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Lipid signature may flag schizophrenia
Although such a test remains a long way off, investigators said, the identification of the unique lipid signature is a critical first step. However, one expert noted that the lipid signature not accurately differentiating patients with schizophrenia from those with bipolar disorder (BD) and major depressive disorder (MDD) limits the findings’ applicability.
The profile includes 77 lipids identified from a large analysis of many different classes of lipid species. Lipids such as cholesterol and triglycerides made up only a small fraction of the classes assessed.
The investigators noted that some of the lipids in the profile associated with schizophrenia are involved in determining cell membrane structure and fluidity or cell-to-cell messaging, which could be important to synaptic function.
“These 77 lipids jointly constitute a lipidomic profile that discriminated between individuals with schizophrenia and individuals without a mental health diagnosis with very high accuracy,” investigator Eva C. Schulte, MD, PhD, of the Institute of Psychiatric Phenomics and Genomics (IPPG) and the department of psychiatry and psychotherapy at University Hospital of Ludwig-Maximilians-University, Munich, told this news organization.
“Of note, we did not see large profile differences between patients with a first psychotic episode who had only been treated for a few days and individuals on long-term antipsychotic therapy,” Dr. Schulte said.
The findings were published online in JAMA Psychiatry.
Detailed analysis
Lipid profiles in patients with psychiatric diagnoses have been reported previously, but those studies were small and did not identify a reliable signature independent of demographic and environmental factors.
For the current study, researchers analyzed blood plasma lipid levels from 980 individuals with severe psychiatric illness and 572 people without mental illness from three cohorts in China, Germany, Austria, and Russia.
The study sample included patients with schizophrenia (n = 478), BD (n = 184), and MDD (n = 256), as well as 104 patients with a first psychotic episode who had no long-term psychopharmacology use.
Results showed 77 lipids in 14 classes were significantly altered between participants with schizophrenia and the healthy control in all three cohorts.
The most prominent alterations at the lipid class level included increases in ceramide, triacylglyceride, and phosphatidylcholine and decreases in acylcarnitine and phosphatidylcholine plasmalogen (P < .05 for each cohort).
Schizophrenia-associated lipid differences were similar between patients with high and low symptom severity (P < .001), suggesting that the lipid alterations might represent a trait of the psychiatric disorder.
No medication effect
Most patients in the study received long-term antipsychotic medication, which has been shown previously to affect some plasma lipid compounds.
So, to assess a possible effect of medication, the investigators evaluated 13 patients with schizophrenia who were not medicated for at least 6 months prior to blood sample collection and the cohort of patients with a first psychotic episode who had been medicated for less than 1 week.
Comparison of the lipid intensity differences between the healthy controls group and either participants receiving medication or those who were not medicated revealed highly correlated alterations in both patient groups (P < .001).
“Taken together, these results indicate that the identified schizophrenia-associated alterations cannot be attributed to medication effects,” the investigators wrote.
Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were similar to those of schizophrenia but not identical.
Researchers isolated 97 lipids altered in the MDD cohorts and 47 in the BPD cohorts – with 30 and 28, respectively, overlapping with the schizophrenia-associated features and seven of the lipids found among all three disorders.
Although this was significantly more than expected by chance (P < .001), it was not strong enough to demonstrate a clear association, the investigators wrote.
“The profiles were very successful at differentiating individuals with severe mental health conditions from individuals without a diagnosed mental health condition, but much less so at differentiating between the different diagnostic entities,” coinvestigator Thomas G. Schulze, MD, director of IPPG, said in an interview.
“An important caveat, however, is that the available sample sizes for bipolar disorder and major depressive disorder were smaller than those for schizophrenia, which makes a direct comparison between these difficult,” added Dr. Schulze, clinical professor in psychiatry and behavioral sciences at State University of New York, Syracuse.
More work remains
Although the study is thought to be the largest to date to examine lipid profiles associated with serious psychiatric illness, much work remains, Dr. Schulze noted.
“At this time, based on these first results, no clinical diagnostic test can be derived from these results,” he said.
He added that the development of reliable biomarkers based on lipidomic profiles would require large prospective randomized trials, complemented by observational studies assessing full lipidomic profiles across the lifespan.
Researchers also need to better understand the exact mechanism by which lipid alterations are associated with schizophrenia and other illnesses.
Physiologically, the investigated lipids have many additional functions, such as determining cell membrane structure and fluidity or cell-to-cell messaging.
Dr. Schulte noted that several lipid species may be involved in determining mechanisms important to synaptic function, such as cell membrane fluidity and vesicle release.
“As is commonly known, alterations in synaptic function underly many severe psychiatric disorders,” she said. “Changes in lipid species could theoretically be related to these synaptic alterations.”
A better marker needed
In a comment, Stephen Strakowski, MD, professor and vice chair of research in the department of psychiatry, Indiana University, Indianapolis and Evansville, noted that while the findings are interesting, they don’t really offer the kind of information clinicians who treat patients with serious mental illness need most.
“Do we need a marker to tell us if someone’s got a major mental illness compared to a healthy person?” asked Dr. Strakowski, who was not part of the study. “The answer to that is no. We already know how to do that.”
A truly useful marker would help clinicians differentiate between schizophrenia, bipolar disorder, major depression, or another serious mental illness, he said.
“That’s the marker that would be most helpful,” he added. “This can’t address that, but perhaps it could be a step to start designing a test for that.”
Dr. Strakowksi noted that the findings do not clarify whether the lipid profile found in patients with schizophrenia predates diagnosis or whether it is a result of the mental illness, an unrelated illness, or another factor that could be critical in treating patients.
However, he was quick to point out the limitations don’t diminish the importance of the study.
“It’s a large dataset that’s cross-national, cross-diagnostic that says there appears to be a signal here that there’s something about lipid profiles that may be independent of treatment that could be worth understanding,” Dr. Strakowksi said.
“It allows us to think about developing different models based on lipid profiles, and that’s important,” he added.
The study was funded by the National Key R&D Program of China, National One Thousand Foreign Experts Plan, Moscow Center for Innovative Technologies in Healthcare, European Union’s Horizon 2020 Research and Innovation Programme, NARSAD Young Investigator Grant, German Research Foundation, German Ministry for Education and Research, the Dr. Lisa Oehler Foundation, and the Munich Clinician Scientist Program. Dr. Schulze and Dr. Schulte reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although such a test remains a long way off, investigators said, the identification of the unique lipid signature is a critical first step. However, one expert noted that the lipid signature not accurately differentiating patients with schizophrenia from those with bipolar disorder (BD) and major depressive disorder (MDD) limits the findings’ applicability.
The profile includes 77 lipids identified from a large analysis of many different classes of lipid species. Lipids such as cholesterol and triglycerides made up only a small fraction of the classes assessed.
The investigators noted that some of the lipids in the profile associated with schizophrenia are involved in determining cell membrane structure and fluidity or cell-to-cell messaging, which could be important to synaptic function.
“These 77 lipids jointly constitute a lipidomic profile that discriminated between individuals with schizophrenia and individuals without a mental health diagnosis with very high accuracy,” investigator Eva C. Schulte, MD, PhD, of the Institute of Psychiatric Phenomics and Genomics (IPPG) and the department of psychiatry and psychotherapy at University Hospital of Ludwig-Maximilians-University, Munich, told this news organization.
“Of note, we did not see large profile differences between patients with a first psychotic episode who had only been treated for a few days and individuals on long-term antipsychotic therapy,” Dr. Schulte said.
The findings were published online in JAMA Psychiatry.
Detailed analysis
Lipid profiles in patients with psychiatric diagnoses have been reported previously, but those studies were small and did not identify a reliable signature independent of demographic and environmental factors.
For the current study, researchers analyzed blood plasma lipid levels from 980 individuals with severe psychiatric illness and 572 people without mental illness from three cohorts in China, Germany, Austria, and Russia.
The study sample included patients with schizophrenia (n = 478), BD (n = 184), and MDD (n = 256), as well as 104 patients with a first psychotic episode who had no long-term psychopharmacology use.
Results showed 77 lipids in 14 classes were significantly altered between participants with schizophrenia and the healthy control in all three cohorts.
The most prominent alterations at the lipid class level included increases in ceramide, triacylglyceride, and phosphatidylcholine and decreases in acylcarnitine and phosphatidylcholine plasmalogen (P < .05 for each cohort).
Schizophrenia-associated lipid differences were similar between patients with high and low symptom severity (P < .001), suggesting that the lipid alterations might represent a trait of the psychiatric disorder.
No medication effect
Most patients in the study received long-term antipsychotic medication, which has been shown previously to affect some plasma lipid compounds.
So, to assess a possible effect of medication, the investigators evaluated 13 patients with schizophrenia who were not medicated for at least 6 months prior to blood sample collection and the cohort of patients with a first psychotic episode who had been medicated for less than 1 week.
Comparison of the lipid intensity differences between the healthy controls group and either participants receiving medication or those who were not medicated revealed highly correlated alterations in both patient groups (P < .001).
“Taken together, these results indicate that the identified schizophrenia-associated alterations cannot be attributed to medication effects,” the investigators wrote.
Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were similar to those of schizophrenia but not identical.
Researchers isolated 97 lipids altered in the MDD cohorts and 47 in the BPD cohorts – with 30 and 28, respectively, overlapping with the schizophrenia-associated features and seven of the lipids found among all three disorders.
Although this was significantly more than expected by chance (P < .001), it was not strong enough to demonstrate a clear association, the investigators wrote.
“The profiles were very successful at differentiating individuals with severe mental health conditions from individuals without a diagnosed mental health condition, but much less so at differentiating between the different diagnostic entities,” coinvestigator Thomas G. Schulze, MD, director of IPPG, said in an interview.
“An important caveat, however, is that the available sample sizes for bipolar disorder and major depressive disorder were smaller than those for schizophrenia, which makes a direct comparison between these difficult,” added Dr. Schulze, clinical professor in psychiatry and behavioral sciences at State University of New York, Syracuse.
More work remains
Although the study is thought to be the largest to date to examine lipid profiles associated with serious psychiatric illness, much work remains, Dr. Schulze noted.
“At this time, based on these first results, no clinical diagnostic test can be derived from these results,” he said.
He added that the development of reliable biomarkers based on lipidomic profiles would require large prospective randomized trials, complemented by observational studies assessing full lipidomic profiles across the lifespan.
Researchers also need to better understand the exact mechanism by which lipid alterations are associated with schizophrenia and other illnesses.
Physiologically, the investigated lipids have many additional functions, such as determining cell membrane structure and fluidity or cell-to-cell messaging.
Dr. Schulte noted that several lipid species may be involved in determining mechanisms important to synaptic function, such as cell membrane fluidity and vesicle release.
“As is commonly known, alterations in synaptic function underly many severe psychiatric disorders,” she said. “Changes in lipid species could theoretically be related to these synaptic alterations.”
A better marker needed
In a comment, Stephen Strakowski, MD, professor and vice chair of research in the department of psychiatry, Indiana University, Indianapolis and Evansville, noted that while the findings are interesting, they don’t really offer the kind of information clinicians who treat patients with serious mental illness need most.
“Do we need a marker to tell us if someone’s got a major mental illness compared to a healthy person?” asked Dr. Strakowski, who was not part of the study. “The answer to that is no. We already know how to do that.”
A truly useful marker would help clinicians differentiate between schizophrenia, bipolar disorder, major depression, or another serious mental illness, he said.
“That’s the marker that would be most helpful,” he added. “This can’t address that, but perhaps it could be a step to start designing a test for that.”
Dr. Strakowksi noted that the findings do not clarify whether the lipid profile found in patients with schizophrenia predates diagnosis or whether it is a result of the mental illness, an unrelated illness, or another factor that could be critical in treating patients.
However, he was quick to point out the limitations don’t diminish the importance of the study.
“It’s a large dataset that’s cross-national, cross-diagnostic that says there appears to be a signal here that there’s something about lipid profiles that may be independent of treatment that could be worth understanding,” Dr. Strakowksi said.
“It allows us to think about developing different models based on lipid profiles, and that’s important,” he added.
The study was funded by the National Key R&D Program of China, National One Thousand Foreign Experts Plan, Moscow Center for Innovative Technologies in Healthcare, European Union’s Horizon 2020 Research and Innovation Programme, NARSAD Young Investigator Grant, German Research Foundation, German Ministry for Education and Research, the Dr. Lisa Oehler Foundation, and the Munich Clinician Scientist Program. Dr. Schulze and Dr. Schulte reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although such a test remains a long way off, investigators said, the identification of the unique lipid signature is a critical first step. However, one expert noted that the lipid signature not accurately differentiating patients with schizophrenia from those with bipolar disorder (BD) and major depressive disorder (MDD) limits the findings’ applicability.
The profile includes 77 lipids identified from a large analysis of many different classes of lipid species. Lipids such as cholesterol and triglycerides made up only a small fraction of the classes assessed.
The investigators noted that some of the lipids in the profile associated with schizophrenia are involved in determining cell membrane structure and fluidity or cell-to-cell messaging, which could be important to synaptic function.
“These 77 lipids jointly constitute a lipidomic profile that discriminated between individuals with schizophrenia and individuals without a mental health diagnosis with very high accuracy,” investigator Eva C. Schulte, MD, PhD, of the Institute of Psychiatric Phenomics and Genomics (IPPG) and the department of psychiatry and psychotherapy at University Hospital of Ludwig-Maximilians-University, Munich, told this news organization.
“Of note, we did not see large profile differences between patients with a first psychotic episode who had only been treated for a few days and individuals on long-term antipsychotic therapy,” Dr. Schulte said.
The findings were published online in JAMA Psychiatry.
Detailed analysis
Lipid profiles in patients with psychiatric diagnoses have been reported previously, but those studies were small and did not identify a reliable signature independent of demographic and environmental factors.
For the current study, researchers analyzed blood plasma lipid levels from 980 individuals with severe psychiatric illness and 572 people without mental illness from three cohorts in China, Germany, Austria, and Russia.
The study sample included patients with schizophrenia (n = 478), BD (n = 184), and MDD (n = 256), as well as 104 patients with a first psychotic episode who had no long-term psychopharmacology use.
Results showed 77 lipids in 14 classes were significantly altered between participants with schizophrenia and the healthy control in all three cohorts.
The most prominent alterations at the lipid class level included increases in ceramide, triacylglyceride, and phosphatidylcholine and decreases in acylcarnitine and phosphatidylcholine plasmalogen (P < .05 for each cohort).
Schizophrenia-associated lipid differences were similar between patients with high and low symptom severity (P < .001), suggesting that the lipid alterations might represent a trait of the psychiatric disorder.
No medication effect
Most patients in the study received long-term antipsychotic medication, which has been shown previously to affect some plasma lipid compounds.
So, to assess a possible effect of medication, the investigators evaluated 13 patients with schizophrenia who were not medicated for at least 6 months prior to blood sample collection and the cohort of patients with a first psychotic episode who had been medicated for less than 1 week.
Comparison of the lipid intensity differences between the healthy controls group and either participants receiving medication or those who were not medicated revealed highly correlated alterations in both patient groups (P < .001).
“Taken together, these results indicate that the identified schizophrenia-associated alterations cannot be attributed to medication effects,” the investigators wrote.
Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were similar to those of schizophrenia but not identical.
Researchers isolated 97 lipids altered in the MDD cohorts and 47 in the BPD cohorts – with 30 and 28, respectively, overlapping with the schizophrenia-associated features and seven of the lipids found among all three disorders.
Although this was significantly more than expected by chance (P < .001), it was not strong enough to demonstrate a clear association, the investigators wrote.
“The profiles were very successful at differentiating individuals with severe mental health conditions from individuals without a diagnosed mental health condition, but much less so at differentiating between the different diagnostic entities,” coinvestigator Thomas G. Schulze, MD, director of IPPG, said in an interview.
“An important caveat, however, is that the available sample sizes for bipolar disorder and major depressive disorder were smaller than those for schizophrenia, which makes a direct comparison between these difficult,” added Dr. Schulze, clinical professor in psychiatry and behavioral sciences at State University of New York, Syracuse.
More work remains
Although the study is thought to be the largest to date to examine lipid profiles associated with serious psychiatric illness, much work remains, Dr. Schulze noted.
“At this time, based on these first results, no clinical diagnostic test can be derived from these results,” he said.
He added that the development of reliable biomarkers based on lipidomic profiles would require large prospective randomized trials, complemented by observational studies assessing full lipidomic profiles across the lifespan.
Researchers also need to better understand the exact mechanism by which lipid alterations are associated with schizophrenia and other illnesses.
Physiologically, the investigated lipids have many additional functions, such as determining cell membrane structure and fluidity or cell-to-cell messaging.
Dr. Schulte noted that several lipid species may be involved in determining mechanisms important to synaptic function, such as cell membrane fluidity and vesicle release.
“As is commonly known, alterations in synaptic function underly many severe psychiatric disorders,” she said. “Changes in lipid species could theoretically be related to these synaptic alterations.”
A better marker needed
In a comment, Stephen Strakowski, MD, professor and vice chair of research in the department of psychiatry, Indiana University, Indianapolis and Evansville, noted that while the findings are interesting, they don’t really offer the kind of information clinicians who treat patients with serious mental illness need most.
“Do we need a marker to tell us if someone’s got a major mental illness compared to a healthy person?” asked Dr. Strakowski, who was not part of the study. “The answer to that is no. We already know how to do that.”
A truly useful marker would help clinicians differentiate between schizophrenia, bipolar disorder, major depression, or another serious mental illness, he said.
“That’s the marker that would be most helpful,” he added. “This can’t address that, but perhaps it could be a step to start designing a test for that.”
Dr. Strakowksi noted that the findings do not clarify whether the lipid profile found in patients with schizophrenia predates diagnosis or whether it is a result of the mental illness, an unrelated illness, or another factor that could be critical in treating patients.
However, he was quick to point out the limitations don’t diminish the importance of the study.
“It’s a large dataset that’s cross-national, cross-diagnostic that says there appears to be a signal here that there’s something about lipid profiles that may be independent of treatment that could be worth understanding,” Dr. Strakowksi said.
“It allows us to think about developing different models based on lipid profiles, and that’s important,” he added.
The study was funded by the National Key R&D Program of China, National One Thousand Foreign Experts Plan, Moscow Center for Innovative Technologies in Healthcare, European Union’s Horizon 2020 Research and Innovation Programme, NARSAD Young Investigator Grant, German Research Foundation, German Ministry for Education and Research, the Dr. Lisa Oehler Foundation, and the Munich Clinician Scientist Program. Dr. Schulze and Dr. Schulte reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Maintenance therapies boost MM survival rates
These results, published in The Lancet Oncology, are not yet practice-changing, but they add to a growing body of evidence supporting this approach.
“Bearing in mind that ATLAS trial data come from unplanned interim analysis, we found that the benefit of combination therapy (KRd) is clearly seen, especially for standard risk patients. We think that, since there are no vast differences in toxicities, there is quite convincing data for considering KRd maintenance for the post autologous stem cell transplantation treatment of MM patients,” ATLAS study coauthor Andrzej Jakubowiak, MD, professor of medicine at the University of Chicago, said in an interview.
Among patients receiving KRd (n = 93), median PFS was 59 months (95% confidence interval) compared with 41 months in the R group (hazard ratio, 0.51, P = .012). These results come from data collected between 2016 and 2020, from 12 academic and clinical centers in the United States and Poland. The cohort included 180 adults randomly assigned to each study arm, (47% were female, median age 59 years) The most common adverse events were neutropenia 48% vs. 60%, thrombocytopenia 13% vs. 7%, and lower respiratory tract infections 8% vs. 1% in the KRd and R groups, respectively. Serious adverse events were reported in 30% of patients in the KRd arm (including one death due to severe pneumonia) and 22% in the R group.
“As expected, there is a slightly higher toxicity in the KRd arm but mostly low-grade events occurred. We believe in KRd maintenance because it provides a longer remission for a relatively small price. The longer a patient is in remission, the better chance that, if relapse does occur, there will be more therapeutic options available to return to remission,” said Dr. Jakubowiak.
Although all patients in the trial received stem cell therapy, the induction therapies were varied.
“We designed the study similarly to the CALGB maintenance trial, one of the key phase 3 trials leading to the approval of lenalidomide as post transplantation maintenance. With so many changes currently occurring MM therapies, having a fixed induction can be its own limitation. Importantly, with our study design we found that all comers may benefit from KRd maintenance,” he said.
It is important to note that KRd treatment occurred for 36 cycles unless a patient withdrew, died, or achieved minimal residual disease (MRD) status.
“Per study design, the duration of KRd treatment was shortened to eight cycles for patients without high-risk cytogenetics who achieved MRD-negativity after cycle six. For these patients, treatment was converted from KRd to R maintenance as of cycle nine. Despite treatment deescalation, this subset of patients (44% of all KRd patients) contributed strongly to KRd PFS. While this approach will need to be validated in a randomized setting, the results provide a proof of concept that if you achieve MRD-negative status and have standard risk cytogenetics, you don’t have to go on a long KRd treatment,” said Dr. Jakubowiak.
Urvi Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, noted the importance of the study as “the first randomized phase-3 trial suggesting progression free survival superiority of an alternative maintenance therapy to lenalidomide alone.”
Dr. Shah did have concerns about the applicability of the study, especially regarding the use of varied induction regimens, saying, “Only 11%-13% of patients in this study got lenalidomide during induction and 4%-6% got carfilzomib induction. Therefore, most patients were getting new drugs during maintenance different from their induction agents, which has the downside of leaving fewer options for patients when they relapse.”
Asked about these concerns, Dr. Jakubowiak responded, “Our team’s perspective is to ‘buy’ the longest remission possible using the most effective available treatment strategy. If we do this, there is a good chance that when the patient relapses, we will have availability of new drugs.”
He added the caveat: “There’s a small proportion of patients who will be progressing while on treatment and will be potentially more challenging to treat if already given KRd. It has been proposed that KRd maintenance might be primarily considered for patients with high-risk cytogenetics. However, at this interim analysis, there were not enough events in high-risk patients to comment on KRd’s usefulness as a maintenance therapy in this population.”
The KRd arm of the ATLAS trial had a high dropout-rate for reasons other than toxicity and death, but “because consent for collecting data was discontinued, we can’t really dig deeper into explaining why they dropped out, but half of the patients who discontinued in the KRd arm did so after already completing KRd treatment and were already on R maintenance. Once taking this into consideration, the dropout rates in both arms are similar, and the data does not appear skewed,” said Dr. Jakubowiak.
In conclusion, Dr. Jakubowiak noted that the phase-2 FORTE trial, also published recently in The Lancet Oncology, provides supportive data for maintenance therapy with KR versus K.
“It is quite important that the results of both trials be presented to public so that people know that KR or KRd could be reasonably considered for posttransplant maintenance,” he said.
Dr. Shah opined that as yet, the results of neither study were practice changing for maintenance therapy in the United States. She said she would consider using KR maintenance for select patients with high-risk myeloma who received these drugs as induction therapy and where there was concern about early progression, given that this aggressive treatment allows for a longer time in remission.
Dr. Shah noted that in these trials, overall survival data on dual maintenance is still being awaited, and that those results would be important when considering whether to switch patients to a more expensive, toxic, and involved therapy that required regular infusion visits for maintenance.
What Dr. Shah found the most groundbreaking and applicable aspect of the study was that “in the ATLAS trial, they’re adapting treatments to disease response, and if patients achieve MRD negativity, which we know is the best kind of response, therapy was deescalated to lenalidomide single agent. I think this is something that we will see more of in newer study designs and this will help individualize patient treatments to their response.”
Dr. Jakubowiak disclosed consulting fees and honoraria for lectures and presentations from AbbVie, Amgen, Celgene (Bristol Myers Squibb), Gracell, GlaxoSmithKline, Janssen, and Sanofi-Aventis. Dr. Shah disclosed ties with Sanofi, Bristol Myers Squibb and Janssen.
These results, published in The Lancet Oncology, are not yet practice-changing, but they add to a growing body of evidence supporting this approach.
“Bearing in mind that ATLAS trial data come from unplanned interim analysis, we found that the benefit of combination therapy (KRd) is clearly seen, especially for standard risk patients. We think that, since there are no vast differences in toxicities, there is quite convincing data for considering KRd maintenance for the post autologous stem cell transplantation treatment of MM patients,” ATLAS study coauthor Andrzej Jakubowiak, MD, professor of medicine at the University of Chicago, said in an interview.
Among patients receiving KRd (n = 93), median PFS was 59 months (95% confidence interval) compared with 41 months in the R group (hazard ratio, 0.51, P = .012). These results come from data collected between 2016 and 2020, from 12 academic and clinical centers in the United States and Poland. The cohort included 180 adults randomly assigned to each study arm, (47% were female, median age 59 years) The most common adverse events were neutropenia 48% vs. 60%, thrombocytopenia 13% vs. 7%, and lower respiratory tract infections 8% vs. 1% in the KRd and R groups, respectively. Serious adverse events were reported in 30% of patients in the KRd arm (including one death due to severe pneumonia) and 22% in the R group.
“As expected, there is a slightly higher toxicity in the KRd arm but mostly low-grade events occurred. We believe in KRd maintenance because it provides a longer remission for a relatively small price. The longer a patient is in remission, the better chance that, if relapse does occur, there will be more therapeutic options available to return to remission,” said Dr. Jakubowiak.
Although all patients in the trial received stem cell therapy, the induction therapies were varied.
“We designed the study similarly to the CALGB maintenance trial, one of the key phase 3 trials leading to the approval of lenalidomide as post transplantation maintenance. With so many changes currently occurring MM therapies, having a fixed induction can be its own limitation. Importantly, with our study design we found that all comers may benefit from KRd maintenance,” he said.
It is important to note that KRd treatment occurred for 36 cycles unless a patient withdrew, died, or achieved minimal residual disease (MRD) status.
“Per study design, the duration of KRd treatment was shortened to eight cycles for patients without high-risk cytogenetics who achieved MRD-negativity after cycle six. For these patients, treatment was converted from KRd to R maintenance as of cycle nine. Despite treatment deescalation, this subset of patients (44% of all KRd patients) contributed strongly to KRd PFS. While this approach will need to be validated in a randomized setting, the results provide a proof of concept that if you achieve MRD-negative status and have standard risk cytogenetics, you don’t have to go on a long KRd treatment,” said Dr. Jakubowiak.
Urvi Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, noted the importance of the study as “the first randomized phase-3 trial suggesting progression free survival superiority of an alternative maintenance therapy to lenalidomide alone.”
Dr. Shah did have concerns about the applicability of the study, especially regarding the use of varied induction regimens, saying, “Only 11%-13% of patients in this study got lenalidomide during induction and 4%-6% got carfilzomib induction. Therefore, most patients were getting new drugs during maintenance different from their induction agents, which has the downside of leaving fewer options for patients when they relapse.”
Asked about these concerns, Dr. Jakubowiak responded, “Our team’s perspective is to ‘buy’ the longest remission possible using the most effective available treatment strategy. If we do this, there is a good chance that when the patient relapses, we will have availability of new drugs.”
He added the caveat: “There’s a small proportion of patients who will be progressing while on treatment and will be potentially more challenging to treat if already given KRd. It has been proposed that KRd maintenance might be primarily considered for patients with high-risk cytogenetics. However, at this interim analysis, there were not enough events in high-risk patients to comment on KRd’s usefulness as a maintenance therapy in this population.”
The KRd arm of the ATLAS trial had a high dropout-rate for reasons other than toxicity and death, but “because consent for collecting data was discontinued, we can’t really dig deeper into explaining why they dropped out, but half of the patients who discontinued in the KRd arm did so after already completing KRd treatment and were already on R maintenance. Once taking this into consideration, the dropout rates in both arms are similar, and the data does not appear skewed,” said Dr. Jakubowiak.
In conclusion, Dr. Jakubowiak noted that the phase-2 FORTE trial, also published recently in The Lancet Oncology, provides supportive data for maintenance therapy with KR versus K.
“It is quite important that the results of both trials be presented to public so that people know that KR or KRd could be reasonably considered for posttransplant maintenance,” he said.
Dr. Shah opined that as yet, the results of neither study were practice changing for maintenance therapy in the United States. She said she would consider using KR maintenance for select patients with high-risk myeloma who received these drugs as induction therapy and where there was concern about early progression, given that this aggressive treatment allows for a longer time in remission.
Dr. Shah noted that in these trials, overall survival data on dual maintenance is still being awaited, and that those results would be important when considering whether to switch patients to a more expensive, toxic, and involved therapy that required regular infusion visits for maintenance.
What Dr. Shah found the most groundbreaking and applicable aspect of the study was that “in the ATLAS trial, they’re adapting treatments to disease response, and if patients achieve MRD negativity, which we know is the best kind of response, therapy was deescalated to lenalidomide single agent. I think this is something that we will see more of in newer study designs and this will help individualize patient treatments to their response.”
Dr. Jakubowiak disclosed consulting fees and honoraria for lectures and presentations from AbbVie, Amgen, Celgene (Bristol Myers Squibb), Gracell, GlaxoSmithKline, Janssen, and Sanofi-Aventis. Dr. Shah disclosed ties with Sanofi, Bristol Myers Squibb and Janssen.
These results, published in The Lancet Oncology, are not yet practice-changing, but they add to a growing body of evidence supporting this approach.
“Bearing in mind that ATLAS trial data come from unplanned interim analysis, we found that the benefit of combination therapy (KRd) is clearly seen, especially for standard risk patients. We think that, since there are no vast differences in toxicities, there is quite convincing data for considering KRd maintenance for the post autologous stem cell transplantation treatment of MM patients,” ATLAS study coauthor Andrzej Jakubowiak, MD, professor of medicine at the University of Chicago, said in an interview.
Among patients receiving KRd (n = 93), median PFS was 59 months (95% confidence interval) compared with 41 months in the R group (hazard ratio, 0.51, P = .012). These results come from data collected between 2016 and 2020, from 12 academic and clinical centers in the United States and Poland. The cohort included 180 adults randomly assigned to each study arm, (47% were female, median age 59 years) The most common adverse events were neutropenia 48% vs. 60%, thrombocytopenia 13% vs. 7%, and lower respiratory tract infections 8% vs. 1% in the KRd and R groups, respectively. Serious adverse events were reported in 30% of patients in the KRd arm (including one death due to severe pneumonia) and 22% in the R group.
