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Best meds for insomnia identified?
In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.
However, eszopiclone may cause substantial side effects – and safety data on lemborexant were inconclusive, the researchers note.
Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.
For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, United Kingdom, noted during a press briefing.
“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Dr. Cipriani said.
The findings were published online in The Lancet.
Prevalent, debilitating
Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity.
Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.
However, “insomnia drugs are not all created equal. Even within the same drug class there are differences,” Dr. Cipriani said.
In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).
Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference range, 0.36-0.83; high-to-moderate certainty of evidence).
In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27-0.71; moderate-to-very low certainty of evidence).
“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.
Best available evidence
What little long-term data is available suggest eszopiclone and lemborexant are more effective than placebo. Plus, eszopiclone is more effective than ramelteon and zolpidem but with “very low” certainty of evidence, the researchers report.
“There was insufficient evidence to support the prescription of benzodiazepines and zolpidem in long-term treatment,” they write.
Another problem was lack of data on other important outcomes, they add.
“We wanted to look at hangover effects, daytime sleepiness, [and] rebound effect, but often there was no data reported in trials. We need to collect data about these outcomes because they matter to clinicians and patients,” Dr. Cipriani said.
Summing up, the researchers note the current findings represent the “best available evidence base to guide the choice about pharmacological treatment for insomnia disorder in adults and will assist in shared decisionmaking between patients, carers, and their clinicians, as well as policy makers.”
They caution, however, that all statements comparing the merits of one drug with another “should be tempered by the potential limitations of the current analysis, the quality of the available evidence, the characteristics of the patient populations, and the uncertainties that might result from choice of dose or treatment setting.”
In addition, it is important to also consider nonpharmacologic treatments for insomnia disorder, as they are supported by “high-quality evidence and recommended as first-line treatment by guidelines,” the investigator write.
Shared decisionmaking
In an accompanying editorial, Myrto Samara, MD, University of Thessaly, Larissa, Greece, agrees with the researchers that discussion with patients is key.
“For insomnia treatment, patient-physician shared decisionmaking is crucial to decide when a pharmacological intervention is deemed necessary and which drug [is] to be given by considering the trade-offs for efficacy and side effects,” Dr. Samara writes.
The study was funded by the UK National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center. Dr. Cipriani has received research and consultancy fees from the Italian Network for Pediatric Trials, CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials of seltorexant in depression that are sponsored by Janssen. Dr. Samara has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.
However, eszopiclone may cause substantial side effects – and safety data on lemborexant were inconclusive, the researchers note.
Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.
For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, United Kingdom, noted during a press briefing.
“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Dr. Cipriani said.
The findings were published online in The Lancet.
Prevalent, debilitating
Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity.
Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.
However, “insomnia drugs are not all created equal. Even within the same drug class there are differences,” Dr. Cipriani said.
In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).
Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference range, 0.36-0.83; high-to-moderate certainty of evidence).
In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27-0.71; moderate-to-very low certainty of evidence).
“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.
Best available evidence
What little long-term data is available suggest eszopiclone and lemborexant are more effective than placebo. Plus, eszopiclone is more effective than ramelteon and zolpidem but with “very low” certainty of evidence, the researchers report.
“There was insufficient evidence to support the prescription of benzodiazepines and zolpidem in long-term treatment,” they write.
Another problem was lack of data on other important outcomes, they add.
“We wanted to look at hangover effects, daytime sleepiness, [and] rebound effect, but often there was no data reported in trials. We need to collect data about these outcomes because they matter to clinicians and patients,” Dr. Cipriani said.
Summing up, the researchers note the current findings represent the “best available evidence base to guide the choice about pharmacological treatment for insomnia disorder in adults and will assist in shared decisionmaking between patients, carers, and their clinicians, as well as policy makers.”
They caution, however, that all statements comparing the merits of one drug with another “should be tempered by the potential limitations of the current analysis, the quality of the available evidence, the characteristics of the patient populations, and the uncertainties that might result from choice of dose or treatment setting.”
In addition, it is important to also consider nonpharmacologic treatments for insomnia disorder, as they are supported by “high-quality evidence and recommended as first-line treatment by guidelines,” the investigator write.
Shared decisionmaking
In an accompanying editorial, Myrto Samara, MD, University of Thessaly, Larissa, Greece, agrees with the researchers that discussion with patients is key.
“For insomnia treatment, patient-physician shared decisionmaking is crucial to decide when a pharmacological intervention is deemed necessary and which drug [is] to be given by considering the trade-offs for efficacy and side effects,” Dr. Samara writes.
The study was funded by the UK National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center. Dr. Cipriani has received research and consultancy fees from the Italian Network for Pediatric Trials, CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials of seltorexant in depression that are sponsored by Janssen. Dr. Samara has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a comprehensive comparative-effectiveness analysis, lemborexant and eszopiclone showed the best efficacy, acceptability, and tolerability for acute and long-term insomnia treatment.
However, eszopiclone may cause substantial side effects – and safety data on lemborexant were inconclusive, the researchers note.
Not surprisingly, short-acting, intermediate-acting, and long-acting benzodiazepines were effective in the acute treatment of insomnia, but they have unfavorable tolerability and safety profiles, and there are no long-term data on these issues.
For many insomnia medications, there is a “striking” and “appalling” lack of long-term data, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry, University of Oxford, United Kingdom, noted during a press briefing.
“This is a call for regulators to raise the bar and ask for long-term data when companies submit an application for licensing insomnia drugs,” Dr. Cipriani said.
The findings were published online in The Lancet.
Prevalent, debilitating
Insomnia is highly prevalent, affecting up to 1 in 5 adults, and can have a profound impact on health, well-being, and productivity.
Sleep hygiene and cognitive-behavioral therapy for insomnia (CBT-I) are recommended first-line treatments, but they are often unavailable, which often leads patients and clinicians to turn to medications.
However, “insomnia drugs are not all created equal. Even within the same drug class there are differences,” Dr. Cipriani said.
In a large-scale systematic review and network meta-analysis, the researchers analyzed data from 154 double-blind, randomized controlled trials of medications (licensed or not) used for acute and long-term treatment of insomnia in 44,089 adults (mean age, 51.7 years; 63% women).
Results showed, for the acute treatment of insomnia, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more effective than placebo (standardized mean difference range, 0.36-0.83; high-to-moderate certainty of evidence).
In addition, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more effective than melatonin, ramelteon, and zaleplon (SMD, 0.27-0.71; moderate-to-very low certainty of evidence).
“Our results show that the melatonergic drugs melatonin and ramelteon are not really effective. The data do not support the regular use of these drugs,” co-investigator Phil Cowen, PhD, professor of psychopharmacology, University of Oxford, said at the briefing.
Best available evidence
What little long-term data is available suggest eszopiclone and lemborexant are more effective than placebo. Plus, eszopiclone is more effective than ramelteon and zolpidem but with “very low” certainty of evidence, the researchers report.
“There was insufficient evidence to support the prescription of benzodiazepines and zolpidem in long-term treatment,” they write.
Another problem was lack of data on other important outcomes, they add.
“We wanted to look at hangover effects, daytime sleepiness, [and] rebound effect, but often there was no data reported in trials. We need to collect data about these outcomes because they matter to clinicians and patients,” Dr. Cipriani said.
Summing up, the researchers note the current findings represent the “best available evidence base to guide the choice about pharmacological treatment for insomnia disorder in adults and will assist in shared decisionmaking between patients, carers, and their clinicians, as well as policy makers.”
They caution, however, that all statements comparing the merits of one drug with another “should be tempered by the potential limitations of the current analysis, the quality of the available evidence, the characteristics of the patient populations, and the uncertainties that might result from choice of dose or treatment setting.”
In addition, it is important to also consider nonpharmacologic treatments for insomnia disorder, as they are supported by “high-quality evidence and recommended as first-line treatment by guidelines,” the investigator write.
Shared decisionmaking
In an accompanying editorial, Myrto Samara, MD, University of Thessaly, Larissa, Greece, agrees with the researchers that discussion with patients is key.
“For insomnia treatment, patient-physician shared decisionmaking is crucial to decide when a pharmacological intervention is deemed necessary and which drug [is] to be given by considering the trade-offs for efficacy and side effects,” Dr. Samara writes.
The study was funded by the UK National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center. Dr. Cipriani has received research and consultancy fees from the Italian Network for Pediatric Trials, CARIPLO Foundation, and Angelini Pharma, and is the chief and principal investigator of two trials of seltorexant in depression that are sponsored by Janssen. Dr. Samara has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET
Many people becoming reinfected as BA.5 dominates new COVID-19 cases
When the COVID-19 pandemic first began, the general thought was that once people were infected, they were then protected from the virus.
It’s hard to say how many. The ABC News analysis found at least 1.6 million reinfections in 24 states, but the actual number is probably a lot higher.
“These are not the real numbers because many people are not reporting cases,” Ali Mokdad, MD, an epidemiologist with the University of Washington, Seattle, told ABC.
The latest variant, BA.5, has become the dominant strain in the United States, making up more than 65% of all COVID-19 cases as of July 13, according to data from the CDC.
Prior infections and vaccines aren’t providing as much protection against the newly dominant BA.5 strain as they did against earlier variants.
But evidence doesn’t show this subvariant of Omicron to be more harmful than earlier, less transmissible versions.
Several factors are contributing to rising reinfections, experts say. For example, fewer people are wearing masks than in the first year or so of the pandemic. Dr. Mokdad said just 18% of Americans reported always wearing a mask in public at the end of May, down from 44% the year before.
The emergence of the Omicron variant, of which BA.5 is a subvariant, is indicating that less protection is being offered by prior infections.
A version of this article first appeared on WebMD.com.
When the COVID-19 pandemic first began, the general thought was that once people were infected, they were then protected from the virus.
It’s hard to say how many. The ABC News analysis found at least 1.6 million reinfections in 24 states, but the actual number is probably a lot higher.
“These are not the real numbers because many people are not reporting cases,” Ali Mokdad, MD, an epidemiologist with the University of Washington, Seattle, told ABC.
The latest variant, BA.5, has become the dominant strain in the United States, making up more than 65% of all COVID-19 cases as of July 13, according to data from the CDC.
Prior infections and vaccines aren’t providing as much protection against the newly dominant BA.5 strain as they did against earlier variants.
But evidence doesn’t show this subvariant of Omicron to be more harmful than earlier, less transmissible versions.
Several factors are contributing to rising reinfections, experts say. For example, fewer people are wearing masks than in the first year or so of the pandemic. Dr. Mokdad said just 18% of Americans reported always wearing a mask in public at the end of May, down from 44% the year before.
The emergence of the Omicron variant, of which BA.5 is a subvariant, is indicating that less protection is being offered by prior infections.
A version of this article first appeared on WebMD.com.
When the COVID-19 pandemic first began, the general thought was that once people were infected, they were then protected from the virus.
It’s hard to say how many. The ABC News analysis found at least 1.6 million reinfections in 24 states, but the actual number is probably a lot higher.
“These are not the real numbers because many people are not reporting cases,” Ali Mokdad, MD, an epidemiologist with the University of Washington, Seattle, told ABC.
The latest variant, BA.5, has become the dominant strain in the United States, making up more than 65% of all COVID-19 cases as of July 13, according to data from the CDC.
Prior infections and vaccines aren’t providing as much protection against the newly dominant BA.5 strain as they did against earlier variants.
But evidence doesn’t show this subvariant of Omicron to be more harmful than earlier, less transmissible versions.
Several factors are contributing to rising reinfections, experts say. For example, fewer people are wearing masks than in the first year or so of the pandemic. Dr. Mokdad said just 18% of Americans reported always wearing a mask in public at the end of May, down from 44% the year before.
The emergence of the Omicron variant, of which BA.5 is a subvariant, is indicating that less protection is being offered by prior infections.
A version of this article first appeared on WebMD.com.
Neural networks can distinguish PsA from rheumatoid arthritis on MRI
Hand images are sufficient
NEW YORK – On the basis of MRI images of the hand, a neural network has been trained to distinguish seronegative and seropositive rheumatoid arthritis (RA) from psoriatic arthritis (PsA) as well as from each other, according to a study that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
In the work so far, the neural network was correct about 70% of the time in the absence of any further clinical analyses, according to David Simon, MD, a rheumatologist in the department of internal medicine at Friedrich-Alexander University, Erlangen, Germany.
