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Pediatric epilepsy surgery may improve cognition and behavior
CHARLOTTE, NC – according to a study presented at the annual meeting of the Child Neurology Society. The presence of comorbidities such as mood disorders and autism may influence the likelihood of perceived improvement, whereas the type of surgery may not.
“The parents and the families of the patients perceive that, even if the patients are not completely seizure free, the behavior and cognitive outcomes are better if there is some sort of seizure improvement,” said Trishna Kantamneni, MD, director of pediatric epilepsy at UC Davis in Sacramento.
To assess behavioral and cognitive outcomes following pediatric epilepsy surgery and to identify factors that predict improvement, Dr. Kantamneni and colleagues at the Cleveland Clinic Epilepsy Center retrospectively reviewed 126 patients younger than 18 years who underwent epilepsy surgery for medically refractory epilepsy during 2009-2016.
The primary outcome measure was the Impact of Childhood Neurologic Disability Scale (ICNDS), a parent-reported scale that assesses the behavior, cognition, and physical or neurologic disability of children with epilepsy. Parents completed the ICNDS preoperatively and at 6, 12, and 24 months after surgery. The researchers constructed separate linear mixed effects models to identify predictors of postoperative changes in ICNDS score.
Of the 126 patients, 62.7% were male, the median duration of epilepsy was 4.7 years, and 69.8% were seizure-free at the 2-year follow-up. Postoperative ICNDS scores were available for 103 patients at 6 months and for 54 patients at 24 months.
Before surgery, the average total ICNDS score was 55.7. At 6 months after surgery, the average score was 34.6, and at 24 months, it was 32.1, representing significant improvement from baseline.
In addition, behavior, cognition, and epilepsy subscores also improved post operatively, and the improvement persisted through 24 months. ICNDS scores significantly improved “even in patients who were not seizure-free after surgery,” by an average of about 22 points, the researchers said.
The absence of comorbid autism, cognitive impairment, and global developmental impairment and the absence of anxiety, depression, and ADHD were predictors of improved total ICNDS scores. Tumor pathology and being seizure free at 2 years also predicted improved scores. Duration and type of epilepsy, the number of antiepileptic drugs that patients were taking before surgery, and lobe of surgery were not predictive of improved ICNDS scores.
Dr. Kantamneni had no relevant disclosures.
SOURCE: Kantamneni T et al. CNS 2019, Abstract 51.
CHARLOTTE, NC – according to a study presented at the annual meeting of the Child Neurology Society. The presence of comorbidities such as mood disorders and autism may influence the likelihood of perceived improvement, whereas the type of surgery may not.
“The parents and the families of the patients perceive that, even if the patients are not completely seizure free, the behavior and cognitive outcomes are better if there is some sort of seizure improvement,” said Trishna Kantamneni, MD, director of pediatric epilepsy at UC Davis in Sacramento.
To assess behavioral and cognitive outcomes following pediatric epilepsy surgery and to identify factors that predict improvement, Dr. Kantamneni and colleagues at the Cleveland Clinic Epilepsy Center retrospectively reviewed 126 patients younger than 18 years who underwent epilepsy surgery for medically refractory epilepsy during 2009-2016.
The primary outcome measure was the Impact of Childhood Neurologic Disability Scale (ICNDS), a parent-reported scale that assesses the behavior, cognition, and physical or neurologic disability of children with epilepsy. Parents completed the ICNDS preoperatively and at 6, 12, and 24 months after surgery. The researchers constructed separate linear mixed effects models to identify predictors of postoperative changes in ICNDS score.
Of the 126 patients, 62.7% were male, the median duration of epilepsy was 4.7 years, and 69.8% were seizure-free at the 2-year follow-up. Postoperative ICNDS scores were available for 103 patients at 6 months and for 54 patients at 24 months.
Before surgery, the average total ICNDS score was 55.7. At 6 months after surgery, the average score was 34.6, and at 24 months, it was 32.1, representing significant improvement from baseline.
In addition, behavior, cognition, and epilepsy subscores also improved post operatively, and the improvement persisted through 24 months. ICNDS scores significantly improved “even in patients who were not seizure-free after surgery,” by an average of about 22 points, the researchers said.
The absence of comorbid autism, cognitive impairment, and global developmental impairment and the absence of anxiety, depression, and ADHD were predictors of improved total ICNDS scores. Tumor pathology and being seizure free at 2 years also predicted improved scores. Duration and type of epilepsy, the number of antiepileptic drugs that patients were taking before surgery, and lobe of surgery were not predictive of improved ICNDS scores.
Dr. Kantamneni had no relevant disclosures.
SOURCE: Kantamneni T et al. CNS 2019, Abstract 51.
CHARLOTTE, NC – according to a study presented at the annual meeting of the Child Neurology Society. The presence of comorbidities such as mood disorders and autism may influence the likelihood of perceived improvement, whereas the type of surgery may not.
“The parents and the families of the patients perceive that, even if the patients are not completely seizure free, the behavior and cognitive outcomes are better if there is some sort of seizure improvement,” said Trishna Kantamneni, MD, director of pediatric epilepsy at UC Davis in Sacramento.
To assess behavioral and cognitive outcomes following pediatric epilepsy surgery and to identify factors that predict improvement, Dr. Kantamneni and colleagues at the Cleveland Clinic Epilepsy Center retrospectively reviewed 126 patients younger than 18 years who underwent epilepsy surgery for medically refractory epilepsy during 2009-2016.
The primary outcome measure was the Impact of Childhood Neurologic Disability Scale (ICNDS), a parent-reported scale that assesses the behavior, cognition, and physical or neurologic disability of children with epilepsy. Parents completed the ICNDS preoperatively and at 6, 12, and 24 months after surgery. The researchers constructed separate linear mixed effects models to identify predictors of postoperative changes in ICNDS score.
Of the 126 patients, 62.7% were male, the median duration of epilepsy was 4.7 years, and 69.8% were seizure-free at the 2-year follow-up. Postoperative ICNDS scores were available for 103 patients at 6 months and for 54 patients at 24 months.
Before surgery, the average total ICNDS score was 55.7. At 6 months after surgery, the average score was 34.6, and at 24 months, it was 32.1, representing significant improvement from baseline.
In addition, behavior, cognition, and epilepsy subscores also improved post operatively, and the improvement persisted through 24 months. ICNDS scores significantly improved “even in patients who were not seizure-free after surgery,” by an average of about 22 points, the researchers said.
The absence of comorbid autism, cognitive impairment, and global developmental impairment and the absence of anxiety, depression, and ADHD were predictors of improved total ICNDS scores. Tumor pathology and being seizure free at 2 years also predicted improved scores. Duration and type of epilepsy, the number of antiepileptic drugs that patients were taking before surgery, and lobe of surgery were not predictive of improved ICNDS scores.
Dr. Kantamneni had no relevant disclosures.
SOURCE: Kantamneni T et al. CNS 2019, Abstract 51.
REPORTING FROM CNS 2019
Delay in EEG monitoring associated with increased seizure duration in pediatric refractory status epilepticus
CHARLOTTE, NC – , according to a multicenter study that was presented at the annual meeting of the Child Neurology Society. Delays in initiating EEG monitoring are associated with longer seizure duration in this patient population.
Neurologists are advised to initiate continuous EEG monitoring rapidly for all cases of pediatric refractory status epilepticus. Little information is available, however, about patterns in the timing of EEG placement. In addition, the relationship between delays in the initiation of continuous EEG and outcomes of refractory status epilepticus are unknown. Dmitry Tchapyjnikov, MD, assistant professor of child neurology at Duke University in Durham, N.C., and colleagues evaluated trends in the time to continuous EEG initiation and examined whether delays are associated with longer seizure duration in children with refractory status epilepticus.
A retrospective analysis of pSERG data
Dr. Tchapyjnikov and colleagues analyzed data from 11 hospitals participating in the Pediatric Status Epilepticus Research Group (pSERG), a prospective, observational cohort. They focused on pediatric patients who were admitted from 2011 to 2017 with refractory status epilepticus, which they defined as a seizure that persisted after treatment with two or more antiseizure medications (ASMs), one of which had to be a nonbenzodiazepine ASM, or a continuous infusion. Eligible patients were between 1 month and 21 years old and had convulsive seizures at onset. Patients who had EEG placement before seizure onset were excluded.
The investigators included in their study 121 patients who had seizure durations of 3 or more hours. Based on an exploratory analysis of various time-point cutoffs, Dr. Tchapyjnikov and colleagues defined delayed continuous EEG placement as placement at more than 5 hours after seizure onset. They used the Kaplan–Meier estimator to assess time to continuous EEG and used covariate-adjusted proportional hazards models to examine the association between delay in continuous EEG placement and seizure duration.
EEG placement overall was delayed
The median time to continuous EEG placement after seizure onset was 9 hours. Approximately 4% of the children had continuous EEG placed within 1 hour, and 74% had it placed within 24 hours.
The investigators found that seizure onset outside the study hospital was associated with a higher likelihood of delayed time to EEG placement. “Females seemed to be more likely to have timely EEG placement,” said Dr. Tchapyjnikov. “I don’t have a physiological explanation for that.” The researchers saw no difference in treatment between patients who had timely EEG placement and those who had delayed EEG placement.
About 68% of children were having seizures at the time of continuous EEG placement. A presumed seizure etiology of CNS infection was associated with a higher likelihood of being in status epilepticus at the time of EEG placement. A history of epilepsy, developmental delay, or home ASM use, however, was associated with a lower likelihood of being in status epilepticus at time of EEG placement.
Dr. Tchapyjnikov’s group found that the 24-hour cumulative probability of seizure resolution was lower among patients who did not have continuous EEG initiation within 5 hours, compared with those who did (56% vs.70%). The association remained significant after the investigators adjusted the data for covariates that were independently associated with 24-hour seizure resolution (hazard ratio, 0.31).
The investigators included in their analysis patients who had seizure resolution before EEG placement, because restricting the analysis to patients who have persistent status epilepticus would have overemphasized the benefits of EEG, according to Dr. Tchapyjnikov. “Looking at the overall hazard ratios is a more conservative way of looking at these data.”