“As expected, there is a slightly higher toxicity in the KRd arm but mostly low-grade events occurred. We believe in KRd maintenance because it provides a longer remission for a relatively small price. The longer a patient is in remission, the better chance that, if relapse does occur, there will be more therapeutic options available to return to remission,” said Dr. Jakubowiak.
Although all patients in the trial received stem cell therapy, the induction therapies were varied.
“We designed the study similarly to the CALGB maintenance trial, one of the key phase 3 trials leading to the approval of lenalidomide as post transplantation maintenance. With so many changes currently occurring MM therapies, having a fixed induction can be its own limitation. Importantly, with our study design we found that all comers may benefit from KRd maintenance,” he said.
It is important to note that KRd treatment occurred for 36 cycles unless a patient withdrew, died, or achieved minimal residual disease (MRD) status.
“Per study design, the duration of KRd treatment was shortened to eight cycles for patients without high-risk cytogenetics who achieved MRD-negativity after cycle six. For these patients, treatment was converted from KRd to R maintenance as of cycle nine. Despite treatment deescalation, this subset of patients (44% of all KRd patients) contributed strongly to KRd PFS. While this approach will need to be validated in a randomized setting, the results provide a proof of concept that if you achieve MRD-negative status and have standard risk cytogenetics, you don’t have to go on a long KRd treatment,” said Dr. Jakubowiak.
Urvi Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, noted the importance of the study as “the first randomized phase-3 trial suggesting progression free survival superiority of an alternative maintenance therapy to lenalidomide alone.”
Dr. Shah did have concerns about the applicability of the study, especially regarding the use of varied induction regimens, saying, “Only 11%-13% of patients in this study got lenalidomide during induction and 4%-6% got carfilzomib induction. Therefore, most patients were getting new drugs during maintenance different from their induction agents, which has the downside of leaving fewer options for patients when they relapse.”
Asked about these concerns, Dr. Jakubowiak responded, “Our team’s perspective is to ‘buy’ the longest remission possible using the most effective available treatment strategy. If we do this, there is a good chance that when the patient relapses, we will have availability of new drugs.”
He added the caveat: “There’s a small proportion of patients who will be progressing while on treatment and will be potentially more challenging to treat if already given KRd. It has been proposed that KRd maintenance might be primarily considered for patients with high-risk cytogenetics. However, at this interim analysis, there were not enough events in high-risk patients to comment on KRd’s usefulness as a maintenance therapy in this population.”
The KRd arm of the ATLAS trial had a high dropout-rate for reasons other than toxicity and death, but “because consent for collecting data was discontinued, we can’t really dig deeper into explaining why they dropped out, but half of the patients who discontinued in the KRd arm did so after already completing KRd treatment and were already on R maintenance. Once taking this into consideration, the dropout rates in both arms are similar, and the data does not appear skewed,” said Dr. Jakubowiak.
In conclusion, Dr. Jakubowiak noted that the phase-2 FORTE trial, also published recently in The Lancet Oncology, provides supportive data for maintenance therapy with KR versus K.
“It is quite important that the results of both trials be presented to public so that people know that KR or KRd could be reasonably considered for posttransplant maintenance,” he said.
Dr. Shah opined that as yet, the results of neither study were practice changing for maintenance therapy in the United States. She said she would consider using KR maintenance for select patients with high-risk myeloma who received these drugs as induction therapy and where there was concern about early progression, given that this aggressive treatment allows for a longer time in remission.
Dr. Shah noted that in these trials, overall survival data on dual maintenance is still being awaited, and that those results would be important when considering whether to switch patients to a more expensive, toxic, and involved therapy that required regular infusion visits for maintenance.
What Dr. Shah found the most groundbreaking and applicable aspect of the study was that “in the ATLAS trial, they’re adapting treatments to disease response, and if patients achieve MRD negativity, which we know is the best kind of response, therapy was deescalated to lenalidomide single agent. I think this is something that we will see more of in newer study designs and this will help individualize patient treatments to their response.”
Dr. Jakubowiak disclosed consulting fees and honoraria for lectures and presentations from AbbVie, Amgen, Celgene (Bristol Myers Squibb), Gracell, GlaxoSmithKline, Janssen, and Sanofi-Aventis. Dr. Shah disclosed ties with Sanofi, Bristol Myers Squibb and Janssen.
Autism linked to problems with cardiovascular health
People with autism are more likely to face diabetes, high cholesterol, and heart disease than those without the neurologic condition, according to a study published in JAMA Pediatrics. Researchers also found that children with autism are especially likely to develop diabetes compared with their peers, and are at greater risk of hypertension, too.
While the link between autism and risk for obesity and gastrointestinal ailments is well-established, the new findings suggest that clinicians who care for these patients – particularly children – should focus on cardiometabolic health more broadly.
“Clinicians who are treating kids with autism need to pay more attention to this,” said Chanaka N. Kahathuduwa, MD, PhD, MPhil, of the department of neurology at Texas Tech University Health Sciences Center, in Lubbock, and a coauthor of the new study.
A pediatrician may prescribe an atypical antipsychotic medication such as risperidone to regulate the behavior of an autistic child, Dr. Kahathuduwa said, which may increase their cholesterol levels. Although this or similar drugs may be necessary in some cases, Dr. Kahathuduwa advised that clinicians explore other treatment options first.
Mining data from previously published studies
For the new analysis, Dr. Kahathuduwa and his colleagues pooled the results of 34 previously published studies, which included medical records of more than 276,000 people with autism and close to 8 million people without the condition.
Study participants were an average age of 31 years, and 47% were female. Some studies reported age ranges that enabled the researchers to differentiate between children and adults.
People with autism were 64% more likely to develop type 1 diabetes, 146% more likely to experience type 2 diabetes, and 46% more likely to have heart disease, overall, the study found. Children with autism were almost twice as likely as their peers to develop diabetes (184%) and high blood pressure (154%).
The study found associations, not causation, and does not include detailed data about medication prescribing patterns. While it would be ideal to understand why autism is linked to cardiometabolic risk, to address the link most effectively, Dr. Kahathuduwa said the causes likely are multifactorial. Medication history and genetics each play a role in a way that is hard to untangle. Even so, Dr. Kahathuduwa said he hoped the findings prompt clinicians to reevaluate how they treat their patients with autism.
“This may be an eye opener,” he said.
An editorial accompanying the study noted that people with autism may die up to 30 years earlier than people without autism, in part because of the physical health problems surfaced in the new research. They also are more likely than others to attempt suicide.
Elizabeth M. Weir, PhD, of the Autism Research Centre at the University of Cambridge (England) and author of the editorial, argued that current health delivery models often fail autistic people by not taking their needs into account.
Dr. Weir told this news organization that making adjustments such as dimming the lights for a light-sensitive patient or allowing people with autism to bring an advocate to appointments could build rapport.
“I diagnose autism pretty much every day and I know families get so overwhelmed with all the recommendations that we give,” said Sonia Monteiro, MD, a developmental and behavioral pediatrician at Texas Children’s Hospital in Houston. Still, Dr. Monteiro said clinicians should help parents of children with autism address the potential long-term cardiovascular risks – but to do so by layering in the information rather than merely adding more bullet points to an already long presentation.
“We know this information now, but finding a way to share that with families without overwhelming them even more, I think is challenging,” Dr. Monteiro said. “But it’s not something we can ignore.”
Dr. Kahathuduwa, Dr. Weir, and Dr. Monteiro report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People with autism are more likely to face diabetes, high cholesterol, and heart disease than those without the neurologic condition, according to a study published in JAMA Pediatrics. Researchers also found that children with autism are especially likely to develop diabetes compared with their peers, and are at greater risk of hypertension, too.
While the link between autism and risk for obesity and gastrointestinal ailments is well-established, the new findings suggest that clinicians who care for these patients – particularly children – should focus on cardiometabolic health more broadly.
“Clinicians who are treating kids with autism need to pay more attention to this,” said Chanaka N. Kahathuduwa, MD, PhD, MPhil, of the department of neurology at Texas Tech University Health Sciences Center, in Lubbock, and a coauthor of the new study.
A pediatrician may prescribe an atypical antipsychotic medication such as risperidone to regulate the behavior of an autistic child, Dr. Kahathuduwa said, which may increase their cholesterol levels. Although this or similar drugs may be necessary in some cases, Dr. Kahathuduwa advised that clinicians explore other treatment options first.
Mining data from previously published studies
For the new analysis, Dr. Kahathuduwa and his colleagues pooled the results of 34 previously published studies, which included medical records of more than 276,000 people with autism and close to 8 million people without the condition.
Study participants were an average age of 31 years, and 47% were female. Some studies reported age ranges that enabled the researchers to differentiate between children and adults.
People with autism were 64% more likely to develop type 1 diabetes, 146% more likely to experience type 2 diabetes, and 46% more likely to have heart disease, overall, the study found. Children with autism were almost twice as likely as their peers to develop diabetes (184%) and high blood pressure (154%).
The study found associations, not causation, and does not include detailed data about medication prescribing patterns. While it would be ideal to understand why autism is linked to cardiometabolic risk, to address the link most effectively, Dr. Kahathuduwa said the causes likely are multifactorial. Medication history and genetics each play a role in a way that is hard to untangle. Even so, Dr. Kahathuduwa said he hoped the findings prompt clinicians to reevaluate how they treat their patients with autism.
“This may be an eye opener,” he said.
An editorial accompanying the study noted that people with autism may die up to 30 years earlier than people without autism, in part because of the physical health problems surfaced in the new research. They also are more likely than others to attempt suicide.
Elizabeth M. Weir, PhD, of the Autism Research Centre at the University of Cambridge (England) and author of the editorial, argued that current health delivery models often fail autistic people by not taking their needs into account.
Dr. Weir told this news organization that making adjustments such as dimming the lights for a light-sensitive patient or allowing people with autism to bring an advocate to appointments could build rapport.
“I diagnose autism pretty much every day and I know families get so overwhelmed with all the recommendations that we give,” said Sonia Monteiro, MD, a developmental and behavioral pediatrician at Texas Children’s Hospital in Houston. Still, Dr. Monteiro said clinicians should help parents of children with autism address the potential long-term cardiovascular risks – but to do so by layering in the information rather than merely adding more bullet points to an already long presentation.
“We know this information now, but finding a way to share that with families without overwhelming them even more, I think is challenging,” Dr. Monteiro said. “But it’s not something we can ignore.”
Dr. Kahathuduwa, Dr. Weir, and Dr. Monteiro report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People with autism are more likely to face diabetes, high cholesterol, and heart disease than those without the neurologic condition, according to a study published in JAMA Pediatrics. Researchers also found that children with autism are especially likely to develop diabetes compared with their peers, and are at greater risk of hypertension, too.
While the link between autism and risk for obesity and gastrointestinal ailments is well-established, the new findings suggest that clinicians who care for these patients – particularly children – should focus on cardiometabolic health more broadly.
“Clinicians who are treating kids with autism need to pay more attention to this,” said Chanaka N. Kahathuduwa, MD, PhD, MPhil, of the department of neurology at Texas Tech University Health Sciences Center, in Lubbock, and a coauthor of the new study.
A pediatrician may prescribe an atypical antipsychotic medication such as risperidone to regulate the behavior of an autistic child, Dr. Kahathuduwa said, which may increase their cholesterol levels. Although this or similar drugs may be necessary in some cases, Dr. Kahathuduwa advised that clinicians explore other treatment options first.
Mining data from previously published studies
For the new analysis, Dr. Kahathuduwa and his colleagues pooled the results of 34 previously published studies, which included medical records of more than 276,000 people with autism and close to 8 million people without the condition.
Study participants were an average age of 31 years, and 47% were female. Some studies reported age ranges that enabled the researchers to differentiate between children and adults.
People with autism were 64% more likely to develop type 1 diabetes, 146% more likely to experience type 2 diabetes, and 46% more likely to have heart disease, overall, the study found. Children with autism were almost twice as likely as their peers to develop diabetes (184%) and high blood pressure (154%).
The study found associations, not causation, and does not include detailed data about medication prescribing patterns. While it would be ideal to understand why autism is linked to cardiometabolic risk, to address the link most effectively, Dr. Kahathuduwa said the causes likely are multifactorial. Medication history and genetics each play a role in a way that is hard to untangle. Even so, Dr. Kahathuduwa said he hoped the findings prompt clinicians to reevaluate how they treat their patients with autism.
“This may be an eye opener,” he said.
An editorial accompanying the study noted that people with autism may die up to 30 years earlier than people without autism, in part because of the physical health problems surfaced in the new research. They also are more likely than others to attempt suicide.
Elizabeth M. Weir, PhD, of the Autism Research Centre at the University of Cambridge (England) and author of the editorial, argued that current health delivery models often fail autistic people by not taking their needs into account.
Dr. Weir told this news organization that making adjustments such as dimming the lights for a light-sensitive patient or allowing people with autism to bring an advocate to appointments could build rapport.
“I diagnose autism pretty much every day and I know families get so overwhelmed with all the recommendations that we give,” said Sonia Monteiro, MD, a developmental and behavioral pediatrician at Texas Children’s Hospital in Houston. Still, Dr. Monteiro said clinicians should help parents of children with autism address the potential long-term cardiovascular risks – but to do so by layering in the information rather than merely adding more bullet points to an already long presentation.
“We know this information now, but finding a way to share that with families without overwhelming them even more, I think is challenging,” Dr. Monteiro said. “But it’s not something we can ignore.”
Dr. Kahathuduwa, Dr. Weir, and Dr. Monteiro report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Washington medical board charges doctor with spreading COVID misinformation
Doctors and professional organizations are standing guard, hoping to protect patients from any harm that results from mistruths spread by colleagues.
Case in point: Several physicians and the American Board of Pathology filed complaints with Washington and Idaho medical boards alleging that Ryan Cole, MD, a board-certified pathologist who practices in Boise, Idaho, but who also holds a license in Washington, has spread antivaccine and pro-ivermectin statements on social media. Dr. Cole is one of the founders of America’s Frontline Doctors, a right-wing political organization. Dr. Cole did not respond to a request for comment.
Gary W. Procop, MD, CEO, American Board of Pathology, told this news organization that “as physicians and board-certified pathologists, we have a public trust, and we must be accountable to patients, society, and the profession. Misinformation can cause real harm to patients, which may include death. Misinformation diverts patients away from lifesaving vaccination and other preventive measures, promotes viral transmission, and recommends ineffective therapies that may be toxic instead of evidence-based medical care.”
Cavalcade of complaints
Several doctors also chimed in with formal complaints alleging that Cole is spreading unreliable information, according to a report from KTVB News. For example, a Boise doctor wrote in his complaint that Dr. Cole is “a major purveyor of misinformation” and called it “amazing” that the physician was continuing to publicly support debunked information about COVID-19 more than a year into the pandemic. The doctor also stated, “Cole is a health menace, abusing his status as a physician to mislead the public.”
As a result of such complaints, the Washington medical board has charged Cole with COVID-19–related violations. It is unclear whether or not the Idaho medical board will sanction the doctor. At least 12 medical boards have sanctioned doctors for similar violations since the start of the pandemic.
