Federal Practitioner

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

A version of this article first appeared on Medscape.com.

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

A version of this article first appeared on Medscape.com.

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

A version of this article first appeared on Medscape.com.

PARIS – Adults who are easily angered may have experienced trauma during childhood, according to new findings that investigators believe warrant routine trauma screening for patents with depression and/or anxiety.

Investigators examined data on more than 2,250 individuals who were asked about trauma during childhood and a subsequent tendency toward anger or angry outbursts 4 years later.

Results showed that emotional neglect during childhood was associated with approximately a 40% increased likelihood of subsequent anger, while psychological abuse was linked to a 30% increased likelihood.

Childhood physical abuse was also significantly associated with anger in adults, with an increased risk of approximately 40%. The researchers found no link between childhood sexual abuse and adult anger.

“We can’t definitively say that the trauma causes the anger, but the link is clear,” study investigator Nienke De Bles, PhD student, department of psychiatry, Leiden (the Netherlands) University Medical Center, said in a news release.

“Being easily angered can have several consequences,” she continued. “It can make personal interactions more difficult, and it can have consequences for your mental health and well-being, but people who get angry easily also have a greater tendency to discontinue psychiatric treatment, so this anger may mean that it reduces their chances of a better life,” she added.

Ms. De Bles believes that “it should be standard practice to ask depression and anxiety sufferers about anger and past trauma, even if the patient is not exhibiting current anger.”

The findings were presented at the European Psychiatric Association 2023 Congress.
 

A ‘red flag’ for abuse

“Psychiatric treatments for past trauma may differ from treatments for depression, so psychiatrists need to try to understand the cause so that they can offer the correct treatment to each patient,” said Ms. De Bles.

Ms. De Bles noted that childhood trauma has many negative consequences later in life and that it is associated with a higher prevalence of adult depression and anxiety.

“There are several potential mechanisms for psychopathology in the context of childhood trauma, and emotion regulation seems to be one of the key mechanisms,” she said.

The researchers previously found that anger was highly prevalent among patients with affective disorders. It was present in 30% of those with current anxiety or depressive disorder and in 40% of those with comorbid depression and anxiety with a tendency toward anger versus 5% of healthy control persons.

Other studies have shown that anger is associated with poor treatment outcomes and dropping out of treatment.

To further investigate the link between childhood trauma and anger in adulthood, the researchers examined data on 2,271 participants in the Netherlands Study of Depression and Anxiety (NESDA).

Childhood trauma was assessed at baseline using the semistructured Childhood Trauma Interview. Anger was measured at a 4-year follow-up using the Spielberger Trait Anger Subscale, the Anger Attacks Questionnaire, and the borderline and antisocial subscales of the Personality Disorder Questionnaire 4 to identify cluster B personality traits.

Results showed that emotional neglect during childhood was significantly associated with trait anger in adulthood, at an adjusted odds ratio of 1.42 (P < .001), anger attacks (OR, 1.35; P = .004), and borderline (OR, 1.76; P < .001) and antisocial (OR, 1.88; P = .001) personality traits.

Childhood psychological abuse was also significantly associated with later trait anger (OR, 1.28; P = .002), anger attacks (OR, 1.31; P = .024), and borderline (OR, 1.77; P < .001) and antisocial (OR, 1.69; P = .011) traits.

There was also a significant association between childhood psychical abuse and trait anger in adulthood (OR, 1.37; P < .001), anger attacks (OR, 1.48; P = .004), and borderline (OR, 1.71; P < .001) and antisocial (OR, 1.98; P = .002) traits.

There was no significant association between sexual abuse experienced in childhood and later anger or personality traits.

Ms. De Bles said the findings suggest “there is indeed a relationship between childhood trauma and anger in adulthood, and this is something that might be interesting for clinicians, as anger could be a red flag for a history of childhood trauma.”

She said in an interview that anger is a “very normal human emotion” but that it has not been as widely studied as sadness and anxiety.

She suggested that future research could examine the use of trauma-based therapies for patients with a history of childhood trauma and anger.
 

Overlooked, neglected

Commenting on the findings, Nur Hani Zainal, PhD, department of healthcare policy, Harvard Medical School, Boston, said the findings are “very consistent with the current biopsychosocial models in psychiatry and clinical psychology.”

Dr. Zainal, who was coauthor of a recent study that showed that anger appears to mediate the relationship between childhood trauma and adult psychopathology, said the current study offers a “good, incremental contribution” to the literature.

She noted there are “good uses” for the emotion of anger, as “sometimes we need anger to set healthy boundaries for ourselves.” However, she agreed that, as an aspect of depression, anxiety, and posttraumatic stress disorder, it is often “overlooked.”

Dr. Zainal said that the findings reinforce the importance of thoroughly evaluating adult patients’ experiences during childhood.

Julian Beezhold, MD, secretary general of the EPA and a consultant psychiatrist with the Norwich (England) Medical School, University of East Anglia, commented in the release that anger is a “somewhat neglected symptom.

“The findings are in line with what we see in day-to-day clinical practice and will hopefully help increase the awareness of the importance of both anger and associated childhood trauma.”

The infrastructure for the NESDA study is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development and financial contributions by participating universities and mental health care organizations. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PARIS – Adults who are easily angered may have experienced trauma during childhood, according to new findings that investigators believe warrant routine trauma screening for patents with depression and/or anxiety.

Investigators examined data on more than 2,250 individuals who were asked about trauma during childhood and a subsequent tendency toward anger or angry outbursts 4 years later.

Results showed that emotional neglect during childhood was associated with approximately a 40% increased likelihood of subsequent anger, while psychological abuse was linked to a 30% increased likelihood.

Childhood physical abuse was also significantly associated with anger in adults, with an increased risk of approximately 40%. The researchers found no link between childhood sexual abuse and adult anger.

“We can’t definitively say that the trauma causes the anger, but the link is clear,” study investigator Nienke De Bles, PhD student, department of psychiatry, Leiden (the Netherlands) University Medical Center, said in a news release.

“Being easily angered can have several consequences,” she continued. “It can make personal interactions more difficult, and it can have consequences for your mental health and well-being, but people who get angry easily also have a greater tendency to discontinue psychiatric treatment, so this anger may mean that it reduces their chances of a better life,” she added.

Ms. De Bles believes that “it should be standard practice to ask depression and anxiety sufferers about anger and past trauma, even if the patient is not exhibiting current anger.”

The findings were presented at the European Psychiatric Association 2023 Congress.
 

A ‘red flag’ for abuse

“Psychiatric treatments for past trauma may differ from treatments for depression, so psychiatrists need to try to understand the cause so that they can offer the correct treatment to each patient,” said Ms. De Bles.

Ms. De Bles noted that childhood trauma has many negative consequences later in life and that it is associated with a higher prevalence of adult depression and anxiety.

“There are several potential mechanisms for psychopathology in the context of childhood trauma, and emotion regulation seems to be one of the key mechanisms,” she said.

The researchers previously found that anger was highly prevalent among patients with affective disorders. It was present in 30% of those with current anxiety or depressive disorder and in 40% of those with comorbid depression and anxiety with a tendency toward anger versus 5% of healthy control persons.

Other studies have shown that anger is associated with poor treatment outcomes and dropping out of treatment.

To further investigate the link between childhood trauma and anger in adulthood, the researchers examined data on 2,271 participants in the Netherlands Study of Depression and Anxiety (NESDA).

Childhood trauma was assessed at baseline using the semistructured Childhood Trauma Interview. Anger was measured at a 4-year follow-up using the Spielberger Trait Anger Subscale, the Anger Attacks Questionnaire, and the borderline and antisocial subscales of the Personality Disorder Questionnaire 4 to identify cluster B personality traits.

Results showed that emotional neglect during childhood was significantly associated with trait anger in adulthood, at an adjusted odds ratio of 1.42 (P < .001), anger attacks (OR, 1.35; P = .004), and borderline (OR, 1.76; P < .001) and antisocial (OR, 1.88; P = .001) personality traits.

Childhood psychological abuse was also significantly associated with later trait anger (OR, 1.28; P = .002), anger attacks (OR, 1.31; P = .024), and borderline (OR, 1.77; P < .001) and antisocial (OR, 1.69; P = .011) traits.

There was also a significant association between childhood psychical abuse and trait anger in adulthood (OR, 1.37; P < .001), anger attacks (OR, 1.48; P = .004), and borderline (OR, 1.71; P < .001) and antisocial (OR, 1.98; P = .002) traits.

There was no significant association between sexual abuse experienced in childhood and later anger or personality traits.

Ms. De Bles said the findings suggest “there is indeed a relationship between childhood trauma and anger in adulthood, and this is something that might be interesting for clinicians, as anger could be a red flag for a history of childhood trauma.”

She said in an interview that anger is a “very normal human emotion” but that it has not been as widely studied as sadness and anxiety.

She suggested that future research could examine the use of trauma-based therapies for patients with a history of childhood trauma and anger.
 

Overlooked, neglected

Commenting on the findings, Nur Hani Zainal, PhD, department of healthcare policy, Harvard Medical School, Boston, said the findings are “very consistent with the current biopsychosocial models in psychiatry and clinical psychology.”

Dr. Zainal, who was coauthor of a recent study that showed that anger appears to mediate the relationship between childhood trauma and adult psychopathology, said the current study offers a “good, incremental contribution” to the literature.

She noted there are “good uses” for the emotion of anger, as “sometimes we need anger to set healthy boundaries for ourselves.” However, she agreed that, as an aspect of depression, anxiety, and posttraumatic stress disorder, it is often “overlooked.”

Dr. Zainal said that the findings reinforce the importance of thoroughly evaluating adult patients’ experiences during childhood.

Julian Beezhold, MD, secretary general of the EPA and a consultant psychiatrist with the Norwich (England) Medical School, University of East Anglia, commented in the release that anger is a “somewhat neglected symptom.

“The findings are in line with what we see in day-to-day clinical practice and will hopefully help increase the awareness of the importance of both anger and associated childhood trauma.”

The infrastructure for the NESDA study is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development and financial contributions by participating universities and mental health care organizations. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PARIS – Adults who are easily angered may have experienced trauma during childhood, according to new findings that investigators believe warrant routine trauma screening for patents with depression and/or anxiety.

Investigators examined data on more than 2,250 individuals who were asked about trauma during childhood and a subsequent tendency toward anger or angry outbursts 4 years later.

Results showed that emotional neglect during childhood was associated with approximately a 40% increased likelihood of subsequent anger, while psychological abuse was linked to a 30% increased likelihood.

Childhood physical abuse was also significantly associated with anger in adults, with an increased risk of approximately 40%. The researchers found no link between childhood sexual abuse and adult anger.

“We can’t definitively say that the trauma causes the anger, but the link is clear,” study investigator Nienke De Bles, PhD student, department of psychiatry, Leiden (the Netherlands) University Medical Center, said in a news release.

“Being easily angered can have several consequences,” she continued. “It can make personal interactions more difficult, and it can have consequences for your mental health and well-being, but people who get angry easily also have a greater tendency to discontinue psychiatric treatment, so this anger may mean that it reduces their chances of a better life,” she added.

Ms. De Bles believes that “it should be standard practice to ask depression and anxiety sufferers about anger and past trauma, even if the patient is not exhibiting current anger.”

The findings were presented at the European Psychiatric Association 2023 Congress.
 

A ‘red flag’ for abuse

“Psychiatric treatments for past trauma may differ from treatments for depression, so psychiatrists need to try to understand the cause so that they can offer the correct treatment to each patient,” said Ms. De Bles.

Ms. De Bles noted that childhood trauma has many negative consequences later in life and that it is associated with a higher prevalence of adult depression and anxiety.

“There are several potential mechanisms for psychopathology in the context of childhood trauma, and emotion regulation seems to be one of the key mechanisms,” she said.

The researchers previously found that anger was highly prevalent among patients with affective disorders. It was present in 30% of those with current anxiety or depressive disorder and in 40% of those with comorbid depression and anxiety with a tendency toward anger versus 5% of healthy control persons.

Other studies have shown that anger is associated with poor treatment outcomes and dropping out of treatment.

To further investigate the link between childhood trauma and anger in adulthood, the researchers examined data on 2,271 participants in the Netherlands Study of Depression and Anxiety (NESDA).

Childhood trauma was assessed at baseline using the semistructured Childhood Trauma Interview. Anger was measured at a 4-year follow-up using the Spielberger Trait Anger Subscale, the Anger Attacks Questionnaire, and the borderline and antisocial subscales of the Personality Disorder Questionnaire 4 to identify cluster B personality traits.

Results showed that emotional neglect during childhood was significantly associated with trait anger in adulthood, at an adjusted odds ratio of 1.42 (P < .001), anger attacks (OR, 1.35; P = .004), and borderline (OR, 1.76; P < .001) and antisocial (OR, 1.88; P = .001) personality traits.

Childhood psychological abuse was also significantly associated with later trait anger (OR, 1.28; P = .002), anger attacks (OR, 1.31; P = .024), and borderline (OR, 1.77; P < .001) and antisocial (OR, 1.69; P = .011) traits.

There was also a significant association between childhood psychical abuse and trait anger in adulthood (OR, 1.37; P < .001), anger attacks (OR, 1.48; P = .004), and borderline (OR, 1.71; P < .001) and antisocial (OR, 1.98; P = .002) traits.

There was no significant association between sexual abuse experienced in childhood and later anger or personality traits.

Ms. De Bles said the findings suggest “there is indeed a relationship between childhood trauma and anger in adulthood, and this is something that might be interesting for clinicians, as anger could be a red flag for a history of childhood trauma.”

She said in an interview that anger is a “very normal human emotion” but that it has not been as widely studied as sadness and anxiety.

She suggested that future research could examine the use of trauma-based therapies for patients with a history of childhood trauma and anger.
 

Overlooked, neglected

Commenting on the findings, Nur Hani Zainal, PhD, department of healthcare policy, Harvard Medical School, Boston, said the findings are “very consistent with the current biopsychosocial models in psychiatry and clinical psychology.”

Dr. Zainal, who was coauthor of a recent study that showed that anger appears to mediate the relationship between childhood trauma and adult psychopathology, said the current study offers a “good, incremental contribution” to the literature.

She noted there are “good uses” for the emotion of anger, as “sometimes we need anger to set healthy boundaries for ourselves.” However, she agreed that, as an aspect of depression, anxiety, and posttraumatic stress disorder, it is often “overlooked.”

Dr. Zainal said that the findings reinforce the importance of thoroughly evaluating adult patients’ experiences during childhood.

Julian Beezhold, MD, secretary general of the EPA and a consultant psychiatrist with the Norwich (England) Medical School, University of East Anglia, commented in the release that anger is a “somewhat neglected symptom.

“The findings are in line with what we see in day-to-day clinical practice and will hopefully help increase the awareness of the importance of both anger and associated childhood trauma.”

The infrastructure for the NESDA study is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development and financial contributions by participating universities and mental health care organizations. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The investigational interleukin-17A inhibitor izokibep showed higher response rates across a number of symptoms in adults with psoriatic arthritis (PsA) in an extension of its phase 2 trial out to 46 weeks, according to an announcement reporting some of the long-term data by the drug’s developer, Acelyrin.

Izokibep is an antibody mimetic designed to inhibit IL-17A that the company says has “high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.”

“Patients want both rapid and meaningful improvement of their symptoms, as well as lasting – and ideally improving – resolution of disease over time. Building on the 16-week data for izokibep reported at EULAR and ACR [American College of Rheumatology] last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” Philip J. Mease, MD, director of rheumatology research at the Swedish Medical Center and clinical professor at the University of Washington, both in Seattle, and an investigator in the izokibep PsA program, said in the announcement.

The phase 2 trial tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active PsA. For inclusion in the trial, patients had to have at least three swollen and at least three tender joints and an inadequate response to prior therapy including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors. At week 16, the placebo group transitioned to 80 mg izokibep every 2 weeks and the trial treatment period continued for up to 46 weeks.

The trial’s primary endpoint of a 50% or higher level of improvement in ACR response criteria (ACR 50) was achieved by 48% of those on the 40 mg dose at week 16 and by 50% at week 46. For the 80-mg group, this rate rose from 52% to 79%. In the group that went from placebo to 80 mg, the ACR 50 rose from 13% with placebo to 73% with izokibep at week 46.

Resolution of enthesitis, measured by the Leeds Enthesitis Index, among those on the 40 mg dose, was achieved by 63% at week 16 and 83% at week 46, and among those on the 80 mg dose, 88% at week 16 and 89% at week 46. Those on placebo who switched to 80 mg of izokibep at week 16 had an 80% rate of enthesitis resolution at week 46.

Total resolution of skin involvement – 100% clearance of psoriasis based on the Psoriasis Area Severity Index (PASI) – was observed at 46 weeks in 50% of those on 40 mg, 71% of those on 80 mg, and 67% of those on 80 mg after week 16.

In its announcement, Acelyrin did not report withdrawal rates from the study after 16 weeks and through 46 weeks, although the statement said that izokibep “was generally well tolerated through 46 weeks, which is in line with previous trials of izokibep.” The most common adverse event was localized injection site reactions, with the majority graded mild to moderate in severity. They were generally the size of a quarter to half-dollar, and typically presented within the first few injections, after which they declined in incidence. In the trial, a case of vulvar cancer was determined to be potentially drug related, the company said.

Acelyrin is currently conducting a phase 2b/3 trial in PsA evaluating a range of doses, including significantly higher doses than in the phase 2 trial, that the company said “could potentially result in better ACR, PASI, and enthesitis resolution responses.”

The drug has been tested at doses up to 160 mg, in some cases for up to 3 years, in more than 400 patients with psoriasis, spondyloarthritis, noninfective uveitis, and hidradenitis suppurativa.

The full 46-week data from this trial will be presented at a future scientific meeting, according to the company.

The investigational interleukin-17A inhibitor izokibep showed higher response rates across a number of symptoms in adults with psoriatic arthritis (PsA) in an extension of its phase 2 trial out to 46 weeks, according to an announcement reporting some of the long-term data by the drug’s developer, Acelyrin.

Izokibep is an antibody mimetic designed to inhibit IL-17A that the company says has “high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.”

“Patients want both rapid and meaningful improvement of their symptoms, as well as lasting – and ideally improving – resolution of disease over time. Building on the 16-week data for izokibep reported at EULAR and ACR [American College of Rheumatology] last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” Philip J. Mease, MD, director of rheumatology research at the Swedish Medical Center and clinical professor at the University of Washington, both in Seattle, and an investigator in the izokibep PsA program, said in the announcement.

The phase 2 trial tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active PsA. For inclusion in the trial, patients had to have at least three swollen and at least three tender joints and an inadequate response to prior therapy including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors. At week 16, the placebo group transitioned to 80 mg izokibep every 2 weeks and the trial treatment period continued for up to 46 weeks.

The trial’s primary endpoint of a 50% or higher level of improvement in ACR response criteria (ACR 50) was achieved by 48% of those on the 40 mg dose at week 16 and by 50% at week 46. For the 80-mg group, this rate rose from 52% to 79%. In the group that went from placebo to 80 mg, the ACR 50 rose from 13% with placebo to 73% with izokibep at week 46.

Resolution of enthesitis, measured by the Leeds Enthesitis Index, among those on the 40 mg dose, was achieved by 63% at week 16 and 83% at week 46, and among those on the 80 mg dose, 88% at week 16 and 89% at week 46. Those on placebo who switched to 80 mg of izokibep at week 16 had an 80% rate of enthesitis resolution at week 46.

Total resolution of skin involvement – 100% clearance of psoriasis based on the Psoriasis Area Severity Index (PASI) – was observed at 46 weeks in 50% of those on 40 mg, 71% of those on 80 mg, and 67% of those on 80 mg after week 16.

In its announcement, Acelyrin did not report withdrawal rates from the study after 16 weeks and through 46 weeks, although the statement said that izokibep “was generally well tolerated through 46 weeks, which is in line with previous trials of izokibep.” The most common adverse event was localized injection site reactions, with the majority graded mild to moderate in severity. They were generally the size of a quarter to half-dollar, and typically presented within the first few injections, after which they declined in incidence. In the trial, a case of vulvar cancer was determined to be potentially drug related, the company said.

Acelyrin is currently conducting a phase 2b/3 trial in PsA evaluating a range of doses, including significantly higher doses than in the phase 2 trial, that the company said “could potentially result in better ACR, PASI, and enthesitis resolution responses.”

The drug has been tested at doses up to 160 mg, in some cases for up to 3 years, in more than 400 patients with psoriasis, spondyloarthritis, noninfective uveitis, and hidradenitis suppurativa.

The full 46-week data from this trial will be presented at a future scientific meeting, according to the company.

The investigational interleukin-17A inhibitor izokibep showed higher response rates across a number of symptoms in adults with psoriatic arthritis (PsA) in an extension of its phase 2 trial out to 46 weeks, according to an announcement reporting some of the long-term data by the drug’s developer, Acelyrin.

Izokibep is an antibody mimetic designed to inhibit IL-17A that the company says has “high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.”

“Patients want both rapid and meaningful improvement of their symptoms, as well as lasting – and ideally improving – resolution of disease over time. Building on the 16-week data for izokibep reported at EULAR and ACR [American College of Rheumatology] last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” Philip J. Mease, MD, director of rheumatology research at the Swedish Medical Center and clinical professor at the University of Washington, both in Seattle, and an investigator in the izokibep PsA program, said in the announcement.

The phase 2 trial tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active PsA. For inclusion in the trial, patients had to have at least three swollen and at least three tender joints and an inadequate response to prior therapy including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors. At week 16, the placebo group transitioned to 80 mg izokibep every 2 weeks and the trial treatment period continued for up to 46 weeks.

The trial’s primary endpoint of a 50% or higher level of improvement in ACR response criteria (ACR 50) was achieved by 48% of those on the 40 mg dose at week 16 and by 50% at week 46. For the 80-mg group, this rate rose from 52% to 79%. In the group that went from placebo to 80 mg, the ACR 50 rose from 13% with placebo to 73% with izokibep at week 46.

Resolution of enthesitis, measured by the Leeds Enthesitis Index, among those on the 40 mg dose, was achieved by 63% at week 16 and 83% at week 46, and among those on the 80 mg dose, 88% at week 16 and 89% at week 46. Those on placebo who switched to 80 mg of izokibep at week 16 had an 80% rate of enthesitis resolution at week 46.

Total resolution of skin involvement – 100% clearance of psoriasis based on the Psoriasis Area Severity Index (PASI) – was observed at 46 weeks in 50% of those on 40 mg, 71% of those on 80 mg, and 67% of those on 80 mg after week 16.

In its announcement, Acelyrin did not report withdrawal rates from the study after 16 weeks and through 46 weeks, although the statement said that izokibep “was generally well tolerated through 46 weeks, which is in line with previous trials of izokibep.” The most common adverse event was localized injection site reactions, with the majority graded mild to moderate in severity. They were generally the size of a quarter to half-dollar, and typically presented within the first few injections, after which they declined in incidence. In the trial, a case of vulvar cancer was determined to be potentially drug related, the company said.

Acelyrin is currently conducting a phase 2b/3 trial in PsA evaluating a range of doses, including significantly higher doses than in the phase 2 trial, that the company said “could potentially result in better ACR, PASI, and enthesitis resolution responses.”

The drug has been tested at doses up to 160 mg, in some cases for up to 3 years, in more than 400 patients with psoriasis, spondyloarthritis, noninfective uveitis, and hidradenitis suppurativa.

The full 46-week data from this trial will be presented at a future scientific meeting, according to the company.

In a new scientific statement, the American Heart Association highlighted the importance of incorporating nonbiological risk factors and social determinants of health in cardiovascular disease (CVD) risk assessment for women, particularly women from different racial and ethnic backgrounds.
 

CVD risk assessment in women is multifaceted and goes well beyond traditional risk factors to include sex-specific biological risk factors, as well as social, behavioral, and environmental factors, the writing group noted.

They said a greater focus on addressing all CVD risk factors among women from underrepresented races and ethnicities is warranted to avert future CVD.

The scientific statement was published online in Circulation.
 

Look beyond traditional risk factors

“Risk assessment is the first step in preventing heart disease, yet there are many limitations to traditional risk factors and their ability to comprehensively estimate a woman’s risk for cardiovascular disease,” Jennifer H. Mieres, MD, vice chair of the writing group and professor of cardiology at Hofstra University, Hempstead, N.Y., said in a news release. 

“The delivery of equitable cardiovascular health care for women depends on improving the knowledge and awareness of all members of the healthcare team about the full spectrum of cardiovascular risk factors for women, including female-specific and female-predominant risk factors,” Dr. Mieres added.

Female-specific factors that should be included in CVD risk assessment include pregnancy-related conditions such as preeclampsia, preterm delivery, and gestational diabetes, the writing group said.

Other factors include menstrual cycle history; types of birth control and/or hormone replacement therapy used; polycystic ovarian syndrome (PCOS), which affects 10% of women of reproductive age and is associated with increased CVD risk; and autoimmune disorders, depression, and PTSD, all of which are more common in women and are also associated with higher risk for CVD.

The statement also highlights the key role that social determinants of health (SDOH) play in the development of CVD in women, particularly women from diverse racial and ethnic backgrounds. SDOH include education level, economic stability, neighborhood safety, working conditions, environmental hazards, and access to quality health care.

“It is critical that risk assessment be expanded to include [SDOH] as risk factors if we are to improve health outcomes in all women,” Laxmi Mehta, MD, chair of the writing group and director of preventative cardiology and women’s cardiovascular health at Ohio State University Wexner Medical Center, Columbus, said in the news release.

“It is also important for the health care team to consider [SDOH] when working with women on shared decisions about cardiovascular disease prevention and treatment,” Dr. Mehta noted.
 

No one-size-fits-all approach

The statement highlighted significant differences in CVD risk among women of different racial and ethnic backgrounds and provides detailed CV risk factor profiles for non-Hispanic Black, Hispanic/Latinx, Asian and American Indian/Alaska Native women.

It noted that language barriers, discrimination, acculturation, and health care access disproportionately affect women of underrepresented racial and ethnic groups. These factors result in a higher prevalence of CVD and significant challenges in CVD diagnosis and treatment.

“When customizing CVD prevention and treatment strategies to improve cardiovascular health for women, a one-size-fits-all approach is unlikely to be successful,” Dr. Mieres said.

“We must be cognizant of the complex interplay of sex, race and ethnicity, as well as social determinants of health, and how they impact the risk of cardiovascular disease and adverse outcomes in order to avert future CVD morbidity and mortality,” Dr. Mieres added.

Looking ahead, the writing group said future CVD prevention guidelines could be strengthened by including culturally-specific lifestyle recommendations.

They also said community-based approaches, faith-based community partnerships, and peer support to encourage a healthy lifestyle could play a key role in preventing CVD among all women.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology, the Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifelong Congenital Heart Disease and Heart Health in the Young, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.

A version of this article first appeared on Medscape.com.

In a new scientific statement, the American Heart Association highlighted the importance of incorporating nonbiological risk factors and social determinants of health in cardiovascular disease (CVD) risk assessment for women, particularly women from different racial and ethnic backgrounds.
 

CVD risk assessment in women is multifaceted and goes well beyond traditional risk factors to include sex-specific biological risk factors, as well as social, behavioral, and environmental factors, the writing group noted.

They said a greater focus on addressing all CVD risk factors among women from underrepresented races and ethnicities is warranted to avert future CVD.

The scientific statement was published online in Circulation.
 

Look beyond traditional risk factors

“Risk assessment is the first step in preventing heart disease, yet there are many limitations to traditional risk factors and their ability to comprehensively estimate a woman’s risk for cardiovascular disease,” Jennifer H. Mieres, MD, vice chair of the writing group and professor of cardiology at Hofstra University, Hempstead, N.Y., said in a news release. 

“The delivery of equitable cardiovascular health care for women depends on improving the knowledge and awareness of all members of the healthcare team about the full spectrum of cardiovascular risk factors for women, including female-specific and female-predominant risk factors,” Dr. Mieres added.

Female-specific factors that should be included in CVD risk assessment include pregnancy-related conditions such as preeclampsia, preterm delivery, and gestational diabetes, the writing group said.

Other factors include menstrual cycle history; types of birth control and/or hormone replacement therapy used; polycystic ovarian syndrome (PCOS), which affects 10% of women of reproductive age and is associated with increased CVD risk; and autoimmune disorders, depression, and PTSD, all of which are more common in women and are also associated with higher risk for CVD.

The statement also highlights the key role that social determinants of health (SDOH) play in the development of CVD in women, particularly women from diverse racial and ethnic backgrounds. SDOH include education level, economic stability, neighborhood safety, working conditions, environmental hazards, and access to quality health care.

“It is critical that risk assessment be expanded to include [SDOH] as risk factors if we are to improve health outcomes in all women,” Laxmi Mehta, MD, chair of the writing group and director of preventative cardiology and women’s cardiovascular health at Ohio State University Wexner Medical Center, Columbus, said in the news release.

“It is also important for the health care team to consider [SDOH] when working with women on shared decisions about cardiovascular disease prevention and treatment,” Dr. Mehta noted.
 

No one-size-fits-all approach

The statement highlighted significant differences in CVD risk among women of different racial and ethnic backgrounds and provides detailed CV risk factor profiles for non-Hispanic Black, Hispanic/Latinx, Asian and American Indian/Alaska Native women.

It noted that language barriers, discrimination, acculturation, and health care access disproportionately affect women of underrepresented racial and ethnic groups. These factors result in a higher prevalence of CVD and significant challenges in CVD diagnosis and treatment.

“When customizing CVD prevention and treatment strategies to improve cardiovascular health for women, a one-size-fits-all approach is unlikely to be successful,” Dr. Mieres said.

“We must be cognizant of the complex interplay of sex, race and ethnicity, as well as social determinants of health, and how they impact the risk of cardiovascular disease and adverse outcomes in order to avert future CVD morbidity and mortality,” Dr. Mieres added.

Looking ahead, the writing group said future CVD prevention guidelines could be strengthened by including culturally-specific lifestyle recommendations.

They also said community-based approaches, faith-based community partnerships, and peer support to encourage a healthy lifestyle could play a key role in preventing CVD among all women.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology, the Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifelong Congenital Heart Disease and Heart Health in the Young, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.

A version of this article first appeared on Medscape.com.

In a new scientific statement, the American Heart Association highlighted the importance of incorporating nonbiological risk factors and social determinants of health in cardiovascular disease (CVD) risk assessment for women, particularly women from different racial and ethnic backgrounds.
 

CVD risk assessment in women is multifaceted and goes well beyond traditional risk factors to include sex-specific biological risk factors, as well as social, behavioral, and environmental factors, the writing group noted.

They said a greater focus on addressing all CVD risk factors among women from underrepresented races and ethnicities is warranted to avert future CVD.

The scientific statement was published online in Circulation.
 

Look beyond traditional risk factors

“Risk assessment is the first step in preventing heart disease, yet there are many limitations to traditional risk factors and their ability to comprehensively estimate a woman’s risk for cardiovascular disease,” Jennifer H. Mieres, MD, vice chair of the writing group and professor of cardiology at Hofstra University, Hempstead, N.Y., said in a news release. 

“The delivery of equitable cardiovascular health care for women depends on improving the knowledge and awareness of all members of the healthcare team about the full spectrum of cardiovascular risk factors for women, including female-specific and female-predominant risk factors,” Dr. Mieres added.

Female-specific factors that should be included in CVD risk assessment include pregnancy-related conditions such as preeclampsia, preterm delivery, and gestational diabetes, the writing group said.

Other factors include menstrual cycle history; types of birth control and/or hormone replacement therapy used; polycystic ovarian syndrome (PCOS), which affects 10% of women of reproductive age and is associated with increased CVD risk; and autoimmune disorders, depression, and PTSD, all of which are more common in women and are also associated with higher risk for CVD.

The statement also highlights the key role that social determinants of health (SDOH) play in the development of CVD in women, particularly women from diverse racial and ethnic backgrounds. SDOH include education level, economic stability, neighborhood safety, working conditions, environmental hazards, and access to quality health care.

“It is critical that risk assessment be expanded to include [SDOH] as risk factors if we are to improve health outcomes in all women,” Laxmi Mehta, MD, chair of the writing group and director of preventative cardiology and women’s cardiovascular health at Ohio State University Wexner Medical Center, Columbus, said in the news release.

“It is also important for the health care team to consider [SDOH] when working with women on shared decisions about cardiovascular disease prevention and treatment,” Dr. Mehta noted.
 

No one-size-fits-all approach

The statement highlighted significant differences in CVD risk among women of different racial and ethnic backgrounds and provides detailed CV risk factor profiles for non-Hispanic Black, Hispanic/Latinx, Asian and American Indian/Alaska Native women.

It noted that language barriers, discrimination, acculturation, and health care access disproportionately affect women of underrepresented racial and ethnic groups. These factors result in a higher prevalence of CVD and significant challenges in CVD diagnosis and treatment.

“When customizing CVD prevention and treatment strategies to improve cardiovascular health for women, a one-size-fits-all approach is unlikely to be successful,” Dr. Mieres said.

“We must be cognizant of the complex interplay of sex, race and ethnicity, as well as social determinants of health, and how they impact the risk of cardiovascular disease and adverse outcomes in order to avert future CVD morbidity and mortality,” Dr. Mieres added.

Looking ahead, the writing group said future CVD prevention guidelines could be strengthened by including culturally-specific lifestyle recommendations.

They also said community-based approaches, faith-based community partnerships, and peer support to encourage a healthy lifestyle could play a key role in preventing CVD among all women.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology, the Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifelong Congenital Heart Disease and Heart Health in the Young, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.

A version of this article first appeared on Medscape.com.

The American Society of Echocardiography (ASE) has issued guidance on all critical aspects of training for cardiology and anesthesiology trainees and postgraduate echocardiographers who plan to specialize in interventional echocardiography (IE).

The guideline outlines requirements of the training institution, the duration and core competencies of training, minimal procedural volume for competency in IE, and knowledge of specific structural health disease (SHD) procedures.

The 16-page guideline was published online  in the Journal of the American Society of Echocardiography.
 

Specific skill set

IE is the primary imaging modality used to support and guide SHD interventions, such as heart valve replacements and other cardiac catheterization procedures, the writing group notes.

They say the “emerging specialty” of IE requires a specific set of skills to support an array of transcatheter therapies, with successful outcomes highly dependent on the skill of the echocardiography team.

“IE techniques are unique since imaging is performed in real-time, it is highly dependent on 3D and non-standard views, and it has immediate and profound implications for patient management,” Stephen H. Little, MD, ASE president and co-chair of the guideline writing group, says in a news release.

“Additionally, IE requires candid, accurate, and timely communication with other members of the multidisciplinary SHD team,” Dr. Little adds.

The new ASE guideline expands on the 2019 statement on echocardiography training put forward by the American College of Cardiology, American Heart Association, and ASE, by focusing specifically on interventional echocardiographers.

It outlines core competencies common to all transcatheter therapies, as well as specific transcatheter procedures. It provides consensus recommendations for specific knowledge, experience, and skills to be learned and demonstrated within an IE training program or during postgraduate training.

A “core principle” in the guideline states that the length of IE training or achieved number of procedures performed are less important than the demonstration of procedure-specific competencies within the milestone domains of knowledge, skill, and communication.

“Transcatheter therapies for SHD continue to grow at a rapid pace, which means that the demand for skilled interventional echocardiographers has steadily increased,” Vera H. Rigolin, MD, co-chair of the guideline writing, says in the release.

“Training standards are needed to ensure that interventional echocardiographers have the necessary expertise to provide fast, accurate, and high-quality image acquisition and interpretation in real-time,” Dr. Rigolin adds.

In addition, the guidelines states that use of simulation training has a role in IE training.

Virtual and simulation training could shorten the learning curve for trainees and, when combined with remote learning, could permit societies to standardize a teaching curriculum and allow the trainee to complete training in a reasonable timeframe. Simulator training may also improve access to training and thus promote diversity and inclusivity, the writing group says.

The guideline has been endorsed by 21 ASE international partners.

Writing group co-chairs Little and Rigolin have declared no conflicts of interest. A complete list of disclosures for the writing group is available with the original article.

A version of this article first appeared on Medscape.com.

The American Society of Echocardiography (ASE) has issued guidance on all critical aspects of training for cardiology and anesthesiology trainees and postgraduate echocardiographers who plan to specialize in interventional echocardiography (IE).

The guideline outlines requirements of the training institution, the duration and core competencies of training, minimal procedural volume for competency in IE, and knowledge of specific structural health disease (SHD) procedures.

The 16-page guideline was published online  in the Journal of the American Society of Echocardiography.
 

Specific skill set

IE is the primary imaging modality used to support and guide SHD interventions, such as heart valve replacements and other cardiac catheterization procedures, the writing group notes.

They say the “emerging specialty” of IE requires a specific set of skills to support an array of transcatheter therapies, with successful outcomes highly dependent on the skill of the echocardiography team.

“IE techniques are unique since imaging is performed in real-time, it is highly dependent on 3D and non-standard views, and it has immediate and profound implications for patient management,” Stephen H. Little, MD, ASE president and co-chair of the guideline writing group, says in a news release.

“Additionally, IE requires candid, accurate, and timely communication with other members of the multidisciplinary SHD team,” Dr. Little adds.

The new ASE guideline expands on the 2019 statement on echocardiography training put forward by the American College of Cardiology, American Heart Association, and ASE, by focusing specifically on interventional echocardiographers.

It outlines core competencies common to all transcatheter therapies, as well as specific transcatheter procedures. It provides consensus recommendations for specific knowledge, experience, and skills to be learned and demonstrated within an IE training program or during postgraduate training.

A “core principle” in the guideline states that the length of IE training or achieved number of procedures performed are less important than the demonstration of procedure-specific competencies within the milestone domains of knowledge, skill, and communication.

“Transcatheter therapies for SHD continue to grow at a rapid pace, which means that the demand for skilled interventional echocardiographers has steadily increased,” Vera H. Rigolin, MD, co-chair of the guideline writing, says in the release.

“Training standards are needed to ensure that interventional echocardiographers have the necessary expertise to provide fast, accurate, and high-quality image acquisition and interpretation in real-time,” Dr. Rigolin adds.

In addition, the guidelines states that use of simulation training has a role in IE training.

Virtual and simulation training could shorten the learning curve for trainees and, when combined with remote learning, could permit societies to standardize a teaching curriculum and allow the trainee to complete training in a reasonable timeframe. Simulator training may also improve access to training and thus promote diversity and inclusivity, the writing group says.

The guideline has been endorsed by 21 ASE international partners.

Writing group co-chairs Little and Rigolin have declared no conflicts of interest. A complete list of disclosures for the writing group is available with the original article.

A version of this article first appeared on Medscape.com.

The American Society of Echocardiography (ASE) has issued guidance on all critical aspects of training for cardiology and anesthesiology trainees and postgraduate echocardiographers who plan to specialize in interventional echocardiography (IE).

The guideline outlines requirements of the training institution, the duration and core competencies of training, minimal procedural volume for competency in IE, and knowledge of specific structural health disease (SHD) procedures.

The 16-page guideline was published online  in the Journal of the American Society of Echocardiography.
 

Specific skill set

IE is the primary imaging modality used to support and guide SHD interventions, such as heart valve replacements and other cardiac catheterization procedures, the writing group notes.

They say the “emerging specialty” of IE requires a specific set of skills to support an array of transcatheter therapies, with successful outcomes highly dependent on the skill of the echocardiography team.

“IE techniques are unique since imaging is performed in real-time, it is highly dependent on 3D and non-standard views, and it has immediate and profound implications for patient management,” Stephen H. Little, MD, ASE president and co-chair of the guideline writing group, says in a news release.

“Additionally, IE requires candid, accurate, and timely communication with other members of the multidisciplinary SHD team,” Dr. Little adds.

The new ASE guideline expands on the 2019 statement on echocardiography training put forward by the American College of Cardiology, American Heart Association, and ASE, by focusing specifically on interventional echocardiographers.

It outlines core competencies common to all transcatheter therapies, as well as specific transcatheter procedures. It provides consensus recommendations for specific knowledge, experience, and skills to be learned and demonstrated within an IE training program or during postgraduate training.

A “core principle” in the guideline states that the length of IE training or achieved number of procedures performed are less important than the demonstration of procedure-specific competencies within the milestone domains of knowledge, skill, and communication.

“Transcatheter therapies for SHD continue to grow at a rapid pace, which means that the demand for skilled interventional echocardiographers has steadily increased,” Vera H. Rigolin, MD, co-chair of the guideline writing, says in the release.

“Training standards are needed to ensure that interventional echocardiographers have the necessary expertise to provide fast, accurate, and high-quality image acquisition and interpretation in real-time,” Dr. Rigolin adds.

In addition, the guidelines states that use of simulation training has a role in IE training.

Virtual and simulation training could shorten the learning curve for trainees and, when combined with remote learning, could permit societies to standardize a teaching curriculum and allow the trainee to complete training in a reasonable timeframe. Simulator training may also improve access to training and thus promote diversity and inclusivity, the writing group says.

The guideline has been endorsed by 21 ASE international partners.

Writing group co-chairs Little and Rigolin have declared no conflicts of interest. A complete list of disclosures for the writing group is available with the original article.

A version of this article first appeared on Medscape.com.

Older adults in cities are at lower risk of serious psychological distress – and potentially of later cognitive impairment and dementia – when they live close to so-called green and blue spaces, which can include public parks, community gardens, cemeteries, and bodies of water.

