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Telehealth parent-child interaction therapy improved behavior in children with developmental delay
The children received the therapy with their parents or caregivers, who were more likely to demonstrate positive parenting behaviors than parents in the control group, authors of the new research published in JAMA Pediatrics found.
Approximately 13% of children have some form of developmental delay (DD) and more than half of these children also have at least one mental health disorder, which makes behavior problems a common and ongoing challenge, Daniel M. Bagner, PhD, a psychologist at Florida International University, Miami, and colleagues wrote.
Clinic-based interventions such as parent-child interaction therapy (PCIT) have been effective for improving behavior in children with DD, the researchers said. PCIT involves in-session caregiver coaching using a 1-way mirror and a wireless earpiece worn by the caregiver.
Barriers to the use of PCIT, especially in marginalized and low-income communities, include transportation, clinician shortages, and stigma-related concerns about a clinic visit, the researchers wrote. Technology now allows for Internet-delivered PCIT to reach more children and families, but its effectiveness for children with DD has not been well studied.
In the new study, the researchers randomized 150 children with DD and externalizing behavior problems to up to 20 weeks of Internet-delivered parent-child interaction therapy (iPCIT) or to referral as usual (RAU, the control group). The children were randomized after completion of early intervention services within 3 months of their third birthday, and participated in the sessions with a parent or caregiver. Most of the participants were from economically disadvantaged households and underrepresented ethnic backgrounds.
The iPCIT intervention was conducted weekly with a remote therapist and lasted for 1-1.5 hours; approximately half of the families received the intervention in Spanish.
The primary outcome was rating on the Child Behavior Checklist (CBCL) and assessment of children and caregivers using the Dyadic Parent-Child Interaction Coding System, fourth edition (DPICS). Assessments occurred at baseline and at week 20 (post treatment), with follow ups at 6 and 12 months.
Scores on the CBCL in the iPCIT group decreased from a mean of 61.18 at baseline to 53.83 post intervention. Scores for the control group started at 64.05 and decreased to 59.49 post intervention. At 6-12 months, the scores for both groups remained stable.
Children who received iPCIT with their parent or caregiver also showed significantly lower levels of externalizing behavior problems, compared with the RAU controls post treatment, and at 6-month and 12-month follow-ups based on the Cohen d measure of standardized effect size for differences between groups.
Significantly more children in the iPCIT group showed clinically significant improvements in externalizing problems at post treatment, compared with the RAU group (74% vs. 42%; P < .001) and at 6 months’ follow-up (73% vs. 45%; P = .002). However, the differences from baseline were not significantly different between the two groups after 12 months, which suggests that the effects may wane over time, the researchers noted.
In addition, the rate of child compliance with parent commands, as measured by a cleanup task, approximately doubled by the 12-month follow-up among children in the iPCIT group versus an increase of approximately one-third in the RAU group.
For secondary outcome measures related to caregiver behaviors, the proportion of observed positive parenting behaviors increased in the iPCIT group during the course of the intervention (postintervention odds ratio, 1.10), and the proportion of controlling and critical behaviors decreased (postintervention OR, 1.40). Harsh and inconsistent discipline decreased in both groups based on self-reports, but the decrease was steeper in iPCIT families.
iPCIT did not have a greater impact than RAU in reducing caregiver stress. The researchers wrote that they were not surprised by the lack of stress reduction “given mixed findings on the impact of parenting interventions on stress in caregivers of children with DD.”
Data support iPCIT potential
Overall, the results support findings from previous studies of clinic-based PCIT for children with DD and previous studies of telehealth interventions for typically developing children, the researchers said.
“Moreover, iPCIT-treated children not only showed reductions in behavior problems, such as aggression, but demonstrated higher rates of following directions, which is especially important for children entering kindergarten,” they wrote.
The findings were limited by several factors including the narrow focus on the primary and secondary outcomes, the use of data from a single site in a single metropolitan area – which may limit generalizability – and the lack of comparison between iPCIT and a clinic-based PCIT control group, the researchers noted. The equipment in the current study was provided to families; therefore, differences in treatment response could not be attributed to differences in technology.
The study represents the first known randomized controlled trial to evaluate a telehealth parenting intervention for children with, according to the researchers. The results suggest that technology can be leveraged to help these patients, including those from ethnic minority families who may be underserved by clinic-based care in overcoming barriers to treatment such as transportation and availability of clinicians. Use of iPCIT could be a critical resource as young children with DD complete Part C services and enter the school system.
Practical pediatric takeaways
“This was a great study, well-designed and very important and helpful for pediatric providers,” Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.
“Young children with developmental delay and/or mental and behavioral health disorders require early identification and intervention,” said Dr. Haut. However, obstacles to intervention include stigma or parental denial of the disorder, as well as more practical challenges related to transportation, time to access a clinic or office, potential long length of treatment, and cost.
“Despite availability of state programs for young children, follow up and continued services can be challenging to complete. Once the child outgrows the state program finding alternative therapy can be difficult with the current shortage of pediatric mental health providers,” Dr. Haut noted.
