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Anhedonia emerges as a major transdiagnostic treatment target
SAN FRANCISCO – Anhedonia is the symptom dimension that cuts most strongly across the diagnostic boundaries of anxiety and depression and contributes most to the characteristically poor quality of life in both, Emily C. Livermore reported at the annual conference of the Anxiety and Depression Association of America.
“Our results suggest that anhedonia may have a disproportionate impact on disability from depression and anxiety and may be an important target for tailoring treatment and assessing treatment outcomes,” declared Ms. Livermore, a doctoral student in clinical psychology at Stanford (Calif.) University.
She presented a study of 121 adults with anxiety or depressive symptoms. The study was conducted under the auspices of the National Institute of Mental Health’s Research Domain Criteria (RDoC) initiative. The RDoC program is intended to promote a new way of studying mental disorders based on dimensional psychological constructs independent of traditional psychiatric diagnoses, which in some circles are now dismissed as “silos.” In keeping with the RDoC goals, Ms. Livermore and her coinvestigators examined diagnosis-independent dimensions of symptoms and how they affected quality of life.
The investigators obtained a comprehensive picture of the participants’ symptoms and quality of life by having them complete the Penn State Worry Questionnaire, the Mood and Anxiety Symptoms Questionnaire, the Depression Anxiety Stress Scale, and the World Health Organization Quality of Life – Brief Version.
The investigators then mapped the symptoms and their interconnections in order to identify what they called transdiagnostic symptom factor dimensions. They found four of them, which they termed anhedonia, worry, tension, and anxious arousal, a dimension encompassing physical symptoms including shortness of breath and heart palpitations.
Next, using regression analyses, they examined the relationship between levels of those four symptom factor dimensions and the four quality of life domains captured in the WHO instrument, namely, physical, psychologic, environmental, and social quality of life. Study participants averaged unhealthily low quality of life scores on two of these domains – the psychological and social – as defined by scores more than one standard deviation below normative.
Of the four symptom dimensions, anhedonia stood out as having moderate to-strong negative associations with all four quality of life domains. The other three symptom dimensions showed no or only weak associations with the four quality of life domains, with the exception of anxious arousal, which displayed a moderate relationship with physical quality of life.
Ms. Livermore reported having no financial conflicts regarding the study, which was funded by the National Institute of Mental Health.
SAN FRANCISCO – Anhedonia is the symptom dimension that cuts most strongly across the diagnostic boundaries of anxiety and depression and contributes most to the characteristically poor quality of life in both, Emily C. Livermore reported at the annual conference of the Anxiety and Depression Association of America.
“Our results suggest that anhedonia may have a disproportionate impact on disability from depression and anxiety and may be an important target for tailoring treatment and assessing treatment outcomes,” declared Ms. Livermore, a doctoral student in clinical psychology at Stanford (Calif.) University.
She presented a study of 121 adults with anxiety or depressive symptoms. The study was conducted under the auspices of the National Institute of Mental Health’s Research Domain Criteria (RDoC) initiative. The RDoC program is intended to promote a new way of studying mental disorders based on dimensional psychological constructs independent of traditional psychiatric diagnoses, which in some circles are now dismissed as “silos.” In keeping with the RDoC goals, Ms. Livermore and her coinvestigators examined diagnosis-independent dimensions of symptoms and how they affected quality of life.
The investigators obtained a comprehensive picture of the participants’ symptoms and quality of life by having them complete the Penn State Worry Questionnaire, the Mood and Anxiety Symptoms Questionnaire, the Depression Anxiety Stress Scale, and the World Health Organization Quality of Life – Brief Version.
The investigators then mapped the symptoms and their interconnections in order to identify what they called transdiagnostic symptom factor dimensions. They found four of them, which they termed anhedonia, worry, tension, and anxious arousal, a dimension encompassing physical symptoms including shortness of breath and heart palpitations.
Next, using regression analyses, they examined the relationship between levels of those four symptom factor dimensions and the four quality of life domains captured in the WHO instrument, namely, physical, psychologic, environmental, and social quality of life. Study participants averaged unhealthily low quality of life scores on two of these domains – the psychological and social – as defined by scores more than one standard deviation below normative.
Of the four symptom dimensions, anhedonia stood out as having moderate to-strong negative associations with all four quality of life domains. The other three symptom dimensions showed no or only weak associations with the four quality of life domains, with the exception of anxious arousal, which displayed a moderate relationship with physical quality of life.
Ms. Livermore reported having no financial conflicts regarding the study, which was funded by the National Institute of Mental Health.
SAN FRANCISCO – Anhedonia is the symptom dimension that cuts most strongly across the diagnostic boundaries of anxiety and depression and contributes most to the characteristically poor quality of life in both, Emily C. Livermore reported at the annual conference of the Anxiety and Depression Association of America.
“Our results suggest that anhedonia may have a disproportionate impact on disability from depression and anxiety and may be an important target for tailoring treatment and assessing treatment outcomes,” declared Ms. Livermore, a doctoral student in clinical psychology at Stanford (Calif.) University.
She presented a study of 121 adults with anxiety or depressive symptoms. The study was conducted under the auspices of the National Institute of Mental Health’s Research Domain Criteria (RDoC) initiative. The RDoC program is intended to promote a new way of studying mental disorders based on dimensional psychological constructs independent of traditional psychiatric diagnoses, which in some circles are now dismissed as “silos.” In keeping with the RDoC goals, Ms. Livermore and her coinvestigators examined diagnosis-independent dimensions of symptoms and how they affected quality of life.
The investigators obtained a comprehensive picture of the participants’ symptoms and quality of life by having them complete the Penn State Worry Questionnaire, the Mood and Anxiety Symptoms Questionnaire, the Depression Anxiety Stress Scale, and the World Health Organization Quality of Life – Brief Version.
The investigators then mapped the symptoms and their interconnections in order to identify what they called transdiagnostic symptom factor dimensions. They found four of them, which they termed anhedonia, worry, tension, and anxious arousal, a dimension encompassing physical symptoms including shortness of breath and heart palpitations.
Next, using regression analyses, they examined the relationship between levels of those four symptom factor dimensions and the four quality of life domains captured in the WHO instrument, namely, physical, psychologic, environmental, and social quality of life. Study participants averaged unhealthily low quality of life scores on two of these domains – the psychological and social – as defined by scores more than one standard deviation below normative.
Of the four symptom dimensions, anhedonia stood out as having moderate to-strong negative associations with all four quality of life domains. The other three symptom dimensions showed no or only weak associations with the four quality of life domains, with the exception of anxious arousal, which displayed a moderate relationship with physical quality of life.
Ms. Livermore reported having no financial conflicts regarding the study, which was funded by the National Institute of Mental Health.
AT THE ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: Anhedonia has a disproportionate negative impact on all of the major quality of life domains in both anxiety and depression.
Data source: A cross-sectional study of 121 adults with clinically significant anxiety or depression symptoms.
Disclosures: The presenter reported having no financial conflicts regarding the study, which was funded by the National Institute of Mental Health.
ADHD – not OCD – called the key comorbidity in pediatric hoarding
SAN FRANCISCO – Most of the pediatric hoarding literature focuses on hoarding accompanied by obsessive-compulsive disorder. But, “I want to highlight that [attention-deficit/hyperactivity disorder] is across the board something that seems to come up in child hoarding behaviors quite a bit, mirroring the adult literature, which is that hoarding behavior may be much more strongly associated with ADHD than it is with OCD,” Jennifer M. Park, PhD, said at the annual conference of the Anxiety and Depression Association of America.
