and improve vaccine access in rural areas, he said.
A version of this article first appeared on Medscape.com.
FROM THE MMWR
AD outcomes improved with lebrikizumab and topical steroids
, according to results of the 16-week phase 3 ADhere trial.
“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.
The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.
At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.
After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.
Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.
Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).
Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”
The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.
The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.
“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”
“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”
On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”
Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”
The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.
A version of this article first appeared on Medscape.com.
, according to results of the 16-week phase 3 ADhere trial.
“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.
The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.
At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.
After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.
Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.
Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).
Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”
The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.
The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.
“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”
“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”
On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”
Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”
The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.
A version of this article first appeared on Medscape.com.
, according to results of the 16-week phase 3 ADhere trial.
“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.
The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.
At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.
After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.
Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.
Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).
Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”
The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.
The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.
“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”
“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”
On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”
Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”
The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.
A version of this article first appeared on Medscape.com.
FROM JAMA DERMATOLOGY
Children and COVID: ED visits and hospitalizations start to fall again
Emergency department visits and hospitalizations for COVID-19 in children appear to be following the declining trend set by weekly cases since early December, based on data from the Centers for Disease Control and Prevention.
. New cases took a different path that had the weekly total falling through November before taking a big jump during the week of Nov. 27 to Dec. 3 – the count doubled from 30,000 the previous week to 63,000 – and then decreased again, the CDC reported.
The proportion of ED visits with COVID, which was down to 1.0% of all ED visits (7-day average) for children aged 0-4 years on Nov. 4, was up to 3.2% on Jan. 3 but slipped to 2.5% as of Jan. 10. The patterns for older children are similar, with some differences in timing and lower peaks (1.7% for 12- to 15-year-olds and 1.9% for those aged 16-17), according to the CDC’s COVID Data Tracker.
The trend for new hospital admissions of children with confirmed COVID showed a similar rise through December, and the latest data for the very beginning of January suggest an even faster drop, although there is more of a reporting lag with hospitalization data, compared with ED visits, the CDC noted.
The most current data (Dec. 30 to Jan. 5) available from the American Academy of Pediatrics and the Children’s Hospital Association show less volatility in the number of weekly cases through November and December, with the peak being about 48,000 in mid-December. The AAP/CHA totals for the last 2 weeks, however, were both higher than the CDC’s corresponding counts, which are more preliminary and subject to revision.
The CDC puts the total number of COVID cases in children at 16.7 million – about 17.2% of all cases – as of Jan. 11, with 1,981 deaths reported so far. The AAP and CHA are not tracking deaths, but their case total as of Jan. 5 was 15.2 million, which represents 18.1% of cases in all ages. The AAP/CHA report is based on data reported publicly by an ever-decreasing number of states and territories.
Emergency department visits and hospitalizations for COVID-19 in children appear to be following the declining trend set by weekly cases since early December, based on data from the Centers for Disease Control and Prevention.
. New cases took a different path that had the weekly total falling through November before taking a big jump during the week of Nov. 27 to Dec. 3 – the count doubled from 30,000 the previous week to 63,000 – and then decreased again, the CDC reported.
The proportion of ED visits with COVID, which was down to 1.0% of all ED visits (7-day average) for children aged 0-4 years on Nov. 4, was up to 3.2% on Jan. 3 but slipped to 2.5% as of Jan. 10. The patterns for older children are similar, with some differences in timing and lower peaks (1.7% for 12- to 15-year-olds and 1.9% for those aged 16-17), according to the CDC’s COVID Data Tracker.
The trend for new hospital admissions of children with confirmed COVID showed a similar rise through December, and the latest data for the very beginning of January suggest an even faster drop, although there is more of a reporting lag with hospitalization data, compared with ED visits, the CDC noted.
The most current data (Dec. 30 to Jan. 5) available from the American Academy of Pediatrics and the Children’s Hospital Association show less volatility in the number of weekly cases through November and December, with the peak being about 48,000 in mid-December. The AAP/CHA totals for the last 2 weeks, however, were both higher than the CDC’s corresponding counts, which are more preliminary and subject to revision.
The CDC puts the total number of COVID cases in children at 16.7 million – about 17.2% of all cases – as of Jan. 11, with 1,981 deaths reported so far. The AAP and CHA are not tracking deaths, but their case total as of Jan. 5 was 15.2 million, which represents 18.1% of cases in all ages. The AAP/CHA report is based on data reported publicly by an ever-decreasing number of states and territories.
Emergency department visits and hospitalizations for COVID-19 in children appear to be following the declining trend set by weekly cases since early December, based on data from the Centers for Disease Control and Prevention.
. New cases took a different path that had the weekly total falling through November before taking a big jump during the week of Nov. 27 to Dec. 3 – the count doubled from 30,000 the previous week to 63,000 – and then decreased again, the CDC reported.
The proportion of ED visits with COVID, which was down to 1.0% of all ED visits (7-day average) for children aged 0-4 years on Nov. 4, was up to 3.2% on Jan. 3 but slipped to 2.5% as of Jan. 10. The patterns for older children are similar, with some differences in timing and lower peaks (1.7% for 12- to 15-year-olds and 1.9% for those aged 16-17), according to the CDC’s COVID Data Tracker.
The trend for new hospital admissions of children with confirmed COVID showed a similar rise through December, and the latest data for the very beginning of January suggest an even faster drop, although there is more of a reporting lag with hospitalization data, compared with ED visits, the CDC noted.
The most current data (Dec. 30 to Jan. 5) available from the American Academy of Pediatrics and the Children’s Hospital Association show less volatility in the number of weekly cases through November and December, with the peak being about 48,000 in mid-December. The AAP/CHA totals for the last 2 weeks, however, were both higher than the CDC’s corresponding counts, which are more preliminary and subject to revision.
The CDC puts the total number of COVID cases in children at 16.7 million – about 17.2% of all cases – as of Jan. 11, with 1,981 deaths reported so far. The AAP and CHA are not tracking deaths, but their case total as of Jan. 5 was 15.2 million, which represents 18.1% of cases in all ages. The AAP/CHA report is based on data reported publicly by an ever-decreasing number of states and territories.
Ecopipam reduces Tourette’s tics without common side effects in phase 2 trial
Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.
Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.
Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.
First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.
The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.
They were randomly assigned 1:1 to ecopipam or placebo.
Significant reduction in tic severity
Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.
The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).
Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.
One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.
“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
Headaches, insomnia among side effects
Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.
The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).
A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.
Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.
Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.
Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.
“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.
The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.
Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.
Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.
Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.
First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.
The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.
They were randomly assigned 1:1 to ecopipam or placebo.
Significant reduction in tic severity
Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.
The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).
Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.
One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.
“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
Headaches, insomnia among side effects
Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.
The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).
A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.
Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.
Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.
Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.
“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.
The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.
Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.
Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.
Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.
First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.
The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.
They were randomly assigned 1:1 to ecopipam or placebo.
Significant reduction in tic severity
Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.
The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).
Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.
One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.
“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
Headaches, insomnia among side effects
Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.
The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).
A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.
Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.
Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.
Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.
“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.
The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.
FROM PEDIATRICS
Vision screening at well-child visits cost-effective for detecting amblyopia
Screening for amblyopia during primary care visits is more cost-effective than screening in school settings and optometric examinations in kindergarten-aged children in Toronto, data suggest.
Because of the low prevalence of amblyopia among young children, a population-based screening program may not warrant the resources required, despite the added health benefits of a universal program, according to the researchers.
“Amblyopia is a public health problem. For this reason, population-wide approaches to detect and treat amblyopia are critical, and approaches such as school screening and mandated optometry exams have been recommended and introduced in some jurisdictions,” study author Afua Oteng Asare, OD, PhD, a research assistant professor at the University of Utah in Salt Lake City, told this news organization. Dr. Asare conducted the study as a PhD student at the University of Toronto.
“With increasing budgeting constraints and limited resources, policymakers are relying more on economic analyses that measure value-for-money to inform their decisions on programming,” she said. “Evidence comparing the cost-effectiveness of vision-testing approaches to the status quo is, however, limited.”
The study was published in JAMA Network Open.
Analyzing costs
Despite recommendations for routine testing, a notable percentage of children in Canada and the United States don’t receive an annual vision exam. The percentage is even higher among children from low-income households, said Dr. Asare. Universal screening in schools and mandatory optometric examinations may improve vision care. But the cost-effectiveness of these measures is unknown for certain conditions, such as amblyopia, the prevalence of which ranges between 3% and 5% in young children.
In Ontario, Canada’s largest province with about 3 million children, universal funding for children’s annual comprehensive eye exams and vision screening during well-child visits is provided through provincial health insurance.
In 2018, the Ontario Ministry of Health introduced guidelines for administering vision screening in kindergartens by public health departments. However, school-based screening has been difficult to introduce because of increasing costs and budgeting constraints, the authors wrote. As an alternative to underfunded programs, optometric associations in Canada have advocated for physicians to recommend early childhood optometric exams.
The investigators analyzed the incremental costs and health benefits, from the perspective of the Ontario government, of public health school screening and optometrist-based vision exams, compared with standard vision screening conducted during well-child visits with primary care physicians. They focused on the aim of detecting amblyopia and amblyopia-related risk factors in children between ages 3 and 5 years in Toronto.