“I was surprised to see that this study treatment phase was completed prior to the COVID-19 pandemic, when telehealth was not as popular a mode for health care and was not utilized to the extent that it is now, especially for pediatric care,” said Dr. Haut. “I was not surprised at the results, as the traditional mode of PCIT includes therapy and training in a space that may not be as familiar to the child as their home environment, and would include live presence of the therapist/s, which may add to anxiety for both the parent and child.”
That almost half of the parents participating in the study had graduated from college and/or completed graduate degrees “may have contributed to some of the success of this study,” Dr. Haut noted.
Benefits and barriers
“The COVID-19 pandemic brought significant change to the frequency of use and overall success of telehealth services,” Dr. Haut said. “Additional provider education in aspects such as provider technique and the use of medical devices with improved specific health care technology assisted in advancing the experience and opportunity for successful telehealth visits. Telehealth therapy offers a cost-effective option for any pediatric patients and for providers, as the time and space commitment for the patient visit can be considerably less than live office visits.
“Unfortunately, there are still overall barriers that I have personally experienced with telehealth, including interruptions in connectivity, background noise, and lack of an available computer or tablet; and with the use of cell phones not always allowing full inclusion of the caregiver and child,” said Dr. Haut. Children with DD, behavioral problems, or other mental health disorders may pose challenges for parents to manage at home while simultaneously trying to fully focus on the therapy in an online setting.
Although the current study is encouraging, “larger studies focused on specific or individual pediatric mental health and/or behavioral disorders may offer more information for providers, and better document the success of telehealth delivery of services,” Dr. Haut said.
The study was supported by the National Institute of Child Health and Human Development. Dr. Bagner disclosed funding from the National Institutes of Health. He also disclosed personal fees from PCIT International to train clinicians in PCIT supported by a grant from the Florida Department of Children and Families outside the current study. Dr. Haut had no financial conflicts to disclose, but serves on the editorial advisory board of Pediatric News.
The children received the therapy with their parents or caregivers, who were more likely to demonstrate positive parenting behaviors than parents in the control group, authors of the new research published in JAMA Pediatrics found.
Approximately 13% of children have some form of developmental delay (DD) and more than half of these children also have at least one mental health disorder, which makes behavior problems a common and ongoing challenge, Daniel M. Bagner, PhD, a psychologist at Florida International University, Miami, and colleagues wrote.
Clinic-based interventions such as parent-child interaction therapy (PCIT) have been effective for improving behavior in children with DD, the researchers said. PCIT involves in-session caregiver coaching using a 1-way mirror and a wireless earpiece worn by the caregiver.
Barriers to the use of PCIT, especially in marginalized and low-income communities, include transportation, clinician shortages, and stigma-related concerns about a clinic visit, the researchers wrote. Technology now allows for Internet-delivered PCIT to reach more children and families, but its effectiveness for children with DD has not been well studied.
In the new study, the researchers randomized 150 children with DD and externalizing behavior problems to up to 20 weeks of Internet-delivered parent-child interaction therapy (iPCIT) or to referral as usual (RAU, the control group). The children were randomized after completion of early intervention services within 3 months of their third birthday, and participated in the sessions with a parent or caregiver. Most of the participants were from economically disadvantaged households and underrepresented ethnic backgrounds.
The iPCIT intervention was conducted weekly with a remote therapist and lasted for 1-1.5 hours; approximately half of the families received the intervention in Spanish.
The primary outcome was rating on the Child Behavior Checklist (CBCL) and assessment of children and caregivers using the Dyadic Parent-Child Interaction Coding System, fourth edition (DPICS). Assessments occurred at baseline and at week 20 (post treatment), with follow ups at 6 and 12 months.
Scores on the CBCL in the iPCIT group decreased from a mean of 61.18 at baseline to 53.83 post intervention. Scores for the control group started at 64.05 and decreased to 59.49 post intervention. At 6-12 months, the scores for both groups remained stable.
Children who received iPCIT with their parent or caregiver also showed significantly lower levels of externalizing behavior problems, compared with the RAU controls post treatment, and at 6-month and 12-month follow-ups based on the Cohen d measure of standardized effect size for differences between groups.
Significantly more children in the iPCIT group showed clinically significant improvements in externalizing problems at post treatment, compared with the RAU group (74% vs. 42%; P < .001) and at 6 months’ follow-up (73% vs. 45%; P = .002). However, the differences from baseline were not significantly different between the two groups after 12 months, which suggests that the effects may wane over time, the researchers noted.
In addition, the rate of child compliance with parent commands, as measured by a cleanup task, approximately doubled by the 12-month follow-up among children in the iPCIT group versus an increase of approximately one-third in the RAU group.
For secondary outcome measures related to caregiver behaviors, the proportion of observed positive parenting behaviors increased in the iPCIT group during the course of the intervention (postintervention odds ratio, 1.10), and the proportion of controlling and critical behaviors decreased (postintervention OR, 1.40). Harsh and inconsistent discipline decreased in both groups based on self-reports, but the decrease was steeper in iPCIT families.
iPCIT did not have a greater impact than RAU in reducing caregiver stress. The researchers wrote that they were not surprised by the lack of stress reduction “given mixed findings on the impact of parenting interventions on stress in caregivers of children with DD.”
