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Liver disease does not worsen IVF outcomes
Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.
The study, published online in the American Journal of Gastroenterology, compared women with and those without chronic liver disease who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.
“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers wrote.
Women with liver disease may experience impaired fertility. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.
leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease,” the authors wrote.
The literature about ART treatment outcomes for women with liver disease was limited and may not reflect current therapy protocols, researchers found.
“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with liver disease,” they wrote.
Similar outcomes
Researchers identified 295 women with liver disease (mean age, 37.8 ± 5.2 years) who underwent 1,033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.
The control group consisted of all the women at the treatment center without liver disease who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.
The mean age of the patients with liver disease was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with liver disease, and there were differences in baseline levels of selected hormones, compared with control participants. In addition, among those with liver disease, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs. 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs. 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs. 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs. 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs. 2.7 ± 2.4; P < .05), compared with control participants.
Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.
A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the liver disease group and the control group.
“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers wrote.
Data for patient counseling
The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai, New York, said.
“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she said.
The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in liver diseases at the Icahn School.
Women with liver disease whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.
The study’s findings are “encouraging,” said Monika Sarkar, MD, associate professor of medicine in gastroenterology at the University of California, San Francisco.
“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients – namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
Differences in oocyte numbers
Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the liver disease group, compared with 609 in the control group, noted Dr. Sarkar, who was not involved with the study.
“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Dr. Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”
The data suggest that fewer eggs are retrieved per cycle from patients with liver disease, “which ultimately will lower the success per cycle,” Dr. Sarkar said.
“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”
As more research on ART outcomes in women with liver disease is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Dr. Sarkar said.
Ms. Lee, Dr. Kushner, and Dr. Sarkar report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.
The study, published online in the American Journal of Gastroenterology, compared women with and those without chronic liver disease who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.
“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers wrote.
Women with liver disease may experience impaired fertility. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.
leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease,” the authors wrote.
The literature about ART treatment outcomes for women with liver disease was limited and may not reflect current therapy protocols, researchers found.
“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with liver disease,” they wrote.
Similar outcomes
Researchers identified 295 women with liver disease (mean age, 37.8 ± 5.2 years) who underwent 1,033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.
The control group consisted of all the women at the treatment center without liver disease who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.
The mean age of the patients with liver disease was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with liver disease, and there were differences in baseline levels of selected hormones, compared with control participants. In addition, among those with liver disease, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs. 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs. 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs. 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs. 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs. 2.7 ± 2.4; P < .05), compared with control participants.
Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.
A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the liver disease group and the control group.
“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers wrote.
Data for patient counseling
The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai, New York, said.
“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she said.
The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in liver diseases at the Icahn School.
Women with liver disease whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.
The study’s findings are “encouraging,” said Monika Sarkar, MD, associate professor of medicine in gastroenterology at the University of California, San Francisco.
“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients – namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
Differences in oocyte numbers
Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the liver disease group, compared with 609 in the control group, noted Dr. Sarkar, who was not involved with the study.
“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Dr. Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”
The data suggest that fewer eggs are retrieved per cycle from patients with liver disease, “which ultimately will lower the success per cycle,” Dr. Sarkar said.
“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”
As more research on ART outcomes in women with liver disease is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Dr. Sarkar said.
Ms. Lee, Dr. Kushner, and Dr. Sarkar report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.
The study, published online in the American Journal of Gastroenterology, compared women with and those without chronic liver disease who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.
“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers wrote.
Women with liver disease may experience impaired fertility. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.
leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease,” the authors wrote.
The literature about ART treatment outcomes for women with liver disease was limited and may not reflect current therapy protocols, researchers found.
“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with liver disease,” they wrote.
Similar outcomes
Researchers identified 295 women with liver disease (mean age, 37.8 ± 5.2 years) who underwent 1,033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.
The control group consisted of all the women at the treatment center without liver disease who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.
The mean age of the patients with liver disease was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with liver disease, and there were differences in baseline levels of selected hormones, compared with control participants. In addition, among those with liver disease, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs. 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs. 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs. 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs. 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs. 2.7 ± 2.4; P < .05), compared with control participants.
Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.
A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the liver disease group and the control group.
“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers wrote.
Data for patient counseling
The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai, New York, said.
“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she said.
The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in liver diseases at the Icahn School.
Women with liver disease whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.
The study’s findings are “encouraging,” said Monika Sarkar, MD, associate professor of medicine in gastroenterology at the University of California, San Francisco.
“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients – namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
Differences in oocyte numbers
Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the liver disease group, compared with 609 in the control group, noted Dr. Sarkar, who was not involved with the study.
“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Dr. Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”
The data suggest that fewer eggs are retrieved per cycle from patients with liver disease, “which ultimately will lower the success per cycle,” Dr. Sarkar said.
“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”
As more research on ART outcomes in women with liver disease is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Dr. Sarkar said.
Ms. Lee, Dr. Kushner, and Dr. Sarkar report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Progress, gaps as pediatricians expand mental health roles
but a review of electronic health records highlights areas for improvement in delivering the care.
The findings were published online in Pediatrics.
The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
Encouraging signs
The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.
Three areas for improvement
The researchers identified three main shortfall areas and suggested improvements.
PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.
Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.
The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
Half are seeing only their primary care pediatrician
About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.
Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.
Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.
Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.
It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”
He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”
“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
Most concerning statistics
Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.
Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.
“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.
The authors and Dr. Butter declared no relevant financial relationships.
but a review of electronic health records highlights areas for improvement in delivering the care.
The findings were published online in Pediatrics.
The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
Encouraging signs
The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.
Three areas for improvement
The researchers identified three main shortfall areas and suggested improvements.
PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.
Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.
The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
Half are seeing only their primary care pediatrician
About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.
Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.
Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.
Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.
It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”
He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”
“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
Most concerning statistics
Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.
Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.
“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.
The authors and Dr. Butter declared no relevant financial relationships.
but a review of electronic health records highlights areas for improvement in delivering the care.
The findings were published online in Pediatrics.
The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
Encouraging signs
The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.
Three areas for improvement
The researchers identified three main shortfall areas and suggested improvements.
PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.
Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.
The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
Half are seeing only their primary care pediatrician
About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.
Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.
Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.
Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.
It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”
He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”
“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
Most concerning statistics
Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.
Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.
“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.
The authors and Dr. Butter declared no relevant financial relationships.
FROM PEDIATRICS
Integrating addiction medicine with primary care cost effective: Study
Integrating buprenorphine and harm eduction tools into primary care may improve clinical outcomes, increase costs only modestly, and be cost effective in health systems, authors conclude in an original investigation in JAMA Network Open.
A team led by Raagini Jawa, MD, MPH, with the Center for Research on Healthcare, University of Pittsburgh, set out to analyze costs of the interventions versus increased benefit in extending life expectancy.
Their analysis found that, compared with the status quo, integrating buprenorphine and harm reduction kits (syringes, wound care supplies, etc.) reduced drug use–related deaths by 33% and was cost effective.
“Our results suggest that integrated addiction care in primary care has the potential to save lives and increase nonemergency health care use, which is consistent with prior literature,” the authors write. “Colocated addiction services within primary care is pragmatic and effective and has comparable quality to specialty care. We found that onsite BUP [buprenorphine prescribing] plus HR [harm reduction] provides better outcomes than BUP alone at a lower cost.”
Three strategies compared
Using a microsimulation model of 2.25 million people in the United States who inject opioids, with an average age of 44 (69% of them male), the researchers tested three strategies:
- Status quo. PCP refers to addiction care.
- BUP. PCP services plus onsite buprenorphine prescribing with referral to off-site harm reduction kits.
- BUP plus HR. PCP services plus on-site buprenorphine prescribing and harm reduction kits.
The model is the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death.
The status quo (referral for treatment) resulted in 1,162 overdose deaths per 10,000 people (95% credible interval, 1,144-2,303), whereas both BUP and BUP plus HR resulted in about 160 fewer deaths per 10,000 people (95% Crl for BUP, 802-1718; 95% CrI for BUP plus HR, 692-1,810).
Compared with the status quo strategy, life expectancy was lengthened with the BUP strategy by 2.65 years and BUP plus HR by 2.71 years.
Researchers found the average discounted lifetime cost per person of both the BUP strategy and the BUP plus HR strategy were higher than the average status quo.
“The dominating strategy was BUP plus HR,” the authors write. “Compared with status quo, BUP plus HR was cost effective (incremental cost-effectiveness ratio [ICER], $34,400 per life year).”
Cost for primary care practices
Comparatively, over a 5-year period, BUP plus HR was found to cost an individual PCP practice approximately $13,000.
That cost includes direct costs for resources and opportunity costs, the authors write. These costs could be offset by health care system savings.
“These costs included those for X-waiver training, which has been eliminated; thus, we expect this to cost less. Put another way, our findings inform ways to reinvest health care dollars as financial incentives for PCPs to adopt this new paradigm. Public health departments could provide grants or harm reduction kit supplies directly to PCPs to offset these costs as they do in some places with syringe service programs and/or increase Medicaid reimbursements for providing addiction care in primary care,” they write.
Data help make the case
Dinah Applewhite, MD, a primary care physician and addiction medicine specialist at Massachusetts General Hospital in Boston, who was not part of the study, said clinicians there have seen the benefits of integrating various aspects of addiction medicine into primary care but these data on outcomes and cost-effectiveness can help make the case to hospital leaders, legislators, and grant providers.
The primary care setting also provides a chance to engage patients around their injection practice and explore ways to minimize risk, she said.
“By offering them these kits, it lets them know your priority is their safety and well-being,” Dr. Applewhite said.
She noted that the linkage to primary care was low for patients who inject drugs, which speaks to the need for models in addition to this one, such as bringing primary care clinicians into syringe service programs.
“The medical establishment has a lot to learn from these programs,” she said.
Practices need support
She said it’s important to note that primary care practices need support from administrative leaders, philanthropists, and grant providers to help cover the costs.
“It’s one of the barriers to doing this,” she said. “There isn’t a mechanism to pay for this.”
Sarah Bagley, MD, a primary care physician at Boston Medical Center and medical director of BMC’s Center for Addiction Treatment for Adolescents/Young Adults Who Use Substances told this publication she was excited to see that the addition of harm reduction kits to buprenorphine seemed to have the optimal effect in improving outcomes. People with substance abuse disorders should feel they are welcome in primary care even if they are not yet ready to stop drug use, she said.
She said she was also glad to see increased life expectancy with these interventions. The news of overdose deaths contributing to a decrease in life expectancy can be overwhelming, she said.
But this study, she says, offers a road map for addressing the overdose crisis “by including harm reduction in the substance abuse care we provide.”