Previous to this work, “there has been no study that has exclusively used hand MRI data and deep learning without requiring further expert input for the classification of arthritides,” Dr. Simon said.
In fact, when demographic and clinical data were added, there was no improvement in the performance of patient classification relative to the deep learning classification alone, according to the data presented by Dr. Simon.
The images were evaluated with residual neural networks (ResNet), which represents a sophisticated form of deep learning to facilitate the flow of information across the network layers as they form to improve accuracy in their ability to distinguish one form of disease from the other. The training was performed on images from the T1 coronal, T2 corona1, T1 coronal fat suppressed with contrast, T1 axial fat suppressed with contrast, and T2 fat suppressed axial sequences.
The study included hand MRI scans from 135 patients with seronegative RA, 190 with seropositive RA, 177 with PsA, and 147 with psoriasis. The performance was judged on the basis of area under the receiver operating characteristics curve (AUROC) with and without input of clinical characteristics. Patients who had psoriasis without clinical arthritis were included as a control population.
The AUROC for accuracy was 75% for seropositive RA relative to PsA, 74% for seronegative RA relative to PsA, and 67% for seropositive relative to seronegative RA. Of the patients who had psoriasis without arthritis, 98% were classified as PsA and 2% as RA.
Subsequent to the classification of the patients with psoriasis, 14 of the 147 (9.5%) have developed PsA so far over a relatively short follow-up. All of these were among those identified as PsA by neural network evaluation of the hand MRIs.
This suggests that “a PsA-like pattern may be present early in the course of psoriatic disease,” Dr. Simon said.
In the groups with joint disease, who had mean ages ranging from 56 to 65, the mean disease durations were 2.6 years for those with seropositive RA, 1.3 years for those with seronegative RA, and 0.8 years for those with PsA. The patients with psoriasis were younger (mean age, 40.5 years) but had a longer disease duration (mean 4.2 years).
All of the MRI sequences were relevant for classification, but contrast did not appear to help with accuracy.
“If the images with contrast enhancement were deleted, the loss of performance was only marginal,” Dr. Simon reported.
The accuracy of neural networks increases with data, making it likely that further refinements in methodology will lead to a greater degree of accuracy, according to Dr. Simon. While the methodology is not yet ready for routine use in the clinic, the study demonstrates that neural network analysis of hand MRI to distinguish forms of arthritis “is possible.” Further studies are planned toward the goal of creating a viable clinical tool.
“Of course, if we could create an accurate tool with ultrasound, this would be even more practical,” said Dr. Simon, recognizing the value of an office tool, but he cautioned that this would be far more challenging.
“The precision of MRI is an important factor for effective neural network training,” he said.
Utility: ‘In challenging cases if the accuracy improves’?
A viable method for objectively and rapidly distinguishing inflammatory joint diseases, particularly in patients with an ambiguous clinical presentation, is an unmet need, according to Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center, Seattle.
Although the data presented are promising, Dr. Mease said in an interview that he believes there is a fair amount of work to be done before imaging analysis based on deep learning makes its way into routine clinical care. He is also hoping for methods to distinguish RA from PsA that are easier and less expensive, such as serum biomarkers. However, he agreed that a MRI-based tool could be useful when differentiating disease that is challenging.
“MRI is an expensive way for routine classification of disease, but this approach could be useful in challenging cases if the accuracy improves,” he said.
Meanwhile, other clinical researchers might want to test the principle. “You can try it,” said Dr. Simon, who reported that his team has made the methodology publicly available.
Dr. Simon reported no conflicts of interest. Dr. Mease reported financial relationships with more than 10 pharmaceutical companies, most of which make products used for the treatment of inflammatory joint diseases.
Hand images are sufficient
Hand images are sufficient
NEW YORK – On the basis of MRI images of the hand, a neural network has been trained to distinguish seronegative and seropositive rheumatoid arthritis (RA) from psoriatic arthritis (PsA) as well as from each other, according to a study that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
In the work so far, the neural network was correct about 70% of the time in the absence of any further clinical analyses, according to David Simon, MD, a rheumatologist in the department of internal medicine at Friedrich-Alexander University, Erlangen, Germany.
Previous to this work, “there has been no study that has exclusively used hand MRI data and deep learning without requiring further expert input for the classification of arthritides,” Dr. Simon said.
In fact, when demographic and clinical data were added, there was no improvement in the performance of patient classification relative to the deep learning classification alone, according to the data presented by Dr. Simon.
The images were evaluated with residual neural networks (ResNet), which represents a sophisticated form of deep learning to facilitate the flow of information across the network layers as they form to improve accuracy in their ability to distinguish one form of disease from the other. The training was performed on images from the T1 coronal, T2 corona1, T1 coronal fat suppressed with contrast, T1 axial fat suppressed with contrast, and T2 fat suppressed axial sequences.
The study included hand MRI scans from 135 patients with seronegative RA, 190 with seropositive RA, 177 with PsA, and 147 with psoriasis. The performance was judged on the basis of area under the receiver operating characteristics curve (AUROC) with and without input of clinical characteristics. Patients who had psoriasis without clinical arthritis were included as a control population.
The AUROC for accuracy was 75% for seropositive RA relative to PsA, 74% for seronegative RA relative to PsA, and 67% for seropositive relative to seronegative RA. Of the patients who had psoriasis without arthritis, 98% were classified as PsA and 2% as RA.
Subsequent to the classification of the patients with psoriasis, 14 of the 147 (9.5%) have developed PsA so far over a relatively short follow-up. All of these were among those identified as PsA by neural network evaluation of the hand MRIs.
This suggests that “a PsA-like pattern may be present early in the course of psoriatic disease,” Dr. Simon said.
In the groups with joint disease, who had mean ages ranging from 56 to 65, the mean disease durations were 2.6 years for those with seropositive RA, 1.3 years for those with seronegative RA, and 0.8 years for those with PsA. The patients with psoriasis were younger (mean age, 40.5 years) but had a longer disease duration (mean 4.2 years).
All of the MRI sequences were relevant for classification, but contrast did not appear to help with accuracy.
“If the images with contrast enhancement were deleted, the loss of performance was only marginal,” Dr. Simon reported.
The accuracy of neural networks increases with data, making it likely that further refinements in methodology will lead to a greater degree of accuracy, according to Dr. Simon. While the methodology is not yet ready for routine use in the clinic, the study demonstrates that neural network analysis of hand MRI to distinguish forms of arthritis “is possible.” Further studies are planned toward the goal of creating a viable clinical tool.
“Of course, if we could create an accurate tool with ultrasound, this would be even more practical,” said Dr. Simon, recognizing the value of an office tool, but he cautioned that this would be far more challenging.
“The precision of MRI is an important factor for effective neural network training,” he said.
Utility: ‘In challenging cases if the accuracy improves’?
A viable method for objectively and rapidly distinguishing inflammatory joint diseases, particularly in patients with an ambiguous clinical presentation, is an unmet need, according to Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center, Seattle.
Although the data presented are promising, Dr. Mease said in an interview that he believes there is a fair amount of work to be done before imaging analysis based on deep learning makes its way into routine clinical care. He is also hoping for methods to distinguish RA from PsA that are easier and less expensive, such as serum biomarkers. However, he agreed that a MRI-based tool could be useful when differentiating disease that is challenging.
“MRI is an expensive way for routine classification of disease, but this approach could be useful in challenging cases if the accuracy improves,” he said.
Meanwhile, other clinical researchers might want to test the principle. “You can try it,” said Dr. Simon, who reported that his team has made the methodology publicly available.
Dr. Simon reported no conflicts of interest. Dr. Mease reported financial relationships with more than 10 pharmaceutical companies, most of which make products used for the treatment of inflammatory joint diseases.
NEW YORK – On the basis of MRI images of the hand, a neural network has been trained to distinguish seronegative and seropositive rheumatoid arthritis (RA) from psoriatic arthritis (PsA) as well as from each other, according to a study that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
In the work so far, the neural network was correct about 70% of the time in the absence of any further clinical analyses, according to David Simon, MD, a rheumatologist in the department of internal medicine at Friedrich-Alexander University, Erlangen, Germany.
Previous to this work, “there has been no study that has exclusively used hand MRI data and deep learning without requiring further expert input for the classification of arthritides,” Dr. Simon said.
In fact, when demographic and clinical data were added, there was no improvement in the performance of patient classification relative to the deep learning classification alone, according to the data presented by Dr. Simon.
The images were evaluated with residual neural networks (ResNet), which represents a sophisticated form of deep learning to facilitate the flow of information across the network layers as they form to improve accuracy in their ability to distinguish one form of disease from the other. The training was performed on images from the T1 coronal, T2 corona1, T1 coronal fat suppressed with contrast, T1 axial fat suppressed with contrast, and T2 fat suppressed axial sequences.
The study included hand MRI scans from 135 patients with seronegative RA, 190 with seropositive RA, 177 with PsA, and 147 with psoriasis. The performance was judged on the basis of area under the receiver operating characteristics curve (AUROC) with and without input of clinical characteristics. Patients who had psoriasis without clinical arthritis were included as a control population.
The AUROC for accuracy was 75% for seropositive RA relative to PsA, 74% for seronegative RA relative to PsA, and 67% for seropositive relative to seronegative RA. Of the patients who had psoriasis without arthritis, 98% were classified as PsA and 2% as RA.
Subsequent to the classification of the patients with psoriasis, 14 of the 147 (9.5%) have developed PsA so far over a relatively short follow-up. All of these were among those identified as PsA by neural network evaluation of the hand MRIs.
This suggests that “a PsA-like pattern may be present early in the course of psoriatic disease,” Dr. Simon said.
In the groups with joint disease, who had mean ages ranging from 56 to 65, the mean disease durations were 2.6 years for those with seropositive RA, 1.3 years for those with seronegative RA, and 0.8 years for those with PsA. The patients with psoriasis were younger (mean age, 40.5 years) but had a longer disease duration (mean 4.2 years).
All of the MRI sequences were relevant for classification, but contrast did not appear to help with accuracy.
“If the images with contrast enhancement were deleted, the loss of performance was only marginal,” Dr. Simon reported.
The accuracy of neural networks increases with data, making it likely that further refinements in methodology will lead to a greater degree of accuracy, according to Dr. Simon. While the methodology is not yet ready for routine use in the clinic, the study demonstrates that neural network analysis of hand MRI to distinguish forms of arthritis “is possible.” Further studies are planned toward the goal of creating a viable clinical tool.
“Of course, if we could create an accurate tool with ultrasound, this would be even more practical,” said Dr. Simon, recognizing the value of an office tool, but he cautioned that this would be far more challenging.
“The precision of MRI is an important factor for effective neural network training,” he said.
Utility: ‘In challenging cases if the accuracy improves’?
A viable method for objectively and rapidly distinguishing inflammatory joint diseases, particularly in patients with an ambiguous clinical presentation, is an unmet need, according to Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center, Seattle.
Although the data presented are promising, Dr. Mease said in an interview that he believes there is a fair amount of work to be done before imaging analysis based on deep learning makes its way into routine clinical care. He is also hoping for methods to distinguish RA from PsA that are easier and less expensive, such as serum biomarkers. However, he agreed that a MRI-based tool could be useful when differentiating disease that is challenging.
“MRI is an expensive way for routine classification of disease, but this approach could be useful in challenging cases if the accuracy improves,” he said.
Meanwhile, other clinical researchers might want to test the principle. “You can try it,” said Dr. Simon, who reported that his team has made the methodology publicly available.
Dr. Simon reported no conflicts of interest. Dr. Mease reported financial relationships with more than 10 pharmaceutical companies, most of which make products used for the treatment of inflammatory joint diseases.
AT GRAPPA 2022
A healthy White male presented with a rash consisting of erythematous to purpuric macules
Vasculitis is a process in which blood vessels become inflamed and necrotic. Classic small vessel vasculitis reveals a leukocytoclastic vasculitis and most commonly presents as palpable purpura. .” A form of EIV has been described in the literature as “Disney dermatitis.” It is often seen in healthy adults after a long day of walking at the parks. Other forms of exercise, such as jogging, hiking, or swimming, may also cause the condition.