Data support iPCIT potential
Overall, the results support findings from previous studies of clinic-based PCIT for children with DD and previous studies of telehealth interventions for typically developing children, the researchers said.
“Moreover, iPCIT-treated children not only showed reductions in behavior problems, such as aggression, but demonstrated higher rates of following directions, which is especially important for children entering kindergarten,” they wrote.
The findings were limited by several factors including the narrow focus on the primary and secondary outcomes, the use of data from a single site in a single metropolitan area – which may limit generalizability – and the lack of comparison between iPCIT and a clinic-based PCIT control group, the researchers noted. The equipment in the current study was provided to families; therefore, differences in treatment response could not be attributed to differences in technology.
The study represents the first known randomized controlled trial to evaluate a telehealth parenting intervention for children with, according to the researchers. The results suggest that technology can be leveraged to help these patients, including those from ethnic minority families who may be underserved by clinic-based care in overcoming barriers to treatment such as transportation and availability of clinicians. Use of iPCIT could be a critical resource as young children with DD complete Part C services and enter the school system.
Practical pediatric takeaways
“This was a great study, well-designed and very important and helpful for pediatric providers,” Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.
“Young children with developmental delay and/or mental and behavioral health disorders require early identification and intervention,” said Dr. Haut. However, obstacles to intervention include stigma or parental denial of the disorder, as well as more practical challenges related to transportation, time to access a clinic or office, potential long length of treatment, and cost.
“Despite availability of state programs for young children, follow up and continued services can be challenging to complete. Once the child outgrows the state program finding alternative therapy can be difficult with the current shortage of pediatric mental health providers,” Dr. Haut noted.
“I was surprised to see that this study treatment phase was completed prior to the COVID-19 pandemic, when telehealth was not as popular a mode for health care and was not utilized to the extent that it is now, especially for pediatric care,” said Dr. Haut. “I was not surprised at the results, as the traditional mode of PCIT includes therapy and training in a space that may not be as familiar to the child as their home environment, and would include live presence of the therapist/s, which may add to anxiety for both the parent and child.”
That almost half of the parents participating in the study had graduated from college and/or completed graduate degrees “may have contributed to some of the success of this study,” Dr. Haut noted.
Benefits and barriers
“The COVID-19 pandemic brought significant change to the frequency of use and overall success of telehealth services,” Dr. Haut said. “Additional provider education in aspects such as provider technique and the use of medical devices with improved specific health care technology assisted in advancing the experience and opportunity for successful telehealth visits. Telehealth therapy offers a cost-effective option for any pediatric patients and for providers, as the time and space commitment for the patient visit can be considerably less than live office visits.
“Unfortunately, there are still overall barriers that I have personally experienced with telehealth, including interruptions in connectivity, background noise, and lack of an available computer or tablet; and with the use of cell phones not always allowing full inclusion of the caregiver and child,” said Dr. Haut. Children with DD, behavioral problems, or other mental health disorders may pose challenges for parents to manage at home while simultaneously trying to fully focus on the therapy in an online setting.
Although the current study is encouraging, “larger studies focused on specific or individual pediatric mental health and/or behavioral disorders may offer more information for providers, and better document the success of telehealth delivery of services,” Dr. Haut said.
The study was supported by the National Institute of Child Health and Human Development. Dr. Bagner disclosed funding from the National Institutes of Health. He also disclosed personal fees from PCIT International to train clinicians in PCIT supported by a grant from the Florida Department of Children and Families outside the current study. Dr. Haut had no financial conflicts to disclose, but serves on the editorial advisory board of Pediatric News.
The children received the therapy with their parents or caregivers, who were more likely to demonstrate positive parenting behaviors than parents in the control group, authors of the new research published in JAMA Pediatrics found.
Approximately 13% of children have some form of developmental delay (DD) and more than half of these children also have at least one mental health disorder, which makes behavior problems a common and ongoing challenge, Daniel M. Bagner, PhD, a psychologist at Florida International University, Miami, and colleagues wrote.
Clinic-based interventions such as parent-child interaction therapy (PCIT) have been effective for improving behavior in children with DD, the researchers said. PCIT involves in-session caregiver coaching using a 1-way mirror and a wireless earpiece worn by the caregiver.
Barriers to the use of PCIT, especially in marginalized and low-income communities, include transportation, clinician shortages, and stigma-related concerns about a clinic visit, the researchers wrote. Technology now allows for Internet-delivered PCIT to reach more children and families, but its effectiveness for children with DD has not been well studied.
In the new study, the researchers randomized 150 children with DD and externalizing behavior problems to up to 20 weeks of Internet-delivered parent-child interaction therapy (iPCIT) or to referral as usual (RAU, the control group). The children were randomized after completion of early intervention services within 3 months of their third birthday, and participated in the sessions with a parent or caregiver. Most of the participants were from economically disadvantaged households and underrepresented ethnic backgrounds.
The iPCIT intervention was conducted weekly with a remote therapist and lasted for 1-1.5 hours; approximately half of the families received the intervention in Spanish.