The statement of charges from the Washington medical board contends that since March 2021, Dr. Cole has made numerous misleading statements regarding the COVID-19 pandemic, vaccines, the use of ivermectin to treat COVID-19, and the effectiveness of masks.
In addition, the statement alleges that Dr. Cole treated several COVID-19 patients via telemedicine. During these sessions, he prescribed ivermectin, an antiparasite drug that has not been found to have any effectiveness in treating, curing, or preventing COVID-19. One of the patients died after receiving this treatment, according to the complaint.
Citing a study published in the New England Journal of Medicine, Dr. Procop pointed out that use of ivermectin, which is not approved by the U.S. Food and Drug Administration to treat COVID-19, is particularly troubling.
“There is a concern whenever an ineffective treatment is prescribed when more effective and scientifically proven therapies are available. Therapeutics have potential side effects, and toxicities have been associated with the use of ivermectin,” Dr. Procop said. “The benefits of therapy should always outweigh the risks of treatment.”
If the Washington medical board finds that Dr. Cole has engaged in unprofessional conduct, possible sanctions include revocation or suspension of his license. Washington state law also provides for a range of other possible sanctions, including restriction or limitation of his practice, requiring that he complete a specific program of remedial education or treatment, monitoring of his practice, censure or reprimand, probation, a fine of up to $5,000 for each violation, or refunding fees that his practice has billed to and collected from patients. Dr. Cole had until January 30 to respond to the medical board’s statement.
“The American Board of Pathology supports the actions of the Washington State Medical Board regarding their inquiries into any physician that holds license in their state who makes false and misleading medical claims, or provides medical care beyond their scope of practice, as indicated by their training,” Dr. Procop said.
Law in limbo
While medical boards are seeking to sanction professionals who spread falsehoods, the pause button has been hit on the California law that allows regulators to punish doctors for spreading false information about COVID-19 vaccinations and treatments.
The law went into effect Jan. 1 but was temporarily halted when U.S. District Judge William B. Shubb of the Eastern District of California granted a preliminary injunction against the law on Jan. 25, according to a report in the Sacramento Bee.
Mr. Shubb said the measure’s definition of “misinformation” was “unconstitutionally vague” under the due process clause of the 14th Amendment. He also criticized the law’s definition of “misinformation” as being “grammatically incoherent.”
A version of this article first appeared on Medscape.com.
Doctors and professional organizations are standing guard, hoping to protect patients from any harm that results from mistruths spread by colleagues.
Case in point: Several physicians and the American Board of Pathology filed complaints with Washington and Idaho medical boards alleging that Ryan Cole, MD, a board-certified pathologist who practices in Boise, Idaho, but who also holds a license in Washington, has spread antivaccine and pro-ivermectin statements on social media. Dr. Cole is one of the founders of America’s Frontline Doctors, a right-wing political organization. Dr. Cole did not respond to a request for comment.
Gary W. Procop, MD, CEO, American Board of Pathology, told this news organization that “as physicians and board-certified pathologists, we have a public trust, and we must be accountable to patients, society, and the profession. Misinformation can cause real harm to patients, which may include death. Misinformation diverts patients away from lifesaving vaccination and other preventive measures, promotes viral transmission, and recommends ineffective therapies that may be toxic instead of evidence-based medical care.”
Cavalcade of complaints
Several doctors also chimed in with formal complaints alleging that Cole is spreading unreliable information, according to a report from KTVB News. For example, a Boise doctor wrote in his complaint that Dr. Cole is “a major purveyor of misinformation” and called it “amazing” that the physician was continuing to publicly support debunked information about COVID-19 more than a year into the pandemic. The doctor also stated, “Cole is a health menace, abusing his status as a physician to mislead the public.”
As a result of such complaints, the Washington medical board has charged Cole with COVID-19–related violations. It is unclear whether or not the Idaho medical board will sanction the doctor. At least 12 medical boards have sanctioned doctors for similar violations since the start of the pandemic.
The statement of charges from the Washington medical board contends that since March 2021, Dr. Cole has made numerous misleading statements regarding the COVID-19 pandemic, vaccines, the use of ivermectin to treat COVID-19, and the effectiveness of masks.
In addition, the statement alleges that Dr. Cole treated several COVID-19 patients via telemedicine. During these sessions, he prescribed ivermectin, an antiparasite drug that has not been found to have any effectiveness in treating, curing, or preventing COVID-19. One of the patients died after receiving this treatment, according to the complaint.
Citing a study published in the New England Journal of Medicine, Dr. Procop pointed out that use of ivermectin, which is not approved by the U.S. Food and Drug Administration to treat COVID-19, is particularly troubling.
“There is a concern whenever an ineffective treatment is prescribed when more effective and scientifically proven therapies are available. Therapeutics have potential side effects, and toxicities have been associated with the use of ivermectin,” Dr. Procop said. “The benefits of therapy should always outweigh the risks of treatment.”
If the Washington medical board finds that Dr. Cole has engaged in unprofessional conduct, possible sanctions include revocation or suspension of his license. Washington state law also provides for a range of other possible sanctions, including restriction or limitation of his practice, requiring that he complete a specific program of remedial education or treatment, monitoring of his practice, censure or reprimand, probation, a fine of up to $5,000 for each violation, or refunding fees that his practice has billed to and collected from patients. Dr. Cole had until January 30 to respond to the medical board’s statement.
“The American Board of Pathology supports the actions of the Washington State Medical Board regarding their inquiries into any physician that holds license in their state who makes false and misleading medical claims, or provides medical care beyond their scope of practice, as indicated by their training,” Dr. Procop said.
Law in limbo
While medical boards are seeking to sanction professionals who spread falsehoods, the pause button has been hit on the California law that allows regulators to punish doctors for spreading false information about COVID-19 vaccinations and treatments.
The law went into effect Jan. 1 but was temporarily halted when U.S. District Judge William B. Shubb of the Eastern District of California granted a preliminary injunction against the law on Jan. 25, according to a report in the Sacramento Bee.
Mr. Shubb said the measure’s definition of “misinformation” was “unconstitutionally vague” under the due process clause of the 14th Amendment. He also criticized the law’s definition of “misinformation” as being “grammatically incoherent.”
A version of this article first appeared on Medscape.com.
Doctors and professional organizations are standing guard, hoping to protect patients from any harm that results from mistruths spread by colleagues.
Case in point: Several physicians and the American Board of Pathology filed complaints with Washington and Idaho medical boards alleging that Ryan Cole, MD, a board-certified pathologist who practices in Boise, Idaho, but who also holds a license in Washington, has spread antivaccine and pro-ivermectin statements on social media. Dr. Cole is one of the founders of America’s Frontline Doctors, a right-wing political organization. Dr. Cole did not respond to a request for comment.
Gary W. Procop, MD, CEO, American Board of Pathology, told this news organization that “as physicians and board-certified pathologists, we have a public trust, and we must be accountable to patients, society, and the profession. Misinformation can cause real harm to patients, which may include death. Misinformation diverts patients away from lifesaving vaccination and other preventive measures, promotes viral transmission, and recommends ineffective therapies that may be toxic instead of evidence-based medical care.”
Cavalcade of complaints
Several doctors also chimed in with formal complaints alleging that Cole is spreading unreliable information, according to a report from KTVB News. For example, a Boise doctor wrote in his complaint that Dr. Cole is “a major purveyor of misinformation” and called it “amazing” that the physician was continuing to publicly support debunked information about COVID-19 more than a year into the pandemic. The doctor also stated, “Cole is a health menace, abusing his status as a physician to mislead the public.”
As a result of such complaints, the Washington medical board has charged Cole with COVID-19–related violations. It is unclear whether or not the Idaho medical board will sanction the doctor. At least 12 medical boards have sanctioned doctors for similar violations since the start of the pandemic.
The statement of charges from the Washington medical board contends that since March 2021, Dr. Cole has made numerous misleading statements regarding the COVID-19 pandemic, vaccines, the use of ivermectin to treat COVID-19, and the effectiveness of masks.
In addition, the statement alleges that Dr. Cole treated several COVID-19 patients via telemedicine. During these sessions, he prescribed ivermectin, an antiparasite drug that has not been found to have any effectiveness in treating, curing, or preventing COVID-19. One of the patients died after receiving this treatment, according to the complaint.
Citing a study published in the New England Journal of Medicine, Dr. Procop pointed out that use of ivermectin, which is not approved by the U.S. Food and Drug Administration to treat COVID-19, is particularly troubling.
“There is a concern whenever an ineffective treatment is prescribed when more effective and scientifically proven therapies are available. Therapeutics have potential side effects, and toxicities have been associated with the use of ivermectin,” Dr. Procop said. “The benefits of therapy should always outweigh the risks of treatment.”
If the Washington medical board finds that Dr. Cole has engaged in unprofessional conduct, possible sanctions include revocation or suspension of his license. Washington state law also provides for a range of other possible sanctions, including restriction or limitation of his practice, requiring that he complete a specific program of remedial education or treatment, monitoring of his practice, censure or reprimand, probation, a fine of up to $5,000 for each violation, or refunding fees that his practice has billed to and collected from patients. Dr. Cole had until January 30 to respond to the medical board’s statement.
“The American Board of Pathology supports the actions of the Washington State Medical Board regarding their inquiries into any physician that holds license in their state who makes false and misleading medical claims, or provides medical care beyond their scope of practice, as indicated by their training,” Dr. Procop said.
Law in limbo
While medical boards are seeking to sanction professionals who spread falsehoods, the pause button has been hit on the California law that allows regulators to punish doctors for spreading false information about COVID-19 vaccinations and treatments.
The law went into effect Jan. 1 but was temporarily halted when U.S. District Judge William B. Shubb of the Eastern District of California granted a preliminary injunction against the law on Jan. 25, according to a report in the Sacramento Bee.
Mr. Shubb said the measure’s definition of “misinformation” was “unconstitutionally vague” under the due process clause of the 14th Amendment. He also criticized the law’s definition of “misinformation” as being “grammatically incoherent.”
A version of this article first appeared on Medscape.com.
Can AI conquer the late-shift dip in colonoscopy quality?
AI systems “may be a potential tool for minimizing time-related degradation of colonoscopy quality and further maintaining high quality and homogeneity of colonoscopies in high-workload centers,” Honggang Yu, MD, with the department of gastroenterology, Renmin Hospital of Wuhan (China) University, said in an interview.
The study was published online in JAMA Network Open.
Fatigue a factor?
Adenoma detection rate (ADR) is a critical quality measure of screening colonoscopy. Time of day is a well-known factor related to suboptimal ADR – with morning colonoscopies associated with improved ADR and afternoon colonoscopies with reduced ADR, Dr. Yu and colleagues write.
“However, an objective approach to solve this problem is still lacking,” Dr. Yu said. AI systems have been shown to improve the ADR, but the performance of AI during different times of the day remains unknown.
This cohort study is a secondary analysis of two prospective randomized controlled trials, in which a total of 1,780 consecutive patients were randomly allocated to either conventional colonoscopy or AI-assisted colonoscopy. The ADR for early and late colonoscopy sessions per half day were then compared.
Colonoscopy procedures were divided into two groups according to the end time of the procedure. The early group included procedures started in the early session per half day (8:00 a.m.–10:59 a.m. or 1:00 p.m.–2:59 p.m.). The late group included procedures started in the later session per half day (11:00 a.m.–12:59 p.m. or 3:00 p.m.–4:59 p.m.).
A total of 1,041 procedures were performed in the early sessions (357 conventional and 684 AI assisted). A total of 739 procedures were performed in the late sessions (263 conventional and 476 AI assisted).
In the unassisted colonoscopy group, later sessions per half day were associated with a decline in ADR (early vs. late, 13.73% vs. 5.7%; P = .005; odds ratio, 2.42; 95% confidence interval, 1.31-4.47).
With AI assistance, however, no such association was found in the ADR (early vs. late, 22.95% vs. 22.06%; P = .78; OR, 0.96; 95% CI, 0.71-1.29). AI provided the highest assistance capability in the last hour per half day.
The decline in ADR in late sessions (vs. early sessions) was evident in different colonoscopy settings. The investigators say accrual of endoscopist fatigue may be an independent factor of time-related degradation of colonoscopy quality.
More exploration required
“We’re excited about the great potential of using the power of AI to assist endoscopists in quality control or disease diagnosis in colonoscopy practice, but it’s too early to see AI as the standard,” Dr. Yu told this news organization.
“Despite recent achievements in the design and validation of AI systems, much more exploration is required in the clinical application of AI,” Dr. Yu said.
Dr. Yu further explained that, in addition to regulatory approval, the results of AI output must be trusted by the endoscopist, which remains a challenge for current AI systems that lack interpretability.
“Therefore, at the current stage of AI development, AI models can only serve as an extra reminder to assist endoscopists in colonoscopy,” Dr. Yu said.
This study was supported by the Innovation Team Project of Health Commission of Hubei Province. The authors have indicated no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
This article was updated 2/1/23.
AI systems “may be a potential tool for minimizing time-related degradation of colonoscopy quality and further maintaining high quality and homogeneity of colonoscopies in high-workload centers,” Honggang Yu, MD, with the department of gastroenterology, Renmin Hospital of Wuhan (China) University, said in an interview.
The study was published online in JAMA Network Open.
Fatigue a factor?
Adenoma detection rate (ADR) is a critical quality measure of screening colonoscopy. Time of day is a well-known factor related to suboptimal ADR – with morning colonoscopies associated with improved ADR and afternoon colonoscopies with reduced ADR, Dr. Yu and colleagues write.
“However, an objective approach to solve this problem is still lacking,” Dr. Yu said. AI systems have been shown to improve the ADR, but the performance of AI during different times of the day remains unknown.
This cohort study is a secondary analysis of two prospective randomized controlled trials, in which a total of 1,780 consecutive patients were randomly allocated to either conventional colonoscopy or AI-assisted colonoscopy. The ADR for early and late colonoscopy sessions per half day were then compared.
Colonoscopy procedures were divided into two groups according to the end time of the procedure. The early group included procedures started in the early session per half day (8:00 a.m.–10:59 a.m. or 1:00 p.m.–2:59 p.m.). The late group included procedures started in the later session per half day (11:00 a.m.–12:59 p.m. or 3:00 p.m.–4:59 p.m.).
A total of 1,041 procedures were performed in the early sessions (357 conventional and 684 AI assisted). A total of 739 procedures were performed in the late sessions (263 conventional and 476 AI assisted).
In the unassisted colonoscopy group, later sessions per half day were associated with a decline in ADR (early vs. late, 13.73% vs. 5.7%; P = .005; odds ratio, 2.42; 95% confidence interval, 1.31-4.47).
With AI assistance, however, no such association was found in the ADR (early vs. late, 22.95% vs. 22.06%; P = .78; OR, 0.96; 95% CI, 0.71-1.29). AI provided the highest assistance capability in the last hour per half day.
The decline in ADR in late sessions (vs. early sessions) was evident in different colonoscopy settings. The investigators say accrual of endoscopist fatigue may be an independent factor of time-related degradation of colonoscopy quality.