The study was not supported by external funding. Dr. Tchapyjnikov had no relevant disclosures.
CHARLOTTE, NC – , according to a multicenter study that was presented at the annual meeting of the Child Neurology Society. Delays in initiating EEG monitoring are associated with longer seizure duration in this patient population.
Neurologists are advised to initiate continuous EEG monitoring rapidly for all cases of pediatric refractory status epilepticus. Little information is available, however, about patterns in the timing of EEG placement. In addition, the relationship between delays in the initiation of continuous EEG and outcomes of refractory status epilepticus are unknown. Dmitry Tchapyjnikov, MD, assistant professor of child neurology at Duke University in Durham, N.C., and colleagues evaluated trends in the time to continuous EEG initiation and examined whether delays are associated with longer seizure duration in children with refractory status epilepticus.
A retrospective analysis of pSERG data
Dr. Tchapyjnikov and colleagues analyzed data from 11 hospitals participating in the Pediatric Status Epilepticus Research Group (pSERG), a prospective, observational cohort. They focused on pediatric patients who were admitted from 2011 to 2017 with refractory status epilepticus, which they defined as a seizure that persisted after treatment with two or more antiseizure medications (ASMs), one of which had to be a nonbenzodiazepine ASM, or a continuous infusion. Eligible patients were between 1 month and 21 years old and had convulsive seizures at onset. Patients who had EEG placement before seizure onset were excluded.
The investigators included in their study 121 patients who had seizure durations of 3 or more hours. Based on an exploratory analysis of various time-point cutoffs, Dr. Tchapyjnikov and colleagues defined delayed continuous EEG placement as placement at more than 5 hours after seizure onset. They used the Kaplan–Meier estimator to assess time to continuous EEG and used covariate-adjusted proportional hazards models to examine the association between delay in continuous EEG placement and seizure duration.
EEG placement overall was delayed
The median time to continuous EEG placement after seizure onset was 9 hours. Approximately 4% of the children had continuous EEG placed within 1 hour, and 74% had it placed within 24 hours.
The investigators found that seizure onset outside the study hospital was associated with a higher likelihood of delayed time to EEG placement. “Females seemed to be more likely to have timely EEG placement,” said Dr. Tchapyjnikov. “I don’t have a physiological explanation for that.” The researchers saw no difference in treatment between patients who had timely EEG placement and those who had delayed EEG placement.
About 68% of children were having seizures at the time of continuous EEG placement. A presumed seizure etiology of CNS infection was associated with a higher likelihood of being in status epilepticus at the time of EEG placement. A history of epilepsy, developmental delay, or home ASM use, however, was associated with a lower likelihood of being in status epilepticus at time of EEG placement.
Dr. Tchapyjnikov’s group found that the 24-hour cumulative probability of seizure resolution was lower among patients who did not have continuous EEG initiation within 5 hours, compared with those who did (56% vs.70%). The association remained significant after the investigators adjusted the data for covariates that were independently associated with 24-hour seizure resolution (hazard ratio, 0.31).
The investigators included in their analysis patients who had seizure resolution before EEG placement, because restricting the analysis to patients who have persistent status epilepticus would have overemphasized the benefits of EEG, according to Dr. Tchapyjnikov. “Looking at the overall hazard ratios is a more conservative way of looking at these data.”
The study was not supported by external funding. Dr. Tchapyjnikov had no relevant disclosures.
CHARLOTTE, NC – , according to a multicenter study that was presented at the annual meeting of the Child Neurology Society. Delays in initiating EEG monitoring are associated with longer seizure duration in this patient population.
Neurologists are advised to initiate continuous EEG monitoring rapidly for all cases of pediatric refractory status epilepticus. Little information is available, however, about patterns in the timing of EEG placement. In addition, the relationship between delays in the initiation of continuous EEG and outcomes of refractory status epilepticus are unknown. Dmitry Tchapyjnikov, MD, assistant professor of child neurology at Duke University in Durham, N.C., and colleagues evaluated trends in the time to continuous EEG initiation and examined whether delays are associated with longer seizure duration in children with refractory status epilepticus.
A retrospective analysis of pSERG data
Dr. Tchapyjnikov and colleagues analyzed data from 11 hospitals participating in the Pediatric Status Epilepticus Research Group (pSERG), a prospective, observational cohort. They focused on pediatric patients who were admitted from 2011 to 2017 with refractory status epilepticus, which they defined as a seizure that persisted after treatment with two or more antiseizure medications (ASMs), one of which had to be a nonbenzodiazepine ASM, or a continuous infusion. Eligible patients were between 1 month and 21 years old and had convulsive seizures at onset. Patients who had EEG placement before seizure onset were excluded.
The investigators included in their study 121 patients who had seizure durations of 3 or more hours. Based on an exploratory analysis of various time-point cutoffs, Dr. Tchapyjnikov and colleagues defined delayed continuous EEG placement as placement at more than 5 hours after seizure onset. They used the Kaplan–Meier estimator to assess time to continuous EEG and used covariate-adjusted proportional hazards models to examine the association between delay in continuous EEG placement and seizure duration.
EEG placement overall was delayed
The median time to continuous EEG placement after seizure onset was 9 hours. Approximately 4% of the children had continuous EEG placed within 1 hour, and 74% had it placed within 24 hours.
The investigators found that seizure onset outside the study hospital was associated with a higher likelihood of delayed time to EEG placement. “Females seemed to be more likely to have timely EEG placement,” said Dr. Tchapyjnikov. “I don’t have a physiological explanation for that.” The researchers saw no difference in treatment between patients who had timely EEG placement and those who had delayed EEG placement.
About 68% of children were having seizures at the time of continuous EEG placement. A presumed seizure etiology of CNS infection was associated with a higher likelihood of being in status epilepticus at the time of EEG placement. A history of epilepsy, developmental delay, or home ASM use, however, was associated with a lower likelihood of being in status epilepticus at time of EEG placement.
Dr. Tchapyjnikov’s group found that the 24-hour cumulative probability of seizure resolution was lower among patients who did not have continuous EEG initiation within 5 hours, compared with those who did (56% vs.70%). The association remained significant after the investigators adjusted the data for covariates that were independently associated with 24-hour seizure resolution (hazard ratio, 0.31).
The investigators included in their analysis patients who had seizure resolution before EEG placement, because restricting the analysis to patients who have persistent status epilepticus would have overemphasized the benefits of EEG, according to Dr. Tchapyjnikov. “Looking at the overall hazard ratios is a more conservative way of looking at these data.”
The study was not supported by external funding. Dr. Tchapyjnikov had no relevant disclosures.
REPORTING FROM CNS 2019
ICD-10 codes for EVALI released
The Centers for Disease Control and Prevention has issued coding guidance to help track e-cigarette, or vaping, product use–associated lung injury (EVALI).
The purpose of the coding guidelines “is to provide official diagnosis coding guidance for healthcare encounters related to the 2019 health care encounters and deaths related to” EVALI, CDC stated in a document detailing the coding update. The document was posted on the CDC website. The guidance is consistent with current clinical knowledge about e-cigarette, or vaping, related disorders.
CDC noted in the document that the guidance “is intended to be used in conjunction with current ICD-10-CM classification,” and the codes provided “are intended to provide e-cigarette, or vaping, product use coding guidance only.”
The codes are intended to track a number of areas related to EVALI, including lung-related complications, poisoning and toxicity, and substance use, abuse, and dependence.
The following conditions associated with EVALI are covered in the new coding guidance:
- Bronchitis and pneumonitis caused by chemicals, gases, and fumes.
- Bronchitis and pneumonitis caused by chemicals, gases, fumes, and vapors; includes chemical pneumonitis.
- Pneumonitis caused by inhalation of oils and essences; includes lipoid pneumonia.
- Acute respiratory distress syndrome.
- Pulmonary eosinophilia, not elsewhere classified.
- Acute interstitial pneumonitis.
The document notes that the coding guidance has been approved by the National Center for Health Statistics, the American Health Information Management Association, the American Hospital Association, and the Centers for Medicare & Medicaid Services.
The Centers for Disease Control and Prevention has issued coding guidance to help track e-cigarette, or vaping, product use–associated lung injury (EVALI).
The purpose of the coding guidelines “is to provide official diagnosis coding guidance for healthcare encounters related to the 2019 health care encounters and deaths related to” EVALI, CDC stated in a document detailing the coding update. The document was posted on the CDC website. The guidance is consistent with current clinical knowledge about e-cigarette, or vaping, related disorders.
CDC noted in the document that the guidance “is intended to be used in conjunction with current ICD-10-CM classification,” and the codes provided “are intended to provide e-cigarette, or vaping, product use coding guidance only.”
The codes are intended to track a number of areas related to EVALI, including lung-related complications, poisoning and toxicity, and substance use, abuse, and dependence.
The following conditions associated with EVALI are covered in the new coding guidance:
- Bronchitis and pneumonitis caused by chemicals, gases, and fumes.
- Bronchitis and pneumonitis caused by chemicals, gases, fumes, and vapors; includes chemical pneumonitis.
- Pneumonitis caused by inhalation of oils and essences; includes lipoid pneumonia.
- Acute respiratory distress syndrome.
- Pulmonary eosinophilia, not elsewhere classified.
- Acute interstitial pneumonitis.
The document notes that the coding guidance has been approved by the National Center for Health Statistics, the American Health Information Management Association, the American Hospital Association, and the Centers for Medicare & Medicaid Services.
The Centers for Disease Control and Prevention has issued coding guidance to help track e-cigarette, or vaping, product use–associated lung injury (EVALI).
The purpose of the coding guidelines “is to provide official diagnosis coding guidance for healthcare encounters related to the 2019 health care encounters and deaths related to” EVALI, CDC stated in a document detailing the coding update. The document was posted on the CDC website. The guidance is consistent with current clinical knowledge about e-cigarette, or vaping, related disorders.
CDC noted in the document that the guidance “is intended to be used in conjunction with current ICD-10-CM classification,” and the codes provided “are intended to provide e-cigarette, or vaping, product use coding guidance only.”