Multiple studies have established that the prevalence of child hoarding is 2%-3.7%. Onset is typically at age 11-15 years. The course is chronic, and it’s a condition that typically exacerbates over time.
“A lot of the adult literature has shown that hoarding behavior actually starts in childhood. In many retrospective reports, adults say, ‘I’ve had these problems ever since I was a kid,’ ” according to Dr. Park, a psychologist affiliated with Stanford (Calif.) University.
Yet childhood hoarding is not widely perceived as problematic. Indeed, many parents and clinicians view it as developmentally appropriate. That’s to a great extent because the presentation of child hoarding behavior often is very different from and less disturbing than adult hoarding for the obvious reason that parents can limit the amount of clutter in the home.
“I have a bunch of kids who have quite significant hoarding behavior, but the parents are really on top of making sure all of that is left in the closet or within the child’s playroom, or maybe a certain section of the house,” Dr. Park said. “They’re able to keep it contained.”
Also, children and young adolescents lack the resources to accumulate massive clutter. They can’t drive, and have little or no money, so they can’t go on compulsive shopping sprees. “What I have seen in the kids that I work with is they make up for that by collecting things like paper and sticks, rocks, wrappers – anything that might be free, or knickknacks they can pick up along the way,” she said.
The cognitive-behavioral model of hoarding was first described 2 decades ago. It names three main factors as key to maintaining hoarding behaviors: emotional attachment and beliefs associated with one’s possessions, often including anthropomorphization; avoidance behaviors due to severe distress at the prospect of discarding stuff; and information-processing deficits.
“The idea here is that deficits in executive function – things like planning, organization, and inhibition – these are known in an extensive literature to be really strongly associated with ADHD, and executive function deficits link well with hoarding disorder as well,” Dr. Park continued.
Dr. Park was the first author of a recent multicenter study of 431 youths aged 6-17 diagnosed with OCD. They were participants in the OCD Collaborative Genetics Study and the OCD Collaborative Genetics Association Study, during which they completed the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Hoarding Rating Scale–Interview. Clinically significant levels of hoarding compulsions were identified in 113 subjects. Compared with the group with OCD but not hoarding, the OCD/hoarding group had significantly lower scores – meaning problematic deficits – on nearly all of the executive function subscales on the BRIEF, including working memory, emotional control, and planning/organization.
The two groups did not differ significantly in the prevalence of full DSM-IV ADHD. But the hoarding group had significantly more inattention and hyperactivity symptoms, and in a multivariate analysis adjusted for age, sex, and ADHD symptoms, deficits in executive function as measured on the BRIEF instrument were the strongest predictor of hoarding severity in the study population (J Psychiatr Res. 2016 Nov;82:141-8).
In another study by Dr. Park and her coinvestigators involving 99 youth diagnosed with ADHD, the severity of inattention and hyperactivity/impulsivity predicted clinically significant hoarding, whereas nonhoarding OCD symptoms did not (J Atten Disord. 2016 Jul;20[7]:617-26).
In an earlier report by other investigators on 109 children seeking treatment for an anxiety disorder, 22% of the study population proved to have elevated levels of hoarding symptoms. They scored significantly higher than the nonhoarding group on measures of obsession-compulsion, anxiety, inattention, thought problems, rule breaking, aggression, social problems, major depression, and overall functional impairment. But of note, attention problems were a significantly stronger predictor of hoarding symptoms than were OCD or anxiety symptoms (J Anxiety Disord. 2015 Dec;36:9-14).
Discussant Eric Storch, PhD, said that it’s important for clinicians and parents to start taking child hoarding seriously as a legitimate treatment target.
“We know that if you start treatment early, you’re more likely to be successful versus when you start at age 57 and the clutter is 9 or 10 on a scale of 10,” said Dr. Storch, professor of pediatrics and director of clinical research for developmental pediatrics at the University of South Florida, Tampa.
Dr. Park reported having no financial conflicts of interest regarding her presentation.
SAN FRANCISCO – Most of the pediatric hoarding literature focuses on hoarding accompanied by obsessive-compulsive disorder. But, “I want to highlight that [attention-deficit/hyperactivity disorder] is across the board something that seems to come up in child hoarding behaviors quite a bit, mirroring the adult literature, which is that hoarding behavior may be much more strongly associated with ADHD than it is with OCD,” Jennifer M. Park, PhD, said at the annual conference of the Anxiety and Depression Association of America.
Multiple studies have established that the prevalence of child hoarding is 2%-3.7%. Onset is typically at age 11-15 years. The course is chronic, and it’s a condition that typically exacerbates over time.
“A lot of the adult literature has shown that hoarding behavior actually starts in childhood. In many retrospective reports, adults say, ‘I’ve had these problems ever since I was a kid,’ ” according to Dr. Park, a psychologist affiliated with Stanford (Calif.) University.
Yet childhood hoarding is not widely perceived as problematic. Indeed, many parents and clinicians view it as developmentally appropriate. That’s to a great extent because the presentation of child hoarding behavior often is very different from and less disturbing than adult hoarding for the obvious reason that parents can limit the amount of clutter in the home.
“I have a bunch of kids who have quite significant hoarding behavior, but the parents are really on top of making sure all of that is left in the closet or within the child’s playroom, or maybe a certain section of the house,” Dr. Park said. “They’re able to keep it contained.”
Also, children and young adolescents lack the resources to accumulate massive clutter. They can’t drive, and have little or no money, so they can’t go on compulsive shopping sprees. “What I have seen in the kids that I work with is they make up for that by collecting things like paper and sticks, rocks, wrappers – anything that might be free, or knickknacks they can pick up along the way,” she said.
The cognitive-behavioral model of hoarding was first described 2 decades ago. It names three main factors as key to maintaining hoarding behaviors: emotional attachment and beliefs associated with one’s possessions, often including anthropomorphization; avoidance behaviors due to severe distress at the prospect of discarding stuff; and information-processing deficits.
“The idea here is that deficits in executive function – things like planning, organization, and inhibition – these are known in an extensive literature to be really strongly associated with ADHD, and executive function deficits link well with hoarding disorder as well,” Dr. Park continued.
Dr. Park was the first author of a recent multicenter study of 431 youths aged 6-17 diagnosed with OCD. They were participants in the OCD Collaborative Genetics Study and the OCD Collaborative Genetics Association Study, during which they completed the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Hoarding Rating Scale–Interview. Clinically significant levels of hoarding compulsions were identified in 113 subjects. Compared with the group with OCD but not hoarding, the OCD/hoarding group had significantly lower scores – meaning problematic deficits – on nearly all of the executive function subscales on the BRIEF, including working memory, emotional control, and planning/organization.
The two groups did not differ significantly in the prevalence of full DSM-IV ADHD. But the hoarding group had significantly more inattention and hyperactivity symptoms, and in a multivariate analysis adjusted for age, sex, and ADHD symptoms, deficits in executive function as measured on the BRIEF instrument were the strongest predictor of hoarding severity in the study population (J Psychiatr Res. 2016 Nov;82:141-8).
In another study by Dr. Park and her coinvestigators involving 99 youth diagnosed with ADHD, the severity of inattention and hyperactivity/impulsivity predicted clinically significant hoarding, whereas nonhoarding OCD symptoms did not (J Atten Disord. 2016 Jul;20[7]:617-26).