The primary outcome was rating on the Child Behavior Checklist (CBCL) and assessment of children and caregivers using the Dyadic Parent-Child Interaction Coding System, fourth edition (DPICS). Assessments occurred at baseline and at week 20 (post treatment), with follow ups at 6 and 12 months.
Scores on the CBCL in the iPCIT group decreased from a mean of 61.18 at baseline to 53.83 post intervention. Scores for the control group started at 64.05 and decreased to 59.49 post intervention. At 6-12 months, the scores for both groups remained stable.
Children who received iPCIT with their parent or caregiver also showed significantly lower levels of externalizing behavior problems, compared with the RAU controls post treatment, and at 6-month and 12-month follow-ups based on the Cohen d measure of standardized effect size for differences between groups.
Significantly more children in the iPCIT group showed clinically significant improvements in externalizing problems at post treatment, compared with the RAU group (74% vs. 42%; P < .001) and at 6 months’ follow-up (73% vs. 45%; P = .002). However, the differences from baseline were not significantly different between the two groups after 12 months, which suggests that the effects may wane over time, the researchers noted.
In addition, the rate of child compliance with parent commands, as measured by a cleanup task, approximately doubled by the 12-month follow-up among children in the iPCIT group versus an increase of approximately one-third in the RAU group.
For secondary outcome measures related to caregiver behaviors, the proportion of observed positive parenting behaviors increased in the iPCIT group during the course of the intervention (postintervention odds ratio, 1.10), and the proportion of controlling and critical behaviors decreased (postintervention OR, 1.40). Harsh and inconsistent discipline decreased in both groups based on self-reports, but the decrease was steeper in iPCIT families.
iPCIT did not have a greater impact than RAU in reducing caregiver stress. The researchers wrote that they were not surprised by the lack of stress reduction “given mixed findings on the impact of parenting interventions on stress in caregivers of children with DD.”
Data support iPCIT potential
Overall, the results support findings from previous studies of clinic-based PCIT for children with DD and previous studies of telehealth interventions for typically developing children, the researchers said.
“Moreover, iPCIT-treated children not only showed reductions in behavior problems, such as aggression, but demonstrated higher rates of following directions, which is especially important for children entering kindergarten,” they wrote.
The findings were limited by several factors including the narrow focus on the primary and secondary outcomes, the use of data from a single site in a single metropolitan area – which may limit generalizability – and the lack of comparison between iPCIT and a clinic-based PCIT control group, the researchers noted. The equipment in the current study was provided to families; therefore, differences in treatment response could not be attributed to differences in technology.
The study represents the first known randomized controlled trial to evaluate a telehealth parenting intervention for children with, according to the researchers. The results suggest that technology can be leveraged to help these patients, including those from ethnic minority families who may be underserved by clinic-based care in overcoming barriers to treatment such as transportation and availability of clinicians. Use of iPCIT could be a critical resource as young children with DD complete Part C services and enter the school system.
Practical pediatric takeaways
“This was a great study, well-designed and very important and helpful for pediatric providers,” Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.
“Young children with developmental delay and/or mental and behavioral health disorders require early identification and intervention,” said Dr. Haut. However, obstacles to intervention include stigma or parental denial of the disorder, as well as more practical challenges related to transportation, time to access a clinic or office, potential long length of treatment, and cost.
“Despite availability of state programs for young children, follow up and continued services can be challenging to complete. Once the child outgrows the state program finding alternative therapy can be difficult with the current shortage of pediatric mental health providers,” Dr. Haut noted.
“I was surprised to see that this study treatment phase was completed prior to the COVID-19 pandemic, when telehealth was not as popular a mode for health care and was not utilized to the extent that it is now, especially for pediatric care,” said Dr. Haut. “I was not surprised at the results, as the traditional mode of PCIT includes therapy and training in a space that may not be as familiar to the child as their home environment, and would include live presence of the therapist/s, which may add to anxiety for both the parent and child.”
That almost half of the parents participating in the study had graduated from college and/or completed graduate degrees “may have contributed to some of the success of this study,” Dr. Haut noted.
Benefits and barriers
“The COVID-19 pandemic brought significant change to the frequency of use and overall success of telehealth services,” Dr. Haut said. “Additional provider education in aspects such as provider technique and the use of medical devices with improved specific health care technology assisted in advancing the experience and opportunity for successful telehealth visits. Telehealth therapy offers a cost-effective option for any pediatric patients and for providers, as the time and space commitment for the patient visit can be considerably less than live office visits.
“Unfortunately, there are still overall barriers that I have personally experienced with telehealth, including interruptions in connectivity, background noise, and lack of an available computer or tablet; and with the use of cell phones not always allowing full inclusion of the caregiver and child,” said Dr. Haut. Children with DD, behavioral problems, or other mental health disorders may pose challenges for parents to manage at home while simultaneously trying to fully focus on the therapy in an online setting.
Although the current study is encouraging, “larger studies focused on specific or individual pediatric mental health and/or behavioral disorders may offer more information for providers, and better document the success of telehealth delivery of services,” Dr. Haut said.