The codes are intended to track a number of areas related to EVALI, including lung-related complications, poisoning and toxicity, and substance use, abuse, and dependence.
The following conditions associated with EVALI are covered in the new coding guidance:
- Bronchitis and pneumonitis caused by chemicals, gases, and fumes.
- Bronchitis and pneumonitis caused by chemicals, gases, fumes, and vapors; includes chemical pneumonitis.
- Pneumonitis caused by inhalation of oils and essences; includes lipoid pneumonia.
- Acute respiratory distress syndrome.
- Pulmonary eosinophilia, not elsewhere classified.
- Acute interstitial pneumonitis.
The document notes that the coding guidance has been approved by the National Center for Health Statistics, the American Health Information Management Association, the American Hospital Association, and the Centers for Medicare & Medicaid Services.
Infographic: Inpatient Dermatology Consultations
Does AED prophylaxis delay seizure onset in children with brain tumors?
CHARLOTTE, N.C. – according to research presented at the annual meeting of the Child Neurology Society. Levetiracetam, oxcarbazepine, and phenytoin are the most common initial prophylactic AEDs administered to children with brain tumors, the researchers said.
The literature indicates that between 20% and 35% of children with brain tumors have seizures, and up to half of these patients have seizure as their presenting symptom. Common practice is to prescribe antiseizure medication after a child has had a first seizure, because the risk for recurrence is high. In 2000, the American Academy of Neurology discouraged prophylactic use of AEDs in children, citing a lack of evidence for efficacy. Most of the data that it reviewed, however, came from adults.
Michelle Yun, a medical student at Weill Cornell Medical College, New York, and colleagues used national Medicaid claims data that had been collected between 2009 and 2012 for children with seizures to conduct a retrospective, observational, case-control study. They included children aged 0-20 years with a diagnosis of brain tumor, a seizure diagnosis within 6 months after brain tumor diagnosis, an AED prescription, and 12 continuous months of Medicaid coverage following brain tumor diagnosis in their analysis. The investigators defined seizure prophylaxis as AED prescription within 30 days after brain tumor diagnosis but before a first seizure diagnosis.
The exposure in the study was AED prescription within 45 days of diagnosis, and the outcome was the time to first seizure. Ms. Yun and colleagues also analyzed the most common initial prophylactic AEDs and the proportion of cases with first seizure diagnosis after prophylactic AED discontinuation, which was defined as a treatment gap longer than 30 days. The study covariates included age, sex, race, ethnicity, and medical comorbidities.
In all, 218 children were included in the study; 40 received AED prophylaxis and 26 received it within 45 days of brain tumor diagnosis. Patients with and without AED prophylaxis were well matched on all covariates.
At 1 year, Ms. Yun and colleagues saw no difference in time to first seizure between the two groups. The median time to first seizure was 75 days in the prophylaxis group and 80 days in the no-prophylaxis group. The researchers observed a transient separation between the two groups, however, in the early months after brain tumor diagnosis. When they examined children who had a seizure during the first 6 months of follow-up, the median time to diagnosis of first seizure was 68 days in children with prophylaxis and 34 days in the no-prophylaxis group. The difference between groups was statistically significant. “When we added all the covariates of interest, we found that there was a protective effect in these children with early seizures,” said Ms. Yun.
Among the study limitations that Ms. Yun acknowledged were its observational, retrospective design and its small sample size. Medicaid data themselves are limited, since states do not report them in a uniform manner, and the data do not include much clinical information. “Something that would be helpful is a prospective clinical study,” Ms. Yun concluded.
The Weill Cornell Clinical and Translational Science Center and the American Academy of Neurology provided funding for the study. The Pediatric Epilepsy Research Foundation provided the Medicaid data. Ms. Yun had no relevant disclosures.
SOURCE: Yun M et al. CNS 2019, Abstract PL2-1.
CHARLOTTE, N.C. – according to research presented at the annual meeting of the Child Neurology Society. Levetiracetam, oxcarbazepine, and phenytoin are the most common initial prophylactic AEDs administered to children with brain tumors, the researchers said.
The literature indicates that between 20% and 35% of children with brain tumors have seizures, and up to half of these patients have seizure as their presenting symptom. Common practice is to prescribe antiseizure medication after a child has had a first seizure, because the risk for recurrence is high. In 2000, the American Academy of Neurology discouraged prophylactic use of AEDs in children, citing a lack of evidence for efficacy. Most of the data that it reviewed, however, came from adults.
Michelle Yun, a medical student at Weill Cornell Medical College, New York, and colleagues used national Medicaid claims data that had been collected between 2009 and 2012 for children with seizures to conduct a retrospective, observational, case-control study. They included children aged 0-20 years with a diagnosis of brain tumor, a seizure diagnosis within 6 months after brain tumor diagnosis, an AED prescription, and 12 continuous months of Medicaid coverage following brain tumor diagnosis in their analysis. The investigators defined seizure prophylaxis as AED prescription within 30 days after brain tumor diagnosis but before a first seizure diagnosis.
The exposure in the study was AED prescription within 45 days of diagnosis, and the outcome was the time to first seizure. Ms. Yun and colleagues also analyzed the most common initial prophylactic AEDs and the proportion of cases with first seizure diagnosis after prophylactic AED discontinuation, which was defined as a treatment gap longer than 30 days. The study covariates included age, sex, race, ethnicity, and medical comorbidities.
In all, 218 children were included in the study; 40 received AED prophylaxis and 26 received it within 45 days of brain tumor diagnosis. Patients with and without AED prophylaxis were well matched on all covariates.
At 1 year, Ms. Yun and colleagues saw no difference in time to first seizure between the two groups. The median time to first seizure was 75 days in the prophylaxis group and 80 days in the no-prophylaxis group. The researchers observed a transient separation between the two groups, however, in the early months after brain tumor diagnosis. When they examined children who had a seizure during the first 6 months of follow-up, the median time to diagnosis of first seizure was 68 days in children with prophylaxis and 34 days in the no-prophylaxis group. The difference between groups was statistically significant. “When we added all the covariates of interest, we found that there was a protective effect in these children with early seizures,” said Ms. Yun.
Among the study limitations that Ms. Yun acknowledged were its observational, retrospective design and its small sample size. Medicaid data themselves are limited, since states do not report them in a uniform manner, and the data do not include much clinical information. “Something that would be helpful is a prospective clinical study,” Ms. Yun concluded.
The Weill Cornell Clinical and Translational Science Center and the American Academy of Neurology provided funding for the study. The Pediatric Epilepsy Research Foundation provided the Medicaid data. Ms. Yun had no relevant disclosures.
SOURCE: Yun M et al. CNS 2019, Abstract PL2-1.
CHARLOTTE, N.C. – according to research presented at the annual meeting of the Child Neurology Society. Levetiracetam, oxcarbazepine, and phenytoin are the most common initial prophylactic AEDs administered to children with brain tumors, the researchers said.
The literature indicates that between 20% and 35% of children with brain tumors have seizures, and up to half of these patients have seizure as their presenting symptom. Common practice is to prescribe antiseizure medication after a child has had a first seizure, because the risk for recurrence is high. In 2000, the American Academy of Neurology discouraged prophylactic use of AEDs in children, citing a lack of evidence for efficacy. Most of the data that it reviewed, however, came from adults.
Michelle Yun, a medical student at Weill Cornell Medical College, New York, and colleagues used national Medicaid claims data that had been collected between 2009 and 2012 for children with seizures to conduct a retrospective, observational, case-control study. They included children aged 0-20 years with a diagnosis of brain tumor, a seizure diagnosis within 6 months after brain tumor diagnosis, an AED prescription, and 12 continuous months of Medicaid coverage following brain tumor diagnosis in their analysis. The investigators defined seizure prophylaxis as AED prescription within 30 days after brain tumor diagnosis but before a first seizure diagnosis.
The exposure in the study was AED prescription within 45 days of diagnosis, and the outcome was the time to first seizure. Ms. Yun and colleagues also analyzed the most common initial prophylactic AEDs and the proportion of cases with first seizure diagnosis after prophylactic AED discontinuation, which was defined as a treatment gap longer than 30 days. The study covariates included age, sex, race, ethnicity, and medical comorbidities.
In all, 218 children were included in the study; 40 received AED prophylaxis and 26 received it within 45 days of brain tumor diagnosis. Patients with and without AED prophylaxis were well matched on all covariates.
At 1 year, Ms. Yun and colleagues saw no difference in time to first seizure between the two groups. The median time to first seizure was 75 days in the prophylaxis group and 80 days in the no-prophylaxis group. The researchers observed a transient separation between the two groups, however, in the early months after brain tumor diagnosis. When they examined children who had a seizure during the first 6 months of follow-up, the median time to diagnosis of first seizure was 68 days in children with prophylaxis and 34 days in the no-prophylaxis group. The difference between groups was statistically significant. “When we added all the covariates of interest, we found that there was a protective effect in these children with early seizures,” said Ms. Yun.
Among the study limitations that Ms. Yun acknowledged were its observational, retrospective design and its small sample size. Medicaid data themselves are limited, since states do not report them in a uniform manner, and the data do not include much clinical information. “Something that would be helpful is a prospective clinical study,” Ms. Yun concluded.
The Weill Cornell Clinical and Translational Science Center and the American Academy of Neurology provided funding for the study. The Pediatric Epilepsy Research Foundation provided the Medicaid data. Ms. Yun had no relevant disclosures.
SOURCE: Yun M et al. CNS 2019, Abstract PL2-1.
REPORTING FROM CNS 2019
TNF level–based dosing of infliximab does not increase RA remission rate
A new study has indicated that tailoring dosage of infliximab based on serum levels of tumor necrosis factor–alpha did not increase the sustained remission rate in rheumatoid arthritis patients.
“The results did not support our initial hypothesis that deep remission and subsequent sustained discontinuation of infliximab can be achieved by intensive and finely tuned treatments with appropriate doses of TNF [tumor necrosis factor] inhibitors,” wrote Yoshiya Tanaka, MD, PhD, of the University of Occupational and Environmental Health, Kitakyushu, Japan. The study was published in Annals of the Rheumatic Diseases.