In an earlier report by other investigators on 109 children seeking treatment for an anxiety disorder, 22% of the study population proved to have elevated levels of hoarding symptoms. They scored significantly higher than the nonhoarding group on measures of obsession-compulsion, anxiety, inattention, thought problems, rule breaking, aggression, social problems, major depression, and overall functional impairment. But of note, attention problems were a significantly stronger predictor of hoarding symptoms than were OCD or anxiety symptoms (J Anxiety Disord. 2015 Dec;36:9-14).
Discussant Eric Storch, PhD, said that it’s important for clinicians and parents to start taking child hoarding seriously as a legitimate treatment target.
“We know that if you start treatment early, you’re more likely to be successful versus when you start at age 57 and the clutter is 9 or 10 on a scale of 10,” said Dr. Storch, professor of pediatrics and director of clinical research for developmental pediatrics at the University of South Florida, Tampa.
Dr. Park reported having no financial conflicts of interest regarding her presentation.
SAN FRANCISCO – Most of the pediatric hoarding literature focuses on hoarding accompanied by obsessive-compulsive disorder. But, “I want to highlight that [attention-deficit/hyperactivity disorder] is across the board something that seems to come up in child hoarding behaviors quite a bit, mirroring the adult literature, which is that hoarding behavior may be much more strongly associated with ADHD than it is with OCD,” Jennifer M. Park, PhD, said at the annual conference of the Anxiety and Depression Association of America.
Multiple studies have established that the prevalence of child hoarding is 2%-3.7%. Onset is typically at age 11-15 years. The course is chronic, and it’s a condition that typically exacerbates over time.
“A lot of the adult literature has shown that hoarding behavior actually starts in childhood. In many retrospective reports, adults say, ‘I’ve had these problems ever since I was a kid,’ ” according to Dr. Park, a psychologist affiliated with Stanford (Calif.) University.
Yet childhood hoarding is not widely perceived as problematic. Indeed, many parents and clinicians view it as developmentally appropriate. That’s to a great extent because the presentation of child hoarding behavior often is very different from and less disturbing than adult hoarding for the obvious reason that parents can limit the amount of clutter in the home.
“I have a bunch of kids who have quite significant hoarding behavior, but the parents are really on top of making sure all of that is left in the closet or within the child’s playroom, or maybe a certain section of the house,” Dr. Park said. “They’re able to keep it contained.”
Also, children and young adolescents lack the resources to accumulate massive clutter. They can’t drive, and have little or no money, so they can’t go on compulsive shopping sprees. “What I have seen in the kids that I work with is they make up for that by collecting things like paper and sticks, rocks, wrappers – anything that might be free, or knickknacks they can pick up along the way,” she said.
The cognitive-behavioral model of hoarding was first described 2 decades ago. It names three main factors as key to maintaining hoarding behaviors: emotional attachment and beliefs associated with one’s possessions, often including anthropomorphization; avoidance behaviors due to severe distress at the prospect of discarding stuff; and information-processing deficits.
“The idea here is that deficits in executive function – things like planning, organization, and inhibition – these are known in an extensive literature to be really strongly associated with ADHD, and executive function deficits link well with hoarding disorder as well,” Dr. Park continued.
Dr. Park was the first author of a recent multicenter study of 431 youths aged 6-17 diagnosed with OCD. They were participants in the OCD Collaborative Genetics Study and the OCD Collaborative Genetics Association Study, during which they completed the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Hoarding Rating Scale–Interview. Clinically significant levels of hoarding compulsions were identified in 113 subjects. Compared with the group with OCD but not hoarding, the OCD/hoarding group had significantly lower scores – meaning problematic deficits – on nearly all of the executive function subscales on the BRIEF, including working memory, emotional control, and planning/organization.
The two groups did not differ significantly in the prevalence of full DSM-IV ADHD. But the hoarding group had significantly more inattention and hyperactivity symptoms, and in a multivariate analysis adjusted for age, sex, and ADHD symptoms, deficits in executive function as measured on the BRIEF instrument were the strongest predictor of hoarding severity in the study population (J Psychiatr Res. 2016 Nov;82:141-8).
In another study by Dr. Park and her coinvestigators involving 99 youth diagnosed with ADHD, the severity of inattention and hyperactivity/impulsivity predicted clinically significant hoarding, whereas nonhoarding OCD symptoms did not (J Atten Disord. 2016 Jul;20[7]:617-26).
In an earlier report by other investigators on 109 children seeking treatment for an anxiety disorder, 22% of the study population proved to have elevated levels of hoarding symptoms. They scored significantly higher than the nonhoarding group on measures of obsession-compulsion, anxiety, inattention, thought problems, rule breaking, aggression, social problems, major depression, and overall functional impairment. But of note, attention problems were a significantly stronger predictor of hoarding symptoms than were OCD or anxiety symptoms (J Anxiety Disord. 2015 Dec;36:9-14).
Discussant Eric Storch, PhD, said that it’s important for clinicians and parents to start taking child hoarding seriously as a legitimate treatment target.
“We know that if you start treatment early, you’re more likely to be successful versus when you start at age 57 and the clutter is 9 or 10 on a scale of 10,” said Dr. Storch, professor of pediatrics and director of clinical research for developmental pediatrics at the University of South Florida, Tampa.
Dr. Park reported having no financial conflicts of interest regarding her presentation.
EXPERT ANALYSIS FROM ANXIETY AND DEPRESSION CONFERENCE 2017
Transradial PCI in acute coronary syndrome causes less kidney damage
PARIS – Transradial-access percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) results in a significantly lower risk of acute kidney injury (AKI), compared with the transfemoral approach, according to a new analysis from the large randomized MATRIX trial.
The results of this prespecified secondary subgroup analysis of MATRIX suggest it’s time to update the classic “five golden rules” for reduction of contrast medium–induced AKI by adding a sixth. “Use a transradial approach,” Bernardo Cortese, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
He reported on 8,210 participants in the MATRIX trial (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) who were randomized to transradial- or transfemoral-access PCI for non–ST-elevation MI or ST-elevation MI.
The primary results of the 78-site, four-country European study, previously published, showed that transradial PCI reduced the composite risk of death, MI, stroke, or major bleeding by 17%, compared with transfemoral PCI, a benefit mainly driven by a marked reduction in clinically important bleeding (Lancet. 2015 Jun 20;385[9986]:2465-76).
Left unanswered by the primary analysis was the question of whether transradial PCI in ACS patients also reduced AKI risk, as had previously been suggested by a meta-analysis of observational studies (Int J Cardiol. 2015 Jan 20;179:309-11). In designing the MATRIX trial, Dr. Cortese and the other investigators decided to address that issue separately in a prespecified secondary analysis known as AKI-MATRIX. For this purpose, AKI was defined as either a post-PCI in-hospital increase in serum creatinine level of more than 25%, compared with the preangiography baseline, or an absolute increase in serum creatinine of greater than 0.5 mg/dL.
AKI occurred in 15.4% of ACS patients who underwent PCI with transradial access and 17.3% of those randomized to transfemoral access, for a significant 13% relative risk reduction. This was accomplished without any increase in the volume of contrast media required. The average was 200 mL in both study groups.