She pointed out that the study showed that costs increase per patient with both interventions, compared with the status quo. The study found that health care costs per person during a lifetime increased, compared with the status quo, by 69.1% for BUP and 74.3% for BUP plus HR.
But it’s important to understand the reason for that, she said: “The cost was higher because people were staying alive.”
She said it may help to compare giving optimal care to people who have substance abuse disorders with giving optimal care to people with other chronic conditions, such as diabetes, who may not always adhere to recommended diets or treatment regimens.
“We still invite those patients in and work with them based on where they are,” she said.
Growing epidemic
The researchers point to the urgent need for solutions given the U.S. opioid epidemic, which has led to increasing numbers of overdoses and injection drug use–related infections, such as infective endocarditis, and severe skin and soft tissue infections.
They point out that primary care providers are the largest clinical workforce in the United States, but few of their practices offer comprehensive addiction care onsite.
“Primary care practices are a practical place to integrate addiction services, where PCPs can prescribe buprenorphine and deliver harm reduction kits,” they write.
Coauthor Dr. Kimmel reports personal fees from Massachusetts Department of Public Health, Bureau of Substance Addiction Services Overdose Education and Prevention Program, and American Academy of Addiction Psychiatry, Opioid Response Network for harm reduction education outside the submitted work and previous consulting with Abt Associates on a Massachusetts Department of Public Health–funded project to improve access to medications for opioid use disorder treatment. Dr. Applewhite and Dr. Bagley report no relevant financial relationships.
Integrating buprenorphine and harm eduction tools into primary care may improve clinical outcomes, increase costs only modestly, and be cost effective in health systems, authors conclude in an original investigation in JAMA Network Open.
A team led by Raagini Jawa, MD, MPH, with the Center for Research on Healthcare, University of Pittsburgh, set out to analyze costs of the interventions versus increased benefit in extending life expectancy.
Their analysis found that, compared with the status quo, integrating buprenorphine and harm reduction kits (syringes, wound care supplies, etc.) reduced drug use–related deaths by 33% and was cost effective.
“Our results suggest that integrated addiction care in primary care has the potential to save lives and increase nonemergency health care use, which is consistent with prior literature,” the authors write. “Colocated addiction services within primary care is pragmatic and effective and has comparable quality to specialty care. We found that onsite BUP [buprenorphine prescribing] plus HR [harm reduction] provides better outcomes than BUP alone at a lower cost.”
Three strategies compared
Using a microsimulation model of 2.25 million people in the United States who inject opioids, with an average age of 44 (69% of them male), the researchers tested three strategies:
- Status quo. PCP refers to addiction care.
- BUP. PCP services plus onsite buprenorphine prescribing with referral to off-site harm reduction kits.
- BUP plus HR. PCP services plus on-site buprenorphine prescribing and harm reduction kits.
The model is the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death.
The status quo (referral for treatment) resulted in 1,162 overdose deaths per 10,000 people (95% credible interval, 1,144-2,303), whereas both BUP and BUP plus HR resulted in about 160 fewer deaths per 10,000 people (95% Crl for BUP, 802-1718; 95% CrI for BUP plus HR, 692-1,810).
Compared with the status quo strategy, life expectancy was lengthened with the BUP strategy by 2.65 years and BUP plus HR by 2.71 years.
Researchers found the average discounted lifetime cost per person of both the BUP strategy and the BUP plus HR strategy were higher than the average status quo.
“The dominating strategy was BUP plus HR,” the authors write. “Compared with status quo, BUP plus HR was cost effective (incremental cost-effectiveness ratio [ICER], $34,400 per life year).”
Cost for primary care practices
Comparatively, over a 5-year period, BUP plus HR was found to cost an individual PCP practice approximately $13,000.
That cost includes direct costs for resources and opportunity costs, the authors write. These costs could be offset by health care system savings.
“These costs included those for X-waiver training, which has been eliminated; thus, we expect this to cost less. Put another way, our findings inform ways to reinvest health care dollars as financial incentives for PCPs to adopt this new paradigm. Public health departments could provide grants or harm reduction kit supplies directly to PCPs to offset these costs as they do in some places with syringe service programs and/or increase Medicaid reimbursements for providing addiction care in primary care,” they write.
Data help make the case
Dinah Applewhite, MD, a primary care physician and addiction medicine specialist at Massachusetts General Hospital in Boston, who was not part of the study, said clinicians there have seen the benefits of integrating various aspects of addiction medicine into primary care but these data on outcomes and cost-effectiveness can help make the case to hospital leaders, legislators, and grant providers.
The primary care setting also provides a chance to engage patients around their injection practice and explore ways to minimize risk, she said.
“By offering them these kits, it lets them know your priority is their safety and well-being,” Dr. Applewhite said.
She noted that the linkage to primary care was low for patients who inject drugs, which speaks to the need for models in addition to this one, such as bringing primary care clinicians into syringe service programs.
“The medical establishment has a lot to learn from these programs,” she said.
Practices need support
She said it’s important to note that primary care practices need support from administrative leaders, philanthropists, and grant providers to help cover the costs.
“It’s one of the barriers to doing this,” she said. “There isn’t a mechanism to pay for this.”
Sarah Bagley, MD, a primary care physician at Boston Medical Center and medical director of BMC’s Center for Addiction Treatment for Adolescents/Young Adults Who Use Substances told this publication she was excited to see that the addition of harm reduction kits to buprenorphine seemed to have the optimal effect in improving outcomes. People with substance abuse disorders should feel they are welcome in primary care even if they are not yet ready to stop drug use, she said.
She said she was also glad to see increased life expectancy with these interventions. The news of overdose deaths contributing to a decrease in life expectancy can be overwhelming, she said.
But this study, she says, offers a road map for addressing the overdose crisis “by including harm reduction in the substance abuse care we provide.”
She pointed out that the study showed that costs increase per patient with both interventions, compared with the status quo. The study found that health care costs per person during a lifetime increased, compared with the status quo, by 69.1% for BUP and 74.3% for BUP plus HR.
But it’s important to understand the reason for that, she said: “The cost was higher because people were staying alive.”
She said it may help to compare giving optimal care to people who have substance abuse disorders with giving optimal care to people with other chronic conditions, such as diabetes, who may not always adhere to recommended diets or treatment regimens.
“We still invite those patients in and work with them based on where they are,” she said.
Growing epidemic
The researchers point to the urgent need for solutions given the U.S. opioid epidemic, which has led to increasing numbers of overdoses and injection drug use–related infections, such as infective endocarditis, and severe skin and soft tissue infections.
They point out that primary care providers are the largest clinical workforce in the United States, but few of their practices offer comprehensive addiction care onsite.
“Primary care practices are a practical place to integrate addiction services, where PCPs can prescribe buprenorphine and deliver harm reduction kits,” they write.
Coauthor Dr. Kimmel reports personal fees from Massachusetts Department of Public Health, Bureau of Substance Addiction Services Overdose Education and Prevention Program, and American Academy of Addiction Psychiatry, Opioid Response Network for harm reduction education outside the submitted work and previous consulting with Abt Associates on a Massachusetts Department of Public Health–funded project to improve access to medications for opioid use disorder treatment. Dr. Applewhite and Dr. Bagley report no relevant financial relationships.
Integrating buprenorphine and harm eduction tools into primary care may improve clinical outcomes, increase costs only modestly, and be cost effective in health systems, authors conclude in an original investigation in JAMA Network Open.
A team led by Raagini Jawa, MD, MPH, with the Center for Research on Healthcare, University of Pittsburgh, set out to analyze costs of the interventions versus increased benefit in extending life expectancy.
Their analysis found that, compared with the status quo, integrating buprenorphine and harm reduction kits (syringes, wound care supplies, etc.) reduced drug use–related deaths by 33% and was cost effective.
“Our results suggest that integrated addiction care in primary care has the potential to save lives and increase nonemergency health care use, which is consistent with prior literature,” the authors write. “Colocated addiction services within primary care is pragmatic and effective and has comparable quality to specialty care. We found that onsite BUP [buprenorphine prescribing] plus HR [harm reduction] provides better outcomes than BUP alone at a lower cost.”
Three strategies compared
Using a microsimulation model of 2.25 million people in the United States who inject opioids, with an average age of 44 (69% of them male), the researchers tested three strategies:
- Status quo. PCP refers to addiction care.
- BUP. PCP services plus onsite buprenorphine prescribing with referral to off-site harm reduction kits.
- BUP plus HR. PCP services plus on-site buprenorphine prescribing and harm reduction kits.
The model is the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death.
The status quo (referral for treatment) resulted in 1,162 overdose deaths per 10,000 people (95% credible interval, 1,144-2,303), whereas both BUP and BUP plus HR resulted in about 160 fewer deaths per 10,000 people (95% Crl for BUP, 802-1718; 95% CrI for BUP plus HR, 692-1,810).
Compared with the status quo strategy, life expectancy was lengthened with the BUP strategy by 2.65 years and BUP plus HR by 2.71 years.
Researchers found the average discounted lifetime cost per person of both the BUP strategy and the BUP plus HR strategy were higher than the average status quo.
“The dominating strategy was BUP plus HR,” the authors write. “Compared with status quo, BUP plus HR was cost effective (incremental cost-effectiveness ratio [ICER], $34,400 per life year).”
Cost for primary care practices
Comparatively, over a 5-year period, BUP plus HR was found to cost an individual PCP practice approximately $13,000.
That cost includes direct costs for resources and opportunity costs, the authors write. These costs could be offset by health care system savings.
“These costs included those for X-waiver training, which has been eliminated; thus, we expect this to cost less. Put another way, our findings inform ways to reinvest health care dollars as financial incentives for PCPs to adopt this new paradigm. Public health departments could provide grants or harm reduction kit supplies directly to PCPs to offset these costs as they do in some places with syringe service programs and/or increase Medicaid reimbursements for providing addiction care in primary care,” they write.
Data help make the case
Dinah Applewhite, MD, a primary care physician and addiction medicine specialist at Massachusetts General Hospital in Boston, who was not part of the study, said clinicians there have seen the benefits of integrating various aspects of addiction medicine into primary care but these data on outcomes and cost-effectiveness can help make the case to hospital leaders, legislators, and grant providers.
The primary care setting also provides a chance to engage patients around their injection practice and explore ways to minimize risk, she said.
“By offering them these kits, it lets them know your priority is their safety and well-being,” Dr. Applewhite said.
She noted that the linkage to primary care was low for patients who inject drugs, which speaks to the need for models in addition to this one, such as bringing primary care clinicians into syringe service programs.