To determine if levels of TNF-alpha should initiate an increase in infliximab dosage, the researchers launched a multicenter, randomized trial of 337 patients with infliximab-naive RA. Patients were assigned to two groups: standard infliximab treatment of 3 mg/kg at weeks 0, 2, 6, and then every 8 weeks (n = 167) or programmed infliximab treatment (n = 170) in which the dose was adjusted at week 14 based on low, intermediate, or high levels of baseline TNF-alpha.
Patients with low levels (below 0.55 pg/mL) continued receiving 3 mg/kg every 8 weeks. Intermediate levels (between 0.55 and 1.65 pg/mL) meant an increase to 6 mg/kg every 8 weeks. High levels (1.65 pg/mL or higher) meant an increase to 6 mg/kg at week 14 and to 10 mg/kg at week 22 and every 8 weeks afterward. The goal was to discontinue infliximab at 54 weeks and reassess 1 year later.
After 54 weeks, 39.4% of patients in the programmed group and 32.3% of patients in the standard group achieved remission, defined as a Simplified Disease Activity Index (SDAI) score of 3.3 or lower. After 106 weeks, 23.5% of the programmed group and 21.6% of the standard group had maintained discontinuation of infliximab (–2.2% difference; 95% confidence interval, –6.6% to 11.0%; P = .631). After analysis, the most significant predictor of sustained discontinuation was a baseline SDAI less than 26.
The authors acknowledged their study’s limitations, including the initial version of the study not being double blinded. In addition, they noted that the short length of treatment and the low dosage overall “might not be intense enough to achieve differences in disease control between the two groups.”
The study was supported by a research grant from the Ministry of Health, Labor and Welfare of Japan. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, speaking fees, and/or honoraria from various medical and pharmaceutical companies.
SOURCE: Tanaka Y et al. Ann Rheum Dis. 2019 Oct 19. doi: 10.1136/annrheumdis-2019-216169.
A new study has indicated that tailoring dosage of infliximab based on serum levels of tumor necrosis factor–alpha did not increase the sustained remission rate in rheumatoid arthritis patients.
“The results did not support our initial hypothesis that deep remission and subsequent sustained discontinuation of infliximab can be achieved by intensive and finely tuned treatments with appropriate doses of TNF [tumor necrosis factor] inhibitors,” wrote Yoshiya Tanaka, MD, PhD, of the University of Occupational and Environmental Health, Kitakyushu, Japan. The study was published in Annals of the Rheumatic Diseases.
To determine if levels of TNF-alpha should initiate an increase in infliximab dosage, the researchers launched a multicenter, randomized trial of 337 patients with infliximab-naive RA. Patients were assigned to two groups: standard infliximab treatment of 3 mg/kg at weeks 0, 2, 6, and then every 8 weeks (n = 167) or programmed infliximab treatment (n = 170) in which the dose was adjusted at week 14 based on low, intermediate, or high levels of baseline TNF-alpha.
Patients with low levels (below 0.55 pg/mL) continued receiving 3 mg/kg every 8 weeks. Intermediate levels (between 0.55 and 1.65 pg/mL) meant an increase to 6 mg/kg every 8 weeks. High levels (1.65 pg/mL or higher) meant an increase to 6 mg/kg at week 14 and to 10 mg/kg at week 22 and every 8 weeks afterward. The goal was to discontinue infliximab at 54 weeks and reassess 1 year later.
After 54 weeks, 39.4% of patients in the programmed group and 32.3% of patients in the standard group achieved remission, defined as a Simplified Disease Activity Index (SDAI) score of 3.3 or lower. After 106 weeks, 23.5% of the programmed group and 21.6% of the standard group had maintained discontinuation of infliximab (–2.2% difference; 95% confidence interval, –6.6% to 11.0%; P = .631). After analysis, the most significant predictor of sustained discontinuation was a baseline SDAI less than 26.
The authors acknowledged their study’s limitations, including the initial version of the study not being double blinded. In addition, they noted that the short length of treatment and the low dosage overall “might not be intense enough to achieve differences in disease control between the two groups.”
The study was supported by a research grant from the Ministry of Health, Labor and Welfare of Japan. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, speaking fees, and/or honoraria from various medical and pharmaceutical companies.
SOURCE: Tanaka Y et al. Ann Rheum Dis. 2019 Oct 19. doi: 10.1136/annrheumdis-2019-216169.
A new study has indicated that tailoring dosage of infliximab based on serum levels of tumor necrosis factor–alpha did not increase the sustained remission rate in rheumatoid arthritis patients.
“The results did not support our initial hypothesis that deep remission and subsequent sustained discontinuation of infliximab can be achieved by intensive and finely tuned treatments with appropriate doses of TNF [tumor necrosis factor] inhibitors,” wrote Yoshiya Tanaka, MD, PhD, of the University of Occupational and Environmental Health, Kitakyushu, Japan. The study was published in Annals of the Rheumatic Diseases.
To determine if levels of TNF-alpha should initiate an increase in infliximab dosage, the researchers launched a multicenter, randomized trial of 337 patients with infliximab-naive RA. Patients were assigned to two groups: standard infliximab treatment of 3 mg/kg at weeks 0, 2, 6, and then every 8 weeks (n = 167) or programmed infliximab treatment (n = 170) in which the dose was adjusted at week 14 based on low, intermediate, or high levels of baseline TNF-alpha.
Patients with low levels (below 0.55 pg/mL) continued receiving 3 mg/kg every 8 weeks. Intermediate levels (between 0.55 and 1.65 pg/mL) meant an increase to 6 mg/kg every 8 weeks. High levels (1.65 pg/mL or higher) meant an increase to 6 mg/kg at week 14 and to 10 mg/kg at week 22 and every 8 weeks afterward. The goal was to discontinue infliximab at 54 weeks and reassess 1 year later.
After 54 weeks, 39.4% of patients in the programmed group and 32.3% of patients in the standard group achieved remission, defined as a Simplified Disease Activity Index (SDAI) score of 3.3 or lower. After 106 weeks, 23.5% of the programmed group and 21.6% of the standard group had maintained discontinuation of infliximab (–2.2% difference; 95% confidence interval, –6.6% to 11.0%; P = .631). After analysis, the most significant predictor of sustained discontinuation was a baseline SDAI less than 26.
The authors acknowledged their study’s limitations, including the initial version of the study not being double blinded. In addition, they noted that the short length of treatment and the low dosage overall “might not be intense enough to achieve differences in disease control between the two groups.”
The study was supported by a research grant from the Ministry of Health, Labor and Welfare of Japan. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, speaking fees, and/or honoraria from various medical and pharmaceutical companies.
SOURCE: Tanaka Y et al. Ann Rheum Dis. 2019 Oct 19. doi: 10.1136/annrheumdis-2019-216169.
FROM ANNALS OF THE RHEUMATIC DISEASES
Dr. Paul Aisen Q&A: Aducanumab for Alzheimer’s
In the wake of Biogen and Eisai’s Oct. 22 announcement about plans to apply to the Food and Drug Administration next year for the regulatory approval of the investigational monoclonal antibody aducanumab as a treatment for Alzheimer’s disease, we spoke with Paul Aisen, MD, the founding director of the Alzheimer’s Therapy Research Institute at the University of Southern California, Los Angeles, for his views on the news. He has been a consultant for Biogen and is a member of the aducanumab steering committee.
Q: What was your first reaction when you heard about the plan to submit an application for aducanumab to the FDA?
A: My initial reaction is that this provides terrific support for the amyloid hypothesis, and is consistent with the early aducanumab studies showing significant reductions in brain amyloid with resulting clinical improvement.
My next thought was that these data are going to be very, very challenging to analyze because both of these trials were stopped early, and one was clearly negative. We really need to scrutinize the data, but even at this point I would say this strongly supports targeting amyloid. The scrutiny will begin in detail at the Clinical Trials in Alzheimer’s Disease conference in December, when Biogen will likely release detailed data. A lot of people will analyze it, and I think that’s great. It’s beneficial to bring different perspectives.
We have had a terribly frustrating series of disappointments in the field. After the futility analysis of aducanumab and the multiple failures of BACE [beta-secretase] inhibitors, many were convinced we were barking up the wrong tree. I think these results, although complicated, should resurrect the enthusiasm for targeting amyloid.
Q: What is different about aducanumab from other antibodies tested – and rejected – in Alzheimer’s drug development?
A: There are lots of antibodies that have been tested in clinical trials. They all differ in terms of their affinity for amyloid beta. Some target monomers of the protein. Some target dimers. Some target fibrils. Some tie up amyloid and some reduce it. Aducanumab directly attacks brain plaques, reducing the plaque load in the brain. It carries a liability of amyloid-related imaging abnormalities [ARIA], but it also allows us to assess the impact that removing plaques might have on downstream events, including biomarkers. Overall, these data show that aducanumab did remove brain plaques and that removing them had a beneficial effect on cognition and function, and also a favorable effect on downstream biomarkers.
But again, we must be cautious because this is a complex data set taken from a post hoc analysis of two different terminated trials.
Q: We see some statistically significant differences in cognitive and functional outcomes. What would that mean for patients on an everyday basis?
A: Well, everyone is different, so that’s hard to say. A 25% slowing of functional decline on the Clinical Dementia Rating Scale sum of boxes (CDR-SB) might mean that, at the end of a year, there’s not a significant change in memory, or that there’s better social function. If both trials had been completed and if people had 18 months of high-dose aducanumab, the slowing of functional decline on the CDR-SB might in fact be greater than reported. Again, we’re having to draw conclusions from interrupted trials.
Q: This suggestion you make of a potentially continuous slowing of decline – are you suggesting that aducanumab might slow decline to the point of stopping it altogether? If an elderly patient has little or no progression until death would that, in effect, be considered a “cure?”
A: I don’t think it is possible to cure AD once the disease is clinically evident. These are studies of people with early AD, late mild cognitive impairment, and mild dementia. At that stage, there’s already a loss of synapses that won’t come back, and these studies don’t suggest that aducanumab can cure that. But what if people took it earlier, when the brain is still functioning normally? Some of us have argued for many years that earlier intervention is the way to go. And since we can now identify people [with brain plaques] before they become symptomatic, there is the possibility that if we removed them, we could stop progression.
Q: Are there any plans to study aducanumab as a preventive agent?
A: A grant has been awarded for this, but it was put on hold after the futility analysis. I don’t know when or if that will go forward.
(Editor’s note: The National Institutes of Health previously awarded Banner Health a $32 million, 5-year grant to examine this. The 2-year prevention study of aducanumab is aimed at cognitively unimpaired 65- to 80-year-old patients with PET-confirmed amyloid brain plaques. It was to be a multicenter, double-blind, placebo-controlled trial using Alzheimer’s biomarker endpoints as primary outcomes, along with cognitive and clinical changes, safety, and tolerability. The study was put on hold after Biogen discontinued the aducanumab development program in March. Investigators are considering whether to resurrect plans considering the new data. The study is intended to be a public-private partnership, with additional unspecified funding from Biogen plus $10 million from philanthropic sources. It has three intended goals: To find an approved prevention therapy as early as 2023, ahead of the National Plan to Address Alzheimer’s Disease’s goal of an effective prevention strategy by 2025; to advance the use of surrogate biomarkers to rapidly test and support accelerated approval of prevention therapies in almost everyone at biomarker or genetic risk, even in earlier preclinical Alzheimer’s stages when some treatments may have their greatest benefit; and to help make it possible to conduct prevention trials in at-risk persons even before they have extensive amyloid plaques, when some treatments may have their greatest benefit.)
Q: It seems like rolling this out to an enormous population of patients is going to be difficult, if not impossible. Are people really going to be able to commit to what could be a lifetime of monthly intravenous infusions of a medicine that could be expensive, as therapeutic antibodies generally are?
A: I would say, nothing about this disease is easy. It’s devastating and horrible. And if someone is diagnosed at this stage, I would think that individual would embrace any opportunity to treat it. My hope is that we will be able to prescreen people with an effective blood test for amyloid that would be part of a regular testing protocol once they reach a certain age. Those with positive results would be referred for more testing, including amyloid brain imaging.
In the wake of Biogen and Eisai’s Oct. 22 announcement about plans to apply to the Food and Drug Administration next year for the regulatory approval of the investigational monoclonal antibody aducanumab as a treatment for Alzheimer’s disease, we spoke with Paul Aisen, MD, the founding director of the Alzheimer’s Therapy Research Institute at the University of Southern California, Los Angeles, for his views on the news. He has been a consultant for Biogen and is a member of the aducanumab steering committee.
Q: What was your first reaction when you heard about the plan to submit an application for aducanumab to the FDA?
A: My initial reaction is that this provides terrific support for the amyloid hypothesis, and is consistent with the early aducanumab studies showing significant reductions in brain amyloid with resulting clinical improvement.
My next thought was that these data are going to be very, very challenging to analyze because both of these trials were stopped early, and one was clearly negative. We really need to scrutinize the data, but even at this point I would say this strongly supports targeting amyloid. The scrutiny will begin in detail at the Clinical Trials in Alzheimer’s Disease conference in December, when Biogen will likely release detailed data. A lot of people will analyze it, and I think that’s great. It’s beneficial to bring different perspectives.
We have had a terribly frustrating series of disappointments in the field. After the futility analysis of aducanumab and the multiple failures of BACE [beta-secretase] inhibitors, many were convinced we were barking up the wrong tree. I think these results, although complicated, should resurrect the enthusiasm for targeting amyloid.
Q: What is different about aducanumab from other antibodies tested – and rejected – in Alzheimer’s drug development?
A: There are lots of antibodies that have been tested in clinical trials. They all differ in terms of their affinity for amyloid beta. Some target monomers of the protein. Some target dimers. Some target fibrils. Some tie up amyloid and some reduce it. Aducanumab directly attacks brain plaques, reducing the plaque load in the brain. It carries a liability of amyloid-related imaging abnormalities [ARIA], but it also allows us to assess the impact that removing plaques might have on downstream events, including biomarkers. Overall, these data show that aducanumab did remove brain plaques and that removing them had a beneficial effect on cognition and function, and also a favorable effect on downstream biomarkers.
But again, we must be cautious because this is a complex data set taken from a post hoc analysis of two different terminated trials.
Q: We see some statistically significant differences in cognitive and functional outcomes. What would that mean for patients on an everyday basis?
A: Well, everyone is different, so that’s hard to say. A 25% slowing of functional decline on the Clinical Dementia Rating Scale sum of boxes (CDR-SB) might mean that, at the end of a year, there’s not a significant change in memory, or that there’s better social function. If both trials had been completed and if people had 18 months of high-dose aducanumab, the slowing of functional decline on the CDR-SB might in fact be greater than reported. Again, we’re having to draw conclusions from interrupted trials.
Q: This suggestion you make of a potentially continuous slowing of decline – are you suggesting that aducanumab might slow decline to the point of stopping it altogether? If an elderly patient has little or no progression until death would that, in effect, be considered a “cure?”
A: I don’t think it is possible to cure AD once the disease is clinically evident. These are studies of people with early AD, late mild cognitive impairment, and mild dementia. At that stage, there’s already a loss of synapses that won’t come back, and these studies don’t suggest that aducanumab can cure that. But what if people took it earlier, when the brain is still functioning normally? Some of us have argued for many years that earlier intervention is the way to go. And since we can now identify people [with brain plaques] before they become symptomatic, there is the possibility that if we removed them, we could stop progression.
Q: Are there any plans to study aducanumab as a preventive agent?
A: A grant has been awarded for this, but it was put on hold after the futility analysis. I don’t know when or if that will go forward.
(Editor’s note: The National Institutes of Health previously awarded Banner Health a $32 million, 5-year grant to examine this. The 2-year prevention study of aducanumab is aimed at cognitively unimpaired 65- to 80-year-old patients with PET-confirmed amyloid brain plaques. It was to be a multicenter, double-blind, placebo-controlled trial using Alzheimer’s biomarker endpoints as primary outcomes, along with cognitive and clinical changes, safety, and tolerability. The study was put on hold after Biogen discontinued the aducanumab development program in March. Investigators are considering whether to resurrect plans considering the new data. The study is intended to be a public-private partnership, with additional unspecified funding from Biogen plus $10 million from philanthropic sources. It has three intended goals: To find an approved prevention therapy as early as 2023, ahead of the National Plan to Address Alzheimer’s Disease’s goal of an effective prevention strategy by 2025; to advance the use of surrogate biomarkers to rapidly test and support accelerated approval of prevention therapies in almost everyone at biomarker or genetic risk, even in earlier preclinical Alzheimer’s stages when some treatments may have their greatest benefit; and to help make it possible to conduct prevention trials in at-risk persons even before they have extensive amyloid plaques, when some treatments may have their greatest benefit.)
Q: It seems like rolling this out to an enormous population of patients is going to be difficult, if not impossible. Are people really going to be able to commit to what could be a lifetime of monthly intravenous infusions of a medicine that could be expensive, as therapeutic antibodies generally are?
A: I would say, nothing about this disease is easy. It’s devastating and horrible. And if someone is diagnosed at this stage, I would think that individual would embrace any opportunity to treat it. My hope is that we will be able to prescreen people with an effective blood test for amyloid that would be part of a regular testing protocol once they reach a certain age. Those with positive results would be referred for more testing, including amyloid brain imaging.
In the wake of Biogen and Eisai’s Oct. 22 announcement about plans to apply to the Food and Drug Administration next year for the regulatory approval of the investigational monoclonal antibody aducanumab as a treatment for Alzheimer’s disease, we spoke with Paul Aisen, MD, the founding director of the Alzheimer’s Therapy Research Institute at the University of Southern California, Los Angeles, for his views on the news. He has been a consultant for Biogen and is a member of the aducanumab steering committee.
Q: What was your first reaction when you heard about the plan to submit an application for aducanumab to the FDA?
A: My initial reaction is that this provides terrific support for the amyloid hypothesis, and is consistent with the early aducanumab studies showing significant reductions in brain amyloid with resulting clinical improvement.
My next thought was that these data are going to be very, very challenging to analyze because both of these trials were stopped early, and one was clearly negative. We really need to scrutinize the data, but even at this point I would say this strongly supports targeting amyloid. The scrutiny will begin in detail at the Clinical Trials in Alzheimer’s Disease conference in December, when Biogen will likely release detailed data. A lot of people will analyze it, and I think that’s great. It’s beneficial to bring different perspectives.
We have had a terribly frustrating series of disappointments in the field. After the futility analysis of aducanumab and the multiple failures of BACE [beta-secretase] inhibitors, many were convinced we were barking up the wrong tree. I think these results, although complicated, should resurrect the enthusiasm for targeting amyloid.
Q: What is different about aducanumab from other antibodies tested – and rejected – in Alzheimer’s drug development?
A: There are lots of antibodies that have been tested in clinical trials. They all differ in terms of their affinity for amyloid beta. Some target monomers of the protein. Some target dimers. Some target fibrils. Some tie up amyloid and some reduce it. Aducanumab directly attacks brain plaques, reducing the plaque load in the brain. It carries a liability of amyloid-related imaging abnormalities [ARIA], but it also allows us to assess the impact that removing plaques might have on downstream events, including biomarkers. Overall, these data show that aducanumab did remove brain plaques and that removing them had a beneficial effect on cognition and function, and also a favorable effect on downstream biomarkers.
But again, we must be cautious because this is a complex data set taken from a post hoc analysis of two different terminated trials.
Q: We see some statistically significant differences in cognitive and functional outcomes. What would that mean for patients on an everyday basis?
A: Well, everyone is different, so that’s hard to say. A 25% slowing of functional decline on the Clinical Dementia Rating Scale sum of boxes (CDR-SB) might mean that, at the end of a year, there’s not a significant change in memory, or that there’s better social function. If both trials had been completed and if people had 18 months of high-dose aducanumab, the slowing of functional decline on the CDR-SB might in fact be greater than reported. Again, we’re having to draw conclusions from interrupted trials.
Q: This suggestion you make of a potentially continuous slowing of decline – are you suggesting that aducanumab might slow decline to the point of stopping it altogether? If an elderly patient has little or no progression until death would that, in effect, be considered a “cure?”
A: I don’t think it is possible to cure AD once the disease is clinically evident. These are studies of people with early AD, late mild cognitive impairment, and mild dementia. At that stage, there’s already a loss of synapses that won’t come back, and these studies don’t suggest that aducanumab can cure that. But what if people took it earlier, when the brain is still functioning normally? Some of us have argued for many years that earlier intervention is the way to go. And since we can now identify people [with brain plaques] before they become symptomatic, there is the possibility that if we removed them, we could stop progression.
Q: Are there any plans to study aducanumab as a preventive agent?
A: A grant has been awarded for this, but it was put on hold after the futility analysis. I don’t know when or if that will go forward.
(Editor’s note: The National Institutes of Health previously awarded Banner Health a $32 million, 5-year grant to examine this. The 2-year prevention study of aducanumab is aimed at cognitively unimpaired 65- to 80-year-old patients with PET-confirmed amyloid brain plaques. It was to be a multicenter, double-blind, placebo-controlled trial using Alzheimer’s biomarker endpoints as primary outcomes, along with cognitive and clinical changes, safety, and tolerability. The study was put on hold after Biogen discontinued the aducanumab development program in March. Investigators are considering whether to resurrect plans considering the new data. The study is intended to be a public-private partnership, with additional unspecified funding from Biogen plus $10 million from philanthropic sources. It has three intended goals: To find an approved prevention therapy as early as 2023, ahead of the National Plan to Address Alzheimer’s Disease’s goal of an effective prevention strategy by 2025; to advance the use of surrogate biomarkers to rapidly test and support accelerated approval of prevention therapies in almost everyone at biomarker or genetic risk, even in earlier preclinical Alzheimer’s stages when some treatments may have their greatest benefit; and to help make it possible to conduct prevention trials in at-risk persons even before they have extensive amyloid plaques, when some treatments may have their greatest benefit.)
Q: It seems like rolling this out to an enormous population of patients is going to be difficult, if not impossible. Are people really going to be able to commit to what could be a lifetime of monthly intravenous infusions of a medicine that could be expensive, as therapeutic antibodies generally are?
A: I would say, nothing about this disease is easy. It’s devastating and horrible. And if someone is diagnosed at this stage, I would think that individual would embrace any opportunity to treat it. My hope is that we will be able to prescreen people with an effective blood test for amyloid that would be part of a regular testing protocol once they reach a certain age. Those with positive results would be referred for more testing, including amyloid brain imaging.
PASI-75 with ixekizumab approaches 90% in pediatric psoriasis study
MADRID – The interleukin-17A inhibitor , Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The results bode well for an underserved population.
“I think all of us know that there is still a vulnerable population that remains a high-risk population because of the limited number of therapies available for them, and that is children,” said Dr. Papp, a dermatologist and president of Probity Medical Research, Inc., of Waterloo, Ont.
At present, etanercept, one of the earliest biologics to become available, and a relatively less effective one, is the only biologic approved for treatment of pediatric psoriasis. However, Lilly, which sponsored the phase 3 ixekizumab study, has announced that based upon the highly positive findings the company plans to seek Food and Drug Administration approval for an expanded indication for the medication in pediatric psoriasis. The company now markets ixekizumab for the approved indications of treatment of adults with moderate to severe plaque psoriasis, active psoriatic arthritis, or active ankylosing spondylitis.
The 12-week, double-blind, multicenter phase 3 trial known as IXORA-PEDS included 115 pediatric psoriasis patients randomized to weight-based ixekizumab, 30 on weight-based etanercept, and 58 on placebo. At the 12-week mark, everyone was switched to open-label ixekizumab in a long-term extension study. Children weighing less than 25 kg received a 40-mg loading dose of ixekizumab, followed by a maintenance dose of 20 mg by subcutaneous injection every 4 weeks. Patients weighing 25-50 kg got a starting dose of 80 mg, then 40 mg for maintenance therapy. Those who weighed more than 50 kg got the usual adult dosing: a 160-mg loading dose followed by 80 mg every 4 weeks. Etanercept was dosed at 0.8 mg/kg once weekly.
The coprimary endpoints were the proportion of subjects achieving a static Physician’s Global Assessment (sPGA) of 0 or 1 – that is, clear or almost clear skin – at week 12, and the PASI 75 response rate.
An sPGA of 0 or 1 at week 12 was documented in 81% of the ixekizumab group, 11% on placebo, and 40% of etanercept-treated patients, who on average had more severe baseline disease than did the other two groups.
The PASI 75 rate was 89% with ixekizumab, 25% for placebo, and 63% on etanercept. But Dr. Papp indicated that’s too low a bar. “I don’t think PASI 75s are the standard any longer,” he said.
More revealing was the PASI 90 rate: 78% with the IL-17A inhibitor, 5% in placebo-treated controls, and 40% with etanercept.
And then there’s the PASI 100 response rate: 50% with ixekizumab, 2% for placebo, and 17% for etanercept.
“I think this is very telling. I’ll leave it as a tantalizing comment that if one looks at the slope of the curve, it doesn’t yet seem to have reached its plateau at week 12 – and this is very similar to the pattern that we see in the adult population. I don’t have the long-term extension efficacy data, but I am, like you, very interested in seeing where this PASI 100 response rate finally plateaus,” Dr. Papp said.
He did, however, have the combined safety data for the 12-week double-blind phase plus the open-label extension, which he described as essentially the same as the adult experience. Injection-site reactions occurred in 19% of pediatric patients on ixekizumab, but they were generally mild and there were few if any treatment discontinuations for that reason. There was a 2% incidence of Crohn’s disease. Candidiasis and other infections were rare.
Seventy-one percent of the ixekizumab group had at least a 4-point improvement in itch on a 10-point self-rated scale by week 12, as did 20% of placebo-treated controls. A Dermatologic Life Quality Index score of 0 or 1 at week 12, indicative of no or minimal impact of psoriasis on quality of life, was documented in 64% of the ixekizumab group and 23% of controls.
Dr. Papp reported serving as a consultant, investigator, and/or speaker for Lilly and more than three dozen other pharmaceutical companies.
SOURCE: Papp KA. EADV Late breaker.
MADRID – The interleukin-17A inhibitor , Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The results bode well for an underserved population.
“I think all of us know that there is still a vulnerable population that remains a high-risk population because of the limited number of therapies available for them, and that is children,” said Dr. Papp, a dermatologist and president of Probity Medical Research, Inc., of Waterloo, Ont.
At present, etanercept, one of the earliest biologics to become available, and a relatively less effective one, is the only biologic approved for treatment of pediatric psoriasis. However, Lilly, which sponsored the phase 3 ixekizumab study, has announced that based upon the highly positive findings the company plans to seek Food and Drug Administration approval for an expanded indication for the medication in pediatric psoriasis. The company now markets ixekizumab for the approved indications of treatment of adults with moderate to severe plaque psoriasis, active psoriatic arthritis, or active ankylosing spondylitis.
The 12-week, double-blind, multicenter phase 3 trial known as IXORA-PEDS included 115 pediatric psoriasis patients randomized to weight-based ixekizumab, 30 on weight-based etanercept, and 58 on placebo. At the 12-week mark, everyone was switched to open-label ixekizumab in a long-term extension study. Children weighing less than 25 kg received a 40-mg loading dose of ixekizumab, followed by a maintenance dose of 20 mg by subcutaneous injection every 4 weeks. Patients weighing 25-50 kg got a starting dose of 80 mg, then 40 mg for maintenance therapy. Those who weighed more than 50 kg got the usual adult dosing: a 160-mg loading dose followed by 80 mg every 4 weeks. Etanercept was dosed at 0.8 mg/kg once weekly.
The coprimary endpoints were the proportion of subjects achieving a static Physician’s Global Assessment (sPGA) of 0 or 1 – that is, clear or almost clear skin – at week 12, and the PASI 75 response rate.
An sPGA of 0 or 1 at week 12 was documented in 81% of the ixekizumab group, 11% on placebo, and 40% of etanercept-treated patients, who on average had more severe baseline disease than did the other two groups.
The PASI 75 rate was 89% with ixekizumab, 25% for placebo, and 63% on etanercept. But Dr. Papp indicated that’s too low a bar. “I don’t think PASI 75s are the standard any longer,” he said.
More revealing was the PASI 90 rate: 78% with the IL-17A inhibitor, 5% in placebo-treated controls, and 40% with etanercept.
And then there’s the PASI 100 response rate: 50% with ixekizumab, 2% for placebo, and 17% for etanercept.
“I think this is very telling. I’ll leave it as a tantalizing comment that if one looks at the slope of the curve, it doesn’t yet seem to have reached its plateau at week 12 – and this is very similar to the pattern that we see in the adult population. I don’t have the long-term extension efficacy data, but I am, like you, very interested in seeing where this PASI 100 response rate finally plateaus,” Dr. Papp said.
He did, however, have the combined safety data for the 12-week double-blind phase plus the open-label extension, which he described as essentially the same as the adult experience. Injection-site reactions occurred in 19% of pediatric patients on ixekizumab, but they were generally mild and there were few if any treatment discontinuations for that reason. There was a 2% incidence of Crohn’s disease. Candidiasis and other infections were rare.
Seventy-one percent of the ixekizumab group had at least a 4-point improvement in itch on a 10-point self-rated scale by week 12, as did 20% of placebo-treated controls. A Dermatologic Life Quality Index score of 0 or 1 at week 12, indicative of no or minimal impact of psoriasis on quality of life, was documented in 64% of the ixekizumab group and 23% of controls.
Dr. Papp reported serving as a consultant, investigator, and/or speaker for Lilly and more than three dozen other pharmaceutical companies.
SOURCE: Papp KA. EADV Late breaker.
MADRID – The interleukin-17A inhibitor , Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The results bode well for an underserved population.
“I think all of us know that there is still a vulnerable population that remains a high-risk population because of the limited number of therapies available for them, and that is children,” said Dr. Papp, a dermatologist and president of Probity Medical Research, Inc., of Waterloo, Ont.
At present, etanercept, one of the earliest biologics to become available, and a relatively less effective one, is the only biologic approved for treatment of pediatric psoriasis. However, Lilly, which sponsored the phase 3 ixekizumab study, has announced that based upon the highly positive findings the company plans to seek Food and Drug Administration approval for an expanded indication for the medication in pediatric psoriasis. The company now markets ixekizumab for the approved indications of treatment of adults with moderate to severe plaque psoriasis, active psoriatic arthritis, or active ankylosing spondylitis.
The 12-week, double-blind, multicenter phase 3 trial known as IXORA-PEDS included 115 pediatric psoriasis patients randomized to weight-based ixekizumab, 30 on weight-based etanercept, and 58 on placebo. At the 12-week mark, everyone was switched to open-label ixekizumab in a long-term extension study. Children weighing less than 25 kg received a 40-mg loading dose of ixekizumab, followed by a maintenance dose of 20 mg by subcutaneous injection every 4 weeks. Patients weighing 25-50 kg got a starting dose of 80 mg, then 40 mg for maintenance therapy. Those who weighed more than 50 kg got the usual adult dosing: a 160-mg loading dose followed by 80 mg every 4 weeks. Etanercept was dosed at 0.8 mg/kg once weekly.
The coprimary endpoints were the proportion of subjects achieving a static Physician’s Global Assessment (sPGA) of 0 or 1 – that is, clear or almost clear skin – at week 12, and the PASI 75 response rate.
An sPGA of 0 or 1 at week 12 was documented in 81% of the ixekizumab group, 11% on placebo, and 40% of etanercept-treated patients, who on average had more severe baseline disease than did the other two groups.
The PASI 75 rate was 89% with ixekizumab, 25% for placebo, and 63% on etanercept. But Dr. Papp indicated that’s too low a bar. “I don’t think PASI 75s are the standard any longer,” he said.
More revealing was the PASI 90 rate: 78% with the IL-17A inhibitor, 5% in placebo-treated controls, and 40% with etanercept.
And then there’s the PASI 100 response rate: 50% with ixekizumab, 2% for placebo, and 17% for etanercept.
“I think this is very telling. I’ll leave it as a tantalizing comment that if one looks at the slope of the curve, it doesn’t yet seem to have reached its plateau at week 12 – and this is very similar to the pattern that we see in the adult population. I don’t have the long-term extension efficacy data, but I am, like you, very interested in seeing where this PASI 100 response rate finally plateaus,” Dr. Papp said.
He did, however, have the combined safety data for the 12-week double-blind phase plus the open-label extension, which he described as essentially the same as the adult experience. Injection-site reactions occurred in 19% of pediatric patients on ixekizumab, but they were generally mild and there were few if any treatment discontinuations for that reason. There was a 2% incidence of Crohn’s disease. Candidiasis and other infections were rare.
Seventy-one percent of the ixekizumab group had at least a 4-point improvement in itch on a 10-point self-rated scale by week 12, as did 20% of placebo-treated controls. A Dermatologic Life Quality Index score of 0 or 1 at week 12, indicative of no or minimal impact of psoriasis on quality of life, was documented in 64% of the ixekizumab group and 23% of controls.
Dr. Papp reported serving as a consultant, investigator, and/or speaker for Lilly and more than three dozen other pharmaceutical companies.
SOURCE: Papp KA. EADV Late breaker.
REPORTING FROM THE EADV CONGRESS
Omalizumab results for asthma varied with fixed airflow obstruction, reversibility
NEW ORLEANS – A new analysis suggests However, exacerbation reductions were greatest in patients with high reversibility, and omalizumab only improved lung function significantly in FAO-negative patients with high reversibility.
Nicola Hanania, MD, of Baylor College of Medicine, Houston, presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from a post hoc analysis of the phase 3 EXTRA study (NCT00314574). This 48-week study enrolled patients who had inadequately controlled, severe asthma despite receiving high-dose inhaled corticosteroids and long-acting beta-agonists.
The patients were randomized to receive omalizumab (n = 427) or placebo (n = 421). Baseline characteristics were similar between the treatment arms.
FAO presence was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio less than 70%. High reversibility was defined as an increase in FEV1 of 12% or greater after albuterol administration.Omalizumab reduced exacerbations regardless of FAO, but the exacerbation relative rate reductions were greatest in FAO-positive and -negative subgroups with high reversibility.
The exacerbation relative rate reductions with omalizumab versus placebo were as follows:
- 24.8% in the overall population.
- 6.0% in FAO-positive patients with low reversibility.
- 59.8% in FAO-positive patients with high reversibility.
- 17.4% in FAO-negative patients with low reversibility.
- 44.3% in FAO-negative patients with high reversibility.
“So bronchodilator reversibility at baseline was … a correlate of more significant exacerbation reduction than … low reversibility,” Dr. Hanania said. “But the fixed airflow obstruction, whether it was present or not, did not really matter.”
As for lung function improvement, omalizumab conferred a marginal benefit for the overall population, but the improvement was “much more significant” in the FAO-negative patients with high reversibility, according to Dr. Hanania.
At week 48, the least-square mean treatment difference (omalizumab vs. placebo) for absolute FEV1 change from baseline was:
- 68 mL in the overall population.
- 17 mL in FAO-positive patients with low reversibility.
- 2 mL in FAO-positive patients with high reversibility.
- 34 mL in FAO-negative patients with low reversibility.
- 104 mL in FAO-negative patients with high reversibility.
“As lung function improvement by omalizumab appeared to be driven by reversibility, asthma with lower reversibility and fixed airflow obstruction may represent a different phenotype,” Dr. Hanania said. “I think this needs to be looked at.”
This research was funded by Genentech and Novartis. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.869.
NEW ORLEANS – A new analysis suggests However, exacerbation reductions were greatest in patients with high reversibility, and omalizumab only improved lung function significantly in FAO-negative patients with high reversibility.
Nicola Hanania, MD, of Baylor College of Medicine, Houston, presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from a post hoc analysis of the phase 3 EXTRA study (NCT00314574). This 48-week study enrolled patients who had inadequately controlled, severe asthma despite receiving high-dose inhaled corticosteroids and long-acting beta-agonists.
The patients were randomized to receive omalizumab (n = 427) or placebo (n = 421). Baseline characteristics were similar between the treatment arms.
FAO presence was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio less than 70%. High reversibility was defined as an increase in FEV1 of 12% or greater after albuterol administration.Omalizumab reduced exacerbations regardless of FAO, but the exacerbation relative rate reductions were greatest in FAO-positive and -negative subgroups with high reversibility.
The exacerbation relative rate reductions with omalizumab versus placebo were as follows:
- 24.8% in the overall population.
- 6.0% in FAO-positive patients with low reversibility.
- 59.8% in FAO-positive patients with high reversibility.
- 17.4% in FAO-negative patients with low reversibility.
- 44.3% in FAO-negative patients with high reversibility.
“So bronchodilator reversibility at baseline was … a correlate of more significant exacerbation reduction than … low reversibility,” Dr. Hanania said. “But the fixed airflow obstruction, whether it was present or not, did not really matter.”
As for lung function improvement, omalizumab conferred a marginal benefit for the overall population, but the improvement was “much more significant” in the FAO-negative patients with high reversibility, according to Dr. Hanania.
At week 48, the least-square mean treatment difference (omalizumab vs. placebo) for absolute FEV1 change from baseline was:
- 68 mL in the overall population.
- 17 mL in FAO-positive patients with low reversibility.
- 2 mL in FAO-positive patients with high reversibility.
- 34 mL in FAO-negative patients with low reversibility.
- 104 mL in FAO-negative patients with high reversibility.
“As lung function improvement by omalizumab appeared to be driven by reversibility, asthma with lower reversibility and fixed airflow obstruction may represent a different phenotype,” Dr. Hanania said. “I think this needs to be looked at.”
This research was funded by Genentech and Novartis. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.869.
NEW ORLEANS – A new analysis suggests However, exacerbation reductions were greatest in patients with high reversibility, and omalizumab only improved lung function significantly in FAO-negative patients with high reversibility.
Nicola Hanania, MD, of Baylor College of Medicine, Houston, presented these findings at the annual meeting of the American College of Chest Physicians.
The findings are from a post hoc analysis of the phase 3 EXTRA study (NCT00314574). This 48-week study enrolled patients who had inadequately controlled, severe asthma despite receiving high-dose inhaled corticosteroids and long-acting beta-agonists.
The patients were randomized to receive omalizumab (n = 427) or placebo (n = 421). Baseline characteristics were similar between the treatment arms.
FAO presence was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio less than 70%. High reversibility was defined as an increase in FEV1 of 12% or greater after albuterol administration.Omalizumab reduced exacerbations regardless of FAO, but the exacerbation relative rate reductions were greatest in FAO-positive and -negative subgroups with high reversibility.
The exacerbation relative rate reductions with omalizumab versus placebo were as follows:
- 24.8% in the overall population.
- 6.0% in FAO-positive patients with low reversibility.
- 59.8% in FAO-positive patients with high reversibility.
- 17.4% in FAO-negative patients with low reversibility.
- 44.3% in FAO-negative patients with high reversibility.
“So bronchodilator reversibility at baseline was … a correlate of more significant exacerbation reduction than … low reversibility,” Dr. Hanania said. “But the fixed airflow obstruction, whether it was present or not, did not really matter.”
As for lung function improvement, omalizumab conferred a marginal benefit for the overall population, but the improvement was “much more significant” in the FAO-negative patients with high reversibility, according to Dr. Hanania.
At week 48, the least-square mean treatment difference (omalizumab vs. placebo) for absolute FEV1 change from baseline was:
- 68 mL in the overall population.
- 17 mL in FAO-positive patients with low reversibility.
- 2 mL in FAO-positive patients with high reversibility.
- 34 mL in FAO-negative patients with low reversibility.
- 104 mL in FAO-negative patients with high reversibility.
“As lung function improvement by omalizumab appeared to be driven by reversibility, asthma with lower reversibility and fixed airflow obstruction may represent a different phenotype,” Dr. Hanania said. “I think this needs to be looked at.”
This research was funded by Genentech and Novartis. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.869.
REPORTING FROM CHEST 2019
Demeaning patient behavior takes emotional toll on physicians
Despite an increasingly diverse workforce, a new study has found that many patients remain biased toward certain physicians, which can produce substantial negative – and occasionally positive – effects.
“Addressing demeaning behavior from patients will require a concerted effort from medical schools and hospital leadership to create an environment that respects the diversity of patients and physicians alike,” wrote Margaret Wheeler, MD, of the University of California, San Francisco (UCSF) and her coauthors. The study was published in JAMA Internal Medicine.
To determine the perspectives of physicians and trainees in regard to patient bias, along with potential barriers to responding effectively, the researchers led 13 focus groups attended by internal 11 medicine hospitalist physicians, 26 internal medicine residents, and 13 medical students affiliated with the UCSF School of Medicine. In terms of gender, 26 participants identified as women, 22 as men, and 2 as gender nonconforming. In terms of racial and ethnic diversity, 26 were white, 8 were Latinx, 7 were Asian, 3 were South Asian, 1 was Middle Eastern, and 5 were black.
In describing biased and demeaning patient behavior, the participants recalled remarks that ranged from refusal of care and questioning the clinician’s role to ethnic jokes, questions as to their ethnic backgrounds, inappropriate flirtations or compliments. The effects of these behaviors on the participants included negative responses like carrying an emotional burden and withdrawing from work, along with positive responses like an increased desire for self-growth and to pursue leadership opportunities.
Barriers to addressing these behaviors included a lack of support, uncertainty as to the appropriate response, and a fear of being perceived as unprofessional. Deciding how to respond – or to respond at all – was often dictated by the level of support from colleagues, a professional responsibility to peers, and the presence of a positive role model who would’ve done the same.
The authors acknowledged their study’s limitations, including only knowing the views of those who were interviewed. In addition, all participants came from a medical school located in a diverse city that embraces different cultures, meaning their findings “may not reflect the experiences of physicians in other geographic regions.”
The study was supported by the Greenwall Foundation. The authors reported no conflicts of interest.
SOURCE: Wheeler M et al. JAMA Intern Med. 2019 Oct 28. doi: 10.1001/jamainternmed.2019.4122.
The results of the patient bias study from Wheeler et al are troubling, but not surprising.
As the physician workforce becomes more diverse in regard to race, ethnicity, sex, gender identity, and sexual orientation, considering and addressing the negative impacts of demeaning patient interactions becomes increasingly important. And though a recent analysis stated a decline in biases between 2007 and 2016, discriminatory and disrespectful treatment remains the norm for members of many minority groups.
Strategies to address these behaviors include codes of professional ethics offering guidance on responding to disrespectful behavior, antidiscrimination training for all health professionals, and health care leaders themselves practicing and preaching respectfulness and civility within their institutions.
Patients can only be expected to behave respectfully towards physicians if the culture of health care is also respectful.
When anyone, including a patient, exhibits biased and disrespectful behavior, silence is not golden. It is tacit approval. We all have the responsibility to speak and act.
Lisa A. Cooper, MD, and Mary Catherine Beach, MD, of Johns Hopkins University in Baltimore; and David R. Williams, PhD, of Harvard University, Boston, made these comments in an accompanying editorial (JAMA Intern Med. 2019 Oct 28. doi: 10.1001/jamainternmed.2019.4100). They reported no conflicts of interest.
The results of the patient bias study from Wheeler et al are troubling, but not surprising.
As the physician workforce becomes more diverse in regard to race, ethnicity, sex, gender identity, and sexual orientation, considering and addressing the negative impacts of demeaning patient interactions becomes increasingly important. And though a recent analysis stated a decline in biases between 2007 and 2016, discriminatory and disrespectful treatment remains the norm for members of many minority groups.
Strategies to address these behaviors include codes of professional ethics offering guidance on responding to disrespectful behavior, antidiscrimination training for all health professionals, and health care leaders themselves practicing and preaching respectfulness and civility within their institutions.
Patients can only be expected to behave respectfully towards physicians if the culture of health care is also respectful.
When anyone, including a patient, exhibits biased and disrespectful behavior, silence is not golden. It is tacit approval. We all have the responsibility to speak and act.
Lisa A. Cooper, MD, and Mary Catherine Beach, MD, of Johns Hopkins University in Baltimore; and David R. Williams, PhD, of Harvard University, Boston, made these comments in an accompanying editorial (JAMA Intern Med. 2019 Oct 28. doi: 10.1001/jamainternmed.2019.4100). They reported no conflicts of interest.
The results of the patient bias study from Wheeler et al are troubling, but not surprising.
As the physician workforce becomes more diverse in regard to race, ethnicity, sex, gender identity, and sexual orientation, considering and addressing the negative impacts of demeaning patient interactions becomes increasingly important. And though a recent analysis stated a decline in biases between 2007 and 2016, discriminatory and disrespectful treatment remains the norm for members of many minority groups.
Strategies to address these behaviors include codes of professional ethics offering guidance on responding to disrespectful behavior, antidiscrimination training for all health professionals, and health care leaders themselves practicing and preaching respectfulness and civility within their institutions.
Patients can only be expected to behave respectfully towards physicians if the culture of health care is also respectful.
When anyone, including a patient, exhibits biased and disrespectful behavior, silence is not golden. It is tacit approval. We all have the responsibility to speak and act.
Lisa A. Cooper, MD, and Mary Catherine Beach, MD, of Johns Hopkins University in Baltimore; and David R. Williams, PhD, of Harvard University, Boston, made these comments in an accompanying editorial (JAMA Intern Med. 2019 Oct 28. doi: 10.1001/jamainternmed.2019.4100). They reported no conflicts of interest.
Despite an increasingly diverse workforce, a new study has found that many patients remain biased toward certain physicians, which can produce substantial negative – and occasionally positive – effects.
“Addressing demeaning behavior from patients will require a concerted effort from medical schools and hospital leadership to create an environment that respects the diversity of patients and physicians alike,” wrote Margaret Wheeler, MD, of the University of California, San Francisco (UCSF) and her coauthors. The study was published in JAMA Internal Medicine.
To determine the perspectives of physicians and trainees in regard to patient bias, along with potential barriers to responding effectively, the researchers led 13 focus groups attended by internal 11 medicine hospitalist physicians, 26 internal medicine residents, and 13 medical students affiliated with the UCSF School of Medicine. In terms of gender, 26 participants identified as women, 22 as men, and 2 as gender nonconforming. In terms of racial and ethnic diversity, 26 were white, 8 were Latinx, 7 were Asian, 3 were South Asian, 1 was Middle Eastern, and 5 were black.
In describing biased and demeaning patient behavior, the participants recalled remarks that ranged from refusal of care and questioning the clinician’s role to ethnic jokes, questions as to their ethnic backgrounds, inappropriate flirtations or compliments. The effects of these behaviors on the participants included negative responses like carrying an emotional burden and withdrawing from work, along with positive responses like an increased desire for self-growth and to pursue leadership opportunities.
Barriers to addressing these behaviors included a lack of support, uncertainty as to the appropriate response, and a fear of being perceived as unprofessional. Deciding how to respond – or to respond at all – was often dictated by the level of support from colleagues, a professional responsibility to peers, and the presence of a positive role model who would’ve done the same.
The authors acknowledged their study’s limitations, including only knowing the views of those who were interviewed. In addition, all participants came from a medical school located in a diverse city that embraces different cultures, meaning their findings “may not reflect the experiences of physicians in other geographic regions.”
The study was supported by the Greenwall Foundation. The authors reported no conflicts of interest.
SOURCE: Wheeler M et al. JAMA Intern Med. 2019 Oct 28. doi: 10.1001/jamainternmed.2019.4122.
Despite an increasingly diverse workforce, a new study has found that many patients remain biased toward certain physicians, which can produce substantial negative – and occasionally positive – effects.
“Addressing demeaning behavior from patients will require a concerted effort from medical schools and hospital leadership to create an environment that respects the diversity of patients and physicians alike,” wrote Margaret Wheeler, MD, of the University of California, San Francisco (UCSF) and her coauthors. The study was published in JAMA Internal Medicine.
To determine the perspectives of physicians and trainees in regard to patient bias, along with potential barriers to responding effectively, the researchers led 13 focus groups attended by internal 11 medicine hospitalist physicians, 26 internal medicine residents, and 13 medical students affiliated with the UCSF School of Medicine. In terms of gender, 26 participants identified as women, 22 as men, and 2 as gender nonconforming. In terms of racial and ethnic diversity, 26 were white, 8 were Latinx, 7 were Asian, 3 were South Asian, 1 was Middle Eastern, and 5 were black.
In describing biased and demeaning patient behavior, the participants recalled remarks that ranged from refusal of care and questioning the clinician’s role to ethnic jokes, questions as to their ethnic backgrounds, inappropriate flirtations or compliments. The effects of these behaviors on the participants included negative responses like carrying an emotional burden and withdrawing from work, along with positive responses like an increased desire for self-growth and to pursue leadership opportunities.
Barriers to addressing these behaviors included a lack of support, uncertainty as to the appropriate response, and a fear of being perceived as unprofessional. Deciding how to respond – or to respond at all – was often dictated by the level of support from colleagues, a professional responsibility to peers, and the presence of a positive role model who would’ve done the same.
The authors acknowledged their study’s limitations, including only knowing the views of those who were interviewed. In addition, all participants came from a medical school located in a diverse city that embraces different cultures, meaning their findings “may not reflect the experiences of physicians in other geographic regions.”
The study was supported by the Greenwall Foundation. The authors reported no conflicts of interest.
SOURCE: Wheeler M et al. JAMA Intern Med. 2019 Oct 28. doi: 10.1001/jamainternmed.2019.4122.
FROM JAMA INTERNAL MEDICINE