The reduction in AKI achieved with transradial-access PCI was seen in all patient subgroups, including those at increased AKI risk because of an estimated glomerular filtration rate below 60 mL/min, age 75 or older, Killup class III or IV, or a Mehran score greater than 10.
Dr. Cortese proposed several possible mechanisms for the observed reduction in AKI seen with transradial-access PCI. The major factor in his view is that the transradial approach entails less bleeding, as earlier demonstrated in the primary analysis – and bleeding has been associated with impaired renal perfusion in several prior studies. Also, it’s plausible that the passage of the catheter across the renal arteries during the transfemoral approach dislodges atherosclerotic debris, which then travels down the renal vessels.
The five golden rules for preventing contrast media–induced AKI, he noted, are
1. Discontinue nephrotoxic drugs before the procedure.
2. Identify high-risk patients.
3. Hydrate them.
4. Choose an ideal contrast medium.
5. Adapt the dose of contrast medium to the patient’s specific situation.
Discussant Jacek Legutko, MD, PhD, of Jagiellonian University in Krakow, Poland, said the primary results of the MATRIX trial published in 2015 have had a major impact on Polish interventional cardiology, where transradial PCI is now used in 80% of PCIs. The AKI study results will reinforce this trend, he added.
“You have shown something opposite to what we’ve thought in the past, that maybe, with a radial approach, we would use more contrast medium, which is a risk factor for AKI. In your study – at least in ACS with very experienced transradial operators – there was no increase in contrast volume, and the risk of AKI decreased,” Dr. Legutko said.
Asked about the possibility that transradial PCI might be associated with an increased risk of embolization to the brain, much as the transfemoral approach might cause embolization to the kidneys, Dr. Cortese said there was no significant difference between the two AKI-MATRIX study arms in rates of transient ischemic attack or stroke.
“I did my first transradial PCI in 2003, and I haven’t seen any increase in these events or later dementia,” he added.
The prespecified secondary analysis of the MATRIX trial was conducted without commercial support. The presenter reported serving as a consultant to Abbott, AstraZeneca, Daiichi Sankyo, Eli Lilly, and Stentys.
Simultaneous with his presentation in Paris, the AKI-MATRIX study was published online at www.sciencedirect.com/science/article/pii/S0735109717368973.
PARIS – Transradial-access percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) results in a significantly lower risk of acute kidney injury (AKI), compared with the transfemoral approach, according to a new analysis from the large randomized MATRIX trial.
The results of this prespecified secondary subgroup analysis of MATRIX suggest it’s time to update the classic “five golden rules” for reduction of contrast medium–induced AKI by adding a sixth. “Use a transradial approach,” Bernardo Cortese, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
He reported on 8,210 participants in the MATRIX trial (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) who were randomized to transradial- or transfemoral-access PCI for non–ST-elevation MI or ST-elevation MI.
The primary results of the 78-site, four-country European study, previously published, showed that transradial PCI reduced the composite risk of death, MI, stroke, or major bleeding by 17%, compared with transfemoral PCI, a benefit mainly driven by a marked reduction in clinically important bleeding (Lancet. 2015 Jun 20;385[9986]:2465-76).
Left unanswered by the primary analysis was the question of whether transradial PCI in ACS patients also reduced AKI risk, as had previously been suggested by a meta-analysis of observational studies (Int J Cardiol. 2015 Jan 20;179:309-11). In designing the MATRIX trial, Dr. Cortese and the other investigators decided to address that issue separately in a prespecified secondary analysis known as AKI-MATRIX. For this purpose, AKI was defined as either a post-PCI in-hospital increase in serum creatinine level of more than 25%, compared with the preangiography baseline, or an absolute increase in serum creatinine of greater than 0.5 mg/dL.
AKI occurred in 15.4% of ACS patients who underwent PCI with transradial access and 17.3% of those randomized to transfemoral access, for a significant 13% relative risk reduction. This was accomplished without any increase in the volume of contrast media required. The average was 200 mL in both study groups.
The reduction in AKI achieved with transradial-access PCI was seen in all patient subgroups, including those at increased AKI risk because of an estimated glomerular filtration rate below 60 mL/min, age 75 or older, Killup class III or IV, or a Mehran score greater than 10.
Dr. Cortese proposed several possible mechanisms for the observed reduction in AKI seen with transradial-access PCI. The major factor in his view is that the transradial approach entails less bleeding, as earlier demonstrated in the primary analysis – and bleeding has been associated with impaired renal perfusion in several prior studies. Also, it’s plausible that the passage of the catheter across the renal arteries during the transfemoral approach dislodges atherosclerotic debris, which then travels down the renal vessels.
The five golden rules for preventing contrast media–induced AKI, he noted, are
1. Discontinue nephrotoxic drugs before the procedure.
2. Identify high-risk patients.
3. Hydrate them.
4. Choose an ideal contrast medium.
5. Adapt the dose of contrast medium to the patient’s specific situation.
Discussant Jacek Legutko, MD, PhD, of Jagiellonian University in Krakow, Poland, said the primary results of the MATRIX trial published in 2015 have had a major impact on Polish interventional cardiology, where transradial PCI is now used in 80% of PCIs. The AKI study results will reinforce this trend, he added.
“You have shown something opposite to what we’ve thought in the past, that maybe, with a radial approach, we would use more contrast medium, which is a risk factor for AKI. In your study – at least in ACS with very experienced transradial operators – there was no increase in contrast volume, and the risk of AKI decreased,” Dr. Legutko said.
Asked about the possibility that transradial PCI might be associated with an increased risk of embolization to the brain, much as the transfemoral approach might cause embolization to the kidneys, Dr. Cortese said there was no significant difference between the two AKI-MATRIX study arms in rates of transient ischemic attack or stroke.
“I did my first transradial PCI in 2003, and I haven’t seen any increase in these events or later dementia,” he added.
The prespecified secondary analysis of the MATRIX trial was conducted without commercial support. The presenter reported serving as a consultant to Abbott, AstraZeneca, Daiichi Sankyo, Eli Lilly, and Stentys.
Simultaneous with his presentation in Paris, the AKI-MATRIX study was published online at www.sciencedirect.com/science/article/pii/S0735109717368973.
PARIS – Transradial-access percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) results in a significantly lower risk of acute kidney injury (AKI), compared with the transfemoral approach, according to a new analysis from the large randomized MATRIX trial.
The results of this prespecified secondary subgroup analysis of MATRIX suggest it’s time to update the classic “five golden rules” for reduction of contrast medium–induced AKI by adding a sixth. “Use a transradial approach,” Bernardo Cortese, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
He reported on 8,210 participants in the MATRIX trial (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) who were randomized to transradial- or transfemoral-access PCI for non–ST-elevation MI or ST-elevation MI.
The primary results of the 78-site, four-country European study, previously published, showed that transradial PCI reduced the composite risk of death, MI, stroke, or major bleeding by 17%, compared with transfemoral PCI, a benefit mainly driven by a marked reduction in clinically important bleeding (Lancet. 2015 Jun 20;385[9986]:2465-76).
Left unanswered by the primary analysis was the question of whether transradial PCI in ACS patients also reduced AKI risk, as had previously been suggested by a meta-analysis of observational studies (Int J Cardiol. 2015 Jan 20;179:309-11). In designing the MATRIX trial, Dr. Cortese and the other investigators decided to address that issue separately in a prespecified secondary analysis known as AKI-MATRIX. For this purpose, AKI was defined as either a post-PCI in-hospital increase in serum creatinine level of more than 25%, compared with the preangiography baseline, or an absolute increase in serum creatinine of greater than 0.5 mg/dL.
