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SUDEP may explain 3% of all sudden deaths in children
– new research shows.
Just a few years ago, the message regarding SUDEP was that “it’s very rare in children so you don’t need to worry about it,” said study investigator Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.
These new study results should refocus the message that “the condition is rare, but not as rare as we thought it was,” she said.
The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
Population-based study
Most of the research examining the pediatric SUDEP rate in the United States is based on convenience samples, with few population-based studies.
The investigators used data from the National Institutes of Health/Centers for Disease Control and Prevention Sudden Death in the Young Case Registry. The CDC set up the registry several years ago to record cases of sudden infant death syndrome and sudden deaths in children resulting from violence, trauma, and abuse. Its mandate has since expanded, and the registry now includes data on sudden cardiac death and SUDEP in children.
The current study included children with SUDEP or cardiac/SUDEP who were aged 0-17 years from several states or jurisdictions from 2015 to 2017. Cases were deemed to be SUDEP if the patient had a history of epilepsy, with or without evidence of seizure at the time of death, but excluding status epilepticus.
Criteria for cardiac/SUDEP cases included having a family history of a heritable cardiac condition or sudden death before age 50 years, a personal history of cardiac disease, or a clinical history suggestive of a cardiac disorder, such as death during exertion.
This second category, said Dr. Whittemore, might capture children with Dravet syndrome, a type of epilepsy caused by a genetic mutation that affects both the heart and the brain. “In these cases, it’s sometimes difficult to tell if the child died due to a heart complication or due to epilepsy,” she said.
The analysis included 1,776 cases. Of these, 3% were categorized as SUDEP, and 1% were categorized as cardiac/SUDEP.
The relatively high prevalence of SUDEP was somewhat unexpected, inasmuch as previous reports estimated the rate to be 0.5%-1%, said Dr. Whittemore.
She noted that the current study is population based and included all cases of child death, whereas past reports relied on death certificates. “That probably missed a lot of deaths because they weren’t recorded accurately on the death certificate or weren’t reported in a way that anyone could ascertain that it was a death in someone that had epilepsy.”
Racial differences
Autopsy rates were lower for SUDEP (70%), compared with other categories of death in the registry (81%-100%).
In most jurisdictions, parents must give consent for an autopsy to be performed for a child, and many parents who have suffered such a sudden loss don’t want further investigation, said Dr. Whittemore. “If you know your child had epilepsy, doing an autopsy really isn’t going to tell you very much. You already know they had epilepsy; you may not know the cause of the epilepsy, but an autopsy isn’t going to reveal as much as it would in children with sudden cardiac death.”
SUDEP was equally common in boys and girls. However, the SUDEP mortality rate was higher in Black children (0.32/100,000) than in White children (0.22/100,000). It’s unclear from this study why this is so, but another study that examined SUDEP rates by ZIP code suggested that the higher rate may be caused by socioeconomic factors, said Dr. Whittemore. “Black children from a lower-income family who don’t have access to care may not be getting as good treatment and so have more uncontrolled seizures, which may lead to higher incidence of SUDEP.”
SUDEP occurred at all ages, but mortality rates were highest among patients aged 0-1 year (0.53/100,000) and in those aged 14-17 years (0.31/100,000). Dr. Whittemore speculated that SUDEP rates were higher among the youngest patients because their seizures have just started, and it may be more difficult to bring them under control. In the past, some of these cases may have been classified as sudden infant death syndrome but are now recognized as SUDEP.
As for the older group, research shows that puberty can result in poorer seizure control, which may put teens at elevated risk for SUDEP, said Dr. Whittemore. She added that, as teens continue to age, SUDEP risk may continue to increase. Dr. Whittemore suggested that young adults who head off to college may stop taking their antiseizure medications or consume alcohol while taking these drugs.
Failure of arousal
The study results revealed that most SUDEP cases occurred during sleep without a witness. Dr. Whittemore believes that sleeping with one’s face in a pillow may prevent the reflex required to turn the head to breathe. “It’s sort of a failure of arousal that is potentially the underlying mechanism.”
In some cases, there are signs children had a seizure just prior to death, said Dr. Whittemore.
The researchers have now collected information for 2018 and 2019 and plan to add these data to the current 3-year results. “We will now expand our analysis to include these new numbers to make sure the trends we saw in those 3 years are continuing,” said Dr. Whittemore. The new results should help raise awareness that SUDEP is not as rare as previously believed.
Parents of children with epilepsy can take steps to help reduce the risk for SUDEP, she added. For example, they can use night monitors, and for the children at highest risk (e.g., those with Dravet syndrome), they can use an “alarm blanket” that alerts them when the child moves.
Much is still unknown
Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, New York, who has participated in SUDEP research, said it “raises important questions about SUDEP in children and about racial disparities in SUDEP.”
The understanding of SUDEP so far “leaves much to be desired,” said Dr. Goldenholz. “We don’t yet know why it happens, and we don’t yet know how to prevent it.” The current study “brings a couple of new data points to the table which need further validation, confirmation, and explanation.”
The Sudden Death in Young Case Registry is supported by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the CDC. The investigators and Dr. Goldenholz disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
– new research shows.
Just a few years ago, the message regarding SUDEP was that “it’s very rare in children so you don’t need to worry about it,” said study investigator Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.
These new study results should refocus the message that “the condition is rare, but not as rare as we thought it was,” she said.
The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
Population-based study
Most of the research examining the pediatric SUDEP rate in the United States is based on convenience samples, with few population-based studies.
The investigators used data from the National Institutes of Health/Centers for Disease Control and Prevention Sudden Death in the Young Case Registry. The CDC set up the registry several years ago to record cases of sudden infant death syndrome and sudden deaths in children resulting from violence, trauma, and abuse. Its mandate has since expanded, and the registry now includes data on sudden cardiac death and SUDEP in children.
The current study included children with SUDEP or cardiac/SUDEP who were aged 0-17 years from several states or jurisdictions from 2015 to 2017. Cases were deemed to be SUDEP if the patient had a history of epilepsy, with or without evidence of seizure at the time of death, but excluding status epilepticus.
Criteria for cardiac/SUDEP cases included having a family history of a heritable cardiac condition or sudden death before age 50 years, a personal history of cardiac disease, or a clinical history suggestive of a cardiac disorder, such as death during exertion.
This second category, said Dr. Whittemore, might capture children with Dravet syndrome, a type of epilepsy caused by a genetic mutation that affects both the heart and the brain. “In these cases, it’s sometimes difficult to tell if the child died due to a heart complication or due to epilepsy,” she said.
The analysis included 1,776 cases. Of these, 3% were categorized as SUDEP, and 1% were categorized as cardiac/SUDEP.
The relatively high prevalence of SUDEP was somewhat unexpected, inasmuch as previous reports estimated the rate to be 0.5%-1%, said Dr. Whittemore.
She noted that the current study is population based and included all cases of child death, whereas past reports relied on death certificates. “That probably missed a lot of deaths because they weren’t recorded accurately on the death certificate or weren’t reported in a way that anyone could ascertain that it was a death in someone that had epilepsy.”
Racial differences
Autopsy rates were lower for SUDEP (70%), compared with other categories of death in the registry (81%-100%).
In most jurisdictions, parents must give consent for an autopsy to be performed for a child, and many parents who have suffered such a sudden loss don’t want further investigation, said Dr. Whittemore. “If you know your child had epilepsy, doing an autopsy really isn’t going to tell you very much. You already know they had epilepsy; you may not know the cause of the epilepsy, but an autopsy isn’t going to reveal as much as it would in children with sudden cardiac death.”
SUDEP was equally common in boys and girls. However, the SUDEP mortality rate was higher in Black children (0.32/100,000) than in White children (0.22/100,000). It’s unclear from this study why this is so, but another study that examined SUDEP rates by ZIP code suggested that the higher rate may be caused by socioeconomic factors, said Dr. Whittemore. “Black children from a lower-income family who don’t have access to care may not be getting as good treatment and so have more uncontrolled seizures, which may lead to higher incidence of SUDEP.”
SUDEP occurred at all ages, but mortality rates were highest among patients aged 0-1 year (0.53/100,000) and in those aged 14-17 years (0.31/100,000). Dr. Whittemore speculated that SUDEP rates were higher among the youngest patients because their seizures have just started, and it may be more difficult to bring them under control. In the past, some of these cases may have been classified as sudden infant death syndrome but are now recognized as SUDEP.
As for the older group, research shows that puberty can result in poorer seizure control, which may put teens at elevated risk for SUDEP, said Dr. Whittemore. She added that, as teens continue to age, SUDEP risk may continue to increase. Dr. Whittemore suggested that young adults who head off to college may stop taking their antiseizure medications or consume alcohol while taking these drugs.
Failure of arousal
The study results revealed that most SUDEP cases occurred during sleep without a witness. Dr. Whittemore believes that sleeping with one’s face in a pillow may prevent the reflex required to turn the head to breathe. “It’s sort of a failure of arousal that is potentially the underlying mechanism.”
In some cases, there are signs children had a seizure just prior to death, said Dr. Whittemore.
The researchers have now collected information for 2018 and 2019 and plan to add these data to the current 3-year results. “We will now expand our analysis to include these new numbers to make sure the trends we saw in those 3 years are continuing,” said Dr. Whittemore. The new results should help raise awareness that SUDEP is not as rare as previously believed.
Parents of children with epilepsy can take steps to help reduce the risk for SUDEP, she added. For example, they can use night monitors, and for the children at highest risk (e.g., those with Dravet syndrome), they can use an “alarm blanket” that alerts them when the child moves.
Much is still unknown
Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, New York, who has participated in SUDEP research, said it “raises important questions about SUDEP in children and about racial disparities in SUDEP.”
The understanding of SUDEP so far “leaves much to be desired,” said Dr. Goldenholz. “We don’t yet know why it happens, and we don’t yet know how to prevent it.” The current study “brings a couple of new data points to the table which need further validation, confirmation, and explanation.”
The Sudden Death in Young Case Registry is supported by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the CDC. The investigators and Dr. Goldenholz disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
– new research shows.
Just a few years ago, the message regarding SUDEP was that “it’s very rare in children so you don’t need to worry about it,” said study investigator Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.
These new study results should refocus the message that “the condition is rare, but not as rare as we thought it was,” she said.
The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
Population-based study
Most of the research examining the pediatric SUDEP rate in the United States is based on convenience samples, with few population-based studies.
The investigators used data from the National Institutes of Health/Centers for Disease Control and Prevention Sudden Death in the Young Case Registry. The CDC set up the registry several years ago to record cases of sudden infant death syndrome and sudden deaths in children resulting from violence, trauma, and abuse. Its mandate has since expanded, and the registry now includes data on sudden cardiac death and SUDEP in children.
The current study included children with SUDEP or cardiac/SUDEP who were aged 0-17 years from several states or jurisdictions from 2015 to 2017. Cases were deemed to be SUDEP if the patient had a history of epilepsy, with or without evidence of seizure at the time of death, but excluding status epilepticus.
Criteria for cardiac/SUDEP cases included having a family history of a heritable cardiac condition or sudden death before age 50 years, a personal history of cardiac disease, or a clinical history suggestive of a cardiac disorder, such as death during exertion.
This second category, said Dr. Whittemore, might capture children with Dravet syndrome, a type of epilepsy caused by a genetic mutation that affects both the heart and the brain. “In these cases, it’s sometimes difficult to tell if the child died due to a heart complication or due to epilepsy,” she said.
The analysis included 1,776 cases. Of these, 3% were categorized as SUDEP, and 1% were categorized as cardiac/SUDEP.
The relatively high prevalence of SUDEP was somewhat unexpected, inasmuch as previous reports estimated the rate to be 0.5%-1%, said Dr. Whittemore.
She noted that the current study is population based and included all cases of child death, whereas past reports relied on death certificates. “That probably missed a lot of deaths because they weren’t recorded accurately on the death certificate or weren’t reported in a way that anyone could ascertain that it was a death in someone that had epilepsy.”
Racial differences
Autopsy rates were lower for SUDEP (70%), compared with other categories of death in the registry (81%-100%).
In most jurisdictions, parents must give consent for an autopsy to be performed for a child, and many parents who have suffered such a sudden loss don’t want further investigation, said Dr. Whittemore. “If you know your child had epilepsy, doing an autopsy really isn’t going to tell you very much. You already know they had epilepsy; you may not know the cause of the epilepsy, but an autopsy isn’t going to reveal as much as it would in children with sudden cardiac death.”
SUDEP was equally common in boys and girls. However, the SUDEP mortality rate was higher in Black children (0.32/100,000) than in White children (0.22/100,000). It’s unclear from this study why this is so, but another study that examined SUDEP rates by ZIP code suggested that the higher rate may be caused by socioeconomic factors, said Dr. Whittemore. “Black children from a lower-income family who don’t have access to care may not be getting as good treatment and so have more uncontrolled seizures, which may lead to higher incidence of SUDEP.”
SUDEP occurred at all ages, but mortality rates were highest among patients aged 0-1 year (0.53/100,000) and in those aged 14-17 years (0.31/100,000). Dr. Whittemore speculated that SUDEP rates were higher among the youngest patients because their seizures have just started, and it may be more difficult to bring them under control. In the past, some of these cases may have been classified as sudden infant death syndrome but are now recognized as SUDEP.
As for the older group, research shows that puberty can result in poorer seizure control, which may put teens at elevated risk for SUDEP, said Dr. Whittemore. She added that, as teens continue to age, SUDEP risk may continue to increase. Dr. Whittemore suggested that young adults who head off to college may stop taking their antiseizure medications or consume alcohol while taking these drugs.
Failure of arousal
The study results revealed that most SUDEP cases occurred during sleep without a witness. Dr. Whittemore believes that sleeping with one’s face in a pillow may prevent the reflex required to turn the head to breathe. “It’s sort of a failure of arousal that is potentially the underlying mechanism.”
In some cases, there are signs children had a seizure just prior to death, said Dr. Whittemore.
The researchers have now collected information for 2018 and 2019 and plan to add these data to the current 3-year results. “We will now expand our analysis to include these new numbers to make sure the trends we saw in those 3 years are continuing,” said Dr. Whittemore. The new results should help raise awareness that SUDEP is not as rare as previously believed.
Parents of children with epilepsy can take steps to help reduce the risk for SUDEP, she added. For example, they can use night monitors, and for the children at highest risk (e.g., those with Dravet syndrome), they can use an “alarm blanket” that alerts them when the child moves.
Much is still unknown
Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, New York, who has participated in SUDEP research, said it “raises important questions about SUDEP in children and about racial disparities in SUDEP.”
The understanding of SUDEP so far “leaves much to be desired,” said Dr. Goldenholz. “We don’t yet know why it happens, and we don’t yet know how to prevent it.” The current study “brings a couple of new data points to the table which need further validation, confirmation, and explanation.”
The Sudden Death in Young Case Registry is supported by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the CDC. The investigators and Dr. Goldenholz disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AES 2020
Rechallenge ‘reasonable’ for some with small-cell lung cancer
In a phase 3 trial, carboplatin plus etoposide significantly prolonged progression-free survival (PFS), when compared with topotecan, in patients with advanced or relapsed, sensitive SCLC.