For the analysis, the research team simulated a hypothetical cohort of 25,000 children over 15 years in a probabilistic health state transition model. They incorporated various assumptions, including that children had irreversible vision impairment if not diagnosed by an optometrist. In addition, incremental costs were adjusted to favor the standard screening strategy during well-child visits.
In the school-based and primary care scenarios, children with a positive or inconclusive test result were referred to an optometrist for diagnosis and treatment, which would incur the cost of an optometric evaluation. If positive, children were treated with prescription glasses and additional patching for amblyopia.
The research team measured outcomes as incremental quality-adjusted life-years (QALYs), and health utilities were derived from data on adults, because of the lack of data on children under age 6 years with amblyopia or amblyopia risk factors. The researchers also estimated direct costs to the Ontario government, including visits with primary care doctors, optometrists, public health nurses, and contract screeners, as well as prescription glasses for children with vision impairment who receive social assistance. Costs were expressed in Canadian dollars (CAD).
Overall, compared with the primary care screening strategy, the school screening and optometric examination strategies were generally less costly and had more health benefits. The incremental difference in cost was a savings per child of $84.09 CAD for school screening and $74.47 CAD for optometric examinations. Optometric examinations yielded the largest gain in QALYs, compared with the primary care screening strategy, producing average QALYs of 0.0508 per child.
However, only 20% of school screening iterations and 29% of optometric exam iterations were cost-effective, relative to the primary care screening strategy, at a willingness-to-pay threshold of $50,000 CAD per QALY gained. For instance, when comparing optometric exams with primary care screenings, if the cost of vision screening was $11.50 CAD, the incremental cost-effectiveness ratio would be $77.95 CAD per QALY gained.
Results ‘make sense’
“We were initially surprised that the alternative screening programs were not cost-effective, compared to status quo vision screening in well-child visits,” said Dr. Asare. “However, the results make sense, considering the study’s universal approach (screening all children regardless of their vision status) and the study’s consideration only of amblyopia, and not of refractive errors, which are even more common in kindergarten children.”
Dr. Asare noted the lack of current data on the rate of vision screenings conducted in childhood by primary care practitioners and on referrals to eye care providers for children with abnormal screenings. Data on vision health disparities and barriers to accessing vision care in young children also are scarce.
“My ultimate research goal is to create and evaluate evidence-based, cost-effective interventions to be used at the point of care by pediatric primary care providers to improve the quality of vision care for children, especially those from socioeconomically deprived backgrounds,” she said. “The take-home message is that school vision screening and mandated eye exams are excellent programs, but they may not be suitable for all contexts.”
Additional studies are needed to look at the cost-effectiveness of the different screening strategies for other aspects included in childhood vision tests, including binocular vision problems, refractive disorders, myopia, allergies, and rare eye diseases.
Significant underestimation?
Susan Leat, PhD, a researcher and professor emerita at the University of Waterloo (Ont.) School of Optometry and Vision Science, said, “This study only considers amblyopia, and not all eye diseases and disorders, which significantly underestimates the cost-effectiveness of optometric eye exams.”
Dr. Leat, who wasn’t involved with this study, has researched pediatric optometry and visual development. She and colleagues are developing new tools to test visual acuity in young children.
“If all disorders were taken into account, then optometric testing would be by far the most cost-effective,” she said. “Optometrists can detect all disorders, including more subtle disorders, which if uncorrected or untreated, can impact a child’s early learning.”
The study authors reported no funding for the study. Dr. Asare and Dr. Leat reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
Screening for amblyopia during primary care visits is more cost-effective than screening in school settings and optometric examinations in kindergarten-aged children in Toronto, data suggest.
Because of the low prevalence of amblyopia among young children, a population-based screening program may not warrant the resources required, despite the added health benefits of a universal program, according to the researchers.
“Amblyopia is a public health problem. For this reason, population-wide approaches to detect and treat amblyopia are critical, and approaches such as school screening and mandated optometry exams have been recommended and introduced in some jurisdictions,” study author Afua Oteng Asare, OD, PhD, a research assistant professor at the University of Utah in Salt Lake City, told this news organization. Dr. Asare conducted the study as a PhD student at the University of Toronto.
“With increasing budgeting constraints and limited resources, policymakers are relying more on economic analyses that measure value-for-money to inform their decisions on programming,” she said. “Evidence comparing the cost-effectiveness of vision-testing approaches to the status quo is, however, limited.”
The study was published in JAMA Network Open.
Analyzing costs
Despite recommendations for routine testing, a notable percentage of children in Canada and the United States don’t receive an annual vision exam. The percentage is even higher among children from low-income households, said Dr. Asare. Universal screening in schools and mandatory optometric examinations may improve vision care. But the cost-effectiveness of these measures is unknown for certain conditions, such as amblyopia, the prevalence of which ranges between 3% and 5% in young children.
In Ontario, Canada’s largest province with about 3 million children, universal funding for children’s annual comprehensive eye exams and vision screening during well-child visits is provided through provincial health insurance.
In 2018, the Ontario Ministry of Health introduced guidelines for administering vision screening in kindergartens by public health departments. However, school-based screening has been difficult to introduce because of increasing costs and budgeting constraints, the authors wrote. As an alternative to underfunded programs, optometric associations in Canada have advocated for physicians to recommend early childhood optometric exams.
The investigators analyzed the incremental costs and health benefits, from the perspective of the Ontario government, of public health school screening and optometrist-based vision exams, compared with standard vision screening conducted during well-child visits with primary care physicians. They focused on the aim of detecting amblyopia and amblyopia-related risk factors in children between ages 3 and 5 years in Toronto.
For the analysis, the research team simulated a hypothetical cohort of 25,000 children over 15 years in a probabilistic health state transition model. They incorporated various assumptions, including that children had irreversible vision impairment if not diagnosed by an optometrist. In addition, incremental costs were adjusted to favor the standard screening strategy during well-child visits.
In the school-based and primary care scenarios, children with a positive or inconclusive test result were referred to an optometrist for diagnosis and treatment, which would incur the cost of an optometric evaluation. If positive, children were treated with prescription glasses and additional patching for amblyopia.
The research team measured outcomes as incremental quality-adjusted life-years (QALYs), and health utilities were derived from data on adults, because of the lack of data on children under age 6 years with amblyopia or amblyopia risk factors. The researchers also estimated direct costs to the Ontario government, including visits with primary care doctors, optometrists, public health nurses, and contract screeners, as well as prescription glasses for children with vision impairment who receive social assistance. Costs were expressed in Canadian dollars (CAD).
Overall, compared with the primary care screening strategy, the school screening and optometric examination strategies were generally less costly and had more health benefits. The incremental difference in cost was a savings per child of $84.09 CAD for school screening and $74.47 CAD for optometric examinations. Optometric examinations yielded the largest gain in QALYs, compared with the primary care screening strategy, producing average QALYs of 0.0508 per child.
However, only 20% of school screening iterations and 29% of optometric exam iterations were cost-effective, relative to the primary care screening strategy, at a willingness-to-pay threshold of $50,000 CAD per QALY gained. For instance, when comparing optometric exams with primary care screenings, if the cost of vision screening was $11.50 CAD, the incremental cost-effectiveness ratio would be $77.95 CAD per QALY gained.
Results ‘make sense’
“We were initially surprised that the alternative screening programs were not cost-effective, compared to status quo vision screening in well-child visits,” said Dr. Asare. “However, the results make sense, considering the study’s universal approach (screening all children regardless of their vision status) and the study’s consideration only of amblyopia, and not of refractive errors, which are even more common in kindergarten children.”
Dr. Asare noted the lack of current data on the rate of vision screenings conducted in childhood by primary care practitioners and on referrals to eye care providers for children with abnormal screenings. Data on vision health disparities and barriers to accessing vision care in young children also are scarce.
“My ultimate research goal is to create and evaluate evidence-based, cost-effective interventions to be used at the point of care by pediatric primary care providers to improve the quality of vision care for children, especially those from socioeconomically deprived backgrounds,” she said. “The take-home message is that school vision screening and mandated eye exams are excellent programs, but they may not be suitable for all contexts.”
Additional studies are needed to look at the cost-effectiveness of the different screening strategies for other aspects included in childhood vision tests, including binocular vision problems, refractive disorders, myopia, allergies, and rare eye diseases.
Significant underestimation?
Susan Leat, PhD, a researcher and professor emerita at the University of Waterloo (Ont.) School of Optometry and Vision Science, said, “This study only considers amblyopia, and not all eye diseases and disorders, which significantly underestimates the cost-effectiveness of optometric eye exams.”
Dr. Leat, who wasn’t involved with this study, has researched pediatric optometry and visual development. She and colleagues are developing new tools to test visual acuity in young children.
“If all disorders were taken into account, then optometric testing would be by far the most cost-effective,” she said. “Optometrists can detect all disorders, including more subtle disorders, which if uncorrected or untreated, can impact a child’s early learning.”
The study authors reported no funding for the study. Dr. Asare and Dr. Leat reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
Screening for amblyopia during primary care visits is more cost-effective than screening in school settings and optometric examinations in kindergarten-aged children in Toronto, data suggest.