AKI occurred in 15.4% of ACS patients who underwent PCI with transradial access and 17.3% of those randomized to transfemoral access, for a significant 13% relative risk reduction. This was accomplished without any increase in the volume of contrast media required. The average was 200 mL in both study groups.
The reduction in AKI achieved with transradial-access PCI was seen in all patient subgroups, including those at increased AKI risk because of an estimated glomerular filtration rate below 60 mL/min, age 75 or older, Killup class III or IV, or a Mehran score greater than 10.
Dr. Cortese proposed several possible mechanisms for the observed reduction in AKI seen with transradial-access PCI. The major factor in his view is that the transradial approach entails less bleeding, as earlier demonstrated in the primary analysis – and bleeding has been associated with impaired renal perfusion in several prior studies. Also, it’s plausible that the passage of the catheter across the renal arteries during the transfemoral approach dislodges atherosclerotic debris, which then travels down the renal vessels.
The five golden rules for preventing contrast media–induced AKI, he noted, are
1. Discontinue nephrotoxic drugs before the procedure.
2. Identify high-risk patients.
3. Hydrate them.
4. Choose an ideal contrast medium.
5. Adapt the dose of contrast medium to the patient’s specific situation.
Discussant Jacek Legutko, MD, PhD, of Jagiellonian University in Krakow, Poland, said the primary results of the MATRIX trial published in 2015 have had a major impact on Polish interventional cardiology, where transradial PCI is now used in 80% of PCIs. The AKI study results will reinforce this trend, he added.
“You have shown something opposite to what we’ve thought in the past, that maybe, with a radial approach, we would use more contrast medium, which is a risk factor for AKI. In your study – at least in ACS with very experienced transradial operators – there was no increase in contrast volume, and the risk of AKI decreased,” Dr. Legutko said.
Asked about the possibility that transradial PCI might be associated with an increased risk of embolization to the brain, much as the transfemoral approach might cause embolization to the kidneys, Dr. Cortese said there was no significant difference between the two AKI-MATRIX study arms in rates of transient ischemic attack or stroke.
“I did my first transradial PCI in 2003, and I haven’t seen any increase in these events or later dementia,” he added.
The prespecified secondary analysis of the MATRIX trial was conducted without commercial support. The presenter reported serving as a consultant to Abbott, AstraZeneca, Daiichi Sankyo, Eli Lilly, and Stentys.
Simultaneous with his presentation in Paris, the AKI-MATRIX study was published online at www.sciencedirect.com/science/article/pii/S0735109717368973.
AT EUROPCR
Key clinical point:
Major finding: Transradial-access PCI for ACS resulted in a 13% lower risk of acute kidney injury than the transfemoral approach.
Data source: A four-country European randomized trial of transradial- vs. transfemoral-access PCI in more than 8,200 patients with ACS.
Disclosures: This prespecified secondary analysis of the MATRIX trial was conducted without commercial support. The presenter reported serving as a consultant to Abbott, AstraZeneca, Daiichi Sankyo, Eli Lilly, and Stentys.
BIO-RESORT: A mandate to prescreen PCI patients for silent diabetes
PARIS – Undetected diabetes and prediabetes are pervasive in patients undergoing percutaneous coronary intervention, and they’re associated with a sharply increased risk of major adverse cardiovascular events, according to the results of the potentially practice-changing BIO-RESORT Silent Diabetes Study, Clemens von Birgelen, MD, PhD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Our data support screening PCI all-comers for silent diabetes, which may help identify patients with an increased event risk and improve their therapy,” said Dr. von Birgelen, professor of cardiology at the Thoraxcentrum of Twente, a high-volume center for cardiac interventions in Enschede, the Netherlands.
A substantial one-third of subjects turned out to have abnormal glucose tolerance according to World Health Organization criteria and an International Expert Committee Report (Diabetes Care. 2009 Jul;32[7]:1327-34). In a multivariate analysis, their 1-year rate of the primary study endpoint – target vessel failure, a composite of cardiac death, target vessel-related MI, or target vessel revascularization – was an adjusted 2.2 times greater than in the 788 normoglycemic patients.
Moreover, among the 7% of study participants who met diagnostic criteria for silent diabetes, the risk of target vessel failure was more than 4.4 times greater than in the normoglycemic group.
“To a very great extent, periprocedural MI is the driving force behind this difference that we saw. From a biological point of view, I think that the vulnerability of the vessel in the diabetic or prediabetic patient features more brittle plaque with a higher risk of cholesterol embolization, and with more plaque mass that can be pushed to the side so that side branch vessels can become occluded, leading to periprocedural MI,” he observed.
Glucose metabolism was assessed in all participants by two methods using the conventional cutoffs: a 2-hour oral glucose tolerance test (OGTT), and the combination of fasting plasma glucose and hemoglobin A1c. By OGTT, 7% of patients had silent, previously unrecognized diabetes and another 13% had prediabetes. Using the combination of fasting plasma glucose and HbA1c, a total of 25% of subjects had silent diabetes or prediabetes. Fully 33% of participants had abnormal glucose metabolism by one yardstick or the other.
“What we have seen is there is a group of patients that are missed with either. With the OGTT you don’t see all the diabetics, and with HbA1c and fasting blood glucose you also miss some patients,” said Dr. von Birgelen.
The 1-year cumulative incidence of target vessel failure was 13.2% in patients with silent diabetes as identified by the OGTT and 12.1% in those detected by the alternative method, compared with rates of 2.8% and 3.1%, respectively, in normoglycemic PCI patients. The event rate was 6.1% in patients with prediabetes by OGTT and similar at 5.5% in those found to be prediabetic based on fasting blood glucose and HbA1c, versus rates of 2.8% and 3.1%, respectively, in normoglycemic patients.
“The findings of this study suggest that post-PCI event risk associated with hyperglycemia is a continuum without a clear threshold effect, extending well beyond the threshold that currently defines diabetes,” Dr. von Birgelen said.
Once again, it’s worth emphasizing that the elevated target vessel failure rates seen in patients with abnormal glucose metabolism were due mostly to increased rates of acute MI within the first 24 hours after PCI. The target vessel–related MI rate was 10.3% in patients with silent diabetes, compared with just 1.8% in normoglycemic controls.
Asked what the take-home message for clinicians is from this study, he noted that the Netherlands has a relatively low prevalence of diabetes, and a highly developed primary care medicine system.
“We have a very good one-to-one relationship between the patient and the GP. So if we find 7% silent diabetes and up to one-third of patients with undetected abnormal glucose tolerance in a country with a relatively low prevalence of diabetes, you may expect that in other countries with a higher prevalence and perhaps a less developed primary care system the rate may be much, much higher,” Dr. von Birgelen cautioned.
The implications for the daily clinical practice of interventional cardiology are clear, he continued: “We’ve seen in several trials that the new stents are doing a fantastic job. So if we want to further improve the outcomes in our patients we have to do something else. We should look for subgroups of our PCI patients who have a particularly high risk. And we all realize that diabetics are such a problem, but I think we have shown that the prediabetic patients are also important. So we should identify and pretreat these patients, perhaps with aggressive lipid-lowering therapy during the weeks before a scheduled elective PCI.”
“There are data showing that with aggressive lipid-lowering you might reduce the risk of periprocedural MI,” the cardiologist noted.
As a practical matter, screening via fasting blood glucose and HbA1c is probably the way to go in clinical practice, according to Dr. von Birgelen.
“In this study, we performed the OGTT because it is still considered by many the gold standard. But there is increasing evidence favoring HbA1c data and fasting blood glucose,” he said.
Other possible pre-PCI interventions worthy of consideration in patients found to have previously unsuspected abnormal glucose tolerance might include medical therapy aimed at normalizing glucose metabolism, as well as perhaps resorting to the most potent forms of dual-antiplatelet therapy in patients with stable angina who have impaired glucose tolerance. However, these are possibilities that should be tested in randomized controlled trials before widespread adoption, he added.
The BIO-RESORT Silent Diabetes Study, which will continue for 5 years of post-PCI follow-up, is a prespecified substudy of the previously reported BIO-RESORT trial, which addressed another issue entirely. It was a three-arm, patient-blinded clinical trial comparing 1-year safety and efficacy outcomes in nearly 3,500 PCI patients randomized to PCI with very thin strut biodegradable polymer everolimus- or sirolimus-eluting stents or a durable polymer zotarolimus-eluting stent. Outcomes proved noninferior across the three treatment groups (Lancet. 2016 Nov 26;388[10060]:2607-17).
Dr. von Birgelen observed that the silent diabetes study broke new ground. Prior studies of PCI outcomes in patients with unrecognized diabetes were limited to recipients of plain old balloon angioplasty, bare metal, or first-generation drug-eluting stents. And studies of PCI in patients with unrecognized prediabetes are virtually nonexistent.
As the principal investigator for both the parent BIO-RESORT trial and the silent diabetes substudy, Dr. von Birgelen received research grants from Biotronik, Boston Scientific, and Medtronic, the cosponsors. He applauded the three companies for funding the silent diabetes substudy in the interest of science even though it had no commercial relevance to their stent businesses.
PARIS – Undetected diabetes and prediabetes are pervasive in patients undergoing percutaneous coronary intervention, and they’re associated with a sharply increased risk of major adverse cardiovascular events, according to the results of the potentially practice-changing BIO-RESORT Silent Diabetes Study, Clemens von Birgelen, MD, PhD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Our data support screening PCI all-comers for silent diabetes, which may help identify patients with an increased event risk and improve their therapy,” said Dr. von Birgelen, professor of cardiology at the Thoraxcentrum of Twente, a high-volume center for cardiac interventions in Enschede, the Netherlands.
A substantial one-third of subjects turned out to have abnormal glucose tolerance according to World Health Organization criteria and an International Expert Committee Report (Diabetes Care. 2009 Jul;32[7]:1327-34). In a multivariate analysis, their 1-year rate of the primary study endpoint – target vessel failure, a composite of cardiac death, target vessel-related MI, or target vessel revascularization – was an adjusted 2.2 times greater than in the 788 normoglycemic patients.
Moreover, among the 7% of study participants who met diagnostic criteria for silent diabetes, the risk of target vessel failure was more than 4.4 times greater than in the normoglycemic group.
“To a very great extent, periprocedural MI is the driving force behind this difference that we saw. From a biological point of view, I think that the vulnerability of the vessel in the diabetic or prediabetic patient features more brittle plaque with a higher risk of cholesterol embolization, and with more plaque mass that can be pushed to the side so that side branch vessels can become occluded, leading to periprocedural MI,” he observed.
Glucose metabolism was assessed in all participants by two methods using the conventional cutoffs: a 2-hour oral glucose tolerance test (OGTT), and the combination of fasting plasma glucose and hemoglobin A1c. By OGTT, 7% of patients had silent, previously unrecognized diabetes and another 13% had prediabetes. Using the combination of fasting plasma glucose and HbA1c, a total of 25% of subjects had silent diabetes or prediabetes. Fully 33% of participants had abnormal glucose metabolism by one yardstick or the other.
“What we have seen is there is a group of patients that are missed with either. With the OGTT you don’t see all the diabetics, and with HbA1c and fasting blood glucose you also miss some patients,” said Dr. von Birgelen.
The 1-year cumulative incidence of target vessel failure was 13.2% in patients with silent diabetes as identified by the OGTT and 12.1% in those detected by the alternative method, compared with rates of 2.8% and 3.1%, respectively, in normoglycemic PCI patients. The event rate was 6.1% in patients with prediabetes by OGTT and similar at 5.5% in those found to be prediabetic based on fasting blood glucose and HbA1c, versus rates of 2.8% and 3.1%, respectively, in normoglycemic patients.
“The findings of this study suggest that post-PCI event risk associated with hyperglycemia is a continuum without a clear threshold effect, extending well beyond the threshold that currently defines diabetes,” Dr. von Birgelen said.
Once again, it’s worth emphasizing that the elevated target vessel failure rates seen in patients with abnormal glucose metabolism were due mostly to increased rates of acute MI within the first 24 hours after PCI. The target vessel–related MI rate was 10.3% in patients with silent diabetes, compared with just 1.8% in normoglycemic controls.
Asked what the take-home message for clinicians is from this study, he noted that the Netherlands has a relatively low prevalence of diabetes, and a highly developed primary care medicine system.
“We have a very good one-to-one relationship between the patient and the GP. So if we find 7% silent diabetes and up to one-third of patients with undetected abnormal glucose tolerance in a country with a relatively low prevalence of diabetes, you may expect that in other countries with a higher prevalence and perhaps a less developed primary care system the rate may be much, much higher,” Dr. von Birgelen cautioned.
The implications for the daily clinical practice of interventional cardiology are clear, he continued: “We’ve seen in several trials that the new stents are doing a fantastic job. So if we want to further improve the outcomes in our patients we have to do something else. We should look for subgroups of our PCI patients who have a particularly high risk. And we all realize that diabetics are such a problem, but I think we have shown that the prediabetic patients are also important. So we should identify and pretreat these patients, perhaps with aggressive lipid-lowering therapy during the weeks before a scheduled elective PCI.”
“There are data showing that with aggressive lipid-lowering you might reduce the risk of periprocedural MI,” the cardiologist noted.
As a practical matter, screening via fasting blood glucose and HbA1c is probably the way to go in clinical practice, according to Dr. von Birgelen.
“In this study, we performed the OGTT because it is still considered by many the gold standard. But there is increasing evidence favoring HbA1c data and fasting blood glucose,” he said.
Other possible pre-PCI interventions worthy of consideration in patients found to have previously unsuspected abnormal glucose tolerance might include medical therapy aimed at normalizing glucose metabolism, as well as perhaps resorting to the most potent forms of dual-antiplatelet therapy in patients with stable angina who have impaired glucose tolerance. However, these are possibilities that should be tested in randomized controlled trials before widespread adoption, he added.
The BIO-RESORT Silent Diabetes Study, which will continue for 5 years of post-PCI follow-up, is a prespecified substudy of the previously reported BIO-RESORT trial, which addressed another issue entirely. It was a three-arm, patient-blinded clinical trial comparing 1-year safety and efficacy outcomes in nearly 3,500 PCI patients randomized to PCI with very thin strut biodegradable polymer everolimus- or sirolimus-eluting stents or a durable polymer zotarolimus-eluting stent. Outcomes proved noninferior across the three treatment groups (Lancet. 2016 Nov 26;388[10060]:2607-17).
Dr. von Birgelen observed that the silent diabetes study broke new ground. Prior studies of PCI outcomes in patients with unrecognized diabetes were limited to recipients of plain old balloon angioplasty, bare metal, or first-generation drug-eluting stents. And studies of PCI in patients with unrecognized prediabetes are virtually nonexistent.
As the principal investigator for both the parent BIO-RESORT trial and the silent diabetes substudy, Dr. von Birgelen received research grants from Biotronik, Boston Scientific, and Medtronic, the cosponsors. He applauded the three companies for funding the silent diabetes substudy in the interest of science even though it had no commercial relevance to their stent businesses.
PARIS – Undetected diabetes and prediabetes are pervasive in patients undergoing percutaneous coronary intervention, and they’re associated with a sharply increased risk of major adverse cardiovascular events, according to the results of the potentially practice-changing BIO-RESORT Silent Diabetes Study, Clemens von Birgelen, MD, PhD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Our data support screening PCI all-comers for silent diabetes, which may help identify patients with an increased event risk and improve their therapy,” said Dr. von Birgelen, professor of cardiology at the Thoraxcentrum of Twente, a high-volume center for cardiac interventions in Enschede, the Netherlands.
A substantial one-third of subjects turned out to have abnormal glucose tolerance according to World Health Organization criteria and an International Expert Committee Report (Diabetes Care. 2009 Jul;32[7]:1327-34). In a multivariate analysis, their 1-year rate of the primary study endpoint – target vessel failure, a composite of cardiac death, target vessel-related MI, or target vessel revascularization – was an adjusted 2.2 times greater than in the 788 normoglycemic patients.
Moreover, among the 7% of study participants who met diagnostic criteria for silent diabetes, the risk of target vessel failure was more than 4.4 times greater than in the normoglycemic group.
“To a very great extent, periprocedural MI is the driving force behind this difference that we saw. From a biological point of view, I think that the vulnerability of the vessel in the diabetic or prediabetic patient features more brittle plaque with a higher risk of cholesterol embolization, and with more plaque mass that can be pushed to the side so that side branch vessels can become occluded, leading to periprocedural MI,” he observed.
Glucose metabolism was assessed in all participants by two methods using the conventional cutoffs: a 2-hour oral glucose tolerance test (OGTT), and the combination of fasting plasma glucose and hemoglobin A1c. By OGTT, 7% of patients had silent, previously unrecognized diabetes and another 13% had prediabetes. Using the combination of fasting plasma glucose and HbA1c, a total of 25% of subjects had silent diabetes or prediabetes. Fully 33% of participants had abnormal glucose metabolism by one yardstick or the other.
“What we have seen is there is a group of patients that are missed with either. With the OGTT you don’t see all the diabetics, and with HbA1c and fasting blood glucose you also miss some patients,” said Dr. von Birgelen.
The 1-year cumulative incidence of target vessel failure was 13.2% in patients with silent diabetes as identified by the OGTT and 12.1% in those detected by the alternative method, compared with rates of 2.8% and 3.1%, respectively, in normoglycemic PCI patients. The event rate was 6.1% in patients with prediabetes by OGTT and similar at 5.5% in those found to be prediabetic based on fasting blood glucose and HbA1c, versus rates of 2.8% and 3.1%, respectively, in normoglycemic patients.
“The findings of this study suggest that post-PCI event risk associated with hyperglycemia is a continuum without a clear threshold effect, extending well beyond the threshold that currently defines diabetes,” Dr. von Birgelen said.
Once again, it’s worth emphasizing that the elevated target vessel failure rates seen in patients with abnormal glucose metabolism were due mostly to increased rates of acute MI within the first 24 hours after PCI. The target vessel–related MI rate was 10.3% in patients with silent diabetes, compared with just 1.8% in normoglycemic controls.
Asked what the take-home message for clinicians is from this study, he noted that the Netherlands has a relatively low prevalence of diabetes, and a highly developed primary care medicine system.
“We have a very good one-to-one relationship between the patient and the GP. So if we find 7% silent diabetes and up to one-third of patients with undetected abnormal glucose tolerance in a country with a relatively low prevalence of diabetes, you may expect that in other countries with a higher prevalence and perhaps a less developed primary care system the rate may be much, much higher,” Dr. von Birgelen cautioned.
The implications for the daily clinical practice of interventional cardiology are clear, he continued: “We’ve seen in several trials that the new stents are doing a fantastic job. So if we want to further improve the outcomes in our patients we have to do something else. We should look for subgroups of our PCI patients who have a particularly high risk. And we all realize that diabetics are such a problem, but I think we have shown that the prediabetic patients are also important. So we should identify and pretreat these patients, perhaps with aggressive lipid-lowering therapy during the weeks before a scheduled elective PCI.”
“There are data showing that with aggressive lipid-lowering you might reduce the risk of periprocedural MI,” the cardiologist noted.
As a practical matter, screening via fasting blood glucose and HbA1c is probably the way to go in clinical practice, according to Dr. von Birgelen.
“In this study, we performed the OGTT because it is still considered by many the gold standard. But there is increasing evidence favoring HbA1c data and fasting blood glucose,” he said.
Other possible pre-PCI interventions worthy of consideration in patients found to have previously unsuspected abnormal glucose tolerance might include medical therapy aimed at normalizing glucose metabolism, as well as perhaps resorting to the most potent forms of dual-antiplatelet therapy in patients with stable angina who have impaired glucose tolerance. However, these are possibilities that should be tested in randomized controlled trials before widespread adoption, he added.
The BIO-RESORT Silent Diabetes Study, which will continue for 5 years of post-PCI follow-up, is a prespecified substudy of the previously reported BIO-RESORT trial, which addressed another issue entirely. It was a three-arm, patient-blinded clinical trial comparing 1-year safety and efficacy outcomes in nearly 3,500 PCI patients randomized to PCI with very thin strut biodegradable polymer everolimus- or sirolimus-eluting stents or a durable polymer zotarolimus-eluting stent. Outcomes proved noninferior across the three treatment groups (Lancet. 2016 Nov 26;388[10060]:2607-17).
Dr. von Birgelen observed that the silent diabetes study broke new ground. Prior studies of PCI outcomes in patients with unrecognized diabetes were limited to recipients of plain old balloon angioplasty, bare metal, or first-generation drug-eluting stents. And studies of PCI in patients with unrecognized prediabetes are virtually nonexistent.
As the principal investigator for both the parent BIO-RESORT trial and the silent diabetes substudy, Dr. von Birgelen received research grants from Biotronik, Boston Scientific, and Medtronic, the cosponsors. He applauded the three companies for funding the silent diabetes substudy in the interest of science even though it had no commercial relevance to their stent businesses.
AT EUROPCR
Key clinical point:
Major finding: One-third of patients undergoing PCI have unsuspected silent diabetes or prediabetes, placing them at increased risk for major adverse cardiac events.
Data source: This prospective observational study included 988 patients not known to have diabetes who underwent screening for abnormal glucose tolerance 6 weeks after PCI with stenting.
Disclosures: The study was cosponsored by Biotronik, Boston Scientific, and Medtronic.