More exploration required
“We’re excited about the great potential of using the power of AI to assist endoscopists in quality control or disease diagnosis in colonoscopy practice, but it’s too early to see AI as the standard,” Dr. Yu told this news organization.
“Despite recent achievements in the design and validation of AI systems, much more exploration is required in the clinical application of AI,” Dr. Yu said.
Dr. Yu further explained that, in addition to regulatory approval, the results of AI output must be trusted by the endoscopist, which remains a challenge for current AI systems that lack interpretability.
“Therefore, at the current stage of AI development, AI models can only serve as an extra reminder to assist endoscopists in colonoscopy,” Dr. Yu said.
This study was supported by the Innovation Team Project of Health Commission of Hubei Province. The authors have indicated no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
This article was updated 2/1/23.
AI systems “may be a potential tool for minimizing time-related degradation of colonoscopy quality and further maintaining high quality and homogeneity of colonoscopies in high-workload centers,” Honggang Yu, MD, with the department of gastroenterology, Renmin Hospital of Wuhan (China) University, said in an interview.
The study was published online in JAMA Network Open.
Fatigue a factor?
Adenoma detection rate (ADR) is a critical quality measure of screening colonoscopy. Time of day is a well-known factor related to suboptimal ADR – with morning colonoscopies associated with improved ADR and afternoon colonoscopies with reduced ADR, Dr. Yu and colleagues write.
“However, an objective approach to solve this problem is still lacking,” Dr. Yu said. AI systems have been shown to improve the ADR, but the performance of AI during different times of the day remains unknown.
This cohort study is a secondary analysis of two prospective randomized controlled trials, in which a total of 1,780 consecutive patients were randomly allocated to either conventional colonoscopy or AI-assisted colonoscopy. The ADR for early and late colonoscopy sessions per half day were then compared.
Colonoscopy procedures were divided into two groups according to the end time of the procedure. The early group included procedures started in the early session per half day (8:00 a.m.–10:59 a.m. or 1:00 p.m.–2:59 p.m.). The late group included procedures started in the later session per half day (11:00 a.m.–12:59 p.m. or 3:00 p.m.–4:59 p.m.).
A total of 1,041 procedures were performed in the early sessions (357 conventional and 684 AI assisted). A total of 739 procedures were performed in the late sessions (263 conventional and 476 AI assisted).
In the unassisted colonoscopy group, later sessions per half day were associated with a decline in ADR (early vs. late, 13.73% vs. 5.7%; P = .005; odds ratio, 2.42; 95% confidence interval, 1.31-4.47).
With AI assistance, however, no such association was found in the ADR (early vs. late, 22.95% vs. 22.06%; P = .78; OR, 0.96; 95% CI, 0.71-1.29). AI provided the highest assistance capability in the last hour per half day.
The decline in ADR in late sessions (vs. early sessions) was evident in different colonoscopy settings. The investigators say accrual of endoscopist fatigue may be an independent factor of time-related degradation of colonoscopy quality.
More exploration required
“We’re excited about the great potential of using the power of AI to assist endoscopists in quality control or disease diagnosis in colonoscopy practice, but it’s too early to see AI as the standard,” Dr. Yu told this news organization.
“Despite recent achievements in the design and validation of AI systems, much more exploration is required in the clinical application of AI,” Dr. Yu said.
Dr. Yu further explained that, in addition to regulatory approval, the results of AI output must be trusted by the endoscopist, which remains a challenge for current AI systems that lack interpretability.
“Therefore, at the current stage of AI development, AI models can only serve as an extra reminder to assist endoscopists in colonoscopy,” Dr. Yu said.
This study was supported by the Innovation Team Project of Health Commission of Hubei Province. The authors have indicated no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
This article was updated 2/1/23.
FROM JAMA NETWORK OPEN
Pandemic pregnancy-linked deaths up 35% from 2019
Pregnancy-associated deaths, including drug-related deaths and homicide, were up 35% in 2020, compared with prepandemic 2019, new research indicates.
The data also show a 7.1% decrease in pregnancy-related suicides in 2020 from 2019.
The study, led by Claire E. Margerison, PhD, with the department of epidemiology and biostatistics at Michigan State University, East Lansing, included 4,528 pregnancy-associated deaths. The rate of deaths per 100,000 live births from April to December 2020 was 66.9 (95% confidence interval, 63.9-70.1). The comparative rate from April to December 2019 was 49.6. Researchers looked at that time period because the pandemic started in March 2020.
The findings were published online in JAMA Open Network.
Drug-related deaths up 55.3%
During the study period, drug deaths increased 55.3% and deaths from homicide increased 41.2%. Deaths from obstetric and other causes (mainly vehicle crashes) increased 28.4% and 56.7%, respectively, according to Dr. Margerison's group.
“Although pregnancy-associated deaths increased over time, increases from 2019 to 2020 were substantially larger than increases from 2018 to 2019,” the authors wrote.
The findings align with deaths in the general population in that time frame, they added.
Another study – this one looking at all-cause and cause-specific mortality from 2019 to 2020 in recently pregnant women, also published in JAMA Network Open, found significant racial and ethnic disparities in rates and cause of death.
According to the study, “Compared with non-Hispanic White women, mortality rates were three- to fivefold higher among American Indian or Alaska Native women for every cause, including suicide. Likewise, these findings suggest that non-Hispanic Black women experienced significantly higher mortality rates across causes, with the highest rates for homicide.”
Dr. Margerison and colleagues did not try to answer what caused the increases but pointed to the fentanyl epidemic, the murder of George Floyd, and COVID-19–related economic strain as potential stressors. They also suggest fewer screenings during the pandemic may have played a role.
Prevention opportunities missed
“Although pregnancy is considered an opportunity for screening and prevention related to physical, mental, and behavioral health, our data suggest that such opportunities were missed for hundreds of pregnant people during the pandemic,” the authors wrote.
Researchers analyzed cross-sectional U.S. death certificates from Jan. 1, 2018, to Dec. 31, 2020, for female U.S. residents ages 15-44 years. They then obtained the count for live births for the same population and time frame from the Centers for Disease Control and Prevention WONDER database.
They were able to identify pregnancy-associated deaths as the 2003 Revised Death Certificate contains a standardized pregnancy checkbox that asks whether the person was pregnant at the time of death, within 42 days of death, or within 43 days to 1 year of death.
Researchers also included deaths with ICD-10 codes linked with death from obstetric causes.
Deaths from overdose, suicide, and homicide are making up large and growing proportions of all deaths during pregnancy and in the first year postpartum, the authors report.
Dr. Margerison and coauthors, in research published in 2022, reported that these causes account for more than one-fifth of all pregnancy-related deaths. They also reported that drug-related deaths and homicides in this population have increased over the past 10 years.
“Substantial racial and ethnic inequities in these deaths exist,” they wrote in that paper.
The authors concluded in the current research: “Our study findings suggest that there is a need for prevention and intervention efforts, including harm-reduction strategies, tailored to pregnant and postpartum women, particularly during times of population stress and decreased utilization of preventive care, such as a pandemic.”
Dr. Margerison and coauthors reported receiving grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the study. One coauthor received personal fees from the World Health Organization and Population Reference Bureau outside the submitted work. One coauthor reported receiving grant support from the National Institutes of Mental Health during the study.
*This story was updated on 2/1.
Pregnancy-associated deaths, including drug-related deaths and homicide, were up 35% in 2020, compared with prepandemic 2019, new research indicates.
The data also show a 7.1% decrease in pregnancy-related suicides in 2020 from 2019.
The study, led by Claire E. Margerison, PhD, with the department of epidemiology and biostatistics at Michigan State University, East Lansing, included 4,528 pregnancy-associated deaths. The rate of deaths per 100,000 live births from April to December 2020 was 66.9 (95% confidence interval, 63.9-70.1). The comparative rate from April to December 2019 was 49.6. Researchers looked at that time period because the pandemic started in March 2020.
The findings were published online in JAMA Open Network.
Drug-related deaths up 55.3%
During the study period, drug deaths increased 55.3% and deaths from homicide increased 41.2%. Deaths from obstetric and other causes (mainly vehicle crashes) increased 28.4% and 56.7%, respectively, according to Dr. Margerison's group.
“Although pregnancy-associated deaths increased over time, increases from 2019 to 2020 were substantially larger than increases from 2018 to 2019,” the authors wrote.
The findings align with deaths in the general population in that time frame, they added.
Another study – this one looking at all-cause and cause-specific mortality from 2019 to 2020 in recently pregnant women, also published in JAMA Network Open, found significant racial and ethnic disparities in rates and cause of death.
According to the study, “Compared with non-Hispanic White women, mortality rates were three- to fivefold higher among American Indian or Alaska Native women for every cause, including suicide. Likewise, these findings suggest that non-Hispanic Black women experienced significantly higher mortality rates across causes, with the highest rates for homicide.”
Dr. Margerison and colleagues did not try to answer what caused the increases but pointed to the fentanyl epidemic, the murder of George Floyd, and COVID-19–related economic strain as potential stressors. They also suggest fewer screenings during the pandemic may have played a role.
Prevention opportunities missed
“Although pregnancy is considered an opportunity for screening and prevention related to physical, mental, and behavioral health, our data suggest that such opportunities were missed for hundreds of pregnant people during the pandemic,” the authors wrote.
Researchers analyzed cross-sectional U.S. death certificates from Jan. 1, 2018, to Dec. 31, 2020, for female U.S. residents ages 15-44 years. They then obtained the count for live births for the same population and time frame from the Centers for Disease Control and Prevention WONDER database.
They were able to identify pregnancy-associated deaths as the 2003 Revised Death Certificate contains a standardized pregnancy checkbox that asks whether the person was pregnant at the time of death, within 42 days of death, or within 43 days to 1 year of death.
Researchers also included deaths with ICD-10 codes linked with death from obstetric causes.
Deaths from overdose, suicide, and homicide are making up large and growing proportions of all deaths during pregnancy and in the first year postpartum, the authors report.
Dr. Margerison and coauthors, in research published in 2022, reported that these causes account for more than one-fifth of all pregnancy-related deaths. They also reported that drug-related deaths and homicides in this population have increased over the past 10 years.
“Substantial racial and ethnic inequities in these deaths exist,” they wrote in that paper.
The authors concluded in the current research: “Our study findings suggest that there is a need for prevention and intervention efforts, including harm-reduction strategies, tailored to pregnant and postpartum women, particularly during times of population stress and decreased utilization of preventive care, such as a pandemic.”
Dr. Margerison and coauthors reported receiving grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the study. One coauthor received personal fees from the World Health Organization and Population Reference Bureau outside the submitted work. One coauthor reported receiving grant support from the National Institutes of Mental Health during the study.
*This story was updated on 2/1.
Pregnancy-associated deaths, including drug-related deaths and homicide, were up 35% in 2020, compared with prepandemic 2019, new research indicates.
The data also show a 7.1% decrease in pregnancy-related suicides in 2020 from 2019.
The study, led by Claire E. Margerison, PhD, with the department of epidemiology and biostatistics at Michigan State University, East Lansing, included 4,528 pregnancy-associated deaths. The rate of deaths per 100,000 live births from April to December 2020 was 66.9 (95% confidence interval, 63.9-70.1). The comparative rate from April to December 2019 was 49.6. Researchers looked at that time period because the pandemic started in March 2020.
The findings were published online in JAMA Open Network.
Drug-related deaths up 55.3%
During the study period, drug deaths increased 55.3% and deaths from homicide increased 41.2%. Deaths from obstetric and other causes (mainly vehicle crashes) increased 28.4% and 56.7%, respectively, according to Dr. Margerison's group.
“Although pregnancy-associated deaths increased over time, increases from 2019 to 2020 were substantially larger than increases from 2018 to 2019,” the authors wrote.
The findings align with deaths in the general population in that time frame, they added.
Another study – this one looking at all-cause and cause-specific mortality from 2019 to 2020 in recently pregnant women, also published in JAMA Network Open, found significant racial and ethnic disparities in rates and cause of death.
According to the study, “Compared with non-Hispanic White women, mortality rates were three- to fivefold higher among American Indian or Alaska Native women for every cause, including suicide. Likewise, these findings suggest that non-Hispanic Black women experienced significantly higher mortality rates across causes, with the highest rates for homicide.”
Dr. Margerison and colleagues did not try to answer what caused the increases but pointed to the fentanyl epidemic, the murder of George Floyd, and COVID-19–related economic strain as potential stressors. They also suggest fewer screenings during the pandemic may have played a role.
Prevention opportunities missed
“Although pregnancy is considered an opportunity for screening and prevention related to physical, mental, and behavioral health, our data suggest that such opportunities were missed for hundreds of pregnant people during the pandemic,” the authors wrote.
Researchers analyzed cross-sectional U.S. death certificates from Jan. 1, 2018, to Dec. 31, 2020, for female U.S. residents ages 15-44 years. They then obtained the count for live births for the same population and time frame from the Centers for Disease Control and Prevention WONDER database.
They were able to identify pregnancy-associated deaths as the 2003 Revised Death Certificate contains a standardized pregnancy checkbox that asks whether the person was pregnant at the time of death, within 42 days of death, or within 43 days to 1 year of death.
Researchers also included deaths with ICD-10 codes linked with death from obstetric causes.
Deaths from overdose, suicide, and homicide are making up large and growing proportions of all deaths during pregnancy and in the first year postpartum, the authors report.
Dr. Margerison and coauthors, in research published in 2022, reported that these causes account for more than one-fifth of all pregnancy-related deaths. They also reported that drug-related deaths and homicides in this population have increased over the past 10 years.
“Substantial racial and ethnic inequities in these deaths exist,” they wrote in that paper.
The authors concluded in the current research: “Our study findings suggest that there is a need for prevention and intervention efforts, including harm-reduction strategies, tailored to pregnant and postpartum women, particularly during times of population stress and decreased utilization of preventive care, such as a pandemic.”
Dr. Margerison and coauthors reported receiving grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the study. One coauthor received personal fees from the World Health Organization and Population Reference Bureau outside the submitted work. One coauthor reported receiving grant support from the National Institutes of Mental Health during the study.
*This story was updated on 2/1.
FROM JAMA NETWORK OPEN
Kid with glasses: Many children live far from pediatric eye care
More than 2,800 counties in the United States lack a practicing pediatric ophthalmologist, limiting easy access to specialized eye care, a new study found.
The review of public, online pediatric ophthalmology directories found 1,056 pediatric ophthalmologists registered. The majority of these doctors practiced in densely populated areas, leaving many poor and rural residents across the United States without a nearby doctor to visit, and with the burden of spending time and money to get care for their children.
Travel for that care may be out of reach for some, according to Hannah Walsh, a medical student at the University of Miami, who led the study published in JAMA Ophthalmology.
Ms. Walsh’s research found that the median income of families living in a county without a pediatric ophthalmologist was nearly $17,000 lower than that for families with access to such specialists (95% confidence interval, −$18,544 to −$14,389; P < .001). These families were also less likely to own a car.
“We found that counties that didn’t have access to ophthalmic care for pediatrics were already disproportionately affected by lower socioeconomic status,” she said.
Children often receive routine vision screenings through their primary care clinician, but children who fail a routine screening may need to visit a pediatric ophthalmologist for a full eye examination, according to the American Academy of Ophthalmology.