Because of the low prevalence of amblyopia among young children, a population-based screening program may not warrant the resources required, despite the added health benefits of a universal program, according to the researchers.
“Amblyopia is a public health problem. For this reason, population-wide approaches to detect and treat amblyopia are critical, and approaches such as school screening and mandated optometry exams have been recommended and introduced in some jurisdictions,” study author Afua Oteng Asare, OD, PhD, a research assistant professor at the University of Utah in Salt Lake City, told this news organization. Dr. Asare conducted the study as a PhD student at the University of Toronto.
“With increasing budgeting constraints and limited resources, policymakers are relying more on economic analyses that measure value-for-money to inform their decisions on programming,” she said. “Evidence comparing the cost-effectiveness of vision-testing approaches to the status quo is, however, limited.”
The study was published in JAMA Network Open.
Analyzing costs
Despite recommendations for routine testing, a notable percentage of children in Canada and the United States don’t receive an annual vision exam. The percentage is even higher among children from low-income households, said Dr. Asare. Universal screening in schools and mandatory optometric examinations may improve vision care. But the cost-effectiveness of these measures is unknown for certain conditions, such as amblyopia, the prevalence of which ranges between 3% and 5% in young children.
In Ontario, Canada’s largest province with about 3 million children, universal funding for children’s annual comprehensive eye exams and vision screening during well-child visits is provided through provincial health insurance.
In 2018, the Ontario Ministry of Health introduced guidelines for administering vision screening in kindergartens by public health departments. However, school-based screening has been difficult to introduce because of increasing costs and budgeting constraints, the authors wrote. As an alternative to underfunded programs, optometric associations in Canada have advocated for physicians to recommend early childhood optometric exams.
The investigators analyzed the incremental costs and health benefits, from the perspective of the Ontario government, of public health school screening and optometrist-based vision exams, compared with standard vision screening conducted during well-child visits with primary care physicians. They focused on the aim of detecting amblyopia and amblyopia-related risk factors in children between ages 3 and 5 years in Toronto.
For the analysis, the research team simulated a hypothetical cohort of 25,000 children over 15 years in a probabilistic health state transition model. They incorporated various assumptions, including that children had irreversible vision impairment if not diagnosed by an optometrist. In addition, incremental costs were adjusted to favor the standard screening strategy during well-child visits.
In the school-based and primary care scenarios, children with a positive or inconclusive test result were referred to an optometrist for diagnosis and treatment, which would incur the cost of an optometric evaluation. If positive, children were treated with prescription glasses and additional patching for amblyopia.
The research team measured outcomes as incremental quality-adjusted life-years (QALYs), and health utilities were derived from data on adults, because of the lack of data on children under age 6 years with amblyopia or amblyopia risk factors. The researchers also estimated direct costs to the Ontario government, including visits with primary care doctors, optometrists, public health nurses, and contract screeners, as well as prescription glasses for children with vision impairment who receive social assistance. Costs were expressed in Canadian dollars (CAD).
Overall, compared with the primary care screening strategy, the school screening and optometric examination strategies were generally less costly and had more health benefits. The incremental difference in cost was a savings per child of $84.09 CAD for school screening and $74.47 CAD for optometric examinations. Optometric examinations yielded the largest gain in QALYs, compared with the primary care screening strategy, producing average QALYs of 0.0508 per child.
However, only 20% of school screening iterations and 29% of optometric exam iterations were cost-effective, relative to the primary care screening strategy, at a willingness-to-pay threshold of $50,000 CAD per QALY gained. For instance, when comparing optometric exams with primary care screenings, if the cost of vision screening was $11.50 CAD, the incremental cost-effectiveness ratio would be $77.95 CAD per QALY gained.
Results ‘make sense’
“We were initially surprised that the alternative screening programs were not cost-effective, compared to status quo vision screening in well-child visits,” said Dr. Asare. “However, the results make sense, considering the study’s universal approach (screening all children regardless of their vision status) and the study’s consideration only of amblyopia, and not of refractive errors, which are even more common in kindergarten children.”
Dr. Asare noted the lack of current data on the rate of vision screenings conducted in childhood by primary care practitioners and on referrals to eye care providers for children with abnormal screenings. Data on vision health disparities and barriers to accessing vision care in young children also are scarce.
“My ultimate research goal is to create and evaluate evidence-based, cost-effective interventions to be used at the point of care by pediatric primary care providers to improve the quality of vision care for children, especially those from socioeconomically deprived backgrounds,” she said. “The take-home message is that school vision screening and mandated eye exams are excellent programs, but they may not be suitable for all contexts.”
Additional studies are needed to look at the cost-effectiveness of the different screening strategies for other aspects included in childhood vision tests, including binocular vision problems, refractive disorders, myopia, allergies, and rare eye diseases.
Significant underestimation?
Susan Leat, PhD, a researcher and professor emerita at the University of Waterloo (Ont.) School of Optometry and Vision Science, said, “This study only considers amblyopia, and not all eye diseases and disorders, which significantly underestimates the cost-effectiveness of optometric eye exams.”
Dr. Leat, who wasn’t involved with this study, has researched pediatric optometry and visual development. She and colleagues are developing new tools to test visual acuity in young children.
“If all disorders were taken into account, then optometric testing would be by far the most cost-effective,” she said. “Optometrists can detect all disorders, including more subtle disorders, which if uncorrected or untreated, can impact a child’s early learning.”
The study authors reported no funding for the study. Dr. Asare and Dr. Leat reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Health risks low for children exposed in utero to cancer and chemo
Children who were exposed in utero to maternal cancer and treatment do not appear to have any long-term health consequences as a result of this exposure, a nationwide Danish study suggests.
The study evaluated live-born children between January 1978 and December 2018 whose mothers were diagnosed with cancer during pregnancy. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality and no increased risk of congenital malformations.
Researchers also determined that exposure to chemotherapy was not associated with somatic diseases and congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy.
“These findings suggest that fetal exposure to maternal cancer and treatment did not have implications for the long-term somatic and psychiatric health of the children, which is reassuring for the affected families and their health care providers,” the researchers commented.
The paper was published online in the Journal of Clinical Oncology.
Approached for comment, Katherine Van Loon, MD, MPH, director of the Global Cancer Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, said the results offer “promising news.”
“In the balance between administering needed oncologic therapy to save a mother’s life versus considering potential risks to the fetus, this data is reassuring that there is not an increased risk of catastrophic outcomes for the fetus,” Dr. Van Loon said. She noted, however, that the exposed children were not prospectively evaluated for adverse outcomes, which may have been more subtle that this study could detect.
The authors used data from the Danish Civil Registration System and Danish Medical Birth Register. They found that of 2,526,163 live-born children, 690 (0.03%) were exposed to maternal cancer in utero. Children born to mothers younger than 15 years or older than 54 years and children with an outcome diagnosis were excluded from the study.
Researchers found that children exposed to maternal cancer in utero did not demonstrate a higher overall mortality than the unexposed reference group; adjusted hazard ratio, 0.8 (95% confidence interval, 0.4-1.5). There was also no excess of congenital malformations (aHR, 1.0 [95% CI, 0.8-1.2]). In addition, there were no excesses of puberty disturbances or respiratory, cardiovascular, urinary tract, or neurologic disease.
Researchers also conducted a subgroup analysis on in utero exposure to chemotherapy, which involved 1,053,109 children born after 2002. There were 378 (0.03%) children exposed to maternal cancer in utero, and 42 (12.5%) who were exposed to chemotherapy. Chemotherapy was given during the second trimester in 73.8% of the mothers and during the third trimester in 26.2%.
No deaths or events of cancer, autism spectrum disorder, ADHD, hearing loss, or suppressed myelopoiesis were identified during follow-up of the 42 children exposed to chemotherapy in utero.
Dr. Van Loon said many cancer treatments are safe during pregnancy but added that every situation is nuanced with a number of variables to consider.
“All treatment decisions must take into account the diagnosis and prognosis of the mother, the gestational age of the fetus, and the potential teratogenic effects of the proposed treatments,” she said.
The study was supported by grants from the Research Fund of Rigshospitalet, Copenhagen University Hospital, the Novo Nordisk Foundation, Johannes Clemmesen Research Foundation, Helsefonden, Holm Memorial Foundation, and the Danish Cancer Research Foundation. Researcher disclosures are listed in the study paper.
A version of this article first appeared on Medscape.com.
Children who were exposed in utero to maternal cancer and treatment do not appear to have any long-term health consequences as a result of this exposure, a nationwide Danish study suggests.
The study evaluated live-born children between January 1978 and December 2018 whose mothers were diagnosed with cancer during pregnancy. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality and no increased risk of congenital malformations.
Researchers also determined that exposure to chemotherapy was not associated with somatic diseases and congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy.
“These findings suggest that fetal exposure to maternal cancer and treatment did not have implications for the long-term somatic and psychiatric health of the children, which is reassuring for the affected families and their health care providers,” the researchers commented.
The paper was published online in the Journal of Clinical Oncology.
Approached for comment, Katherine Van Loon, MD, MPH, director of the Global Cancer Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, said the results offer “promising news.”