“The medical establishment has a lot to learn from these programs,” she said.
Practices need support
She said it’s important to note that primary care practices need support from administrative leaders, philanthropists, and grant providers to help cover the costs.
“It’s one of the barriers to doing this,” she said. “There isn’t a mechanism to pay for this.”
Sarah Bagley, MD, a primary care physician at Boston Medical Center and medical director of BMC’s Center for Addiction Treatment for Adolescents/Young Adults Who Use Substances told this publication she was excited to see that the addition of harm reduction kits to buprenorphine seemed to have the optimal effect in improving outcomes. People with substance abuse disorders should feel they are welcome in primary care even if they are not yet ready to stop drug use, she said.
She said she was also glad to see increased life expectancy with these interventions. The news of overdose deaths contributing to a decrease in life expectancy can be overwhelming, she said.
But this study, she says, offers a road map for addressing the overdose crisis “by including harm reduction in the substance abuse care we provide.”
She pointed out that the study showed that costs increase per patient with both interventions, compared with the status quo. The study found that health care costs per person during a lifetime increased, compared with the status quo, by 69.1% for BUP and 74.3% for BUP plus HR.
But it’s important to understand the reason for that, she said: “The cost was higher because people were staying alive.”
She said it may help to compare giving optimal care to people who have substance abuse disorders with giving optimal care to people with other chronic conditions, such as diabetes, who may not always adhere to recommended diets or treatment regimens.
“We still invite those patients in and work with them based on where they are,” she said.
Growing epidemic
The researchers point to the urgent need for solutions given the U.S. opioid epidemic, which has led to increasing numbers of overdoses and injection drug use–related infections, such as infective endocarditis, and severe skin and soft tissue infections.
They point out that primary care providers are the largest clinical workforce in the United States, but few of their practices offer comprehensive addiction care onsite.
“Primary care practices are a practical place to integrate addiction services, where PCPs can prescribe buprenorphine and deliver harm reduction kits,” they write.
Coauthor Dr. Kimmel reports personal fees from Massachusetts Department of Public Health, Bureau of Substance Addiction Services Overdose Education and Prevention Program, and American Academy of Addiction Psychiatry, Opioid Response Network for harm reduction education outside the submitted work and previous consulting with Abt Associates on a Massachusetts Department of Public Health–funded project to improve access to medications for opioid use disorder treatment. Dr. Applewhite and Dr. Bagley report no relevant financial relationships.
JAMA NETWORK OPEN
FDA clears first patch to treat axillary hyperhidrosis
The Food and Drug Administration on April 13 cleared the first patch to reduce excessive underarm sweating for adults with primary axillary hyperhidrosis.
The single-use, disposable, prescription-only patch will be marketed as Brella. It consists of a sodium sheet with an adhesive overlay. A health care provider applies it to the patient’s underarm for up to 3 minutes and then repeats the process on the other underarm.
The developer, Candesant Biomedical, says the patch uses the company’s patented targeted alkali thermolysis (TAT) technology, which was built on the principle that heat is generated when sodium reacts with water in sweat. “The thermal energy created by the sodium sheet is precisely localized, microtargeting sweat glands to significantly reduce sweat production,” according to the company’s press release announcing the FDA decision.
FDA clearance was based on data from the pivotal randomized, double-blind, multicenter SAHARA study, which indicated that the product is effective and well tolerated.
Patients experienced a reduction in sweat that was maintained for 3 months or longer, according to trial results.
The SAHARA trial results were reported in a late-breaking abstract at the annual meeting of the American Academy of Dermatology in March.
The trial enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 (indicating frequent sweating or sweating that always interferes with daily activities). Trial participants were randomly assigned to receive either an active TAT or a sham patch, which was applied for up to 3 minutes.
At the meeting, lead investigator David M. Pariser, MD, a dermatologist practicing in Norfolk, Va., reported that at 4 weeks, 63.6% of patients in the active patch group achieved an HDSS score of 1 or 2, compared with 44.2% of those in the sham treatment group (P = .0332). Also, 43.2% of those in the active-patch group achieved an improvement of 2 points or greater on the HDSS, as compared with 16.3% of those in the sham treatment group (P = .0107) .
In addition, 9.1% of those in the active-patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” Dr. Pariser said at the meeting.
As for adverse events (AEs), 13 patients in the active-patch group experienced AEs at the treatment site. Six patients experienced erythema; four experienced erosion; two experienced burning, itching, or stinging; and one had underarm odor.
“The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” Dr. Pariser said. He noted that most AEs resolved in fewer than 2 weeks, and all AEs were mild to moderate.
According to the International Hyperhidrosis Society, about 1.3 million people in the United States have axillary hyperhidrosis, and about a third report that sweating is barely tolerable and frequently interferes with daily activities or is intolerable and always interferes with daily activities.
The patch will be available within months in select U.S. markets beginning in late summer. The company says the markets will be listed on its website.
A company representative told this news organization that because it is an in-office procedure, pricing will vary, depending on the practice. “With that said, Candesant expects doctors will charge about the same for one session of the Brella SweatControl Patch as they would for a high-end, in-office facial or chemical peel,” the representative said.
Dr. Pariser is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol-Myers Squibb, the Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration on April 13 cleared the first patch to reduce excessive underarm sweating for adults with primary axillary hyperhidrosis.
The single-use, disposable, prescription-only patch will be marketed as Brella. It consists of a sodium sheet with an adhesive overlay. A health care provider applies it to the patient’s underarm for up to 3 minutes and then repeats the process on the other underarm.
The developer, Candesant Biomedical, says the patch uses the company’s patented targeted alkali thermolysis (TAT) technology, which was built on the principle that heat is generated when sodium reacts with water in sweat. “The thermal energy created by the sodium sheet is precisely localized, microtargeting sweat glands to significantly reduce sweat production,” according to the company’s press release announcing the FDA decision.
FDA clearance was based on data from the pivotal randomized, double-blind, multicenter SAHARA study, which indicated that the product is effective and well tolerated.
Patients experienced a reduction in sweat that was maintained for 3 months or longer, according to trial results.
The SAHARA trial results were reported in a late-breaking abstract at the annual meeting of the American Academy of Dermatology in March.
The trial enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 (indicating frequent sweating or sweating that always interferes with daily activities). Trial participants were randomly assigned to receive either an active TAT or a sham patch, which was applied for up to 3 minutes.
At the meeting, lead investigator David M. Pariser, MD, a dermatologist practicing in Norfolk, Va., reported that at 4 weeks, 63.6% of patients in the active patch group achieved an HDSS score of 1 or 2, compared with 44.2% of those in the sham treatment group (P = .0332). Also, 43.2% of those in the active-patch group achieved an improvement of 2 points or greater on the HDSS, as compared with 16.3% of those in the sham treatment group (P = .0107) .
In addition, 9.1% of those in the active-patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” Dr. Pariser said at the meeting.
As for adverse events (AEs), 13 patients in the active-patch group experienced AEs at the treatment site. Six patients experienced erythema; four experienced erosion; two experienced burning, itching, or stinging; and one had underarm odor.
“The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” Dr. Pariser said. He noted that most AEs resolved in fewer than 2 weeks, and all AEs were mild to moderate.
According to the International Hyperhidrosis Society, about 1.3 million people in the United States have axillary hyperhidrosis, and about a third report that sweating is barely tolerable and frequently interferes with daily activities or is intolerable and always interferes with daily activities.
The patch will be available within months in select U.S. markets beginning in late summer. The company says the markets will be listed on its website.
A company representative told this news organization that because it is an in-office procedure, pricing will vary, depending on the practice. “With that said, Candesant expects doctors will charge about the same for one session of the Brella SweatControl Patch as they would for a high-end, in-office facial or chemical peel,” the representative said.
Dr. Pariser is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol-Myers Squibb, the Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration on April 13 cleared the first patch to reduce excessive underarm sweating for adults with primary axillary hyperhidrosis.
The single-use, disposable, prescription-only patch will be marketed as Brella. It consists of a sodium sheet with an adhesive overlay. A health care provider applies it to the patient’s underarm for up to 3 minutes and then repeats the process on the other underarm.
The developer, Candesant Biomedical, says the patch uses the company’s patented targeted alkali thermolysis (TAT) technology, which was built on the principle that heat is generated when sodium reacts with water in sweat. “The thermal energy created by the sodium sheet is precisely localized, microtargeting sweat glands to significantly reduce sweat production,” according to the company’s press release announcing the FDA decision.
FDA clearance was based on data from the pivotal randomized, double-blind, multicenter SAHARA study, which indicated that the product is effective and well tolerated.
Patients experienced a reduction in sweat that was maintained for 3 months or longer, according to trial results.
The SAHARA trial results were reported in a late-breaking abstract at the annual meeting of the American Academy of Dermatology in March.
The trial enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 (indicating frequent sweating or sweating that always interferes with daily activities). Trial participants were randomly assigned to receive either an active TAT or a sham patch, which was applied for up to 3 minutes.
At the meeting, lead investigator David M. Pariser, MD, a dermatologist practicing in Norfolk, Va., reported that at 4 weeks, 63.6% of patients in the active patch group achieved an HDSS score of 1 or 2, compared with 44.2% of those in the sham treatment group (P = .0332). Also, 43.2% of those in the active-patch group achieved an improvement of 2 points or greater on the HDSS, as compared with 16.3% of those in the sham treatment group (P = .0107) .
In addition, 9.1% of those in the active-patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” Dr. Pariser said at the meeting.
As for adverse events (AEs), 13 patients in the active-patch group experienced AEs at the treatment site. Six patients experienced erythema; four experienced erosion; two experienced burning, itching, or stinging; and one had underarm odor.
“The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” Dr. Pariser said. He noted that most AEs resolved in fewer than 2 weeks, and all AEs were mild to moderate.
According to the International Hyperhidrosis Society, about 1.3 million people in the United States have axillary hyperhidrosis, and about a third report that sweating is barely tolerable and frequently interferes with daily activities or is intolerable and always interferes with daily activities.
The patch will be available within months in select U.S. markets beginning in late summer. The company says the markets will be listed on its website.
A company representative told this news organization that because it is an in-office procedure, pricing will vary, depending on the practice. “With that said, Candesant expects doctors will charge about the same for one session of the Brella SweatControl Patch as they would for a high-end, in-office facial or chemical peel,” the representative said.
Dr. Pariser is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol-Myers Squibb, the Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.
A version of this article originally appeared on Medscape.com.
Racial disparities not found in chronic hepatitis B treatment initiation
Researchers studying differences in treatment initiation for chronic hepatitis B (CHB) among a large, multiracial cohort in North America did not find evidence of disparities by race or socioeconomic status.