All patients had responded to first-line platinum plus etoposide, but they experienced relapse or progression 90 days or more after completing that treatment, according to study author Nathalie Baize, MD, of Angers University Hospital in France, and colleagues.
For this trial, Dr. Baize and colleagues enrolled 164 patients with advanced or relapsed SCLC. The median age of the 162 evaluable patients was 64 years, about two-thirds were men, and about 60% had an Eastern Cooperative Oncology Group performance status of 1.
The patients were randomized 1:1 to intravenous carboplatin (area under the curve 5 mg/mL per min on day 1) plus intravenous etoposide (100 mg/m² from day 1 to day 3) or to oral topotecan (2.3 mg/m² from day 1 to day 5 for six cycles). Primary prophylactic filgrastim was recommended for all patients in both treatment groups.
Results: Survival and adverse events
The median follow-up was 22.7 months. The median PFS was significantly longer in the combination therapy arm, at 4.7 months versus 2.7 months in the topotecan arm (stratified hazard ratio 0.57, P = .0041).
The median overall survival was similar in both arms, at 7.5 months in the carboplatin-etoposide arm and 7.4 months in the topotecan arm.
Patients in the carboplatin-etoposide arm had a significantly higher objective response rate, at 49% versus 25% in the topotecan arm (P = .0024).
The most common grade 3-4 adverse events (in the topotecan and combination arms, respectively) were neutropenia (22% vs. 14%), thrombocytopenia (36% vs. 31%), and anemia (21% vs. 25%).
Serious adverse events with hospitalization were reported in 37% of patients in the carboplatin-etoposide arm 43% in the topotecan arm. Febrile neutropenia with sepsis led to two treatment-related deaths in the topotecan group but none in the carboplatin-etoposide group.
Reasonable option for some
Based on the results of this trial, Dr. Baize and colleagues concluded that carboplatin-etoposide rechallenge “can be considered a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer.”
However, while this trial was enrolling patients, immunotherapy and chemotherapy combinations became the standard of care in SCLC, Oscar Arrieta, MD, of Instituto Nacional de Cancerología in Mexico City, and colleagues noted in a related editorial.
Therefore, “reasonable doubts emerge regarding the application of this strategy in patients receiving immunotherapy,” Dr. Arrieta and colleagues wrote.
The editorialists urged conduct of a randomized trial to evaluate rechallenge with carboplatin plus etoposide versus lurbinectedin, which was approved earlier this year by the Food and Drug Administration for the treatment of sensitive and resistant relapsed SCLC.
Commenting on the choice between a platinum-etoposide combination and lurbinectedin, Sarah Goldberg, MD, of Yale University, New Haven, Conn., noted that she and her colleagues have been using the chemotherapy combination for several years.
“This trial confirms that practice and that it’s still a reasonable option for some patients,” Dr. Goldberg said in an interview.
For patients who had a very good first-line response to platinum-etoposide, longer than 180 days (even longer than the 90-day standard in the current trial), she said, “it seems like a rechallenge with platinum-etoposide would potentially be even more effective, and I’d save lurbinectedin for a later line.
“With refractory disease, less than 90 days, I would consider lurbinectedin,” Dr. Goldberg said.
This study was funded by Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie). The researchers disclosed relationships with Pfizer, Roche, AbbVie, and many other companies. Dr. Arrieta disclosed relationships with AstraZeneca, Boehringer Ingelheim, Roche, Lilly, Merck, Pfizer, and Bristol-Myers Squibb. The other editorialists declared no competing interests. Dr. Goldberg disclosed relationships with AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, Blueprint Medicine, Sanofi Genzyme, Daiichi Sankyo, and Regeneron.
SOURCE: Baize N et al. Lancet Oncol. 2020;21:1224-33.
In a phase 3 trial, carboplatin plus etoposide significantly prolonged progression-free survival (PFS), when compared with topotecan, in patients with advanced or relapsed, sensitive SCLC.
All patients had responded to first-line platinum plus etoposide, but they experienced relapse or progression 90 days or more after completing that treatment, according to study author Nathalie Baize, MD, of Angers University Hospital in France, and colleagues.
For this trial, Dr. Baize and colleagues enrolled 164 patients with advanced or relapsed SCLC. The median age of the 162 evaluable patients was 64 years, about two-thirds were men, and about 60% had an Eastern Cooperative Oncology Group performance status of 1.
The patients were randomized 1:1 to intravenous carboplatin (area under the curve 5 mg/mL per min on day 1) plus intravenous etoposide (100 mg/m² from day 1 to day 3) or to oral topotecan (2.3 mg/m² from day 1 to day 5 for six cycles). Primary prophylactic filgrastim was recommended for all patients in both treatment groups.
Results: Survival and adverse events
The median follow-up was 22.7 months. The median PFS was significantly longer in the combination therapy arm, at 4.7 months versus 2.7 months in the topotecan arm (stratified hazard ratio 0.57, P = .0041).
The median overall survival was similar in both arms, at 7.5 months in the carboplatin-etoposide arm and 7.4 months in the topotecan arm.
Patients in the carboplatin-etoposide arm had a significantly higher objective response rate, at 49% versus 25% in the topotecan arm (P = .0024).
The most common grade 3-4 adverse events (in the topotecan and combination arms, respectively) were neutropenia (22% vs. 14%), thrombocytopenia (36% vs. 31%), and anemia (21% vs. 25%).
Serious adverse events with hospitalization were reported in 37% of patients in the carboplatin-etoposide arm 43% in the topotecan arm. Febrile neutropenia with sepsis led to two treatment-related deaths in the topotecan group but none in the carboplatin-etoposide group.
Reasonable option for some
Based on the results of this trial, Dr. Baize and colleagues concluded that carboplatin-etoposide rechallenge “can be considered a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer.”
However, while this trial was enrolling patients, immunotherapy and chemotherapy combinations became the standard of care in SCLC, Oscar Arrieta, MD, of Instituto Nacional de Cancerología in Mexico City, and colleagues noted in a related editorial.
Therefore, “reasonable doubts emerge regarding the application of this strategy in patients receiving immunotherapy,” Dr. Arrieta and colleagues wrote.
The editorialists urged conduct of a randomized trial to evaluate rechallenge with carboplatin plus etoposide versus lurbinectedin, which was approved earlier this year by the Food and Drug Administration for the treatment of sensitive and resistant relapsed SCLC.
Commenting on the choice between a platinum-etoposide combination and lurbinectedin, Sarah Goldberg, MD, of Yale University, New Haven, Conn., noted that she and her colleagues have been using the chemotherapy combination for several years.
“This trial confirms that practice and that it’s still a reasonable option for some patients,” Dr. Goldberg said in an interview.
For patients who had a very good first-line response to platinum-etoposide, longer than 180 days (even longer than the 90-day standard in the current trial), she said, “it seems like a rechallenge with platinum-etoposide would potentially be even more effective, and I’d save lurbinectedin for a later line.
“With refractory disease, less than 90 days, I would consider lurbinectedin,” Dr. Goldberg said.
This study was funded by Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie). The researchers disclosed relationships with Pfizer, Roche, AbbVie, and many other companies. Dr. Arrieta disclosed relationships with AstraZeneca, Boehringer Ingelheim, Roche, Lilly, Merck, Pfizer, and Bristol-Myers Squibb. The other editorialists declared no competing interests. Dr. Goldberg disclosed relationships with AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, Blueprint Medicine, Sanofi Genzyme, Daiichi Sankyo, and Regeneron.
SOURCE: Baize N et al. Lancet Oncol. 2020;21:1224-33.
In a phase 3 trial, carboplatin plus etoposide significantly prolonged progression-free survival (PFS), when compared with topotecan, in patients with advanced or relapsed, sensitive SCLC.
All patients had responded to first-line platinum plus etoposide, but they experienced relapse or progression 90 days or more after completing that treatment, according to study author Nathalie Baize, MD, of Angers University Hospital in France, and colleagues.
For this trial, Dr. Baize and colleagues enrolled 164 patients with advanced or relapsed SCLC. The median age of the 162 evaluable patients was 64 years, about two-thirds were men, and about 60% had an Eastern Cooperative Oncology Group performance status of 1.
The patients were randomized 1:1 to intravenous carboplatin (area under the curve 5 mg/mL per min on day 1) plus intravenous etoposide (100 mg/m² from day 1 to day 3) or to oral topotecan (2.3 mg/m² from day 1 to day 5 for six cycles). Primary prophylactic filgrastim was recommended for all patients in both treatment groups.
Results: Survival and adverse events
The median follow-up was 22.7 months. The median PFS was significantly longer in the combination therapy arm, at 4.7 months versus 2.7 months in the topotecan arm (stratified hazard ratio 0.57, P = .0041).
The median overall survival was similar in both arms, at 7.5 months in the carboplatin-etoposide arm and 7.4 months in the topotecan arm.
Patients in the carboplatin-etoposide arm had a significantly higher objective response rate, at 49% versus 25% in the topotecan arm (P = .0024).
The most common grade 3-4 adverse events (in the topotecan and combination arms, respectively) were neutropenia (22% vs. 14%), thrombocytopenia (36% vs. 31%), and anemia (21% vs. 25%).
Serious adverse events with hospitalization were reported in 37% of patients in the carboplatin-etoposide arm 43% in the topotecan arm. Febrile neutropenia with sepsis led to two treatment-related deaths in the topotecan group but none in the carboplatin-etoposide group.
Reasonable option for some
Based on the results of this trial, Dr. Baize and colleagues concluded that carboplatin-etoposide rechallenge “can be considered a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer.”
However, while this trial was enrolling patients, immunotherapy and chemotherapy combinations became the standard of care in SCLC, Oscar Arrieta, MD, of Instituto Nacional de Cancerología in Mexico City, and colleagues noted in a related editorial.
Therefore, “reasonable doubts emerge regarding the application of this strategy in patients receiving immunotherapy,” Dr. Arrieta and colleagues wrote.
The editorialists urged conduct of a randomized trial to evaluate rechallenge with carboplatin plus etoposide versus lurbinectedin, which was approved earlier this year by the Food and Drug Administration for the treatment of sensitive and resistant relapsed SCLC.
Commenting on the choice between a platinum-etoposide combination and lurbinectedin, Sarah Goldberg, MD, of Yale University, New Haven, Conn., noted that she and her colleagues have been using the chemotherapy combination for several years.
“This trial confirms that practice and that it’s still a reasonable option for some patients,” Dr. Goldberg said in an interview.
For patients who had a very good first-line response to platinum-etoposide, longer than 180 days (even longer than the 90-day standard in the current trial), she said, “it seems like a rechallenge with platinum-etoposide would potentially be even more effective, and I’d save lurbinectedin for a later line.
“With refractory disease, less than 90 days, I would consider lurbinectedin,” Dr. Goldberg said.
This study was funded by Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie). The researchers disclosed relationships with Pfizer, Roche, AbbVie, and many other companies. Dr. Arrieta disclosed relationships with AstraZeneca, Boehringer Ingelheim, Roche, Lilly, Merck, Pfizer, and Bristol-Myers Squibb. The other editorialists declared no competing interests. Dr. Goldberg disclosed relationships with AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, Blueprint Medicine, Sanofi Genzyme, Daiichi Sankyo, and Regeneron.
SOURCE: Baize N et al. Lancet Oncol. 2020;21:1224-33.
FROM LANCET ONCOLOGY
Fracking sites tied to increased heart failure hospitalizations
Living near hydraulic fracturing is associated with increased risk of hospitalization in people with heart failure (HF), a new study from Pennsylvania suggests.
The link was strongest among those with more severe heart failure but patients with either HF phenotype showed this association of increased risk with exposure to fracking activities, according to the investigators, led by Tara P. McAlexander, PhD, MPH, Drexel University Dornsife School of Public Health in Philadelphia.
“Our understanding has expanded well beyond the famous Harvard Six Cities study to know that it’s not just a short-term uptick in air pollution that›s going to send someone to the hospital a couple days later,” said Dr. McAlexander in an interview, referring to the study conducted from the mid-1970s through 1991. “We know that people who live in these environments and are exposed for long periods of time may have long-term detrimental effects.”
Although questions remain about specific mechanisms and how best to assess exposure, the evidence is mounting in a way that is consistent with the biologic hypotheses of how fracking would adversely affect health, Dr. McAlexander said. “We have many studies now on adverse pregnancy and birth outcomes, and that’s just the tip of the iceberg.”
Pennsylvania is a hot spot for fracking, also known as unconventional natural gas development (UNGD), with more than 12,000 wells drilled in the Marcellus shale since 2004. The shale extends from upstate New York in the north to northeastern Kentucky and Tennessee in the south and covers about 72,000 square miles. Last year, Pennsylvania pledged $3 million to study clusters of rare pediatric cancers and asthma near fracking operations. A recent grand jury report concluded government officials failed to protect residents from the health effects of fracking.
Fracking involves a cascade of activities that can trigger neural circuitry, sympathetic activation, and inflammation – all well-known pathways that potentiate heart failure, said Sanjay Rajagopalan, MD, who has researched the health effects of air pollution for two decades and was not involved with the study.
“If you think about it, it’s like environmental perturbation on steroids in some ways where they are pulling the trigger from a variety of different ways: noise, air pollution, social displacement, psychosocial impacts, economic disparities. So it’s not at all surprising that they saw an association,” said Dr. Rajagopalan, chief of cardiovascular medicine at University Hospitals Harrington Heart & Vascular Institute and director of the Case Western Cardiovascular Research Institute, both in Cleveland, Ohio.
As reported in the Journal of the American College of Cardiology, Dr. McAlexander and colleagues at Johns Hopkins University, Baltimore, used electronic health data from the Geisinger Health System to identify 9,054 patients with heart failure seen between 2008 and 2015. Of these, 5,839 patients had an incident HF hospitalization and 3,215 served as controls. Geisinger operates 13 hospitals and two research centers in 45 of Pennsylvania’s 67 counties, serving more than 3 million of the state’s residents.
Patients’ residential addresses were used to identify latitude and longitude coordinates that were matched with 9,669 UNGD wells in Pennsylvania and the location of major and minor roadways. The researchers also calculated a measure of community socioeconomic deprivation.
The adjusted odds of hospitalization were higher for patients in the highest quartile of exposure for three of the four UNGD phases: pad preparation (odds ratio, 1.70; 95% confidence interval, 1.35-2.13), stimulation or the actual fracking (OR, 1.80; 95% CI, 1.35-2.40), and production (OR, 1.62; 95% CI, 1.07-2.45).
Dr. McAlexander said she initially thought the lack of association with drilling (OR, 0.97; 95% CI, 0.75-1.27) was a mistake but noted that the drilling metric reflects a shorter time period than, for example, 30 days needed to clear the well pad and bring in the necessary equipment.
Stronger associations between pad preparation, fracking, and production are also consistent with the known increases in air pollution, traffic, and noise associated with these phases.
Individuals with more severe HF had greater odds of hospitalization, but the effect sizes were generally comparable between HF with preserved versus reduced ejection fraction. For those with the highest exposure to fracking, the odds ratios for hospitalization reached 2.25 (95% CI, 1.56-3.25) and 2.09 (95% CI, 1.44-3.03), respectively.