Clinically, EIV affects the lower legs and presents as purpuric macules. Edema may be present. Lesions may be asymptomatic or may present with pruritus or burning. Diagnosis is often made clinically. Skin biopsies for H&E and DIF (direct immunofluorescence) can help distinguish the type of vasculitis that is present. Laboratory tests may be needed to exclude other causes of vasculitis. Episodes may be recurrent.
Henoch-Schönlein purpura (HSP), also called anaphylactoid purpura, is a subtype of small-vessel vasculitis where IgA immunoglobulin is deposited in the vessel walls. It is the most common form of vasculitis is children (usually ages 4-8). In addition to skin, organs such as joints, kidneys, and intestines can be involved. Schamberg’s disease, or capillaritis, is also called pigmented purpura. In this benign condition, leakage from capillaries results in erythematous to brown patches on the lower extremities. A true vasculitis is not seen. The brown discoloration is due to hemosiderin deposition. Cryoglobulinemia is a rare condition in which abnormal immunoglobulin complexes deposit in tissues and vessels. Leukocytoclastic vasculitis is present in small vessels. Palpable purpura and livedo may be seen clinically, and systemic symptoms may be present.
Treatment of EIV is largely supportive as lesions will resolve on their own over 3-4 weeks. Postinflammatory hyperpigmentation may result. Temporary cessation of exercise and compression stockings can help speed up the resolution of lesions. Systemic medications used in the treatment of severe vasculitis, such as systemic steroids, dapsone, and colchicine, are not needed in EIV.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Vasculitis is a process in which blood vessels become inflamed and necrotic. Classic small vessel vasculitis reveals a leukocytoclastic vasculitis and most commonly presents as palpable purpura. .” A form of EIV has been described in the literature as “Disney dermatitis.” It is often seen in healthy adults after a long day of walking at the parks. Other forms of exercise, such as jogging, hiking, or swimming, may also cause the condition.
Clinically, EIV affects the lower legs and presents as purpuric macules. Edema may be present. Lesions may be asymptomatic or may present with pruritus or burning. Diagnosis is often made clinically. Skin biopsies for H&E and DIF (direct immunofluorescence) can help distinguish the type of vasculitis that is present. Laboratory tests may be needed to exclude other causes of vasculitis. Episodes may be recurrent.
Henoch-Schönlein purpura (HSP), also called anaphylactoid purpura, is a subtype of small-vessel vasculitis where IgA immunoglobulin is deposited in the vessel walls. It is the most common form of vasculitis is children (usually ages 4-8). In addition to skin, organs such as joints, kidneys, and intestines can be involved. Schamberg’s disease, or capillaritis, is also called pigmented purpura. In this benign condition, leakage from capillaries results in erythematous to brown patches on the lower extremities. A true vasculitis is not seen. The brown discoloration is due to hemosiderin deposition. Cryoglobulinemia is a rare condition in which abnormal immunoglobulin complexes deposit in tissues and vessels. Leukocytoclastic vasculitis is present in small vessels. Palpable purpura and livedo may be seen clinically, and systemic symptoms may be present.
Treatment of EIV is largely supportive as lesions will resolve on their own over 3-4 weeks. Postinflammatory hyperpigmentation may result. Temporary cessation of exercise and compression stockings can help speed up the resolution of lesions. Systemic medications used in the treatment of severe vasculitis, such as systemic steroids, dapsone, and colchicine, are not needed in EIV.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Vasculitis is a process in which blood vessels become inflamed and necrotic. Classic small vessel vasculitis reveals a leukocytoclastic vasculitis and most commonly presents as palpable purpura. .” A form of EIV has been described in the literature as “Disney dermatitis.” It is often seen in healthy adults after a long day of walking at the parks. Other forms of exercise, such as jogging, hiking, or swimming, may also cause the condition.
Clinically, EIV affects the lower legs and presents as purpuric macules. Edema may be present. Lesions may be asymptomatic or may present with pruritus or burning. Diagnosis is often made clinically. Skin biopsies for H&E and DIF (direct immunofluorescence) can help distinguish the type of vasculitis that is present. Laboratory tests may be needed to exclude other causes of vasculitis. Episodes may be recurrent.
Henoch-Schönlein purpura (HSP), also called anaphylactoid purpura, is a subtype of small-vessel vasculitis where IgA immunoglobulin is deposited in the vessel walls. It is the most common form of vasculitis is children (usually ages 4-8). In addition to skin, organs such as joints, kidneys, and intestines can be involved. Schamberg’s disease, or capillaritis, is also called pigmented purpura. In this benign condition, leakage from capillaries results in erythematous to brown patches on the lower extremities. A true vasculitis is not seen. The brown discoloration is due to hemosiderin deposition. Cryoglobulinemia is a rare condition in which abnormal immunoglobulin complexes deposit in tissues and vessels. Leukocytoclastic vasculitis is present in small vessels. Palpable purpura and livedo may be seen clinically, and systemic symptoms may be present.
Treatment of EIV is largely supportive as lesions will resolve on their own over 3-4 weeks. Postinflammatory hyperpigmentation may result. Temporary cessation of exercise and compression stockings can help speed up the resolution of lesions. Systemic medications used in the treatment of severe vasculitis, such as systemic steroids, dapsone, and colchicine, are not needed in EIV.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Violent patient throws scalding oil on MD; other patient dangers
Ralph Newman, MD, got a taste of how dangerous medicine could be at age 10, when he witnessed a physician being shot by a patient.
“I was visiting a friend whose father was a psychiatrist,” Dr. Newman recalled. “We were playing in the living room when the doorbell rang. My friend went to the door and opened it. Then I heard a shot. I ran to the front hall and saw my friend’s father slumped at the bottom of the stairs. He had come down the stairs to see who was there. It was a patient armed with a shotgun.”
As a result of the shooting, a large portion of the psychiatrist’s intestines was removed. In spite of this traumatic incident, Dr. Newman went on to become a psychiatrist – who treated many violent prisoners. “I knew it was dangerous,” he said, “but I rationalized that I wouldn’t be attacked because I would be nicer.”
That attitude seemed to work until 2002, when a prisoner threw boiling oil on him. Dr. Newman was working at the Federal Medical Center Butner, a facility for prisoners in North Carolina. “A prisoner I had been treating was denied parole, based on my recommendation,” he said. “From then on, he was looking for a way to exact revenge.”
“One day I was sitting in the nursing station, typing up notes,” Dr. Newman said. “Two new nurses, who were also there, had forgotten to lock the door, and the prisoner noticed that. He heated up some baby oil in a microwave, which was available to prisoners at the time. Then he walked into the office, threw the oil on my back, and came at me with a sharp pencil.”
Dr. Newman said the nurses fled to an adjoining office, locked the door, and wouldn’t let him in. He went into another office and collapsed in exhaustion. He was saved by an inmate who came on the scene, fended off the attacker, and called for help.
“I was taken to the burn unit,” Dr. Newman recalled. “I had second- and third-degree burns on 9% of my body. It was extremely painful. It took me 45 days to recover enough to get back to work.” The two nurses were fired.
Doctors take threats by patients more seriously now
When orthopedic surgeon Preston Phillips, MD, was killed by a patient in Tulsa, Okla., on June 1, Jennifer M. Weiss, MD, recognized the potential danger to physicians.
“The news left me feeling very shaken,” said Dr. Weiss, a pediatric orthopedic surgeon at Southern California Permanente Medical Group, Los Angeles. “Every orthopedic surgeon I talked to about it felt shaken.”
Dr. Weiss said the impact of that event prompted her to take a patient’s abuse more seriously than she might have previously. “Before the killing, my colleagues and I might have swept the incident under the rug, but we reported it to the authorities,” she said.
“What happened was I told a parent of a school-aged child that the child wasn’t ready to go back to sports,” Dr. Weiss says. “This parent was incredibly triggered – screaming and making verbal threats. The parent was standing between me and the door, so I couldn’t get out.”
Coworkers down the hall heard the yelling and helped Dr. Weiss get out of the room. “The parent was escorted out of the building, and the incident was reported to our risk management team,” she said.
Shooters/killers vs. agitated patients
Patients who shoot to kill are very different from agitated patients seen by many doctors on a regular basis – particularly in emergency departments (EDs), psychiatric units, and pain clinics, said Scott Zeller, MD, a psychiatrist who is vice president of Acute Psychiatric Medicine at Vituity, a multistate physician partnership based in Emeryville, California.
“Agitated patients have trouble communicating their needs and can become physically and verbally aggressive,” Dr. Zeller said. He reports that there are 1.7 million such incidents a year in this country, but most of the incidents of verbal aggression can be kept from exploding into physical violence.
Shooters, however, are very hard to stop because they usually plan the action in advance, Dr. Zeller said. He recalled the 2017 murder of Todd Graham, MD, a friend from medical school. Dr. Graham, an orthopedic surgeon in South Bend, Ind., was gunned down by the husband of one of his patients after Dr. Graham declined to prescribe opioids for her.
Playing down the risk of violence
Doctors may play down the risk of violence, even after they have experienced it personally. “Patients can get angry and may make threatening comments,” Dr. Weiss said. “A lot of doctors just brush it off.”
Simple remarks can set off violence-prone patients, as happened to James P. Phillips, MD, director of disaster and operational medicine at George Washington University, Washington. He recalled asking a prisoner who was visiting his hospital to “lower the volume,” and the man exploded. “Even though he was handcuffed to the bed, he heaved an oxygen tank into a window,” Dr. Phillips said. “He said he would be coming back to kill me.”
Sometimes threats or other types of verbal abuse can be as destructive as physical violence. Diann Krywko, MD, an emergency physician at the Medical University of South Carolina (MUSC) Health, Charleston, has had some tough assignments. She worked in EDs in Detroit and Flint, Mich., for a decade before coming to MUSC, where she serves as director of wellness, health, and resilience. One of the incidents that has bothered her the most involved a threat.
It happened when Dr. Krywko denied a patient’s request for narcotics. “She was very angry and said she’d come to my home and cut my children’s heads off,” Dr. Krywko said. “To this day, what she said horrifies me. I still see her smile as she said that.”
Dr. Krywko considered filing for a restraining order against the patient but didn’t because the patient could have learned her address. Dr. Phillips said fear of retaliation is one reason many doctors don’t report threats from patients. “The patient you report knows where you work and may come there to take revenge,” he said. “Also, you may have to continue caring for the person who punched you.”
Online threats also may cause a great deal of angst. Dr. Phillips said he received many online threats when was a medical analyst for CNN in 2020. “Someone sent my address to his Twitter followers, and they shared it with others, so now the whole world knows where I live,” he said. “I had to upgrade security at my home.”
How to deal with volatile patients
Being nice may not always work, but in many cases, it can keep a volatile situation from exploding, according to Dr. Krywko.
“When patients begin to show signs of agitation or are already there, we always try to verbally deescalate the situation, which involves listening,” Dr. Krywko said. “They want someone to hear them out.”
Doctors speak to patients from a position of authority, but Dr. Krywko advises that they should not be too blunt. “Don’t tell patients they’re wrong,” she said. “Even if they may be incorrect, they feel their viewpoint is valid. Encourage a dialogue with words like, ‘Tell me more,’ ” Dr. Krywko said.
Defending yourself
Doctors may have little warning of an impending attack because a patient’s mood can change quickly. This happened several years ago to Jennifer Casaletto, MD, an emergency physician in Charlotte, N.C.
“A man was brought into my ED by ambulance,” she said. “He seemed very calm for a long while, but then he became completely unhinged. A male nurse placed himself between the patient and others and was attacked. He got hurt but was able to continue working.”
Dr. Zeller said health care teams sometimes overreact when patients lash out. “The old-fashioned way to deal with an agitated patient is to call in the cavalry – everyone does a group takedown,” he said. “The patient is put in restraints and heavily sedated. This is not good for anybody. Not only is it likely to injure and traumatize the patient, it can also injure the care team.”
Many hospital EDs have security guards. “I feel safer when a hospital has armed security guards, but they need to be well trained,” Dr. Casaletto said. “Many small hospitals and freestanding EDs do not have security officers at all, or the guards are undertrained or told not to touch anybody.”