.
That gap suggests that treatment guidelines need to be simplified and that efforts to increase hepatitis B virus (HBV) awareness and train more clinicians are needed to achieve the World Health Organization’s goal of eliminating HBV by 2030, the researchers write.
The Hepatitis B Research Network study was published online in JAMA Network Open.
The prevalence of CHB in the United States is estimated at 2.4 million. It disproportionately affects persons of Asian or African descent, the investigators note. Their study examined whether treatment initiation and outcomes differ between African American and Black, Asian, and White participants, as well as between African American and Black participants born in North America and East or West Africa.
The research involved 1,550 adult patients: 1,157 Asian American, 193 African American or Black (39 born in the United States, 90 in East Africa, 53 in West Africa, and 11 elsewhere), 157 White, and 43 who identified as being of “other races.” All had CHB but were not receiving antiviral treatment at enrollment.
Participants came from 20 centers in the United States and one in Canada. They underwent clinical and laboratory assessments and could receive anti-HBV treatment after they enrolled. Enrollment was from Jan. 14, 2011, to Jan. 28, 2018. Participants were followed at 12 and 24 weeks and every 24 weeks thereafter in the longitudinal cohort study by Mandana Khalili, MD, division of gastroenterology and hepatology, University of California, San Francisco, and colleagues.
Information on patients’ country of birth, duration of U.S. or Canadian residency, educational level, employment, insurance, prior antiviral treatment, family history of HBV or hepatocellular carcinoma (HCC), and mode of transmission were collected by research coordinators.
Treatment initiation
During the study period, slightly fewer than one-third (32.5%) of the participants initiated treatment. The incidences were 4.8 per 100 person-years in African American or Black participants, 9.9 per 100 person-years in Asian participants, 6.6 per 100 person-years in White participants, and 7.9 per 100 person-years in those of other races (P < .001).
A lower percentage of African American and Black participants (14%) met the American Association for the Study of Liver Diseases treatment criteria, compared with Asian (22%) and White (27%) participants (P = .01).
When the researchers compared cumulative probability of initiating treatment by race for those who met criteria for treatment, they found no significant differences by race.
At 72 weeks, initiation probability was 0.45 for African American and Black patients and 0.51 for Asian and White patients (P = .68). Similarly, among African American and Black participants who met treatment criteria, there were no significant differences in cumulative probability of treatment by region of birth.
The cumulative percentage of treatment initiation for those who met guideline-based criteria was 62%.
“Among participants with a treatment indication, treatment rates did not differ significantly by race, despite marked differences in educational level, income, and type of health care insurance across the racial groups,” the researchers write. “Moreover, race was not an independent estimator of treatment initiation when adjusting for known factors associated with a higher risk of adverse clinical outcomes, namely, HBV DNA, disease severity, sex, and age.”
Adverse liver outcomes (hepatic decompensation, HCC, liver transplant, and death) were rare and did not vary significantly by race, the researchers write.
One study limitation is that participants were linked to specialty liver clinics, so the findings may not be generalizable to patients who receive care in other settings, the authors note.
The results are “reassuring,” said senior author Anna S. Lok, MD, division of gastroenterology and hepatology at University of Michigan in Ann Arbor. However, she noted, study participants had already overcome barriers to receiving care at major academic centers.
“Once you get into the big academic liver centers, then maybe everything is equal, but in the real world, a lot of people don’t ever get to the big liver centers,” she said. The question becomes: “Are we serving only a portion of the patient population?”
Many factors drive the decision to undergo treatment, including the doctor’s opinion as to need and the patient’s desire to receive treatment, she said.
The study participants who were more likely to get treated were those with higher-level disease who had a stronger indication for treatment, Dr. Lok said.
Finding the disparities
Centers for Disease Control and Prevention statistics show that Black people are 3.9 times more likely to have CHB and 2.5 times more likely to die from it than White people, notes H. Nina Kim, MD, with the department of medicine, University of Washington, Seattle, in an accompanying invited commentary.
“The fact that we have not observed racial disparities in treatment initiation does not mean none exist; it means we have to look harder to find them,” she writes.
“We need to examine whether our guidelines for HBV treatment are so complex that it becomes the purview of specialists, thereby restricting access and deepening inequities,” Dr. Kim adds. “We should look closely at retention in care, the step that precedes treatment, and stratify this outcome by race and ethnicity.”
Primary care physicians in some regions might find it difficult to manage patients who have hepatitis B because they see so few of them, Dr. Lok noted.
Dr. Khalili has received grants and consulting fees from Gilead Sciences Inc and grants from Intercept Pharmaceuticals outside the submitted work. Dr. Lok has received grants from Target and consultant fees from Abbott, Ambys, Arbutus, Chroma, Clear B, Enanta, Enochian, GNI, GlaxoSmithKline, Eli Lilly, and Virion outside the submitted work. Coauthors have received grants, consulting fees, or personal fees from Bayer, Boston Scientific, Exact Sciences, Fujifilm Medical Sciences, Gilead Sciences, Glycotest, Redhill Biopharma, Target RWE, MedEd Design, Pontifax, Global Life, the Lynx Group, AstraZeneca, Eisai, Novartis Venture Fund, Grail, QED Therapeutics, Genentech, Hepion Pharmaceuticals, Roche, Abbott, AbbVie, and Pfizer. Dr. Kim has received grants from Gilead Sciences (paid to her institution) outside the submitted work.
A version of this article first appeared on Medscape.com.
Researchers studying differences in treatment initiation for chronic hepatitis B (CHB) among a large, multiracial cohort in North America did not find evidence of disparities by race or socioeconomic status.
.
That gap suggests that treatment guidelines need to be simplified and that efforts to increase hepatitis B virus (HBV) awareness and train more clinicians are needed to achieve the World Health Organization’s goal of eliminating HBV by 2030, the researchers write.
The Hepatitis B Research Network study was published online in JAMA Network Open.
The prevalence of CHB in the United States is estimated at 2.4 million. It disproportionately affects persons of Asian or African descent, the investigators note. Their study examined whether treatment initiation and outcomes differ between African American and Black, Asian, and White participants, as well as between African American and Black participants born in North America and East or West Africa.
The research involved 1,550 adult patients: 1,157 Asian American, 193 African American or Black (39 born in the United States, 90 in East Africa, 53 in West Africa, and 11 elsewhere), 157 White, and 43 who identified as being of “other races.” All had CHB but were not receiving antiviral treatment at enrollment.
Participants came from 20 centers in the United States and one in Canada. They underwent clinical and laboratory assessments and could receive anti-HBV treatment after they enrolled. Enrollment was from Jan. 14, 2011, to Jan. 28, 2018. Participants were followed at 12 and 24 weeks and every 24 weeks thereafter in the longitudinal cohort study by Mandana Khalili, MD, division of gastroenterology and hepatology, University of California, San Francisco, and colleagues.
Information on patients’ country of birth, duration of U.S. or Canadian residency, educational level, employment, insurance, prior antiviral treatment, family history of HBV or hepatocellular carcinoma (HCC), and mode of transmission were collected by research coordinators.
Treatment initiation
During the study period, slightly fewer than one-third (32.5%) of the participants initiated treatment. The incidences were 4.8 per 100 person-years in African American or Black participants, 9.9 per 100 person-years in Asian participants, 6.6 per 100 person-years in White participants, and 7.9 per 100 person-years in those of other races (P < .001).
A lower percentage of African American and Black participants (14%) met the American Association for the Study of Liver Diseases treatment criteria, compared with Asian (22%) and White (27%) participants (P = .01).
When the researchers compared cumulative probability of initiating treatment by race for those who met criteria for treatment, they found no significant differences by race.
At 72 weeks, initiation probability was 0.45 for African American and Black patients and 0.51 for Asian and White patients (P = .68). Similarly, among African American and Black participants who met treatment criteria, there were no significant differences in cumulative probability of treatment by region of birth.
The cumulative percentage of treatment initiation for those who met guideline-based criteria was 62%.
“Among participants with a treatment indication, treatment rates did not differ significantly by race, despite marked differences in educational level, income, and type of health care insurance across the racial groups,” the researchers write. “Moreover, race was not an independent estimator of treatment initiation when adjusting for known factors associated with a higher risk of adverse clinical outcomes, namely, HBV DNA, disease severity, sex, and age.”
Adverse liver outcomes (hepatic decompensation, HCC, liver transplant, and death) were rare and did not vary significantly by race, the researchers write.
One study limitation is that participants were linked to specialty liver clinics, so the findings may not be generalizable to patients who receive care in other settings, the authors note.
The results are “reassuring,” said senior author Anna S. Lok, MD, division of gastroenterology and hepatology at University of Michigan in Ann Arbor. However, she noted, study participants had already overcome barriers to receiving care at major academic centers.
“Once you get into the big academic liver centers, then maybe everything is equal, but in the real world, a lot of people don’t ever get to the big liver centers,” she said. The question becomes: “Are we serving only a portion of the patient population?”
Many factors drive the decision to undergo treatment, including the doctor’s opinion as to need and the patient’s desire to receive treatment, she said.
The study participants who were more likely to get treated were those with higher-level disease who had a stronger indication for treatment, Dr. Lok said.
Finding the disparities
Centers for Disease Control and Prevention statistics show that Black people are 3.9 times more likely to have CHB and 2.5 times more likely to die from it than White people, notes H. Nina Kim, MD, with the department of medicine, University of Washington, Seattle, in an accompanying invited commentary.
“The fact that we have not observed racial disparities in treatment initiation does not mean none exist; it means we have to look harder to find them,” she writes.
“We need to examine whether our guidelines for HBV treatment are so complex that it becomes the purview of specialists, thereby restricting access and deepening inequities,” Dr. Kim adds. “We should look closely at retention in care, the step that precedes treatment, and stratify this outcome by race and ethnicity.”
Primary care physicians in some regions might find it difficult to manage patients who have hepatitis B because they see so few of them, Dr. Lok noted.
Dr. Khalili has received grants and consulting fees from Gilead Sciences Inc and grants from Intercept Pharmaceuticals outside the submitted work. Dr. Lok has received grants from Target and consultant fees from Abbott, Ambys, Arbutus, Chroma, Clear B, Enanta, Enochian, GNI, GlaxoSmithKline, Eli Lilly, and Virion outside the submitted work. Coauthors have received grants, consulting fees, or personal fees from Bayer, Boston Scientific, Exact Sciences, Fujifilm Medical Sciences, Gilead Sciences, Glycotest, Redhill Biopharma, Target RWE, MedEd Design, Pontifax, Global Life, the Lynx Group, AstraZeneca, Eisai, Novartis Venture Fund, Grail, QED Therapeutics, Genentech, Hepion Pharmaceuticals, Roche, Abbott, AbbVie, and Pfizer. Dr. Kim has received grants from Gilead Sciences (paid to her institution) outside the submitted work.
A version of this article first appeared on Medscape.com.
Researchers studying differences in treatment initiation for chronic hepatitis B (CHB) among a large, multiracial cohort in North America did not find evidence of disparities by race or socioeconomic status.
.
That gap suggests that treatment guidelines need to be simplified and that efforts to increase hepatitis B virus (HBV) awareness and train more clinicians are needed to achieve the World Health Organization’s goal of eliminating HBV by 2030, the researchers write.
The Hepatitis B Research Network study was published online in JAMA Network Open.
The prevalence of CHB in the United States is estimated at 2.4 million. It disproportionately affects persons of Asian or African descent, the investigators note. Their study examined whether treatment initiation and outcomes differ between African American and Black, Asian, and White participants, as well as between African American and Black participants born in North America and East or West Africa.
The research involved 1,550 adult patients: 1,157 Asian American, 193 African American or Black (39 born in the United States, 90 in East Africa, 53 in West Africa, and 11 elsewhere), 157 White, and 43 who identified as being of “other races.” All had CHB but were not receiving antiviral treatment at enrollment.
Participants came from 20 centers in the United States and one in Canada. They underwent clinical and laboratory assessments and could receive anti-HBV treatment after they enrolled. Enrollment was from Jan. 14, 2011, to Jan. 28, 2018. Participants were followed at 12 and 24 weeks and every 24 weeks thereafter in the longitudinal cohort study by Mandana Khalili, MD, division of gastroenterology and hepatology, University of California, San Francisco, and colleagues.
Information on patients’ country of birth, duration of U.S. or Canadian residency, educational level, employment, insurance, prior antiviral treatment, family history of HBV or hepatocellular carcinoma (HCC), and mode of transmission were collected by research coordinators.
Treatment initiation
During the study period, slightly fewer than one-third (32.5%) of the participants initiated treatment. The incidences were 4.8 per 100 person-years in African American or Black participants, 9.9 per 100 person-years in Asian participants, 6.6 per 100 person-years in White participants, and 7.9 per 100 person-years in those of other races (P < .001).
A lower percentage of African American and Black participants (14%) met the American Association for the Study of Liver Diseases treatment criteria, compared with Asian (22%) and White (27%) participants (P = .01).
When the researchers compared cumulative probability of initiating treatment by race for those who met criteria for treatment, they found no significant differences by race.
At 72 weeks, initiation probability was 0.45 for African American and Black patients and 0.51 for Asian and White patients (P = .68). Similarly, among African American and Black participants who met treatment criteria, there were no significant differences in cumulative probability of treatment by region of birth.
The cumulative percentage of treatment initiation for those who met guideline-based criteria was 62%.
“Among participants with a treatment indication, treatment rates did not differ significantly by race, despite marked differences in educational level, income, and type of health care insurance across the racial groups,” the researchers write. “Moreover, race was not an independent estimator of treatment initiation when adjusting for known factors associated with a higher risk of adverse clinical outcomes, namely, HBV DNA, disease severity, sex, and age.”
Adverse liver outcomes (hepatic decompensation, HCC, liver transplant, and death) were rare and did not vary significantly by race, the researchers write.
One study limitation is that participants were linked to specialty liver clinics, so the findings may not be generalizable to patients who receive care in other settings, the authors note.
The results are “reassuring,” said senior author Anna S. Lok, MD, division of gastroenterology and hepatology at University of Michigan in Ann Arbor. However, she noted, study participants had already overcome barriers to receiving care at major academic centers.
“Once you get into the big academic liver centers, then maybe everything is equal, but in the real world, a lot of people don’t ever get to the big liver centers,” she said. The question becomes: “Are we serving only a portion of the patient population?”
Many factors drive the decision to undergo treatment, including the doctor’s opinion as to need and the patient’s desire to receive treatment, she said.
The study participants who were more likely to get treated were those with higher-level disease who had a stronger indication for treatment, Dr. Lok said.
Finding the disparities
Centers for Disease Control and Prevention statistics show that Black people are 3.9 times more likely to have CHB and 2.5 times more likely to die from it than White people, notes H. Nina Kim, MD, with the department of medicine, University of Washington, Seattle, in an accompanying invited commentary.
“The fact that we have not observed racial disparities in treatment initiation does not mean none exist; it means we have to look harder to find them,” she writes.
“We need to examine whether our guidelines for HBV treatment are so complex that it becomes the purview of specialists, thereby restricting access and deepening inequities,” Dr. Kim adds. “We should look closely at retention in care, the step that precedes treatment, and stratify this outcome by race and ethnicity.”
Primary care physicians in some regions might find it difficult to manage patients who have hepatitis B because they see so few of them, Dr. Lok noted.
Dr. Khalili has received grants and consulting fees from Gilead Sciences Inc and grants from Intercept Pharmaceuticals outside the submitted work. Dr. Lok has received grants from Target and consultant fees from Abbott, Ambys, Arbutus, Chroma, Clear B, Enanta, Enochian, GNI, GlaxoSmithKline, Eli Lilly, and Virion outside the submitted work. Coauthors have received grants, consulting fees, or personal fees from Bayer, Boston Scientific, Exact Sciences, Fujifilm Medical Sciences, Gilead Sciences, Glycotest, Redhill Biopharma, Target RWE, MedEd Design, Pontifax, Global Life, the Lynx Group, AstraZeneca, Eisai, Novartis Venture Fund, Grail, QED Therapeutics, Genentech, Hepion Pharmaceuticals, Roche, Abbott, AbbVie, and Pfizer. Dr. Kim has received grants from Gilead Sciences (paid to her institution) outside the submitted work.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
SARS-CoV-2 crosses placenta and infects brains of two infants: ‘This is a first’
, according to a study published online today in Pediatrics .
One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.
Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.
“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
Both infants negative for the virus at birth
The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.
Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.
Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.
Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.
“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.
Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.
Seizures started on day 1 of life
The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.
“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.
Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.
Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.
The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.
Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.
Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
Mothers had very different presentations
Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.
One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.
In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.
He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
Instances are rare
The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.
Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”
Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.
Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.
, according to a study published online today in Pediatrics .
One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.
Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.
“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
Both infants negative for the virus at birth
The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.
Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.
Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.
Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.
“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.
Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.
Seizures started on day 1 of life
The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.
“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.
Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.
Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.
The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.
Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.
Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
Mothers had very different presentations
Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.
One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.
In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.
He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
Instances are rare
The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.
Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”
Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.
Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.
, according to a study published online today in Pediatrics .
One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.
Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.
“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
Both infants negative for the virus at birth
The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.
Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.
Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.
Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.
“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.
Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.
Seizures started on day 1 of life
The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.
“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.
Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.
Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.
The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.
Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.
Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
Mothers had very different presentations
Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.
One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.
In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.
He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
Instances are rare
The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.
Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”
Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.
Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.
FROM PEDIATRICS
Infant and maternal weight gain together amplify obesity risk
Rapid weight gain (RWG) in infants and the mother’s prepregnancy overweight have a synergistic effect in increasing the odds that a child will develop overweight or obesity, new research suggests.
Findings were published online in Pediatrics.
Each factor has independently been associated with higher risk of childhood obesity but whether the two factors together exacerbate the risk has not been well studied, according to the authors led by Stephanie Gilley, MD, PhD, department of pediatrics, section of nutrition, University of Colorado at Denver, Aurora.
“Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity,” the authors conclude.
Dr. Gilley’s team studied mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort. RWG was defined as a weight-for-age z score increase of at least 0.67 from birth to 3-7 months.
They found that RWG boosted the link between prepregnancy body mass index (ppBMI) and BMI z score, especially in female infants. Females exposed to both maternal obesity with RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) “nearly at the cutoff for classification of obesity,” compared with those exposed to normal ppBMI with no RWG, who had an average childhood BMI at the 51st percentile.
“Currently, our nutrition recommendations as pediatricians are that all children are fed the same, essentially, after they’re born. We don’t have different growth parameters or different trajectories or targets for children who may have had different in utero exposures,” Dr. Gilley said.
Do some children need more monitoring for RWG?
Though we can’t necessarily draw conclusions from this one study, she says, the findings raise the question of whether children who were exposed in utero to obesity should be monitored for RWG more closely.
Lydia Shook, MD, Mass General Brigham maternal-fetal specialist and codirector of the Diabetes in Pregnancy Program at Massachusetts General Hospital in Boston, said she was struck by the finding in this study that with female infants, but not males, RWG significantly modified the association between ppBMI and early childhood BMI z scores.
“It’s an interesting finding and should be followed up with larger cohorts,” she said, noting that some previous studies have shown males are more vulnerable to maternal obesity and RWG.
“[Often] when we stratify by sex, you really need larger groups to be able to see the differences well,” Dr. Shook said.
She said she also found it interesting that when the researchers adjusted for breastfeeding status or caloric intake in childhood, the findings did not substantially change.
“That’s something that would warrant further investigation in an observational study or controlled trial,” Dr. Shook said.
Preventing rapid weight gain
The authors note that they did not consider possible interventions for preventing RGW in the study, although there are many, Dr. Gilley said.
Dr. Gilley also noted that a limitation of this study is that the population studied was primarily White.
Recent studies have shown the benefits of responsive parenting (RP) interventions, including a large study in 2022 geared toward Black families to teach better infant sleep practices as a way to prevent rapid weight gain.
That study, which tested the SAAF intervention, (Strong African American Families) found that “RP infants were nearly half as likely to experience upward crossing of two major weight-for-age percentile lines (14.1%), compared with control infants (24.2%); P = .09; odds ratio, 0.52; 95% confidence interval, 0.24-1.12.”
Along with sleep interventions, Dr. Gilley said, some researchers are studying the effects on RWG of better paternal engagement, or more involvement with the Women, Infants, and Children program, particularly with lower-income families.
Other studies have looked at breastfeeding vs. formula feeding – “but there have been mixed results there” – and responsive feeding practices, such as teaching families to recognize when a baby is full.
Dr. Gilley said she hopes this work will help broaden the thinking when it comes to infant weight gain.
“We spend a lot of time thinking about babies who are not growing fast enough and very little time thinking about babies who are growing too fast,” she said, “especially in those first 4-6 months of life.”
Dr. Gilley points to a study that illustrates that point. Pesch et al. concluded in a 2021 study based on interviews that pediatricians “are uncertain about the concept, definition, management, and long-term risks of rapid infant weight gain.”
Authors and Dr. Gilley declare no relevant financial relationships.
Rapid weight gain (RWG) in infants and the mother’s prepregnancy overweight have a synergistic effect in increasing the odds that a child will develop overweight or obesity, new research suggests.
Findings were published online in Pediatrics.
Each factor has independently been associated with higher risk of childhood obesity but whether the two factors together exacerbate the risk has not been well studied, according to the authors led by Stephanie Gilley, MD, PhD, department of pediatrics, section of nutrition, University of Colorado at Denver, Aurora.
“Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity,” the authors conclude.
Dr. Gilley’s team studied mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort. RWG was defined as a weight-for-age z score increase of at least 0.67 from birth to 3-7 months.
They found that RWG boosted the link between prepregnancy body mass index (ppBMI) and BMI z score, especially in female infants. Females exposed to both maternal obesity with RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) “nearly at the cutoff for classification of obesity,” compared with those exposed to normal ppBMI with no RWG, who had an average childhood BMI at the 51st percentile.
“Currently, our nutrition recommendations as pediatricians are that all children are fed the same, essentially, after they’re born. We don’t have different growth parameters or different trajectories or targets for children who may have had different in utero exposures,” Dr. Gilley said.
Do some children need more monitoring for RWG?
Though we can’t necessarily draw conclusions from this one study, she says, the findings raise the question of whether children who were exposed in utero to obesity should be monitored for RWG more closely.
Lydia Shook, MD, Mass General Brigham maternal-fetal specialist and codirector of the Diabetes in Pregnancy Program at Massachusetts General Hospital in Boston, said she was struck by the finding in this study that with female infants, but not males, RWG significantly modified the association between ppBMI and early childhood BMI z scores.
“It’s an interesting finding and should be followed up with larger cohorts,” she said, noting that some previous studies have shown males are more vulnerable to maternal obesity and RWG.
“[Often] when we stratify by sex, you really need larger groups to be able to see the differences well,” Dr. Shook said.
She said she also found it interesting that when the researchers adjusted for breastfeeding status or caloric intake in childhood, the findings did not substantially change.
“That’s something that would warrant further investigation in an observational study or controlled trial,” Dr. Shook said.
Preventing rapid weight gain
The authors note that they did not consider possible interventions for preventing RGW in the study, although there are many, Dr. Gilley said.
Dr. Gilley also noted that a limitation of this study is that the population studied was primarily White.
Recent studies have shown the benefits of responsive parenting (RP) interventions, including a large study in 2022 geared toward Black families to teach better infant sleep practices as a way to prevent rapid weight gain.
That study, which tested the SAAF intervention, (Strong African American Families) found that “RP infants were nearly half as likely to experience upward crossing of two major weight-for-age percentile lines (14.1%), compared with control infants (24.2%); P = .09; odds ratio, 0.52; 95% confidence interval, 0.24-1.12.”
Along with sleep interventions, Dr. Gilley said, some researchers are studying the effects on RWG of better paternal engagement, or more involvement with the Women, Infants, and Children program, particularly with lower-income families.
Other studies have looked at breastfeeding vs. formula feeding – “but there have been mixed results there” – and responsive feeding practices, such as teaching families to recognize when a baby is full.
Dr. Gilley said she hopes this work will help broaden the thinking when it comes to infant weight gain.
“We spend a lot of time thinking about babies who are not growing fast enough and very little time thinking about babies who are growing too fast,” she said, “especially in those first 4-6 months of life.”
Dr. Gilley points to a study that illustrates that point. Pesch et al. concluded in a 2021 study based on interviews that pediatricians “are uncertain about the concept, definition, management, and long-term risks of rapid infant weight gain.”
Authors and Dr. Gilley declare no relevant financial relationships.
Rapid weight gain (RWG) in infants and the mother’s prepregnancy overweight have a synergistic effect in increasing the odds that a child will develop overweight or obesity, new research suggests.
Findings were published online in Pediatrics.
Each factor has independently been associated with higher risk of childhood obesity but whether the two factors together exacerbate the risk has not been well studied, according to the authors led by Stephanie Gilley, MD, PhD, department of pediatrics, section of nutrition, University of Colorado at Denver, Aurora.
“Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity,” the authors conclude.
Dr. Gilley’s team studied mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort. RWG was defined as a weight-for-age z score increase of at least 0.67 from birth to 3-7 months.
They found that RWG boosted the link between prepregnancy body mass index (ppBMI) and BMI z score, especially in female infants. Females exposed to both maternal obesity with RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) “nearly at the cutoff for classification of obesity,” compared with those exposed to normal ppBMI with no RWG, who had an average childhood BMI at the 51st percentile.
“Currently, our nutrition recommendations as pediatricians are that all children are fed the same, essentially, after they’re born. We don’t have different growth parameters or different trajectories or targets for children who may have had different in utero exposures,” Dr. Gilley said.
Do some children need more monitoring for RWG?
Though we can’t necessarily draw conclusions from this one study, she says, the findings raise the question of whether children who were exposed in utero to obesity should be monitored for RWG more closely.
Lydia Shook, MD, Mass General Brigham maternal-fetal specialist and codirector of the Diabetes in Pregnancy Program at Massachusetts General Hospital in Boston, said she was struck by the finding in this study that with female infants, but not males, RWG significantly modified the association between ppBMI and early childhood BMI z scores.
“It’s an interesting finding and should be followed up with larger cohorts,” she said, noting that some previous studies have shown males are more vulnerable to maternal obesity and RWG.
“[Often] when we stratify by sex, you really need larger groups to be able to see the differences well,” Dr. Shook said.
She said she also found it interesting that when the researchers adjusted for breastfeeding status or caloric intake in childhood, the findings did not substantially change.
“That’s something that would warrant further investigation in an observational study or controlled trial,” Dr. Shook said.
Preventing rapid weight gain
The authors note that they did not consider possible interventions for preventing RGW in the study, although there are many, Dr. Gilley said.
Dr. Gilley also noted that a limitation of this study is that the population studied was primarily White.
Recent studies have shown the benefits of responsive parenting (RP) interventions, including a large study in 2022 geared toward Black families to teach better infant sleep practices as a way to prevent rapid weight gain.
That study, which tested the SAAF intervention, (Strong African American Families) found that “RP infants were nearly half as likely to experience upward crossing of two major weight-for-age percentile lines (14.1%), compared with control infants (24.2%); P = .09; odds ratio, 0.52; 95% confidence interval, 0.24-1.12.”
Along with sleep interventions, Dr. Gilley said, some researchers are studying the effects on RWG of better paternal engagement, or more involvement with the Women, Infants, and Children program, particularly with lower-income families.
Other studies have looked at breastfeeding vs. formula feeding – “but there have been mixed results there” – and responsive feeding practices, such as teaching families to recognize when a baby is full.
Dr. Gilley said she hopes this work will help broaden the thinking when it comes to infant weight gain.
“We spend a lot of time thinking about babies who are not growing fast enough and very little time thinking about babies who are growing too fast,” she said, “especially in those first 4-6 months of life.”
Dr. Gilley points to a study that illustrates that point. Pesch et al. concluded in a 2021 study based on interviews that pediatricians “are uncertain about the concept, definition, management, and long-term risks of rapid infant weight gain.”
Authors and Dr. Gilley declare no relevant financial relationships.
FROM PEDIATRICS
Frustration over iPLEDGE evident at FDA meeting
During 2 days of after the chaotic rollout of the new REMS platform at the end of 2021.
On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.
However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.
The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.
Lockout based on outdated reasoning
John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.
“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.
Among the barriers is the 19-day lockout period for people who can get pregnant and miss the 7-day window for picking up their prescriptions. They must then wait 19 days to get a pregnancy test to clear them for receiving the medication.
Gregory Wedin, PharmD, pharmacovigilance and risk management director of Upsher-Smith Laboratories, who spoke on behalf of the Isotretinoin Products Manufacturer Group (IPMG), which manages iPLEDGE, said, “The rationale for the 19-day wait is to ensure the next confirmatory pregnancy test is completed after the most fertile period of the menstrual cycle is passed.”
Many don’t have a monthly cycle
But Dr. Barbieri said that reasoning is outdated.
“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”
He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.
Communication with IPMG
Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.
“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”
Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.
She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.
In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”
Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.
“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”
IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
Monthly attestation for counseling patients who cannot get pregnant
Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”
He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.
“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
Home pregnancy testing
The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.
During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.
Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.
“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.
Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
Workaround to avoid falsification
Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.
“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”
Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.
“Home pregnancy tests are highly sensitive, equal to the ones done in CLIA-certified labs, and highly accurate when interpreted by a dermatology provider,” said Dr. Graber, who spoke on behalf of the AARS during the open public hearing.
“Notably, CLIA [Clinical Laboratory Improvement Amendments] certification is not required by other REMS programs” for teratogenic drugs, she added.
Dr. Graber said it’s important to note that in the time the pandemic exceptions have been made for isotretinoin patients, “there has been no reported spike in pregnancy in the past three years.
“We do have some data to show that it is not imposing additional harms,” she said.
Suggestions for improvement
At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.
Dr. Green advocated for the addition of an iPLEDGE mobile app.
“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.
Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.
The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”
Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
Exceptions for long-acting contraceptives?
Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.
“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”
She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
Prescriptions for emergency contraception
Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.
“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”
Dr. Dublin also called for better transparency surrounding the role of IPMG.
She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.
“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
During 2 days of after the chaotic rollout of the new REMS platform at the end of 2021.
On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.
However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.
The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.
Lockout based on outdated reasoning
John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.
“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.
Among the barriers is the 19-day lockout period for people who can get pregnant and miss the 7-day window for picking up their prescriptions. They must then wait 19 days to get a pregnancy test to clear them for receiving the medication.
Gregory Wedin, PharmD, pharmacovigilance and risk management director of Upsher-Smith Laboratories, who spoke on behalf of the Isotretinoin Products Manufacturer Group (IPMG), which manages iPLEDGE, said, “The rationale for the 19-day wait is to ensure the next confirmatory pregnancy test is completed after the most fertile period of the menstrual cycle is passed.”
Many don’t have a monthly cycle
But Dr. Barbieri said that reasoning is outdated.
“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”
He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.
Communication with IPMG
Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.
“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”
Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.
She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.
In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”
Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.
“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”
IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
Monthly attestation for counseling patients who cannot get pregnant
Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”
He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.
“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
Home pregnancy testing
The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.
During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.
Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.
“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.
Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
Workaround to avoid falsification
Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.
“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”
Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.
“Home pregnancy tests are highly sensitive, equal to the ones done in CLIA-certified labs, and highly accurate when interpreted by a dermatology provider,” said Dr. Graber, who spoke on behalf of the AARS during the open public hearing.
“Notably, CLIA [Clinical Laboratory Improvement Amendments] certification is not required by other REMS programs” for teratogenic drugs, she added.
Dr. Graber said it’s important to note that in the time the pandemic exceptions have been made for isotretinoin patients, “there has been no reported spike in pregnancy in the past three years.
“We do have some data to show that it is not imposing additional harms,” she said.
Suggestions for improvement
At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.
Dr. Green advocated for the addition of an iPLEDGE mobile app.
“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.
Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.
The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”
Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
Exceptions for long-acting contraceptives?
Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.
“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”
She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
Prescriptions for emergency contraception
Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.
“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”
Dr. Dublin also called for better transparency surrounding the role of IPMG.
She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.
“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
During 2 days of after the chaotic rollout of the new REMS platform at the end of 2021.
On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.
However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.
The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.
Lockout based on outdated reasoning
John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.
“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.
Among the barriers is the 19-day lockout period for people who can get pregnant and miss the 7-day window for picking up their prescriptions. They must then wait 19 days to get a pregnancy test to clear them for receiving the medication.
Gregory Wedin, PharmD, pharmacovigilance and risk management director of Upsher-Smith Laboratories, who spoke on behalf of the Isotretinoin Products Manufacturer Group (IPMG), which manages iPLEDGE, said, “The rationale for the 19-day wait is to ensure the next confirmatory pregnancy test is completed after the most fertile period of the menstrual cycle is passed.”
Many don’t have a monthly cycle
But Dr. Barbieri said that reasoning is outdated.
“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”
He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.
Communication with IPMG
Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.
“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”
Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.
She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.
In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”
Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.
“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”
IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
Monthly attestation for counseling patients who cannot get pregnant
Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”
He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.
“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
Home pregnancy testing
The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.
During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.
Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.
“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.
Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
Workaround to avoid falsification
Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.
“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”
Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.
“Home pregnancy tests are highly sensitive, equal to the ones done in CLIA-certified labs, and highly accurate when interpreted by a dermatology provider,” said Dr. Graber, who spoke on behalf of the AARS during the open public hearing.
“Notably, CLIA [Clinical Laboratory Improvement Amendments] certification is not required by other REMS programs” for teratogenic drugs, she added.
Dr. Graber said it’s important to note that in the time the pandemic exceptions have been made for isotretinoin patients, “there has been no reported spike in pregnancy in the past three years.
“We do have some data to show that it is not imposing additional harms,” she said.
Suggestions for improvement
At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.
Dr. Green advocated for the addition of an iPLEDGE mobile app.
“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.
Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.
The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”
Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
Exceptions for long-acting contraceptives?
Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.
“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”
She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
Prescriptions for emergency contraception
Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.
“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”
Dr. Dublin also called for better transparency surrounding the role of IPMG.
She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.
“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
Sleep duration of Black infants increased by intervention
An intervention tailored for Black first-time mothers helped increase their infants’ sleep time, researchers have found, a notable result as many studies have shown Black infants get less sleep on average than White infants.
Less sleep has historically put Black children at higher risk for negative outcomes including obesity and poorer social-emotional functioning and cognitive development. These disparities persist into adulthood, the researchers note, as previous studies have shown.
Justin A. Lavner, PhD, with the department of psychology at the University of Georgia in Athens, led this post hoc secondary analysis of the Sleep SAAF (Strong African American Families) study, a randomized clinical trial of 234 participants comparing a responsive parenting (RP) intervention with a safety control group over the first 16 weeks post partum. The original analysis studied the effects of the intervention on rapid weight gain.
In the original analysis, the authors write that “From birth to 2, the prevalence of high weight for length (above the 95th percentile) is 25% higher among African American children compared to White children. From age 2 to 19, the rate of obesity is more than 50% higher among African American children compared to White children. Similar disparities persist into adulthood: rates of obesity are approximately 25% higher among African American adults compared to White adults.”
The differences in early rapid weight gain may be driving the disparities, the authors write.
Elements of the intervention
The intervention in the current analysis included materials delivered at the 3- and 8-week home visits focused on soothing and crying, feeding, and interactive play in the babies’ first months. Families were recruited from Augusta University Medical Center in Augusta, Ga., and had home visits at 1, 3, 8, and 16 weeks post partum.
Mothers got a packet of handouts and facilitators walked through the information with them. The measures involved hands-on activities, discussion, and videos, all tailored for Black families, the authors state.
Mothers were taught about responding appropriately at night when their baby cries, including giving the baby a couple of minutes to fall back to sleep independently and by using calming messages, such as shushing or white noise, before picking the baby up.
Babies learn to fall asleep on their own
They also learned to put infants to bed early (ideally by 8 p.m.) so the babies would be calm but awake and could learn to fall asleep on their own.
The control group’s guidance was matched for intensity and session length but focused on sleep and home safety, such as reducing the risk of sudden infant death syndrome (SIDS), keeping the baby’s sleep area close to, but away from, the mother’s bed, and preventing shaken baby syndrome.
In both groups, the 3-week visit session lasted about 90-120 minutes and the 8-week visit lasted about 45-60 minutes.
Longer sleep with the intervention
A total of 212 Black mothers, average age 22.7, were randomized – 108 to the RP group and 104 to the control group. Answers on questionnaires were analyzed and at 16 weeks post partum, infants in the RP group (relative to controls) had:
- Longer reported nighttime sleep (mean difference, 40 minutes [95% confidence interval, 3-77]).
- Longer total sleep duration (mean difference, 73 minutes [95% CI, 14-131]).
- Fewer nighttime wakings (mean difference, −0.4 wakings [95% CI, −0.6 to −0.1]).
- Greater likelihood of meeting guidelines of at least 12 hours of sleep per day (risk ratio, 1.4 [95% CI, 1.1 to 1.8]) than controls.
Findings were published in JAMA Network Open.
Additionally, mothers in the RP group more frequently reported they engaged in practices such as letting babies have a few minutes to fall back to sleep on their own (RR, 1.6 [95% CI, 1.0-2.6]) and being less likely to feed their infant just before the baby’s bedtime (RR, 0.5 [95% CI, 0.3-0.8]).
In an accompanying invited commentary, Sarah M. Honaker, PhD, department of pediatrics, Indiana University, Indianapolis, and Alicia Chung, EdD, Center for Early Childhood Health and Development at New York University, write that though the added average sleep duration is one of the most significant findings, there is a possibility of desirability bias because it was reported by the mothers after specific guidance by the facilitators.
“Nonetheless,” the editorialists write, “even if the true effect were half as small, this additional sleep duration could yield notable benefits in infant development if the effect persisted over time. The difference in night wakings between the intervention and control groups (1.8 vs 1.5 per night) at 16 weeks postpartum was statistically significant, though it is unclear whether this difference is clinically meaningful to families.”
They note that it is unclear from the study how the intervention was culturally adapted and how the adaptation might have affected outcomes.
Sleep intervention trials have focused on White families
The editorialists write that much is known about the benefits of behavioral sleep intervention in controlled trials and general population settings, and no adverse effects on infant attachment or cortisol levels have been linked to the interventions.
However, they add, “Unfortunately, this substantial progress in our understanding of infant BSI [behavioral sleep intervention] comes with a caveat, in that most previous studies have been performed with White families from mid-to-high socioeconomic backgrounds.”
Dr. Honaker and Dr. Chung write, “[I]t is important to note that much work remains to examine the acceptability, feasibility, and efficacy of infant BSI in other groups that have been historically marginalized.”
Dr. Lavner and colleagues point out that before their study, there had been little emphasis on interventions to encourage better sleep in general for Black infants, “as most early sleep interventions for this population have focused on SIDS prevention.”
“To our knowledge, Sleep SAAF is the first study to show any benefits of [an] RP intervention on sleep and sleep practices among Black infants and their families,” they write.
The researchers note that a limitation of the study is that the study sample was limited to Black first-time mothers recruited from a single medical center in Georgia.
The study by Dr. Lavner et al. was funded by the National Institutes of Health, a Harrington Faculty Fellowship from the University of Texas, and an award from the Penn State Clinical and Translational Sciences Institute supported by the National Center for Advancing Translational Sciences. Editorialist Dr. Honaker reported receiving grants from Nationwide Children’s Hospital (parent grant, Centers for Disease Control and Prevention) to evaluate the acceptability of infant behavioral sleep intervention in Black families.
An intervention tailored for Black first-time mothers helped increase their infants’ sleep time, researchers have found, a notable result as many studies have shown Black infants get less sleep on average than White infants.
Less sleep has historically put Black children at higher risk for negative outcomes including obesity and poorer social-emotional functioning and cognitive development. These disparities persist into adulthood, the researchers note, as previous studies have shown.
Justin A. Lavner, PhD, with the department of psychology at the University of Georgia in Athens, led this post hoc secondary analysis of the Sleep SAAF (Strong African American Families) study, a randomized clinical trial of 234 participants comparing a responsive parenting (RP) intervention with a safety control group over the first 16 weeks post partum. The original analysis studied the effects of the intervention on rapid weight gain.
In the original analysis, the authors write that “From birth to 2, the prevalence of high weight for length (above the 95th percentile) is 25% higher among African American children compared to White children. From age 2 to 19, the rate of obesity is more than 50% higher among African American children compared to White children. Similar disparities persist into adulthood: rates of obesity are approximately 25% higher among African American adults compared to White adults.”
The differences in early rapid weight gain may be driving the disparities, the authors write.
Elements of the intervention
The intervention in the current analysis included materials delivered at the 3- and 8-week home visits focused on soothing and crying, feeding, and interactive play in the babies’ first months. Families were recruited from Augusta University Medical Center in Augusta, Ga., and had home visits at 1, 3, 8, and 16 weeks post partum.
Mothers got a packet of handouts and facilitators walked through the information with them. The measures involved hands-on activities, discussion, and videos, all tailored for Black families, the authors state.
Mothers were taught about responding appropriately at night when their baby cries, including giving the baby a couple of minutes to fall back to sleep independently and by using calming messages, such as shushing or white noise, before picking the baby up.
Babies learn to fall asleep on their own
They also learned to put infants to bed early (ideally by 8 p.m.) so the babies would be calm but awake and could learn to fall asleep on their own.
The control group’s guidance was matched for intensity and session length but focused on sleep and home safety, such as reducing the risk of sudden infant death syndrome (SIDS), keeping the baby’s sleep area close to, but away from, the mother’s bed, and preventing shaken baby syndrome.
In both groups, the 3-week visit session lasted about 90-120 minutes and the 8-week visit lasted about 45-60 minutes.
Longer sleep with the intervention
A total of 212 Black mothers, average age 22.7, were randomized – 108 to the RP group and 104 to the control group. Answers on questionnaires were analyzed and at 16 weeks post partum, infants in the RP group (relative to controls) had:
- Longer reported nighttime sleep (mean difference, 40 minutes [95% confidence interval, 3-77]).
- Longer total sleep duration (mean difference, 73 minutes [95% CI, 14-131]).
- Fewer nighttime wakings (mean difference, −0.4 wakings [95% CI, −0.6 to −0.1]).
- Greater likelihood of meeting guidelines of at least 12 hours of sleep per day (risk ratio, 1.4 [95% CI, 1.1 to 1.8]) than controls.
Findings were published in JAMA Network Open.
Additionally, mothers in the RP group more frequently reported they engaged in practices such as letting babies have a few minutes to fall back to sleep on their own (RR, 1.6 [95% CI, 1.0-2.6]) and being less likely to feed their infant just before the baby’s bedtime (RR, 0.5 [95% CI, 0.3-0.8]).
In an accompanying invited commentary, Sarah M. Honaker, PhD, department of pediatrics, Indiana University, Indianapolis, and Alicia Chung, EdD, Center for Early Childhood Health and Development at New York University, write that though the added average sleep duration is one of the most significant findings, there is a possibility of desirability bias because it was reported by the mothers after specific guidance by the facilitators.
“Nonetheless,” the editorialists write, “even if the true effect were half as small, this additional sleep duration could yield notable benefits in infant development if the effect persisted over time. The difference in night wakings between the intervention and control groups (1.8 vs 1.5 per night) at 16 weeks postpartum was statistically significant, though it is unclear whether this difference is clinically meaningful to families.”
They note that it is unclear from the study how the intervention was culturally adapted and how the adaptation might have affected outcomes.
Sleep intervention trials have focused on White families
The editorialists write that much is known about the benefits of behavioral sleep intervention in controlled trials and general population settings, and no adverse effects on infant attachment or cortisol levels have been linked to the interventions.
However, they add, “Unfortunately, this substantial progress in our understanding of infant BSI [behavioral sleep intervention] comes with a caveat, in that most previous studies have been performed with White families from mid-to-high socioeconomic backgrounds.”
Dr. Honaker and Dr. Chung write, “[I]t is important to note that much work remains to examine the acceptability, feasibility, and efficacy of infant BSI in other groups that have been historically marginalized.”
Dr. Lavner and colleagues point out that before their study, there had been little emphasis on interventions to encourage better sleep in general for Black infants, “as most early sleep interventions for this population have focused on SIDS prevention.”
“To our knowledge, Sleep SAAF is the first study to show any benefits of [an] RP intervention on sleep and sleep practices among Black infants and their families,” they write.
The researchers note that a limitation of the study is that the study sample was limited to Black first-time mothers recruited from a single medical center in Georgia.
The study by Dr. Lavner et al. was funded by the National Institutes of Health, a Harrington Faculty Fellowship from the University of Texas, and an award from the Penn State Clinical and Translational Sciences Institute supported by the National Center for Advancing Translational Sciences. Editorialist Dr. Honaker reported receiving grants from Nationwide Children’s Hospital (parent grant, Centers for Disease Control and Prevention) to evaluate the acceptability of infant behavioral sleep intervention in Black families.
An intervention tailored for Black first-time mothers helped increase their infants’ sleep time, researchers have found, a notable result as many studies have shown Black infants get less sleep on average than White infants.
Less sleep has historically put Black children at higher risk for negative outcomes including obesity and poorer social-emotional functioning and cognitive development. These disparities persist into adulthood, the researchers note, as previous studies have shown.
Justin A. Lavner, PhD, with the department of psychology at the University of Georgia in Athens, led this post hoc secondary analysis of the Sleep SAAF (Strong African American Families) study, a randomized clinical trial of 234 participants comparing a responsive parenting (RP) intervention with a safety control group over the first 16 weeks post partum. The original analysis studied the effects of the intervention on rapid weight gain.
In the original analysis, the authors write that “From birth to 2, the prevalence of high weight for length (above the 95th percentile) is 25% higher among African American children compared to White children. From age 2 to 19, the rate of obesity is more than 50% higher among African American children compared to White children. Similar disparities persist into adulthood: rates of obesity are approximately 25% higher among African American adults compared to White adults.”
The differences in early rapid weight gain may be driving the disparities, the authors write.
Elements of the intervention
The intervention in the current analysis included materials delivered at the 3- and 8-week home visits focused on soothing and crying, feeding, and interactive play in the babies’ first months. Families were recruited from Augusta University Medical Center in Augusta, Ga., and had home visits at 1, 3, 8, and 16 weeks post partum.
Mothers got a packet of handouts and facilitators walked through the information with them. The measures involved hands-on activities, discussion, and videos, all tailored for Black families, the authors state.
Mothers were taught about responding appropriately at night when their baby cries, including giving the baby a couple of minutes to fall back to sleep independently and by using calming messages, such as shushing or white noise, before picking the baby up.
Babies learn to fall asleep on their own
They also learned to put infants to bed early (ideally by 8 p.m.) so the babies would be calm but awake and could learn to fall asleep on their own.
The control group’s guidance was matched for intensity and session length but focused on sleep and home safety, such as reducing the risk of sudden infant death syndrome (SIDS), keeping the baby’s sleep area close to, but away from, the mother’s bed, and preventing shaken baby syndrome.
In both groups, the 3-week visit session lasted about 90-120 minutes and the 8-week visit lasted about 45-60 minutes.
Longer sleep with the intervention
A total of 212 Black mothers, average age 22.7, were randomized – 108 to the RP group and 104 to the control group. Answers on questionnaires were analyzed and at 16 weeks post partum, infants in the RP group (relative to controls) had:
- Longer reported nighttime sleep (mean difference, 40 minutes [95% confidence interval, 3-77]).
- Longer total sleep duration (mean difference, 73 minutes [95% CI, 14-131]).
- Fewer nighttime wakings (mean difference, −0.4 wakings [95% CI, −0.6 to −0.1]).
- Greater likelihood of meeting guidelines of at least 12 hours of sleep per day (risk ratio, 1.4 [95% CI, 1.1 to 1.8]) than controls.
Findings were published in JAMA Network Open.
Additionally, mothers in the RP group more frequently reported they engaged in practices such as letting babies have a few minutes to fall back to sleep on their own (RR, 1.6 [95% CI, 1.0-2.6]) and being less likely to feed their infant just before the baby’s bedtime (RR, 0.5 [95% CI, 0.3-0.8]).
In an accompanying invited commentary, Sarah M. Honaker, PhD, department of pediatrics, Indiana University, Indianapolis, and Alicia Chung, EdD, Center for Early Childhood Health and Development at New York University, write that though the added average sleep duration is one of the most significant findings, there is a possibility of desirability bias because it was reported by the mothers after specific guidance by the facilitators.
“Nonetheless,” the editorialists write, “even if the true effect were half as small, this additional sleep duration could yield notable benefits in infant development if the effect persisted over time. The difference in night wakings between the intervention and control groups (1.8 vs 1.5 per night) at 16 weeks postpartum was statistically significant, though it is unclear whether this difference is clinically meaningful to families.”
They note that it is unclear from the study how the intervention was culturally adapted and how the adaptation might have affected outcomes.
Sleep intervention trials have focused on White families
The editorialists write that much is known about the benefits of behavioral sleep intervention in controlled trials and general population settings, and no adverse effects on infant attachment or cortisol levels have been linked to the interventions.
However, they add, “Unfortunately, this substantial progress in our understanding of infant BSI [behavioral sleep intervention] comes with a caveat, in that most previous studies have been performed with White families from mid-to-high socioeconomic backgrounds.”
Dr. Honaker and Dr. Chung write, “[I]t is important to note that much work remains to examine the acceptability, feasibility, and efficacy of infant BSI in other groups that have been historically marginalized.”
Dr. Lavner and colleagues point out that before their study, there had been little emphasis on interventions to encourage better sleep in general for Black infants, “as most early sleep interventions for this population have focused on SIDS prevention.”
“To our knowledge, Sleep SAAF is the first study to show any benefits of [an] RP intervention on sleep and sleep practices among Black infants and their families,” they write.
The researchers note that a limitation of the study is that the study sample was limited to Black first-time mothers recruited from a single medical center in Georgia.
The study by Dr. Lavner et al. was funded by the National Institutes of Health, a Harrington Faculty Fellowship from the University of Texas, and an award from the Penn State Clinical and Translational Sciences Institute supported by the National Center for Advancing Translational Sciences. Editorialist Dr. Honaker reported receiving grants from Nationwide Children’s Hospital (parent grant, Centers for Disease Control and Prevention) to evaluate the acceptability of infant behavioral sleep intervention in Black families.
FROM JAMA NETWORK OPEN
FDA panels vote to modify isotretinoin iPLEDGE REMS
At a joint meeting of a drug for severe, nodular acne that is highly teratogenic.
The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.
Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.
Listed options and the number of votes for each were:
- Only with the first prescription as part of patient enrollment (10)
- Monthly (1)
- Every 120 days (6)
- Some other frequency (5)
For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.
Lack of data
On both questions, several advisory committee members cited a lack of data on which they could base their decision.
On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.
“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”
The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.
The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.
They were also tasked with discussing other REMS requirements without taking a vote on each topic.
Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.
The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
A version of this article first appeared on Medscape.com.
At a joint meeting of a drug for severe, nodular acne that is highly teratogenic.
The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.
Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.
Listed options and the number of votes for each were:
- Only with the first prescription as part of patient enrollment (10)
- Monthly (1)
- Every 120 days (6)
- Some other frequency (5)
For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.
Lack of data
On both questions, several advisory committee members cited a lack of data on which they could base their decision.
On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.
“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”
The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.
The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.
They were also tasked with discussing other REMS requirements without taking a vote on each topic.
Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.
The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
A version of this article first appeared on Medscape.com.
At a joint meeting of a drug for severe, nodular acne that is highly teratogenic.
The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.
Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.
Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.
“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”
The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.
Listed options and the number of votes for each were:
- Only with the first prescription as part of patient enrollment (10)
- Monthly (1)
- Every 120 days (6)
- Some other frequency (5)
For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.
Lack of data
On both questions, several advisory committee members cited a lack of data on which they could base their decision.
On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.
“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”
The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.
The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.
They were also tasked with discussing other REMS requirements without taking a vote on each topic.
Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.
The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.
The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.
A version of this article first appeared on Medscape.com.