Notably, patients who could be phenotyped versus those who could not were more likely to die, to be hospitalized for HF, and to have a higher Charlson Comorbidity Index and other relevant diagnoses like myocardial infarction.
“Clinicians need to be increasingly aware that the environments their patients are in are a huge factor in their disease progression and outlook,” McAlexander said. “We know that UNGD, specifically now, is something that could be impacting a heart failure patient’s survival.”
She also suggested that the findings may also spur more advocacy work and “across-silo” collaboration between clinicians and environmental researchers.
Dr. Rajagopalan said there is increasing recognition that physicians need to be aware of environmental health links as extreme events like the California and Oregon wildfires and coastal flooding become increasingly common. “Unfortunately, unconventional is becoming the new convention.”
The problem for many physicians, however, is just having enough bandwidth to get through the day and get enough learning to keep above water, he said. Artificial intelligence could be used to seed electronic medical records with other personalized information from a bevy of sources including smartphones and the internet of things, but fundamental changes are also needed in the educational process to emphasize the environment.
“It’s going to take a huge societal shift in the way we view commodities, what we consider healthy, etc, but it can happen very quickly because all it takes is a crisis like COVID-19 to bring people to their knees and make them understand how this is going to take over our lives over the next decade,” Dr. Rajagopalan said.
The scientific community has been calling for “good” epidemiologic studies on the health effects of fracking since the early 2010s, Barrak Alahmad, MBChB, MPH, Harvard T.H. Chan School of Public Health, and Haitham Khraishah, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, point out in an accompanying editorial.
The current study applied “extensive and rigorous methods” involving both the design and statistical approach, including use of a negative control analysis to assess for sources of spurious causal inference, several sensitivity analyses, and controlled for a wide range of covariates.
“Their results were consistent and robust across all these measures,” the editorialists wrote. “Most importantly, the effect size is probably too large to be explained away by an unmeasured confounder.”
Dr. Alahmad and Dr. Khraishah call for advancements in exposure assessment, citing a recent study reporting that ambient particle radioactivity near unconventional oil and gas sites could induce adverse health effects. Other unmet needs include a better understanding of racial disparities in the impacts of fracking and a fine-tuning of cause-specific cardiovascular morbidity and mortality.
The study was supported by training grants from the National Institute of Environmental Health Sciences to Dr. McAlexander and principal investigator Brian Schwartz, MD. The authors, Dr. Rajagopalan, Dr. Alahmad, and Dr. Khraishah have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Living near hydraulic fracturing is associated with increased risk of hospitalization in people with heart failure (HF), a new study from Pennsylvania suggests.
The link was strongest among those with more severe heart failure but patients with either HF phenotype showed this association of increased risk with exposure to fracking activities, according to the investigators, led by Tara P. McAlexander, PhD, MPH, Drexel University Dornsife School of Public Health in Philadelphia.
“Our understanding has expanded well beyond the famous Harvard Six Cities study to know that it’s not just a short-term uptick in air pollution that›s going to send someone to the hospital a couple days later,” said Dr. McAlexander in an interview, referring to the study conducted from the mid-1970s through 1991. “We know that people who live in these environments and are exposed for long periods of time may have long-term detrimental effects.”
Although questions remain about specific mechanisms and how best to assess exposure, the evidence is mounting in a way that is consistent with the biologic hypotheses of how fracking would adversely affect health, Dr. McAlexander said. “We have many studies now on adverse pregnancy and birth outcomes, and that’s just the tip of the iceberg.”
Pennsylvania is a hot spot for fracking, also known as unconventional natural gas development (UNGD), with more than 12,000 wells drilled in the Marcellus shale since 2004. The shale extends from upstate New York in the north to northeastern Kentucky and Tennessee in the south and covers about 72,000 square miles. Last year, Pennsylvania pledged $3 million to study clusters of rare pediatric cancers and asthma near fracking operations. A recent grand jury report concluded government officials failed to protect residents from the health effects of fracking.
Fracking involves a cascade of activities that can trigger neural circuitry, sympathetic activation, and inflammation – all well-known pathways that potentiate heart failure, said Sanjay Rajagopalan, MD, who has researched the health effects of air pollution for two decades and was not involved with the study.
“If you think about it, it’s like environmental perturbation on steroids in some ways where they are pulling the trigger from a variety of different ways: noise, air pollution, social displacement, psychosocial impacts, economic disparities. So it’s not at all surprising that they saw an association,” said Dr. Rajagopalan, chief of cardiovascular medicine at University Hospitals Harrington Heart & Vascular Institute and director of the Case Western Cardiovascular Research Institute, both in Cleveland, Ohio.
As reported in the Journal of the American College of Cardiology, Dr. McAlexander and colleagues at Johns Hopkins University, Baltimore, used electronic health data from the Geisinger Health System to identify 9,054 patients with heart failure seen between 2008 and 2015. Of these, 5,839 patients had an incident HF hospitalization and 3,215 served as controls. Geisinger operates 13 hospitals and two research centers in 45 of Pennsylvania’s 67 counties, serving more than 3 million of the state’s residents.
Patients’ residential addresses were used to identify latitude and longitude coordinates that were matched with 9,669 UNGD wells in Pennsylvania and the location of major and minor roadways. The researchers also calculated a measure of community socioeconomic deprivation.
The adjusted odds of hospitalization were higher for patients in the highest quartile of exposure for three of the four UNGD phases: pad preparation (odds ratio, 1.70; 95% confidence interval, 1.35-2.13), stimulation or the actual fracking (OR, 1.80; 95% CI, 1.35-2.40), and production (OR, 1.62; 95% CI, 1.07-2.45).
Dr. McAlexander said she initially thought the lack of association with drilling (OR, 0.97; 95% CI, 0.75-1.27) was a mistake but noted that the drilling metric reflects a shorter time period than, for example, 30 days needed to clear the well pad and bring in the necessary equipment.
Stronger associations between pad preparation, fracking, and production are also consistent with the known increases in air pollution, traffic, and noise associated with these phases.
Individuals with more severe HF had greater odds of hospitalization, but the effect sizes were generally comparable between HF with preserved versus reduced ejection fraction. For those with the highest exposure to fracking, the odds ratios for hospitalization reached 2.25 (95% CI, 1.56-3.25) and 2.09 (95% CI, 1.44-3.03), respectively.
Notably, patients who could be phenotyped versus those who could not were more likely to die, to be hospitalized for HF, and to have a higher Charlson Comorbidity Index and other relevant diagnoses like myocardial infarction.
“Clinicians need to be increasingly aware that the environments their patients are in are a huge factor in their disease progression and outlook,” McAlexander said. “We know that UNGD, specifically now, is something that could be impacting a heart failure patient’s survival.”
She also suggested that the findings may also spur more advocacy work and “across-silo” collaboration between clinicians and environmental researchers.
Dr. Rajagopalan said there is increasing recognition that physicians need to be aware of environmental health links as extreme events like the California and Oregon wildfires and coastal flooding become increasingly common. “Unfortunately, unconventional is becoming the new convention.”
The problem for many physicians, however, is just having enough bandwidth to get through the day and get enough learning to keep above water, he said. Artificial intelligence could be used to seed electronic medical records with other personalized information from a bevy of sources including smartphones and the internet of things, but fundamental changes are also needed in the educational process to emphasize the environment.
“It’s going to take a huge societal shift in the way we view commodities, what we consider healthy, etc, but it can happen very quickly because all it takes is a crisis like COVID-19 to bring people to their knees and make them understand how this is going to take over our lives over the next decade,” Dr. Rajagopalan said.
The scientific community has been calling for “good” epidemiologic studies on the health effects of fracking since the early 2010s, Barrak Alahmad, MBChB, MPH, Harvard T.H. Chan School of Public Health, and Haitham Khraishah, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, point out in an accompanying editorial.
The current study applied “extensive and rigorous methods” involving both the design and statistical approach, including use of a negative control analysis to assess for sources of spurious causal inference, several sensitivity analyses, and controlled for a wide range of covariates.
“Their results were consistent and robust across all these measures,” the editorialists wrote. “Most importantly, the effect size is probably too large to be explained away by an unmeasured confounder.”
Dr. Alahmad and Dr. Khraishah call for advancements in exposure assessment, citing a recent study reporting that ambient particle radioactivity near unconventional oil and gas sites could induce adverse health effects. Other unmet needs include a better understanding of racial disparities in the impacts of fracking and a fine-tuning of cause-specific cardiovascular morbidity and mortality.
The study was supported by training grants from the National Institute of Environmental Health Sciences to Dr. McAlexander and principal investigator Brian Schwartz, MD. The authors, Dr. Rajagopalan, Dr. Alahmad, and Dr. Khraishah have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Living near hydraulic fracturing is associated with increased risk of hospitalization in people with heart failure (HF), a new study from Pennsylvania suggests.
The link was strongest among those with more severe heart failure but patients with either HF phenotype showed this association of increased risk with exposure to fracking activities, according to the investigators, led by Tara P. McAlexander, PhD, MPH, Drexel University Dornsife School of Public Health in Philadelphia.
“Our understanding has expanded well beyond the famous Harvard Six Cities study to know that it’s not just a short-term uptick in air pollution that›s going to send someone to the hospital a couple days later,” said Dr. McAlexander in an interview, referring to the study conducted from the mid-1970s through 1991. “We know that people who live in these environments and are exposed for long periods of time may have long-term detrimental effects.”
Although questions remain about specific mechanisms and how best to assess exposure, the evidence is mounting in a way that is consistent with the biologic hypotheses of how fracking would adversely affect health, Dr. McAlexander said. “We have many studies now on adverse pregnancy and birth outcomes, and that’s just the tip of the iceberg.”
Pennsylvania is a hot spot for fracking, also known as unconventional natural gas development (UNGD), with more than 12,000 wells drilled in the Marcellus shale since 2004. The shale extends from upstate New York in the north to northeastern Kentucky and Tennessee in the south and covers about 72,000 square miles. Last year, Pennsylvania pledged $3 million to study clusters of rare pediatric cancers and asthma near fracking operations. A recent grand jury report concluded government officials failed to protect residents from the health effects of fracking.
Fracking involves a cascade of activities that can trigger neural circuitry, sympathetic activation, and inflammation – all well-known pathways that potentiate heart failure, said Sanjay Rajagopalan, MD, who has researched the health effects of air pollution for two decades and was not involved with the study.
“If you think about it, it’s like environmental perturbation on steroids in some ways where they are pulling the trigger from a variety of different ways: noise, air pollution, social displacement, psychosocial impacts, economic disparities. So it’s not at all surprising that they saw an association,” said Dr. Rajagopalan, chief of cardiovascular medicine at University Hospitals Harrington Heart & Vascular Institute and director of the Case Western Cardiovascular Research Institute, both in Cleveland, Ohio.
As reported in the Journal of the American College of Cardiology, Dr. McAlexander and colleagues at Johns Hopkins University, Baltimore, used electronic health data from the Geisinger Health System to identify 9,054 patients with heart failure seen between 2008 and 2015. Of these, 5,839 patients had an incident HF hospitalization and 3,215 served as controls. Geisinger operates 13 hospitals and two research centers in 45 of Pennsylvania’s 67 counties, serving more than 3 million of the state’s residents.
Patients’ residential addresses were used to identify latitude and longitude coordinates that were matched with 9,669 UNGD wells in Pennsylvania and the location of major and minor roadways. The researchers also calculated a measure of community socioeconomic deprivation.
The adjusted odds of hospitalization were higher for patients in the highest quartile of exposure for three of the four UNGD phases: pad preparation (odds ratio, 1.70; 95% confidence interval, 1.35-2.13), stimulation or the actual fracking (OR, 1.80; 95% CI, 1.35-2.40), and production (OR, 1.62; 95% CI, 1.07-2.45).
Dr. McAlexander said she initially thought the lack of association with drilling (OR, 0.97; 95% CI, 0.75-1.27) was a mistake but noted that the drilling metric reflects a shorter time period than, for example, 30 days needed to clear the well pad and bring in the necessary equipment.
Stronger associations between pad preparation, fracking, and production are also consistent with the known increases in air pollution, traffic, and noise associated with these phases.
Individuals with more severe HF had greater odds of hospitalization, but the effect sizes were generally comparable between HF with preserved versus reduced ejection fraction. For those with the highest exposure to fracking, the odds ratios for hospitalization reached 2.25 (95% CI, 1.56-3.25) and 2.09 (95% CI, 1.44-3.03), respectively.
Notably, patients who could be phenotyped versus those who could not were more likely to die, to be hospitalized for HF, and to have a higher Charlson Comorbidity Index and other relevant diagnoses like myocardial infarction.
“Clinicians need to be increasingly aware that the environments their patients are in are a huge factor in their disease progression and outlook,” McAlexander said. “We know that UNGD, specifically now, is something that could be impacting a heart failure patient’s survival.”
She also suggested that the findings may also spur more advocacy work and “across-silo” collaboration between clinicians and environmental researchers.
Dr. Rajagopalan said there is increasing recognition that physicians need to be aware of environmental health links as extreme events like the California and Oregon wildfires and coastal flooding become increasingly common. “Unfortunately, unconventional is becoming the new convention.”
The problem for many physicians, however, is just having enough bandwidth to get through the day and get enough learning to keep above water, he said. Artificial intelligence could be used to seed electronic medical records with other personalized information from a bevy of sources including smartphones and the internet of things, but fundamental changes are also needed in the educational process to emphasize the environment.
“It’s going to take a huge societal shift in the way we view commodities, what we consider healthy, etc, but it can happen very quickly because all it takes is a crisis like COVID-19 to bring people to their knees and make them understand how this is going to take over our lives over the next decade,” Dr. Rajagopalan said.
The scientific community has been calling for “good” epidemiologic studies on the health effects of fracking since the early 2010s, Barrak Alahmad, MBChB, MPH, Harvard T.H. Chan School of Public Health, and Haitham Khraishah, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, point out in an accompanying editorial.
The current study applied “extensive and rigorous methods” involving both the design and statistical approach, including use of a negative control analysis to assess for sources of spurious causal inference, several sensitivity analyses, and controlled for a wide range of covariates.
“Their results were consistent and robust across all these measures,” the editorialists wrote. “Most importantly, the effect size is probably too large to be explained away by an unmeasured confounder.”
Dr. Alahmad and Dr. Khraishah call for advancements in exposure assessment, citing a recent study reporting that ambient particle radioactivity near unconventional oil and gas sites could induce adverse health effects. Other unmet needs include a better understanding of racial disparities in the impacts of fracking and a fine-tuning of cause-specific cardiovascular morbidity and mortality.
The study was supported by training grants from the National Institute of Environmental Health Sciences to Dr. McAlexander and principal investigator Brian Schwartz, MD. The authors, Dr. Rajagopalan, Dr. Alahmad, and Dr. Khraishah have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Calcium burden drives CV risk whether coronary disease is obstructive or not
Coronary artery calcium (CAC) score as a measure of plaque burden more reliably predicts future cardiovascular (CV) risk in patients with suspected coronary disease (CAD) than whether or not the disease is obstructive, a large retrospective study suggests.
Indeed, CV risk went up in tandem with growing plaque burden regardless of whether there was obstructive disease in any coronary artery, defined as a 50% or greater stenosis by computed tomographic angiography (CTA).