In many electronic health record systems, doctors can flag violent patients so future caregivers can be forewarned. However, Dr. Zeller advises against writing about patients’ violence or rudeness in the medical record, because patients can have access to it and might take revenge.
Rising violence from patients
“It feels like it has become much more dangerous to work in the ED,” said Hasan Gokal, MD, an emergency physician working in EDs at the Texas Medical Center. “Just last week, a woman pulled out a gun and fired it in an ED near Houston.”
The statistics back up Dr. Gokal’s assessment. Injuries caused by violent attacks against medical professionals grew by 67% from 2011 to 2018, according to the U.S. Bureau of Labor Statistics. Those levels rose even more during the COVID-19 pandemic – the assault rate in hospitals rose 23% just in 2020.
Dr. Krywko said she had “a patient who said she wanted to hurt the next person who irritated her, and that happened to me. She jumped out of her bed swinging and punching, and I wasn’t ready for it. I yelled for help and the care team came.”
“The rise in violence has to do with a decline in respect for authority,” Dr. Phillips said. “Some people now believe doctors are lying to them about the need for COVID precautions because they are taking money from the vaccine companies. The pandemic has exacerbated violence in every way.”
Dr. Phillips said that a growing lack of resources had led to more anger among patients. “There are fewer nurses and reduced physician coverage,” he said. “That means longer wait times for patients, which increases patients’ frustrations.”
Dr. Weiss said patients have higher expectations. “In sports medicine, the expectations are incredible,” she said. “Parents want their kids to get back to playing as soon as possible.”
“Hospitals in particular are soft targets for violence,” Dr. Phillips said. “People know you can’t assault a flight attendant, because it’s a federal offense, but there is no such federal offense for violence against health care personnel.”
A version of this article first appeared on Medscape.com.
Ralph Newman, MD, got a taste of how dangerous medicine could be at age 10, when he witnessed a physician being shot by a patient.
“I was visiting a friend whose father was a psychiatrist,” Dr. Newman recalled. “We were playing in the living room when the doorbell rang. My friend went to the door and opened it. Then I heard a shot. I ran to the front hall and saw my friend’s father slumped at the bottom of the stairs. He had come down the stairs to see who was there. It was a patient armed with a shotgun.”
As a result of the shooting, a large portion of the psychiatrist’s intestines was removed. In spite of this traumatic incident, Dr. Newman went on to become a psychiatrist – who treated many violent prisoners. “I knew it was dangerous,” he said, “but I rationalized that I wouldn’t be attacked because I would be nicer.”
That attitude seemed to work until 2002, when a prisoner threw boiling oil on him. Dr. Newman was working at the Federal Medical Center Butner, a facility for prisoners in North Carolina. “A prisoner I had been treating was denied parole, based on my recommendation,” he said. “From then on, he was looking for a way to exact revenge.”
“One day I was sitting in the nursing station, typing up notes,” Dr. Newman said. “Two new nurses, who were also there, had forgotten to lock the door, and the prisoner noticed that. He heated up some baby oil in a microwave, which was available to prisoners at the time. Then he walked into the office, threw the oil on my back, and came at me with a sharp pencil.”
Dr. Newman said the nurses fled to an adjoining office, locked the door, and wouldn’t let him in. He went into another office and collapsed in exhaustion. He was saved by an inmate who came on the scene, fended off the attacker, and called for help.
“I was taken to the burn unit,” Dr. Newman recalled. “I had second- and third-degree burns on 9% of my body. It was extremely painful. It took me 45 days to recover enough to get back to work.” The two nurses were fired.
Doctors take threats by patients more seriously now
When orthopedic surgeon Preston Phillips, MD, was killed by a patient in Tulsa, Okla., on June 1, Jennifer M. Weiss, MD, recognized the potential danger to physicians.
“The news left me feeling very shaken,” said Dr. Weiss, a pediatric orthopedic surgeon at Southern California Permanente Medical Group, Los Angeles. “Every orthopedic surgeon I talked to about it felt shaken.”
Dr. Weiss said the impact of that event prompted her to take a patient’s abuse more seriously than she might have previously. “Before the killing, my colleagues and I might have swept the incident under the rug, but we reported it to the authorities,” she said.
“What happened was I told a parent of a school-aged child that the child wasn’t ready to go back to sports,” Dr. Weiss says. “This parent was incredibly triggered – screaming and making verbal threats. The parent was standing between me and the door, so I couldn’t get out.”
Coworkers down the hall heard the yelling and helped Dr. Weiss get out of the room. “The parent was escorted out of the building, and the incident was reported to our risk management team,” she said.
Shooters/killers vs. agitated patients
Patients who shoot to kill are very different from agitated patients seen by many doctors on a regular basis – particularly in emergency departments (EDs), psychiatric units, and pain clinics, said Scott Zeller, MD, a psychiatrist who is vice president of Acute Psychiatric Medicine at Vituity, a multistate physician partnership based in Emeryville, California.
“Agitated patients have trouble communicating their needs and can become physically and verbally aggressive,” Dr. Zeller said. He reports that there are 1.7 million such incidents a year in this country, but most of the incidents of verbal aggression can be kept from exploding into physical violence.
Shooters, however, are very hard to stop because they usually plan the action in advance, Dr. Zeller said. He recalled the 2017 murder of Todd Graham, MD, a friend from medical school. Dr. Graham, an orthopedic surgeon in South Bend, Ind., was gunned down by the husband of one of his patients after Dr. Graham declined to prescribe opioids for her.
Playing down the risk of violence
Doctors may play down the risk of violence, even after they have experienced it personally. “Patients can get angry and may make threatening comments,” Dr. Weiss said. “A lot of doctors just brush it off.”
Simple remarks can set off violence-prone patients, as happened to James P. Phillips, MD, director of disaster and operational medicine at George Washington University, Washington. He recalled asking a prisoner who was visiting his hospital to “lower the volume,” and the man exploded. “Even though he was handcuffed to the bed, he heaved an oxygen tank into a window,” Dr. Phillips said. “He said he would be coming back to kill me.”
Sometimes threats or other types of verbal abuse can be as destructive as physical violence. Diann Krywko, MD, an emergency physician at the Medical University of South Carolina (MUSC) Health, Charleston, has had some tough assignments. She worked in EDs in Detroit and Flint, Mich., for a decade before coming to MUSC, where she serves as director of wellness, health, and resilience. One of the incidents that has bothered her the most involved a threat.
It happened when Dr. Krywko denied a patient’s request for narcotics. “She was very angry and said she’d come to my home and cut my children’s heads off,” Dr. Krywko said. “To this day, what she said horrifies me. I still see her smile as she said that.”
Dr. Krywko considered filing for a restraining order against the patient but didn’t because the patient could have learned her address. Dr. Phillips said fear of retaliation is one reason many doctors don’t report threats from patients. “The patient you report knows where you work and may come there to take revenge,” he said. “Also, you may have to continue caring for the person who punched you.”
Online threats also may cause a great deal of angst. Dr. Phillips said he received many online threats when was a medical analyst for CNN in 2020. “Someone sent my address to his Twitter followers, and they shared it with others, so now the whole world knows where I live,” he said. “I had to upgrade security at my home.”
How to deal with volatile patients
Being nice may not always work, but in many cases, it can keep a volatile situation from exploding, according to Dr. Krywko.
“When patients begin to show signs of agitation or are already there, we always try to verbally deescalate the situation, which involves listening,” Dr. Krywko said. “They want someone to hear them out.”
Doctors speak to patients from a position of authority, but Dr. Krywko advises that they should not be too blunt. “Don’t tell patients they’re wrong,” she said. “Even if they may be incorrect, they feel their viewpoint is valid. Encourage a dialogue with words like, ‘Tell me more,’ ” Dr. Krywko said.
Defending yourself
Doctors may have little warning of an impending attack because a patient’s mood can change quickly. This happened several years ago to Jennifer Casaletto, MD, an emergency physician in Charlotte, N.C.
“A man was brought into my ED by ambulance,” she said. “He seemed very calm for a long while, but then he became completely unhinged. A male nurse placed himself between the patient and others and was attacked. He got hurt but was able to continue working.”
Dr. Zeller said health care teams sometimes overreact when patients lash out. “The old-fashioned way to deal with an agitated patient is to call in the cavalry – everyone does a group takedown,” he said. “The patient is put in restraints and heavily sedated. This is not good for anybody. Not only is it likely to injure and traumatize the patient, it can also injure the care team.”
Many hospital EDs have security guards. “I feel safer when a hospital has armed security guards, but they need to be well trained,” Dr. Casaletto said. “Many small hospitals and freestanding EDs do not have security officers at all, or the guards are undertrained or told not to touch anybody.”
In many electronic health record systems, doctors can flag violent patients so future caregivers can be forewarned. However, Dr. Zeller advises against writing about patients’ violence or rudeness in the medical record, because patients can have access to it and might take revenge.
Rising violence from patients
“It feels like it has become much more dangerous to work in the ED,” said Hasan Gokal, MD, an emergency physician working in EDs at the Texas Medical Center. “Just last week, a woman pulled out a gun and fired it in an ED near Houston.”
The statistics back up Dr. Gokal’s assessment. Injuries caused by violent attacks against medical professionals grew by 67% from 2011 to 2018, according to the U.S. Bureau of Labor Statistics. Those levels rose even more during the COVID-19 pandemic – the assault rate in hospitals rose 23% just in 2020.
Dr. Krywko said she had “a patient who said she wanted to hurt the next person who irritated her, and that happened to me. She jumped out of her bed swinging and punching, and I wasn’t ready for it. I yelled for help and the care team came.”
“The rise in violence has to do with a decline in respect for authority,” Dr. Phillips said. “Some people now believe doctors are lying to them about the need for COVID precautions because they are taking money from the vaccine companies. The pandemic has exacerbated violence in every way.”
Dr. Phillips said that a growing lack of resources had led to more anger among patients. “There are fewer nurses and reduced physician coverage,” he said. “That means longer wait times for patients, which increases patients’ frustrations.”
Dr. Weiss said patients have higher expectations. “In sports medicine, the expectations are incredible,” she said. “Parents want their kids to get back to playing as soon as possible.”
“Hospitals in particular are soft targets for violence,” Dr. Phillips said. “People know you can’t assault a flight attendant, because it’s a federal offense, but there is no such federal offense for violence against health care personnel.”
A version of this article first appeared on Medscape.com.
Ralph Newman, MD, got a taste of how dangerous medicine could be at age 10, when he witnessed a physician being shot by a patient.
“I was visiting a friend whose father was a psychiatrist,” Dr. Newman recalled. “We were playing in the living room when the doorbell rang. My friend went to the door and opened it. Then I heard a shot. I ran to the front hall and saw my friend’s father slumped at the bottom of the stairs. He had come down the stairs to see who was there. It was a patient armed with a shotgun.”
As a result of the shooting, a large portion of the psychiatrist’s intestines was removed. In spite of this traumatic incident, Dr. Newman went on to become a psychiatrist – who treated many violent prisoners. “I knew it was dangerous,” he said, “but I rationalized that I wouldn’t be attacked because I would be nicer.”
That attitude seemed to work until 2002, when a prisoner threw boiling oil on him. Dr. Newman was working at the Federal Medical Center Butner, a facility for prisoners in North Carolina. “A prisoner I had been treating was denied parole, based on my recommendation,” he said. “From then on, he was looking for a way to exact revenge.”
“One day I was sitting in the nursing station, typing up notes,” Dr. Newman said. “Two new nurses, who were also there, had forgotten to lock the door, and the prisoner noticed that. He heated up some baby oil in a microwave, which was available to prisoners at the time. Then he walked into the office, threw the oil on my back, and came at me with a sharp pencil.”
Dr. Newman said the nurses fled to an adjoining office, locked the door, and wouldn’t let him in. He went into another office and collapsed in exhaustion. He was saved by an inmate who came on the scene, fended off the attacker, and called for help.
“I was taken to the burn unit,” Dr. Newman recalled. “I had second- and third-degree burns on 9% of my body. It was extremely painful. It took me 45 days to recover enough to get back to work.” The two nurses were fired.