“In the balance between administering needed oncologic therapy to save a mother’s life versus considering potential risks to the fetus, this data is reassuring that there is not an increased risk of catastrophic outcomes for the fetus,” Dr. Van Loon said. She noted, however, that the exposed children were not prospectively evaluated for adverse outcomes, which may have been more subtle that this study could detect.
The authors used data from the Danish Civil Registration System and Danish Medical Birth Register. They found that of 2,526,163 live-born children, 690 (0.03%) were exposed to maternal cancer in utero. Children born to mothers younger than 15 years or older than 54 years and children with an outcome diagnosis were excluded from the study.
Researchers found that children exposed to maternal cancer in utero did not demonstrate a higher overall mortality than the unexposed reference group; adjusted hazard ratio, 0.8 (95% confidence interval, 0.4-1.5). There was also no excess of congenital malformations (aHR, 1.0 [95% CI, 0.8-1.2]). In addition, there were no excesses of puberty disturbances or respiratory, cardiovascular, urinary tract, or neurologic disease.
Researchers also conducted a subgroup analysis on in utero exposure to chemotherapy, which involved 1,053,109 children born after 2002. There were 378 (0.03%) children exposed to maternal cancer in utero, and 42 (12.5%) who were exposed to chemotherapy. Chemotherapy was given during the second trimester in 73.8% of the mothers and during the third trimester in 26.2%.
No deaths or events of cancer, autism spectrum disorder, ADHD, hearing loss, or suppressed myelopoiesis were identified during follow-up of the 42 children exposed to chemotherapy in utero.
Dr. Van Loon said many cancer treatments are safe during pregnancy but added that every situation is nuanced with a number of variables to consider.
“All treatment decisions must take into account the diagnosis and prognosis of the mother, the gestational age of the fetus, and the potential teratogenic effects of the proposed treatments,” she said.
The study was supported by grants from the Research Fund of Rigshospitalet, Copenhagen University Hospital, the Novo Nordisk Foundation, Johannes Clemmesen Research Foundation, Helsefonden, Holm Memorial Foundation, and the Danish Cancer Research Foundation. Researcher disclosures are listed in the study paper.
A version of this article first appeared on Medscape.com.
Children who were exposed in utero to maternal cancer and treatment do not appear to have any long-term health consequences as a result of this exposure, a nationwide Danish study suggests.
The study evaluated live-born children between January 1978 and December 2018 whose mothers were diagnosed with cancer during pregnancy. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality and no increased risk of congenital malformations.
Researchers also determined that exposure to chemotherapy was not associated with somatic diseases and congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy.
“These findings suggest that fetal exposure to maternal cancer and treatment did not have implications for the long-term somatic and psychiatric health of the children, which is reassuring for the affected families and their health care providers,” the researchers commented.
The paper was published online in the Journal of Clinical Oncology.
Approached for comment, Katherine Van Loon, MD, MPH, director of the Global Cancer Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, said the results offer “promising news.”
“In the balance between administering needed oncologic therapy to save a mother’s life versus considering potential risks to the fetus, this data is reassuring that there is not an increased risk of catastrophic outcomes for the fetus,” Dr. Van Loon said. She noted, however, that the exposed children were not prospectively evaluated for adverse outcomes, which may have been more subtle that this study could detect.
The authors used data from the Danish Civil Registration System and Danish Medical Birth Register. They found that of 2,526,163 live-born children, 690 (0.03%) were exposed to maternal cancer in utero. Children born to mothers younger than 15 years or older than 54 years and children with an outcome diagnosis were excluded from the study.
Researchers found that children exposed to maternal cancer in utero did not demonstrate a higher overall mortality than the unexposed reference group; adjusted hazard ratio, 0.8 (95% confidence interval, 0.4-1.5). There was also no excess of congenital malformations (aHR, 1.0 [95% CI, 0.8-1.2]). In addition, there were no excesses of puberty disturbances or respiratory, cardiovascular, urinary tract, or neurologic disease.
Researchers also conducted a subgroup analysis on in utero exposure to chemotherapy, which involved 1,053,109 children born after 2002. There were 378 (0.03%) children exposed to maternal cancer in utero, and 42 (12.5%) who were exposed to chemotherapy. Chemotherapy was given during the second trimester in 73.8% of the mothers and during the third trimester in 26.2%.
No deaths or events of cancer, autism spectrum disorder, ADHD, hearing loss, or suppressed myelopoiesis were identified during follow-up of the 42 children exposed to chemotherapy in utero.
Dr. Van Loon said many cancer treatments are safe during pregnancy but added that every situation is nuanced with a number of variables to consider.
“All treatment decisions must take into account the diagnosis and prognosis of the mother, the gestational age of the fetus, and the potential teratogenic effects of the proposed treatments,” she said.
The study was supported by grants from the Research Fund of Rigshospitalet, Copenhagen University Hospital, the Novo Nordisk Foundation, Johannes Clemmesen Research Foundation, Helsefonden, Holm Memorial Foundation, and the Danish Cancer Research Foundation. Researcher disclosures are listed in the study paper.
A version of this article first appeared on Medscape.com.
Mood disorder? Assessment in primary care
The assessment and diagnosis of bipolar disorder in youth has a complicated and controversial history. I recall from my child and adolescent fellowship training that there was a thinly veiled faculty argument about the diagnosis itself with strong opinions on each side. To revisit this quandary, I reviewed the most up-to-date literature and outlined a case-based approach to the initial screening assessment. Certainly, the assessment by a child and adolescent psychiatrist would be the standard for diagnosis, but we do know that the pediatrician’s office may be the first setting for a child and parent to present with mood symptoms and concerns about bipolar disorder. What can you do to address this adolescent, Carrie, and her mother’s concerns?
Case
Carrie is a 17-year-old girl who has struggled through her childhood and adolescence with anxious and depressive symptoms which have ebbed and flowed with major life stressors, including her parent’s divorce. She has tried cognitive-behavioral therapy and selective serotonin reuptake inhibitors, but the SSRI seemed to cause feelings of anxiousness and agitation, so she stopped it within weeks.
Her mother presents to you concerned that Carrie has had a more persistently irritable mood toward her, often just wanting to be with her friends or otherwise isolate in her room when home to study.
Most concerning to her mother is that Carrie, as a straight A student, has also developed a pattern of staying up all night to study for tests and then “crashes” and sleeps through the weekend, avoiding her mother and only brightening with her friends.
To complicate matters, Carrie’s biological father had type 1 bipolar disorder and an addiction. Her mother comes to you with an initially nonparticipatory Carrie in tow and says: “My former husband began his manic episodes with a lack of sleep and Carrie is so irritable towards me. I feel like I am walking on eggshells all the time. Could this be bipolar disorder?”
Case discussion
First, it’s always useful to frame a visit stating that you will spend some time with the patient and some time with both the patient and parent. Emphasizing confidentiality about issues such as drug use, which can be comorbid with mood symptoms and go undetected in high-achieving students such as Carrie, is also important. Further emphasizing that information will not be reflexively shared with the parent unless the child presents a danger to herself or others is also paramount to receive an honest report of symptoms.
Second, there are many signs and symptoms of bipolar disorder that naturally overlap with other conditions such as distractibility with attention-deficit/hyperactivity disorder, or irritability in either a unipolar depression or disruptive mood dysregulation disorder.1 You are looking for an episodic (not chronic) course of symptoms with episodes that last over 5 days for hypomania and over the course of weeks for mania all while meeting all the classic criteria for bipolar disorder.
Note that the broadening of diagnostic criteria has been thought to contribute to an inflated sense of prevalence. The actual expert estimate of prevalence is around 0.8%-1.8% in pediatric populations, although there is a large published range depending on whether the criteria are modified or not.2 Use of the unmodified criteria from the DSM-5 is the recommended approach. Bipolar disorder is exceedingly rare in prepubertal children, and it would be more common for prodromal symptoms such as Carrie’s to emerge and escalate over the teenage years, culminating in a clearer diagnosis in the later teens or 20s.3
In my screening questions, I find the idea of an “infatiguable state” is the most pathognomonic one in considering mania in bipolar disorder.4 Carrie’s “crashing” after nights of studying shows that she clearly fatigues. Patients with bipolar disorder within episodes of hypomania or mania have a seismic shift in perceived energy and a matching lack of ability to sleep that can affect their thought processes, speech, and decision-making. At first blush, Carrie’s history does not indicate current symptoms of bipolar disorder.3
Case, continued
When you meet with Carrie alone she shares that she has been experimenting with prescribed stimulants from her older college-aged brother in order to study and ace her tests. She is also experimenting with alcohol and marijuana with her friends. You provide her the CRAFFT tool to deepen your screening of this issue.5
With her mother, you administer the Parent General Behavior Inventory6 and the and the Child Mania Rating Scale7. From these scales, you note that the irritability is more specific to Carrie’s family than pan-present in school and with friends. Her lack of sleep occurs at high-pressure and discreet times.