Ms. Walsh and colleagues pulled data in March 2022 on the demographics of pediatric ophthalmologists from online directories hosted by the AAO and the American Association of Pediatric Ophthalmology and Strabismus. Ms. Walsh cautioned that the directories might include eye doctors who are no longer practicing, or there might be specialists who had not registered for the databases.
Yasmin Bradfield, MD, a pediatric ophthalmologist at the University of Wisconsin–Madison, noted that after the study published, pediatric ophthalmologists from Vermont and New Mexico notified study authors and AAPOS that they are practicing in the states.
Dr. Bradfield, a board member of AAPOS who also heads the organization’s recruitment task force, said the organization is aware of only one state – Wyoming – without a currently practicing pediatric ophthalmologist.
But based on the March 2022 data, Ms. Walsh and her colleagues found four states – New Mexico, North Dakota, South Dakota, and Vermont – did not have any pediatric ophthalmologists listed in directories for the organizations. Meanwhile, the country’s most populous states – California, New York, Florida, and Texas – had the most pediatric ophthalmologists.
For every million people, the study identified 7.7 pediatric ophthalmologists nationwide.
Julius T. Oatts, MD, the lead author of an accompanying editorial, said the findings are “valuable and sobering.” Even in San Francisco, where Dr. Oatts practices, most pediatric eye specialists have 6-month wait lists, he said.
Not fixing the shortage of children’s eye doctors could carry lifetime consequences, Dr. Oatts and his colleagues warned.
“Vision and eye health represent an important health barrier to learning in children,” Dr. Oatts and his colleagues wrote. “Lack of access to pediatric vision screening and care also contributes to the academic achievement gap and educational disparities.”
Dr. Bradfield said that disparities in pediatric ophthalmology care could leave some children at risk for losing their vision or never being able to see 20/20. Parents living in areas without a specialist may decide to instead visit an optometrist, but they are not trained to treat serious cases, such as strabismus, and only test and diagnose vision changes, according to AAPOS.
“If we don’t get to the kids in time, they can lose vision permanently, even if it’s something as simple as they just need glasses as a toddler,” Dr. Bradfield said.
Dr. Bradfield said AAPOS is recruiting new pediatric ophthalmologists by offering fellowships for medical students to attend the association’s annual conference and creating shadowing opportunities for students. The society also will release a survey of pediatric ophthalmology salaries to dispel rumors that the specialty does not have lucrative wages.
Ms. Walsh said she was interested in looking at disparities in pediatric ophthalmology care, in part, because she was surprised by how few of her classmates attending medical school were interested in the field of study.
“I hope it encourages ophthalmologists to consider pediatric ophthalmology, or to consider volunteering their time, or going to underserved areas to provide care to families that really are in need,” she said.
Coauthor Jayanth Sridhar, MD, reported receiving personal fees from Alcon, Apellis, Allergan, Dutch Ophthalmic Research Center, Genentech, OcuTerra Therapeutics, and Regeneron outside the submitted work. The other authors and the editorialists report no relevant financial relationships.
*This article was updated on 2/2/2023.
A version of this article first appeared on Medscape.com.
More than 2,800 counties in the United States lack a practicing pediatric ophthalmologist, limiting easy access to specialized eye care, a new study found.
The review of public, online pediatric ophthalmology directories found 1,056 pediatric ophthalmologists registered. The majority of these doctors practiced in densely populated areas, leaving many poor and rural residents across the United States without a nearby doctor to visit, and with the burden of spending time and money to get care for their children.
Travel for that care may be out of reach for some, according to Hannah Walsh, a medical student at the University of Miami, who led the study published in JAMA Ophthalmology.
Ms. Walsh’s research found that the median income of families living in a county without a pediatric ophthalmologist was nearly $17,000 lower than that for families with access to such specialists (95% confidence interval, −$18,544 to −$14,389; P < .001). These families were also less likely to own a car.
“We found that counties that didn’t have access to ophthalmic care for pediatrics were already disproportionately affected by lower socioeconomic status,” she said.
Children often receive routine vision screenings through their primary care clinician, but children who fail a routine screening may need to visit a pediatric ophthalmologist for a full eye examination, according to the American Academy of Ophthalmology.
Ms. Walsh and colleagues pulled data in March 2022 on the demographics of pediatric ophthalmologists from online directories hosted by the AAO and the American Association of Pediatric Ophthalmology and Strabismus. Ms. Walsh cautioned that the directories might include eye doctors who are no longer practicing, or there might be specialists who had not registered for the databases.
Yasmin Bradfield, MD, a pediatric ophthalmologist at the University of Wisconsin–Madison, noted that after the study published, pediatric ophthalmologists from Vermont and New Mexico notified study authors and AAPOS that they are practicing in the states.
Dr. Bradfield, a board member of AAPOS who also heads the organization’s recruitment task force, said the organization is aware of only one state – Wyoming – without a currently practicing pediatric ophthalmologist.
But based on the March 2022 data, Ms. Walsh and her colleagues found four states – New Mexico, North Dakota, South Dakota, and Vermont – did not have any pediatric ophthalmologists listed in directories for the organizations. Meanwhile, the country’s most populous states – California, New York, Florida, and Texas – had the most pediatric ophthalmologists.
For every million people, the study identified 7.7 pediatric ophthalmologists nationwide.
Julius T. Oatts, MD, the lead author of an accompanying editorial, said the findings are “valuable and sobering.” Even in San Francisco, where Dr. Oatts practices, most pediatric eye specialists have 6-month wait lists, he said.
Not fixing the shortage of children’s eye doctors could carry lifetime consequences, Dr. Oatts and his colleagues warned.
“Vision and eye health represent an important health barrier to learning in children,” Dr. Oatts and his colleagues wrote. “Lack of access to pediatric vision screening and care also contributes to the academic achievement gap and educational disparities.”
Dr. Bradfield said that disparities in pediatric ophthalmology care could leave some children at risk for losing their vision or never being able to see 20/20. Parents living in areas without a specialist may decide to instead visit an optometrist, but they are not trained to treat serious cases, such as strabismus, and only test and diagnose vision changes, according to AAPOS.
“If we don’t get to the kids in time, they can lose vision permanently, even if it’s something as simple as they just need glasses as a toddler,” Dr. Bradfield said.
Dr. Bradfield said AAPOS is recruiting new pediatric ophthalmologists by offering fellowships for medical students to attend the association’s annual conference and creating shadowing opportunities for students. The society also will release a survey of pediatric ophthalmology salaries to dispel rumors that the specialty does not have lucrative wages.
Ms. Walsh said she was interested in looking at disparities in pediatric ophthalmology care, in part, because she was surprised by how few of her classmates attending medical school were interested in the field of study.
“I hope it encourages ophthalmologists to consider pediatric ophthalmology, or to consider volunteering their time, or going to underserved areas to provide care to families that really are in need,” she said.
Coauthor Jayanth Sridhar, MD, reported receiving personal fees from Alcon, Apellis, Allergan, Dutch Ophthalmic Research Center, Genentech, OcuTerra Therapeutics, and Regeneron outside the submitted work. The other authors and the editorialists report no relevant financial relationships.
*This article was updated on 2/2/2023.
A version of this article first appeared on Medscape.com.
More than 2,800 counties in the United States lack a practicing pediatric ophthalmologist, limiting easy access to specialized eye care, a new study found.
The review of public, online pediatric ophthalmology directories found 1,056 pediatric ophthalmologists registered. The majority of these doctors practiced in densely populated areas, leaving many poor and rural residents across the United States without a nearby doctor to visit, and with the burden of spending time and money to get care for their children.
Travel for that care may be out of reach for some, according to Hannah Walsh, a medical student at the University of Miami, who led the study published in JAMA Ophthalmology.
Ms. Walsh’s research found that the median income of families living in a county without a pediatric ophthalmologist was nearly $17,000 lower than that for families with access to such specialists (95% confidence interval, −$18,544 to −$14,389; P < .001). These families were also less likely to own a car.
“We found that counties that didn’t have access to ophthalmic care for pediatrics were already disproportionately affected by lower socioeconomic status,” she said.
Children often receive routine vision screenings through their primary care clinician, but children who fail a routine screening may need to visit a pediatric ophthalmologist for a full eye examination, according to the American Academy of Ophthalmology.
Ms. Walsh and colleagues pulled data in March 2022 on the demographics of pediatric ophthalmologists from online directories hosted by the AAO and the American Association of Pediatric Ophthalmology and Strabismus. Ms. Walsh cautioned that the directories might include eye doctors who are no longer practicing, or there might be specialists who had not registered for the databases.
Yasmin Bradfield, MD, a pediatric ophthalmologist at the University of Wisconsin–Madison, noted that after the study published, pediatric ophthalmologists from Vermont and New Mexico notified study authors and AAPOS that they are practicing in the states.
Dr. Bradfield, a board member of AAPOS who also heads the organization’s recruitment task force, said the organization is aware of only one state – Wyoming – without a currently practicing pediatric ophthalmologist.
But based on the March 2022 data, Ms. Walsh and her colleagues found four states – New Mexico, North Dakota, South Dakota, and Vermont – did not have any pediatric ophthalmologists listed in directories for the organizations. Meanwhile, the country’s most populous states – California, New York, Florida, and Texas – had the most pediatric ophthalmologists.
For every million people, the study identified 7.7 pediatric ophthalmologists nationwide.
Julius T. Oatts, MD, the lead author of an accompanying editorial, said the findings are “valuable and sobering.” Even in San Francisco, where Dr. Oatts practices, most pediatric eye specialists have 6-month wait lists, he said.
Not fixing the shortage of children’s eye doctors could carry lifetime consequences, Dr. Oatts and his colleagues warned.
“Vision and eye health represent an important health barrier to learning in children,” Dr. Oatts and his colleagues wrote. “Lack of access to pediatric vision screening and care also contributes to the academic achievement gap and educational disparities.”
Dr. Bradfield said that disparities in pediatric ophthalmology care could leave some children at risk for losing their vision or never being able to see 20/20. Parents living in areas without a specialist may decide to instead visit an optometrist, but they are not trained to treat serious cases, such as strabismus, and only test and diagnose vision changes, according to AAPOS.
“If we don’t get to the kids in time, they can lose vision permanently, even if it’s something as simple as they just need glasses as a toddler,” Dr. Bradfield said.
Dr. Bradfield said AAPOS is recruiting new pediatric ophthalmologists by offering fellowships for medical students to attend the association’s annual conference and creating shadowing opportunities for students. The society also will release a survey of pediatric ophthalmology salaries to dispel rumors that the specialty does not have lucrative wages.
Ms. Walsh said she was interested in looking at disparities in pediatric ophthalmology care, in part, because she was surprised by how few of her classmates attending medical school were interested in the field of study.
“I hope it encourages ophthalmologists to consider pediatric ophthalmology, or to consider volunteering their time, or going to underserved areas to provide care to families that really are in need,” she said.
Coauthor Jayanth Sridhar, MD, reported receiving personal fees from Alcon, Apellis, Allergan, Dutch Ophthalmic Research Center, Genentech, OcuTerra Therapeutics, and Regeneron outside the submitted work. The other authors and the editorialists report no relevant financial relationships.
*This article was updated on 2/2/2023.
A version of this article first appeared on Medscape.com.
Similar brain atrophy in obesity and Alzheimer’s disease
Comparisons of MRI scans for more than 1,000 participants indicate correlations between the two conditions, especially in areas of gray matter thinning, suggesting that managing excess weight might slow cognitive decline and lower the risk for AD, according to the researchers.
However, brain maps of obesity did not correlate with maps of amyloid or tau protein accumulation.
“The fact that obesity-related brain atrophy did not correlate with the distribution of amyloid and tau proteins in AD was not what we expected,” study author Filip Morys, PhD, a postdoctoral researcher at McGill University, Montreal, said in an interview. “But it might just show that the specific mechanisms underpinning obesity- and Alzheimer’s disease–related neurodegeneration are different. This remains to be confirmed.”
The study was published in the Journal of Alzheimer’s Disease.
Cortical Thinning
The current study was prompted by the team’s earlier study, which showed that obesity-related neurodegeneration patterns were visually similar to those of AD, said Dr. Morys. “It was known previously that obesity is a risk factor for AD, but we wanted to directly compare brain atrophy patterns in both, which is what we did in this new study.”
The researchers analyzed data from a pooled sample of more than 1,300 participants. From the ADNI database, the researchers selected participants with AD and age- and sex-matched cognitively healthy controls. From the UK Biobank, the researchers drew a sample of lean, overweight, and obese participants without neurologic disease.
To determine how the weight status of patients with AD affects the correspondence between AD and obesity maps, they categorized participants with AD and healthy controls from the ADNI database into lean, overweight, and obese subgroups.
Then, to investigate mechanisms that might drive the similarities between obesity-related brain atrophy and AD-related amyloid-beta accumulation, they looked for overlapping areas in PET brain maps between patients with these outcomes.
The investigations showed that obesity maps were highly correlated with AD maps, but not with amyloid-beta or tau protein maps. The researchers also found significant correlations between obesity and the lean individuals with AD.
Brain regions with the highest similarities between obesity and AD were located mainly in the left temporal and bilateral prefrontal cortices.
“Our research confirms that obesity-related gray matter atrophy resembles that of AD,” the authors concluded. “Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD.”
Upcoming research “will focus on investigating how weight loss can affect the risk for AD, other dementias, and cognitive decline in general,” said Dr. Morys. “At this point, our study suggests that obesity prevention, weight loss, but also decreasing other metabolic risk factors related to obesity, such as type-2 diabetes or hypertension, might reduce the risk for AD and have beneficial effects on cognition.”
Lifestyle habits
Commenting on the findings, Claire Sexton, DPhil, vice president of scientific programs and outreach at the Alzheimer’s Association, cautioned that a single cross-sectional study isn’t conclusive. “Previous studies have illustrated that the relationship between obesity and dementia is complex. Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits, like regular exercise, a heart-healthy diet and staying socially and cognitively engaged.”
The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to study how targeting these risk factors in combination may reduce risk for cognitive decline in older adults.
The work was supported by a Foundation Scheme award from the Canadian Institutes of Health Research. Dr. Morys received a postdoctoral fellowship from Fonds de Recherche du Quebec – Santé. Data collection and sharing were funded by the Alzheimer’s Disease Neuroimaging Initiative, the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and multiple pharmaceutical companies and other private sector organizations. Dr. Morys and Dr. Sexton reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Comparisons of MRI scans for more than 1,000 participants indicate correlations between the two conditions, especially in areas of gray matter thinning, suggesting that managing excess weight might slow cognitive decline and lower the risk for AD, according to the researchers.
However, brain maps of obesity did not correlate with maps of amyloid or tau protein accumulation.
“The fact that obesity-related brain atrophy did not correlate with the distribution of amyloid and tau proteins in AD was not what we expected,” study author Filip Morys, PhD, a postdoctoral researcher at McGill University, Montreal, said in an interview. “But it might just show that the specific mechanisms underpinning obesity- and Alzheimer’s disease–related neurodegeneration are different. This remains to be confirmed.”
The study was published in the Journal of Alzheimer’s Disease.