Doctors take threats by patients more seriously now
When orthopedic surgeon Preston Phillips, MD, was killed by a patient in Tulsa, Okla., on June 1, Jennifer M. Weiss, MD, recognized the potential danger to physicians.
“The news left me feeling very shaken,” said Dr. Weiss, a pediatric orthopedic surgeon at Southern California Permanente Medical Group, Los Angeles. “Every orthopedic surgeon I talked to about it felt shaken.”
Dr. Weiss said the impact of that event prompted her to take a patient’s abuse more seriously than she might have previously. “Before the killing, my colleagues and I might have swept the incident under the rug, but we reported it to the authorities,” she said.
“What happened was I told a parent of a school-aged child that the child wasn’t ready to go back to sports,” Dr. Weiss says. “This parent was incredibly triggered – screaming and making verbal threats. The parent was standing between me and the door, so I couldn’t get out.”
Coworkers down the hall heard the yelling and helped Dr. Weiss get out of the room. “The parent was escorted out of the building, and the incident was reported to our risk management team,” she said.
Shooters/killers vs. agitated patients
Patients who shoot to kill are very different from agitated patients seen by many doctors on a regular basis – particularly in emergency departments (EDs), psychiatric units, and pain clinics, said Scott Zeller, MD, a psychiatrist who is vice president of Acute Psychiatric Medicine at Vituity, a multistate physician partnership based in Emeryville, California.
“Agitated patients have trouble communicating their needs and can become physically and verbally aggressive,” Dr. Zeller said. He reports that there are 1.7 million such incidents a year in this country, but most of the incidents of verbal aggression can be kept from exploding into physical violence.
Shooters, however, are very hard to stop because they usually plan the action in advance, Dr. Zeller said. He recalled the 2017 murder of Todd Graham, MD, a friend from medical school. Dr. Graham, an orthopedic surgeon in South Bend, Ind., was gunned down by the husband of one of his patients after Dr. Graham declined to prescribe opioids for her.
Playing down the risk of violence
Doctors may play down the risk of violence, even after they have experienced it personally. “Patients can get angry and may make threatening comments,” Dr. Weiss said. “A lot of doctors just brush it off.”
Simple remarks can set off violence-prone patients, as happened to James P. Phillips, MD, director of disaster and operational medicine at George Washington University, Washington. He recalled asking a prisoner who was visiting his hospital to “lower the volume,” and the man exploded. “Even though he was handcuffed to the bed, he heaved an oxygen tank into a window,” Dr. Phillips said. “He said he would be coming back to kill me.”
Sometimes threats or other types of verbal abuse can be as destructive as physical violence. Diann Krywko, MD, an emergency physician at the Medical University of South Carolina (MUSC) Health, Charleston, has had some tough assignments. She worked in EDs in Detroit and Flint, Mich., for a decade before coming to MUSC, where she serves as director of wellness, health, and resilience. One of the incidents that has bothered her the most involved a threat.
It happened when Dr. Krywko denied a patient’s request for narcotics. “She was very angry and said she’d come to my home and cut my children’s heads off,” Dr. Krywko said. “To this day, what she said horrifies me. I still see her smile as she said that.”
Dr. Krywko considered filing for a restraining order against the patient but didn’t because the patient could have learned her address. Dr. Phillips said fear of retaliation is one reason many doctors don’t report threats from patients. “The patient you report knows where you work and may come there to take revenge,” he said. “Also, you may have to continue caring for the person who punched you.”
Online threats also may cause a great deal of angst. Dr. Phillips said he received many online threats when was a medical analyst for CNN in 2020. “Someone sent my address to his Twitter followers, and they shared it with others, so now the whole world knows where I live,” he said. “I had to upgrade security at my home.”
How to deal with volatile patients
Being nice may not always work, but in many cases, it can keep a volatile situation from exploding, according to Dr. Krywko.
“When patients begin to show signs of agitation or are already there, we always try to verbally deescalate the situation, which involves listening,” Dr. Krywko said. “They want someone to hear them out.”
Doctors speak to patients from a position of authority, but Dr. Krywko advises that they should not be too blunt. “Don’t tell patients they’re wrong,” she said. “Even if they may be incorrect, they feel their viewpoint is valid. Encourage a dialogue with words like, ‘Tell me more,’ ” Dr. Krywko said.
Defending yourself
Doctors may have little warning of an impending attack because a patient’s mood can change quickly. This happened several years ago to Jennifer Casaletto, MD, an emergency physician in Charlotte, N.C.
“A man was brought into my ED by ambulance,” she said. “He seemed very calm for a long while, but then he became completely unhinged. A male nurse placed himself between the patient and others and was attacked. He got hurt but was able to continue working.”
Dr. Zeller said health care teams sometimes overreact when patients lash out. “The old-fashioned way to deal with an agitated patient is to call in the cavalry – everyone does a group takedown,” he said. “The patient is put in restraints and heavily sedated. This is not good for anybody. Not only is it likely to injure and traumatize the patient, it can also injure the care team.”
Many hospital EDs have security guards. “I feel safer when a hospital has armed security guards, but they need to be well trained,” Dr. Casaletto said. “Many small hospitals and freestanding EDs do not have security officers at all, or the guards are undertrained or told not to touch anybody.”
In many electronic health record systems, doctors can flag violent patients so future caregivers can be forewarned. However, Dr. Zeller advises against writing about patients’ violence or rudeness in the medical record, because patients can have access to it and might take revenge.
Rising violence from patients
“It feels like it has become much more dangerous to work in the ED,” said Hasan Gokal, MD, an emergency physician working in EDs at the Texas Medical Center. “Just last week, a woman pulled out a gun and fired it in an ED near Houston.”
The statistics back up Dr. Gokal’s assessment. Injuries caused by violent attacks against medical professionals grew by 67% from 2011 to 2018, according to the U.S. Bureau of Labor Statistics. Those levels rose even more during the COVID-19 pandemic – the assault rate in hospitals rose 23% just in 2020.
Dr. Krywko said she had “a patient who said she wanted to hurt the next person who irritated her, and that happened to me. She jumped out of her bed swinging and punching, and I wasn’t ready for it. I yelled for help and the care team came.”
“The rise in violence has to do with a decline in respect for authority,” Dr. Phillips said. “Some people now believe doctors are lying to them about the need for COVID precautions because they are taking money from the vaccine companies. The pandemic has exacerbated violence in every way.”
Dr. Phillips said that a growing lack of resources had led to more anger among patients. “There are fewer nurses and reduced physician coverage,” he said. “That means longer wait times for patients, which increases patients’ frustrations.”
Dr. Weiss said patients have higher expectations. “In sports medicine, the expectations are incredible,” she said. “Parents want their kids to get back to playing as soon as possible.”
“Hospitals in particular are soft targets for violence,” Dr. Phillips said. “People know you can’t assault a flight attendant, because it’s a federal offense, but there is no such federal offense for violence against health care personnel.”
A version of this article first appeared on Medscape.com.
Marital status plays modest role in gastric cancer overall survival
, according to research published in the Journal of Investigative Medicine.
Tumor size remained the largest contributor to overall survival, but marital status was among several other significant factors, such as age, race, gender, treatment style, and pathologic stage, that can provide insight into a patient’s likelihood of overall survival, as it does with several other cancers.
“Married patients had the best prognosis, followed by single patients, and the prognosis of separated patients was the worst,” write Lixiang Zhang and colleagues at the First Affiliated Hospital of Anhui Medical University, Hefei, China. “We speculate that this might be due to the fact that married patients had better financial conditions and emotional encouragement, while separated patients might be more likely to experience financial difficulties [and] emotional loss.”
The results were not necessarily surprising to Richard M. Peek, Jr., MD, director of the division of gastroenterology and a professor of medicine at Vanderbilt University Medical Center, who was not involved in the research.
“Marital status is a reflection of support systems, and a strong support system is a prognosticator for increased compliance with medical appointments and medical therapies,” Dr. Peek told this news organization. “It is something to consider when somebody is being treated for gastric cancer, because if they don’t have a strong support system – and marital status can be a proxy for that – then they may need more intensive follow-up and surveillance, for example, than somebody who does not have that support system.”
Exploring the marital status–cancer survival connection
Gastric cancer is the third leading cause of cancer deaths across the world, causing 780,000 deaths in 2018, the authors note. Yet it’s difficult to accurately predict the prognosis in patients who undergo treatment for early stage gastric cancer. Previous research has found marital status to be associated with survival in prostate, cervical, and rectal cancers.
Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare Cancer Center, Utah, told this news organization that the connection between marital status and cancer outcomes has been described previously, including in an even larger analysis using the U.S. Surveillance, Epidemiology, and End Results (SEER) database from 2013. That study found that “unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer.”
In this study, the researchers compared marital status and survival rates among 3,647 patients with early-stage gastric cancer, using data from the SEER database. The study only included patients with tumors in the lamina propria, mucosa, and submucosa and excluded those with distant metastasis or distant lymph node metastases, a second cancer, no data on chemotherapy received, or unknown survival time.
Because they were using a nomogram and building a new predictive nomogram that would include marital status, the researchers divided the patient population into a training set of 2,719 patients and a testing set of 928 patients. Using overall survival as the primary endpoint, the analysis included the variables of “age at diagnosis, race, gender, tumor location, histology, grade, stage_T and stage_N, surgery in the primary site, lymph node dissection, chemotherapy, radiation, tumor size, insurance, and marital status,” the authors report.
Among the study population, 53.7% were married, 17.3% were widowed, 14% were single and never married, 7.5% were divorced, 1.1% were separated, and the status of 6.4% was unknown. Age at diagnosis, race, gender, histology, tumor grade, stage T, stage N, surgery type, tumor size, and insurance status were all significantly different between the marital status subgroups.
Married patients had the best prognosis, with an average overall survival of 72 months, compared with an average 60 months in widowed persons, the group with the poorest overall survival. Overall survival was higher in married women (76 months) than in married men (69 months). The same pattern held for women (62 months) and men (52 months) who had been widowed.
“It is worthy to note that survival was significantly better in divorced female patients than in divorced male patients,” the authors report. “Survival was better in female patients than in male patients” across all marital groups.
What long-term relationships reveal
These findings do not mean that simply getting married changes one’s likelihood of survival, however. Rather, a long-term relationship is revealing about other aspects in a person’s life.
“I think it represents more stability in the supportive relationship that you need to really deal with a serious disease like cancer,” Dr. Peek said.
If a patient does not have a long-term partner, their care team can ask other questions to get a sense of what their support network is like, Dr. Peek added. “We want to know, does anybody else live in the house with them? Do they have adequate transportation? Can they make medical appointments? Do they have somebody who can help with the medical issues that are going to come up? Do they have family in the area?”
Cancer treatment requires a multidisciplinary approach, and having someone other than just the patient around to help bring together the different aspects of care from different care teams can make a difference in how the patient fares, Dr. Peek explained. Patients without a strong support system may need closer follow-up and other accommodations, he said.
Providers “may schedule their clinical appointments closer together if they don’t have a support system, or they may be able to reach out and offer transportation assistance and those kinds of things that somebody living alone may need,” Dr. Peek said. Outside resources may be a higher priority for those who lack a support system at home, he added.
Dr. Peek also noted other factors that may play a role in a patient’s survival that these researchers did not have the data to address, such as socioeconomic status, employment, alcohol use, smoking, and infection with Helicobacter pylori, the strongest known risk factor for gastric cancer.
A potentially relevant limitation of the study is that it probably has some selection bias, because the patients who were included probably had the means to have received an earlier diagnosis, said Dr. Lewis, who was not involved in the research.
“Furthermore, just in terms of the group sizes, the baseline characteristics section makes it clear that the preponderance of patients were married, lending that group more statistical weight,” Dr. Lewis said.
“Of the seven attributes in the nomogram, the impact of the marital status seems comparatively meager relative to conventional clinicopathology risk factors like T stage,” he added.
“All in all, I think this study reinforces our awareness that socioeconomic status and social determinants of health play a huge role in cancer outcomes, but it’s not entirely clear that’s modifiable just by getting married,” Dr. Lewis said. “There is a saying in oncology that ‘expensive liquor causes less cancer than cheap liquor,’ which is not negating the carcinogenicity of alcohol but rather identifying different outcomes by socioeconomic status.”