At this point, you reassure Carrie and her mother that Carrie does not present with symptoms of bipolar disorder but that certainly you will continue screening assessments over time, as they are a good means to track symptoms. You also recommend that Carrie consider mood tracking so she can develop insights into her mood and its relationship to sleep and other events as she prepares for college.8
Case discussion, continued
The strongest risk factor for bipolar disorder in youth is family history (specifically a parent) with bipolar disorder).9 If there is the chance to explore the parent’s illness with open-ended questions, you will want to hear about the parent’s age of symptom onset, course of treatment, any hospitalizations, and stabilizing medications because this has prognostic power for your patient. It is important to ensure that the parent indeed has a diagnosis of bipolar disorder and that it is not just being used colloquially to characterize an adult who has labile moods from hour to hour or day to day. This would give undue anticipatory anxiety to a youth about their risk, which is up to 8- to 10-fold greater with a parent with bipolar disorder.9
Even with a strong family history, we do not often see bipolar disorder emerge in prepubertal children.10,11 There may be still concerning prodromal symptoms in which a diagnosis of unipolar depression with more irritable features and mood lability seems more commonly complicated by substance use, as with Carrie.
Activation with an SSRI, as in Carrie’s case, even if not resulting in full mania or hypomania, can also be a soft sign of the serotonergic sensitivity present in bipolar disorder. However, if there are not additional symptoms of bipolar disorder and you are concerned based on family history alone, you do not want to withhold antidepressant treatment because fear of risk. You would want to consider a “dose low and go slow” titration process with more frequent monitoring.
A diagnostic interview with a child and adolescent psychiatrist and administration of scales such as the Young Mania Rating Scale and the Modified Child Depression Rating Scale are the standard means to assess for bipolar symptoms.12 Considering the dearth of child psychiatrists nationally, it would be useful to improve one’s screening in primary care so as to not inadvertently “refer out” all patients for whom mood dysregulation is a concern.
There is also a more expanded tool that includes several scales integrated with clinical information (parent’s age of mood disorder onset, child’s age) which can culminate in a risk score.13
Lastly, I provide my patients with a handout of the Young Mania Rating Scale to take home as a reference and to complete before our next visit.14
You can repeat scales to monitor for more striking bipolar disorder signs and symptoms that emerge over the course of one’s longitudinal treatment of a pediatric patient. This can be an ongoing, episodic assessment since the emergence of bipolar disorder has been shown to range from the teenage years and beyond into the 20s and sometimes 30s.
Case, continued
Carrie presents to you again while in her first semester of college at the age of 19. She is taking a leave of absence after she began experimenting with cocaine at college and had a manic episode characterized by a lack of sleep without fatigue, persistent unabating energy, rapid and pressured speech, and ultimately, concern from her college friends. She was admitted to a psychiatric unit and stabilized on a second-generation antipsychotic, risperidone, which has solid evidence for mania, but she and you are now concerned about longer-term metabolic effects.15,16
You discuss monitoring her lipid profile and hemoglobin A1c, in addition to weight gain and waist circumference. She has connected with a therapist and psychiatrist through the college counseling center and hopes to return next semester with a fresh start and commitment to sobriety and social rhythms therapy known to be helpful for patients with bipolar disorder.17
While it is challenging to manage a chronic illness at her age, she feels hopeful that she can make better choices for her overall health with your support and the support of her family and mental health team.
Dr. Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center, Burlington, where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
References
1. Bipolar Disord. 2016 Jan 9 doi: 10.1111/bdi.12358.
2. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
3. Am J Psychiatry. 2018 Dec 11. doi: 10.1176/appi.ajp.2018.18040461.
4. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2016.
5. The CRAFFT tool.
6. General Behavior Inventory. Parent Version (P-GBI) Short Form – H/B (Revised Version, 2008).
7. Child Mania Rating Scale, Parent Version (CMRS-P).
8. https://www.moodtracker.com.
9. J Clin Psychiatry. 2000 Sep. doi: 10.4088/jcp.v61n0906.
10. Int J Bipolar Disord. 2020 Apr 20. doi: 10.1186/s40345-020-00185-2.
11. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
12. Bipolar Disord. 2017 Sep 25. doi: 10.1111/bdi.12556.
13. www.cabsresearch.pitt.edu/bpriskcalculator/.
14. Parent Version of the Young Mania Rating Scale (PYMRS).
15. Arch Gen Psychiatry. 2012 Jan 2. doi: 10.1001/archgenpsychiatry.2011.1508.
16. The Carlat Child Psychiatry Report. “Bipolar Disorder” Newburyport, Mass.: Carlat Publishing, 2012.
17. https://www.ipsrt.org/.
The assessment and diagnosis of bipolar disorder in youth has a complicated and controversial history. I recall from my child and adolescent fellowship training that there was a thinly veiled faculty argument about the diagnosis itself with strong opinions on each side. To revisit this quandary, I reviewed the most up-to-date literature and outlined a case-based approach to the initial screening assessment. Certainly, the assessment by a child and adolescent psychiatrist would be the standard for diagnosis, but we do know that the pediatrician’s office may be the first setting for a child and parent to present with mood symptoms and concerns about bipolar disorder. What can you do to address this adolescent, Carrie, and her mother’s concerns?
Case
Carrie is a 17-year-old girl who has struggled through her childhood and adolescence with anxious and depressive symptoms which have ebbed and flowed with major life stressors, including her parent’s divorce. She has tried cognitive-behavioral therapy and selective serotonin reuptake inhibitors, but the SSRI seemed to cause feelings of anxiousness and agitation, so she stopped it within weeks.
Her mother presents to you concerned that Carrie has had a more persistently irritable mood toward her, often just wanting to be with her friends or otherwise isolate in her room when home to study.
Most concerning to her mother is that Carrie, as a straight A student, has also developed a pattern of staying up all night to study for tests and then “crashes” and sleeps through the weekend, avoiding her mother and only brightening with her friends.
To complicate matters, Carrie’s biological father had type 1 bipolar disorder and an addiction. Her mother comes to you with an initially nonparticipatory Carrie in tow and says: “My former husband began his manic episodes with a lack of sleep and Carrie is so irritable towards me. I feel like I am walking on eggshells all the time. Could this be bipolar disorder?”
Case discussion
First, it’s always useful to frame a visit stating that you will spend some time with the patient and some time with both the patient and parent. Emphasizing confidentiality about issues such as drug use, which can be comorbid with mood symptoms and go undetected in high-achieving students such as Carrie, is also important. Further emphasizing that information will not be reflexively shared with the parent unless the child presents a danger to herself or others is also paramount to receive an honest report of symptoms.
Second, there are many signs and symptoms of bipolar disorder that naturally overlap with other conditions such as distractibility with attention-deficit/hyperactivity disorder, or irritability in either a unipolar depression or disruptive mood dysregulation disorder.1 You are looking for an episodic (not chronic) course of symptoms with episodes that last over 5 days for hypomania and over the course of weeks for mania all while meeting all the classic criteria for bipolar disorder.
Note that the broadening of diagnostic criteria has been thought to contribute to an inflated sense of prevalence. The actual expert estimate of prevalence is around 0.8%-1.8% in pediatric populations, although there is a large published range depending on whether the criteria are modified or not.2 Use of the unmodified criteria from the DSM-5 is the recommended approach. Bipolar disorder is exceedingly rare in prepubertal children, and it would be more common for prodromal symptoms such as Carrie’s to emerge and escalate over the teenage years, culminating in a clearer diagnosis in the later teens or 20s.3
In my screening questions, I find the idea of an “infatiguable state” is the most pathognomonic one in considering mania in bipolar disorder.4 Carrie’s “crashing” after nights of studying shows that she clearly fatigues. Patients with bipolar disorder within episodes of hypomania or mania have a seismic shift in perceived energy and a matching lack of ability to sleep that can affect their thought processes, speech, and decision-making. At first blush, Carrie’s history does not indicate current symptoms of bipolar disorder.3
Case, continued
When you meet with Carrie alone she shares that she has been experimenting with prescribed stimulants from her older college-aged brother in order to study and ace her tests. She is also experimenting with alcohol and marijuana with her friends. You provide her the CRAFFT tool to deepen your screening of this issue.5
With her mother, you administer the Parent General Behavior Inventory6 and the and the Child Mania Rating Scale7. From these scales, you note that the irritability is more specific to Carrie’s family than pan-present in school and with friends. Her lack of sleep occurs at high-pressure and discreet times.
At this point, you reassure Carrie and her mother that Carrie does not present with symptoms of bipolar disorder but that certainly you will continue screening assessments over time, as they are a good means to track symptoms. You also recommend that Carrie consider mood tracking so she can develop insights into her mood and its relationship to sleep and other events as she prepares for college.8
Case discussion, continued
The strongest risk factor for bipolar disorder in youth is family history (specifically a parent) with bipolar disorder).9 If there is the chance to explore the parent’s illness with open-ended questions, you will want to hear about the parent’s age of symptom onset, course of treatment, any hospitalizations, and stabilizing medications because this has prognostic power for your patient. It is important to ensure that the parent indeed has a diagnosis of bipolar disorder and that it is not just being used colloquially to characterize an adult who has labile moods from hour to hour or day to day. This would give undue anticipatory anxiety to a youth about their risk, which is up to 8- to 10-fold greater with a parent with bipolar disorder.9
Even with a strong family history, we do not often see bipolar disorder emerge in prepubertal children.10,11 There may be still concerning prodromal symptoms in which a diagnosis of unipolar depression with more irritable features and mood lability seems more commonly complicated by substance use, as with Carrie.