Cortical Thinning
The current study was prompted by the team’s earlier study, which showed that obesity-related neurodegeneration patterns were visually similar to those of AD, said Dr. Morys. “It was known previously that obesity is a risk factor for AD, but we wanted to directly compare brain atrophy patterns in both, which is what we did in this new study.”
The researchers analyzed data from a pooled sample of more than 1,300 participants. From the ADNI database, the researchers selected participants with AD and age- and sex-matched cognitively healthy controls. From the UK Biobank, the researchers drew a sample of lean, overweight, and obese participants without neurologic disease.
To determine how the weight status of patients with AD affects the correspondence between AD and obesity maps, they categorized participants with AD and healthy controls from the ADNI database into lean, overweight, and obese subgroups.
Then, to investigate mechanisms that might drive the similarities between obesity-related brain atrophy and AD-related amyloid-beta accumulation, they looked for overlapping areas in PET brain maps between patients with these outcomes.
The investigations showed that obesity maps were highly correlated with AD maps, but not with amyloid-beta or tau protein maps. The researchers also found significant correlations between obesity and the lean individuals with AD.
Brain regions with the highest similarities between obesity and AD were located mainly in the left temporal and bilateral prefrontal cortices.
“Our research confirms that obesity-related gray matter atrophy resembles that of AD,” the authors concluded. “Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD.”
Upcoming research “will focus on investigating how weight loss can affect the risk for AD, other dementias, and cognitive decline in general,” said Dr. Morys. “At this point, our study suggests that obesity prevention, weight loss, but also decreasing other metabolic risk factors related to obesity, such as type-2 diabetes or hypertension, might reduce the risk for AD and have beneficial effects on cognition.”
Lifestyle habits
Commenting on the findings, Claire Sexton, DPhil, vice president of scientific programs and outreach at the Alzheimer’s Association, cautioned that a single cross-sectional study isn’t conclusive. “Previous studies have illustrated that the relationship between obesity and dementia is complex. Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits, like regular exercise, a heart-healthy diet and staying socially and cognitively engaged.”
The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to study how targeting these risk factors in combination may reduce risk for cognitive decline in older adults.
The work was supported by a Foundation Scheme award from the Canadian Institutes of Health Research. Dr. Morys received a postdoctoral fellowship from Fonds de Recherche du Quebec – Santé. Data collection and sharing were funded by the Alzheimer’s Disease Neuroimaging Initiative, the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and multiple pharmaceutical companies and other private sector organizations. Dr. Morys and Dr. Sexton reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Comparisons of MRI scans for more than 1,000 participants indicate correlations between the two conditions, especially in areas of gray matter thinning, suggesting that managing excess weight might slow cognitive decline and lower the risk for AD, according to the researchers.
However, brain maps of obesity did not correlate with maps of amyloid or tau protein accumulation.
“The fact that obesity-related brain atrophy did not correlate with the distribution of amyloid and tau proteins in AD was not what we expected,” study author Filip Morys, PhD, a postdoctoral researcher at McGill University, Montreal, said in an interview. “But it might just show that the specific mechanisms underpinning obesity- and Alzheimer’s disease–related neurodegeneration are different. This remains to be confirmed.”
The study was published in the Journal of Alzheimer’s Disease.
Cortical Thinning
The current study was prompted by the team’s earlier study, which showed that obesity-related neurodegeneration patterns were visually similar to those of AD, said Dr. Morys. “It was known previously that obesity is a risk factor for AD, but we wanted to directly compare brain atrophy patterns in both, which is what we did in this new study.”
The researchers analyzed data from a pooled sample of more than 1,300 participants. From the ADNI database, the researchers selected participants with AD and age- and sex-matched cognitively healthy controls. From the UK Biobank, the researchers drew a sample of lean, overweight, and obese participants without neurologic disease.
To determine how the weight status of patients with AD affects the correspondence between AD and obesity maps, they categorized participants with AD and healthy controls from the ADNI database into lean, overweight, and obese subgroups.
Then, to investigate mechanisms that might drive the similarities between obesity-related brain atrophy and AD-related amyloid-beta accumulation, they looked for overlapping areas in PET brain maps between patients with these outcomes.
The investigations showed that obesity maps were highly correlated with AD maps, but not with amyloid-beta or tau protein maps. The researchers also found significant correlations between obesity and the lean individuals with AD.
Brain regions with the highest similarities between obesity and AD were located mainly in the left temporal and bilateral prefrontal cortices.
“Our research confirms that obesity-related gray matter atrophy resembles that of AD,” the authors concluded. “Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD.”
Upcoming research “will focus on investigating how weight loss can affect the risk for AD, other dementias, and cognitive decline in general,” said Dr. Morys. “At this point, our study suggests that obesity prevention, weight loss, but also decreasing other metabolic risk factors related to obesity, such as type-2 diabetes or hypertension, might reduce the risk for AD and have beneficial effects on cognition.”
Lifestyle habits
Commenting on the findings, Claire Sexton, DPhil, vice president of scientific programs and outreach at the Alzheimer’s Association, cautioned that a single cross-sectional study isn’t conclusive. “Previous studies have illustrated that the relationship between obesity and dementia is complex. Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits, like regular exercise, a heart-healthy diet and staying socially and cognitively engaged.”
The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to study how targeting these risk factors in combination may reduce risk for cognitive decline in older adults.
The work was supported by a Foundation Scheme award from the Canadian Institutes of Health Research. Dr. Morys received a postdoctoral fellowship from Fonds de Recherche du Quebec – Santé. Data collection and sharing were funded by the Alzheimer’s Disease Neuroimaging Initiative, the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and multiple pharmaceutical companies and other private sector organizations. Dr. Morys and Dr. Sexton reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE
Expert gives tips on less-discussed dermatologic diseases
ORLANDO – , according to Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington.
These semi-forsaken diseases are important not to miss and can “also be quite challenging when we think about their management,” he said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dr. Friedman, also director of the GW dermatology residency program, reviewed several of these diseases – along with tips for management – during a session at the meeting.
. It does not always have the classic ring pattern for which it is best known, he said. And in patients with darker skin tones, it is characterized by more of a brown or black color, rather than the pink-red color.
Dr. Friedman said that despite a kind of “Pavlovian response” linking GA with diabetes, this link might not be as strong as the field has come to believe, since the studies on which this belief was based included a patient population with narrow demographics. “Maybe GA and type 1 diabetes aren’t necessarily connected,” he said.
Dyslipidemia, on the other hand, has a strong connection with GA, he said. The disease is also linked to thyroid disease and is linked with malignancy, especially in older patients with generalized or atypical presentations of GA, he said.
Spontaneous resolution of the disease is seen within 2 years for 50% to 75% of patients, so “no treatment may be the best treatment,” but antimalarials can be effective, Dr. Friedman said. “I use antimalarials frequently in my practice,” he said. “The key is, they take time to work (4-5 months),” which should be explained to patients.
Antibiotics, he said, can be “somewhat effective,” but in the case of doxycycline at least, the disease can resolve within weeks but then may return when treatment is stopped.
There is some evidence to support using biologics and more recently, Janus kinase (JAK) inhibitors, off-label, to treat GA. Efficacy has been seen with the tumor necrosis factor (TNF) blocker infliximab and with the JAK inhibitor tofacitinib, he said.
Lichen planus (LP). This is another common disease that can go off-script with its presentation. The disease is often described with the “six P’s” indicating the following characteristics: pruritic, polygonal, planar or flat-topped, purple papules, and plaques. But LP “didn’t read the textbook,” Dr. Friedman said.
“The clinical presentation of lichen planus can be quite broad,” he said. “The P’s aren’t always followed as there are a variety of colors and configurations which can be witnessed.”
With LP, there is a clear association with dyslipidemia and diabetes, so “asking the right questions is going to be important” when talking to the patient. There is also a higher risk of autoimmune diseases, especially of the thyroid type, associated with LP, he said.
No treatment has been Food and Drug Administration approved for LP, but some are expected in the future, he said.
For now, he emphasized creativity in the management of patients with LP. “I love oral retinoids for this,” he said. Antimalarials and methotrexate are also options.
In one case Dr. Friedman saw, nothing seemed to work: light therapy for a year; metronidazole; isotretinoin; halobetasol/tazarotene lotion; and the TNF-blocker adalimumab either weren’t effective or resulted in complications in the patient.
Knowing the recent implication of the interleukin (IL)-17 pathway in the pathophysiology of LP, he then tried the anti-IL17 antibody secukinumab. “This patient had a pretty robust response to treatment,” Dr. Friedman said. “He was very excited. The problem, as always, is access, especially for off-label therapies.”
Tumid lupus erythematosus. This disease is characterized by erythematous, edematous, nonscarring plaques on sun-exposed sites. For treatment, Dr. Friedman said antimalarials can be up to 90% effective, sometimes with rapid resolution of the lesions.
“You want to dose below that 5 mg per kg of true body weight to limit the small potential for ocular toxicity over time,” he said. And, he emphasized, “always combine treatment with good sun-protective measures.”
Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.
ORLANDO – , according to Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington.
These semi-forsaken diseases are important not to miss and can “also be quite challenging when we think about their management,” he said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dr. Friedman, also director of the GW dermatology residency program, reviewed several of these diseases – along with tips for management – during a session at the meeting.
. It does not always have the classic ring pattern for which it is best known, he said. And in patients with darker skin tones, it is characterized by more of a brown or black color, rather than the pink-red color.
Dr. Friedman said that despite a kind of “Pavlovian response” linking GA with diabetes, this link might not be as strong as the field has come to believe, since the studies on which this belief was based included a patient population with narrow demographics. “Maybe GA and type 1 diabetes aren’t necessarily connected,” he said.
Dyslipidemia, on the other hand, has a strong connection with GA, he said. The disease is also linked to thyroid disease and is linked with malignancy, especially in older patients with generalized or atypical presentations of GA, he said.
Spontaneous resolution of the disease is seen within 2 years for 50% to 75% of patients, so “no treatment may be the best treatment,” but antimalarials can be effective, Dr. Friedman said. “I use antimalarials frequently in my practice,” he said. “The key is, they take time to work (4-5 months),” which should be explained to patients.
Antibiotics, he said, can be “somewhat effective,” but in the case of doxycycline at least, the disease can resolve within weeks but then may return when treatment is stopped.
There is some evidence to support using biologics and more recently, Janus kinase (JAK) inhibitors, off-label, to treat GA. Efficacy has been seen with the tumor necrosis factor (TNF) blocker infliximab and with the JAK inhibitor tofacitinib, he said.
Lichen planus (LP). This is another common disease that can go off-script with its presentation. The disease is often described with the “six P’s” indicating the following characteristics: pruritic, polygonal, planar or flat-topped, purple papules, and plaques. But LP “didn’t read the textbook,” Dr. Friedman said.
“The clinical presentation of lichen planus can be quite broad,” he said. “The P’s aren’t always followed as there are a variety of colors and configurations which can be witnessed.”
With LP, there is a clear association with dyslipidemia and diabetes, so “asking the right questions is going to be important” when talking to the patient. There is also a higher risk of autoimmune diseases, especially of the thyroid type, associated with LP, he said.
No treatment has been Food and Drug Administration approved for LP, but some are expected in the future, he said.
For now, he emphasized creativity in the management of patients with LP. “I love oral retinoids for this,” he said. Antimalarials and methotrexate are also options.
In one case Dr. Friedman saw, nothing seemed to work: light therapy for a year; metronidazole; isotretinoin; halobetasol/tazarotene lotion; and the TNF-blocker adalimumab either weren’t effective or resulted in complications in the patient.
Knowing the recent implication of the interleukin (IL)-17 pathway in the pathophysiology of LP, he then tried the anti-IL17 antibody secukinumab. “This patient had a pretty robust response to treatment,” Dr. Friedman said. “He was very excited. The problem, as always, is access, especially for off-label therapies.”
Tumid lupus erythematosus. This disease is characterized by erythematous, edematous, nonscarring plaques on sun-exposed sites. For treatment, Dr. Friedman said antimalarials can be up to 90% effective, sometimes with rapid resolution of the lesions.
“You want to dose below that 5 mg per kg of true body weight to limit the small potential for ocular toxicity over time,” he said. And, he emphasized, “always combine treatment with good sun-protective measures.”
Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.
ORLANDO – , according to Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington.
These semi-forsaken diseases are important not to miss and can “also be quite challenging when we think about their management,” he said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dr. Friedman, also director of the GW dermatology residency program, reviewed several of these diseases – along with tips for management – during a session at the meeting.
. It does not always have the classic ring pattern for which it is best known, he said. And in patients with darker skin tones, it is characterized by more of a brown or black color, rather than the pink-red color.
Dr. Friedman said that despite a kind of “Pavlovian response” linking GA with diabetes, this link might not be as strong as the field has come to believe, since the studies on which this belief was based included a patient population with narrow demographics. “Maybe GA and type 1 diabetes aren’t necessarily connected,” he said.
Dyslipidemia, on the other hand, has a strong connection with GA, he said. The disease is also linked to thyroid disease and is linked with malignancy, especially in older patients with generalized or atypical presentations of GA, he said.
Spontaneous resolution of the disease is seen within 2 years for 50% to 75% of patients, so “no treatment may be the best treatment,” but antimalarials can be effective, Dr. Friedman said. “I use antimalarials frequently in my practice,” he said. “The key is, they take time to work (4-5 months),” which should be explained to patients.
Antibiotics, he said, can be “somewhat effective,” but in the case of doxycycline at least, the disease can resolve within weeks but then may return when treatment is stopped.
There is some evidence to support using biologics and more recently, Janus kinase (JAK) inhibitors, off-label, to treat GA. Efficacy has been seen with the tumor necrosis factor (TNF) blocker infliximab and with the JAK inhibitor tofacitinib, he said.
Lichen planus (LP). This is another common disease that can go off-script with its presentation. The disease is often described with the “six P’s” indicating the following characteristics: pruritic, polygonal, planar or flat-topped, purple papules, and plaques. But LP “didn’t read the textbook,” Dr. Friedman said.
“The clinical presentation of lichen planus can be quite broad,” he said. “The P’s aren’t always followed as there are a variety of colors and configurations which can be witnessed.”
With LP, there is a clear association with dyslipidemia and diabetes, so “asking the right questions is going to be important” when talking to the patient. There is also a higher risk of autoimmune diseases, especially of the thyroid type, associated with LP, he said.
No treatment has been Food and Drug Administration approved for LP, but some are expected in the future, he said.
For now, he emphasized creativity in the management of patients with LP. “I love oral retinoids for this,” he said. Antimalarials and methotrexate are also options.
In one case Dr. Friedman saw, nothing seemed to work: light therapy for a year; metronidazole; isotretinoin; halobetasol/tazarotene lotion; and the TNF-blocker adalimumab either weren’t effective or resulted in complications in the patient.
Knowing the recent implication of the interleukin (IL)-17 pathway in the pathophysiology of LP, he then tried the anti-IL17 antibody secukinumab. “This patient had a pretty robust response to treatment,” Dr. Friedman said. “He was very excited. The problem, as always, is access, especially for off-label therapies.”
Tumid lupus erythematosus. This disease is characterized by erythematous, edematous, nonscarring plaques on sun-exposed sites. For treatment, Dr. Friedman said antimalarials can be up to 90% effective, sometimes with rapid resolution of the lesions.