The research was funded by the Natural Science Foundation of Anhui Province. The authors report no relevant financial relationships. Dr. Peek reports no relevant financial relationships. Dr. Lewis reports receiving speaking fees for AstraZeneca/Daiichi Sankyo and having done educational videos for Astellas.
A version of this article first appeared on Medscape.com.
, according to research published in the Journal of Investigative Medicine.
Tumor size remained the largest contributor to overall survival, but marital status was among several other significant factors, such as age, race, gender, treatment style, and pathologic stage, that can provide insight into a patient’s likelihood of overall survival, as it does with several other cancers.
“Married patients had the best prognosis, followed by single patients, and the prognosis of separated patients was the worst,” write Lixiang Zhang and colleagues at the First Affiliated Hospital of Anhui Medical University, Hefei, China. “We speculate that this might be due to the fact that married patients had better financial conditions and emotional encouragement, while separated patients might be more likely to experience financial difficulties [and] emotional loss.”
The results were not necessarily surprising to Richard M. Peek, Jr., MD, director of the division of gastroenterology and a professor of medicine at Vanderbilt University Medical Center, who was not involved in the research.
“Marital status is a reflection of support systems, and a strong support system is a prognosticator for increased compliance with medical appointments and medical therapies,” Dr. Peek told this news organization. “It is something to consider when somebody is being treated for gastric cancer, because if they don’t have a strong support system – and marital status can be a proxy for that – then they may need more intensive follow-up and surveillance, for example, than somebody who does not have that support system.”
Exploring the marital status–cancer survival connection
Gastric cancer is the third leading cause of cancer deaths across the world, causing 780,000 deaths in 2018, the authors note. Yet it’s difficult to accurately predict the prognosis in patients who undergo treatment for early stage gastric cancer. Previous research has found marital status to be associated with survival in prostate, cervical, and rectal cancers.
Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare Cancer Center, Utah, told this news organization that the connection between marital status and cancer outcomes has been described previously, including in an even larger analysis using the U.S. Surveillance, Epidemiology, and End Results (SEER) database from 2013. That study found that “unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer.”
In this study, the researchers compared marital status and survival rates among 3,647 patients with early-stage gastric cancer, using data from the SEER database. The study only included patients with tumors in the lamina propria, mucosa, and submucosa and excluded those with distant metastasis or distant lymph node metastases, a second cancer, no data on chemotherapy received, or unknown survival time.
Because they were using a nomogram and building a new predictive nomogram that would include marital status, the researchers divided the patient population into a training set of 2,719 patients and a testing set of 928 patients. Using overall survival as the primary endpoint, the analysis included the variables of “age at diagnosis, race, gender, tumor location, histology, grade, stage_T and stage_N, surgery in the primary site, lymph node dissection, chemotherapy, radiation, tumor size, insurance, and marital status,” the authors report.
Among the study population, 53.7% were married, 17.3% were widowed, 14% were single and never married, 7.5% were divorced, 1.1% were separated, and the status of 6.4% was unknown. Age at diagnosis, race, gender, histology, tumor grade, stage T, stage N, surgery type, tumor size, and insurance status were all significantly different between the marital status subgroups.
Married patients had the best prognosis, with an average overall survival of 72 months, compared with an average 60 months in widowed persons, the group with the poorest overall survival. Overall survival was higher in married women (76 months) than in married men (69 months). The same pattern held for women (62 months) and men (52 months) who had been widowed.
“It is worthy to note that survival was significantly better in divorced female patients than in divorced male patients,” the authors report. “Survival was better in female patients than in male patients” across all marital groups.
What long-term relationships reveal
These findings do not mean that simply getting married changes one’s likelihood of survival, however. Rather, a long-term relationship is revealing about other aspects in a person’s life.
“I think it represents more stability in the supportive relationship that you need to really deal with a serious disease like cancer,” Dr. Peek said.
If a patient does not have a long-term partner, their care team can ask other questions to get a sense of what their support network is like, Dr. Peek added. “We want to know, does anybody else live in the house with them? Do they have adequate transportation? Can they make medical appointments? Do they have somebody who can help with the medical issues that are going to come up? Do they have family in the area?”
Cancer treatment requires a multidisciplinary approach, and having someone other than just the patient around to help bring together the different aspects of care from different care teams can make a difference in how the patient fares, Dr. Peek explained. Patients without a strong support system may need closer follow-up and other accommodations, he said.
Providers “may schedule their clinical appointments closer together if they don’t have a support system, or they may be able to reach out and offer transportation assistance and those kinds of things that somebody living alone may need,” Dr. Peek said. Outside resources may be a higher priority for those who lack a support system at home, he added.
Dr. Peek also noted other factors that may play a role in a patient’s survival that these researchers did not have the data to address, such as socioeconomic status, employment, alcohol use, smoking, and infection with Helicobacter pylori, the strongest known risk factor for gastric cancer.
A potentially relevant limitation of the study is that it probably has some selection bias, because the patients who were included probably had the means to have received an earlier diagnosis, said Dr. Lewis, who was not involved in the research.
“Furthermore, just in terms of the group sizes, the baseline characteristics section makes it clear that the preponderance of patients were married, lending that group more statistical weight,” Dr. Lewis said.
“Of the seven attributes in the nomogram, the impact of the marital status seems comparatively meager relative to conventional clinicopathology risk factors like T stage,” he added.
“All in all, I think this study reinforces our awareness that socioeconomic status and social determinants of health play a huge role in cancer outcomes, but it’s not entirely clear that’s modifiable just by getting married,” Dr. Lewis said. “There is a saying in oncology that ‘expensive liquor causes less cancer than cheap liquor,’ which is not negating the carcinogenicity of alcohol but rather identifying different outcomes by socioeconomic status.”
The research was funded by the Natural Science Foundation of Anhui Province. The authors report no relevant financial relationships. Dr. Peek reports no relevant financial relationships. Dr. Lewis reports receiving speaking fees for AstraZeneca/Daiichi Sankyo and having done educational videos for Astellas.
A version of this article first appeared on Medscape.com.
, according to research published in the Journal of Investigative Medicine.
Tumor size remained the largest contributor to overall survival, but marital status was among several other significant factors, such as age, race, gender, treatment style, and pathologic stage, that can provide insight into a patient’s likelihood of overall survival, as it does with several other cancers.
“Married patients had the best prognosis, followed by single patients, and the prognosis of separated patients was the worst,” write Lixiang Zhang and colleagues at the First Affiliated Hospital of Anhui Medical University, Hefei, China. “We speculate that this might be due to the fact that married patients had better financial conditions and emotional encouragement, while separated patients might be more likely to experience financial difficulties [and] emotional loss.”
The results were not necessarily surprising to Richard M. Peek, Jr., MD, director of the division of gastroenterology and a professor of medicine at Vanderbilt University Medical Center, who was not involved in the research.
“Marital status is a reflection of support systems, and a strong support system is a prognosticator for increased compliance with medical appointments and medical therapies,” Dr. Peek told this news organization. “It is something to consider when somebody is being treated for gastric cancer, because if they don’t have a strong support system – and marital status can be a proxy for that – then they may need more intensive follow-up and surveillance, for example, than somebody who does not have that support system.”
Exploring the marital status–cancer survival connection
Gastric cancer is the third leading cause of cancer deaths across the world, causing 780,000 deaths in 2018, the authors note. Yet it’s difficult to accurately predict the prognosis in patients who undergo treatment for early stage gastric cancer. Previous research has found marital status to be associated with survival in prostate, cervical, and rectal cancers.
Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare Cancer Center, Utah, told this news organization that the connection between marital status and cancer outcomes has been described previously, including in an even larger analysis using the U.S. Surveillance, Epidemiology, and End Results (SEER) database from 2013. That study found that “unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer.”
In this study, the researchers compared marital status and survival rates among 3,647 patients with early-stage gastric cancer, using data from the SEER database. The study only included patients with tumors in the lamina propria, mucosa, and submucosa and excluded those with distant metastasis or distant lymph node metastases, a second cancer, no data on chemotherapy received, or unknown survival time.
Because they were using a nomogram and building a new predictive nomogram that would include marital status, the researchers divided the patient population into a training set of 2,719 patients and a testing set of 928 patients. Using overall survival as the primary endpoint, the analysis included the variables of “age at diagnosis, race, gender, tumor location, histology, grade, stage_T and stage_N, surgery in the primary site, lymph node dissection, chemotherapy, radiation, tumor size, insurance, and marital status,” the authors report.
Among the study population, 53.7% were married, 17.3% were widowed, 14% were single and never married, 7.5% were divorced, 1.1% were separated, and the status of 6.4% was unknown. Age at diagnosis, race, gender, histology, tumor grade, stage T, stage N, surgery type, tumor size, and insurance status were all significantly different between the marital status subgroups.
Married patients had the best prognosis, with an average overall survival of 72 months, compared with an average 60 months in widowed persons, the group with the poorest overall survival. Overall survival was higher in married women (76 months) than in married men (69 months). The same pattern held for women (62 months) and men (52 months) who had been widowed.
“It is worthy to note that survival was significantly better in divorced female patients than in divorced male patients,” the authors report. “Survival was better in female patients than in male patients” across all marital groups.
What long-term relationships reveal
These findings do not mean that simply getting married changes one’s likelihood of survival, however. Rather, a long-term relationship is revealing about other aspects in a person’s life.
“I think it represents more stability in the supportive relationship that you need to really deal with a serious disease like cancer,” Dr. Peek said.
If a patient does not have a long-term partner, their care team can ask other questions to get a sense of what their support network is like, Dr. Peek added. “We want to know, does anybody else live in the house with them? Do they have adequate transportation? Can they make medical appointments? Do they have somebody who can help with the medical issues that are going to come up? Do they have family in the area?”
Cancer treatment requires a multidisciplinary approach, and having someone other than just the patient around to help bring together the different aspects of care from different care teams can make a difference in how the patient fares, Dr. Peek explained. Patients without a strong support system may need closer follow-up and other accommodations, he said.
Providers “may schedule their clinical appointments closer together if they don’t have a support system, or they may be able to reach out and offer transportation assistance and those kinds of things that somebody living alone may need,” Dr. Peek said. Outside resources may be a higher priority for those who lack a support system at home, he added.
Dr. Peek also noted other factors that may play a role in a patient’s survival that these researchers did not have the data to address, such as socioeconomic status, employment, alcohol use, smoking, and infection with Helicobacter pylori, the strongest known risk factor for gastric cancer.
A potentially relevant limitation of the study is that it probably has some selection bias, because the patients who were included probably had the means to have received an earlier diagnosis, said Dr. Lewis, who was not involved in the research.
“Furthermore, just in terms of the group sizes, the baseline characteristics section makes it clear that the preponderance of patients were married, lending that group more statistical weight,” Dr. Lewis said.
“Of the seven attributes in the nomogram, the impact of the marital status seems comparatively meager relative to conventional clinicopathology risk factors like T stage,” he added.
“All in all, I think this study reinforces our awareness that socioeconomic status and social determinants of health play a huge role in cancer outcomes, but it’s not entirely clear that’s modifiable just by getting married,” Dr. Lewis said. “There is a saying in oncology that ‘expensive liquor causes less cancer than cheap liquor,’ which is not negating the carcinogenicity of alcohol but rather identifying different outcomes by socioeconomic status.”
The research was funded by the Natural Science Foundation of Anhui Province. The authors report no relevant financial relationships. Dr. Peek reports no relevant financial relationships. Dr. Lewis reports receiving speaking fees for AstraZeneca/Daiichi Sankyo and having done educational videos for Astellas.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF INVESTIGATIVE MEDICINE
Ten steps for clinicians to avoid being racist: The Francis commitment
As a Black man who grew up in this country, I can tell you first-hand what it does to you. The scars never go away, and your status is always in question, no matter your title or uniforms of respect. Eventually it wears you down.
I was born into poverty and the segregation of southwest Louisiana. I experienced the dehumanization intended for me: separate drinking fountains and poor foundational education. I was lucky to attend a historically Black college or university (Southern University, Baton Rouge, La.), that gave me my bearings. I then went to some of the very best, predominantly White institutions.
When I looked for a job after training, there were few integrated medical groups, so I started my own. It included practitioners who were White, Black, Jewish, Asian, Middle Eastern, Muslim, Christian, etc. We cross covered and treated patients from every corner of the globe.
In medicine, we treat human beings with disease. The disease should be the only difference that sets us apart. There is absolutely no place for racism.
It is difficult to be called a racist, and I have met only a handful of people in health care whom I would label as such. But racism is structural and institutionalized so that it is often hidden.
One way to overcome this is to make every effort possible to get to know people as individuals. Only then can we see that there are few real differences between us. I would often seek out a colleague from a different culture or race to have lunch with so I could learn more about them.
We all strive for the same things – validation, happiness, love, family, and a future. We all grieve over the same things.
What some caregivers may not realize is that, just as clinicians have been trained to recognize subtle signs and symptoms of disease, minorities can recognize racism immediately during a medical encounter. Our past experiences make us skilled at picking up a lack of eye contact or body language and tone of voice that are dismissive and disrespectful.
A patient who has felt racism may still return for care because of insurance coverage limitations, location, or a lack of alternatives. But trust and loyalty will never develop on the part of this patient, and empathy will be absent on the part of their caregiver.
To counter this in my own practice, I developed the Francis Commitment to avoid any hint of racism or bias toward my patients.
I commit to the following:
1. I see you.
2. I hear you.
3. I accept who you are.
4. I will try to understand how you must feel (empathy).
5. Treating you is very important to me.
6. I would like to gain your trust that I will do my very best to make you better.
7. I value you as a human being and will treat you as if you are family.
8. I care about what happens to you.
9. I want us to work together to fight this disease.
10. I am grateful that you chose me as your caregiver.
The INOVA health care system where I work has undertaken an initiative called What Matters Most to better understand the needs of every patient. We are currently working on a strategy of patient personalization to not only learn about their medical needs but also to discover who they are as a person. We incorporate Social Determinants of Health in our dealings with patients. We also have participated in a program called “A Long Talk”, where we learned that those of us who remain silent when we see or hear racism are responsible for its persistence and growth.
But we must do more. Racism will propagate if we live in silos surrounded by people whose ideas reflect our own. As long as we have nondiversified board rooms, departments, and staff, the problem will persist.
A lot of the biases that we unconsciously carry in our heads and hearts have no basis in reality and were placed there without our permission by parents, society, and friends. But we can replace these divisive thoughts and impulses.
What’s in your heart can only be known and controlled by you. How tolerant we are of racism is up to us: Do you call out racism; do you challenge any inkling of racism from friends or acquaintances; do you put pressure on institutions where you work to diversify in recruiting and hiring?
Think of all the advances in medicine that were achieved by people from different cultures and races. Racism has no place in what we have all devoted our lives to do – take care of our fellow humans.
A version of this article first appeared on Medscape.com.
As a Black man who grew up in this country, I can tell you first-hand what it does to you. The scars never go away, and your status is always in question, no matter your title or uniforms of respect. Eventually it wears you down.
I was born into poverty and the segregation of southwest Louisiana. I experienced the dehumanization intended for me: separate drinking fountains and poor foundational education. I was lucky to attend a historically Black college or university (Southern University, Baton Rouge, La.), that gave me my bearings. I then went to some of the very best, predominantly White institutions.
When I looked for a job after training, there were few integrated medical groups, so I started my own. It included practitioners who were White, Black, Jewish, Asian, Middle Eastern, Muslim, Christian, etc. We cross covered and treated patients from every corner of the globe.
In medicine, we treat human beings with disease. The disease should be the only difference that sets us apart. There is absolutely no place for racism.
It is difficult to be called a racist, and I have met only a handful of people in health care whom I would label as such. But racism is structural and institutionalized so that it is often hidden.
One way to overcome this is to make every effort possible to get to know people as individuals. Only then can we see that there are few real differences between us. I would often seek out a colleague from a different culture or race to have lunch with so I could learn more about them.
We all strive for the same things – validation, happiness, love, family, and a future. We all grieve over the same things.
What some caregivers may not realize is that, just as clinicians have been trained to recognize subtle signs and symptoms of disease, minorities can recognize racism immediately during a medical encounter. Our past experiences make us skilled at picking up a lack of eye contact or body language and tone of voice that are dismissive and disrespectful.
A patient who has felt racism may still return for care because of insurance coverage limitations, location, or a lack of alternatives. But trust and loyalty will never develop on the part of this patient, and empathy will be absent on the part of their caregiver.
To counter this in my own practice, I developed the Francis Commitment to avoid any hint of racism or bias toward my patients.
I commit to the following:
1. I see you.
2. I hear you.
3. I accept who you are.
4. I will try to understand how you must feel (empathy).
5. Treating you is very important to me.
6. I would like to gain your trust that I will do my very best to make you better.
7. I value you as a human being and will treat you as if you are family.
8. I care about what happens to you.
9. I want us to work together to fight this disease.
10. I am grateful that you chose me as your caregiver.
The INOVA health care system where I work has undertaken an initiative called What Matters Most to better understand the needs of every patient. We are currently working on a strategy of patient personalization to not only learn about their medical needs but also to discover who they are as a person. We incorporate Social Determinants of Health in our dealings with patients. We also have participated in a program called “A Long Talk”, where we learned that those of us who remain silent when we see or hear racism are responsible for its persistence and growth.
But we must do more. Racism will propagate if we live in silos surrounded by people whose ideas reflect our own. As long as we have nondiversified board rooms, departments, and staff, the problem will persist.
A lot of the biases that we unconsciously carry in our heads and hearts have no basis in reality and were placed there without our permission by parents, society, and friends. But we can replace these divisive thoughts and impulses.
What’s in your heart can only be known and controlled by you. How tolerant we are of racism is up to us: Do you call out racism; do you challenge any inkling of racism from friends or acquaintances; do you put pressure on institutions where you work to diversify in recruiting and hiring?
Think of all the advances in medicine that were achieved by people from different cultures and races. Racism has no place in what we have all devoted our lives to do – take care of our fellow humans.
A version of this article first appeared on Medscape.com.
As a Black man who grew up in this country, I can tell you first-hand what it does to you. The scars never go away, and your status is always in question, no matter your title or uniforms of respect. Eventually it wears you down.
I was born into poverty and the segregation of southwest Louisiana. I experienced the dehumanization intended for me: separate drinking fountains and poor foundational education. I was lucky to attend a historically Black college or university (Southern University, Baton Rouge, La.), that gave me my bearings. I then went to some of the very best, predominantly White institutions.
When I looked for a job after training, there were few integrated medical groups, so I started my own. It included practitioners who were White, Black, Jewish, Asian, Middle Eastern, Muslim, Christian, etc. We cross covered and treated patients from every corner of the globe.
In medicine, we treat human beings with disease. The disease should be the only difference that sets us apart. There is absolutely no place for racism.
It is difficult to be called a racist, and I have met only a handful of people in health care whom I would label as such. But racism is structural and institutionalized so that it is often hidden.
One way to overcome this is to make every effort possible to get to know people as individuals. Only then can we see that there are few real differences between us. I would often seek out a colleague from a different culture or race to have lunch with so I could learn more about them.
We all strive for the same things – validation, happiness, love, family, and a future. We all grieve over the same things.
What some caregivers may not realize is that, just as clinicians have been trained to recognize subtle signs and symptoms of disease, minorities can recognize racism immediately during a medical encounter. Our past experiences make us skilled at picking up a lack of eye contact or body language and tone of voice that are dismissive and disrespectful.
A patient who has felt racism may still return for care because of insurance coverage limitations, location, or a lack of alternatives. But trust and loyalty will never develop on the part of this patient, and empathy will be absent on the part of their caregiver.
To counter this in my own practice, I developed the Francis Commitment to avoid any hint of racism or bias toward my patients.
I commit to the following:
1. I see you.
2. I hear you.
3. I accept who you are.
4. I will try to understand how you must feel (empathy).
5. Treating you is very important to me.
6. I would like to gain your trust that I will do my very best to make you better.
7. I value you as a human being and will treat you as if you are family.
8. I care about what happens to you.
9. I want us to work together to fight this disease.
10. I am grateful that you chose me as your caregiver.
The INOVA health care system where I work has undertaken an initiative called What Matters Most to better understand the needs of every patient. We are currently working on a strategy of patient personalization to not only learn about their medical needs but also to discover who they are as a person. We incorporate Social Determinants of Health in our dealings with patients. We also have participated in a program called “A Long Talk”, where we learned that those of us who remain silent when we see or hear racism are responsible for its persistence and growth.
But we must do more. Racism will propagate if we live in silos surrounded by people whose ideas reflect our own. As long as we have nondiversified board rooms, departments, and staff, the problem will persist.
A lot of the biases that we unconsciously carry in our heads and hearts have no basis in reality and were placed there without our permission by parents, society, and friends. But we can replace these divisive thoughts and impulses.
What’s in your heart can only be known and controlled by you. How tolerant we are of racism is up to us: Do you call out racism; do you challenge any inkling of racism from friends or acquaintances; do you put pressure on institutions where you work to diversify in recruiting and hiring?
Think of all the advances in medicine that were achieved by people from different cultures and races. Racism has no place in what we have all devoted our lives to do – take care of our fellow humans.
A version of this article first appeared on Medscape.com.
New algorithm for initial PsA treatment choice is driven by T-cell behavior
T-cell behavior
Biologic selection is cytokine based
NEW YORK – An algorithm in development for psoriatic arthritis (PsA) is showing promise for directing patients to the biologic with the greatest likelihood of producing disease control, according to a proof-of-concept study presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
“Our technique involves a more precise functional assay showing exact T-cell behavior, compared to the previous assessments that only analyzed cellular phenotypes,” reported Gizem Ayan, MD, a fellow in rheumatology at Hacettepe University Faculty of Medicine, Ankara, Turkey.
The concept of precision medicine in PsA as well as other autoimmune diseases is not new. Phenotypes and biomarkers have already shown potential for guiding treatment, according to Dr. Ayan, but she said none are yet guideline recommended or proven to improve patient outcomes.
The principle of the new algorithm that she and her coinvestigators are pursing is based on immunophenotype analysis conducted with a flow-cytometric cytokine secretion assay (FCCSA). In the protocol, monocytes obtained from peripheral blood undergo activation before an FCCSA to distinguish patients by their T-cell behavior.
The treatment decision tree is based on median ratios of tumor necrosis factor (TNF)-alpha, interleukin (IL)–22, IL-17, and interferon-gamma expression among CD4+ and CD8+ cells. Based on a yes-or-no response to specific immune patterns, the patient is funneled to a biologic that inhibits a dominant cytokine.
The proof-of-concept study, which enrolled 8 patients with PsA who were naive to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 11 patients with PsA who were naive to biologic DMARDs (bDMARDs), was designed to demonstrate feasibility. It did not test clinical benefit, but it did show that immunophenotyping with this methodology can be performed efficiently.
“From the time a blood sample is obtained, the method provided results within 24 hours,” according to Dr. Ayan, who is now planning a randomized trial to test the ability of the algorithm to improve clinical outcomes.
In the decision tree, there are five yes-no pathways to a treatment choice. The first step of the algorithm is to test the ratio of TNF-alpha to interferon-gamma CD4+ T cells. A “yes’ response is produced if the ratio is greater than or equal to 2. These patients are then evaluated for the ratio of TNF-alpha to interferon-gamma CD8+ T cells. A yes response is produced if the ratio is greater than or equal to 0.5. If yes, they are candidates for a TNF-alpha inhibitor. If no, they are directed to an IL-12/23 inhibitor.
If the answer at the first decision point in the algorithm is a “no,” meaning they do not have a TNF-alpha to interferon-gamma CD4+ ratio of 2 or higher, they are evaluated for percentage of CD4+ T cells expressing IL-22 or IL-17. Is it greater than or equal to 2%? If the answer is “no,” they are candidates for an IL-12/23 inhibitor.