Activation with an SSRI, as in Carrie’s case, even if not resulting in full mania or hypomania, can also be a soft sign of the serotonergic sensitivity present in bipolar disorder. However, if there are not additional symptoms of bipolar disorder and you are concerned based on family history alone, you do not want to withhold antidepressant treatment because fear of risk. You would want to consider a “dose low and go slow” titration process with more frequent monitoring.
A diagnostic interview with a child and adolescent psychiatrist and administration of scales such as the Young Mania Rating Scale and the Modified Child Depression Rating Scale are the standard means to assess for bipolar symptoms.12 Considering the dearth of child psychiatrists nationally, it would be useful to improve one’s screening in primary care so as to not inadvertently “refer out” all patients for whom mood dysregulation is a concern.
There is also a more expanded tool that includes several scales integrated with clinical information (parent’s age of mood disorder onset, child’s age) which can culminate in a risk score.13
Lastly, I provide my patients with a handout of the Young Mania Rating Scale to take home as a reference and to complete before our next visit.14
You can repeat scales to monitor for more striking bipolar disorder signs and symptoms that emerge over the course of one’s longitudinal treatment of a pediatric patient. This can be an ongoing, episodic assessment since the emergence of bipolar disorder has been shown to range from the teenage years and beyond into the 20s and sometimes 30s.
Case, continued
Carrie presents to you again while in her first semester of college at the age of 19. She is taking a leave of absence after she began experimenting with cocaine at college and had a manic episode characterized by a lack of sleep without fatigue, persistent unabating energy, rapid and pressured speech, and ultimately, concern from her college friends. She was admitted to a psychiatric unit and stabilized on a second-generation antipsychotic, risperidone, which has solid evidence for mania, but she and you are now concerned about longer-term metabolic effects.15,16
You discuss monitoring her lipid profile and hemoglobin A1c, in addition to weight gain and waist circumference. She has connected with a therapist and psychiatrist through the college counseling center and hopes to return next semester with a fresh start and commitment to sobriety and social rhythms therapy known to be helpful for patients with bipolar disorder.17
While it is challenging to manage a chronic illness at her age, she feels hopeful that she can make better choices for her overall health with your support and the support of her family and mental health team.
Dr. Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center, Burlington, where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
References
1. Bipolar Disord. 2016 Jan 9 doi: 10.1111/bdi.12358.
2. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
3. Am J Psychiatry. 2018 Dec 11. doi: 10.1176/appi.ajp.2018.18040461.
4. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2016.
5. The CRAFFT tool.
6. General Behavior Inventory. Parent Version (P-GBI) Short Form – H/B (Revised Version, 2008).
7. Child Mania Rating Scale, Parent Version (CMRS-P).
8. https://www.moodtracker.com.
9. J Clin Psychiatry. 2000 Sep. doi: 10.4088/jcp.v61n0906.
10. Int J Bipolar Disord. 2020 Apr 20. doi: 10.1186/s40345-020-00185-2.
11. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
12. Bipolar Disord. 2017 Sep 25. doi: 10.1111/bdi.12556.
13. www.cabsresearch.pitt.edu/bpriskcalculator/.
14. Parent Version of the Young Mania Rating Scale (PYMRS).
15. Arch Gen Psychiatry. 2012 Jan 2. doi: 10.1001/archgenpsychiatry.2011.1508.
16. The Carlat Child Psychiatry Report. “Bipolar Disorder” Newburyport, Mass.: Carlat Publishing, 2012.
17. https://www.ipsrt.org/.
The assessment and diagnosis of bipolar disorder in youth has a complicated and controversial history. I recall from my child and adolescent fellowship training that there was a thinly veiled faculty argument about the diagnosis itself with strong opinions on each side. To revisit this quandary, I reviewed the most up-to-date literature and outlined a case-based approach to the initial screening assessment. Certainly, the assessment by a child and adolescent psychiatrist would be the standard for diagnosis, but we do know that the pediatrician’s office may be the first setting for a child and parent to present with mood symptoms and concerns about bipolar disorder. What can you do to address this adolescent, Carrie, and her mother’s concerns?
Case
Carrie is a 17-year-old girl who has struggled through her childhood and adolescence with anxious and depressive symptoms which have ebbed and flowed with major life stressors, including her parent’s divorce. She has tried cognitive-behavioral therapy and selective serotonin reuptake inhibitors, but the SSRI seemed to cause feelings of anxiousness and agitation, so she stopped it within weeks.
Her mother presents to you concerned that Carrie has had a more persistently irritable mood toward her, often just wanting to be with her friends or otherwise isolate in her room when home to study.
Most concerning to her mother is that Carrie, as a straight A student, has also developed a pattern of staying up all night to study for tests and then “crashes” and sleeps through the weekend, avoiding her mother and only brightening with her friends.
To complicate matters, Carrie’s biological father had type 1 bipolar disorder and an addiction. Her mother comes to you with an initially nonparticipatory Carrie in tow and says: “My former husband began his manic episodes with a lack of sleep and Carrie is so irritable towards me. I feel like I am walking on eggshells all the time. Could this be bipolar disorder?”
Case discussion
First, it’s always useful to frame a visit stating that you will spend some time with the patient and some time with both the patient and parent. Emphasizing confidentiality about issues such as drug use, which can be comorbid with mood symptoms and go undetected in high-achieving students such as Carrie, is also important. Further emphasizing that information will not be reflexively shared with the parent unless the child presents a danger to herself or others is also paramount to receive an honest report of symptoms.
Second, there are many signs and symptoms of bipolar disorder that naturally overlap with other conditions such as distractibility with attention-deficit/hyperactivity disorder, or irritability in either a unipolar depression or disruptive mood dysregulation disorder.1 You are looking for an episodic (not chronic) course of symptoms with episodes that last over 5 days for hypomania and over the course of weeks for mania all while meeting all the classic criteria for bipolar disorder.
Note that the broadening of diagnostic criteria has been thought to contribute to an inflated sense of prevalence. The actual expert estimate of prevalence is around 0.8%-1.8% in pediatric populations, although there is a large published range depending on whether the criteria are modified or not.2 Use of the unmodified criteria from the DSM-5 is the recommended approach. Bipolar disorder is exceedingly rare in prepubertal children, and it would be more common for prodromal symptoms such as Carrie’s to emerge and escalate over the teenage years, culminating in a clearer diagnosis in the later teens or 20s.3
In my screening questions, I find the idea of an “infatiguable state” is the most pathognomonic one in considering mania in bipolar disorder.4 Carrie’s “crashing” after nights of studying shows that she clearly fatigues. Patients with bipolar disorder within episodes of hypomania or mania have a seismic shift in perceived energy and a matching lack of ability to sleep that can affect their thought processes, speech, and decision-making. At first blush, Carrie’s history does not indicate current symptoms of bipolar disorder.3
Case, continued
When you meet with Carrie alone she shares that she has been experimenting with prescribed stimulants from her older college-aged brother in order to study and ace her tests. She is also experimenting with alcohol and marijuana with her friends. You provide her the CRAFFT tool to deepen your screening of this issue.5
With her mother, you administer the Parent General Behavior Inventory6 and the and the Child Mania Rating Scale7. From these scales, you note that the irritability is more specific to Carrie’s family than pan-present in school and with friends. Her lack of sleep occurs at high-pressure and discreet times.
At this point, you reassure Carrie and her mother that Carrie does not present with symptoms of bipolar disorder but that certainly you will continue screening assessments over time, as they are a good means to track symptoms. You also recommend that Carrie consider mood tracking so she can develop insights into her mood and its relationship to sleep and other events as she prepares for college.8
Case discussion, continued
The strongest risk factor for bipolar disorder in youth is family history (specifically a parent) with bipolar disorder).9 If there is the chance to explore the parent’s illness with open-ended questions, you will want to hear about the parent’s age of symptom onset, course of treatment, any hospitalizations, and stabilizing medications because this has prognostic power for your patient. It is important to ensure that the parent indeed has a diagnosis of bipolar disorder and that it is not just being used colloquially to characterize an adult who has labile moods from hour to hour or day to day. This would give undue anticipatory anxiety to a youth about their risk, which is up to 8- to 10-fold greater with a parent with bipolar disorder.9
Even with a strong family history, we do not often see bipolar disorder emerge in prepubertal children.10,11 There may be still concerning prodromal symptoms in which a diagnosis of unipolar depression with more irritable features and mood lability seems more commonly complicated by substance use, as with Carrie.
Activation with an SSRI, as in Carrie’s case, even if not resulting in full mania or hypomania, can also be a soft sign of the serotonergic sensitivity present in bipolar disorder. However, if there are not additional symptoms of bipolar disorder and you are concerned based on family history alone, you do not want to withhold antidepressant treatment because fear of risk. You would want to consider a “dose low and go slow” titration process with more frequent monitoring.