The findings argue for plaque burden as measured by CAC score, rather than percent-stenosis severity, for guiding further treatment decisions in such patients, researchers say.
The research was based on more than 20,000 symptomatic patients referred to diagnostic CTA in the Western Denmark Heart Registry who were then followed for about 4 years for major CV events, including death, myocardial infarction, or stroke.
“What we show is that CAC is important for prognosis, and that patients with no stenosis have similar high risk as patients with stenosis when CAC burden is similar,” Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, said in an interview.
The guidelines “distinguish between primary and secondary prevention patients” based on the presence or absence of obstructive CAD, he said, but “our results challenge this long-held approach. We show that patients with nonobstructive CAD carry similar risk as patients with obstructive CAD.”
In practice, risk tends to be greater in patients with obstructive compared with nonobstructive CAD. But the reason “is simply that they normally have higher atherosclerosis burden,” Dr. Mortensen said. “When you stratify based on atherosclerosis burden, then patients with obstructive and nonobstructive CAD have similar risk.”
The analysis was published online Dec. 7 in the Journal of the American College of Cardiology with Mortensen as lead author.
Until recently, it had long been believed that CV-event risk was driven by ischemia – but “ischemia is just a surrogate for the extent of atherosclerotic disease,” Armin Arbab Zadeh, MD, PhD, MPH, who is not connected with the current study, said in an interview.
The finding that CV risk climbs with growing coronary plaque burden “essentially confirms” other recent studies, but with “added value in showing how well the calcium scores, compared to obstructive disease, track with risk. So it’s definitely a nice extension of the evidence,” said Dr. Zadeh, director of cardiac CT at Johns Hopkins University, Baltimore.
“This study clearly shows that there is no ischemia ‘threshold,’ that the risk starts from mild and goes up with the burden of atherosclerotic disease. We were essentially taught wrong for decades.”
Dr. Mortensen said that the new results “are in line with previous studies showing that atherosclerosis burden is very important for risk.” They also help explain why revascularization of patients with stable angina failed to cut the risk of MI or death in trials like COURAGE, FAME-2, and ISCHEMIA. It’s because “stenosis per se explains little of the risk compared to atherosclerosis burden.”
In the current analysis, for example, about 65% of events were in patients who did not show obstructive CAD at CTA. Its 23,759 patients with symptoms suggestive of CAD were referred for CTA from 2008 through 2017; 5,043 (21.2%) were found to have obstructive disease and 18,716 (78.8%) either had no CAD or nonobstructive disease.
About 4.4% of patients experienced a first major CV event over a median follow-up of 4.3 years. Only events occurring later than 90 days after CTA were counted in an effort to exclude any directly related to revascularization, Dr. Mortensen noted.
The risk of events went up proportionally with both CAC score and the number of coronaries with obstructive disease.
The number of major CV events per 1,000 person-years was 6.2 for patients with a CAC score of 0, of whom 87% had no CAD by CTA, 7% had nonobstructive CAD, and 6% had obstructive CAD.
The corresponding rate was 17.5 among patients with a CAC score >100-399 for a hazard ratio (HR) of 1.7 (95% confidence interval [CI] 1.4-2.1) vs. a CAC score of 0.
And it was 42.3 per 1,000 patient-years among patients with CAC score >1000, HR 3.4 (95% CI, 2.5-4.6) vs. a CAC score of 0. Among those with the highest-tier CAC score, none were without CAD by CTA, 17% had nonobstructive disease, and 83% had obstructive CAD.
The major CV event rate rose similarly by number of coronaries with obstructive disease. It was 6.1 per 1,000 person-years in patients with no CAD. But it was 12.3 in those with nonobstructive disease, HR 1.3 (95% CI 1.1-1.6), up to 34.7 in those with triple-vessel obstructive disease, HR 2.9 (95% CI 2.2-3.9), vs. no CAD.
However, in an analysis with stratification by CAC score tier (0, 1-99, 100-399, 400-1,000, and >1,000), obstructive CAD was not associated with increased major CV-event risk in any stratum. The findings were similar in each subgroup with 1-vessel, 2-vessel, or 3-vessel CAD when stratified by CAC score.
Nor did major CV event risk track with obstructive CAD in analyses by age or after excluding all patients who underwent coronary revascularization within 90 days of CTA, the group reported.
“I believe these results support the use of CTA as a first-line test in patients with symptoms suggestive of CAD, as it provides valuable information for both diagnosis and prognosis in symptomatic patients,” Dr. Mortensen said. Those found to have a higher burden of atherosclerosis, he added, should receive aggressive preventive therapy regardless of whether or not they have obstructive disease.
The evidence from this study and others “supports a CTA-based approach” in such patients, Dr. Zadeh said. “And I would go further to say that a stress test is really inadequate,” in that it “detects the disease at such a late stage, you’re missing the opportunity to identify these patients who have atherosclerotic disease while you can do something about it.”
Its continued use as a first-line test, Dr. Zadeh said, “is essentially, in my mind, dismissing the evidence.”
An accompanying editorial Todd C. Villines, MD, and Patricia Rodriguez Lozano, MD, of the University of Virginia, Charlottesville agreed that “it is time that the traditional definitions of primary and secondary prevention evolve to incorporate CAC and CTA measures of patient risk based on coronary artery plaque burden.”
But they pointed out some limitations of the current study.
“The authors compared CAC with ≥50% stenosis, not CAC to comprehensive, contemporary coronary CTA,” and so “did not assess numerous other well-validated measures of coronary plaque burden that are routinely obtained from coronary CTA that typically improve the prognostic accuracy of coronary CTA beyond stenosis alone.” Also not performed was “plaque quantification on coronary CTA, an emerging field of study.”
The editorialists noted that noncontrast CT as used in the study for CAC scoring “is generally not recommended as a standalone test in symptomatic patients. Most studies have shown that coronary CTA, a test that accurately detects stenosis and identifies all types of coronary atherosclerosis (calcified and noncalcified), has significantly higher diagnostic and prognostic accuracy than CAC when performed in symptomatic patients without known coronary artery disease.”
Dr. Mortensen has disclosed no relevant financial relationships. Disclosures for the other authors are in the report. Dr. Villines and Dr. Rodriguez Lozano have disclosed no relevant financial relationships. Dr. Zadeh disclosed receiving grant support from Canon Medical Systems.
A version of this article originally appeared on Medscape.com.
Coronary artery calcium (CAC) score as a measure of plaque burden more reliably predicts future cardiovascular (CV) risk in patients with suspected coronary disease (CAD) than whether or not the disease is obstructive, a large retrospective study suggests.
Indeed, CV risk went up in tandem with growing plaque burden regardless of whether there was obstructive disease in any coronary artery, defined as a 50% or greater stenosis by computed tomographic angiography (CTA).
The findings argue for plaque burden as measured by CAC score, rather than percent-stenosis severity, for guiding further treatment decisions in such patients, researchers say.
The research was based on more than 20,000 symptomatic patients referred to diagnostic CTA in the Western Denmark Heart Registry who were then followed for about 4 years for major CV events, including death, myocardial infarction, or stroke.
“What we show is that CAC is important for prognosis, and that patients with no stenosis have similar high risk as patients with stenosis when CAC burden is similar,” Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, said in an interview.
The guidelines “distinguish between primary and secondary prevention patients” based on the presence or absence of obstructive CAD, he said, but “our results challenge this long-held approach. We show that patients with nonobstructive CAD carry similar risk as patients with obstructive CAD.”
In practice, risk tends to be greater in patients with obstructive compared with nonobstructive CAD. But the reason “is simply that they normally have higher atherosclerosis burden,” Dr. Mortensen said. “When you stratify based on atherosclerosis burden, then patients with obstructive and nonobstructive CAD have similar risk.”
The analysis was published online Dec. 7 in the Journal of the American College of Cardiology with Mortensen as lead author.
Until recently, it had long been believed that CV-event risk was driven by ischemia – but “ischemia is just a surrogate for the extent of atherosclerotic disease,” Armin Arbab Zadeh, MD, PhD, MPH, who is not connected with the current study, said in an interview.
The finding that CV risk climbs with growing coronary plaque burden “essentially confirms” other recent studies, but with “added value in showing how well the calcium scores, compared to obstructive disease, track with risk. So it’s definitely a nice extension of the evidence,” said Dr. Zadeh, director of cardiac CT at Johns Hopkins University, Baltimore.
“This study clearly shows that there is no ischemia ‘threshold,’ that the risk starts from mild and goes up with the burden of atherosclerotic disease. We were essentially taught wrong for decades.”
Dr. Mortensen said that the new results “are in line with previous studies showing that atherosclerosis burden is very important for risk.” They also help explain why revascularization of patients with stable angina failed to cut the risk of MI or death in trials like COURAGE, FAME-2, and ISCHEMIA. It’s because “stenosis per se explains little of the risk compared to atherosclerosis burden.”
In the current analysis, for example, about 65% of events were in patients who did not show obstructive CAD at CTA. Its 23,759 patients with symptoms suggestive of CAD were referred for CTA from 2008 through 2017; 5,043 (21.2%) were found to have obstructive disease and 18,716 (78.8%) either had no CAD or nonobstructive disease.
About 4.4% of patients experienced a first major CV event over a median follow-up of 4.3 years. Only events occurring later than 90 days after CTA were counted in an effort to exclude any directly related to revascularization, Dr. Mortensen noted.
The risk of events went up proportionally with both CAC score and the number of coronaries with obstructive disease.
The number of major CV events per 1,000 person-years was 6.2 for patients with a CAC score of 0, of whom 87% had no CAD by CTA, 7% had nonobstructive CAD, and 6% had obstructive CAD.
The corresponding rate was 17.5 among patients with a CAC score >100-399 for a hazard ratio (HR) of 1.7 (95% confidence interval [CI] 1.4-2.1) vs. a CAC score of 0.
And it was 42.3 per 1,000 patient-years among patients with CAC score >1000, HR 3.4 (95% CI, 2.5-4.6) vs. a CAC score of 0. Among those with the highest-tier CAC score, none were without CAD by CTA, 17% had nonobstructive disease, and 83% had obstructive CAD.
The major CV event rate rose similarly by number of coronaries with obstructive disease. It was 6.1 per 1,000 person-years in patients with no CAD. But it was 12.3 in those with nonobstructive disease, HR 1.3 (95% CI 1.1-1.6), up to 34.7 in those with triple-vessel obstructive disease, HR 2.9 (95% CI 2.2-3.9), vs. no CAD.
However, in an analysis with stratification by CAC score tier (0, 1-99, 100-399, 400-1,000, and >1,000), obstructive CAD was not associated with increased major CV-event risk in any stratum. The findings were similar in each subgroup with 1-vessel, 2-vessel, or 3-vessel CAD when stratified by CAC score.
Nor did major CV event risk track with obstructive CAD in analyses by age or after excluding all patients who underwent coronary revascularization within 90 days of CTA, the group reported.
“I believe these results support the use of CTA as a first-line test in patients with symptoms suggestive of CAD, as it provides valuable information for both diagnosis and prognosis in symptomatic patients,” Dr. Mortensen said. Those found to have a higher burden of atherosclerosis, he added, should receive aggressive preventive therapy regardless of whether or not they have obstructive disease.
The evidence from this study and others “supports a CTA-based approach” in such patients, Dr. Zadeh said. “And I would go further to say that a stress test is really inadequate,” in that it “detects the disease at such a late stage, you’re missing the opportunity to identify these patients who have atherosclerotic disease while you can do something about it.”
Its continued use as a first-line test, Dr. Zadeh said, “is essentially, in my mind, dismissing the evidence.”
An accompanying editorial Todd C. Villines, MD, and Patricia Rodriguez Lozano, MD, of the University of Virginia, Charlottesville agreed that “it is time that the traditional definitions of primary and secondary prevention evolve to incorporate CAC and CTA measures of patient risk based on coronary artery plaque burden.”
But they pointed out some limitations of the current study.
“The authors compared CAC with ≥50% stenosis, not CAC to comprehensive, contemporary coronary CTA,” and so “did not assess numerous other well-validated measures of coronary plaque burden that are routinely obtained from coronary CTA that typically improve the prognostic accuracy of coronary CTA beyond stenosis alone.” Also not performed was “plaque quantification on coronary CTA, an emerging field of study.”
The editorialists noted that noncontrast CT as used in the study for CAC scoring “is generally not recommended as a standalone test in symptomatic patients. Most studies have shown that coronary CTA, a test that accurately detects stenosis and identifies all types of coronary atherosclerosis (calcified and noncalcified), has significantly higher diagnostic and prognostic accuracy than CAC when performed in symptomatic patients without known coronary artery disease.”
Dr. Mortensen has disclosed no relevant financial relationships. Disclosures for the other authors are in the report. Dr. Villines and Dr. Rodriguez Lozano have disclosed no relevant financial relationships. Dr. Zadeh disclosed receiving grant support from Canon Medical Systems.
A version of this article originally appeared on Medscape.com.
Coronary artery calcium (CAC) score as a measure of plaque burden more reliably predicts future cardiovascular (CV) risk in patients with suspected coronary disease (CAD) than whether or not the disease is obstructive, a large retrospective study suggests.
Indeed, CV risk went up in tandem with growing plaque burden regardless of whether there was obstructive disease in any coronary artery, defined as a 50% or greater stenosis by computed tomographic angiography (CTA).
The findings argue for plaque burden as measured by CAC score, rather than percent-stenosis severity, for guiding further treatment decisions in such patients, researchers say.
The research was based on more than 20,000 symptomatic patients referred to diagnostic CTA in the Western Denmark Heart Registry who were then followed for about 4 years for major CV events, including death, myocardial infarction, or stroke.
“What we show is that CAC is important for prognosis, and that patients with no stenosis have similar high risk as patients with stenosis when CAC burden is similar,” Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, said in an interview.
The guidelines “distinguish between primary and secondary prevention patients” based on the presence or absence of obstructive CAD, he said, but “our results challenge this long-held approach. We show that patients with nonobstructive CAD carry similar risk as patients with obstructive CAD.”
In practice, risk tends to be greater in patients with obstructive compared with nonobstructive CAD. But the reason “is simply that they normally have higher atherosclerosis burden,” Dr. Mortensen said. “When you stratify based on atherosclerosis burden, then patients with obstructive and nonobstructive CAD have similar risk.”
The analysis was published online Dec. 7 in the Journal of the American College of Cardiology with Mortensen as lead author.
Until recently, it had long been believed that CV-event risk was driven by ischemia – but “ischemia is just a surrogate for the extent of atherosclerotic disease,” Armin Arbab Zadeh, MD, PhD, MPH, who is not connected with the current study, said in an interview.
The finding that CV risk climbs with growing coronary plaque burden “essentially confirms” other recent studies, but with “added value in showing how well the calcium scores, compared to obstructive disease, track with risk. So it’s definitely a nice extension of the evidence,” said Dr. Zadeh, director of cardiac CT at Johns Hopkins University, Baltimore.
“This study clearly shows that there is no ischemia ‘threshold,’ that the risk starts from mild and goes up with the burden of atherosclerotic disease. We were essentially taught wrong for decades.”