“You want to dose below that 5 mg per kg of true body weight to limit the small potential for ocular toxicity over time,” he said. And, he emphasized, “always combine treatment with good sun-protective measures.”
Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.
AT ODAC 2023
Long QT syndrome overdiagnosis persists
Five factors underlie the ongoing overdiagnosis and misdiagnosis of long QT syndrome (LQTS), including temporary QT prolongation following vasovagal syncope, a “pseudo”-positive genetic test result, family history of sudden cardiac death, transient QT prolongation, and misinterpretation of the QTc interval, a new study suggests.
Awareness of these characteristics, which led to a diagnostic reversal in 290 of 1,841 (16%) patients, could reduce the burden of overdiagnosis on the health care system and on patients and families, senior author Michael J. Ackerman, MD, PhD, of Mayo Clinic, Rochester, Minn., and colleagues conclude.
“The findings are a disturbing and disappointing sequel to the paper we published about LQTS overdiagnosis back in 2007, which showed that 2 out of every 5 patients who came to Mayo Clinic for a second opinion left without the diagnosis,” Dr. Ackerman told this news organization.
To date, Dr. Ackerman has reversed the diagnosis for 350 patients, he said.
The consequences of an LQTS diagnosis are “profound,” he noted, including years of unnecessary drug therapy, implantation of a cardioverter defibrillator, disqualification from competitive sports, and emotional stress to the individual and family.
By pointing out the five biggest mistakes his team has seen, he said, “we hope to equip the diagnostician with the means to challenge and assess the veracity of a LQTS diagnosis.”
The study was published online in the Journal of the American College of Cardiology.
Time to do better
Dr. Ackerman and colleagues analyzed electronic medical records on 290 of 1,841 (16%) patients who presented with an outside diagnosis of LQTS but subsequently were dismissed as having normal findings. The mean age of these patients at their first Mayo Clinic evaluation was 22, 60% were female, and the mean QTc interval was 427 ±25 milliseconds.
Overall, 38% of misdiagnoses were the result of misinterpretation of clinical factors; 29%, to diagnostic test misinterpretations; 17%, to an apparently positive genetic test in the context of a weak or absent phenotype; and 16%, to a family history of false LQTS or of sudden cardiac or sudden unexplained death.
More specifically, the most common cause of an LQTS misdiagnosis was QT prolongation following vasovagal syncope, which was misinterpreted as LQTS-attributed syncope.
The second most common cause was an apparently positive genetic test for an LQTS gene that turned out to be a benign or likely benign variant.
The third most common cause was an LQTS diagnosis based solely on a family history of sudden unexplained death (26 patients), QT prolongation (11 patients), or sudden cardiac arrest (9 patients).
The fourth most common cause was an isolated event of QT prolongation (44 patients). The transient QT prolongation was observed under myriad conditions unrelated to LQTS. Yet, 31 patients received a diagnosis based solely on the event.
The fifth most common cause was inclusion of the U-wave in the calculation of the QTc interval (40 patients), leading to an inaccurate interpretation of the electrocardiogram.
Dr. Ackerman noted that these LQTS diagnoses were given by heart-rhythm specialists, and most patients self-referred for a second opinion because a family member questioned the diagnosis after doing their own research.
“It’s time that we step up to the plate and do better,” Dr. Ackerman said. The team’s evaluation of the impact of the misdiagnosis on the patients’ lifestyle and quality of life showed that 45% had been restricted from competitive sports (and subsequently resumed sports activity with no adverse events); 80% had been started on beta-blockers (the drugs were discontinued in 84% as a result of the Mayo Clinic evaluation, whereas 16% opted to continue); and 10 of 22 patients (45%) who received an implanted cardioverter device underwent an extraction of the device without complications.
The authors conclude: “Although missing a patient who truly has LQTS can lead to a tragic outcome, the implications of overdiagnosed LQTS are not trivial and are potentially tragic as well.”
‘Tricky diagnosis’
LQTS specialist Peter Aziz, MD, director of pediatric electrophysiology at the Cleveland Clinic, agreed with these findings.
“Most of us ‘channelopathists’ who see LQTS for a living have a good grasp of the disease, but it can be elusive for others,” he said in an interview. “This is a tricky diagnosis. There are ends of the spectrum where people for sure don’t have it and people for sure do. Most clinicians are able to identify that.”
However, he added, “A lot of patients fall into that gray area where it may not be clear at first, even to an expert. But the expert knows how to do a comprehensive evaluation, examining episodes and symptoms and understanding whether they are relevant to LQTS or completely red herrings, and feeling confident about how they calculate the acute interval on an electrocardiogram.”
“All of these may seem mundane, but without the experience, clinicians are vulnerable to miscalculations,” he said. “That’s why our bias, as channelopathists, is that every patient who has a suspected diagnosis or is being treated for LQTS really should see an expert.”
Similarly, Arthur A.M. Wilde, MD, PhD, of the University of Amsterdam, and Peter J. Schwartz, MD, of IRCCS Istituto Auxologico Italiano, Milan, write in a related editorial that it “has to be kept in mind that both diagnostic scores and risk scores are dynamic and can be modified by time and by appropriate therapy.
“Therefore, to make hasty diagnosis of a disease that requires life-long treatment is inappropriate, especially when this is done without the support of adequate, specific experience.”
No commercial funding or relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.
Five factors underlie the ongoing overdiagnosis and misdiagnosis of long QT syndrome (LQTS), including temporary QT prolongation following vasovagal syncope, a “pseudo”-positive genetic test result, family history of sudden cardiac death, transient QT prolongation, and misinterpretation of the QTc interval, a new study suggests.
Awareness of these characteristics, which led to a diagnostic reversal in 290 of 1,841 (16%) patients, could reduce the burden of overdiagnosis on the health care system and on patients and families, senior author Michael J. Ackerman, MD, PhD, of Mayo Clinic, Rochester, Minn., and colleagues conclude.
“The findings are a disturbing and disappointing sequel to the paper we published about LQTS overdiagnosis back in 2007, which showed that 2 out of every 5 patients who came to Mayo Clinic for a second opinion left without the diagnosis,” Dr. Ackerman told this news organization.
To date, Dr. Ackerman has reversed the diagnosis for 350 patients, he said.
The consequences of an LQTS diagnosis are “profound,” he noted, including years of unnecessary drug therapy, implantation of a cardioverter defibrillator, disqualification from competitive sports, and emotional stress to the individual and family.
By pointing out the five biggest mistakes his team has seen, he said, “we hope to equip the diagnostician with the means to challenge and assess the veracity of a LQTS diagnosis.”
The study was published online in the Journal of the American College of Cardiology.
Time to do better
Dr. Ackerman and colleagues analyzed electronic medical records on 290 of 1,841 (16%) patients who presented with an outside diagnosis of LQTS but subsequently were dismissed as having normal findings. The mean age of these patients at their first Mayo Clinic evaluation was 22, 60% were female, and the mean QTc interval was 427 ±25 milliseconds.
Overall, 38% of misdiagnoses were the result of misinterpretation of clinical factors; 29%, to diagnostic test misinterpretations; 17%, to an apparently positive genetic test in the context of a weak or absent phenotype; and 16%, to a family history of false LQTS or of sudden cardiac or sudden unexplained death.
More specifically, the most common cause of an LQTS misdiagnosis was QT prolongation following vasovagal syncope, which was misinterpreted as LQTS-attributed syncope.
The second most common cause was an apparently positive genetic test for an LQTS gene that turned out to be a benign or likely benign variant.
The third most common cause was an LQTS diagnosis based solely on a family history of sudden unexplained death (26 patients), QT prolongation (11 patients), or sudden cardiac arrest (9 patients).
The fourth most common cause was an isolated event of QT prolongation (44 patients). The transient QT prolongation was observed under myriad conditions unrelated to LQTS. Yet, 31 patients received a diagnosis based solely on the event.
The fifth most common cause was inclusion of the U-wave in the calculation of the QTc interval (40 patients), leading to an inaccurate interpretation of the electrocardiogram.
Dr. Ackerman noted that these LQTS diagnoses were given by heart-rhythm specialists, and most patients self-referred for a second opinion because a family member questioned the diagnosis after doing their own research.
“It’s time that we step up to the plate and do better,” Dr. Ackerman said. The team’s evaluation of the impact of the misdiagnosis on the patients’ lifestyle and quality of life showed that 45% had been restricted from competitive sports (and subsequently resumed sports activity with no adverse events); 80% had been started on beta-blockers (the drugs were discontinued in 84% as a result of the Mayo Clinic evaluation, whereas 16% opted to continue); and 10 of 22 patients (45%) who received an implanted cardioverter device underwent an extraction of the device without complications.
The authors conclude: “Although missing a patient who truly has LQTS can lead to a tragic outcome, the implications of overdiagnosed LQTS are not trivial and are potentially tragic as well.”
‘Tricky diagnosis’
LQTS specialist Peter Aziz, MD, director of pediatric electrophysiology at the Cleveland Clinic, agreed with these findings.
“Most of us ‘channelopathists’ who see LQTS for a living have a good grasp of the disease, but it can be elusive for others,” he said in an interview. “This is a tricky diagnosis. There are ends of the spectrum where people for sure don’t have it and people for sure do. Most clinicians are able to identify that.”
However, he added, “A lot of patients fall into that gray area where it may not be clear at first, even to an expert. But the expert knows how to do a comprehensive evaluation, examining episodes and symptoms and understanding whether they are relevant to LQTS or completely red herrings, and feeling confident about how they calculate the acute interval on an electrocardiogram.”
“All of these may seem mundane, but without the experience, clinicians are vulnerable to miscalculations,” he said. “That’s why our bias, as channelopathists, is that every patient who has a suspected diagnosis or is being treated for LQTS really should see an expert.”
Similarly, Arthur A.M. Wilde, MD, PhD, of the University of Amsterdam, and Peter J. Schwartz, MD, of IRCCS Istituto Auxologico Italiano, Milan, write in a related editorial that it “has to be kept in mind that both diagnostic scores and risk scores are dynamic and can be modified by time and by appropriate therapy.
“Therefore, to make hasty diagnosis of a disease that requires life-long treatment is inappropriate, especially when this is done without the support of adequate, specific experience.”
No commercial funding or relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.
Five factors underlie the ongoing overdiagnosis and misdiagnosis of long QT syndrome (LQTS), including temporary QT prolongation following vasovagal syncope, a “pseudo”-positive genetic test result, family history of sudden cardiac death, transient QT prolongation, and misinterpretation of the QTc interval, a new study suggests.
Awareness of these characteristics, which led to a diagnostic reversal in 290 of 1,841 (16%) patients, could reduce the burden of overdiagnosis on the health care system and on patients and families, senior author Michael J. Ackerman, MD, PhD, of Mayo Clinic, Rochester, Minn., and colleagues conclude.
“The findings are a disturbing and disappointing sequel to the paper we published about LQTS overdiagnosis back in 2007, which showed that 2 out of every 5 patients who came to Mayo Clinic for a second opinion left without the diagnosis,” Dr. Ackerman told this news organization.
To date, Dr. Ackerman has reversed the diagnosis for 350 patients, he said.
The consequences of an LQTS diagnosis are “profound,” he noted, including years of unnecessary drug therapy, implantation of a cardioverter defibrillator, disqualification from competitive sports, and emotional stress to the individual and family.
By pointing out the five biggest mistakes his team has seen, he said, “we hope to equip the diagnostician with the means to challenge and assess the veracity of a LQTS diagnosis.”
The study was published online in the Journal of the American College of Cardiology.
Time to do better
Dr. Ackerman and colleagues analyzed electronic medical records on 290 of 1,841 (16%) patients who presented with an outside diagnosis of LQTS but subsequently were dismissed as having normal findings. The mean age of these patients at their first Mayo Clinic evaluation was 22, 60% were female, and the mean QTc interval was 427 ±25 milliseconds.
Overall, 38% of misdiagnoses were the result of misinterpretation of clinical factors; 29%, to diagnostic test misinterpretations; 17%, to an apparently positive genetic test in the context of a weak or absent phenotype; and 16%, to a family history of false LQTS or of sudden cardiac or sudden unexplained death.
More specifically, the most common cause of an LQTS misdiagnosis was QT prolongation following vasovagal syncope, which was misinterpreted as LQTS-attributed syncope.
The second most common cause was an apparently positive genetic test for an LQTS gene that turned out to be a benign or likely benign variant.
The third most common cause was an LQTS diagnosis based solely on a family history of sudden unexplained death (26 patients), QT prolongation (11 patients), or sudden cardiac arrest (9 patients).
The fourth most common cause was an isolated event of QT prolongation (44 patients). The transient QT prolongation was observed under myriad conditions unrelated to LQTS. Yet, 31 patients received a diagnosis based solely on the event.
The fifth most common cause was inclusion of the U-wave in the calculation of the QTc interval (40 patients), leading to an inaccurate interpretation of the electrocardiogram.
Dr. Ackerman noted that these LQTS diagnoses were given by heart-rhythm specialists, and most patients self-referred for a second opinion because a family member questioned the diagnosis after doing their own research.
“It’s time that we step up to the plate and do better,” Dr. Ackerman said. The team’s evaluation of the impact of the misdiagnosis on the patients’ lifestyle and quality of life showed that 45% had been restricted from competitive sports (and subsequently resumed sports activity with no adverse events); 80% had been started on beta-blockers (the drugs were discontinued in 84% as a result of the Mayo Clinic evaluation, whereas 16% opted to continue); and 10 of 22 patients (45%) who received an implanted cardioverter device underwent an extraction of the device without complications.
The authors conclude: “Although missing a patient who truly has LQTS can lead to a tragic outcome, the implications of overdiagnosed LQTS are not trivial and are potentially tragic as well.”
‘Tricky diagnosis’
LQTS specialist Peter Aziz, MD, director of pediatric electrophysiology at the Cleveland Clinic, agreed with these findings.
“Most of us ‘channelopathists’ who see LQTS for a living have a good grasp of the disease, but it can be elusive for others,” he said in an interview. “This is a tricky diagnosis. There are ends of the spectrum where people for sure don’t have it and people for sure do. Most clinicians are able to identify that.”
However, he added, “A lot of patients fall into that gray area where it may not be clear at first, even to an expert. But the expert knows how to do a comprehensive evaluation, examining episodes and symptoms and understanding whether they are relevant to LQTS or completely red herrings, and feeling confident about how they calculate the acute interval on an electrocardiogram.”
“All of these may seem mundane, but without the experience, clinicians are vulnerable to miscalculations,” he said. “That’s why our bias, as channelopathists, is that every patient who has a suspected diagnosis or is being treated for LQTS really should see an expert.”
Similarly, Arthur A.M. Wilde, MD, PhD, of the University of Amsterdam, and Peter J. Schwartz, MD, of IRCCS Istituto Auxologico Italiano, Milan, write in a related editorial that it “has to be kept in mind that both diagnostic scores and risk scores are dynamic and can be modified by time and by appropriate therapy.
“Therefore, to make hasty diagnosis of a disease that requires life-long treatment is inappropriate, especially when this is done without the support of adequate, specific experience.”
No commercial funding or relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY