User login
MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Cut in AFib burden gains traction as gauge of ablation success: PULSED-AF
suggests a new analysis.
It’s the first study tying those outcomes to residual AFib burden after ablation achieved using the emerging pulsed-field ablation (PFA) technology, say researchers. These associations are already established for cath ablation using traditional radiofrequency energy or cryoablation.
The new findings come from a secondary analysis of the recently published PULSED-AF study, which highlighted the ablation efficacy of Medtronic’s investigational PulseSelect PFA system in patients with either paroxysmal AFib (PAF) or persistent AFib.
The trial had entered 300 adult candidates for catheter ablation of recurrent, symptomatic PAF or persistent AFib at 41 centers in Australia, Canada, Europe, Japan, and the United States.
After ablation, 69% of PAF patients and 62% of those who had persistent AFib showed no sign of atrial arrhythmia (AA) over 12 months, based on the trial’s method for estimating AA burden.
Residual AA burden less than 10% was seen in 87% and 82% of those initially with PAF and persistent AFib, respectively. Burdens in that lowest range, compared with greater AA burden, predicted a “clinically meaningful” improvement in QoL scores in PAF patients.
Those who entered the study with persistent AFib showed such improvement – defined as a more than 19-point gain on the Atrial Fibrillation Effect on Quality-of-Life Questionnaire – regardless of postablation AA burden.
Moreover, patients initially with either type of AFib and residual burdens in the lowest range went on to have fewer cardioversions and repeat ablations (P < .01), Atul Verma, MD, McGill University Health Centre, Montreal, reported at the annual scientific sessions of the Heart Rhythm Society.
Dr. Verma, the trial’s principal investigator, is also lead author on the same-day publication of the secondary analysis in Heart Rhythm.
Binary endpoint lacks relevance
The PULSED-AF primary analysis defined ablation efficacy partly as freedom from AA recurrence lasting at least 30 seconds, with or without symptoms, a traditional AFib-ablation trial endpoint that is nonetheless considered clinically unhelpful.
The secondary analysis recasts that binary endpoint as degree of reduction in AFib burden, a continuous variable. That potentially allows AFib ablation efficacy to be assessed in a more nuanced way likely to be more meaningful to patients and the health care system, observed Dr. Verma and colleagues.
The “30-second endpoint” is limited in clinical usefulness and “doesn’t mean much to the patient,” he said at a press conference on the analysis before formally presenting it at the HRS sessions.
Recent AFib ablation trials have explored AA burden as possibly a superior way to assess the procedure’s success “but also to see if it’s better correlated with quality of life and health care outcomes,” Dr. Verma said. “So that’s exactly what we’ve tried to do here using the PULSED-AF data.”
In the secondary analysis, he said, patients’ rate of freedom from the 30-second endpoint was about 70%, but “more than 85% of them had an AFib burden of less than 10%.”
“This efficacy endpoint of 30 seconds of atrial arrhythmia has been challenged and has been seen clinically as insignificant,” agreed Rajeev Pathak, MBBS, PhD, of Australian National University and director of cardiac electrophysiology at Canberra (Australia) Hospital.
In AFib radiofrequency ablation and cryoablation studies “there is clear disconnect between these 30-second episodes of atrial arrhythmias we see and the clinical relevance of health care utilization and quality of life,” said Dr. Pathak, invited discussant for Dr. Verma’s presentation at the sessions.
Now an AFib ablation trial using PFA catheters has yielded similar results, finding AA burden to be “a more objective and relevant measure of success,” he said. “A 30-second endpoint is arbitrary, lacks significance, and is highly dependent on the monitoring strategy.”
The more you look, the more you see
The new secondary analysis included a demonstration that success rates based on the 30-second endpoint indeed vary depending on how subsequent arrhythmias are monitored.
As described by Dr. Verma, PULSED-AF data were assessed for the 30-second endpoint captured using three separate intermittent monitoring strategies that it and other recent ablation trials have used:
- Strategy A: Transtelephonic monitoring weekly and in the event of symptoms, plus 24-hour Holter monitoring at 6 and 12 months and 12-lead ECG at 3, 6, and 12 months
- Strategy B: Transtelephonic monitoring weekly and at symptoms for 3-6 months followed by monthly and at symptoms from 6 to 12 months, plus 24-hour Holter monitoring at 6 and 12 months, plus 12-lead ECG at 3, 6, and 12 months
- Strategy C: The median of two 24-hour Holter monitoring sessions per patient over 12 months
As Dr. Verma reported, rates of freedom from the 30-second endpoint climbed with successive monitoring strategies. The rates for PAF and persistent AFib patients, respectively, were: Strategy A – 70% and 62%, Strategy B – 71% and 68%, Strategy C – 91% and 86%.
“If you’re using the ‘freedom-from-30-seconds’ endpoint, the results that you are going to get are highly dependent on the monitoring strategy,” Dr. Verma said. “The more you look, the more you see.”
Valid estimation of burden
For the main PULSED-AF secondary analysis, the investigators defined AA burden according to findings on either Holter monitoring or the 12-lead ECG. “So as not to bias these results,” Dr. Verma said, “for every patient, we picked the method that gave us the highest atrial arrhythmia burden.”
Ideally, Dr. Verma said in an interview, arrhythmia burden would be determined using devices such as implantable loop recorders. “The problem is, this is expensive and not practical” in both clinical practice and many trials, so PULSED-AF investigators went with the intermittent monitoring strategy to estimate burdens.
Their method appears valid, he said, given that the study identified a statistically relevant 10% AA burden cut off for predicting quality of life improvement or less health care resource use.
“If their residual atrial arrhythmia burden was greater than 10%, they did not have a statistically significant improvement in quality of life,” Dr. Verma observed. And “very few” of them had cardioversions or repeat ablation.
“I couldn’t agree more” that residual AA burden is preferable to the 30-second endpoint for gauging AFib ablation success, Kenneth Ellenbogen, MD, Virginia Commonwealth University Medical Center, Richmond, said in an interview. Dr. Ellenbogen is also director of clinical cardiac electrophysiology and pacing at VCU Health Pauley Heart Center and not associated with PULSED-AF.
That AA burden was linked to health care resource use in the study “is absolutely brilliant,” he said, “because that’s what the bean counters really want at the end of the day. And as doctors we care about patients feeling better – improving quality of life.”
PULSED-AF was funded by Medtronic. Dr. Verma disclosed financial relationships with Bayer, Biosense Webster, Medtronic, Thermedical, Kardium, and Galaxy Medical, as well as and research grants from Adagio Medical. Dr. Ellenbogen disclosed financial relationships with Boston Scientific, Medtronic, Kestra, Hylomorph, Biotronik, MediLynx, Impulse Dynamics USA, Abbott, Biosense Webster, Milestone Pharmaceuticals, Sanofi, Medpace, and Elsevier. Dr. Pathak disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
suggests a new analysis.
It’s the first study tying those outcomes to residual AFib burden after ablation achieved using the emerging pulsed-field ablation (PFA) technology, say researchers. These associations are already established for cath ablation using traditional radiofrequency energy or cryoablation.
The new findings come from a secondary analysis of the recently published PULSED-AF study, which highlighted the ablation efficacy of Medtronic’s investigational PulseSelect PFA system in patients with either paroxysmal AFib (PAF) or persistent AFib.
The trial had entered 300 adult candidates for catheter ablation of recurrent, symptomatic PAF or persistent AFib at 41 centers in Australia, Canada, Europe, Japan, and the United States.
After ablation, 69% of PAF patients and 62% of those who had persistent AFib showed no sign of atrial arrhythmia (AA) over 12 months, based on the trial’s method for estimating AA burden.
Residual AA burden less than 10% was seen in 87% and 82% of those initially with PAF and persistent AFib, respectively. Burdens in that lowest range, compared with greater AA burden, predicted a “clinically meaningful” improvement in QoL scores in PAF patients.
Those who entered the study with persistent AFib showed such improvement – defined as a more than 19-point gain on the Atrial Fibrillation Effect on Quality-of-Life Questionnaire – regardless of postablation AA burden.
Moreover, patients initially with either type of AFib and residual burdens in the lowest range went on to have fewer cardioversions and repeat ablations (P < .01), Atul Verma, MD, McGill University Health Centre, Montreal, reported at the annual scientific sessions of the Heart Rhythm Society.
Dr. Verma, the trial’s principal investigator, is also lead author on the same-day publication of the secondary analysis in Heart Rhythm.
Binary endpoint lacks relevance
The PULSED-AF primary analysis defined ablation efficacy partly as freedom from AA recurrence lasting at least 30 seconds, with or without symptoms, a traditional AFib-ablation trial endpoint that is nonetheless considered clinically unhelpful.
The secondary analysis recasts that binary endpoint as degree of reduction in AFib burden, a continuous variable. That potentially allows AFib ablation efficacy to be assessed in a more nuanced way likely to be more meaningful to patients and the health care system, observed Dr. Verma and colleagues.
The “30-second endpoint” is limited in clinical usefulness and “doesn’t mean much to the patient,” he said at a press conference on the analysis before formally presenting it at the HRS sessions.
Recent AFib ablation trials have explored AA burden as possibly a superior way to assess the procedure’s success “but also to see if it’s better correlated with quality of life and health care outcomes,” Dr. Verma said. “So that’s exactly what we’ve tried to do here using the PULSED-AF data.”
In the secondary analysis, he said, patients’ rate of freedom from the 30-second endpoint was about 70%, but “more than 85% of them had an AFib burden of less than 10%.”
“This efficacy endpoint of 30 seconds of atrial arrhythmia has been challenged and has been seen clinically as insignificant,” agreed Rajeev Pathak, MBBS, PhD, of Australian National University and director of cardiac electrophysiology at Canberra (Australia) Hospital.
In AFib radiofrequency ablation and cryoablation studies “there is clear disconnect between these 30-second episodes of atrial arrhythmias we see and the clinical relevance of health care utilization and quality of life,” said Dr. Pathak, invited discussant for Dr. Verma’s presentation at the sessions.
Now an AFib ablation trial using PFA catheters has yielded similar results, finding AA burden to be “a more objective and relevant measure of success,” he said. “A 30-second endpoint is arbitrary, lacks significance, and is highly dependent on the monitoring strategy.”
The more you look, the more you see
The new secondary analysis included a demonstration that success rates based on the 30-second endpoint indeed vary depending on how subsequent arrhythmias are monitored.
As described by Dr. Verma, PULSED-AF data were assessed for the 30-second endpoint captured using three separate intermittent monitoring strategies that it and other recent ablation trials have used:
- Strategy A: Transtelephonic monitoring weekly and in the event of symptoms, plus 24-hour Holter monitoring at 6 and 12 months and 12-lead ECG at 3, 6, and 12 months
- Strategy B: Transtelephonic monitoring weekly and at symptoms for 3-6 months followed by monthly and at symptoms from 6 to 12 months, plus 24-hour Holter monitoring at 6 and 12 months, plus 12-lead ECG at 3, 6, and 12 months
- Strategy C: The median of two 24-hour Holter monitoring sessions per patient over 12 months
As Dr. Verma reported, rates of freedom from the 30-second endpoint climbed with successive monitoring strategies. The rates for PAF and persistent AFib patients, respectively, were: Strategy A – 70% and 62%, Strategy B – 71% and 68%, Strategy C – 91% and 86%.
“If you’re using the ‘freedom-from-30-seconds’ endpoint, the results that you are going to get are highly dependent on the monitoring strategy,” Dr. Verma said. “The more you look, the more you see.”
Valid estimation of burden
For the main PULSED-AF secondary analysis, the investigators defined AA burden according to findings on either Holter monitoring or the 12-lead ECG. “So as not to bias these results,” Dr. Verma said, “for every patient, we picked the method that gave us the highest atrial arrhythmia burden.”
Ideally, Dr. Verma said in an interview, arrhythmia burden would be determined using devices such as implantable loop recorders. “The problem is, this is expensive and not practical” in both clinical practice and many trials, so PULSED-AF investigators went with the intermittent monitoring strategy to estimate burdens.
Their method appears valid, he said, given that the study identified a statistically relevant 10% AA burden cut off for predicting quality of life improvement or less health care resource use.
“If their residual atrial arrhythmia burden was greater than 10%, they did not have a statistically significant improvement in quality of life,” Dr. Verma observed. And “very few” of them had cardioversions or repeat ablation.
“I couldn’t agree more” that residual AA burden is preferable to the 30-second endpoint for gauging AFib ablation success, Kenneth Ellenbogen, MD, Virginia Commonwealth University Medical Center, Richmond, said in an interview. Dr. Ellenbogen is also director of clinical cardiac electrophysiology and pacing at VCU Health Pauley Heart Center and not associated with PULSED-AF.
That AA burden was linked to health care resource use in the study “is absolutely brilliant,” he said, “because that’s what the bean counters really want at the end of the day. And as doctors we care about patients feeling better – improving quality of life.”
PULSED-AF was funded by Medtronic. Dr. Verma disclosed financial relationships with Bayer, Biosense Webster, Medtronic, Thermedical, Kardium, and Galaxy Medical, as well as and research grants from Adagio Medical. Dr. Ellenbogen disclosed financial relationships with Boston Scientific, Medtronic, Kestra, Hylomorph, Biotronik, MediLynx, Impulse Dynamics USA, Abbott, Biosense Webster, Milestone Pharmaceuticals, Sanofi, Medpace, and Elsevier. Dr. Pathak disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
suggests a new analysis.
It’s the first study tying those outcomes to residual AFib burden after ablation achieved using the emerging pulsed-field ablation (PFA) technology, say researchers. These associations are already established for cath ablation using traditional radiofrequency energy or cryoablation.
The new findings come from a secondary analysis of the recently published PULSED-AF study, which highlighted the ablation efficacy of Medtronic’s investigational PulseSelect PFA system in patients with either paroxysmal AFib (PAF) or persistent AFib.
The trial had entered 300 adult candidates for catheter ablation of recurrent, symptomatic PAF or persistent AFib at 41 centers in Australia, Canada, Europe, Japan, and the United States.
After ablation, 69% of PAF patients and 62% of those who had persistent AFib showed no sign of atrial arrhythmia (AA) over 12 months, based on the trial’s method for estimating AA burden.
Residual AA burden less than 10% was seen in 87% and 82% of those initially with PAF and persistent AFib, respectively. Burdens in that lowest range, compared with greater AA burden, predicted a “clinically meaningful” improvement in QoL scores in PAF patients.
Those who entered the study with persistent AFib showed such improvement – defined as a more than 19-point gain on the Atrial Fibrillation Effect on Quality-of-Life Questionnaire – regardless of postablation AA burden.
Moreover, patients initially with either type of AFib and residual burdens in the lowest range went on to have fewer cardioversions and repeat ablations (P < .01), Atul Verma, MD, McGill University Health Centre, Montreal, reported at the annual scientific sessions of the Heart Rhythm Society.
Dr. Verma, the trial’s principal investigator, is also lead author on the same-day publication of the secondary analysis in Heart Rhythm.
Binary endpoint lacks relevance
The PULSED-AF primary analysis defined ablation efficacy partly as freedom from AA recurrence lasting at least 30 seconds, with or without symptoms, a traditional AFib-ablation trial endpoint that is nonetheless considered clinically unhelpful.