Dr. Mortensen said that the new results “are in line with previous studies showing that atherosclerosis burden is very important for risk.” They also help explain why revascularization of patients with stable angina failed to cut the risk of MI or death in trials like COURAGE, FAME-2, and ISCHEMIA. It’s because “stenosis per se explains little of the risk compared to atherosclerosis burden.”
In the current analysis, for example, about 65% of events were in patients who did not show obstructive CAD at CTA. Its 23,759 patients with symptoms suggestive of CAD were referred for CTA from 2008 through 2017; 5,043 (21.2%) were found to have obstructive disease and 18,716 (78.8%) either had no CAD or nonobstructive disease.
About 4.4% of patients experienced a first major CV event over a median follow-up of 4.3 years. Only events occurring later than 90 days after CTA were counted in an effort to exclude any directly related to revascularization, Dr. Mortensen noted.
The risk of events went up proportionally with both CAC score and the number of coronaries with obstructive disease.
The number of major CV events per 1,000 person-years was 6.2 for patients with a CAC score of 0, of whom 87% had no CAD by CTA, 7% had nonobstructive CAD, and 6% had obstructive CAD.
The corresponding rate was 17.5 among patients with a CAC score >100-399 for a hazard ratio (HR) of 1.7 (95% confidence interval [CI] 1.4-2.1) vs. a CAC score of 0.
And it was 42.3 per 1,000 patient-years among patients with CAC score >1000, HR 3.4 (95% CI, 2.5-4.6) vs. a CAC score of 0. Among those with the highest-tier CAC score, none were without CAD by CTA, 17% had nonobstructive disease, and 83% had obstructive CAD.
The major CV event rate rose similarly by number of coronaries with obstructive disease. It was 6.1 per 1,000 person-years in patients with no CAD. But it was 12.3 in those with nonobstructive disease, HR 1.3 (95% CI 1.1-1.6), up to 34.7 in those with triple-vessel obstructive disease, HR 2.9 (95% CI 2.2-3.9), vs. no CAD.
However, in an analysis with stratification by CAC score tier (0, 1-99, 100-399, 400-1,000, and >1,000), obstructive CAD was not associated with increased major CV-event risk in any stratum. The findings were similar in each subgroup with 1-vessel, 2-vessel, or 3-vessel CAD when stratified by CAC score.
Nor did major CV event risk track with obstructive CAD in analyses by age or after excluding all patients who underwent coronary revascularization within 90 days of CTA, the group reported.
“I believe these results support the use of CTA as a first-line test in patients with symptoms suggestive of CAD, as it provides valuable information for both diagnosis and prognosis in symptomatic patients,” Dr. Mortensen said. Those found to have a higher burden of atherosclerosis, he added, should receive aggressive preventive therapy regardless of whether or not they have obstructive disease.
The evidence from this study and others “supports a CTA-based approach” in such patients, Dr. Zadeh said. “And I would go further to say that a stress test is really inadequate,” in that it “detects the disease at such a late stage, you’re missing the opportunity to identify these patients who have atherosclerotic disease while you can do something about it.”
Its continued use as a first-line test, Dr. Zadeh said, “is essentially, in my mind, dismissing the evidence.”
An accompanying editorial Todd C. Villines, MD, and Patricia Rodriguez Lozano, MD, of the University of Virginia, Charlottesville agreed that “it is time that the traditional definitions of primary and secondary prevention evolve to incorporate CAC and CTA measures of patient risk based on coronary artery plaque burden.”
But they pointed out some limitations of the current study.
“The authors compared CAC with ≥50% stenosis, not CAC to comprehensive, contemporary coronary CTA,” and so “did not assess numerous other well-validated measures of coronary plaque burden that are routinely obtained from coronary CTA that typically improve the prognostic accuracy of coronary CTA beyond stenosis alone.” Also not performed was “plaque quantification on coronary CTA, an emerging field of study.”
The editorialists noted that noncontrast CT as used in the study for CAC scoring “is generally not recommended as a standalone test in symptomatic patients. Most studies have shown that coronary CTA, a test that accurately detects stenosis and identifies all types of coronary atherosclerosis (calcified and noncalcified), has significantly higher diagnostic and prognostic accuracy than CAC when performed in symptomatic patients without known coronary artery disease.”
Dr. Mortensen has disclosed no relevant financial relationships. Disclosures for the other authors are in the report. Dr. Villines and Dr. Rodriguez Lozano have disclosed no relevant financial relationships. Dr. Zadeh disclosed receiving grant support from Canon Medical Systems.
A version of this article originally appeared on Medscape.com.
Study results support screening rosacea patients for cardiometabolic disease
according to the results of a meta-analysis of more than 50,000 patients.
To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.
In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.
Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.
Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
Findings don’t show causality
The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”
However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.
“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.
“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”
Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”
“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.
The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.
SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.
according to the results of a meta-analysis of more than 50,000 patients.
To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.
In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.
Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.
Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
Findings don’t show causality
The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”
However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.
“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.
“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”
Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”
“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.
The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.
SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.
according to the results of a meta-analysis of more than 50,000 patients.
To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.
In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.
Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.
Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
Findings don’t show causality
The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”
However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.
“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.
“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”
Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”
“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.
The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.
SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
‘Worrisome’ rates of suicidal thoughts and behaviors in children with epilepsy
new research suggests. In a study of more than 100 youth with the disorder, more than 40% had depression, 30% had anxiety, and about 1 in 10 exhibited signs of suicidal thoughts and behaviors.
These rates “are really worrisome” and highlight the need to screen all children and young adults with epilepsy for psychiatric disorders, said study author Tatiana Falcone, MD, assistant professor of neurology and child and adolescent psychiatry at the Cleveland Clinic.
“It’s very important to screen for suicidality and for depression and anxiety, even when patients aren’t reporting symptoms,” said Dr. Falcone.
Previous research shows children with epilepsy will attend the emergency room with symptoms such as headache or stomachache “when the main reason for the visit was the kid was suicidal,” Dr. Falcone said. “Unless you ask the specific question: ‘Are you having thoughts about hurting yourself?’ this will go unreported,” she added.
The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
Red flag
Not much is known about suicidality in children and youth with epilepsy except that depression and anxiety – the most common psychiatric comorbidities in this population – appear to contribute to suicidal thoughts.
Dr. Falcone said that she and her colleagues often see children and adolescents with epilepsy in their clinic who have attempted suicide. In recent years, the clinicians have increased efforts to try to identify them before they carry out a successful suicide attempt, said lead investigator Anjali Dagar, MD, clinical research psychiatry fellow at Cleveland Clinic.
The study included 119 patients aged 10-24 years (mean age, 15.8 years; 54.6% female). All attended an epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and did not have a psychiatric diagnosis.
Epilepsy severity ranged among study participants. About half were drug resistant and were at the center for surgical evaluation and the others were newly diagnosed.
Participants filled out questionnaires to self-report psychiatric conditions. The validated screening tools included the Center for Epidemiological Studies Depression Scale for Children (CES-DC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Ask Suicide–Screening Questions (ASQ).
A score of 15 or higher on the CES-DC indicates a risk for depression. On the SCARED test, a score higher than 32 indicates anxiety. Recent research has shown that anxiety is a main risk factor “in moving people from contemplating suicide to actually carrying it out,” Dr. Falcone said.
The ASQ includes four questions about suicidal thoughts and whether respondents have tried to hurt themselves. Dr. Dagar noted that a positive response to any of these questions should raise a red flag.
Very high rates
Results showed that almost one-third (30.2%) of the participants scored positive for anxiety on SCARED and 41.2% scored positive for depression on the CSE-DC. These are “very high” rates, Dr. Falcone said. For comparison, the rate of reported anxiety is less than 10% in school surveys.
In addition, the Centers for Disease Control and Prevention reports about 3% of 2- to 17-year-olds in the general population have depression. Even compared with other chronic illnesses (including diabetes, heart disease, and cancer), children with epilepsy have a higher rate of depression, said Dr. Falcone.
More than 1 in 10 (10.9%) participants in the study exhibited signs of suicidality, as shown by having at least one positive response on the ASQ. “That’s a lot,” and much higher than the estimated rate in the general teen population, Dr. Falcone noted.
She noted that “these are just general kids with epilepsy” who had not been previously diagnosed with a psychiatric disorder.
“Depression, anxiety, and suicidality are very frequent comorbidities in patients with epilepsy; and even if a patient is not reporting any symptoms, we should be asking these questions to help them,” she said.
Study participants who had at least one positive response on the ASQ had a mean score of 32.1 on the SCARED, compared with a mean score of 18.3 for those who did not have a positive response on the ASQ (P = .003).
“We wanted to see if there was a direct association in our sample between anxiety and suicidal thoughts, and we found [that] yes there was,” Dr. Falcone said. There was also an association with depression. More than 26% of participants who scored 16 or higher on the CES-DC indicated at least one positive response on the ASQ. This is significantly higher than those who scored 15 or below on the CES-DC (P < .0001).
Bidirectional relationship
The findings suggest that either depression or anxiety may contribute to suicidal thoughts or behaviors, Dr. Dagar said. “It’s like two hands. It could be anxiety leading to suicidality, or it could be depression, or it could be both.”
Dr. Falcone noted that children with epilepsy who aren’t sure when they’ll get their next seizure, or who are bullied at school for being different, may be especially prone to anxiety or depression.
There’s a bit of a “chicken-and-egg” relationship between depression and epilepsy, a disorder affecting electrical signals in the brain, she said. Previous research has shown that a “bidirectional relationship” is involved.
“Even in patients with depression who are not diagnosed with epilepsy, the incidence of epilepsy is 3% higher just because you have depression,” Dr. Falcone said.
Suicidal youth tend to attempt suicide more than once. Dr. Falcone and colleagues are trying to intervene “at different levels,” be that in the hospital or as an outpatient, to prevent this from happening. “We want to find out what different things we can do to engage them and improve the probability they don’t reattempt,” she said.
All children and youth with epilepsy should be screened for anxiety, depression, and suicidal thoughts and behaviors. From age 10 years, children with epilepsy should be screened at least once a year, but those with a psychiatric disorder should be screened more often, Dr. Falcone added. The investigators note their findings need to be confirmed in larger, more diverse studies.
Importance of screening
Michael Privitera, MD, director of the Epilepsy Center and professor of neurology at the University of Cincinnati Gardner Neuroscience Institute, said the findings reinforce that, as with adults, depression and anxiety are common in children with epilepsy.
“Neurologists should take advantage of the many psychiatric screening tools available to identify these problems in their pediatric and adult patients,” Dr. Privitera said. Even more importantly, screening may help identify those who may be at highest risk of suicide.
The study was funded by the Health Resources Services Administration. The investigators and Dr. Privitera have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests. In a study of more than 100 youth with the disorder, more than 40% had depression, 30% had anxiety, and about 1 in 10 exhibited signs of suicidal thoughts and behaviors.
These rates “are really worrisome” and highlight the need to screen all children and young adults with epilepsy for psychiatric disorders, said study author Tatiana Falcone, MD, assistant professor of neurology and child and adolescent psychiatry at the Cleveland Clinic.
“It’s very important to screen for suicidality and for depression and anxiety, even when patients aren’t reporting symptoms,” said Dr. Falcone.
Previous research shows children with epilepsy will attend the emergency room with symptoms such as headache or stomachache “when the main reason for the visit was the kid was suicidal,” Dr. Falcone said. “Unless you ask the specific question: ‘Are you having thoughts about hurting yourself?’ this will go unreported,” she added.
The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
Red flag
Not much is known about suicidality in children and youth with epilepsy except that depression and anxiety – the most common psychiatric comorbidities in this population – appear to contribute to suicidal thoughts.
Dr. Falcone said that she and her colleagues often see children and adolescents with epilepsy in their clinic who have attempted suicide. In recent years, the clinicians have increased efforts to try to identify them before they carry out a successful suicide attempt, said lead investigator Anjali Dagar, MD, clinical research psychiatry fellow at Cleveland Clinic.
The study included 119 patients aged 10-24 years (mean age, 15.8 years; 54.6% female). All attended an epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and did not have a psychiatric diagnosis.
Epilepsy severity ranged among study participants. About half were drug resistant and were at the center for surgical evaluation and the others were newly diagnosed.
Participants filled out questionnaires to self-report psychiatric conditions. The validated screening tools included the Center for Epidemiological Studies Depression Scale for Children (CES-DC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Ask Suicide–Screening Questions (ASQ).
A score of 15 or higher on the CES-DC indicates a risk for depression. On the SCARED test, a score higher than 32 indicates anxiety. Recent research has shown that anxiety is a main risk factor “in moving people from contemplating suicide to actually carrying it out,” Dr. Falcone said.
The ASQ includes four questions about suicidal thoughts and whether respondents have tried to hurt themselves. Dr. Dagar noted that a positive response to any of these questions should raise a red flag.
Very high rates
Results showed that almost one-third (30.2%) of the participants scored positive for anxiety on SCARED and 41.2% scored positive for depression on the CSE-DC. These are “very high” rates, Dr. Falcone said. For comparison, the rate of reported anxiety is less than 10% in school surveys.
In addition, the Centers for Disease Control and Prevention reports about 3% of 2- to 17-year-olds in the general population have depression. Even compared with other chronic illnesses (including diabetes, heart disease, and cancer), children with epilepsy have a higher rate of depression, said Dr. Falcone.
More than 1 in 10 (10.9%) participants in the study exhibited signs of suicidality, as shown by having at least one positive response on the ASQ. “That’s a lot,” and much higher than the estimated rate in the general teen population, Dr. Falcone noted.
She noted that “these are just general kids with epilepsy” who had not been previously diagnosed with a psychiatric disorder.
“Depression, anxiety, and suicidality are very frequent comorbidities in patients with epilepsy; and even if a patient is not reporting any symptoms, we should be asking these questions to help them,” she said.
Study participants who had at least one positive response on the ASQ had a mean score of 32.1 on the SCARED, compared with a mean score of 18.3 for those who did not have a positive response on the ASQ (P = .003).
“We wanted to see if there was a direct association in our sample between anxiety and suicidal thoughts, and we found [that] yes there was,” Dr. Falcone said. There was also an association with depression. More than 26% of participants who scored 16 or higher on the CES-DC indicated at least one positive response on the ASQ. This is significantly higher than those who scored 15 or below on the CES-DC (P < .0001).
Bidirectional relationship
The findings suggest that either depression or anxiety may contribute to suicidal thoughts or behaviors, Dr. Dagar said. “It’s like two hands. It could be anxiety leading to suicidality, or it could be depression, or it could be both.”
Dr. Falcone noted that children with epilepsy who aren’t sure when they’ll get their next seizure, or who are bullied at school for being different, may be especially prone to anxiety or depression.
There’s a bit of a “chicken-and-egg” relationship between depression and epilepsy, a disorder affecting electrical signals in the brain, she said. Previous research has shown that a “bidirectional relationship” is involved.
“Even in patients with depression who are not diagnosed with epilepsy, the incidence of epilepsy is 3% higher just because you have depression,” Dr. Falcone said.
Suicidal youth tend to attempt suicide more than once. Dr. Falcone and colleagues are trying to intervene “at different levels,” be that in the hospital or as an outpatient, to prevent this from happening. “We want to find out what different things we can do to engage them and improve the probability they don’t reattempt,” she said.