The study was supported by the National Institute of Child Health and Human Development. Dr. Bagner disclosed funding from the National Institutes of Health. He also disclosed personal fees from PCIT International to train clinicians in PCIT supported by a grant from the Florida Department of Children and Families outside the current study. Dr. Haut had no financial conflicts to disclose, but serves on the editorial advisory board of Pediatric News.
FROM JAMA PEDIATRICS
Obesity impacts peripheral airway reactivity, asthma
Peripheral airway response to methacholine was similar among obese adults with and without asthma, although forced expiratory volume was lower for those with asthma, based on data from 53 individuals.
Obesity remains a risk factor for asthma, and obese individuals with asthma tend to have worse control and more severe disease, compared with nonobese asthma patients, wrote Anne E. Dixon, BM, BCh, of the University of Vermont, Burlington, and colleagues.
Previous studies have shown that airway reactivity can occur in obese individuals without airway inflammation, but studies characterizing obese asthma based on lung function are lacking, they said. “Combining spirometry and oscillometry might reveal abnormalities in lung mechanics particularly pertinent to people with obesity and asthma,” the researchers noted.
In a cross-sectional study published in the journal CHEST, the researchers reviewed data from 31 obese adults with asthma and 22 obese adults without asthma. The participants were aged 18 years and older, with forced expiratory volume (FEV1) of at least 60% of predicted. All had class III obesity, with an average BMI of 47.2 kg/m2 for those with asthma and 46.7 kg/m2 for nonasthma controls. Demographic characteristics were similar between the groups.
Airway reactivity was defined as a 20% decrease in FEV1 and/or a 50% change in resistance or reactance at 5 Hz (R5 and X5), at a concentration of 16 mg/mL or less of methacholine. Patients were assessed using spirometry and oscillometry.
For those with asthma, the resistance at 5 Hz, measured by oscillometry, increased by 52% in response to the PC20 methacholine challenge, with an area under the reactance curve (AX) of 361%. For controls without asthma, the resistance at 5 Hz increased by 45%, with an AX of 268% in response to 16 mg/mL of methacholine.
This finding suggests that obesity predisposes individuals to peripheral airway reactivity regardless of asthma status, the researchers wrote in their discussion.
The researchers also identified two distinct groups of asthma patients categorized by respiratory system impedance based on more concordant vs. discordant bronchoconstriction in the central and peripheral airways. The baseline AX for these two groups was 11.8 and 46.7, respectively, with interquartile ranges of 9.9-23.4 and 23.2-53.7, respectively.
The discordant group included only women, and these patients reported significantly more gastroesophageal reflux, increased chest tightness, and more wheezing and asthma exacerbations than the concordant group, which may be related to air trapping, shown on previous studies of obese individuals with asthma, the researchers wrote.
The findings were limited by several factors, including the measurement of airway impedance only at the peak methacholine dose and the measurement of oscillometry after spirometry, the researchers noted. Other limitations included the relatively small study population at a single center, and the focus on obese individuals only.
More research is needed in larger and more diverse patient populations, but the results support the characterization of a subgroup of obese asthma patients with significant peripheral airway dysfunction, the researchers wrote.
“Oscillometry testing can reveal a physiologic phenotype of asthma in obesity that may be related to worse symptoms and more severe disease, and also reveal subclinical abnormalities in people with obesity, but without clinically diagnosed lung disease,” they concluded.
The study was supported in part by the National Institutes of Health. The researchers declared no financial conflicts.
A version of this article first appeared on Medscape.com.
Peripheral airway response to methacholine was similar among obese adults with and without asthma, although forced expiratory volume was lower for those with asthma, based on data from 53 individuals.
Obesity remains a risk factor for asthma, and obese individuals with asthma tend to have worse control and more severe disease, compared with nonobese asthma patients, wrote Anne E. Dixon, BM, BCh, of the University of Vermont, Burlington, and colleagues.
Previous studies have shown that airway reactivity can occur in obese individuals without airway inflammation, but studies characterizing obese asthma based on lung function are lacking, they said. “Combining spirometry and oscillometry might reveal abnormalities in lung mechanics particularly pertinent to people with obesity and asthma,” the researchers noted.
In a cross-sectional study published in the journal CHEST, the researchers reviewed data from 31 obese adults with asthma and 22 obese adults without asthma. The participants were aged 18 years and older, with forced expiratory volume (FEV1) of at least 60% of predicted. All had class III obesity, with an average BMI of 47.2 kg/m2 for those with asthma and 46.7 kg/m2 for nonasthma controls. Demographic characteristics were similar between the groups.
Airway reactivity was defined as a 20% decrease in FEV1 and/or a 50% change in resistance or reactance at 5 Hz (R5 and X5), at a concentration of 16 mg/mL or less of methacholine. Patients were assessed using spirometry and oscillometry.
For those with asthma, the resistance at 5 Hz, measured by oscillometry, increased by 52% in response to the PC20 methacholine challenge, with an area under the reactance curve (AX) of 361%. For controls without asthma, the resistance at 5 Hz increased by 45%, with an AX of 268% in response to 16 mg/mL of methacholine.