The secondary analysis recasts that binary endpoint as degree of reduction in AFib burden, a continuous variable. That potentially allows AFib ablation efficacy to be assessed in a more nuanced way likely to be more meaningful to patients and the health care system, observed Dr. Verma and colleagues.
The “30-second endpoint” is limited in clinical usefulness and “doesn’t mean much to the patient,” he said at a press conference on the analysis before formally presenting it at the HRS sessions.
Recent AFib ablation trials have explored AA burden as possibly a superior way to assess the procedure’s success “but also to see if it’s better correlated with quality of life and health care outcomes,” Dr. Verma said. “So that’s exactly what we’ve tried to do here using the PULSED-AF data.”
In the secondary analysis, he said, patients’ rate of freedom from the 30-second endpoint was about 70%, but “more than 85% of them had an AFib burden of less than 10%.”
“This efficacy endpoint of 30 seconds of atrial arrhythmia has been challenged and has been seen clinically as insignificant,” agreed Rajeev Pathak, MBBS, PhD, of Australian National University and director of cardiac electrophysiology at Canberra (Australia) Hospital.
In AFib radiofrequency ablation and cryoablation studies “there is clear disconnect between these 30-second episodes of atrial arrhythmias we see and the clinical relevance of health care utilization and quality of life,” said Dr. Pathak, invited discussant for Dr. Verma’s presentation at the sessions.
Now an AFib ablation trial using PFA catheters has yielded similar results, finding AA burden to be “a more objective and relevant measure of success,” he said. “A 30-second endpoint is arbitrary, lacks significance, and is highly dependent on the monitoring strategy.”
The more you look, the more you see
The new secondary analysis included a demonstration that success rates based on the 30-second endpoint indeed vary depending on how subsequent arrhythmias are monitored.
As described by Dr. Verma, PULSED-AF data were assessed for the 30-second endpoint captured using three separate intermittent monitoring strategies that it and other recent ablation trials have used:
- Strategy A: Transtelephonic monitoring weekly and in the event of symptoms, plus 24-hour Holter monitoring at 6 and 12 months and 12-lead ECG at 3, 6, and 12 months
- Strategy B: Transtelephonic monitoring weekly and at symptoms for 3-6 months followed by monthly and at symptoms from 6 to 12 months, plus 24-hour Holter monitoring at 6 and 12 months, plus 12-lead ECG at 3, 6, and 12 months
- Strategy C: The median of two 24-hour Holter monitoring sessions per patient over 12 months
As Dr. Verma reported, rates of freedom from the 30-second endpoint climbed with successive monitoring strategies. The rates for PAF and persistent AFib patients, respectively, were: Strategy A – 70% and 62%, Strategy B – 71% and 68%, Strategy C – 91% and 86%.
“If you’re using the ‘freedom-from-30-seconds’ endpoint, the results that you are going to get are highly dependent on the monitoring strategy,” Dr. Verma said. “The more you look, the more you see.”
Valid estimation of burden
For the main PULSED-AF secondary analysis, the investigators defined AA burden according to findings on either Holter monitoring or the 12-lead ECG. “So as not to bias these results,” Dr. Verma said, “for every patient, we picked the method that gave us the highest atrial arrhythmia burden.”
Ideally, Dr. Verma said in an interview, arrhythmia burden would be determined using devices such as implantable loop recorders. “The problem is, this is expensive and not practical” in both clinical practice and many trials, so PULSED-AF investigators went with the intermittent monitoring strategy to estimate burdens.
Their method appears valid, he said, given that the study identified a statistically relevant 10% AA burden cut off for predicting quality of life improvement or less health care resource use.
“If their residual atrial arrhythmia burden was greater than 10%, they did not have a statistically significant improvement in quality of life,” Dr. Verma observed. And “very few” of them had cardioversions or repeat ablation.
“I couldn’t agree more” that residual AA burden is preferable to the 30-second endpoint for gauging AFib ablation success, Kenneth Ellenbogen, MD, Virginia Commonwealth University Medical Center, Richmond, said in an interview. Dr. Ellenbogen is also director of clinical cardiac electrophysiology and pacing at VCU Health Pauley Heart Center and not associated with PULSED-AF.
That AA burden was linked to health care resource use in the study “is absolutely brilliant,” he said, “because that’s what the bean counters really want at the end of the day. And as doctors we care about patients feeling better – improving quality of life.”
PULSED-AF was funded by Medtronic. Dr. Verma disclosed financial relationships with Bayer, Biosense Webster, Medtronic, Thermedical, Kardium, and Galaxy Medical, as well as and research grants from Adagio Medical. Dr. Ellenbogen disclosed financial relationships with Boston Scientific, Medtronic, Kestra, Hylomorph, Biotronik, MediLynx, Impulse Dynamics USA, Abbott, Biosense Webster, Milestone Pharmaceuticals, Sanofi, Medpace, and Elsevier. Dr. Pathak disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM HRS 2023
Earlier anticoagulation safe in stroke with AFib: ELAN
, a new study suggests.
The ELAN trial found that starting DOAC treatment earlier was not associated with an increased risk for intracranial hemorrhage (ICH) but rather was linked to a lower rate of ischemic events.
“We conclude that there is no reason to delay DOAC treatment in these patients. Our results suggest that early DOAC treatment is reasonable; it is unlikely to cause harm, and it is probably better at reducing ischemic events,” lead investigator of the study, Urs Fischer, MD, professor of neurology at University Hospital Basel (Switzerland), commented in an interview.
“This trial will change clinical practice in that we can feel much more reassured that starting DOAC treatment early in these patients will not cause harm,” he said.
Senior investigator Jesse Dawson, MD, professor of stroke medicine at Queen Elizabeth University Hospital, Glasgow, added: “This issue of timing of DOAC treatment causes a lot of anxiety in our daily workload. Clinicians are scared of causing an ICH, so they tend to wait. These results will ease a lot of that anxiety.”
Dr. Fischer presented the results of the ELAN trial at the European Stroke Organisation Conference (ESOC) in Munich. The trial was also simultaneously published online in The New England Journal of Medicine.
He explained that patients presenting with acute ischemic stroke who are found to have atrial fibrillation need to be started on anticoagulation to reduce the risk for a recurrent stroke. But there are no clear guidelines on when to start anticoagulation in these patients at present, with concerns that starting very early may increase the risk for hemorrhagic transformation and ICH.
Based on observations that patients with larger strokes have a higher risk for ICH in the early post-stroke period, some guidelines advise different times for starting anticoagulation for different stroke severities: 1 day for a transient ischemic attack, 3 days for a minor stroke, 6 days for a moderate stroke, and 12 days for a severe stroke – known as the 1-, 3-, 6-, 12-day rule.
“But this is not based on evidence – just on expert opinion,” Dr. Fischer noted. “The ELAN trial was conducted to obtain more solid information on optimal timing for starting anticoagulation and whether we can safely start a DOAC earlier than these guidelines currently advise.”
For the trial, which was conducted in 15 countries, 2,013 patients with an acute ischemic stroke and found to have AFib were randomly selected to start DOAC treatment earlier or later.
The later-treatment strategy followed the current approach of starting treatment at day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke, whereas the earlier-treatment group started DOAC treatment within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke.
In terms of stroke severity, which was defined on imaging-based criteria, 37% of patients had a minor stroke, 40% had a moderate stroke, and 23% had a major stroke.
The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization.
Results showed that this occurred in 2.9% in the early-treatment group and 4.1% in the later-treatment group (risk difference, –1.18 percentage points; 95% confidence interval, –2.84-0.47) by 30 days.
Recurrent ischemic stroke occurred in 1.4% in the early-treatment group and 2.5% in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29-1.07). Symptomatic intracranial hemorrhage occurred in two participants (0.2%) in both groups by 30 days.
The rates of the outcomes increased only slightly more at 90 days than at 30 days, “findings that suggest there was not an excessive risk associated with early anticoagulation through that period,” the researchers report in the NEJM paper.
“Early treatment initiation can therefore be supported if indicated or if desired,” they conclude.
“The most important finding was that among 2,000 patients randomized, there was a very low rate of bleeding complications and no increase in any bleeding complication in the early DOAC group. This has been a major worry about starting anticoagulation early,” Dr. Fischer commented.
“These are very practical findings in that we can keep things simple,” Dr. Dawson added. “If the patient has a big stroke, anticoagulation with a DOAC can now be started at 6 days. For everyone else, we can start DOAC treatment as soon as possible without fear of causing harm. So, we can now confidently give patients with a minor or moderate stroke, as defined by imaging, a beneficial treatment as soon as we establish they are having an ischemic stroke and have AFib.”
Dr. Dawson pointed out that about 25% of patients with ischemic stroke are found to have AFib on admission ECG, and in another 4%-5%, AFib is found in the first 48 hours. “These are the patients we are targeting in this study.”
The researchers note that the trial did not have a statistical superiority or noninferiority design but rather aimed to estimate the treatment effects of early initiation versus later initiation of DOACs.
“This trial was slightly different in that we weren’t testing a strict statistical hypothesis because we didn’t have any data with which to formulate what sort of effect size to aim for, so we performed a qualitative trial to look at what the event rates were with the two approaches,” Dr. Fischer explained. “Our main findings are that ICH rates were not increased with early DOAC treatment and that ischemic event rates were numerically reduced, but because we didn’t have strict statistical limits, we can only say this is a high probability but not a certainty.”
Dr. Dawson added: “We can say from these results that there is a high level of probability that early DOAC treatment does not cause harm and a reasonable probability that it reduces risks of a recurrent stroke or other ischemic event.”
The researchers give an estimate of the effect size for the primary composite endpoint, which combines the major ischemic and bleeding events, ranging from a 2.8% lower risk to a 0.5% higher risk with early DOAC treatment.
“So, it is very likely that the composite endpoint would be lower,” Dr. Dawson said.
Dr. Fischer noted that a previous study (TIMING) tried to address the issue of earlier versus later anticoagulation in these patients but was stopped early after 880 patients had been enrolled because of slow recruitment.
“Results from this study failed to show superiority of early versus late DOAC treatment but they did suggest noninferiority, and they also found no increase in major bleeding complications, which is an added reassurance,” he commented.
Another trial looking at early versus late anticoagulation in these patients, OPTIMAS, is ongoing in the United Kingdom and is aiming to randomize 3,500 patients.
Imaging-based assessment of stroke severity
In the ELAN trial, the definition of stroke severity was based on imaging rather than on the National Institutes of Health Stroke Scale (NIHSS).
“We took a cautious approach by using imaging to define stroke severity. So, when using these results in clinical practice, it is important that patients are selected for the timing of DOAC treatment based on the imaging results,” Dr. Dawson explained. “This is very straightforward, as the size of the stroke can be seen clearly on the routine CT imaging that all patients receive up front. This is a very pragmatic and simple protocol. And advanced imaging is not required.”
He noted that though clinicians tend to use the NIHSS clinical symptom score to define mild, moderate, and severe stroke, the imaging approach is actually more accurate when determining the risk for bleeding and ICH. And though imaging results often correlate with NIHSS scores, there can be some exceptions.
Commenting on the ELAN trial results at the ESOC meeting, Georgios Tsivgoulis, MD, professor of neurology, University of Athens, said that the trial showed that early administration of DOACs in these patients was safe and did not increase the rate of ICH.
“There was a very low ICH rate with only two events in each group. And then there was above a 1% reduction in the composite outcome including ischemic vascular events and bleeding,” he noted.
“This is important because there are many thousands of patients with acute ischemic stroke and AFib, and now we have a large study showing we can treat them with a DOAC early, and this appears to be safe and it appears also be more effective in terms of outcome events,” Dr. Tsivgoulis said.
But he highlighted one important caveat: The majority of patients had mild or moderate stroke.
A version of this article first appeared on Medscape.com.
, a new study suggests.
The ELAN trial found that starting DOAC treatment earlier was not associated with an increased risk for intracranial hemorrhage (ICH) but rather was linked to a lower rate of ischemic events.
“We conclude that there is no reason to delay DOAC treatment in these patients. Our results suggest that early DOAC treatment is reasonable; it is unlikely to cause harm, and it is probably better at reducing ischemic events,” lead investigator of the study, Urs Fischer, MD, professor of neurology at University Hospital Basel (Switzerland), commented in an interview.
“This trial will change clinical practice in that we can feel much more reassured that starting DOAC treatment early in these patients will not cause harm,” he said.
Senior investigator Jesse Dawson, MD, professor of stroke medicine at Queen Elizabeth University Hospital, Glasgow, added: “This issue of timing of DOAC treatment causes a lot of anxiety in our daily workload. Clinicians are scared of causing an ICH, so they tend to wait. These results will ease a lot of that anxiety.”
Dr. Fischer presented the results of the ELAN trial at the European Stroke Organisation Conference (ESOC) in Munich. The trial was also simultaneously published online in The New England Journal of Medicine.
He explained that patients presenting with acute ischemic stroke who are found to have atrial fibrillation need to be started on anticoagulation to reduce the risk for a recurrent stroke. But there are no clear guidelines on when to start anticoagulation in these patients at present, with concerns that starting very early may increase the risk for hemorrhagic transformation and ICH.
Based on observations that patients with larger strokes have a higher risk for ICH in the early post-stroke period, some guidelines advise different times for starting anticoagulation for different stroke severities: 1 day for a transient ischemic attack, 3 days for a minor stroke, 6 days for a moderate stroke, and 12 days for a severe stroke – known as the 1-, 3-, 6-, 12-day rule.
“But this is not based on evidence – just on expert opinion,” Dr. Fischer noted. “The ELAN trial was conducted to obtain more solid information on optimal timing for starting anticoagulation and whether we can safely start a DOAC earlier than these guidelines currently advise.”
For the trial, which was conducted in 15 countries, 2,013 patients with an acute ischemic stroke and found to have AFib were randomly selected to start DOAC treatment earlier or later.
The later-treatment strategy followed the current approach of starting treatment at day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke, whereas the earlier-treatment group started DOAC treatment within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke.
In terms of stroke severity, which was defined on imaging-based criteria, 37% of patients had a minor stroke, 40% had a moderate stroke, and 23% had a major stroke.
The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization.
Results showed that this occurred in 2.9% in the early-treatment group and 4.1% in the later-treatment group (risk difference, –1.18 percentage points; 95% confidence interval, –2.84-0.47) by 30 days.
Recurrent ischemic stroke occurred in 1.4% in the early-treatment group and 2.5% in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29-1.07). Symptomatic intracranial hemorrhage occurred in two participants (0.2%) in both groups by 30 days.
The rates of the outcomes increased only slightly more at 90 days than at 30 days, “findings that suggest there was not an excessive risk associated with early anticoagulation through that period,” the researchers report in the NEJM paper.
“Early treatment initiation can therefore be supported if indicated or if desired,” they conclude.
“The most important finding was that among 2,000 patients randomized, there was a very low rate of bleeding complications and no increase in any bleeding complication in the early DOAC group. This has been a major worry about starting anticoagulation early,” Dr. Fischer commented.