The findings of the study, which was released ahead of its scheduled presentation at the annual meeting of the American Academy of Neurology, build on a growing understanding of the relationship between types and qualities of urban environments and dementia risk.

Adithya Vegaraju, a student at Washington State University, Spokane, led the study, which looked at data from the Washington State Behavioral Risk Factor Surveillance System to assess prevalence of serious psychological distress among 42,980 Washington state residents aged 65 and over.

The data, collected between 2011 and 2019, used a self-reported questionnaire to determine serious psychological distress, which is defined as a level of mental distress considered debilitating enough to warrant treatment.

Mr. Vegaraju and his coauthor Solmaz Amiri, DDes, also of Washington State University, used ZIP codes, along with U.S. census data, to approximate the urban adults’ proximity to green and blue spaces.

After controlling for potential confounders of age, sex, ethnicity, education, and marital status, the investigators found that people living within half a mile of green or blue spaces had a 17% lower risk of experiencing serious psychological distress, compared with people living farther from these spaces, the investigators said in a news release.
 

Implications for cognitive decline and dementia?

Psychological distress in adults has been linked in population-based longitudinal studies to later cognitive decline and dementia. One study in older adults found the risk of dementia to be more than 50% higher among adults aged 50-70 with persistent depression. Blue and green spaces have also been investigated in relation to neurodegenerative disease among older adults; a 2022 study looking at data from some 62 million Medicare beneficiaries found those living in areas with more vegetation saw lower risk of hospitalizations for Alzheimer’s disease and related dementias.

“Since we lack effective prevention methods or treatments for mild cognitive impairment and dementia, we need to get creative in how we look at these issues,” Dr. Amiri commented in a press statement about her and Mr. Vegaraju’s findings. “Our hope is that this study showing better mental health among people living close to parks and water will trigger other studies about how these benefits work and whether this proximity can help prevent or delay mild cognitive impairment and dementia.”

The investigators acknowledged that their findings were limited by reliance on a self-reported measure of psychological distress.
 

A bidirectional connection with depression and dementia

In a comment, Anjum Hajat, PhD, an epidemiologist at University of Washington School of Public Health in Seattle who has also studied the relationship between green space and dementia risk in older adults, noted some further apparent limitations of the new study, for which only an abstract was available at publication.

“It has been shown that people with depression are at higher risk for dementia, but the opposite is also true,” Dr. Hajat commented. “Those with dementia are more likely to develop depression. This bidirectionality makes this study abstract difficult to interpret since the study is based on cross-sectional data: Individuals are not followed over time to see which develops first, dementia or depression.”

Additionally, Dr. Hajat noted, the data used to determine proximity to green and blue spaces did not allow for the calculation of precise distances between subjects’ homes and these spaces.

Mr. Vegaraju and Dr. Amiri’s study had no outside support, and the investigators declared no conflicts of interest. Dr. Hajat declared no conflicts of interest.

Older adults in cities are at lower risk of serious psychological distress – and potentially of later cognitive impairment and dementia – when they live close to so-called green and blue spaces, which can include public parks, community gardens, cemeteries, and bodies of water.

The findings of the study, which was released ahead of its scheduled presentation at the annual meeting of the American Academy of Neurology, build on a growing understanding of the relationship between types and qualities of urban environments and dementia risk.

Adithya Vegaraju, a student at Washington State University, Spokane, led the study, which looked at data from the Washington State Behavioral Risk Factor Surveillance System to assess prevalence of serious psychological distress among 42,980 Washington state residents aged 65 and over.

The data, collected between 2011 and 2019, used a self-reported questionnaire to determine serious psychological distress, which is defined as a level of mental distress considered debilitating enough to warrant treatment.

Mr. Vegaraju and his coauthor Solmaz Amiri, DDes, also of Washington State University, used ZIP codes, along with U.S. census data, to approximate the urban adults’ proximity to green and blue spaces.

After controlling for potential confounders of age, sex, ethnicity, education, and marital status, the investigators found that people living within half a mile of green or blue spaces had a 17% lower risk of experiencing serious psychological distress, compared with people living farther from these spaces, the investigators said in a news release.
 

Implications for cognitive decline and dementia?

Psychological distress in adults has been linked in population-based longitudinal studies to later cognitive decline and dementia. One study in older adults found the risk of dementia to be more than 50% higher among adults aged 50-70 with persistent depression. Blue and green spaces have also been investigated in relation to neurodegenerative disease among older adults; a 2022 study looking at data from some 62 million Medicare beneficiaries found those living in areas with more vegetation saw lower risk of hospitalizations for Alzheimer’s disease and related dementias.

“Since we lack effective prevention methods or treatments for mild cognitive impairment and dementia, we need to get creative in how we look at these issues,” Dr. Amiri commented in a press statement about her and Mr. Vegaraju’s findings. “Our hope is that this study showing better mental health among people living close to parks and water will trigger other studies about how these benefits work and whether this proximity can help prevent or delay mild cognitive impairment and dementia.”

The investigators acknowledged that their findings were limited by reliance on a self-reported measure of psychological distress.
 

A bidirectional connection with depression and dementia

In a comment, Anjum Hajat, PhD, an epidemiologist at University of Washington School of Public Health in Seattle who has also studied the relationship between green space and dementia risk in older adults, noted some further apparent limitations of the new study, for which only an abstract was available at publication.

“It has been shown that people with depression are at higher risk for dementia, but the opposite is also true,” Dr. Hajat commented. “Those with dementia are more likely to develop depression. This bidirectionality makes this study abstract difficult to interpret since the study is based on cross-sectional data: Individuals are not followed over time to see which develops first, dementia or depression.”

Additionally, Dr. Hajat noted, the data used to determine proximity to green and blue spaces did not allow for the calculation of precise distances between subjects’ homes and these spaces.

Mr. Vegaraju and Dr. Amiri’s study had no outside support, and the investigators declared no conflicts of interest. Dr. Hajat declared no conflicts of interest.

Older adults in cities are at lower risk of serious psychological distress – and potentially of later cognitive impairment and dementia – when they live close to so-called green and blue spaces, which can include public parks, community gardens, cemeteries, and bodies of water.

The findings of the study, which was released ahead of its scheduled presentation at the annual meeting of the American Academy of Neurology, build on a growing understanding of the relationship between types and qualities of urban environments and dementia risk.

Adithya Vegaraju, a student at Washington State University, Spokane, led the study, which looked at data from the Washington State Behavioral Risk Factor Surveillance System to assess prevalence of serious psychological distress among 42,980 Washington state residents aged 65 and over.

The data, collected between 2011 and 2019, used a self-reported questionnaire to determine serious psychological distress, which is defined as a level of mental distress considered debilitating enough to warrant treatment.

Mr. Vegaraju and his coauthor Solmaz Amiri, DDes, also of Washington State University, used ZIP codes, along with U.S. census data, to approximate the urban adults’ proximity to green and blue spaces.

After controlling for potential confounders of age, sex, ethnicity, education, and marital status, the investigators found that people living within half a mile of green or blue spaces had a 17% lower risk of experiencing serious psychological distress, compared with people living farther from these spaces, the investigators said in a news release.
 

Implications for cognitive decline and dementia?

Psychological distress in adults has been linked in population-based longitudinal studies to later cognitive decline and dementia. One study in older adults found the risk of dementia to be more than 50% higher among adults aged 50-70 with persistent depression. Blue and green spaces have also been investigated in relation to neurodegenerative disease among older adults; a 2022 study looking at data from some 62 million Medicare beneficiaries found those living in areas with more vegetation saw lower risk of hospitalizations for Alzheimer’s disease and related dementias.

“Since we lack effective prevention methods or treatments for mild cognitive impairment and dementia, we need to get creative in how we look at these issues,” Dr. Amiri commented in a press statement about her and Mr. Vegaraju’s findings. “Our hope is that this study showing better mental health among people living close to parks and water will trigger other studies about how these benefits work and whether this proximity can help prevent or delay mild cognitive impairment and dementia.”

The investigators acknowledged that their findings were limited by reliance on a self-reported measure of psychological distress.
 

A bidirectional connection with depression and dementia

In a comment, Anjum Hajat, PhD, an epidemiologist at University of Washington School of Public Health in Seattle who has also studied the relationship between green space and dementia risk in older adults, noted some further apparent limitations of the new study, for which only an abstract was available at publication.

“It has been shown that people with depression are at higher risk for dementia, but the opposite is also true,” Dr. Hajat commented. “Those with dementia are more likely to develop depression. This bidirectionality makes this study abstract difficult to interpret since the study is based on cross-sectional data: Individuals are not followed over time to see which develops first, dementia or depression.”

Additionally, Dr. Hajat noted, the data used to determine proximity to green and blue spaces did not allow for the calculation of precise distances between subjects’ homes and these spaces.

Mr. Vegaraju and Dr. Amiri’s study had no outside support, and the investigators declared no conflicts of interest. Dr. Hajat declared no conflicts of interest.

Experts recommend that most adults get 7-9 hours of sleep a night. If your patient is among the roughly one-third of people who sleep less (or more), regular exercise may help them dodge possible long-term health consequences such as heart disease and early death.

Plenty of research points to sleep and physical activity as crucial factors affecting life expectancy. Regular exercise can lengthen life, while too little or too much sleep may cut it short.

But evidence is growing that exercise may counteract the negative effects of poor sleep. A 2022 study found that being physically active for at least 25 minutes a day can erase the risk of early death associated with too much sleep or trouble falling asleep. And a 2021 study found that lower levels of physical activity may exacerbate the impact of poor sleep on early death, heart disease, and cancer.

The latest such study, published in the European Journal of Preventive Cardiology, suggests that higher volumes of exercise can virtually eliminate the risk of early death associated with sleeping too little or too long.

This study is unique, the researchers say, because it used accelerometers (motion-tracking sensors) to quantify sleep and physical activity. Other studies asked participants to report their own data, opening the door to false reports and mistakes.

Some 92,000 participants in the United Kingdom (mean age, 62 years; 56% women) wore the activity trackers for a week to measure how much they moved and slept. In the following 7 years, 3,080 participants died, mostly from cardiovascular disease or cancer.

As one might expect, the participants who were least likely to die also exercised the most and slept the “normal” amount (6-8 hours a night, as defined by the study).

Compared with that group, those who exercised the least and slept less than 6 hours were 2.5 times more likely to die during those 7 years (P < .001). Less active persons who got the recommended sleep were 79% more likely to die (P < .001). The risk was slightly higher than that for those who logged more than 8 hours a night.

But those risks disappeared for short- or long-sleeping participants who logged at least 150 minutes a week of moderate to vigorous activity.

“Exercise fights inflammatory and metabolic dysregulations and abnormal sympathetic nervous system activity,” said study author Jihui Zhang, PhD, of the Affiliated Brain Hospital of Guangzhou (China). Those problems are associated with cardiovascular diseases and other potentially fatal conditions.
 

More objective data – with tech

A study’s findings are only as good as the data it relies on. That’s why obtaining objective data not influenced by individual perception is key.

“Self-report questionnaires are prone to misperception, or recall or response bias,” Dr. Zhang explains.

Take sleep, for example. Research reveals that several factors can affect how we judge our sleep. When people have to sleep at irregular times, they often underestimate how many hours they sleep but overestimate how long they nap, found a study in the Journal of Clinical Sleep Medicine.

Another study showed that when people are under a lot of stress, they’ll report more sleep problems than they actually have, as revealed by an Actiheart monitor.

With exercise, participants often report doing more exercise, and doing it at a higher intensity, than objective measurements show they did. At the same time, self-reports typically don’t account for much of the unplanned, low-effort movement people do throughout the day.
 

Staying active when you’re tired

The study raises a practical question: If you don’t get the proper amount of sleep, how are you supposed to find the time, energy, and motivation to exercise?

The solution is to use one to fix the other.

Exercise and sleep have “a robust directional relationship,” Dr. Zhang said. Exercise improves sleep, while better sleep makes it easier to stick with an exercise program.

Ideally, that program will include a mix of cardio and resistance exercise, said Mitch Duncan, PhD, a professor of public health at the University of Newcastle, Australia.

As Dr. Duncan and his co-authors showed in a recent study, “the largest benefits to health occur when people do a combination of both aerobic and muscle-strengthening activity,” Dr. Duncan said.

“In terms of benefits to sleep, there doesn’t seem to be consistent evidence that favors either as being most effective.”

The timing or intensity of exercise doesn’t seem to matter much, either.

“But there is evidence that a greater duration contributes to larger improvements in sleep,” Dr. Duncan said.

In other words, longer workouts are generally better, but they don’t necessarily have to be super-intense.

The strongest evidence of all, however, shows that recent and regular exercise offer the biggest benefits at bedtime.

Today’s workout will improve tonight’s sleep. And the better you sleep tonight, the more likely you are to stick with the program.

A version of this article first appeared on WebMD.com.

Experts recommend that most adults get 7-9 hours of sleep a night. If your patient is among the roughly one-third of people who sleep less (or more), regular exercise may help them dodge possible long-term health consequences such as heart disease and early death.

Plenty of research points to sleep and physical activity as crucial factors affecting life expectancy. Regular exercise can lengthen life, while too little or too much sleep may cut it short.

But evidence is growing that exercise may counteract the negative effects of poor sleep. A 2022 study found that being physically active for at least 25 minutes a day can erase the risk of early death associated with too much sleep or trouble falling asleep. And a 2021 study found that lower levels of physical activity may exacerbate the impact of poor sleep on early death, heart disease, and cancer.

The latest such study, published in the European Journal of Preventive Cardiology, suggests that higher volumes of exercise can virtually eliminate the risk of early death associated with sleeping too little or too long.

This study is unique, the researchers say, because it used accelerometers (motion-tracking sensors) to quantify sleep and physical activity. Other studies asked participants to report their own data, opening the door to false reports and mistakes.

Some 92,000 participants in the United Kingdom (mean age, 62 years; 56% women) wore the activity trackers for a week to measure how much they moved and slept. In the following 7 years, 3,080 participants died, mostly from cardiovascular disease or cancer.

As one might expect, the participants who were least likely to die also exercised the most and slept the “normal” amount (6-8 hours a night, as defined by the study).

Compared with that group, those who exercised the least and slept less than 6 hours were 2.5 times more likely to die during those 7 years (P < .001). Less active persons who got the recommended sleep were 79% more likely to die (P < .001). The risk was slightly higher than that for those who logged more than 8 hours a night.

But those risks disappeared for short- or long-sleeping participants who logged at least 150 minutes a week of moderate to vigorous activity.

“Exercise fights inflammatory and metabolic dysregulations and abnormal sympathetic nervous system activity,” said study author Jihui Zhang, PhD, of the Affiliated Brain Hospital of Guangzhou (China). Those problems are associated with cardiovascular diseases and other potentially fatal conditions.
 

More objective data – with tech

A study’s findings are only as good as the data it relies on. That’s why obtaining objective data not influenced by individual perception is key.

“Self-report questionnaires are prone to misperception, or recall or response bias,” Dr. Zhang explains.

Take sleep, for example. Research reveals that several factors can affect how we judge our sleep. When people have to sleep at irregular times, they often underestimate how many hours they sleep but overestimate how long they nap, found a study in the Journal of Clinical Sleep Medicine.

Another study showed that when people are under a lot of stress, they’ll report more sleep problems than they actually have, as revealed by an Actiheart monitor.

With exercise, participants often report doing more exercise, and doing it at a higher intensity, than objective measurements show they did. At the same time, self-reports typically don’t account for much of the unplanned, low-effort movement people do throughout the day.
 

Staying active when you’re tired

The study raises a practical question: If you don’t get the proper amount of sleep, how are you supposed to find the time, energy, and motivation to exercise?

The solution is to use one to fix the other.

Exercise and sleep have “a robust directional relationship,” Dr. Zhang said. Exercise improves sleep, while better sleep makes it easier to stick with an exercise program.

Ideally, that program will include a mix of cardio and resistance exercise, said Mitch Duncan, PhD, a professor of public health at the University of Newcastle, Australia.

As Dr. Duncan and his co-authors showed in a recent study, “the largest benefits to health occur when people do a combination of both aerobic and muscle-strengthening activity,” Dr. Duncan said.

“In terms of benefits to sleep, there doesn’t seem to be consistent evidence that favors either as being most effective.”

The timing or intensity of exercise doesn’t seem to matter much, either.

“But there is evidence that a greater duration contributes to larger improvements in sleep,” Dr. Duncan said.

In other words, longer workouts are generally better, but they don’t necessarily have to be super-intense.

The strongest evidence of all, however, shows that recent and regular exercise offer the biggest benefits at bedtime.

Today’s workout will improve tonight’s sleep. And the better you sleep tonight, the more likely you are to stick with the program.

A version of this article first appeared on WebMD.com.

Experts recommend that most adults get 7-9 hours of sleep a night. If your patient is among the roughly one-third of people who sleep less (or more), regular exercise may help them dodge possible long-term health consequences such as heart disease and early death.

Plenty of research points to sleep and physical activity as crucial factors affecting life expectancy. Regular exercise can lengthen life, while too little or too much sleep may cut it short.

But evidence is growing that exercise may counteract the negative effects of poor sleep. A 2022 study found that being physically active for at least 25 minutes a day can erase the risk of early death associated with too much sleep or trouble falling asleep. And a 2021 study found that lower levels of physical activity may exacerbate the impact of poor sleep on early death, heart disease, and cancer.

The latest such study, published in the European Journal of Preventive Cardiology, suggests that higher volumes of exercise can virtually eliminate the risk of early death associated with sleeping too little or too long.

This study is unique, the researchers say, because it used accelerometers (motion-tracking sensors) to quantify sleep and physical activity. Other studies asked participants to report their own data, opening the door to false reports and mistakes.

Some 92,000 participants in the United Kingdom (mean age, 62 years; 56% women) wore the activity trackers for a week to measure how much they moved and slept. In the following 7 years, 3,080 participants died, mostly from cardiovascular disease or cancer.

As one might expect, the participants who were least likely to die also exercised the most and slept the “normal” amount (6-8 hours a night, as defined by the study).

Compared with that group, those who exercised the least and slept less than 6 hours were 2.5 times more likely to die during those 7 years (P < .001). Less active persons who got the recommended sleep were 79% more likely to die (P < .001). The risk was slightly higher than that for those who logged more than 8 hours a night.

But those risks disappeared for short- or long-sleeping participants who logged at least 150 minutes a week of moderate to vigorous activity.

“Exercise fights inflammatory and metabolic dysregulations and abnormal sympathetic nervous system activity,” said study author Jihui Zhang, PhD, of the Affiliated Brain Hospital of Guangzhou (China). Those problems are associated with cardiovascular diseases and other potentially fatal conditions.
 

More objective data – with tech

A study’s findings are only as good as the data it relies on. That’s why obtaining objective data not influenced by individual perception is key.

“Self-report questionnaires are prone to misperception, or recall or response bias,” Dr. Zhang explains.

Take sleep, for example. Research reveals that several factors can affect how we judge our sleep. When people have to sleep at irregular times, they often underestimate how many hours they sleep but overestimate how long they nap, found a study in the Journal of Clinical Sleep Medicine.

Another study showed that when people are under a lot of stress, they’ll report more sleep problems than they actually have, as revealed by an Actiheart monitor.

With exercise, participants often report doing more exercise, and doing it at a higher intensity, than objective measurements show they did. At the same time, self-reports typically don’t account for much of the unplanned, low-effort movement people do throughout the day.
 

Staying active when you’re tired

The study raises a practical question: If you don’t get the proper amount of sleep, how are you supposed to find the time, energy, and motivation to exercise?

The solution is to use one to fix the other.

Exercise and sleep have “a robust directional relationship,” Dr. Zhang said. Exercise improves sleep, while better sleep makes it easier to stick with an exercise program.

Ideally, that program will include a mix of cardio and resistance exercise, said Mitch Duncan, PhD, a professor of public health at the University of Newcastle, Australia.

As Dr. Duncan and his co-authors showed in a recent study, “the largest benefits to health occur when people do a combination of both aerobic and muscle-strengthening activity,” Dr. Duncan said.

“In terms of benefits to sleep, there doesn’t seem to be consistent evidence that favors either as being most effective.”

The timing or intensity of exercise doesn’t seem to matter much, either.

“But there is evidence that a greater duration contributes to larger improvements in sleep,” Dr. Duncan said.

In other words, longer workouts are generally better, but they don’t necessarily have to be super-intense.

The strongest evidence of all, however, shows that recent and regular exercise offer the biggest benefits at bedtime.

Today’s workout will improve tonight’s sleep. And the better you sleep tonight, the more likely you are to stick with the program.

A version of this article first appeared on WebMD.com.

Among adults with diabetes but no history of heart failure (HF), taking a NSAID – even for only a month – sharply raises the risk of an HF hospitalization, suggests a prospective, controlled study.
 

Certain subgroups may account for much of the excess risk, the results suggest, including the very elderly, patients with uncontrolled diabetes, those prescribed an NSAID for the first time, and patients already taking both a renin-angiotensin system inhibitor (RASi) and a diuretic.

Such patients with a firm indication for NSAIDs potentially could “be the ones benefiting most from closer follow-up, reduced dosage, or other mitigation strategies,” Anders Holt, MD, said in an interview.

Dr. Holt, of Copenhagen University Hospital and Herlev-Gentofte Hospital in Hellerup, Denmark, is lead author on the analysis of Danish registry data published in the Journal of the American College of Cardiology. He presented essentially the same results in preliminary form at the 2022 annual congress of the European Society of Cardiology.

HF hospitalizations linked to NSAIDs, the published report notes, are often attributed to symptoms from temporary fluid overload, often without worsening cardiac function, that stem from the drugs’ renal effects.

“One could speculate,” Dr. Holt said, that such HF events might be less severe and even associated with better outcomes, compared with other forms of heart failure.

But the current analysis provides a hint to the contrary, he observed. The 5-year mortality was similar for patients with HF linked to NSAIDs and those with other forms of HF, “which could suggest that NSAID-associated heart failure is more than transient fluid overload.”

The drugs may promote HF through direct effects on the heart by any of several proposed mechanisms, including “induction of arrhythmias and heart fibrosis, vasoconstriction, subclinical inflammation, and blood pressure elevation,” Dr. Holt said.

The current study doesn’t determine whether NSAID-associated HF stems from transient fluid overload or direct cardiac effects, but it’s “most likely both.”

In other limitations, the analysis is unable to “reliably explore” whether promotion of HF is an NSAID class effect, a “clinically relevant” point given the drugs’ varying effects on cardiovascular risk, states an accompanying editorial. Nor was it able to determine whether the drugs exert a dose-response effect on HF risk, noted Hassan Khan, MD, PhD, Norton Healthcare, Louisville, Ky., and Setor K. Kunutsor, MD, PhD, University of Leicester (England).

Still, “given the well-established relationship between the use of NSAIDs and increased HF, these findings are not unexpected because type 2 diabetes is also a major risk factor for HF.”

But it may be “premature to issue guideline recommendations based on a single observational study,” the editorialists wrote. “Further robust clinical trial evidence is needed to replicate these results and investigate the relationship of the type and dose of NSAIDs with HF risk. However, it should be realized that short-term or long-term use of NSAIDs may be detrimental to cardiovascular health.”

The analysis covered 23,308 patients from throughout Denmark with a type 2 diabetes diagnosis and no HF history who experienced a first HF hospitalization; their age averaged 76 years and 39% were women.

They served as their own controls; their NSAID exposures at two 28-day periods preceding the HF event, the one immediately before and the other preceding it by 56 days, were compared as the index and control periods, respectively.

Exposure to NSAIDs was defined as obtaining a prescription for celecoxib, diclofenac, ibuprofen, or naproxen, “as these are NSAIDs used primarily in Denmark,” the report states.

The odds ratios for HF hospitalization associated with NSAID exposure within 28 days preceding the event were 1.43 (95% confidence interval, 1.27-1.63) overall, 1.41 (95% CI, 1.16-1.71) for an NSAID given on top of both RASi and diuretics, 1.68 (95% CI, 1.00-2.88) for patients with elevated hemoglobin A1c, 1.78 (95% CI, 1.39-2.28) for those 80 or older, and 2.71 (95% CI, 1.78-4.23) for those with prior NSAID use.

That NSAID use and diabetes are each associated with increased risk for HF is well established, Dr. Holt observed. Yet the drugs had been prescribed to 16% of patients in the study.

“One of the more surprising findings, to me, was the quite substantial use of prescribed NSAIDs in a population of patients with diabetes, a patient group with a well-established cardiovascular risk,” he said.

“This patient group is only growing, so emphasis on the possible associations between even short-term NSAID use and incident heart failure is probably timely and perhaps needed.”

Dr. Holt and the study were supported by grants from Ib Mogens Kristiansens Almene Fond, Helsefonden, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond, Marie og M.B. Richters Fond, and the Dagmar Marshalls Fond. Dr. Khan and Dr. Kunutsor reported no relevant relationships.

A version of this article first appeared on Medscape.com.

Among adults with diabetes but no history of heart failure (HF), taking a NSAID – even for only a month – sharply raises the risk of an HF hospitalization, suggests a prospective, controlled study.
 

Certain subgroups may account for much of the excess risk, the results suggest, including the very elderly, patients with uncontrolled diabetes, those prescribed an NSAID for the first time, and patients already taking both a renin-angiotensin system inhibitor (RASi) and a diuretic.

Such patients with a firm indication for NSAIDs potentially could “be the ones benefiting most from closer follow-up, reduced dosage, or other mitigation strategies,” Anders Holt, MD, said in an interview.

Dr. Holt, of Copenhagen University Hospital and Herlev-Gentofte Hospital in Hellerup, Denmark, is lead author on the analysis of Danish registry data published in the Journal of the American College of Cardiology. He presented essentially the same results in preliminary form at the 2022 annual congress of the European Society of Cardiology.

HF hospitalizations linked to NSAIDs, the published report notes, are often attributed to symptoms from temporary fluid overload, often without worsening cardiac function, that stem from the drugs’ renal effects.

“One could speculate,” Dr. Holt said, that such HF events might be less severe and even associated with better outcomes, compared with other forms of heart failure.

But the current analysis provides a hint to the contrary, he observed. The 5-year mortality was similar for patients with HF linked to NSAIDs and those with other forms of HF, “which could suggest that NSAID-associated heart failure is more than transient fluid overload.”

The drugs may promote HF through direct effects on the heart by any of several proposed mechanisms, including “induction of arrhythmias and heart fibrosis, vasoconstriction, subclinical inflammation, and blood pressure elevation,” Dr. Holt said.

The current study doesn’t determine whether NSAID-associated HF stems from transient fluid overload or direct cardiac effects, but it’s “most likely both.”

In other limitations, the analysis is unable to “reliably explore” whether promotion of HF is an NSAID class effect, a “clinically relevant” point given the drugs’ varying effects on cardiovascular risk, states an accompanying editorial. Nor was it able to determine whether the drugs exert a dose-response effect on HF risk, noted Hassan Khan, MD, PhD, Norton Healthcare, Louisville, Ky., and Setor K. Kunutsor, MD, PhD, University of Leicester (England).

Still, “given the well-established relationship between the use of NSAIDs and increased HF, these findings are not unexpected because type 2 diabetes is also a major risk factor for HF.”

But it may be “premature to issue guideline recommendations based on a single observational study,” the editorialists wrote. “Further robust clinical trial evidence is needed to replicate these results and investigate the relationship of the type and dose of NSAIDs with HF risk. However, it should be realized that short-term or long-term use of NSAIDs may be detrimental to cardiovascular health.”

The analysis covered 23,308 patients from throughout Denmark with a type 2 diabetes diagnosis and no HF history who experienced a first HF hospitalization; their age averaged 76 years and 39% were women.

They served as their own controls; their NSAID exposures at two 28-day periods preceding the HF event, the one immediately before and the other preceding it by 56 days, were compared as the index and control periods, respectively.

Exposure to NSAIDs was defined as obtaining a prescription for celecoxib, diclofenac, ibuprofen, or naproxen, “as these are NSAIDs used primarily in Denmark,” the report states.

The odds ratios for HF hospitalization associated with NSAID exposure within 28 days preceding the event were 1.43 (95% confidence interval, 1.27-1.63) overall, 1.41 (95% CI, 1.16-1.71) for an NSAID given on top of both RASi and diuretics, 1.68 (95% CI, 1.00-2.88) for patients with elevated hemoglobin A1c, 1.78 (95% CI, 1.39-2.28) for those 80 or older, and 2.71 (95% CI, 1.78-4.23) for those with prior NSAID use.

That NSAID use and diabetes are each associated with increased risk for HF is well established, Dr. Holt observed. Yet the drugs had been prescribed to 16% of patients in the study.

“One of the more surprising findings, to me, was the quite substantial use of prescribed NSAIDs in a population of patients with diabetes, a patient group with a well-established cardiovascular risk,” he said.

“This patient group is only growing, so emphasis on the possible associations between even short-term NSAID use and incident heart failure is probably timely and perhaps needed.”

Dr. Holt and the study were supported by grants from Ib Mogens Kristiansens Almene Fond, Helsefonden, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond, Marie og M.B. Richters Fond, and the Dagmar Marshalls Fond. Dr. Khan and Dr. Kunutsor reported no relevant relationships.

A version of this article first appeared on Medscape.com.

Among adults with diabetes but no history of heart failure (HF), taking a NSAID – even for only a month – sharply raises the risk of an HF hospitalization, suggests a prospective, controlled study.
 

Certain subgroups may account for much of the excess risk, the results suggest, including the very elderly, patients with uncontrolled diabetes, those prescribed an NSAID for the first time, and patients already taking both a renin-angiotensin system inhibitor (RASi) and a diuretic.

Such patients with a firm indication for NSAIDs potentially could “be the ones benefiting most from closer follow-up, reduced dosage, or other mitigation strategies,” Anders Holt, MD, said in an interview.

Dr. Holt, of Copenhagen University Hospital and Herlev-Gentofte Hospital in Hellerup, Denmark, is lead author on the analysis of Danish registry data published in the Journal of the American College of Cardiology. He presented essentially the same results in preliminary form at the 2022 annual congress of the European Society of Cardiology.

HF hospitalizations linked to NSAIDs, the published report notes, are often attributed to symptoms from temporary fluid overload, often without worsening cardiac function, that stem from the drugs’ renal effects.

“One could speculate,” Dr. Holt said, that such HF events might be less severe and even associated with better outcomes, compared with other forms of heart failure.

But the current analysis provides a hint to the contrary, he observed. The 5-year mortality was similar for patients with HF linked to NSAIDs and those with other forms of HF, “which could suggest that NSAID-associated heart failure is more than transient fluid overload.”

The drugs may promote HF through direct effects on the heart by any of several proposed mechanisms, including “induction of arrhythmias and heart fibrosis, vasoconstriction, subclinical inflammation, and blood pressure elevation,” Dr. Holt said.

The current study doesn’t determine whether NSAID-associated HF stems from transient fluid overload or direct cardiac effects, but it’s “most likely both.”

In other limitations, the analysis is unable to “reliably explore” whether promotion of HF is an NSAID class effect, a “clinically relevant” point given the drugs’ varying effects on cardiovascular risk, states an accompanying editorial. Nor was it able to determine whether the drugs exert a dose-response effect on HF risk, noted Hassan Khan, MD, PhD, Norton Healthcare, Louisville, Ky., and Setor K. Kunutsor, MD, PhD, University of Leicester (England).

Still, “given the well-established relationship between the use of NSAIDs and increased HF, these findings are not unexpected because type 2 diabetes is also a major risk factor for HF.”

But it may be “premature to issue guideline recommendations based on a single observational study,” the editorialists wrote. “Further robust clinical trial evidence is needed to replicate these results and investigate the relationship of the type and dose of NSAIDs with HF risk. However, it should be realized that short-term or long-term use of NSAIDs may be detrimental to cardiovascular health.”

The analysis covered 23,308 patients from throughout Denmark with a type 2 diabetes diagnosis and no HF history who experienced a first HF hospitalization; their age averaged 76 years and 39% were women.

They served as their own controls; their NSAID exposures at two 28-day periods preceding the HF event, the one immediately before and the other preceding it by 56 days, were compared as the index and control periods, respectively.

Exposure to NSAIDs was defined as obtaining a prescription for celecoxib, diclofenac, ibuprofen, or naproxen, “as these are NSAIDs used primarily in Denmark,” the report states.

The odds ratios for HF hospitalization associated with NSAID exposure within 28 days preceding the event were 1.43 (95% confidence interval, 1.27-1.63) overall, 1.41 (95% CI, 1.16-1.71) for an NSAID given on top of both RASi and diuretics, 1.68 (95% CI, 1.00-2.88) for patients with elevated hemoglobin A1c, 1.78 (95% CI, 1.39-2.28) for those 80 or older, and 2.71 (95% CI, 1.78-4.23) for those with prior NSAID use.

That NSAID use and diabetes are each associated with increased risk for HF is well established, Dr. Holt observed. Yet the drugs had been prescribed to 16% of patients in the study.

“One of the more surprising findings, to me, was the quite substantial use of prescribed NSAIDs in a population of patients with diabetes, a patient group with a well-established cardiovascular risk,” he said.

“This patient group is only growing, so emphasis on the possible associations between even short-term NSAID use and incident heart failure is probably timely and perhaps needed.”

Dr. Holt and the study were supported by grants from Ib Mogens Kristiansens Almene Fond, Helsefonden, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond, Marie og M.B. Richters Fond, and the Dagmar Marshalls Fond. Dr. Khan and Dr. Kunutsor reported no relevant relationships.

A version of this article first appeared on Medscape.com.

Atrial fibrillation (AFib) is a known and serious side effect of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk of atrial fibrillation when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AFib ranged from 0.26 cases per 100 person-years – about the same as placebo – to 4.92 cases, a nearly 20 times’ higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published in JACC: CardioOncology, a journal of the American College of Cardiology.

Actual rates of AFib are probably higher than what they found in this meta-analysis, the authors suspect, because most oncology trials only identify and report severe cases of AFib that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said the investigators, led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, France.

“These findings suggest a global and systemic underreporting and/or underidentification of cardiotoxicity among cancer clinical trial participants,” and AFib reporting is “particularly affected,” they said.
 

Call for routine monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This in turn “leads to a significant underestimation of AFib incidence” and rates “markedly lower than those observed among real-life” patients, the authors pointed out.

To address the issue, Dr. Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AFib and to “clearly define which anticancer drugs are significantly associated” with the condition.

Approached for comment, Michael G. Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, agreed.

“It’s incredibly important” to “identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking,” Dr. Fradley told this news organization.

The investigators said the issue is particularly pressing for drugs known to be associated with AFib. For Bruton’s tyrosine kinase inhibitors such as ibrutinib, for instance, they call for standardize AFib detection in trials “not only on 12-lead ECGs” for symptomatic AFib but also with “longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AFib.”

Dr. Fradley said there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.
 

Details of the meta-analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to Sept. 18, 2020. Almost half were randomized trials, but only seven had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AFib rates per 100 person-years were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AFib rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 person-years.

The team said caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when adverse event reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Dr. Alexandre has received honoraria for presentations and consulting fees from Bayer, BMS, Pfizer, Amgen, and Bioserenity.
 

A version of this article first appeared on Medscape.com.

Atrial fibrillation (AFib) is a known and serious side effect of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk of atrial fibrillation when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AFib ranged from 0.26 cases per 100 person-years – about the same as placebo – to 4.92 cases, a nearly 20 times’ higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published in JACC: CardioOncology, a journal of the American College of Cardiology.

Actual rates of AFib are probably higher than what they found in this meta-analysis, the authors suspect, because most oncology trials only identify and report severe cases of AFib that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said the investigators, led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, France.

“These findings suggest a global and systemic underreporting and/or underidentification of cardiotoxicity among cancer clinical trial participants,” and AFib reporting is “particularly affected,” they said.
 

Call for routine monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This in turn “leads to a significant underestimation of AFib incidence” and rates “markedly lower than those observed among real-life” patients, the authors pointed out.

To address the issue, Dr. Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AFib and to “clearly define which anticancer drugs are significantly associated” with the condition.

Approached for comment, Michael G. Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, agreed.

“It’s incredibly important” to “identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking,” Dr. Fradley told this news organization.

The investigators said the issue is particularly pressing for drugs known to be associated with AFib. For Bruton’s tyrosine kinase inhibitors such as ibrutinib, for instance, they call for standardize AFib detection in trials “not only on 12-lead ECGs” for symptomatic AFib but also with “longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AFib.”

Dr. Fradley said there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.
 

Details of the meta-analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to Sept. 18, 2020. Almost half were randomized trials, but only seven had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AFib rates per 100 person-years were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AFib rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 person-years.

The team said caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when adverse event reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Dr. Alexandre has received honoraria for presentations and consulting fees from Bayer, BMS, Pfizer, Amgen, and Bioserenity.
 

A version of this article first appeared on Medscape.com.

Atrial fibrillation (AFib) is a known and serious side effect of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk of atrial fibrillation when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AFib ranged from 0.26 cases per 100 person-years – about the same as placebo – to 4.92 cases, a nearly 20 times’ higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published in JACC: CardioOncology, a journal of the American College of Cardiology.

Actual rates of AFib are probably higher than what they found in this meta-analysis, the authors suspect, because most oncology trials only identify and report severe cases of AFib that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said the investigators, led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, France.

“These findings suggest a global and systemic underreporting and/or underidentification of cardiotoxicity among cancer clinical trial participants,” and AFib reporting is “particularly affected,” they said.
 

Call for routine monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This in turn “leads to a significant underestimation of AFib incidence” and rates “markedly lower than those observed among real-life” patients, the authors pointed out.

To address the issue, Dr. Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AFib and to “clearly define which anticancer drugs are significantly associated” with the condition.

Approached for comment, Michael G. Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, agreed.

“It’s incredibly important” to “identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking,” Dr. Fradley told this news organization.

The investigators said the issue is particularly pressing for drugs known to be associated with AFib. For Bruton’s tyrosine kinase inhibitors such as ibrutinib, for instance, they call for standardize AFib detection in trials “not only on 12-lead ECGs” for symptomatic AFib but also with “longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AFib.”

Dr. Fradley said there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.
 

Details of the meta-analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to Sept. 18, 2020. Almost half were randomized trials, but only seven had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AFib rates per 100 person-years were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AFib rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 person-years.

The team said caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when adverse event reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Dr. Alexandre has received honoraria for presentations and consulting fees from Bayer, BMS, Pfizer, Amgen, and Bioserenity.
 

A version of this article first appeared on Medscape.com.

PARIS – A single 25-mg dose of a synthetic formulation of psilocybin appears to improve the core symptoms of treatment-resistant depression (TRD), a new analysis of phase 2 trial data suggests.

Known as COMP360, the synthetic agent, a proprietary, purified form of psilocybin, improved symptoms related to mood and anhedonia while leaving aspects such as appetite and weight changes unaffected, reported investigators led by Guy M. Goodwin, PhD, emeritus professor of psychiatry, University of Oxford, England, and chief medical officer, COMPASS Pathways.

The study was presented at the European Psychiatric Association (EPA) 2023 Congress.
 

100 million affected

Affecting up to 100 million people globally, TRD is “not an official diagnosis,” although it is often defined as the failure to elicit a response with at least two antidepressant treatments, said Dr. Goodwin.

Compared to their counterparts with non-TRD, those with TRD experience higher relapse rates, higher rates of suicidal behavior, and more residual symptoms even when they do respond to treatment.

Previous results from the study known as P-TRD indicated that a single 25-mg dose of COMP360 significantly reduced depression scores for up to 12 weeks when given along with psychological support, although a later analysis suggested the effect subsequently dropped off.

The vast majority of the patients in the trial were naive to psychedelics, and so, Dr. Goodwin explained, they undergo a preparation phase during which they receive psychoeducation and have at least two visits with a therapist, who then stays with them during administration of the drug to offer support if they experience psychological distress.

Following the psilocybin session, participants go through a process known as integration, which involves two sessions with a therapist within 2 weeks.

“That, in our view, is essentially about safety, and about identifying problems that have arisen as a result of taking the drug,” said Dr. Goodwin.

The phase 2b trial examined changes in specific depression symptoms after psilocybin treatment in 233 patients with TRD. Participants were a mean age of 39.8 years and 59% were women. They were randomized to receive one of three doses of the drug: a 1-mg dose (n = 79), a 10-mg dose (n = 75), or a 25-mg dose (n = 79).

The primary outcome was changes in individual items on the Montgomery-Åsberg Depression Rating Scale (MADRS) and 16-item Quick Inventory of Depressive Symptomatology–Self Report (QIDS-SR-16) scale.

While the effect on overall depression scores is important, said Dr. Goodwin, many of the items included in the depression assessment scales are “uninformative.”
 

Reduction in ‘core’ symptoms

Participants were assessed by a blinded rater at baseline, day 1, day 2, and at 1, 2, 3, 6, 9, and 12 weeks after administration of COMP360. The primary endpoint was a reduction in individual items on MADRS and scores from baseline to 3 weeks. Individual items on the QIDS-SR-16 were rated by participants at the same time points.

Investigators found the largest mean changes from baseline were on reported and apparent sadness, lassitude, inability to feel, and concentration difficulties, with “very nice and clear dose-related differences,” Dr. Goodwin said.

The results indicate that the significant benefit with the largest dose at 3 weeks versus baseline was confined to items such as inability to feel and reported and apparent sadness on the MADRS and feeling sad and general interest on the QIDS-SR-16 (Table 1).

The results suggest the effect of COMP360 is “on the core symptoms of depression,” said Dr. Goodwin.