This finding suggests that obesity predisposes individuals to peripheral airway reactivity regardless of asthma status, the researchers wrote in their discussion.
The researchers also identified two distinct groups of asthma patients categorized by respiratory system impedance based on more concordant vs. discordant bronchoconstriction in the central and peripheral airways. The baseline AX for these two groups was 11.8 and 46.7, respectively, with interquartile ranges of 9.9-23.4 and 23.2-53.7, respectively.
The discordant group included only women, and these patients reported significantly more gastroesophageal reflux, increased chest tightness, and more wheezing and asthma exacerbations than the concordant group, which may be related to air trapping, shown on previous studies of obese individuals with asthma, the researchers wrote.
The findings were limited by several factors, including the measurement of airway impedance only at the peak methacholine dose and the measurement of oscillometry after spirometry, the researchers noted. Other limitations included the relatively small study population at a single center, and the focus on obese individuals only.
More research is needed in larger and more diverse patient populations, but the results support the characterization of a subgroup of obese asthma patients with significant peripheral airway dysfunction, the researchers wrote.
“Oscillometry testing can reveal a physiologic phenotype of asthma in obesity that may be related to worse symptoms and more severe disease, and also reveal subclinical abnormalities in people with obesity, but without clinically diagnosed lung disease,” they concluded.
The study was supported in part by the National Institutes of Health. The researchers declared no financial conflicts.
A version of this article first appeared on Medscape.com.
Peripheral airway response to methacholine was similar among obese adults with and without asthma, although forced expiratory volume was lower for those with asthma, based on data from 53 individuals.
Obesity remains a risk factor for asthma, and obese individuals with asthma tend to have worse control and more severe disease, compared with nonobese asthma patients, wrote Anne E. Dixon, BM, BCh, of the University of Vermont, Burlington, and colleagues.
Previous studies have shown that airway reactivity can occur in obese individuals without airway inflammation, but studies characterizing obese asthma based on lung function are lacking, they said. “Combining spirometry and oscillometry might reveal abnormalities in lung mechanics particularly pertinent to people with obesity and asthma,” the researchers noted.
In a cross-sectional study published in the journal CHEST, the researchers reviewed data from 31 obese adults with asthma and 22 obese adults without asthma. The participants were aged 18 years and older, with forced expiratory volume (FEV1) of at least 60% of predicted. All had class III obesity, with an average BMI of 47.2 kg/m2 for those with asthma and 46.7 kg/m2 for nonasthma controls. Demographic characteristics were similar between the groups.
Airway reactivity was defined as a 20% decrease in FEV1 and/or a 50% change in resistance or reactance at 5 Hz (R5 and X5), at a concentration of 16 mg/mL or less of methacholine. Patients were assessed using spirometry and oscillometry.
For those with asthma, the resistance at 5 Hz, measured by oscillometry, increased by 52% in response to the PC20 methacholine challenge, with an area under the reactance curve (AX) of 361%. For controls without asthma, the resistance at 5 Hz increased by 45%, with an AX of 268% in response to 16 mg/mL of methacholine.
This finding suggests that obesity predisposes individuals to peripheral airway reactivity regardless of asthma status, the researchers wrote in their discussion.
The researchers also identified two distinct groups of asthma patients categorized by respiratory system impedance based on more concordant vs. discordant bronchoconstriction in the central and peripheral airways. The baseline AX for these two groups was 11.8 and 46.7, respectively, with interquartile ranges of 9.9-23.4 and 23.2-53.7, respectively.
The discordant group included only women, and these patients reported significantly more gastroesophageal reflux, increased chest tightness, and more wheezing and asthma exacerbations than the concordant group, which may be related to air trapping, shown on previous studies of obese individuals with asthma, the researchers wrote.
The findings were limited by several factors, including the measurement of airway impedance only at the peak methacholine dose and the measurement of oscillometry after spirometry, the researchers noted. Other limitations included the relatively small study population at a single center, and the focus on obese individuals only.
More research is needed in larger and more diverse patient populations, but the results support the characterization of a subgroup of obese asthma patients with significant peripheral airway dysfunction, the researchers wrote.
“Oscillometry testing can reveal a physiologic phenotype of asthma in obesity that may be related to worse symptoms and more severe disease, and also reveal subclinical abnormalities in people with obesity, but without clinically diagnosed lung disease,” they concluded.
The study was supported in part by the National Institutes of Health. The researchers declared no financial conflicts.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL CHEST
Berdazimer gel under review at FDA for treating molluscum contagiosum
, the manufacturer announced.
If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.
The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.
The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.
The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.
, the manufacturer announced.
If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.
The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.
The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.
The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.
, the manufacturer announced.
If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.
The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.
The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.
The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.
‘Affect discrepancies’ may underlie negative symptoms in schizophrenia
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
FROM THE JOURNAL OF PSYCHIATRIC RESEARCH
Emergency physicians take issue with AHRQ errors report
The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.
The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.
The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.
“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
Emergency medicine organizations express concerns for accuracy
The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.
The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.
The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.
Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.
All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
Misleading and inadequate evidence
“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.
“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”
The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.
“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.
The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.
“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.
“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.
Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.
“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”
Dr. Glatter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.
The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.
The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.
“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
Emergency medicine organizations express concerns for accuracy
The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.
The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.
The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.
Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.
All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
Misleading and inadequate evidence
“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.
“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”
The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.
“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.
The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.
“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.
“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.
Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.
“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”
Dr. Glatter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.
The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.
The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.
“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
Emergency medicine organizations express concerns for accuracy
The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.
The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.
The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.
Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.
All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
Misleading and inadequate evidence
“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.
“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”
The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.
“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.
The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.
“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.
“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.
Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.
“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”
Dr. Glatter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Defining six asthma subtypes may promote personalized treatment
Six subtypes of asthma that may facilitate personalized treatment were identified and confirmed in a large database review of approximately 50,000 patients, according to a recent study.
Previous studies of asthma subtypes have involved age of disease onset, the presence of allergies, and level of eosinophilic inflammation, and have been limited by factors including small sample size and lack of formal validation, Elsie M.F. Horne, MD, of the Asthma UK Centre for Applied Research, Edinburgh, and colleagues wrote.
In a study published in the International Journal of Medical Informatics, the researchers used data from two databases in the United Kingdom: the Optimum Patient Care Research Database (OPCRD) and the Secure Anonymised Information Linkage Database (SAIL). Each dataset included 50,000 randomly selected nonoverlapping adult asthma patients.
The researchers identified 45 categorical features from primary care electronic health records. The features included those directly linked to asthma, such as medications; and features indirectly linked to asthma, such as comorbidities.
The subtypes were defined by the clinically applicable features of level of inhaled corticosteroid use, level of health care use, and the presence of comorbidities, using multiple correspondence analysis and k-means cluster analysis.
The six asthma subtypes were identified in the OPCRD study population as follows: low inhaled corticosteroid use and low health care utilization (30%); low to medium ICS use (36%); low to medium ICS use and comorbidities (12%); varied ICS use and comorbid chronic obstructive pulmonary disease (4%); high ICS use (10%); and very high ICS use (7%).
The researchers replicated the subtypes with 91%-92% accuracy in an internal dataset and 84%-86% accuracy in an external dataset. “These subtypes generalized well at two future time points, and in an additional EHR database from a different U.K. nation (the SAIL Databank),” they wrote in their discussion.
The findings were limited by several factors including the retrospective design, the possible inclusion of people without asthma because of the cohort selection criteria, and the possible biases associated with the use of EHRs; however, the results were strengthened by the large dataset and the additional validations, the researchers noted.
“Using these subtypes to summarize asthma populations could help with management and resource planning at the practice level, and could be useful for understanding regional differences in the asthma population,” they noted. For example, key clinical implications for individuals in a low health care utilization subtype could include being flagged for barriers to care and misdiagnoses, while those in a high health care utilization subtype could be considered for reassessment of medication and other options.
The study received no outside funding. Lead author Dr. Horne had no financial conflicts to disclose.
Six subtypes of asthma that may facilitate personalized treatment were identified and confirmed in a large database review of approximately 50,000 patients, according to a recent study.
Previous studies of asthma subtypes have involved age of disease onset, the presence of allergies, and level of eosinophilic inflammation, and have been limited by factors including small sample size and lack of formal validation, Elsie M.F. Horne, MD, of the Asthma UK Centre for Applied Research, Edinburgh, and colleagues wrote.
In a study published in the International Journal of Medical Informatics, the researchers used data from two databases in the United Kingdom: the Optimum Patient Care Research Database (OPCRD) and the Secure Anonymised Information Linkage Database (SAIL). Each dataset included 50,000 randomly selected nonoverlapping adult asthma patients.
The researchers identified 45 categorical features from primary care electronic health records. The features included those directly linked to asthma, such as medications; and features indirectly linked to asthma, such as comorbidities.
The subtypes were defined by the clinically applicable features of level of inhaled corticosteroid use, level of health care use, and the presence of comorbidities, using multiple correspondence analysis and k-means cluster analysis.
The six asthma subtypes were identified in the OPCRD study population as follows: low inhaled corticosteroid use and low health care utilization (30%); low to medium ICS use (36%); low to medium ICS use and comorbidities (12%); varied ICS use and comorbid chronic obstructive pulmonary disease (4%); high ICS use (10%); and very high ICS use (7%).
The researchers replicated the subtypes with 91%-92% accuracy in an internal dataset and 84%-86% accuracy in an external dataset. “These subtypes generalized well at two future time points, and in an additional EHR database from a different U.K. nation (the SAIL Databank),” they wrote in their discussion.
The findings were limited by several factors including the retrospective design, the possible inclusion of people without asthma because of the cohort selection criteria, and the possible biases associated with the use of EHRs; however, the results were strengthened by the large dataset and the additional validations, the researchers noted.