“These are very practical findings in that we can keep things simple,” Dr. Dawson added. “If the patient has a big stroke, anticoagulation with a DOAC can now be started at 6 days. For everyone else, we can start DOAC treatment as soon as possible without fear of causing harm. So, we can now confidently give patients with a minor or moderate stroke, as defined by imaging, a beneficial treatment as soon as we establish they are having an ischemic stroke and have AFib.”
Dr. Dawson pointed out that about 25% of patients with ischemic stroke are found to have AFib on admission ECG, and in another 4%-5%, AFib is found in the first 48 hours. “These are the patients we are targeting in this study.”
The researchers note that the trial did not have a statistical superiority or noninferiority design but rather aimed to estimate the treatment effects of early initiation versus later initiation of DOACs.
“This trial was slightly different in that we weren’t testing a strict statistical hypothesis because we didn’t have any data with which to formulate what sort of effect size to aim for, so we performed a qualitative trial to look at what the event rates were with the two approaches,” Dr. Fischer explained. “Our main findings are that ICH rates were not increased with early DOAC treatment and that ischemic event rates were numerically reduced, but because we didn’t have strict statistical limits, we can only say this is a high probability but not a certainty.”
Dr. Dawson added: “We can say from these results that there is a high level of probability that early DOAC treatment does not cause harm and a reasonable probability that it reduces risks of a recurrent stroke or other ischemic event.”
The researchers give an estimate of the effect size for the primary composite endpoint, which combines the major ischemic and bleeding events, ranging from a 2.8% lower risk to a 0.5% higher risk with early DOAC treatment.
“So, it is very likely that the composite endpoint would be lower,” Dr. Dawson said.
Dr. Fischer noted that a previous study (TIMING) tried to address the issue of earlier versus later anticoagulation in these patients but was stopped early after 880 patients had been enrolled because of slow recruitment.
“Results from this study failed to show superiority of early versus late DOAC treatment but they did suggest noninferiority, and they also found no increase in major bleeding complications, which is an added reassurance,” he commented.
Another trial looking at early versus late anticoagulation in these patients, OPTIMAS, is ongoing in the United Kingdom and is aiming to randomize 3,500 patients.
Imaging-based assessment of stroke severity
In the ELAN trial, the definition of stroke severity was based on imaging rather than on the National Institutes of Health Stroke Scale (NIHSS).
“We took a cautious approach by using imaging to define stroke severity. So, when using these results in clinical practice, it is important that patients are selected for the timing of DOAC treatment based on the imaging results,” Dr. Dawson explained. “This is very straightforward, as the size of the stroke can be seen clearly on the routine CT imaging that all patients receive up front. This is a very pragmatic and simple protocol. And advanced imaging is not required.”
He noted that though clinicians tend to use the NIHSS clinical symptom score to define mild, moderate, and severe stroke, the imaging approach is actually more accurate when determining the risk for bleeding and ICH. And though imaging results often correlate with NIHSS scores, there can be some exceptions.
Commenting on the ELAN trial results at the ESOC meeting, Georgios Tsivgoulis, MD, professor of neurology, University of Athens, said that the trial showed that early administration of DOACs in these patients was safe and did not increase the rate of ICH.
“There was a very low ICH rate with only two events in each group. And then there was above a 1% reduction in the composite outcome including ischemic vascular events and bleeding,” he noted.
“This is important because there are many thousands of patients with acute ischemic stroke and AFib, and now we have a large study showing we can treat them with a DOAC early, and this appears to be safe and it appears also be more effective in terms of outcome events,” Dr. Tsivgoulis said.
But he highlighted one important caveat: The majority of patients had mild or moderate stroke.
A version of this article first appeared on Medscape.com.
, a new study suggests.
The ELAN trial found that starting DOAC treatment earlier was not associated with an increased risk for intracranial hemorrhage (ICH) but rather was linked to a lower rate of ischemic events.
“We conclude that there is no reason to delay DOAC treatment in these patients. Our results suggest that early DOAC treatment is reasonable; it is unlikely to cause harm, and it is probably better at reducing ischemic events,” lead investigator of the study, Urs Fischer, MD, professor of neurology at University Hospital Basel (Switzerland), commented in an interview.
“This trial will change clinical practice in that we can feel much more reassured that starting DOAC treatment early in these patients will not cause harm,” he said.
Senior investigator Jesse Dawson, MD, professor of stroke medicine at Queen Elizabeth University Hospital, Glasgow, added: “This issue of timing of DOAC treatment causes a lot of anxiety in our daily workload. Clinicians are scared of causing an ICH, so they tend to wait. These results will ease a lot of that anxiety.”
Dr. Fischer presented the results of the ELAN trial at the European Stroke Organisation Conference (ESOC) in Munich. The trial was also simultaneously published online in The New England Journal of Medicine.
He explained that patients presenting with acute ischemic stroke who are found to have atrial fibrillation need to be started on anticoagulation to reduce the risk for a recurrent stroke. But there are no clear guidelines on when to start anticoagulation in these patients at present, with concerns that starting very early may increase the risk for hemorrhagic transformation and ICH.
Based on observations that patients with larger strokes have a higher risk for ICH in the early post-stroke period, some guidelines advise different times for starting anticoagulation for different stroke severities: 1 day for a transient ischemic attack, 3 days for a minor stroke, 6 days for a moderate stroke, and 12 days for a severe stroke – known as the 1-, 3-, 6-, 12-day rule.
“But this is not based on evidence – just on expert opinion,” Dr. Fischer noted. “The ELAN trial was conducted to obtain more solid information on optimal timing for starting anticoagulation and whether we can safely start a DOAC earlier than these guidelines currently advise.”
For the trial, which was conducted in 15 countries, 2,013 patients with an acute ischemic stroke and found to have AFib were randomly selected to start DOAC treatment earlier or later.
The later-treatment strategy followed the current approach of starting treatment at day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke, whereas the earlier-treatment group started DOAC treatment within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke.
In terms of stroke severity, which was defined on imaging-based criteria, 37% of patients had a minor stroke, 40% had a moderate stroke, and 23% had a major stroke.
The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization.
Results showed that this occurred in 2.9% in the early-treatment group and 4.1% in the later-treatment group (risk difference, –1.18 percentage points; 95% confidence interval, –2.84-0.47) by 30 days.
Recurrent ischemic stroke occurred in 1.4% in the early-treatment group and 2.5% in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29-1.07). Symptomatic intracranial hemorrhage occurred in two participants (0.2%) in both groups by 30 days.
The rates of the outcomes increased only slightly more at 90 days than at 30 days, “findings that suggest there was not an excessive risk associated with early anticoagulation through that period,” the researchers report in the NEJM paper.
“Early treatment initiation can therefore be supported if indicated or if desired,” they conclude.
“The most important finding was that among 2,000 patients randomized, there was a very low rate of bleeding complications and no increase in any bleeding complication in the early DOAC group. This has been a major worry about starting anticoagulation early,” Dr. Fischer commented.
“These are very practical findings in that we can keep things simple,” Dr. Dawson added. “If the patient has a big stroke, anticoagulation with a DOAC can now be started at 6 days. For everyone else, we can start DOAC treatment as soon as possible without fear of causing harm. So, we can now confidently give patients with a minor or moderate stroke, as defined by imaging, a beneficial treatment as soon as we establish they are having an ischemic stroke and have AFib.”
Dr. Dawson pointed out that about 25% of patients with ischemic stroke are found to have AFib on admission ECG, and in another 4%-5%, AFib is found in the first 48 hours. “These are the patients we are targeting in this study.”
The researchers note that the trial did not have a statistical superiority or noninferiority design but rather aimed to estimate the treatment effects of early initiation versus later initiation of DOACs.
“This trial was slightly different in that we weren’t testing a strict statistical hypothesis because we didn’t have any data with which to formulate what sort of effect size to aim for, so we performed a qualitative trial to look at what the event rates were with the two approaches,” Dr. Fischer explained. “Our main findings are that ICH rates were not increased with early DOAC treatment and that ischemic event rates were numerically reduced, but because we didn’t have strict statistical limits, we can only say this is a high probability but not a certainty.”
Dr. Dawson added: “We can say from these results that there is a high level of probability that early DOAC treatment does not cause harm and a reasonable probability that it reduces risks of a recurrent stroke or other ischemic event.”
The researchers give an estimate of the effect size for the primary composite endpoint, which combines the major ischemic and bleeding events, ranging from a 2.8% lower risk to a 0.5% higher risk with early DOAC treatment.
“So, it is very likely that the composite endpoint would be lower,” Dr. Dawson said.
Dr. Fischer noted that a previous study (TIMING) tried to address the issue of earlier versus later anticoagulation in these patients but was stopped early after 880 patients had been enrolled because of slow recruitment.
“Results from this study failed to show superiority of early versus late DOAC treatment but they did suggest noninferiority, and they also found no increase in major bleeding complications, which is an added reassurance,” he commented.
Another trial looking at early versus late anticoagulation in these patients, OPTIMAS, is ongoing in the United Kingdom and is aiming to randomize 3,500 patients.
Imaging-based assessment of stroke severity
In the ELAN trial, the definition of stroke severity was based on imaging rather than on the National Institutes of Health Stroke Scale (NIHSS).
“We took a cautious approach by using imaging to define stroke severity. So, when using these results in clinical practice, it is important that patients are selected for the timing of DOAC treatment based on the imaging results,” Dr. Dawson explained. “This is very straightforward, as the size of the stroke can be seen clearly on the routine CT imaging that all patients receive up front. This is a very pragmatic and simple protocol. And advanced imaging is not required.”
He noted that though clinicians tend to use the NIHSS clinical symptom score to define mild, moderate, and severe stroke, the imaging approach is actually more accurate when determining the risk for bleeding and ICH. And though imaging results often correlate with NIHSS scores, there can be some exceptions.
Commenting on the ELAN trial results at the ESOC meeting, Georgios Tsivgoulis, MD, professor of neurology, University of Athens, said that the trial showed that early administration of DOACs in these patients was safe and did not increase the rate of ICH.
“There was a very low ICH rate with only two events in each group. And then there was above a 1% reduction in the composite outcome including ischemic vascular events and bleeding,” he noted.
“This is important because there are many thousands of patients with acute ischemic stroke and AFib, and now we have a large study showing we can treat them with a DOAC early, and this appears to be safe and it appears also be more effective in terms of outcome events,” Dr. Tsivgoulis said.
But he highlighted one important caveat: The majority of patients had mild or moderate stroke.
A version of this article first appeared on Medscape.com.
FROM ESOC 2023
Half of deaths from homozygous FH occur before age 32 years
MANNHEIM, GERMANY –
The researchers looked at almost 40 patients from the HoFH International Clinical Collaborators (HICC) registry who had died before data entry, finding that they had a mean age of diagnosis of 12 years.
Even those who received treatment had high LDL cholesterol levels, and 70% developed atherosclerotic cardiovascular disease (ASCVD) at a median age of 28 years.
Worryingly, the results showed that the median age at death was 32 years. Results were presented at the annual congress of the European Atherosclerosis Society.
Patients with HoFH “have severe atherosclerotic cardiovascular disease risk,” said study presenter Janneke Mulder, a PhD candidate at the department of internal medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
“Therefore, early diagnosis and initiation of treatments, and also a combination of treatments, is really crucial,” she added.
Call to action
Approached for comment, Maciej Banach, MD, PhD, full professor of cardiology, Polish Mother’s Memorial Hospital Research Institute, Lodz, and Secretary of the EAS, described the results as “terrifying.”
He said in an interview that they are a “call to action,” especially given that so few patients in the study received intensive combination lipid-lowering therapy despite having a baseline LDL cholesterol level that was “very, very high.”
Banach underlined that patients who receive triple lipid-lowering therapy with a high-intensity statin, ezetimibe (Nustendi), and a proprotein convertase subtilisin/kexin type 9 inhibitor, could expect, based on current evidence, to see their LDL cholesterol levels reduced by 85% and be on target.
“Obviously, this is kind of academic,” because in the real-world “this 85% is not observed very often,” but it offers a target for steep reductions in cholesterol levels.
“This is something that we should focus on for these patients from the beginning,” said Dr. Banach, either with a stepwise approach “or for experts in pediatric HoFH, “maybe immediately.”
He emphasized that clinicians have everything at hand to “be both effective in the early diagnosis of HoFH, the earlier the better, and obviously to be effective with its treatment.”
“We should do something to prolong the lives of those people,” because the current results are “terrifying,” Dr. Banach added.
Rare genetic condition
Presenting her findings, Ms. Mulder began by highlighting that HoFH is a “rare genetic condition that occurs due to mutations in cholesterol metabolism.”
This, she continued, leads to “severely increased LDL cholesterol levels, and consequently to very premature cardiovascular disease,” with patients potentially experiencing their first cardiovascular event before age 20 years.
Ms. Mulder pointed out that, although there have been case series in the literature on HoFH, they have had “limited numbers” and patients have typically spent decades being treated at the same lipid management clinic.
To broaden the understanding of the clinical characteristics and management of patients dying with HoFH, the team examined data from the HICC registry, which is “the largest contemporary database of homozygous FH patients,” Ms. Mulder said.
It includes 751 patients with HoFH from 88 centers in 38 countries who were alive in 2010 or later. Data entry was between 2016 and 2020. The current analysis focused on 37 patients who had already died by the time they were included on the registry.
Of those, 49% were women, 38% were of White ethnicity, and 43% were from high-income countries.
The median age at diagnosis was 12 years, Ms. Mulder said, explaining that this is similar to that seen in other studies. The majority (86%) underwent genetic testing, and 92% presented with xanthomas.
Ms. Mulder also noted that, at their final clinical evaluation, which was conducted a median age of 18 years after their initial diagnosis, 43% of patients were recorded as current or former smokers.
In terms of their lipid-lowering therapy, 94% were taking a statin, whereas 68% were on ezetimibe, and 23% were undergoing apheresis.
Ms. Mulder said that the median number of lipid-lowering therapies per patient was two, and that “sadly ... 26% of the deceased patients had only one or no treatment.”
Therefore, perhaps unsurprisingly even those patients who were receiving treatment had LDL cholesterol levels that were “too high,” at 9.4 mmol/L versus 15.6 mmol/L among those who were untreated.
There was a high prevalence of ASCVD, at 70% overall, or 41% for aortic stenosis, 30% for myocardial infarction, 30% for angina pectoris, and 22% each for aortic valve replacement and coronary artery bypass grafting. In addition, 19% underwent percutaneous coronary intervention.
The median age of onset for ASCVD was 28 years. Ms. Mulder pointed out, however, that, as data were not available for all patients, “this might be an underestimation.” About 70% of patients experienced recurrent ASCVD.
There was a wide range in the age at which patients with HoFH died, although the median was, “strikingly,” 32 years, Ms. Mulder said. Death was confirmed as stemming from cardiovascular causes in 76% of cases.
During the postpresentation discussion, session chair Antonio J. Vallejo-Vaz, PhD, from the Research Group of Clinical Epidemiology and Vascular Risk, Institute of Biomedicine of Seville (Spain), highlighted that, if 38% of the patients were of White ethnicity, then the remainder must therefore be from other ethnic groups.
“There could be potential issues with accessibility to lipid centers” for these patients, which could affect the findings, noted Dr. Vallejo-Vaz, who is also chief scientist of the EAS Familial Hypercholesterolaemia Studies Collaboration.
Ms. Mulder agreed, replying that their results, though already striking, may be an underestimation because the patients were all from either high or middle-income countries, “so it would be good to have some data on low-income countries.”
She was also asked about two patients who died at a much older age than did the others, at ages 70 years and 86 years, respectively, and whether they had, for example, a protective genetic mutation.
Ms. Mulder said that they do not yet know, but they are planning an extended case series on these and other long-lived patients so that they can be investigated further.
No funding or relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
MANNHEIM, GERMANY –
The researchers looked at almost 40 patients from the HoFH International Clinical Collaborators (HICC) registry who had died before data entry, finding that they had a mean age of diagnosis of 12 years.
Even those who received treatment had high LDL cholesterol levels, and 70% developed atherosclerotic cardiovascular disease (ASCVD) at a median age of 28 years.
Worryingly, the results showed that the median age at death was 32 years. Results were presented at the annual congress of the European Atherosclerosis Society.
Patients with HoFH “have severe atherosclerotic cardiovascular disease risk,” said study presenter Janneke Mulder, a PhD candidate at the department of internal medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
“Therefore, early diagnosis and initiation of treatments, and also a combination of treatments, is really crucial,” she added.
Call to action
Approached for comment, Maciej Banach, MD, PhD, full professor of cardiology, Polish Mother’s Memorial Hospital Research Institute, Lodz, and Secretary of the EAS, described the results as “terrifying.”
He said in an interview that they are a “call to action,” especially given that so few patients in the study received intensive combination lipid-lowering therapy despite having a baseline LDL cholesterol level that was “very, very high.”
Banach underlined that patients who receive triple lipid-lowering therapy with a high-intensity statin, ezetimibe (Nustendi), and a proprotein convertase subtilisin/kexin type 9 inhibitor, could expect, based on current evidence, to see their LDL cholesterol levels reduced by 85% and be on target.
“Obviously, this is kind of academic,” because in the real-world “this 85% is not observed very often,” but it offers a target for steep reductions in cholesterol levels.
“This is something that we should focus on for these patients from the beginning,” said Dr. Banach, either with a stepwise approach “or for experts in pediatric HoFH, “maybe immediately.”
He emphasized that clinicians have everything at hand to “be both effective in the early diagnosis of HoFH, the earlier the better, and obviously to be effective with its treatment.”
“We should do something to prolong the lives of those people,” because the current results are “terrifying,” Dr. Banach added.
Rare genetic condition
Presenting her findings, Ms. Mulder began by highlighting that HoFH is a “rare genetic condition that occurs due to mutations in cholesterol metabolism.”
This, she continued, leads to “severely increased LDL cholesterol levels, and consequently to very premature cardiovascular disease,” with patients potentially experiencing their first cardiovascular event before age 20 years.
Ms. Mulder pointed out that, although there have been case series in the literature on HoFH, they have had “limited numbers” and patients have typically spent decades being treated at the same lipid management clinic.
To broaden the understanding of the clinical characteristics and management of patients dying with HoFH, the team examined data from the HICC registry, which is “the largest contemporary database of homozygous FH patients,” Ms. Mulder said.
It includes 751 patients with HoFH from 88 centers in 38 countries who were alive in 2010 or later. Data entry was between 2016 and 2020. The current analysis focused on 37 patients who had already died by the time they were included on the registry.
Of those, 49% were women, 38% were of White ethnicity, and 43% were from high-income countries.
The median age at diagnosis was 12 years, Ms. Mulder said, explaining that this is similar to that seen in other studies. The majority (86%) underwent genetic testing, and 92% presented with xanthomas.
Ms. Mulder also noted that, at their final clinical evaluation, which was conducted a median age of 18 years after their initial diagnosis, 43% of patients were recorded as current or former smokers.
In terms of their lipid-lowering therapy, 94% were taking a statin, whereas 68% were on ezetimibe, and 23% were undergoing apheresis.
Ms. Mulder said that the median number of lipid-lowering therapies per patient was two, and that “sadly ... 26% of the deceased patients had only one or no treatment.”
Therefore, perhaps unsurprisingly even those patients who were receiving treatment had LDL cholesterol levels that were “too high,” at 9.4 mmol/L versus 15.6 mmol/L among those who were untreated.
There was a high prevalence of ASCVD, at 70% overall, or 41% for aortic stenosis, 30% for myocardial infarction, 30% for angina pectoris, and 22% each for aortic valve replacement and coronary artery bypass grafting. In addition, 19% underwent percutaneous coronary intervention.
The median age of onset for ASCVD was 28 years. Ms. Mulder pointed out, however, that, as data were not available for all patients, “this might be an underestimation.” About 70% of patients experienced recurrent ASCVD.
There was a wide range in the age at which patients with HoFH died, although the median was, “strikingly,” 32 years, Ms. Mulder said. Death was confirmed as stemming from cardiovascular causes in 76% of cases.
During the postpresentation discussion, session chair Antonio J. Vallejo-Vaz, PhD, from the Research Group of Clinical Epidemiology and Vascular Risk, Institute of Biomedicine of Seville (Spain), highlighted that, if 38% of the patients were of White ethnicity, then the remainder must therefore be from other ethnic groups.
“There could be potential issues with accessibility to lipid centers” for these patients, which could affect the findings, noted Dr. Vallejo-Vaz, who is also chief scientist of the EAS Familial Hypercholesterolaemia Studies Collaboration.
Ms. Mulder agreed, replying that their results, though already striking, may be an underestimation because the patients were all from either high or middle-income countries, “so it would be good to have some data on low-income countries.”
She was also asked about two patients who died at a much older age than did the others, at ages 70 years and 86 years, respectively, and whether they had, for example, a protective genetic mutation.
Ms. Mulder said that they do not yet know, but they are planning an extended case series on these and other long-lived patients so that they can be investigated further.
No funding or relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
MANNHEIM, GERMANY –
The researchers looked at almost 40 patients from the HoFH International Clinical Collaborators (HICC) registry who had died before data entry, finding that they had a mean age of diagnosis of 12 years.
Even those who received treatment had high LDL cholesterol levels, and 70% developed atherosclerotic cardiovascular disease (ASCVD) at a median age of 28 years.
Worryingly, the results showed that the median age at death was 32 years. Results were presented at the annual congress of the European Atherosclerosis Society.
Patients with HoFH “have severe atherosclerotic cardiovascular disease risk,” said study presenter Janneke Mulder, a PhD candidate at the department of internal medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
“Therefore, early diagnosis and initiation of treatments, and also a combination of treatments, is really crucial,” she added.
Call to action
Approached for comment, Maciej Banach, MD, PhD, full professor of cardiology, Polish Mother’s Memorial Hospital Research Institute, Lodz, and Secretary of the EAS, described the results as “terrifying.”
He said in an interview that they are a “call to action,” especially given that so few patients in the study received intensive combination lipid-lowering therapy despite having a baseline LDL cholesterol level that was “very, very high.”
Banach underlined that patients who receive triple lipid-lowering therapy with a high-intensity statin, ezetimibe (Nustendi), and a proprotein convertase subtilisin/kexin type 9 inhibitor, could expect, based on current evidence, to see their LDL cholesterol levels reduced by 85% and be on target.
“Obviously, this is kind of academic,” because in the real-world “this 85% is not observed very often,” but it offers a target for steep reductions in cholesterol levels.
“This is something that we should focus on for these patients from the beginning,” said Dr. Banach, either with a stepwise approach “or for experts in pediatric HoFH, “maybe immediately.”
He emphasized that clinicians have everything at hand to “be both effective in the early diagnosis of HoFH, the earlier the better, and obviously to be effective with its treatment.”
“We should do something to prolong the lives of those people,” because the current results are “terrifying,” Dr. Banach added.
Rare genetic condition
Presenting her findings, Ms. Mulder began by highlighting that HoFH is a “rare genetic condition that occurs due to mutations in cholesterol metabolism.”
This, she continued, leads to “severely increased LDL cholesterol levels, and consequently to very premature cardiovascular disease,” with patients potentially experiencing their first cardiovascular event before age 20 years.
Ms. Mulder pointed out that, although there have been case series in the literature on HoFH, they have had “limited numbers” and patients have typically spent decades being treated at the same lipid management clinic.
To broaden the understanding of the clinical characteristics and management of patients dying with HoFH, the team examined data from the HICC registry, which is “the largest contemporary database of homozygous FH patients,” Ms. Mulder said.
It includes 751 patients with HoFH from 88 centers in 38 countries who were alive in 2010 or later. Data entry was between 2016 and 2020. The current analysis focused on 37 patients who had already died by the time they were included on the registry.
Of those, 49% were women, 38% were of White ethnicity, and 43% were from high-income countries.
The median age at diagnosis was 12 years, Ms. Mulder said, explaining that this is similar to that seen in other studies. The majority (86%) underwent genetic testing, and 92% presented with xanthomas.
Ms. Mulder also noted that, at their final clinical evaluation, which was conducted a median age of 18 years after their initial diagnosis, 43% of patients were recorded as current or former smokers.
In terms of their lipid-lowering therapy, 94% were taking a statin, whereas 68% were on ezetimibe, and 23% were undergoing apheresis.
Ms. Mulder said that the median number of lipid-lowering therapies per patient was two, and that “sadly ... 26% of the deceased patients had only one or no treatment.”
Therefore, perhaps unsurprisingly even those patients who were receiving treatment had LDL cholesterol levels that were “too high,” at 9.4 mmol/L versus 15.6 mmol/L among those who were untreated.
There was a high prevalence of ASCVD, at 70% overall, or 41% for aortic stenosis, 30% for myocardial infarction, 30% for angina pectoris, and 22% each for aortic valve replacement and coronary artery bypass grafting. In addition, 19% underwent percutaneous coronary intervention.
The median age of onset for ASCVD was 28 years. Ms. Mulder pointed out, however, that, as data were not available for all patients, “this might be an underestimation.” About 70% of patients experienced recurrent ASCVD.
There was a wide range in the age at which patients with HoFH died, although the median was, “strikingly,” 32 years, Ms. Mulder said. Death was confirmed as stemming from cardiovascular causes in 76% of cases.
During the postpresentation discussion, session chair Antonio J. Vallejo-Vaz, PhD, from the Research Group of Clinical Epidemiology and Vascular Risk, Institute of Biomedicine of Seville (Spain), highlighted that, if 38% of the patients were of White ethnicity, then the remainder must therefore be from other ethnic groups.
“There could be potential issues with accessibility to lipid centers” for these patients, which could affect the findings, noted Dr. Vallejo-Vaz, who is also chief scientist of the EAS Familial Hypercholesterolaemia Studies Collaboration.
Ms. Mulder agreed, replying that their results, though already striking, may be an underestimation because the patients were all from either high or middle-income countries, “so it would be good to have some data on low-income countries.”
She was also asked about two patients who died at a much older age than did the others, at ages 70 years and 86 years, respectively, and whether they had, for example, a protective genetic mutation.
Ms. Mulder said that they do not yet know, but they are planning an extended case series on these and other long-lived patients so that they can be investigated further.
No funding or relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
Maternal health clinic teams with legal services to aid patients
BALTIMORE – A novel partnership between a legal services program and a maternal health clinic is helping pregnant patients with issues such as housing or employment discrimination.
The Perinatal Legal Assistance and Well-being (P-LAW) program at Georgetown University, Washington, launched 2 years ago as a collaboration between GU’s Health Justice Alliance clinic and the Women’s and Infants Services division of nearby MedStar Washington Hospital Center, integrating attorneys into the health care team to offer no-cost legal aid for its diverse, urban population during the perinatal period. Since then, the effort has assisted more than 120 women.
“Our goal was to see how integrating a lawyer can help address some of those issues that, unfortunately, providers are not able to assist with because they go beyond the hospital or clinic walls,” said Roxana Richardson, JD, the project director and managing attorney for P-LAW, during a poster presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Our initial findings showed that there are issues that patients were facing that needed an intervention from an attorney. We trained the providers and social workers to identify these issues so that we could intervene.”
Improving health by tackling legal barriers
, Ms. Richardson said.
The program is one of few medical-legal partnerships specifically focused on the perinatal population. P-LAW is one component of a larger initiative at MedStar Health called DC Safe Babies Safe Moms. The initiative includes integrated mental health programming, treatment of health conditions that complicate pregnancy, assessments of social determinants of health, expanded support for lactation and nutrition, access to home visiting referrals, and extended postpartum follow-up. The work is supported through the A. James & Alice B. Clark Foundation.
Patients are evaluated for health-harming legal needs as part of a comprehensive social and behavioral health screening at their initial prenatal visit, 28-week appointment, and postpartum visit. Those who screen positive are contacted by a referral specialist on the health care team who confirms the patient has an active legal need and would like to be connected to the P-LAW team. The team then reaches out to conduct a legal intake and determine the appropriate course of action.
From March 2021 through February of this year, Ms. Richardson and others with the program have provided legal representation to 123 patients on 186 legal issues in areas such as public benefits, employment, and housing and family concerns. Services range from advising patients on steps they can take on their own (like reporting a housing condition issue to the Department of Buildings), to sending letters on patients’ behalf, to appearing in court. Most patients served were in their second and third trimesters of pregnancy. The majority were Black or African American, aged 20-34 years, and had incomes below 100% of the federal poverty level.
The most common legal issues were in the areas of public benefits (SNAP/food stamps, cash assistance), employment (parental leave, discrimination), housing (conditions, eviction), and family law (child support, domestic violence). Among the 186 issues, work has been completed on 106 concerns and 33 still have a case open; for 47, the client withdrew or ceased contact, Ms. Richardson reported.
Most times when obstetricians hear concerns like these, they wonder what to do, said Tamika Auguste, MD, chair of obstetrics and gynecology at MedStar Health. Having the P-LAW program as a resource is a huge help, she said. If patients express concerns, or if obstetricians uncover concerns during office visits, doctors can enter a referral directly in the electronic medical record.
Patients are “so relieved,” Dr. Auguste said in an interview, because they often wonder if their doctor can help. “Your doctor is only going to be able to help to a certain point. But to know they’re pregnant and they have this resource, and they’re going to get legal help, has been game-changing for so many patients.”
COVID ... or morning sickness?
In one rewarding case, Ms. Richardson said, a single mother of one child who was pregnant and experiencing hyperemesis explained that her employer would forbid her from working if she had any symptoms similar to COVID-19. The employer mistook her vomiting, nausea, and exhaustion as COVID symptoms and docked her pay. That started a cascade in which earning less meant she was facing eviction and car repossession – and, eventually, overdraft fees and withdrawals from her bank. She was so despondent she was thinking about self-harm, Ms. Richardson said.
With the aid of the P-LAW program, the woman had short-term disability approved within 72 hours, was referred to the hospital for inpatient mental health treatment, and received the care she needed. She ultimately delivered a healthy baby girl and found a new job.
Tiffany Moore Simas, MD, MPH, MEd, chair of the department of obstetrics and gynecology at the University of Massachusetts and UMass Memorial Health in Worcester, said she encounters similar concerns among her patients, with the vast majority having one or more issues with social determinants of health.