If “yes,” they are evaluated for percentage of IL-22 to IL-17 CD4+. If the IL-22 CD4+ percentage is lower than the IL-17 CD4+ percentage, meaning a “yes” to this decision point, they are directed to an IL-17 inhibitor. If the answer at this decision point is “no,” they are directed to an IL-12/23 inhibitor.
Prior to enrollment in this proof-of-concept study, 10 of the bDMARD patients were scheduled to receive an anti-TNF drug and 1 was scheduled to receive an IL-12/23 inhibitor. On the basis of this algorithm, only 5 patients were directed to an anti-TNF drug. Of the remaining, 5 were directed to an IL-17 inhibitor, and 1 was directed to an IL-12/23 inhibitor.
All 19 participants in the proof-of-concept study had peripheral arthritis; their median age was 45 years. Approximately 90% had skin lesions. Axial involvement was present in only one patient. Based on these and other characteristics and the median ratios of the cytokines measured, Dr. Ayan called this a representative population.
Based on the feasibility of this method for subtyping patients by T-cell behavior to guide drug selection, Dr. Ayan anticipates pursuing the additional steps that would show the algorithm makes a difference to patient care, including such adjunctive benefits as more cost-effective treatment selection.
“We aim to develop a treatment decision algorithm that can be implemented in daily practice,” Dr. Ayan said.
Is peripheral blood sampling adequate?
In addition to saying that the algorithm will need to prove that it alters outcomes, Samuel Tzen-yue Hwang, MD, PhD, professor and chair of the department of dermatology at the University of California, Davis, Sacramento, pointed out some potential practical issues.
“Flow cytometry is not typically available as a rapid throughput, and the cost is high,” he said. Moreover, he remains skeptical about performing this algorithm on the basis of peripheral blood samples.
“It is debatable that looking at peripheral cells would provide adequate information about what is taking place at sites of inflammation,” he said. Although it would “be fantastic” to develop an algorithm that required only a peripheral blood sample, he pointed out that “only a fraction of these cells is relevant” to disease activity.
Aspirating fluid from an involved joint “might be more useful,” but it is more work, he added. Yet, Dr. Hwang acknowledged that this approach is intriguing. He agreed that there is considerable heterogeneity among patients with PsA in their response to specific biologics, and a method to better direct patients to the treatment most likely to elicit a response is needed.
Dr. Ayan and Dr. Hwang reported no potential conflicts of interest.
Biologic selection is cytokine based
Biologic selection is cytokine based
NEW YORK – An algorithm in development for psoriatic arthritis (PsA) is showing promise for directing patients to the biologic with the greatest likelihood of producing disease control, according to a proof-of-concept study presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
“Our technique involves a more precise functional assay showing exact T-cell behavior, compared to the previous assessments that only analyzed cellular phenotypes,” reported Gizem Ayan, MD, a fellow in rheumatology at Hacettepe University Faculty of Medicine, Ankara, Turkey.
The concept of precision medicine in PsA as well as other autoimmune diseases is not new. Phenotypes and biomarkers have already shown potential for guiding treatment, according to Dr. Ayan, but she said none are yet guideline recommended or proven to improve patient outcomes.
The principle of the new algorithm that she and her coinvestigators are pursing is based on immunophenotype analysis conducted with a flow-cytometric cytokine secretion assay (FCCSA). In the protocol, monocytes obtained from peripheral blood undergo activation before an FCCSA to distinguish patients by their T-cell behavior.
The treatment decision tree is based on median ratios of tumor necrosis factor (TNF)-alpha, interleukin (IL)–22, IL-17, and interferon-gamma expression among CD4+ and CD8+ cells. Based on a yes-or-no response to specific immune patterns, the patient is funneled to a biologic that inhibits a dominant cytokine.
The proof-of-concept study, which enrolled 8 patients with PsA who were naive to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 11 patients with PsA who were naive to biologic DMARDs (bDMARDs), was designed to demonstrate feasibility. It did not test clinical benefit, but it did show that immunophenotyping with this methodology can be performed efficiently.
“From the time a blood sample is obtained, the method provided results within 24 hours,” according to Dr. Ayan, who is now planning a randomized trial to test the ability of the algorithm to improve clinical outcomes.
In the decision tree, there are five yes-no pathways to a treatment choice. The first step of the algorithm is to test the ratio of TNF-alpha to interferon-gamma CD4+ T cells. A “yes’ response is produced if the ratio is greater than or equal to 2. These patients are then evaluated for the ratio of TNF-alpha to interferon-gamma CD8+ T cells. A yes response is produced if the ratio is greater than or equal to 0.5. If yes, they are candidates for a TNF-alpha inhibitor. If no, they are directed to an IL-12/23 inhibitor.
If the answer at the first decision point in the algorithm is a “no,” meaning they do not have a TNF-alpha to interferon-gamma CD4+ ratio of 2 or higher, they are evaluated for percentage of CD4+ T cells expressing IL-22 or IL-17. Is it greater than or equal to 2%? If the answer is “no,” they are candidates for an IL-12/23 inhibitor.
If “yes,” they are evaluated for percentage of IL-22 to IL-17 CD4+. If the IL-22 CD4+ percentage is lower than the IL-17 CD4+ percentage, meaning a “yes” to this decision point, they are directed to an IL-17 inhibitor. If the answer at this decision point is “no,” they are directed to an IL-12/23 inhibitor.
Prior to enrollment in this proof-of-concept study, 10 of the bDMARD patients were scheduled to receive an anti-TNF drug and 1 was scheduled to receive an IL-12/23 inhibitor. On the basis of this algorithm, only 5 patients were directed to an anti-TNF drug. Of the remaining, 5 were directed to an IL-17 inhibitor, and 1 was directed to an IL-12/23 inhibitor.
All 19 participants in the proof-of-concept study had peripheral arthritis; their median age was 45 years. Approximately 90% had skin lesions. Axial involvement was present in only one patient. Based on these and other characteristics and the median ratios of the cytokines measured, Dr. Ayan called this a representative population.
Based on the feasibility of this method for subtyping patients by T-cell behavior to guide drug selection, Dr. Ayan anticipates pursuing the additional steps that would show the algorithm makes a difference to patient care, including such adjunctive benefits as more cost-effective treatment selection.
“We aim to develop a treatment decision algorithm that can be implemented in daily practice,” Dr. Ayan said.
Is peripheral blood sampling adequate?
In addition to saying that the algorithm will need to prove that it alters outcomes, Samuel Tzen-yue Hwang, MD, PhD, professor and chair of the department of dermatology at the University of California, Davis, Sacramento, pointed out some potential practical issues.
“Flow cytometry is not typically available as a rapid throughput, and the cost is high,” he said. Moreover, he remains skeptical about performing this algorithm on the basis of peripheral blood samples.
“It is debatable that looking at peripheral cells would provide adequate information about what is taking place at sites of inflammation,” he said. Although it would “be fantastic” to develop an algorithm that required only a peripheral blood sample, he pointed out that “only a fraction of these cells is relevant” to disease activity.
Aspirating fluid from an involved joint “might be more useful,” but it is more work, he added. Yet, Dr. Hwang acknowledged that this approach is intriguing. He agreed that there is considerable heterogeneity among patients with PsA in their response to specific biologics, and a method to better direct patients to the treatment most likely to elicit a response is needed.
Dr. Ayan and Dr. Hwang reported no potential conflicts of interest.
NEW YORK – An algorithm in development for psoriatic arthritis (PsA) is showing promise for directing patients to the biologic with the greatest likelihood of producing disease control, according to a proof-of-concept study presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
“Our technique involves a more precise functional assay showing exact T-cell behavior, compared to the previous assessments that only analyzed cellular phenotypes,” reported Gizem Ayan, MD, a fellow in rheumatology at Hacettepe University Faculty of Medicine, Ankara, Turkey.
The concept of precision medicine in PsA as well as other autoimmune diseases is not new. Phenotypes and biomarkers have already shown potential for guiding treatment, according to Dr. Ayan, but she said none are yet guideline recommended or proven to improve patient outcomes.
The principle of the new algorithm that she and her coinvestigators are pursing is based on immunophenotype analysis conducted with a flow-cytometric cytokine secretion assay (FCCSA). In the protocol, monocytes obtained from peripheral blood undergo activation before an FCCSA to distinguish patients by their T-cell behavior.
The treatment decision tree is based on median ratios of tumor necrosis factor (TNF)-alpha, interleukin (IL)–22, IL-17, and interferon-gamma expression among CD4+ and CD8+ cells. Based on a yes-or-no response to specific immune patterns, the patient is funneled to a biologic that inhibits a dominant cytokine.
The proof-of-concept study, which enrolled 8 patients with PsA who were naive to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 11 patients with PsA who were naive to biologic DMARDs (bDMARDs), was designed to demonstrate feasibility. It did not test clinical benefit, but it did show that immunophenotyping with this methodology can be performed efficiently.
“From the time a blood sample is obtained, the method provided results within 24 hours,” according to Dr. Ayan, who is now planning a randomized trial to test the ability of the algorithm to improve clinical outcomes.
In the decision tree, there are five yes-no pathways to a treatment choice. The first step of the algorithm is to test the ratio of TNF-alpha to interferon-gamma CD4+ T cells. A “yes’ response is produced if the ratio is greater than or equal to 2. These patients are then evaluated for the ratio of TNF-alpha to interferon-gamma CD8+ T cells. A yes response is produced if the ratio is greater than or equal to 0.5. If yes, they are candidates for a TNF-alpha inhibitor. If no, they are directed to an IL-12/23 inhibitor.
If the answer at the first decision point in the algorithm is a “no,” meaning they do not have a TNF-alpha to interferon-gamma CD4+ ratio of 2 or higher, they are evaluated for percentage of CD4+ T cells expressing IL-22 or IL-17. Is it greater than or equal to 2%? If the answer is “no,” they are candidates for an IL-12/23 inhibitor.
If “yes,” they are evaluated for percentage of IL-22 to IL-17 CD4+. If the IL-22 CD4+ percentage is lower than the IL-17 CD4+ percentage, meaning a “yes” to this decision point, they are directed to an IL-17 inhibitor. If the answer at this decision point is “no,” they are directed to an IL-12/23 inhibitor.
Prior to enrollment in this proof-of-concept study, 10 of the bDMARD patients were scheduled to receive an anti-TNF drug and 1 was scheduled to receive an IL-12/23 inhibitor. On the basis of this algorithm, only 5 patients were directed to an anti-TNF drug. Of the remaining, 5 were directed to an IL-17 inhibitor, and 1 was directed to an IL-12/23 inhibitor.
All 19 participants in the proof-of-concept study had peripheral arthritis; their median age was 45 years. Approximately 90% had skin lesions. Axial involvement was present in only one patient. Based on these and other characteristics and the median ratios of the cytokines measured, Dr. Ayan called this a representative population.
Based on the feasibility of this method for subtyping patients by T-cell behavior to guide drug selection, Dr. Ayan anticipates pursuing the additional steps that would show the algorithm makes a difference to patient care, including such adjunctive benefits as more cost-effective treatment selection.
“We aim to develop a treatment decision algorithm that can be implemented in daily practice,” Dr. Ayan said.
Is peripheral blood sampling adequate?
In addition to saying that the algorithm will need to prove that it alters outcomes, Samuel Tzen-yue Hwang, MD, PhD, professor and chair of the department of dermatology at the University of California, Davis, Sacramento, pointed out some potential practical issues.
“Flow cytometry is not typically available as a rapid throughput, and the cost is high,” he said. Moreover, he remains skeptical about performing this algorithm on the basis of peripheral blood samples.
“It is debatable that looking at peripheral cells would provide adequate information about what is taking place at sites of inflammation,” he said. Although it would “be fantastic” to develop an algorithm that required only a peripheral blood sample, he pointed out that “only a fraction of these cells is relevant” to disease activity.
Aspirating fluid from an involved joint “might be more useful,” but it is more work, he added. Yet, Dr. Hwang acknowledged that this approach is intriguing. He agreed that there is considerable heterogeneity among patients with PsA in their response to specific biologics, and a method to better direct patients to the treatment most likely to elicit a response is needed.
Dr. Ayan and Dr. Hwang reported no potential conflicts of interest.
T-cell behavior
T-cell behavior
AT GRAPPA 2022