All children and youth with epilepsy should be screened for anxiety, depression, and suicidal thoughts and behaviors. From age 10 years, children with epilepsy should be screened at least once a year, but those with a psychiatric disorder should be screened more often, Dr. Falcone added. The investigators note their findings need to be confirmed in larger, more diverse studies.
Importance of screening
Michael Privitera, MD, director of the Epilepsy Center and professor of neurology at the University of Cincinnati Gardner Neuroscience Institute, said the findings reinforce that, as with adults, depression and anxiety are common in children with epilepsy.
“Neurologists should take advantage of the many psychiatric screening tools available to identify these problems in their pediatric and adult patients,” Dr. Privitera said. Even more importantly, screening may help identify those who may be at highest risk of suicide.
The study was funded by the Health Resources Services Administration. The investigators and Dr. Privitera have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests. In a study of more than 100 youth with the disorder, more than 40% had depression, 30% had anxiety, and about 1 in 10 exhibited signs of suicidal thoughts and behaviors.
These rates “are really worrisome” and highlight the need to screen all children and young adults with epilepsy for psychiatric disorders, said study author Tatiana Falcone, MD, assistant professor of neurology and child and adolescent psychiatry at the Cleveland Clinic.
“It’s very important to screen for suicidality and for depression and anxiety, even when patients aren’t reporting symptoms,” said Dr. Falcone.
Previous research shows children with epilepsy will attend the emergency room with symptoms such as headache or stomachache “when the main reason for the visit was the kid was suicidal,” Dr. Falcone said. “Unless you ask the specific question: ‘Are you having thoughts about hurting yourself?’ this will go unreported,” she added.
The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
Red flag
Not much is known about suicidality in children and youth with epilepsy except that depression and anxiety – the most common psychiatric comorbidities in this population – appear to contribute to suicidal thoughts.
Dr. Falcone said that she and her colleagues often see children and adolescents with epilepsy in their clinic who have attempted suicide. In recent years, the clinicians have increased efforts to try to identify them before they carry out a successful suicide attempt, said lead investigator Anjali Dagar, MD, clinical research psychiatry fellow at Cleveland Clinic.
The study included 119 patients aged 10-24 years (mean age, 15.8 years; 54.6% female). All attended an epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and did not have a psychiatric diagnosis.
Epilepsy severity ranged among study participants. About half were drug resistant and were at the center for surgical evaluation and the others were newly diagnosed.
Participants filled out questionnaires to self-report psychiatric conditions. The validated screening tools included the Center for Epidemiological Studies Depression Scale for Children (CES-DC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Ask Suicide–Screening Questions (ASQ).
A score of 15 or higher on the CES-DC indicates a risk for depression. On the SCARED test, a score higher than 32 indicates anxiety. Recent research has shown that anxiety is a main risk factor “in moving people from contemplating suicide to actually carrying it out,” Dr. Falcone said.
The ASQ includes four questions about suicidal thoughts and whether respondents have tried to hurt themselves. Dr. Dagar noted that a positive response to any of these questions should raise a red flag.
Very high rates
Results showed that almost one-third (30.2%) of the participants scored positive for anxiety on SCARED and 41.2% scored positive for depression on the CSE-DC. These are “very high” rates, Dr. Falcone said. For comparison, the rate of reported anxiety is less than 10% in school surveys.
In addition, the Centers for Disease Control and Prevention reports about 3% of 2- to 17-year-olds in the general population have depression. Even compared with other chronic illnesses (including diabetes, heart disease, and cancer), children with epilepsy have a higher rate of depression, said Dr. Falcone.
More than 1 in 10 (10.9%) participants in the study exhibited signs of suicidality, as shown by having at least one positive response on the ASQ. “That’s a lot,” and much higher than the estimated rate in the general teen population, Dr. Falcone noted.
She noted that “these are just general kids with epilepsy” who had not been previously diagnosed with a psychiatric disorder.
“Depression, anxiety, and suicidality are very frequent comorbidities in patients with epilepsy; and even if a patient is not reporting any symptoms, we should be asking these questions to help them,” she said.
Study participants who had at least one positive response on the ASQ had a mean score of 32.1 on the SCARED, compared with a mean score of 18.3 for those who did not have a positive response on the ASQ (P = .003).
“We wanted to see if there was a direct association in our sample between anxiety and suicidal thoughts, and we found [that] yes there was,” Dr. Falcone said. There was also an association with depression. More than 26% of participants who scored 16 or higher on the CES-DC indicated at least one positive response on the ASQ. This is significantly higher than those who scored 15 or below on the CES-DC (P < .0001).
Bidirectional relationship
The findings suggest that either depression or anxiety may contribute to suicidal thoughts or behaviors, Dr. Dagar said. “It’s like two hands. It could be anxiety leading to suicidality, or it could be depression, or it could be both.”
Dr. Falcone noted that children with epilepsy who aren’t sure when they’ll get their next seizure, or who are bullied at school for being different, may be especially prone to anxiety or depression.
There’s a bit of a “chicken-and-egg” relationship between depression and epilepsy, a disorder affecting electrical signals in the brain, she said. Previous research has shown that a “bidirectional relationship” is involved.
“Even in patients with depression who are not diagnosed with epilepsy, the incidence of epilepsy is 3% higher just because you have depression,” Dr. Falcone said.
Suicidal youth tend to attempt suicide more than once. Dr. Falcone and colleagues are trying to intervene “at different levels,” be that in the hospital or as an outpatient, to prevent this from happening. “We want to find out what different things we can do to engage them and improve the probability they don’t reattempt,” she said.
All children and youth with epilepsy should be screened for anxiety, depression, and suicidal thoughts and behaviors. From age 10 years, children with epilepsy should be screened at least once a year, but those with a psychiatric disorder should be screened more often, Dr. Falcone added. The investigators note their findings need to be confirmed in larger, more diverse studies.
Importance of screening
Michael Privitera, MD, director of the Epilepsy Center and professor of neurology at the University of Cincinnati Gardner Neuroscience Institute, said the findings reinforce that, as with adults, depression and anxiety are common in children with epilepsy.
“Neurologists should take advantage of the many psychiatric screening tools available to identify these problems in their pediatric and adult patients,” Dr. Privitera said. Even more importantly, screening may help identify those who may be at highest risk of suicide.
The study was funded by the Health Resources Services Administration. The investigators and Dr. Privitera have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AES 2020
Radiofrequency ablation blocks hip, shoulder arthritis pain
Osteoarthritis patients report significant pain relief after treatment with cooled radiofrequency ablation, a new technique that “stuns” sensory nerves in shoulder and hip joints to reduce – and sometimes eliminate – pain.
“We send a small current to the sensory nerve to heat up the tissue and disrupt the fibers,” study lead author Felix Gonzalez, MD, of Emory University, Atlanta, said in an interview. “The effect is that the transmission of pain is significantly slowed or halted altogether.
“We damage something to fix something,” Dr. Gonzalez continued. “We target only the problematic nerve and get a very localized effect.”
Two-phase treatment
The treatment is performed in two phases. First, patients with shoulder pain are given an anesthetic to block their suprascapular, lateral pectoral, and axillary sensory articular nerves. Patients with hip pain have their obturator and femoral sensory articular nerves blocked.
A week or two later, the same nerves are treated with cooled radiofrequency ablation. Guided by x-ray imaging, a clinician heats up the affected nerve tissue using the tip of a needle, which is pointed at the nerve. “It’s a 22-gauge needle, slightly thicker than an acupuncture needle,” Dr. Gonzalez explained. “We heat up the nerve for about 2 minutes to about 60 degrees Celsius – it stuns the nerve,” he said.
“The result disrupts or slows down pain transmission while leaving the nerve intact.”
To test the efficacy of the technique, researchers treated 12 shoulders in patients with an average age of 61 years, and 11 hips in patients with an average age of 62 years.
Three months after treatment, patients with hip pain reported improvement in Hip Disability and Osteoarthritis Outcome Score (HOOS) from a baseline of 17.0 to 52.9 (P < .0001).
Shoulder pain was also reduced significantly. Using the American Shoulder and Elbow Surgeons (ASES) score, researchers reported an improvement from 17.2 (±6.6) at baseline to 65.7 (±5.9) at 3 months (P < .0001).
“We are targeting a subset of patients for this that don’t qualify for surgery,” Dr. Gonzalez noted. For patients with a body mass index above 35, or a history of hypertension, heart disease, or multiple strokes, opioids are the most common treatment, he said.
These patients “fall through the cracks,” he explained. Those who have mild to moderate pain are managed with physical therapy and injections, and those with severe pain go into surgery. “But what about the ones in the middle ... who are not eligible for surgery? They are at risk for opioid overuse,” he said. “So this treatment is a good option for them.”
Treats the symptoms, not the cause
“This study shows the efficacy of this method in taking care of shoulder and hip pain,” Luca Maria Sconfienza, MD, PhD, of Galeazzi Orthopedic Hospital in Milan, said in an interview. Dr. Sconfienza was not involved in Dr. Gonzalez’s study.
However, like corticosteroid injections, “the drawback of radiofrequency ablation is the fact that it only treats the symptoms and not the cause, and efficacy is usually limited over time,” she said.
Dr. Sconfienza said this study leaves her with three pertinent questions. “First, whether pain control extends beyond the 3-month follow-up reported by authors in the abstract; second, [what] is the efficacy of this method compared to other interventions (e.g., physical therapy, injections) or to doing nothing; and last, radiofrequency ablation is usually not a cheap treatment, thus a cost-efficacy analysis would be desirable, especially in comparison to other procedures.”
Dr. Gonzalez and Dr. Sconfienza have nothing relevant to disclose.
A version of this article originally appeared on Medscape.com.
Osteoarthritis patients report significant pain relief after treatment with cooled radiofrequency ablation, a new technique that “stuns” sensory nerves in shoulder and hip joints to reduce – and sometimes eliminate – pain.
“We send a small current to the sensory nerve to heat up the tissue and disrupt the fibers,” study lead author Felix Gonzalez, MD, of Emory University, Atlanta, said in an interview. “The effect is that the transmission of pain is significantly slowed or halted altogether.
“We damage something to fix something,” Dr. Gonzalez continued. “We target only the problematic nerve and get a very localized effect.”
Two-phase treatment
The treatment is performed in two phases. First, patients with shoulder pain are given an anesthetic to block their suprascapular, lateral pectoral, and axillary sensory articular nerves. Patients with hip pain have their obturator and femoral sensory articular nerves blocked.
A week or two later, the same nerves are treated with cooled radiofrequency ablation. Guided by x-ray imaging, a clinician heats up the affected nerve tissue using the tip of a needle, which is pointed at the nerve. “It’s a 22-gauge needle, slightly thicker than an acupuncture needle,” Dr. Gonzalez explained. “We heat up the nerve for about 2 minutes to about 60 degrees Celsius – it stuns the nerve,” he said.
“The result disrupts or slows down pain transmission while leaving the nerve intact.”
To test the efficacy of the technique, researchers treated 12 shoulders in patients with an average age of 61 years, and 11 hips in patients with an average age of 62 years.
Three months after treatment, patients with hip pain reported improvement in Hip Disability and Osteoarthritis Outcome Score (HOOS) from a baseline of 17.0 to 52.9 (P < .0001).
Shoulder pain was also reduced significantly. Using the American Shoulder and Elbow Surgeons (ASES) score, researchers reported an improvement from 17.2 (±6.6) at baseline to 65.7 (±5.9) at 3 months (P < .0001).
“We are targeting a subset of patients for this that don’t qualify for surgery,” Dr. Gonzalez noted. For patients with a body mass index above 35, or a history of hypertension, heart disease, or multiple strokes, opioids are the most common treatment, he said.
These patients “fall through the cracks,” he explained. Those who have mild to moderate pain are managed with physical therapy and injections, and those with severe pain go into surgery. “But what about the ones in the middle ... who are not eligible for surgery? They are at risk for opioid overuse,” he said. “So this treatment is a good option for them.”
Treats the symptoms, not the cause
“This study shows the efficacy of this method in taking care of shoulder and hip pain,” Luca Maria Sconfienza, MD, PhD, of Galeazzi Orthopedic Hospital in Milan, said in an interview. Dr. Sconfienza was not involved in Dr. Gonzalez’s study.
However, like corticosteroid injections, “the drawback of radiofrequency ablation is the fact that it only treats the symptoms and not the cause, and efficacy is usually limited over time,” she said.
Dr. Sconfienza said this study leaves her with three pertinent questions. “First, whether pain control extends beyond the 3-month follow-up reported by authors in the abstract; second, [what] is the efficacy of this method compared to other interventions (e.g., physical therapy, injections) or to doing nothing; and last, radiofrequency ablation is usually not a cheap treatment, thus a cost-efficacy analysis would be desirable, especially in comparison to other procedures.”
Dr. Gonzalez and Dr. Sconfienza have nothing relevant to disclose.
A version of this article originally appeared on Medscape.com.
Osteoarthritis patients report significant pain relief after treatment with cooled radiofrequency ablation, a new technique that “stuns” sensory nerves in shoulder and hip joints to reduce – and sometimes eliminate – pain.
“We send a small current to the sensory nerve to heat up the tissue and disrupt the fibers,” study lead author Felix Gonzalez, MD, of Emory University, Atlanta, said in an interview. “The effect is that the transmission of pain is significantly slowed or halted altogether.
“We damage something to fix something,” Dr. Gonzalez continued. “We target only the problematic nerve and get a very localized effect.”
Two-phase treatment
The treatment is performed in two phases. First, patients with shoulder pain are given an anesthetic to block their suprascapular, lateral pectoral, and axillary sensory articular nerves. Patients with hip pain have their obturator and femoral sensory articular nerves blocked.
A week or two later, the same nerves are treated with cooled radiofrequency ablation. Guided by x-ray imaging, a clinician heats up the affected nerve tissue using the tip of a needle, which is pointed at the nerve. “It’s a 22-gauge needle, slightly thicker than an acupuncture needle,” Dr. Gonzalez explained. “We heat up the nerve for about 2 minutes to about 60 degrees Celsius – it stuns the nerve,” he said.
“The result disrupts or slows down pain transmission while leaving the nerve intact.”
To test the efficacy of the technique, researchers treated 12 shoulders in patients with an average age of 61 years, and 11 hips in patients with an average age of 62 years.
Three months after treatment, patients with hip pain reported improvement in Hip Disability and Osteoarthritis Outcome Score (HOOS) from a baseline of 17.0 to 52.9 (P < .0001).
Shoulder pain was also reduced significantly. Using the American Shoulder and Elbow Surgeons (ASES) score, researchers reported an improvement from 17.2 (±6.6) at baseline to 65.7 (±5.9) at 3 months (P < .0001).
“We are targeting a subset of patients for this that don’t qualify for surgery,” Dr. Gonzalez noted. For patients with a body mass index above 35, or a history of hypertension, heart disease, or multiple strokes, opioids are the most common treatment, he said.
These patients “fall through the cracks,” he explained. Those who have mild to moderate pain are managed with physical therapy and injections, and those with severe pain go into surgery. “But what about the ones in the middle ... who are not eligible for surgery? They are at risk for opioid overuse,” he said. “So this treatment is a good option for them.”
Treats the symptoms, not the cause
“This study shows the efficacy of this method in taking care of shoulder and hip pain,” Luca Maria Sconfienza, MD, PhD, of Galeazzi Orthopedic Hospital in Milan, said in an interview. Dr. Sconfienza was not involved in Dr. Gonzalez’s study.
However, like corticosteroid injections, “the drawback of radiofrequency ablation is the fact that it only treats the symptoms and not the cause, and efficacy is usually limited over time,” she said.
Dr. Sconfienza said this study leaves her with three pertinent questions. “First, whether pain control extends beyond the 3-month follow-up reported by authors in the abstract; second, [what] is the efficacy of this method compared to other interventions (e.g., physical therapy, injections) or to doing nothing; and last, radiofrequency ablation is usually not a cheap treatment, thus a cost-efficacy analysis would be desirable, especially in comparison to other procedures.”
Dr. Gonzalez and Dr. Sconfienza have nothing relevant to disclose.
A version of this article originally appeared on Medscape.com.
Extended virus shedding after COVID-19 in some patients with cancer
Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma.
The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine.
Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York.
“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.
Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.
Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said.
Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
Shedding of viable virus
For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).
Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.
There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection.
In total, 78 respiratory samples were collected.
“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”
Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.
For 11 patients, the team obtained serial sample genomes and found that “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma.
The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine.
Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York.
“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.
Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.
Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said.
Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
Shedding of viable virus
For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).
Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.
There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection.
In total, 78 respiratory samples were collected.
“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”
Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.
For 11 patients, the team obtained serial sample genomes and found that “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma.
The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine.
Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York.
“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.
Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.
Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said.
Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
Shedding of viable virus
For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).
Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.
There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection.
In total, 78 respiratory samples were collected.
“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”
Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.
For 11 patients, the team obtained serial sample genomes and found that “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Black race linked to poorer survival in AML
Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.
Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs. 43%). The risk for death was 27% higher for Black patients compared with White patients.
“Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients,” said first author Bhavana Bhatnagar, DO, of the Ohio State University’s Comprehensive Cancer Center, Columbus. “We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is, in and of itself, an independent poor prognostic variable for survival.”
She noted that the persistently poor outcomes of young Black patients that were seen despite similar treatments in clinical trials strongly suggest that additional factors have a bearing on their survival.
The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.
Racial disparities in cancer outcomes remain a challenge. The term “health disparities” describes the differences of health outcomes among different groups, said Chancellor Donald, MD, of Tulane University, New Orleans, who introduced the article at the meeting. “Racial health disparities usually result from an unequal distribution of power and resources, not genetics.
“The examination of health disparities is certainly a worthwhile endeavor,” he continued. “For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the life span of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality.”
Black race a risk factor
For their study, Dr. Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults aged 18-60 years who were diagnosed with AML between 1986 and 2015.
To characterize molecular features, they conducted targeted sequencing of 81 genes in 1,339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.
Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P < .001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n = 1,365; Black patients, n = 160; P = .19). However, the difference was significant between 1996 and 2005 (White patients, n = 2,994; Black patients, n = 480; P = .004). “And it became even more noticeable in the most recent decade,” said Dr. Bhatnagar. “Furthermore, younger Black AML patients were found to have worse survival compared with younger White AML patients.”
Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs. 46%; P = .02) and complete remission rates (71% vs. 71%; P = 1.00). “While relapse rates were slightly higher in Black compared to White patients, this difference did not reach statistical significance,” said Dr. Bhatnagar. “There was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients.”
However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years, vs. 1.4 years for White patients (P = .02). Overall survival was 1.2 years vs. 1.8 years (P = .02).
Relapse rates were slightly higher in Black patients than in White patients, at 71% vs. 59%, but this difference did not reach statistical significance (P = .14).
Differences in biomarkers
With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. “All of these genes are established commonly mutated genes in AML,” said Bhatnagar.
On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, FLT3-ITD and IDH2 mutations were the only mutations associated with a higher risk for death among Black patients.
“This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors,” said Dr. Bhatnagar. “In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.
“Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, “ she said.
Understudied disparities
Although the study showed that Black patients had worse outcomes, “surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials,” noted Elisa Weiss, PhD, senior vice president of education, services, and health research for the Leukemia and Lymphoma Society.
“The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities,” she said in an interview. “In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual’s ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources.”
She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to “advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to health care, services, and programs for blood cancer patients and survivors.”
The research was supported in part by the National Cancer Institute of the National Institutes of Health, other institutions, and through several scholar awards. Dr. Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr. Weiss has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.
Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs. 43%). The risk for death was 27% higher for Black patients compared with White patients.
“Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients,” said first author Bhavana Bhatnagar, DO, of the Ohio State University’s Comprehensive Cancer Center, Columbus. “We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is, in and of itself, an independent poor prognostic variable for survival.”
She noted that the persistently poor outcomes of young Black patients that were seen despite similar treatments in clinical trials strongly suggest that additional factors have a bearing on their survival.
The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.
Racial disparities in cancer outcomes remain a challenge. The term “health disparities” describes the differences of health outcomes among different groups, said Chancellor Donald, MD, of Tulane University, New Orleans, who introduced the article at the meeting. “Racial health disparities usually result from an unequal distribution of power and resources, not genetics.
“The examination of health disparities is certainly a worthwhile endeavor,” he continued. “For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the life span of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality.”
Black race a risk factor
For their study, Dr. Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults aged 18-60 years who were diagnosed with AML between 1986 and 2015.
To characterize molecular features, they conducted targeted sequencing of 81 genes in 1,339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.
Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P < .001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n = 1,365; Black patients, n = 160; P = .19). However, the difference was significant between 1996 and 2005 (White patients, n = 2,994; Black patients, n = 480; P = .004). “And it became even more noticeable in the most recent decade,” said Dr. Bhatnagar. “Furthermore, younger Black AML patients were found to have worse survival compared with younger White AML patients.”
Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs. 46%; P = .02) and complete remission rates (71% vs. 71%; P = 1.00). “While relapse rates were slightly higher in Black compared to White patients, this difference did not reach statistical significance,” said Dr. Bhatnagar. “There was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients.”
However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years, vs. 1.4 years for White patients (P = .02). Overall survival was 1.2 years vs. 1.8 years (P = .02).
Relapse rates were slightly higher in Black patients than in White patients, at 71% vs. 59%, but this difference did not reach statistical significance (P = .14).
Differences in biomarkers
With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. “All of these genes are established commonly mutated genes in AML,” said Bhatnagar.
On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, FLT3-ITD and IDH2 mutations were the only mutations associated with a higher risk for death among Black patients.
“This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors,” said Dr. Bhatnagar. “In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.
“Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, “ she said.
Understudied disparities
Although the study showed that Black patients had worse outcomes, “surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials,” noted Elisa Weiss, PhD, senior vice president of education, services, and health research for the Leukemia and Lymphoma Society.
“The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities,” she said in an interview. “In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual’s ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources.”
She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to “advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to health care, services, and programs for blood cancer patients and survivors.”
The research was supported in part by the National Cancer Institute of the National Institutes of Health, other institutions, and through several scholar awards. Dr. Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr. Weiss has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.
Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs. 43%). The risk for death was 27% higher for Black patients compared with White patients.
“Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients,” said first author Bhavana Bhatnagar, DO, of the Ohio State University’s Comprehensive Cancer Center, Columbus. “We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is, in and of itself, an independent poor prognostic variable for survival.”
She noted that the persistently poor outcomes of young Black patients that were seen despite similar treatments in clinical trials strongly suggest that additional factors have a bearing on their survival.
The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.
Racial disparities in cancer outcomes remain a challenge. The term “health disparities” describes the differences of health outcomes among different groups, said Chancellor Donald, MD, of Tulane University, New Orleans, who introduced the article at the meeting. “Racial health disparities usually result from an unequal distribution of power and resources, not genetics.
“The examination of health disparities is certainly a worthwhile endeavor,” he continued. “For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the life span of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality.”
Black race a risk factor
For their study, Dr. Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults aged 18-60 years who were diagnosed with AML between 1986 and 2015.
To characterize molecular features, they conducted targeted sequencing of 81 genes in 1,339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.
Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P < .001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n = 1,365; Black patients, n = 160; P = .19). However, the difference was significant between 1996 and 2005 (White patients, n = 2,994; Black patients, n = 480; P = .004). “And it became even more noticeable in the most recent decade,” said Dr. Bhatnagar. “Furthermore, younger Black AML patients were found to have worse survival compared with younger White AML patients.”
Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs. 46%; P = .02) and complete remission rates (71% vs. 71%; P = 1.00). “While relapse rates were slightly higher in Black compared to White patients, this difference did not reach statistical significance,” said Dr. Bhatnagar. “There was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients.”
However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years, vs. 1.4 years for White patients (P = .02). Overall survival was 1.2 years vs. 1.8 years (P = .02).
Relapse rates were slightly higher in Black patients than in White patients, at 71% vs. 59%, but this difference did not reach statistical significance (P = .14).
Differences in biomarkers
With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. “All of these genes are established commonly mutated genes in AML,” said Bhatnagar.
On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, FLT3-ITD and IDH2 mutations were the only mutations associated with a higher risk for death among Black patients.
“This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors,” said Dr. Bhatnagar. “In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.
“Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, “ she said.
Understudied disparities
Although the study showed that Black patients had worse outcomes, “surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials,” noted Elisa Weiss, PhD, senior vice president of education, services, and health research for the Leukemia and Lymphoma Society.
“The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities,” she said in an interview. “In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual’s ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources.”
She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to “advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to health care, services, and programs for blood cancer patients and survivors.”
The research was supported in part by the National Cancer Institute of the National Institutes of Health, other institutions, and through several scholar awards. Dr. Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr. Weiss has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
HCV Special Populations: Effective Treatments, Addressing Unmet Needs, and Navigating COVID-19 with Dr. Hugo Rosen
Has the introduction of direct-acting antiviral (DAA) medications had a significant benefit in special populations of patients with hepatitis C virus (HCV)?
Dr. Rosen: Absolutely. The gaps and challenges for particular special populations have been largely overcome with the development of new HCV agents.
For example, we now know that HIV-HCV coinfection—which was a particularly vexing situation because of the significant side effects of interferon-based therapies and the much lower efficacy—has no impact on HCV treatment outcome if we use DAAs. Remarkably, the management, indication of treatment, and follow up of HCV infection are now the same for both patient populations. It is particularly relevant because we know that HIV coinfection leads to a more accelerated development of advanced fibrosis, and we know that fibrosis is the single most important predictor of outcome.
Having said that, HIV-HCV coinfected patients require careful evaluation of any potential drug-drug interactions between the HCV drugs and HIV antiretroviral therapy, and it also requires attention to medication for substance abuse and other co-medications for other comorbidities. If we look at the issue of drug-drug interactions, the good news is that the main culprit in terms of interaction with antiretroviral therapy, was ritonavir. That was approved in combination with other antivirals in 2014, but it is not part of a commonly utilized regimen of DAAs. Simeprevir is also prone to drug interactions with cytochrome P450. This was contraindicated when used with several HIV antiretrovirals, but neither one of those drugs are really used to treat HCV now. Very few clinically significant interactions are expected with sofosbuvir or ledipasvir, so we do not expect to see drug-drug interactions as we did in the first generation of DAAs.
Let us now look at people who inject drugs or use drugs (PWIDs.) I think it clearly is the biggest challenge globally to provide treatment access to these patients. If you consider that 1 person who injects drugs can theoretically infect 20 other subjects, it is imperative to treat this population.
Historically, there has been stigmatization of these patients because of the use of drugs. PWIDs are increasingly being considered to be eligible for treatment, but it is important to underscore that eligibility does not necessarily translate to or equate to access. Adherence to and response to DAA therapy among this patient population represents some additional challenges. Many of these patients are receiving opioid substitution therapy and that has actually been shown to increase the likelihood of success with DAAs, but there is a concern in this patient population of ongoing drug use and HCV reinfection.
When we treat this patient population, we have to be cognizant of these issues and develop strategies that maximize their likelihood of staying on treatment. On average, about 12% of patients who are PWIDs drop out or are lost to follow up, which is problematic. A smaller percentage of those who continue injecting drugs develop reinfection, for example, with a different genotype. We know that DAA-mediated cure does not confer immunity to different strains or even the same strain of virus, and so we need to develop processes to maximize prevention of reinfection. That may include opioid substitution therapy, or needle exchange programs. There are also a lot of data emerging around the world about the benefit of the adjunctive role of behavioral therapy. Again, it all starts with access to DAA treatment in this patient population, and then retreatment if they get reinfected.
The next population is patients with end stage renal disease. It has been a remarkable transformation. These patients in the past would not tolerate interferon-based therapy and would develop severe anemia with ribavirin. Now with DAAs, those complications do not arise. We know that successful HCV therapy improves clinical outcomes in patients who have end stage renal disease. This has been associated with a very significant survival benefit in patients on dialysis. Among diabetic patients who have end stage renal disease, if one achieves sustained virologic response, it reduces the risk of developing extrahepatic manifestations of the disease and that happens regardless of cirrhosis.
Drugs that have been very effective in patients who have chronic renal failure include elbasvir and grazoprevir, as well as glecaprevir and pibrentasvir. We know that the concentration of sofosbuvir is a concern; there are higher concentrations of the primary sofosbuvir metabolite in persons who develop renal impairment, but many studies have demonstrated the safety and efficacy of sofosbuvir-based regimens even in those patients who have an estimated GFR less than 30 mL per minute.
Are there any other unmet needs that still exist in treating any of these special patient populations?
Dr. Rosen: Addressing medical, psychological, social, and addiction-related barriers are all important for PWIDs. As we touched on earlier, there needs to be a deliberate and nuanced approach for these subjects, a multidisciplinary model of care in order to help decrease the high dropout rate. The data that are coming out certainly justifies providing access to these patients, with real-world efficacy at more than 90%. We know that these patients can be treated and that they can achieve a high cure rate.
Appropriately treating patients who have renal failure does remain a challenge. The question is, when do you treat someone who has end stage renal disease and HCV? The answer pivots on the accessibility to organs. We can use HCV positive organs in patients who have either been cured of HCV and now are negative for virus, or in people who have never been exposed to HCV.
You might wonder, what is the rationale for that? The average wait list time for an HCV negative kidney is about 6.6 years. If you are willing to take an HCV positive kidney, it is closer to 4 years. I recently saw a patient who got a kidney transplant, developed kidney allograft failure, and is now being considered for retransplantation. In this situation, if I cure his HCV—which we know we can do with the current therapies very safely—it is potentially going to extend his time waiting for his next kidney.
In this situation, my plan would be to do a fibroscan, which tells me how much scar tissue he has in his liver. If he has fibrosis 0 or 1, I will probably not treat him and put him into the pool that he receives an HCV positive kidney. If, on the other hand, he has fibrosis 3 or 4, I probably will cure his hepatitis C because he is immunosuppressed and he has a significant chance of further developing advanced liver disease and even decompensation.
I think we should treat everybody who has HCV because we know it improves quality of life, it improves liver-related mortality, and it improves all-cause mortality. In the case of patients who have end organ damage and are waiting for transplant, it may prolong their wait time unless the patient is willing to accept that HCV positive organ. Considering the remarkable success in treating HCV post-organ transplant, the use of HCV-positive organs into HCV-negative continues to expand.
What new challenges, if any, has COVID-19 presented in treating these high risk or special populations?
Dr. Rosen: The good news is we have multiple, highly effective pangenotypic DAA regimens.
We know that all patients with HCV should be treated, especially those who have advanced fibrosis. Recent data show that patients who have advanced fibrosis, whether measured by a noninvasive blood test, like FIB-4 or a noninvasive fibroscan have a higher risk of death if they develop COVID-19.
COVID-19 is associated with liver function abnormalities in 20% or more of all patients who contract it, and those patients who develop elevated liver function tests have a higher mortality. It is particularly high in patients who have cirrhosis.
We do not think that patients who have HCV are more prone to develop COVID-19—there are no data to support that. However, if there is evidence that in patients with advanced fibrosis or evidence of hepatic involvement as manifested by elevated liver function tests, those patients have at least a twofold higher chance of mortality.
The other challenge, of course, is what COVID-19 has done to our ability to deliver care. It has made it inconvenient to treat patients. Patients who have advanced fibrosis or cirrhosis who get cured with DAAs also still need surveillance for development of hepatocellular carcinoma. Their risk of developing hepatocellular carcinoma is lower than patients who have not been cured, but there is still a residual risk which often requires imaging COVID-19-related changes have negatively impacted our ability to do that.
Has the introduction of direct-acting antiviral (DAA) medications had a significant benefit in special populations of patients with hepatitis C virus (HCV)?
Dr. Rosen: Absolutely. The gaps and challenges for particular special populations have been largely overcome with the development of new HCV agents.
For example, we now know that HIV-HCV coinfection—which was a particularly vexing situation because of the significant side effects of interferon-based therapies and the much lower efficacy—has no impact on HCV treatment outcome if we use DAAs. Remarkably, the management, indication of treatment, and follow up of HCV infection are now the same for both patient populations. It is particularly relevant because we know that HIV coinfection leads to a more accelerated development of advanced fibrosis, and we know that fibrosis is the single most important predictor of outcome.
Having said that, HIV-HCV coinfected patients require careful evaluation of any potential drug-drug interactions between the HCV drugs and HIV antiretroviral therapy, and it also requires attention to medication for substance abuse and other co-medications for other comorbidities. If we look at the issue of drug-drug interactions, the good news is that the main culprit in terms of interaction with antiretroviral therapy, was ritonavir. That was approved in combination with other antivirals in 2014, but it is not part of a commonly utilized regimen of DAAs. Simeprevir is also prone to drug interactions with cytochrome P450. This was contraindicated when used with several HIV antiretrovirals, but neither one of those drugs are really used to treat HCV now. Very few clinically significant interactions are expected with sofosbuvir or ledipasvir, so we do not expect to see drug-drug interactions as we did in the first generation of DAAs.
Let us now look at people who inject drugs or use drugs (PWIDs.) I think it clearly is the biggest challenge globally to provide treatment access to these patients. If you consider that 1 person who injects drugs can theoretically infect 20 other subjects, it is imperative to treat this population.
Historically, there has been stigmatization of these patients because of the use of drugs. PWIDs are increasingly being considered to be eligible for treatment, but it is important to underscore that eligibility does not necessarily translate to or equate to access. Adherence to and response to DAA therapy among this patient population represents some additional challenges. Many of these patients are receiving opioid substitution therapy and that has actually been shown to increase the likelihood of success with DAAs, but there is a concern in this patient population of ongoing drug use and HCV reinfection.
When we treat this patient population, we have to be cognizant of these issues and develop strategies that maximize their likelihood of staying on treatment. On average, about 12% of patients who are PWIDs drop out or are lost to follow up, which is problematic. A smaller percentage of those who continue injecting drugs develop reinfection, for example, with a different genotype. We know that DAA-mediated cure does not confer immunity to different strains or even the same strain of virus, and so we need to develop processes to maximize prevention of reinfection. That may include opioid substitution therapy, or needle exchange programs. There are also a lot of data emerging around the world about the benefit of the adjunctive role of behavioral therapy. Again, it all starts with access to DAA treatment in this patient population, and then retreatment if they get reinfected.
The next population is patients with end stage renal disease. It has been a remarkable transformation. These patients in the past would not tolerate interferon-based therapy and would develop severe anemia with ribavirin. Now with DAAs, those complications do not arise. We know that successful HCV therapy improves clinical outcomes in patients who have end stage renal disease. This has been associated with a very significant survival benefit in patients on dialysis. Among diabetic patients who have end stage renal disease, if one achieves sustained virologic response, it reduces the risk of developing extrahepatic manifestations of the disease and that happens regardless of cirrhosis.
Drugs that have been very effective in patients who have chronic renal failure include elbasvir and grazoprevir, as well as glecaprevir and pibrentasvir. We know that the concentration of sofosbuvir is a concern; there are higher concentrations of the primary sofosbuvir metabolite in persons who develop renal impairment, but many studies have demonstrated the safety and efficacy of sofosbuvir-based regimens even in those patients who have an estimated GFR less than 30 mL per minute.
Are there any other unmet needs that still exist in treating any of these special patient populations?
Dr. Rosen: Addressing medical, psychological, social, and addiction-related barriers are all important for PWIDs. As we touched on earlier, there needs to be a deliberate and nuanced approach for these subjects, a multidisciplinary model of care in order to help decrease the high dropout rate. The data that are coming out certainly justifies providing access to these patients, with real-world efficacy at more than 90%. We know that these patients can be treated and that they can achieve a high cure rate.
Appropriately treating patients who have renal failure does remain a challenge. The question is, when do you treat someone who has end stage renal disease and HCV? The answer pivots on the accessibility to organs. We can use HCV positive organs in patients who have either been cured of HCV and now are negative for virus, or in people who have never been exposed to HCV.
You might wonder, what is the rationale for that? The average wait list time for an HCV negative kidney is about 6.6 years. If you are willing to take an HCV positive kidney, it is closer to 4 years. I recently saw a patient who got a kidney transplant, developed kidney allograft failure, and is now being considered for retransplantation. In this situation, if I cure his HCV—which we know we can do with the current therapies very safely—it is potentially going to extend his time waiting for his next kidney.
In this situation, my plan would be to do a fibroscan, which tells me how much scar tissue he has in his liver. If he has fibrosis 0 or 1, I will probably not treat him and put him into the pool that he receives an HCV positive kidney. If, on the other hand, he has fibrosis 3 or 4, I probably will cure his hepatitis C because he is immunosuppressed and he has a significant chance of further developing advanced liver disease and even decompensation.
I think we should treat everybody who has HCV because we know it improves quality of life, it improves liver-related mortality, and it improves all-cause mortality. In the case of patients who have end organ damage and are waiting for transplant, it may prolong their wait time unless the patient is willing to accept that HCV positive organ. Considering the remarkable success in treating HCV post-organ transplant, the use of HCV-positive organs into HCV-negative continues to expand.
What new challenges, if any, has COVID-19 presented in treating these high risk or special populations?
Dr. Rosen: The good news is we have multiple, highly effective pangenotypic DAA regimens.
We know that all patients with HCV should be treated, especially those who have advanced fibrosis. Recent data show that patients who have advanced fibrosis, whether measured by a noninvasive blood test, like FIB-4 or a noninvasive fibroscan have a higher risk of death if they develop COVID-19.
COVID-19 is associated with liver function abnormalities in 20% or more of all patients who contract it, and those patients who develop elevated liver function tests have a higher mortality. It is particularly high in patients who have cirrhosis.
We do not think that patients who have HCV are more prone to develop COVID-19—there are no data to support that. However, if there is evidence that in patients with advanced fibrosis or evidence of hepatic involvement as manifested by elevated liver function tests, those patients have at least a twofold higher chance of mortality.
The other challenge, of course, is what COVID-19 has done to our ability to deliver care. It has made it inconvenient to treat patients. Patients who have advanced fibrosis or cirrhosis who get cured with DAAs also still need surveillance for development of hepatocellular carcinoma. Their risk of developing hepatocellular carcinoma is lower than patients who have not been cured, but there is still a residual risk which often requires imaging COVID-19-related changes have negatively impacted our ability to do that.
Has the introduction of direct-acting antiviral (DAA) medications had a significant benefit in special populations of patients with hepatitis C virus (HCV)?
Dr. Rosen: Absolutely. The gaps and challenges for particular special populations have been largely overcome with the development of new HCV agents.
For example, we now know that HIV-HCV coinfection—which was a particularly vexing situation because of the significant side effects of interferon-based therapies and the much lower efficacy—has no impact on HCV treatment outcome if we use DAAs. Remarkably, the management, indication of treatment, and follow up of HCV infection are now the same for both patient populations. It is particularly relevant because we know that HIV coinfection leads to a more accelerated development of advanced fibrosis, and we know that fibrosis is the single most important predictor of outcome.
Having said that, HIV-HCV coinfected patients require careful evaluation of any potential drug-drug interactions between the HCV drugs and HIV antiretroviral therapy, and it also requires attention to medication for substance abuse and other co-medications for other comorbidities. If we look at the issue of drug-drug interactions, the good news is that the main culprit in terms of interaction with antiretroviral therapy, was ritonavir. That was approved in combination with other antivirals in 2014, but it is not part of a commonly utilized regimen of DAAs. Simeprevir is also prone to drug interactions with cytochrome P450. This was contraindicated when used with several HIV antiretrovirals, but neither one of those drugs are really used to treat HCV now. Very few clinically significant interactions are expected with sofosbuvir or ledipasvir, so we do not expect to see drug-drug interactions as we did in the first generation of DAAs.
Let us now look at people who inject drugs or use drugs (PWIDs.) I think it clearly is the biggest challenge globally to provide treatment access to these patients. If you consider that 1 person who injects drugs can theoretically infect 20 other subjects, it is imperative to treat this population.
Historically, there has been stigmatization of these patients because of the use of drugs. PWIDs are increasingly being considered to be eligible for treatment, but it is important to underscore that eligibility does not necessarily translate to or equate to access. Adherence to and response to DAA therapy among this patient population represents some additional challenges. Many of these patients are receiving opioid substitution therapy and that has actually been shown to increase the likelihood of success with DAAs, but there is a concern in this patient population of ongoing drug use and HCV reinfection.
When we treat this patient population, we have to be cognizant of these issues and develop strategies that maximize their likelihood of staying on treatment. On average, about 12% of patients who are PWIDs drop out or are lost to follow up, which is problematic. A smaller percentage of those who continue injecting drugs develop reinfection, for example, with a different genotype. We know that DAA-mediated cure does not confer immunity to different strains or even the same strain of virus, and so we need to develop processes to maximize prevention of reinfection. That may include opioid substitution therapy, or needle exchange programs. There are also a lot of data emerging around the world about the benefit of the adjunctive role of behavioral therapy. Again, it all starts with access to DAA treatment in this patient population, and then retreatment if they get reinfected.
The next population is patients with end stage renal disease. It has been a remarkable transformation. These patients in the past would not tolerate interferon-based therapy and would develop severe anemia with ribavirin. Now with DAAs, those complications do not arise. We know that successful HCV therapy improves clinical outcomes in patients who have end stage renal disease. This has been associated with a very significant survival benefit in patients on dialysis. Among diabetic patients who have end stage renal disease, if one achieves sustained virologic response, it reduces the risk of developing extrahepatic manifestations of the disease and that happens regardless of cirrhosis.
Drugs that have been very effective in patients who have chronic renal failure include elbasvir and grazoprevir, as well as glecaprevir and pibrentasvir. We know that the concentration of sofosbuvir is a concern; there are higher concentrations of the primary sofosbuvir metabolite in persons who develop renal impairment, but many studies have demonstrated the safety and efficacy of sofosbuvir-based regimens even in those patients who have an estimated GFR less than 30 mL per minute.
Are there any other unmet needs that still exist in treating any of these special patient populations?
Dr. Rosen: Addressing medical, psychological, social, and addiction-related barriers are all important for PWIDs. As we touched on earlier, there needs to be a deliberate and nuanced approach for these subjects, a multidisciplinary model of care in order to help decrease the high dropout rate. The data that are coming out certainly justifies providing access to these patients, with real-world efficacy at more than 90%. We know that these patients can be treated and that they can achieve a high cure rate.
Appropriately treating patients who have renal failure does remain a challenge. The question is, when do you treat someone who has end stage renal disease and HCV? The answer pivots on the accessibility to organs. We can use HCV positive organs in patients who have either been cured of HCV and now are negative for virus, or in people who have never been exposed to HCV.
You might wonder, what is the rationale for that? The average wait list time for an HCV negative kidney is about 6.6 years. If you are willing to take an HCV positive kidney, it is closer to 4 years. I recently saw a patient who got a kidney transplant, developed kidney allograft failure, and is now being considered for retransplantation. In this situation, if I cure his HCV—which we know we can do with the current therapies very safely—it is potentially going to extend his time waiting for his next kidney.
In this situation, my plan would be to do a fibroscan, which tells me how much scar tissue he has in his liver. If he has fibrosis 0 or 1, I will probably not treat him and put him into the pool that he receives an HCV positive kidney. If, on the other hand, he has fibrosis 3 or 4, I probably will cure his hepatitis C because he is immunosuppressed and he has a significant chance of further developing advanced liver disease and even decompensation.
I think we should treat everybody who has HCV because we know it improves quality of life, it improves liver-related mortality, and it improves all-cause mortality. In the case of patients who have end organ damage and are waiting for transplant, it may prolong their wait time unless the patient is willing to accept that HCV positive organ. Considering the remarkable success in treating HCV post-organ transplant, the use of HCV-positive organs into HCV-negative continues to expand.
What new challenges, if any, has COVID-19 presented in treating these high risk or special populations?
Dr. Rosen: The good news is we have multiple, highly effective pangenotypic DAA regimens.
We know that all patients with HCV should be treated, especially those who have advanced fibrosis. Recent data show that patients who have advanced fibrosis, whether measured by a noninvasive blood test, like FIB-4 or a noninvasive fibroscan have a higher risk of death if they develop COVID-19.
COVID-19 is associated with liver function abnormalities in 20% or more of all patients who contract it, and those patients who develop elevated liver function tests have a higher mortality. It is particularly high in patients who have cirrhosis.
We do not think that patients who have HCV are more prone to develop COVID-19—there are no data to support that. However, if there is evidence that in patients with advanced fibrosis or evidence of hepatic involvement as manifested by elevated liver function tests, those patients have at least a twofold higher chance of mortality.
The other challenge, of course, is what COVID-19 has done to our ability to deliver care. It has made it inconvenient to treat patients. Patients who have advanced fibrosis or cirrhosis who get cured with DAAs also still need surveillance for development of hepatocellular carcinoma. Their risk of developing hepatocellular carcinoma is lower than patients who have not been cured, but there is still a residual risk which often requires imaging COVID-19-related changes have negatively impacted our ability to do that.