“Using these subtypes to summarize asthma populations could help with management and resource planning at the practice level, and could be useful for understanding regional differences in the asthma population,” they noted. For example, key clinical implications for individuals in a low health care utilization subtype could include being flagged for barriers to care and misdiagnoses, while those in a high health care utilization subtype could be considered for reassessment of medication and other options.
The study received no outside funding. Lead author Dr. Horne had no financial conflicts to disclose.
Six subtypes of asthma that may facilitate personalized treatment were identified and confirmed in a large database review of approximately 50,000 patients, according to a recent study.
Previous studies of asthma subtypes have involved age of disease onset, the presence of allergies, and level of eosinophilic inflammation, and have been limited by factors including small sample size and lack of formal validation, Elsie M.F. Horne, MD, of the Asthma UK Centre for Applied Research, Edinburgh, and colleagues wrote.
In a study published in the International Journal of Medical Informatics, the researchers used data from two databases in the United Kingdom: the Optimum Patient Care Research Database (OPCRD) and the Secure Anonymised Information Linkage Database (SAIL). Each dataset included 50,000 randomly selected nonoverlapping adult asthma patients.
The researchers identified 45 categorical features from primary care electronic health records. The features included those directly linked to asthma, such as medications; and features indirectly linked to asthma, such as comorbidities.
The subtypes were defined by the clinically applicable features of level of inhaled corticosteroid use, level of health care use, and the presence of comorbidities, using multiple correspondence analysis and k-means cluster analysis.
The six asthma subtypes were identified in the OPCRD study population as follows: low inhaled corticosteroid use and low health care utilization (30%); low to medium ICS use (36%); low to medium ICS use and comorbidities (12%); varied ICS use and comorbid chronic obstructive pulmonary disease (4%); high ICS use (10%); and very high ICS use (7%).
The researchers replicated the subtypes with 91%-92% accuracy in an internal dataset and 84%-86% accuracy in an external dataset. “These subtypes generalized well at two future time points, and in an additional EHR database from a different U.K. nation (the SAIL Databank),” they wrote in their discussion.
The findings were limited by several factors including the retrospective design, the possible inclusion of people without asthma because of the cohort selection criteria, and the possible biases associated with the use of EHRs; however, the results were strengthened by the large dataset and the additional validations, the researchers noted.
“Using these subtypes to summarize asthma populations could help with management and resource planning at the practice level, and could be useful for understanding regional differences in the asthma population,” they noted. For example, key clinical implications for individuals in a low health care utilization subtype could include being flagged for barriers to care and misdiagnoses, while those in a high health care utilization subtype could be considered for reassessment of medication and other options.
The study received no outside funding. Lead author Dr. Horne had no financial conflicts to disclose.
FROM THE INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS
New treatments aim to tame vitiligo
LAS VEGAS – in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.
Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.
The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.
Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.
Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.
In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.
Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.
In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.
In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.
Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.
Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.
JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.
Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.
An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.
Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.
Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.
Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.
The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.
Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.
Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.
In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.
Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.
In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.
In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.
Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.
Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.
JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.
Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.
An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.
Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.
Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.
Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.
The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.
Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.
Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.
In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.
Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.
In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.
In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.
Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.
Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.
JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.
Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.
An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.
Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.
Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.
MedscapeLive and this news organization are owned by the same parent company.
AT INNOVATIONS IN DERMATOLOGY
Dapper homolog 2 shows promise for pulmonary fibrosis
Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.
Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.
Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.
In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.
The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.
They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.
The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.
“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.
More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.
“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.
The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.
Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.
Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.
Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.
In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.
The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.
They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.
The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.
“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.
More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.
“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.
The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.
Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.
Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.
Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.
In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.
The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.
They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.
The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.
“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.
More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.
“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.
The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.
FROM THE INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Topical psoriasis treatments
LAS VEGAS – ,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.
However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.
Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.
The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.
In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.
Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
Get proactive to maintain results
With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.
Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,
She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.
What’s new and approved
Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.
Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.
In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.
Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.
Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.
Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.
Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – ,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.
However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.
Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.
The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.
In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.
Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
Get proactive to maintain results
With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.
Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,
She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.
What’s new and approved
Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.
Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.
In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.
Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.
Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.
Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.
Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – ,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.
However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.
Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.
The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.
In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.
Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
Get proactive to maintain results
With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.
Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,
She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.
What’s new and approved
Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.
Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.
In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.
Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.
Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.
Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.
Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.
MedscapeLive and this news organization are owned by the same parent company.
AT INNOVATIONS IN DERMATOLOGY
Fat-free mass index tied to outcomes in underweight COPD patients
Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.
Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.
However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.
In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.
Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).
Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.
Notably, after adjusting for multiple variables, after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.
However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).
Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.
The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.
However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.
The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.
Mr. Machado disclosed financial support from ZonMW.
A version of this article first appeared on Medscape.com.
Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.
Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.
However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.
In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.
Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).
Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.
Notably, after adjusting for multiple variables, after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.
However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).
Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.
The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.
However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.
The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.
Mr. Machado disclosed financial support from ZonMW.
A version of this article first appeared on Medscape.com.
Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.
Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.
However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.
In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.
Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).
Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.
Notably, after adjusting for multiple variables, after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.
However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).
Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.
The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.
However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.
The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.
Mr. Machado disclosed financial support from ZonMW.
A version of this article first appeared on Medscape.com.
From the Journal CHEST