“I think it’s incredible, as we’re trying to address equity in perinatal health and maternal mortality and morbidity, to have a more holistic view of what health means, and all of the social determinants of health, and actually helping our patients address that in real time at their visits and connecting them,” said Dr. Simas, who also is professor of ob/gyn, pediatrics, psychiatry, and population and quantitative health sciences at UMass. “It has really opened my mind to the possibilities of things we need to explore and do differently.”
Ms. Richardson, Dr. Auguste, and Dr. Simas reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BALTIMORE – A novel partnership between a legal services program and a maternal health clinic is helping pregnant patients with issues such as housing or employment discrimination.
The Perinatal Legal Assistance and Well-being (P-LAW) program at Georgetown University, Washington, launched 2 years ago as a collaboration between GU’s Health Justice Alliance clinic and the Women’s and Infants Services division of nearby MedStar Washington Hospital Center, integrating attorneys into the health care team to offer no-cost legal aid for its diverse, urban population during the perinatal period. Since then, the effort has assisted more than 120 women.
“Our goal was to see how integrating a lawyer can help address some of those issues that, unfortunately, providers are not able to assist with because they go beyond the hospital or clinic walls,” said Roxana Richardson, JD, the project director and managing attorney for P-LAW, during a poster presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Our initial findings showed that there are issues that patients were facing that needed an intervention from an attorney. We trained the providers and social workers to identify these issues so that we could intervene.”
Improving health by tackling legal barriers
, Ms. Richardson said.
The program is one of few medical-legal partnerships specifically focused on the perinatal population. P-LAW is one component of a larger initiative at MedStar Health called DC Safe Babies Safe Moms. The initiative includes integrated mental health programming, treatment of health conditions that complicate pregnancy, assessments of social determinants of health, expanded support for lactation and nutrition, access to home visiting referrals, and extended postpartum follow-up. The work is supported through the A. James & Alice B. Clark Foundation.
Patients are evaluated for health-harming legal needs as part of a comprehensive social and behavioral health screening at their initial prenatal visit, 28-week appointment, and postpartum visit. Those who screen positive are contacted by a referral specialist on the health care team who confirms the patient has an active legal need and would like to be connected to the P-LAW team. The team then reaches out to conduct a legal intake and determine the appropriate course of action.
From March 2021 through February of this year, Ms. Richardson and others with the program have provided legal representation to 123 patients on 186 legal issues in areas such as public benefits, employment, and housing and family concerns. Services range from advising patients on steps they can take on their own (like reporting a housing condition issue to the Department of Buildings), to sending letters on patients’ behalf, to appearing in court. Most patients served were in their second and third trimesters of pregnancy. The majority were Black or African American, aged 20-34 years, and had incomes below 100% of the federal poverty level.
The most common legal issues were in the areas of public benefits (SNAP/food stamps, cash assistance), employment (parental leave, discrimination), housing (conditions, eviction), and family law (child support, domestic violence). Among the 186 issues, work has been completed on 106 concerns and 33 still have a case open; for 47, the client withdrew or ceased contact, Ms. Richardson reported.
Most times when obstetricians hear concerns like these, they wonder what to do, said Tamika Auguste, MD, chair of obstetrics and gynecology at MedStar Health. Having the P-LAW program as a resource is a huge help, she said. If patients express concerns, or if obstetricians uncover concerns during office visits, doctors can enter a referral directly in the electronic medical record.
Patients are “so relieved,” Dr. Auguste said in an interview, because they often wonder if their doctor can help. “Your doctor is only going to be able to help to a certain point. But to know they’re pregnant and they have this resource, and they’re going to get legal help, has been game-changing for so many patients.”
COVID ... or morning sickness?
In one rewarding case, Ms. Richardson said, a single mother of one child who was pregnant and experiencing hyperemesis explained that her employer would forbid her from working if she had any symptoms similar to COVID-19. The employer mistook her vomiting, nausea, and exhaustion as COVID symptoms and docked her pay. That started a cascade in which earning less meant she was facing eviction and car repossession – and, eventually, overdraft fees and withdrawals from her bank. She was so despondent she was thinking about self-harm, Ms. Richardson said.
With the aid of the P-LAW program, the woman had short-term disability approved within 72 hours, was referred to the hospital for inpatient mental health treatment, and received the care she needed. She ultimately delivered a healthy baby girl and found a new job.
Tiffany Moore Simas, MD, MPH, MEd, chair of the department of obstetrics and gynecology at the University of Massachusetts and UMass Memorial Health in Worcester, said she encounters similar concerns among her patients, with the vast majority having one or more issues with social determinants of health.
“I think it’s incredible, as we’re trying to address equity in perinatal health and maternal mortality and morbidity, to have a more holistic view of what health means, and all of the social determinants of health, and actually helping our patients address that in real time at their visits and connecting them,” said Dr. Simas, who also is professor of ob/gyn, pediatrics, psychiatry, and population and quantitative health sciences at UMass. “It has really opened my mind to the possibilities of things we need to explore and do differently.”
Ms. Richardson, Dr. Auguste, and Dr. Simas reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BALTIMORE – A novel partnership between a legal services program and a maternal health clinic is helping pregnant patients with issues such as housing or employment discrimination.
The Perinatal Legal Assistance and Well-being (P-LAW) program at Georgetown University, Washington, launched 2 years ago as a collaboration between GU’s Health Justice Alliance clinic and the Women’s and Infants Services division of nearby MedStar Washington Hospital Center, integrating attorneys into the health care team to offer no-cost legal aid for its diverse, urban population during the perinatal period. Since then, the effort has assisted more than 120 women.
“Our goal was to see how integrating a lawyer can help address some of those issues that, unfortunately, providers are not able to assist with because they go beyond the hospital or clinic walls,” said Roxana Richardson, JD, the project director and managing attorney for P-LAW, during a poster presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Our initial findings showed that there are issues that patients were facing that needed an intervention from an attorney. We trained the providers and social workers to identify these issues so that we could intervene.”
Improving health by tackling legal barriers
, Ms. Richardson said.
The program is one of few medical-legal partnerships specifically focused on the perinatal population. P-LAW is one component of a larger initiative at MedStar Health called DC Safe Babies Safe Moms. The initiative includes integrated mental health programming, treatment of health conditions that complicate pregnancy, assessments of social determinants of health, expanded support for lactation and nutrition, access to home visiting referrals, and extended postpartum follow-up. The work is supported through the A. James & Alice B. Clark Foundation.
Patients are evaluated for health-harming legal needs as part of a comprehensive social and behavioral health screening at their initial prenatal visit, 28-week appointment, and postpartum visit. Those who screen positive are contacted by a referral specialist on the health care team who confirms the patient has an active legal need and would like to be connected to the P-LAW team. The team then reaches out to conduct a legal intake and determine the appropriate course of action.
From March 2021 through February of this year, Ms. Richardson and others with the program have provided legal representation to 123 patients on 186 legal issues in areas such as public benefits, employment, and housing and family concerns. Services range from advising patients on steps they can take on their own (like reporting a housing condition issue to the Department of Buildings), to sending letters on patients’ behalf, to appearing in court. Most patients served were in their second and third trimesters of pregnancy. The majority were Black or African American, aged 20-34 years, and had incomes below 100% of the federal poverty level.
The most common legal issues were in the areas of public benefits (SNAP/food stamps, cash assistance), employment (parental leave, discrimination), housing (conditions, eviction), and family law (child support, domestic violence). Among the 186 issues, work has been completed on 106 concerns and 33 still have a case open; for 47, the client withdrew or ceased contact, Ms. Richardson reported.
Most times when obstetricians hear concerns like these, they wonder what to do, said Tamika Auguste, MD, chair of obstetrics and gynecology at MedStar Health. Having the P-LAW program as a resource is a huge help, she said. If patients express concerns, or if obstetricians uncover concerns during office visits, doctors can enter a referral directly in the electronic medical record.
Patients are “so relieved,” Dr. Auguste said in an interview, because they often wonder if their doctor can help. “Your doctor is only going to be able to help to a certain point. But to know they’re pregnant and they have this resource, and they’re going to get legal help, has been game-changing for so many patients.”
COVID ... or morning sickness?
In one rewarding case, Ms. Richardson said, a single mother of one child who was pregnant and experiencing hyperemesis explained that her employer would forbid her from working if she had any symptoms similar to COVID-19. The employer mistook her vomiting, nausea, and exhaustion as COVID symptoms and docked her pay. That started a cascade in which earning less meant she was facing eviction and car repossession – and, eventually, overdraft fees and withdrawals from her bank. She was so despondent she was thinking about self-harm, Ms. Richardson said.
With the aid of the P-LAW program, the woman had short-term disability approved within 72 hours, was referred to the hospital for inpatient mental health treatment, and received the care she needed. She ultimately delivered a healthy baby girl and found a new job.
Tiffany Moore Simas, MD, MPH, MEd, chair of the department of obstetrics and gynecology at the University of Massachusetts and UMass Memorial Health in Worcester, said she encounters similar concerns among her patients, with the vast majority having one or more issues with social determinants of health.
“I think it’s incredible, as we’re trying to address equity in perinatal health and maternal mortality and morbidity, to have a more holistic view of what health means, and all of the social determinants of health, and actually helping our patients address that in real time at their visits and connecting them,” said Dr. Simas, who also is professor of ob/gyn, pediatrics, psychiatry, and population and quantitative health sciences at UMass. “It has really opened my mind to the possibilities of things we need to explore and do differently.”
Ms. Richardson, Dr. Auguste, and Dr. Simas reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ACOG 2023
Harmful emotional hit of antidepressants underappreciated
SAN FRANCISCO – , new research shows.
Emotional blunting can be described as feeling emotionally flat and incapable of finding pleasure. The patient may feel less sadness, guilt, or hopelessness, but that may come at the cost of feeling less joy, surprise, and happiness. Some people with SSRI-induced blunting even report caring less about important relationships.
It’s an issue that needs greater attention, study investigator Mujeeb U. Shad, MD, with Valley Health Services and University of Nevada, Las Vegas, said in an interview.
“Patients may come to the clinic and report feeling emotionally and cognitively flat and not be taken seriously by their provider, but they are genuinely reporting something that is happening to them and decreasing their quality of life,” Dr. Shad explained.
The study was presented at the annual meeting of the American Psychiatric Association.
Something ‘missing’
Dr. Shad said that the genesis for the study came from a resident who noticed that many patients receiving SSRIs reported feeling better and not as bothered by the depression, yet, at the same time, they felt something was “missing. Their families would say, ‘You’re better but you’re not the same person.’ ”
To investigate further, the researchers did a “scoping review” of 25 original studies that assessed antidepressant-related emotional blunting. Until now, there hasn’t been a systematic review of this issue, Dr. Shad said.
Ten of the studies looked at the role of SSRIs in emotional blunting, whereas the other 15 looked at serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and second-generation antipsychotic medications.
The results of the review show that emotional blunting is a significant patient-reported concern. It often presents as a subjective complaint of changed personality, feeling a lesser intensity of overall emotions, and the manifestation of not being oneself often attributed to antidepressant use, the researchers found. Emotional blunting was more commonly associated with SSRIs than with the other medications in the studies.
Common clinical strategies to manage antidepressant-induced emotional blunting reported in the literature include dose reduction or switching to a different antidepressant class; however, the literature did not make the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants.
Dr. Shad said that there is a need to develop valid and reliable measures to assess emotional blunting related to antidepressants.
He noted that optimal patient care should include pre- and posttreatment assessment of emotional blunting. One useful tool is the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants.
Can’t get to the top
Jacob Cross, MD, who wasn’t involved in the study, said that he has seen the impact of antidepressant-related emotional blunting first-hand.
“I’ve had multiple patients report emotional blunting on antidepressant therapy,” Dr. Cross, with the department of psychiatry, Rush Medical College, Chicago, said.
“These patients feel like their emotions are not as high and not as low; so they experience directional improvement, but they’re still not feeling like they can get that top peak emotion. It’s kind of similar to anhedonia. They’re just feeling like a little cut off, like they’re climbing a cliff and just can’t get to that top,” Dr. Cross said.
For a patient with emotional blunting, Dr. Cross said he might “switch to an antidepressant that’s more stimulating like an SNRI from an SSRI. You could also lower the dose and see if that helps, but I usually change the drug class.”
The study had no specific funding. Dr. Shad and Dr. Cross have no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , new research shows.
Emotional blunting can be described as feeling emotionally flat and incapable of finding pleasure. The patient may feel less sadness, guilt, or hopelessness, but that may come at the cost of feeling less joy, surprise, and happiness. Some people with SSRI-induced blunting even report caring less about important relationships.
It’s an issue that needs greater attention, study investigator Mujeeb U. Shad, MD, with Valley Health Services and University of Nevada, Las Vegas, said in an interview.
“Patients may come to the clinic and report feeling emotionally and cognitively flat and not be taken seriously by their provider, but they are genuinely reporting something that is happening to them and decreasing their quality of life,” Dr. Shad explained.
The study was presented at the annual meeting of the American Psychiatric Association.
Something ‘missing’
Dr. Shad said that the genesis for the study came from a resident who noticed that many patients receiving SSRIs reported feeling better and not as bothered by the depression, yet, at the same time, they felt something was “missing. Their families would say, ‘You’re better but you’re not the same person.’ ”
To investigate further, the researchers did a “scoping review” of 25 original studies that assessed antidepressant-related emotional blunting. Until now, there hasn’t been a systematic review of this issue, Dr. Shad said.
Ten of the studies looked at the role of SSRIs in emotional blunting, whereas the other 15 looked at serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and second-generation antipsychotic medications.
The results of the review show that emotional blunting is a significant patient-reported concern. It often presents as a subjective complaint of changed personality, feeling a lesser intensity of overall emotions, and the manifestation of not being oneself often attributed to antidepressant use, the researchers found. Emotional blunting was more commonly associated with SSRIs than with the other medications in the studies.
Common clinical strategies to manage antidepressant-induced emotional blunting reported in the literature include dose reduction or switching to a different antidepressant class; however, the literature did not make the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants.
Dr. Shad said that there is a need to develop valid and reliable measures to assess emotional blunting related to antidepressants.
He noted that optimal patient care should include pre- and posttreatment assessment of emotional blunting. One useful tool is the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants.
Can’t get to the top
Jacob Cross, MD, who wasn’t involved in the study, said that he has seen the impact of antidepressant-related emotional blunting first-hand.
“I’ve had multiple patients report emotional blunting on antidepressant therapy,” Dr. Cross, with the department of psychiatry, Rush Medical College, Chicago, said.
“These patients feel like their emotions are not as high and not as low; so they experience directional improvement, but they’re still not feeling like they can get that top peak emotion. It’s kind of similar to anhedonia. They’re just feeling like a little cut off, like they’re climbing a cliff and just can’t get to that top,” Dr. Cross said.
For a patient with emotional blunting, Dr. Cross said he might “switch to an antidepressant that’s more stimulating like an SNRI from an SSRI. You could also lower the dose and see if that helps, but I usually change the drug class.”
The study had no specific funding. Dr. Shad and Dr. Cross have no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , new research shows.
Emotional blunting can be described as feeling emotionally flat and incapable of finding pleasure. The patient may feel less sadness, guilt, or hopelessness, but that may come at the cost of feeling less joy, surprise, and happiness. Some people with SSRI-induced blunting even report caring less about important relationships.
It’s an issue that needs greater attention, study investigator Mujeeb U. Shad, MD, with Valley Health Services and University of Nevada, Las Vegas, said in an interview.
“Patients may come to the clinic and report feeling emotionally and cognitively flat and not be taken seriously by their provider, but they are genuinely reporting something that is happening to them and decreasing their quality of life,” Dr. Shad explained.
The study was presented at the annual meeting of the American Psychiatric Association.
Something ‘missing’
Dr. Shad said that the genesis for the study came from a resident who noticed that many patients receiving SSRIs reported feeling better and not as bothered by the depression, yet, at the same time, they felt something was “missing. Their families would say, ‘You’re better but you’re not the same person.’ ”
To investigate further, the researchers did a “scoping review” of 25 original studies that assessed antidepressant-related emotional blunting. Until now, there hasn’t been a systematic review of this issue, Dr. Shad said.
Ten of the studies looked at the role of SSRIs in emotional blunting, whereas the other 15 looked at serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and second-generation antipsychotic medications.
The results of the review show that emotional blunting is a significant patient-reported concern. It often presents as a subjective complaint of changed personality, feeling a lesser intensity of overall emotions, and the manifestation of not being oneself often attributed to antidepressant use, the researchers found. Emotional blunting was more commonly associated with SSRIs than with the other medications in the studies.
Common clinical strategies to manage antidepressant-induced emotional blunting reported in the literature include dose reduction or switching to a different antidepressant class; however, the literature did not make the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants.
Dr. Shad said that there is a need to develop valid and reliable measures to assess emotional blunting related to antidepressants.
He noted that optimal patient care should include pre- and posttreatment assessment of emotional blunting. One useful tool is the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants.
Can’t get to the top
Jacob Cross, MD, who wasn’t involved in the study, said that he has seen the impact of antidepressant-related emotional blunting first-hand.
“I’ve had multiple patients report emotional blunting on antidepressant therapy,” Dr. Cross, with the department of psychiatry, Rush Medical College, Chicago, said.
“These patients feel like their emotions are not as high and not as low; so they experience directional improvement, but they’re still not feeling like they can get that top peak emotion. It’s kind of similar to anhedonia. They’re just feeling like a little cut off, like they’re climbing a cliff and just can’t get to that top,” Dr. Cross said.
For a patient with emotional blunting, Dr. Cross said he might “switch to an antidepressant that’s more stimulating like an SNRI from an SSRI. You could also lower the dose and see if that helps, but I usually change the drug class.”
The study had no specific funding. Dr. Shad and Dr. Cross have no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
AT APA 2023
AxSpA remission on TNFi seen in half of patients with comorbid IBD
CLEVELAND – About half (52%) of patients living with both axial spondyloarthritis and inflammatory bowel disease (IBD) reached clinical remission of axSpA at 12 months after starting a tumor necrosis factor inhibitor (TNFi), researchers have found.
The disease course for axSpA among patients with IBD who start anti-TNF agents is not well understood.
Rahul S. Dalal, MD, an advanced fellow in IBD with the division of gastroenterology, hepatology, and endoscopy at Brigham and Women’s Hospital, Boston, and colleagues studied whether certain clinical factors were associated with remission of axSpA after patients with axSpA, who also had Crohn’s disease (CD) or ulcerative colitis (UC), started anti-TNF therapy.
Short IBD duration, adalimumab linked with higher remission odds
They found that those who had IBD for less than 5 years and those taking the TNFi adalimumab (Humira and biosimilars), as opposed to another TNFi, had a higher likelihood of reaching axSpA remission at 1 year. The odds ratios calculated for those factors were statistically significant.
Dr. Dalal said that most of the patients in the study (70%) were prescribed adalimumab, and because the study didn’t compare TNFis head to head, it’s hard to say whether adalimumab should be the preferred treatment for these patients.
“But it’s an interesting question that should be addressed in a bigger study,” he said.
Other TNFis included infliximab (Remicade and biosimilars) in 27%, golimumab (Simponi) in 2%, and certolizumab pegol (Cimzia) in 1%.
He presented the results at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
Study details
Included in the retrospective cohort study were 82 adults with IBD and either ankylosing spondylitis or sacroiliitis who started anti-TNF agents approved for IBD between January 2012 and October 2021 at a large academic center.
Clinical remission of axSpA was the primary outcome, defined as the absence or adequate control of pain and/or stiffness related to axSpA as documented in the rheumatology note 1 year (+/– 2 months) after starting anti-TNF agents.
The secondary outcome was clinical remission of IBD, defined as 2 or less on the simple clinical colitis activity index, a score of less than 5 on the Harvey-Bradshaw Index, or provider assessment with no use of oral or intravenous glucocorticoids for 30 days. Dr. Dalal said 74% in the study reached that endpoint in the study period.
“Some patients had good response to anti-TNF treatments for their IBD but not necessarily for their spondyloarthritis,” he explained.
There were insufficient observations to calculate odds ratios for the variables, including Hispanic ethnicity, endoscopic inflammation, and prior history of using vedolizumab (Entyvio), secukinumab (Cosentyx), and ustekinumab (Stelara), the authors noted.
Dr. Dalal said it’s important to study this population because patients with IBD and axSpA take some of the same medications, but it’s not known how each medication acts in patients.
“We don’t have much data to tell us who’s going to respond to treatments from both diseases simultaneously,” he said.
Conclusions called ‘reassuring’
Jean Liew, MD, a spondyloarthritis specialist at Boston University, who was not part of the study, noted that the team reported univariate associations of clinical factors with achievement of clinical axSpA remission, but no multivariable analyses with adjustment for potential confounders.
She said the finding of half the patients achieving clinical remission is “reassuring, as anecdotally we may find that patients with IBD-associated spondyloarthritis tend to have more difficult-to-treat symptoms as well as more limited treatment options. For example, they cannot use [interleukin]-17 inhibitors.”
She noted the study is small and descriptive and further analyses are limited by the small number of patients.
“I think if a study of the same type could be performed at a larger scale with larger numbers, it could generate more data on which type of patient with IBD-associated spondyloarthritis is more likely to have a good response after starting a TNF inhibitor,” she said. “Of course, the other question is how long those patients would have good disease control while on the TNF inhibitor. What is the persistence of the medication? This study doesn’t ask or answer that question.”
Dr. Dalal added that in future research it will be important to look at response to medications beyond TNFis, especially Janus kinase inhibitors.
That will help show “whether there is a treatment algorithm that can be tailored to this population in terms of what agents to choose first,” he said. “I think we need multicenter studies to do this.”
Dr. Dalal has received grant funding from Pfizer and Janssen and has served as a consultant for Centaur Labs and Janssen. Dr. Liew has no relevant financial relationships.
CLEVELAND – About half (52%) of patients living with both axial spondyloarthritis and inflammatory bowel disease (IBD) reached clinical remission of axSpA at 12 months after starting a tumor necrosis factor inhibitor (TNFi), researchers have found.
The disease course for axSpA among patients with IBD who start anti-TNF agents is not well understood.
Rahul S. Dalal, MD, an advanced fellow in IBD with the division of gastroenterology, hepatology, and endoscopy at Brigham and Women’s Hospital, Boston, and colleagues studied whether certain clinical factors were associated with remission of axSpA after patients with axSpA, who also had Crohn’s disease (CD) or ulcerative colitis (UC), started anti-TNF therapy.
Short IBD duration, adalimumab linked with higher remission odds
They found that those who had IBD for less than 5 years and those taking the TNFi adalimumab (Humira and biosimilars), as opposed to another TNFi, had a higher likelihood of reaching axSpA remission at 1 year. The odds ratios calculated for those factors were statistically significant.
Dr. Dalal said that most of the patients in the study (70%) were prescribed adalimumab, and because the study didn’t compare TNFis head to head, it’s hard to say whether adalimumab should be the preferred treatment for these patients.
“But it’s an interesting question that should be addressed in a bigger study,” he said.
Other TNFis included infliximab (Remicade and biosimilars) in 27%, golimumab (Simponi) in 2%, and certolizumab pegol (Cimzia) in 1%.
He presented the results at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
Study details
Included in the retrospective cohort study were 82 adults with IBD and either ankylosing spondylitis or sacroiliitis who started anti-TNF agents approved for IBD between January 2012 and October 2021 at a large academic center.
Clinical remission of axSpA was the primary outcome, defined as the absence or adequate control of pain and/or stiffness related to axSpA as documented in the rheumatology note 1 year (+/– 2 months) after starting anti-TNF agents.
The secondary outcome was clinical remission of IBD, defined as 2 or less on the simple clinical colitis activity index, a score of less than 5 on the Harvey-Bradshaw Index, or provider assessment with no use of oral or intravenous glucocorticoids for 30 days. Dr. Dalal said 74% in the study reached that endpoint in the study period.
“Some patients had good response to anti-TNF treatments for their IBD but not necessarily for their spondyloarthritis,” he explained.
There were insufficient observations to calculate odds ratios for the variables, including Hispanic ethnicity, endoscopic inflammation, and prior history of using vedolizumab (Entyvio), secukinumab (Cosentyx), and ustekinumab (Stelara), the authors noted.
Dr. Dalal said it’s important to study this population because patients with IBD and axSpA take some of the same medications, but it’s not known how each medication acts in patients.
“We don’t have much data to tell us who’s going to respond to treatments from both diseases simultaneously,” he said.
Conclusions called ‘reassuring’
Jean Liew, MD, a spondyloarthritis specialist at Boston University, who was not part of the study, noted that the team reported univariate associations of clinical factors with achievement of clinical axSpA remission, but no multivariable analyses with adjustment for potential confounders.
She said the finding of half the patients achieving clinical remission is “reassuring, as anecdotally we may find that patients with IBD-associated spondyloarthritis tend to have more difficult-to-treat symptoms as well as more limited treatment options. For example, they cannot use [interleukin]-17 inhibitors.”
She noted the study is small and descriptive and further analyses are limited by the small number of patients.
“I think if a study of the same type could be performed at a larger scale with larger numbers, it could generate more data on which type of patient with IBD-associated spondyloarthritis is more likely to have a good response after starting a TNF inhibitor,” she said. “Of course, the other question is how long those patients would have good disease control while on the TNF inhibitor. What is the persistence of the medication? This study doesn’t ask or answer that question.”
Dr. Dalal added that in future research it will be important to look at response to medications beyond TNFis, especially Janus kinase inhibitors.
That will help show “whether there is a treatment algorithm that can be tailored to this population in terms of what agents to choose first,” he said. “I think we need multicenter studies to do this.”
Dr. Dalal has received grant funding from Pfizer and Janssen and has served as a consultant for Centaur Labs and Janssen. Dr. Liew has no relevant financial relationships.
CLEVELAND – About half (52%) of patients living with both axial spondyloarthritis and inflammatory bowel disease (IBD) reached clinical remission of axSpA at 12 months after starting a tumor necrosis factor inhibitor (TNFi), researchers have found.
The disease course for axSpA among patients with IBD who start anti-TNF agents is not well understood.
Rahul S. Dalal, MD, an advanced fellow in IBD with the division of gastroenterology, hepatology, and endoscopy at Brigham and Women’s Hospital, Boston, and colleagues studied whether certain clinical factors were associated with remission of axSpA after patients with axSpA, who also had Crohn’s disease (CD) or ulcerative colitis (UC), started anti-TNF therapy.
Short IBD duration, adalimumab linked with higher remission odds
They found that those who had IBD for less than 5 years and those taking the TNFi adalimumab (Humira and biosimilars), as opposed to another TNFi, had a higher likelihood of reaching axSpA remission at 1 year. The odds ratios calculated for those factors were statistically significant.
Dr. Dalal said that most of the patients in the study (70%) were prescribed adalimumab, and because the study didn’t compare TNFis head to head, it’s hard to say whether adalimumab should be the preferred treatment for these patients.
“But it’s an interesting question that should be addressed in a bigger study,” he said.
Other TNFis included infliximab (Remicade and biosimilars) in 27%, golimumab (Simponi) in 2%, and certolizumab pegol (Cimzia) in 1%.
He presented the results at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
Study details
Included in the retrospective cohort study were 82 adults with IBD and either ankylosing spondylitis or sacroiliitis who started anti-TNF agents approved for IBD between January 2012 and October 2021 at a large academic center.
Clinical remission of axSpA was the primary outcome, defined as the absence or adequate control of pain and/or stiffness related to axSpA as documented in the rheumatology note 1 year (+/– 2 months) after starting anti-TNF agents.
The secondary outcome was clinical remission of IBD, defined as 2 or less on the simple clinical colitis activity index, a score of less than 5 on the Harvey-Bradshaw Index, or provider assessment with no use of oral or intravenous glucocorticoids for 30 days. Dr. Dalal said 74% in the study reached that endpoint in the study period.
“Some patients had good response to anti-TNF treatments for their IBD but not necessarily for their spondyloarthritis,” he explained.
There were insufficient observations to calculate odds ratios for the variables, including Hispanic ethnicity, endoscopic inflammation, and prior history of using vedolizumab (Entyvio), secukinumab (Cosentyx), and ustekinumab (Stelara), the authors noted.
Dr. Dalal said it’s important to study this population because patients with IBD and axSpA take some of the same medications, but it’s not known how each medication acts in patients.
“We don’t have much data to tell us who’s going to respond to treatments from both diseases simultaneously,” he said.
Conclusions called ‘reassuring’
Jean Liew, MD, a spondyloarthritis specialist at Boston University, who was not part of the study, noted that the team reported univariate associations of clinical factors with achievement of clinical axSpA remission, but no multivariable analyses with adjustment for potential confounders.
She said the finding of half the patients achieving clinical remission is “reassuring, as anecdotally we may find that patients with IBD-associated spondyloarthritis tend to have more difficult-to-treat symptoms as well as more limited treatment options. For example, they cannot use [interleukin]-17 inhibitors.”
She noted the study is small and descriptive and further analyses are limited by the small number of patients.
“I think if a study of the same type could be performed at a larger scale with larger numbers, it could generate more data on which type of patient with IBD-associated spondyloarthritis is more likely to have a good response after starting a TNF inhibitor,” she said. “Of course, the other question is how long those patients would have good disease control while on the TNF inhibitor. What is the persistence of the medication? This study doesn’t ask or answer that question.”
Dr. Dalal added that in future research it will be important to look at response to medications beyond TNFis, especially Janus kinase inhibitors.
That will help show “whether there is a treatment algorithm that can be tailored to this population in terms of what agents to choose first,” he said. “I think we need multicenter studies to do this.”
Dr. Dalal has received grant funding from Pfizer and Janssen and has served as a consultant for Centaur Labs and Janssen. Dr. Liew has no relevant financial relationships.
AT SPARTAN 2023
Sublingual immunotherapy stops onset and worsening of asthma
PARIS – The EfficAPSI study showed with real-world data that sublingual immunotherapy (SLIT) reduces the risks for asthma onset and the worsening of asthma symptoms for patients with allergic rhinitis. The research was presented at the 18th French-language allergy conference.
These results confirm that allergen immunotherapy, or “desensitization,” is indeed an etiologic treatment of this allergic condition.
SLIT encompasses personalized solutions created for an individual specifically for allergies to dust mites, grass, birch, cats, and so on. These preparations are commonly used by allergy specialists when establishing an AIT treatment plan.
In 2017, the French Health Authority published a report indicating that there was insufficient clinical proof regarding the efficacy of SLIT. It subsequently removed injectable forms of these allergen extracts from the list of drugs reimbursed by the state and reduced state reimbursement of sublingual SLIT preparations from 30% to 15%, a step it confirmed in March 2018 and that led to outrage from allergy specialists. The chair of the French allergy society at the time, Jocelyne Just, MD, PhD, argued that conducting double-blind, placebo-controlled studies for all types (grass pollen, birch pollen, dust mites, asthma, allergic rhinitis, subcutaneous injections, sublingual treatments, tablets, liquid preparations) would take decades. Furthermore, meta-analyses on the subject, despite being heterogeneous and unable to answer all questions, are indeed pointing to the effectiveness of SLIT. To supplement existing data and to answer the queries raised by the HAS, several studies have been launched, including EfficAPSI.
The pharmacoepidemiologic EfficAPSI study is the largest retrospective, real-world, longitudinal cohort study ever carried out regarding liquid SLIT using data stored in the French National Health Data System (SNDS). The primary objective of the study was to evaluate the real-world impact of liquid SLIT on the onset and worsening of asthma for patients with allergic rhinitis and to evaluate the impact of sublingual treatments on public health.
A cohort analysis of patients treated with SLIT and control patients treated for allergic rhinitis with or without treatment for asthma was carried out. The patients treated with SLIT for at least 2 consecutive years were anonymously selected from the SNDS using the Stallergenes Greer prescription database.
In all, 99,538 patients who received SLIT were compared with 333,082 control patients (those who had received treatment for allergic rhinitis without taking SLIT). Participants were stratified according to their treatment history for asthma and were paired using a propensity score to minimize comparison bias.
The main definition of the onset of asthma included the first prescription of an asthma medication, hospital admission for asthma, or a diagnosis of chronic asthma. The secondary definition omitted the prescription of any treatment, and the third (sensitive and specific) took into consideration an initial prescription of omalizumab or a prescription of three inhaled corticosteroids (ICSs) associated with or without a long-acting beta-2 agonist (LABA) for a period of 1 year, admission to the hospital, or chronic asthma.
Asthma risk reduced
Among patients with allergic rhinitis without preexisting asthma, liquid SLIT was associated with a significantly lower risk of asthma onset in comparison with the control group (primary hazard ratio: 0.77; secondary HR: 0.66; and tertiary HR: 0.62).
The risk reductions were significant and were consistent regardless of the allergens analyzed (tertiary HR, dust mites: 0.57; grass: 0.52) for all age groups. These new results that were based on the tertiary definition corroborate the results from the primary and secondary definitions.
said study co-author Philippe Devillier, MD, PhD, research director at the respiratory tract diseases center of Foch Hospital, Paris. “These results are consistent with previous studies in the same French health care database, as well as in a German database with SLIT preparations in tablet form. This not only confirms the soundness of the methodology but also the benefit of liquid SLIT as an etiological treatment of respiratory allergies.”
Risk for worsening
Furthermore, in the same study, liquid SLIT treatment was associated with a 27% reduced risk for worsening asthma and a 36% reduced risk for severe asthma. Among patients with allergic rhinitis and preexisting asthma, liquid SLIT was associated with a significantly lower risk for worsening of asthma, compared with the control group (primary HR: 0.73; secondary HR: 0.61; and tertiary HR: 0.64). The primary definition was an initial prescription of an ICS-LABA combination in a patient treated with ICS alone, severe exacerbation of asthma symptoms, hospital admission, or a diagnosis of chronic asthma.
“The risk reductions were significant and consistent for the allergens analyzed,” said study co-author Pascal Demoly, MD, PhD, head of pulmonology at Montpellier University Hospital, France (tertiary HR, dust mites: 0.66; grass: 0.59; birch: 0.34; and cats: 0.77). “This was across all age groups,” he added.
“The results of the EfficAPSI real-world study on health data from the SNDS are consistent with outcomes from clinical trials, suggestive of a reduced risk of asthma onset in patients with allergic rhinitis receiving liquid SLIT, as well as a reduced risk of worsening of preexisting asthma,” said Devillier. “SLIT, in this case in the form of a liquid, thus appears to be an effective etiological treatment, since the use of symptomatic drugs, in particular preventer inhalers, but also reliever inhalers, is lower in patients treated with SLIT over at least two consecutive years, compared with paired control subjects. And it’s the same for the risk of treating asthma in nonasthmatic patients at the start of the study. EfficAPSI is the largest study using data from a comprehensive state drug reimbursement database, allowing us to assess the impact of liquid SLIT on public health. These results, also obtained with other allergen preparations, particularly in tablet form in French and German studies using data from health care databases, demonstrate the consistency of the data regarding the efficacy of SLIT.”
This article was translated from the Medscape French Edition. A version appeared on Medscape.com.
PARIS – The EfficAPSI study showed with real-world data that sublingual immunotherapy (SLIT) reduces the risks for asthma onset and the worsening of asthma symptoms for patients with allergic rhinitis. The research was presented at the 18th French-language allergy conference.
These results confirm that allergen immunotherapy, or “desensitization,” is indeed an etiologic treatment of this allergic condition.
SLIT encompasses personalized solutions created for an individual specifically for allergies to dust mites, grass, birch, cats, and so on. These preparations are commonly used by allergy specialists when establishing an AIT treatment plan.
In 2017, the French Health Authority published a report indicating that there was insufficient clinical proof regarding the efficacy of SLIT. It subsequently removed injectable forms of these allergen extracts from the list of drugs reimbursed by the state and reduced state reimbursement of sublingual SLIT preparations from 30% to 15%, a step it confirmed in March 2018 and that led to outrage from allergy specialists. The chair of the French allergy society at the time, Jocelyne Just, MD, PhD, argued that conducting double-blind, placebo-controlled studies for all types (grass pollen, birch pollen, dust mites, asthma, allergic rhinitis, subcutaneous injections, sublingual treatments, tablets, liquid preparations) would take decades. Furthermore, meta-analyses on the subject, despite being heterogeneous and unable to answer all questions, are indeed pointing to the effectiveness of SLIT. To supplement existing data and to answer the queries raised by the HAS, several studies have been launched, including EfficAPSI.
The pharmacoepidemiologic EfficAPSI study is the largest retrospective, real-world, longitudinal cohort study ever carried out regarding liquid SLIT using data stored in the French National Health Data System (SNDS). The primary objective of the study was to evaluate the real-world impact of liquid SLIT on the onset and worsening of asthma for patients with allergic rhinitis and to evaluate the impact of sublingual treatments on public health.
A cohort analysis of patients treated with SLIT and control patients treated for allergic rhinitis with or without treatment for asthma was carried out. The patients treated with SLIT for at least 2 consecutive years were anonymously selected from the SNDS using the Stallergenes Greer prescription database.
In all, 99,538 patients who received SLIT were compared with 333,082 control patients (those who had received treatment for allergic rhinitis without taking SLIT). Participants were stratified according to their treatment history for asthma and were paired using a propensity score to minimize comparison bias.
The main definition of the onset of asthma included the first prescription of an asthma medication, hospital admission for asthma, or a diagnosis of chronic asthma. The secondary definition omitted the prescription of any treatment, and the third (sensitive and specific) took into consideration an initial prescription of omalizumab or a prescription of three inhaled corticosteroids (ICSs) associated with or without a long-acting beta-2 agonist (LABA) for a period of 1 year, admission to the hospital, or chronic asthma.
Asthma risk reduced
Among patients with allergic rhinitis without preexisting asthma, liquid SLIT was associated with a significantly lower risk of asthma onset in comparison with the control group (primary hazard ratio: 0.77; secondary HR: 0.66; and tertiary HR: 0.62).
The risk reductions were significant and were consistent regardless of the allergens analyzed (tertiary HR, dust mites: 0.57; grass: 0.52) for all age groups. These new results that were based on the tertiary definition corroborate the results from the primary and secondary definitions.
said study co-author Philippe Devillier, MD, PhD, research director at the respiratory tract diseases center of Foch Hospital, Paris. “These results are consistent with previous studies in the same French health care database, as well as in a German database with SLIT preparations in tablet form. This not only confirms the soundness of the methodology but also the benefit of liquid SLIT as an etiological treatment of respiratory allergies.”
Risk for worsening
Furthermore, in the same study, liquid SLIT treatment was associated with a 27% reduced risk for worsening asthma and a 36% reduced risk for severe asthma. Among patients with allergic rhinitis and preexisting asthma, liquid SLIT was associated with a significantly lower risk for worsening of asthma, compared with the control group (primary HR: 0.73; secondary HR: 0.61; and tertiary HR: 0.64). The primary definition was an initial prescription of an ICS-LABA combination in a patient treated with ICS alone, severe exacerbation of asthma symptoms, hospital admission, or a diagnosis of chronic asthma.
“The risk reductions were significant and consistent for the allergens analyzed,” said study co-author Pascal Demoly, MD, PhD, head of pulmonology at Montpellier University Hospital, France (tertiary HR, dust mites: 0.66; grass: 0.59; birch: 0.34; and cats: 0.77). “This was across all age groups,” he added.
“The results of the EfficAPSI real-world study on health data from the SNDS are consistent with outcomes from clinical trials, suggestive of a reduced risk of asthma onset in patients with allergic rhinitis receiving liquid SLIT, as well as a reduced risk of worsening of preexisting asthma,” said Devillier. “SLIT, in this case in the form of a liquid, thus appears to be an effective etiological treatment, since the use of symptomatic drugs, in particular preventer inhalers, but also reliever inhalers, is lower in patients treated with SLIT over at least two consecutive years, compared with paired control subjects. And it’s the same for the risk of treating asthma in nonasthmatic patients at the start of the study. EfficAPSI is the largest study using data from a comprehensive state drug reimbursement database, allowing us to assess the impact of liquid SLIT on public health. These results, also obtained with other allergen preparations, particularly in tablet form in French and German studies using data from health care databases, demonstrate the consistency of the data regarding the efficacy of SLIT.”
This article was translated from the Medscape French Edition. A version appeared on Medscape.com.
PARIS – The EfficAPSI study showed with real-world data that sublingual immunotherapy (SLIT) reduces the risks for asthma onset and the worsening of asthma symptoms for patients with allergic rhinitis. The research was presented at the 18th French-language allergy conference.
These results confirm that allergen immunotherapy, or “desensitization,” is indeed an etiologic treatment of this allergic condition.
SLIT encompasses personalized solutions created for an individual specifically for allergies to dust mites, grass, birch, cats, and so on. These preparations are commonly used by allergy specialists when establishing an AIT treatment plan.
In 2017, the French Health Authority published a report indicating that there was insufficient clinical proof regarding the efficacy of SLIT. It subsequently removed injectable forms of these allergen extracts from the list of drugs reimbursed by the state and reduced state reimbursement of sublingual SLIT preparations from 30% to 15%, a step it confirmed in March 2018 and that led to outrage from allergy specialists. The chair of the French allergy society at the time, Jocelyne Just, MD, PhD, argued that conducting double-blind, placebo-controlled studies for all types (grass pollen, birch pollen, dust mites, asthma, allergic rhinitis, subcutaneous injections, sublingual treatments, tablets, liquid preparations) would take decades. Furthermore, meta-analyses on the subject, despite being heterogeneous and unable to answer all questions, are indeed pointing to the effectiveness of SLIT. To supplement existing data and to answer the queries raised by the HAS, several studies have been launched, including EfficAPSI.
The pharmacoepidemiologic EfficAPSI study is the largest retrospective, real-world, longitudinal cohort study ever carried out regarding liquid SLIT using data stored in the French National Health Data System (SNDS). The primary objective of the study was to evaluate the real-world impact of liquid SLIT on the onset and worsening of asthma for patients with allergic rhinitis and to evaluate the impact of sublingual treatments on public health.
A cohort analysis of patients treated with SLIT and control patients treated for allergic rhinitis with or without treatment for asthma was carried out. The patients treated with SLIT for at least 2 consecutive years were anonymously selected from the SNDS using the Stallergenes Greer prescription database.
In all, 99,538 patients who received SLIT were compared with 333,082 control patients (those who had received treatment for allergic rhinitis without taking SLIT). Participants were stratified according to their treatment history for asthma and were paired using a propensity score to minimize comparison bias.
The main definition of the onset of asthma included the first prescription of an asthma medication, hospital admission for asthma, or a diagnosis of chronic asthma. The secondary definition omitted the prescription of any treatment, and the third (sensitive and specific) took into consideration an initial prescription of omalizumab or a prescription of three inhaled corticosteroids (ICSs) associated with or without a long-acting beta-2 agonist (LABA) for a period of 1 year, admission to the hospital, or chronic asthma.
Asthma risk reduced
Among patients with allergic rhinitis without preexisting asthma, liquid SLIT was associated with a significantly lower risk of asthma onset in comparison with the control group (primary hazard ratio: 0.77; secondary HR: 0.66; and tertiary HR: 0.62).
The risk reductions were significant and were consistent regardless of the allergens analyzed (tertiary HR, dust mites: 0.57; grass: 0.52) for all age groups. These new results that were based on the tertiary definition corroborate the results from the primary and secondary definitions.
said study co-author Philippe Devillier, MD, PhD, research director at the respiratory tract diseases center of Foch Hospital, Paris. “These results are consistent with previous studies in the same French health care database, as well as in a German database with SLIT preparations in tablet form. This not only confirms the soundness of the methodology but also the benefit of liquid SLIT as an etiological treatment of respiratory allergies.”
Risk for worsening
Furthermore, in the same study, liquid SLIT treatment was associated with a 27% reduced risk for worsening asthma and a 36% reduced risk for severe asthma. Among patients with allergic rhinitis and preexisting asthma, liquid SLIT was associated with a significantly lower risk for worsening of asthma, compared with the control group (primary HR: 0.73; secondary HR: 0.61; and tertiary HR: 0.64). The primary definition was an initial prescription of an ICS-LABA combination in a patient treated with ICS alone, severe exacerbation of asthma symptoms, hospital admission, or a diagnosis of chronic asthma.
“The risk reductions were significant and consistent for the allergens analyzed,” said study co-author Pascal Demoly, MD, PhD, head of pulmonology at Montpellier University Hospital, France (tertiary HR, dust mites: 0.66; grass: 0.59; birch: 0.34; and cats: 0.77). “This was across all age groups,” he added.
“The results of the EfficAPSI real-world study on health data from the SNDS are consistent with outcomes from clinical trials, suggestive of a reduced risk of asthma onset in patients with allergic rhinitis receiving liquid SLIT, as well as a reduced risk of worsening of preexisting asthma,” said Devillier. “SLIT, in this case in the form of a liquid, thus appears to be an effective etiological treatment, since the use of symptomatic drugs, in particular preventer inhalers, but also reliever inhalers, is lower in patients treated with SLIT over at least two consecutive years, compared with paired control subjects. And it’s the same for the risk of treating asthma in nonasthmatic patients at the start of the study. EfficAPSI is the largest study using data from a comprehensive state drug reimbursement database, allowing us to assess the impact of liquid SLIT on public health. These results, also obtained with other allergen preparations, particularly in tablet form in French and German studies using data from health care databases, demonstrate the consistency of the data regarding the efficacy of SLIT.”