A diagnostic interview with a child and adolescent psychiatrist and administration of scales such as the Young Mania Rating Scale and the Modified Child Depression Rating Scale are the standard means to assess for bipolar symptoms.12 Considering the dearth of child psychiatrists nationally, it would be useful to improve one’s screening in primary care so as to not inadvertently “refer out” all patients for whom mood dysregulation is a concern.
There is also a more expanded tool that includes several scales integrated with clinical information (parent’s age of mood disorder onset, child’s age) which can culminate in a risk score.13
Lastly, I provide my patients with a handout of the Young Mania Rating Scale to take home as a reference and to complete before our next visit.14
You can repeat scales to monitor for more striking bipolar disorder signs and symptoms that emerge over the course of one’s longitudinal treatment of a pediatric patient. This can be an ongoing, episodic assessment since the emergence of bipolar disorder has been shown to range from the teenage years and beyond into the 20s and sometimes 30s.
Case, continued
Carrie presents to you again while in her first semester of college at the age of 19. She is taking a leave of absence after she began experimenting with cocaine at college and had a manic episode characterized by a lack of sleep without fatigue, persistent unabating energy, rapid and pressured speech, and ultimately, concern from her college friends. She was admitted to a psychiatric unit and stabilized on a second-generation antipsychotic, risperidone, which has solid evidence for mania, but she and you are now concerned about longer-term metabolic effects.15,16
You discuss monitoring her lipid profile and hemoglobin A1c, in addition to weight gain and waist circumference. She has connected with a therapist and psychiatrist through the college counseling center and hopes to return next semester with a fresh start and commitment to sobriety and social rhythms therapy known to be helpful for patients with bipolar disorder.17
While it is challenging to manage a chronic illness at her age, she feels hopeful that she can make better choices for her overall health with your support and the support of her family and mental health team.
Dr. Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center, Burlington, where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
References
1. Bipolar Disord. 2016 Jan 9 doi: 10.1111/bdi.12358.
2. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
3. Am J Psychiatry. 2018 Dec 11. doi: 10.1176/appi.ajp.2018.18040461.
4. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2016.
5. The CRAFFT tool.
6. General Behavior Inventory. Parent Version (P-GBI) Short Form – H/B (Revised Version, 2008).
7. Child Mania Rating Scale, Parent Version (CMRS-P).
8. https://www.moodtracker.com.
9. J Clin Psychiatry. 2000 Sep. doi: 10.4088/jcp.v61n0906.
10. Int J Bipolar Disord. 2020 Apr 20. doi: 10.1186/s40345-020-00185-2.
11. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.
12. Bipolar Disord. 2017 Sep 25. doi: 10.1111/bdi.12556.
13. www.cabsresearch.pitt.edu/bpriskcalculator/.
14. Parent Version of the Young Mania Rating Scale (PYMRS).
15. Arch Gen Psychiatry. 2012 Jan 2. doi: 10.1001/archgenpsychiatry.2011.1508.
16. The Carlat Child Psychiatry Report. “Bipolar Disorder” Newburyport, Mass.: Carlat Publishing, 2012.
17. https://www.ipsrt.org/.
The pediatrician’s office may be the first setting for a child to present with mood symptoms.
Magnesium sulfate shown to reduce risk of cerebral palsy in premature babies
A program to increase the use of magnesium sulfate to reduce the risk of cerebral palsy is effective, say researchers. Giving magnesium sulfate to women at risk of premature birth can reduce the risk of a child having cerebral palsy by a third, and costs just £1 per dose.
However, the authors of the new observational study, published in Archives of Disease in Childhood – Fetal and Neonatal Edition, pointed out that in 2017 only around two-thirds (64%) of eligible women were being given magnesium sulfate in England, Scotland, and Wales, with “wide regional variations.”
To address this, in 2014 the PReCePT (Preventing Cerebral Palsy in Pre Term labor) quality improvement toolkit was developed by both parents and staff with the aim of supporting all maternity units in England to improve maternity staff awareness and increase the use of magnesium sulfate in mothers at risk of giving birth at 30 weeks’ gestation or under. PReCePT provided practical tools and training to support hospital staff to give magnesium sulfate to eligible mothers.
The pilot study in 2015, which involved five maternity units, found an increase in uptake from 21% to 88% associated with the PReCePT approach. Subsequently, in 2018, NHS England funded the National PReCePT Programme, which scaled up the intervention for national roll-out and provided the PReCePT quality toolkit – which includes preterm labor proforma, staff training presentations, parent information leaflet, posters for the unit, and a learning log – to each maternity unit.
Improvement ‘over and above’ expectation
For the first evaluation of a U.K. universally implemented national perinatal quality improvement program to increase administration of an evidence-based drug, researchers, led by University of Bristol, England, set out to evaluate the effectiveness and cost-effectiveness of the National PReCePT Programme in increasing use of magnesium sulfate in preterm births.
Using data from the U.K. National Neonatal Research Database for the year before and the year after PReCePT was implemented in maternity units in England, the researchers performed a before-and-after study that involved 137 maternity units within NHS England. Participants were babies born at 30 weeks’ gestation or under admitted to neonatal units in England, and the main outcome measure was magnesium sulfate uptake before and after the implementation of the National PReCePT Programme. In addition, implementation and lifetime costs were estimated.
During the first year, post implementation of the program, uptake increased by an average of 6.3 percentage points (to 83.1%) across all maternity units in England, which the authors explained was “over and above” the increase that would be expected over time as the practice spread organically. The researchers also found that after adjusting for variations in when maternity units started the program, the increase in use of magnesium sulfate was 9.5 percentage points. “By May 2020, on average 86.4% of eligible mothers were receiving magnesium sulfate,” they said.
Professor John Macleod, NIHR ARC West Director, professor in clinical epidemiology and primary care, University of Bristol, and principal investigator of the evaluation, said: “Our in-depth analysis has been able to demonstrate that the PReCePT program is both effective and cost-effective. The program has increased uptake of magnesium sulfate, which we know is a cost-effective medicine to prevent cerebral palsy, much more quickly than we could have otherwise expected.”
From a societal and lifetime perspective, the health gains and cost savings associated with the National PReCePT Programme generated a “net monetary benefit of £866 per preterm baby,” with the probability of the program being cost-effective being “greater than 95%,” the authors highlighted.
The researchers also estimated that the program’s first year could be associated with a lifetime saving to society of £3 million – which accounts for the costs of the program, of administering the treatment, of cerebral palsy to society over a lifetime, and the associated health gains of avoiding cases. “This is across all the extra babies the program helped get access to the treatment during the first year,” they said.
The authors highlighted that in the five pilot sites, the improved use of magnesium sulfate has been “sustained over the years” since PReCePT was implemented. As the program costs were mostly in the first year of implementation, longer-term national analysis may show that PReCePT is “even more cost-effective over a longer period,” they postulated.
Accelerate uptake
Uptake of new evidence or guidelines is often “slow” due to practical barriers, lack of knowledge, and need for behavior change, and can “take decades to become embedded” in perinatal clinical practice, expressed the authors, which in turn comes at a “high clinical and economic cost.”
Karen Luyt, professor in neonatal medicine, University of Bristol, said: “The PReCePT national quality improvement program demonstrates that a collaborative and coordinated perinatal implementation program supporting every hospital in England can accelerate the uptake of new evidence-based treatments into routine practice, enabling equitable health benefits to babies and ultimately reductions in lifetime societal costs.”
The authors said the PReCePT model “may serve as a blueprint for future interventions to improve perinatal care.”
Professor Lucy Chappell, chief executive officer of the National Institute for Health and Care Research, said: “This important study shows the impact of taking a promising intervention that had been shown to work in a research setting and scaling it up across the country. Giving magnesium sulfate to prevent cerebral palsy in premature babies is a simple, inexpensive intervention that can make such a difference to families and the health service.”
Prof. Macleod added: “We are pleased to have played a part in helping get this cheap yet effective treatment to more babies.”
This work was jointly funded by the National Institute for Health and Care Research Applied Research Collaboration West and the AHSN Network funded by NHS England. The Health Foundation funded the health economics evaluation. The authors declare that the study management group has no competing financial, professional, or personal interests that might have influenced the study design or conduct.
A version of this article first appeared on Medscape UK.
A program to increase the use of magnesium sulfate to reduce the risk of cerebral palsy is effective, say researchers. Giving magnesium sulfate to women at risk of premature birth can reduce the risk of a child having cerebral palsy by a third, and costs just £1 per dose.
However, the authors of the new observational study, published in Archives of Disease in Childhood – Fetal and Neonatal Edition, pointed out that in 2017 only around two-thirds (64%) of eligible women were being given magnesium sulfate in England, Scotland, and Wales, with “wide regional variations.”
To address this, in 2014 the PReCePT (Preventing Cerebral Palsy in Pre Term labor) quality improvement toolkit was developed by both parents and staff with the aim of supporting all maternity units in England to improve maternity staff awareness and increase the use of magnesium sulfate in mothers at risk of giving birth at 30 weeks’ gestation or under. PReCePT provided practical tools and training to support hospital staff to give magnesium sulfate to eligible mothers.
The pilot study in 2015, which involved five maternity units, found an increase in uptake from 21% to 88% associated with the PReCePT approach. Subsequently, in 2018, NHS England funded the National PReCePT Programme, which scaled up the intervention for national roll-out and provided the PReCePT quality toolkit – which includes preterm labor proforma, staff training presentations, parent information leaflet, posters for the unit, and a learning log – to each maternity unit.
Improvement ‘over and above’ expectation
For the first evaluation of a U.K. universally implemented national perinatal quality improvement program to increase administration of an evidence-based drug, researchers, led by University of Bristol, England, set out to evaluate the effectiveness and cost-effectiveness of the National PReCePT Programme in increasing use of magnesium sulfate in preterm births.
Using data from the U.K. National Neonatal Research Database for the year before and the year after PReCePT was implemented in maternity units in England, the researchers performed a before-and-after study that involved 137 maternity units within NHS England. Participants were babies born at 30 weeks’ gestation or under admitted to neonatal units in England, and the main outcome measure was magnesium sulfate uptake before and after the implementation of the National PReCePT Programme. In addition, implementation and lifetime costs were estimated.
During the first year, post implementation of the program, uptake increased by an average of 6.3 percentage points (to 83.1%) across all maternity units in England, which the authors explained was “over and above” the increase that would be expected over time as the practice spread organically. The researchers also found that after adjusting for variations in when maternity units started the program, the increase in use of magnesium sulfate was 9.5 percentage points. “By May 2020, on average 86.4% of eligible mothers were receiving magnesium sulfate,” they said.
Professor John Macleod, NIHR ARC West Director, professor in clinical epidemiology and primary care, University of Bristol, and principal investigator of the evaluation, said: “Our in-depth analysis has been able to demonstrate that the PReCePT program is both effective and cost-effective. The program has increased uptake of magnesium sulfate, which we know is a cost-effective medicine to prevent cerebral palsy, much more quickly than we could have otherwise expected.”
From a societal and lifetime perspective, the health gains and cost savings associated with the National PReCePT Programme generated a “net monetary benefit of £866 per preterm baby,” with the probability of the program being cost-effective being “greater than 95%,” the authors highlighted.
The researchers also estimated that the program’s first year could be associated with a lifetime saving to society of £3 million – which accounts for the costs of the program, of administering the treatment, of cerebral palsy to society over a lifetime, and the associated health gains of avoiding cases. “This is across all the extra babies the program helped get access to the treatment during the first year,” they said.
The authors highlighted that in the five pilot sites, the improved use of magnesium sulfate has been “sustained over the years” since PReCePT was implemented. As the program costs were mostly in the first year of implementation, longer-term national analysis may show that PReCePT is “even more cost-effective over a longer period,” they postulated.
Accelerate uptake
Uptake of new evidence or guidelines is often “slow” due to practical barriers, lack of knowledge, and need for behavior change, and can “take decades to become embedded” in perinatal clinical practice, expressed the authors, which in turn comes at a “high clinical and economic cost.”
Karen Luyt, professor in neonatal medicine, University of Bristol, said: “The PReCePT national quality improvement program demonstrates that a collaborative and coordinated perinatal implementation program supporting every hospital in England can accelerate the uptake of new evidence-based treatments into routine practice, enabling equitable health benefits to babies and ultimately reductions in lifetime societal costs.”
The authors said the PReCePT model “may serve as a blueprint for future interventions to improve perinatal care.”
Professor Lucy Chappell, chief executive officer of the National Institute for Health and Care Research, said: “This important study shows the impact of taking a promising intervention that had been shown to work in a research setting and scaling it up across the country. Giving magnesium sulfate to prevent cerebral palsy in premature babies is a simple, inexpensive intervention that can make such a difference to families and the health service.”
Prof. Macleod added: “We are pleased to have played a part in helping get this cheap yet effective treatment to more babies.”
This work was jointly funded by the National Institute for Health and Care Research Applied Research Collaboration West and the AHSN Network funded by NHS England. The Health Foundation funded the health economics evaluation. The authors declare that the study management group has no competing financial, professional, or personal interests that might have influenced the study design or conduct.
A version of this article first appeared on Medscape UK.
A program to increase the use of magnesium sulfate to reduce the risk of cerebral palsy is effective, say researchers. Giving magnesium sulfate to women at risk of premature birth can reduce the risk of a child having cerebral palsy by a third, and costs just £1 per dose.
However, the authors of the new observational study, published in Archives of Disease in Childhood – Fetal and Neonatal Edition, pointed out that in 2017 only around two-thirds (64%) of eligible women were being given magnesium sulfate in England, Scotland, and Wales, with “wide regional variations.”
To address this, in 2014 the PReCePT (Preventing Cerebral Palsy in Pre Term labor) quality improvement toolkit was developed by both parents and staff with the aim of supporting all maternity units in England to improve maternity staff awareness and increase the use of magnesium sulfate in mothers at risk of giving birth at 30 weeks’ gestation or under. PReCePT provided practical tools and training to support hospital staff to give magnesium sulfate to eligible mothers.
The pilot study in 2015, which involved five maternity units, found an increase in uptake from 21% to 88% associated with the PReCePT approach. Subsequently, in 2018, NHS England funded the National PReCePT Programme, which scaled up the intervention for national roll-out and provided the PReCePT quality toolkit – which includes preterm labor proforma, staff training presentations, parent information leaflet, posters for the unit, and a learning log – to each maternity unit.
Improvement ‘over and above’ expectation
For the first evaluation of a U.K. universally implemented national perinatal quality improvement program to increase administration of an evidence-based drug, researchers, led by University of Bristol, England, set out to evaluate the effectiveness and cost-effectiveness of the National PReCePT Programme in increasing use of magnesium sulfate in preterm births.
Using data from the U.K. National Neonatal Research Database for the year before and the year after PReCePT was implemented in maternity units in England, the researchers performed a before-and-after study that involved 137 maternity units within NHS England. Participants were babies born at 30 weeks’ gestation or under admitted to neonatal units in England, and the main outcome measure was magnesium sulfate uptake before and after the implementation of the National PReCePT Programme. In addition, implementation and lifetime costs were estimated.
During the first year, post implementation of the program, uptake increased by an average of 6.3 percentage points (to 83.1%) across all maternity units in England, which the authors explained was “over and above” the increase that would be expected over time as the practice spread organically. The researchers also found that after adjusting for variations in when maternity units started the program, the increase in use of magnesium sulfate was 9.5 percentage points. “By May 2020, on average 86.4% of eligible mothers were receiving magnesium sulfate,” they said.
Professor John Macleod, NIHR ARC West Director, professor in clinical epidemiology and primary care, University of Bristol, and principal investigator of the evaluation, said: “Our in-depth analysis has been able to demonstrate that the PReCePT program is both effective and cost-effective. The program has increased uptake of magnesium sulfate, which we know is a cost-effective medicine to prevent cerebral palsy, much more quickly than we could have otherwise expected.”
From a societal and lifetime perspective, the health gains and cost savings associated with the National PReCePT Programme generated a “net monetary benefit of £866 per preterm baby,” with the probability of the program being cost-effective being “greater than 95%,” the authors highlighted.
The researchers also estimated that the program’s first year could be associated with a lifetime saving to society of £3 million – which accounts for the costs of the program, of administering the treatment, of cerebral palsy to society over a lifetime, and the associated health gains of avoiding cases. “This is across all the extra babies the program helped get access to the treatment during the first year,” they said.
The authors highlighted that in the five pilot sites, the improved use of magnesium sulfate has been “sustained over the years” since PReCePT was implemented. As the program costs were mostly in the first year of implementation, longer-term national analysis may show that PReCePT is “even more cost-effective over a longer period,” they postulated.
Accelerate uptake
Uptake of new evidence or guidelines is often “slow” due to practical barriers, lack of knowledge, and need for behavior change, and can “take decades to become embedded” in perinatal clinical practice, expressed the authors, which in turn comes at a “high clinical and economic cost.”
Karen Luyt, professor in neonatal medicine, University of Bristol, said: “The PReCePT national quality improvement program demonstrates that a collaborative and coordinated perinatal implementation program supporting every hospital in England can accelerate the uptake of new evidence-based treatments into routine practice, enabling equitable health benefits to babies and ultimately reductions in lifetime societal costs.”
The authors said the PReCePT model “may serve as a blueprint for future interventions to improve perinatal care.”
Professor Lucy Chappell, chief executive officer of the National Institute for Health and Care Research, said: “This important study shows the impact of taking a promising intervention that had been shown to work in a research setting and scaling it up across the country. Giving magnesium sulfate to prevent cerebral palsy in premature babies is a simple, inexpensive intervention that can make such a difference to families and the health service.”
Prof. Macleod added: “We are pleased to have played a part in helping get this cheap yet effective treatment to more babies.”
This work was jointly funded by the National Institute for Health and Care Research Applied Research Collaboration West and the AHSN Network funded by NHS England. The Health Foundation funded the health economics evaluation. The authors declare that the study management group has no competing financial, professional, or personal interests that might have influenced the study design or conduct.
A version of this article first appeared on Medscape UK.