This article was translated from the Medscape French Edition. A version appeared on Medscape.com.
Circulating tumor DNA may predict poor prognosis in breast cancer
a new meta-analysis and systematic review found.
“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.
“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
Methods and results
The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.
The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.
For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.
For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.
The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.
In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
Results show ctDNA detection is associated with worse survival
“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.
“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”
The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
a new meta-analysis and systematic review found.
“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.
“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
Methods and results
The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.
The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.
For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.
For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.
The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.
In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
Results show ctDNA detection is associated with worse survival
“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.
“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”
The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
a new meta-analysis and systematic review found.
“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.
“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
Methods and results
The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.
The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.
For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.
For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.
The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.
In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
Results show ctDNA detection is associated with worse survival
“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.
“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”
The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
ESMO BREAST CANCER 2023
Breast cancer outcomes are worse for Black men
A new study finds that racial disparities in male breast cancer are persisting in the United States.
From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.
“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”
Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
Methods and results
Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).
Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).
Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
Findings reflect the disparities in female breast cancer
In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.
“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.
“You see similar disparities as related to mortality in Black vs. White men,” he noted.
The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.
But, he noted, the study finds that income doesn’t appear to be a factor.
In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”
No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
A new study finds that racial disparities in male breast cancer are persisting in the United States.
From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.
“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”
Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
Methods and results
Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).
Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).
Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
Findings reflect the disparities in female breast cancer
In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.
“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.
“You see similar disparities as related to mortality in Black vs. White men,” he noted.
The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.
But, he noted, the study finds that income doesn’t appear to be a factor.
In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”
No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
A new study finds that racial disparities in male breast cancer are persisting in the United States.
From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.
“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”
Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
Methods and results
Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).
Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).
Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
Findings reflect the disparities in female breast cancer
In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.
“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.
“You see similar disparities as related to mortality in Black vs. White men,” he noted.
The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.
But, he noted, the study finds that income doesn’t appear to be a factor.
In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”
No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
FROM ESMO BREAST CANCER 2023
Eating disorder apps fall short when it comes to privacy
SAN FRANCISCO –
Federal laws require those handling sensitive health information to have policies and security safeguards in place to protect such information, whether it’s stored on paper or electronically.
“As it stands right now, there’s not enough evidence to support using these apps as an adjunct to clinical care,” study author Theodora O’Leary, a 4th-year medical student at Tufts University, Boston, said in an interview. “We need more research on the efficacy of these apps because right now not enough of them meet HIPAA [standards] and don’t have privacy and security measures.”
The findings were presented at the annual meeting of the American Psychiatric Association.
Eating disorders (EDs) are a common mental health condition affecting almost 1 in 10 Americans over their lifetime. Yet only about a third of patients with an eating disorder receive adequate treatment.
The pandemic saw a rise in eating disorders and in the use of mental health apps “to kind of fill the gap because people couldn’t be seen in person,” said Ms. O’Leary.
Inexpensive and accessible
Smartphone apps have a lot of advantages for patients with an ED. For one thing, they’re relatively inexpensive and accessible; most Americans already own one or more devices on which these apps can be used.
They’re also a feasible means of delivering psychological interventions, which are often recommended for EDs. Among these interventions, cognitive-behavioral therapy (CBT) has the largest evidence base for this condition.
Also, as many individuals with an ED may be reluctant to seek treatment because of stigma and shame, the anonymity afforded by an app could increase access to the help they seek.
But Ms. O’Leary warned the Food and Drug Administration does not regulate these apps, and people are sharing their personal health information on them.
The researchers conducted a review of commercially available eating disorder apps by searching the Apple and Google play stores using key phrases such as “eating disorder,” “anorexia,” and “binge eating disorder.”
They found 16 relevant apps that they added to the publicly available apps already in a database at Tufts, for a total of about 36 that were evaluated in the study (the number fluctuates as apps are deleted.)
They then reviewed the apps using the 105 questions based on the APA’s app evaluation model, which covers categories such as efficacy, privacy, accessibility, and clinical applicability. And they used filters to group apps by characteristics such as function, cost, and features.
The vast majority were self-help apps, which include things like journaling, meditation, and information on CBT. Others were reference apps that provide related definitions and sometimes include surveys to determine, for example, if the user has an eating disorder.
About 44% of the apps track mood, and 53% track symptoms. Some 56% include journaling, 42% mindfulness, 53% goal setting, and 42% psychoeducation.
Hybrid care
Only 5% of apps allow for “hybrid” care. This, explained Ms. O’Leary, is when clinicians use their own app to access patients’ apps, allowing them to track food restrictions and therapies, and make comments.
“The hybrid is viewed as the best form of app”, she said. “It’s almost like an adjunct to clinical care.”
Hybrid apps also tend to have patient safety features, she added. And these apps meet HIPAA standards, which only 11% of the apps in the study did.
Only 15% of apps advised patients to take steps in case of an emergency, and 11% had supporting studies. And where there was supporting research, much of it was funded by the app creators, said Ms. O’Leary.
For example, an app provided by Noom (the weight loss program that promises to help change habits and mindsets around food) “has a bunch of feasibility studies but they’re all funded by Noom”, which can introduce bias, she explained.
None of the apps were created by an accredited health care institution, she noted. “And I think only one app out of all the eating disorder apps we looked at was from a nonprofit.”
About 17% of the apps offer help with a “coach” or “expert”. However, these apps often fail to disclose the definition of a coach or state they’re not a replacement for medical care.
Coaching apps more expensive
Additionally, these coaching apps are often some of the most expensive, said Ms. O’Leary.
Daniel E. Gih, MD, associate professor at the University of Nebraska Medical Center, Omaha, helped start an eating disorders program at the University of Michigan and continues to treat patients with eating disorders. He said the increase in the use of eating disorder apps isn’t surprising as the incidence of these disorders increased in the wake of pandemic restrictions, especially among young people.
“Patients are likely doing more research on their medical conditions and trying to crowdsource information or self-treat,” Dr. Gih said.
It’s unclear whether “shame or just the general lack of specialized eating disorder professionals,” including physicians, is driving some of the interest in these apps, he added.
Dr. Gih stressed eating disorder apps should not only include screening for suicidality, but also explicitly tell patients to seek immediate attention if they show certain signs – for example, fainting, chest pain, or blood in emesis.
“The apps may be giving patients false hope or delaying medical care,” he said. “Apps are likely not sufficient enough to replace a multidisciplinary team with experience and expertise in eating disorders.”
Ms. O’Leary and Dr. Gih report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO –
Federal laws require those handling sensitive health information to have policies and security safeguards in place to protect such information, whether it’s stored on paper or electronically.
“As it stands right now, there’s not enough evidence to support using these apps as an adjunct to clinical care,” study author Theodora O’Leary, a 4th-year medical student at Tufts University, Boston, said in an interview. “We need more research on the efficacy of these apps because right now not enough of them meet HIPAA [standards] and don’t have privacy and security measures.”
The findings were presented at the annual meeting of the American Psychiatric Association.
Eating disorders (EDs) are a common mental health condition affecting almost 1 in 10 Americans over their lifetime. Yet only about a third of patients with an eating disorder receive adequate treatment.
The pandemic saw a rise in eating disorders and in the use of mental health apps “to kind of fill the gap because people couldn’t be seen in person,” said Ms. O’Leary.
Inexpensive and accessible
Smartphone apps have a lot of advantages for patients with an ED. For one thing, they’re relatively inexpensive and accessible; most Americans already own one or more devices on which these apps can be used.
They’re also a feasible means of delivering psychological interventions, which are often recommended for EDs. Among these interventions, cognitive-behavioral therapy (CBT) has the largest evidence base for this condition.
Also, as many individuals with an ED may be reluctant to seek treatment because of stigma and shame, the anonymity afforded by an app could increase access to the help they seek.
But Ms. O’Leary warned the Food and Drug Administration does not regulate these apps, and people are sharing their personal health information on them.
The researchers conducted a review of commercially available eating disorder apps by searching the Apple and Google play stores using key phrases such as “eating disorder,” “anorexia,” and “binge eating disorder.”
They found 16 relevant apps that they added to the publicly available apps already in a database at Tufts, for a total of about 36 that were evaluated in the study (the number fluctuates as apps are deleted.)
They then reviewed the apps using the 105 questions based on the APA’s app evaluation model, which covers categories such as efficacy, privacy, accessibility, and clinical applicability. And they used filters to group apps by characteristics such as function, cost, and features.
The vast majority were self-help apps, which include things like journaling, meditation, and information on CBT. Others were reference apps that provide related definitions and sometimes include surveys to determine, for example, if the user has an eating disorder.
About 44% of the apps track mood, and 53% track symptoms. Some 56% include journaling, 42% mindfulness, 53% goal setting, and 42% psychoeducation.
Hybrid care
Only 5% of apps allow for “hybrid” care. This, explained Ms. O’Leary, is when clinicians use their own app to access patients’ apps, allowing them to track food restrictions and therapies, and make comments.
“The hybrid is viewed as the best form of app”, she said. “It’s almost like an adjunct to clinical care.”
Hybrid apps also tend to have patient safety features, she added. And these apps meet HIPAA standards, which only 11% of the apps in the study did.
Only 15% of apps advised patients to take steps in case of an emergency, and 11% had supporting studies. And where there was supporting research, much of it was funded by the app creators, said Ms. O’Leary.
For example, an app provided by Noom (the weight loss program that promises to help change habits and mindsets around food) “has a bunch of feasibility studies but they’re all funded by Noom”, which can introduce bias, she explained.
None of the apps were created by an accredited health care institution, she noted. “And I think only one app out of all the eating disorder apps we looked at was from a nonprofit.”
About 17% of the apps offer help with a “coach” or “expert”. However, these apps often fail to disclose the definition of a coach or state they’re not a replacement for medical care.
Coaching apps more expensive
Additionally, these coaching apps are often some of the most expensive, said Ms. O’Leary.
Daniel E. Gih, MD, associate professor at the University of Nebraska Medical Center, Omaha, helped start an eating disorders program at the University of Michigan and continues to treat patients with eating disorders. He said the increase in the use of eating disorder apps isn’t surprising as the incidence of these disorders increased in the wake of pandemic restrictions, especially among young people.
“Patients are likely doing more research on their medical conditions and trying to crowdsource information or self-treat,” Dr. Gih said.
It’s unclear whether “shame or just the general lack of specialized eating disorder professionals,” including physicians, is driving some of the interest in these apps, he added.
Dr. Gih stressed eating disorder apps should not only include screening for suicidality, but also explicitly tell patients to seek immediate attention if they show certain signs – for example, fainting, chest pain, or blood in emesis.
“The apps may be giving patients false hope or delaying medical care,” he said. “Apps are likely not sufficient enough to replace a multidisciplinary team with experience and expertise in eating disorders.”
Ms. O’Leary and Dr. Gih report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO –
Federal laws require those handling sensitive health information to have policies and security safeguards in place to protect such information, whether it’s stored on paper or electronically.
“As it stands right now, there’s not enough evidence to support using these apps as an adjunct to clinical care,” study author Theodora O’Leary, a 4th-year medical student at Tufts University, Boston, said in an interview. “We need more research on the efficacy of these apps because right now not enough of them meet HIPAA [standards] and don’t have privacy and security measures.”
The findings were presented at the annual meeting of the American Psychiatric Association.
Eating disorders (EDs) are a common mental health condition affecting almost 1 in 10 Americans over their lifetime. Yet only about a third of patients with an eating disorder receive adequate treatment.
The pandemic saw a rise in eating disorders and in the use of mental health apps “to kind of fill the gap because people couldn’t be seen in person,” said Ms. O’Leary.
Inexpensive and accessible
Smartphone apps have a lot of advantages for patients with an ED. For one thing, they’re relatively inexpensive and accessible; most Americans already own one or more devices on which these apps can be used.
They’re also a feasible means of delivering psychological interventions, which are often recommended for EDs. Among these interventions, cognitive-behavioral therapy (CBT) has the largest evidence base for this condition.
Also, as many individuals with an ED may be reluctant to seek treatment because of stigma and shame, the anonymity afforded by an app could increase access to the help they seek.
But Ms. O’Leary warned the Food and Drug Administration does not regulate these apps, and people are sharing their personal health information on them.
The researchers conducted a review of commercially available eating disorder apps by searching the Apple and Google play stores using key phrases such as “eating disorder,” “anorexia,” and “binge eating disorder.”
They found 16 relevant apps that they added to the publicly available apps already in a database at Tufts, for a total of about 36 that were evaluated in the study (the number fluctuates as apps are deleted.)
They then reviewed the apps using the 105 questions based on the APA’s app evaluation model, which covers categories such as efficacy, privacy, accessibility, and clinical applicability. And they used filters to group apps by characteristics such as function, cost, and features.
The vast majority were self-help apps, which include things like journaling, meditation, and information on CBT. Others were reference apps that provide related definitions and sometimes include surveys to determine, for example, if the user has an eating disorder.
About 44% of the apps track mood, and 53% track symptoms. Some 56% include journaling, 42% mindfulness, 53% goal setting, and 42% psychoeducation.
Hybrid care
Only 5% of apps allow for “hybrid” care. This, explained Ms. O’Leary, is when clinicians use their own app to access patients’ apps, allowing them to track food restrictions and therapies, and make comments.
“The hybrid is viewed as the best form of app”, she said. “It’s almost like an adjunct to clinical care.”
Hybrid apps also tend to have patient safety features, she added. And these apps meet HIPAA standards, which only 11% of the apps in the study did.
Only 15% of apps advised patients to take steps in case of an emergency, and 11% had supporting studies. And where there was supporting research, much of it was funded by the app creators, said Ms. O’Leary.
For example, an app provided by Noom (the weight loss program that promises to help change habits and mindsets around food) “has a bunch of feasibility studies but they’re all funded by Noom”, which can introduce bias, she explained.
None of the apps were created by an accredited health care institution, she noted. “And I think only one app out of all the eating disorder apps we looked at was from a nonprofit.”
About 17% of the apps offer help with a “coach” or “expert”. However, these apps often fail to disclose the definition of a coach or state they’re not a replacement for medical care.
Coaching apps more expensive
Additionally, these coaching apps are often some of the most expensive, said Ms. O’Leary.
Daniel E. Gih, MD, associate professor at the University of Nebraska Medical Center, Omaha, helped start an eating disorders program at the University of Michigan and continues to treat patients with eating disorders. He said the increase in the use of eating disorder apps isn’t surprising as the incidence of these disorders increased in the wake of pandemic restrictions, especially among young people.
“Patients are likely doing more research on their medical conditions and trying to crowdsource information or self-treat,” Dr. Gih said.
It’s unclear whether “shame or just the general lack of specialized eating disorder professionals,” including physicians, is driving some of the interest in these apps, he added.
Dr. Gih stressed eating disorder apps should not only include screening for suicidality, but also explicitly tell patients to seek immediate attention if they show certain signs – for example, fainting, chest pain, or blood in emesis.
“The apps may be giving patients false hope or delaying medical care,” he said. “Apps are likely not sufficient enough to replace a multidisciplinary team with experience and expertise in eating disorders.”
Ms. O’Leary and Dr. Gih report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT APA 2023