Predicting functional outcome after pediatric osteomyelitis
MADRID – Ninety percent of children with acute hematogenous osteomyelitis will do fine after their initial course of antibiotics and don’t require long-term follow-up; and the other 10% can be identified within the first few days of hospitalization, Lawson A. Copley, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
The tool that enables physicians to distinguish the 10% of children at high risk for severe orthopedic sequelae is a validated severity of illness score that can be determined within the first several days of hospitalization. The 0-10 score, developed by Dr. Copley and his coinvestigators (J Pediatr Orthop. 2016 Oct 12. doi: 10.1097/BPO.0000000000000879), awards points for the patient’s initial C-reactive protein level, the C-reactive protein levels on hospital days 2-3 and 4-5, the number of febrile days on antibiotic therapy, the band percentage of WBC, ICU admission, and disseminated disease such as endocarditis, septic pulmonary embolism, and deep venous thrombosis.
There is a dearth of long-term follow-up studies of pediatric osteomyelitis. To address this unmet need, he and his coinvestigators have enrolled 198 children with acute hematogenous osteomyelitis in an ongoing prospective study. All were treated with antibiotics until clinical and laboratory resolution of the infection and achievement of a normal erythrocyte sedimentation rate. All patients are being followed in a specialized multidisciplinary clinic at Texas Scottish Rite Hospital for Children directed by Dr. Copley. To date, 118 patients have been seen for their 2-year follow-up visit, which includes radiographs of the previous infection site, an orthopedic exam, and completion of the Pediatric Quality of Life Inventory and the Pediatric Outcomes Data Collection Instrument.
At follow-up, the children fell into three broad categories. Ten percent had severe radiographic and/or clinical sequelae such as limb length discrepancy, visible deformity, limited range of motion, osteonecrosis, physeal arrest, or joint destruction. Roughly 40% had complete resolution with normal function and no growth disturbance or other sequelae. And 50% had clinical resolution with a completely normal physical exam and excellent outcome measures, but minimal radiographic sequelae, mainly consisting of central physeal tenting.
“We think that they’re probably a low-risk group,” he said of that last group.
Children with severe sequelae had greater severity of illness at presentation and a more complicated course of initial therapy than those with complete resolution at 2 years of follow-up. Their mean severity of illness score was 4.9, compared with 1.8 in the 40% of children with complete resolution and 3.4 in those with mild radiographic sequelae.
In a univariate logistic regression analysis, each point increase in initial disease severity score was associated with a 20% bump in the risk of developing severe sequelae, with a predictive area under the curve of 0.67. A multivariate logistic regression analysis identified other independent predictors of severe sequelae: age below 6 years, being culture positive for methicillin-resistant Streptococcus aureus, and osteomyelitis contiguous with septic arthritis or abscess, which ultimately led to osteonecrosis and destruction. Incorporating these additional risk factors along with the initial severity of illness score improved the predictive area under the curve to 0.85.
About one-half of patients seen in the pediatric osteomyelitis clinic were bacteremic on admission, and of those, roughly half continued to be bacteremic despite antibiotic therapy. However, there was no difference in the prevalence of bacteremia between the groups with mild versus severe illness.
Asked how introduction of the severity-of-illness score has affected his surgical approach, Dr. Copley said he has become selectively more surgically aggressive.
“A lot of our children have abscesses that are pretty substantial,” he noted. “We’ve learned the hard way. I’ve been doing this for about 14 years now, and initially I used to do a lot of simple debridement of the infection. Now we’re much more extensive in our approach, so we do fewer surgeries, but those surgeries are more extensive.”
Dr. Copley reported having no financial conflicts regarding his study.
MADRID – Ninety percent of children with acute hematogenous osteomyelitis will do fine after their initial course of antibiotics and don’t require long-term follow-up; and the other 10% can be identified within the first few days of hospitalization, Lawson A. Copley, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
The tool that enables physicians to distinguish the 10% of children at high risk for severe orthopedic sequelae is a validated severity of illness score that can be determined within the first several days of hospitalization. The 0-10 score, developed by Dr. Copley and his coinvestigators (J Pediatr Orthop. 2016 Oct 12. doi: 10.1097/BPO.0000000000000879), awards points for the patient’s initial C-reactive protein level, the C-reactive protein levels on hospital days 2-3 and 4-5, the number of febrile days on antibiotic therapy, the band percentage of WBC, ICU admission, and disseminated disease such as endocarditis, septic pulmonary embolism, and deep venous thrombosis.
There is a dearth of long-term follow-up studies of pediatric osteomyelitis. To address this unmet need, he and his coinvestigators have enrolled 198 children with acute hematogenous osteomyelitis in an ongoing prospective study. All were treated with antibiotics until clinical and laboratory resolution of the infection and achievement of a normal erythrocyte sedimentation rate. All patients are being followed in a specialized multidisciplinary clinic at Texas Scottish Rite Hospital for Children directed by Dr. Copley. To date, 118 patients have been seen for their 2-year follow-up visit, which includes radiographs of the previous infection site, an orthopedic exam, and completion of the Pediatric Quality of Life Inventory and the Pediatric Outcomes Data Collection Instrument.
At follow-up, the children fell into three broad categories. Ten percent had severe radiographic and/or clinical sequelae such as limb length discrepancy, visible deformity, limited range of motion, osteonecrosis, physeal arrest, or joint destruction. Roughly 40% had complete resolution with normal function and no growth disturbance or other sequelae. And 50% had clinical resolution with a completely normal physical exam and excellent outcome measures, but minimal radiographic sequelae, mainly consisting of central physeal tenting.
“We think that they’re probably a low-risk group,” he said of that last group.
Children with severe sequelae had greater severity of illness at presentation and a more complicated course of initial therapy than those with complete resolution at 2 years of follow-up. Their mean severity of illness score was 4.9, compared with 1.8 in the 40% of children with complete resolution and 3.4 in those with mild radiographic sequelae.
In a univariate logistic regression analysis, each point increase in initial disease severity score was associated with a 20% bump in the risk of developing severe sequelae, with a predictive area under the curve of 0.67. A multivariate logistic regression analysis identified other independent predictors of severe sequelae: age below 6 years, being culture positive for methicillin-resistant Streptococcus aureus, and osteomyelitis contiguous with septic arthritis or abscess, which ultimately led to osteonecrosis and destruction. Incorporating these additional risk factors along with the initial severity of illness score improved the predictive area under the curve to 0.85.
About one-half of patients seen in the pediatric osteomyelitis clinic were bacteremic on admission, and of those, roughly half continued to be bacteremic despite antibiotic therapy. However, there was no difference in the prevalence of bacteremia between the groups with mild versus severe illness.
Asked how introduction of the severity-of-illness score has affected his surgical approach, Dr. Copley said he has become selectively more surgically aggressive.
“A lot of our children have abscesses that are pretty substantial,” he noted. “We’ve learned the hard way. I’ve been doing this for about 14 years now, and initially I used to do a lot of simple debridement of the infection. Now we’re much more extensive in our approach, so we do fewer surgeries, but those surgeries are more extensive.”
Dr. Copley reported having no financial conflicts regarding his study.
MADRID – Ninety percent of children with acute hematogenous osteomyelitis will do fine after their initial course of antibiotics and don’t require long-term follow-up; and the other 10% can be identified within the first few days of hospitalization, Lawson A. Copley, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
The tool that enables physicians to distinguish the 10% of children at high risk for severe orthopedic sequelae is a validated severity of illness score that can be determined within the first several days of hospitalization. The 0-10 score, developed by Dr. Copley and his coinvestigators (J Pediatr Orthop. 2016 Oct 12. doi: 10.1097/BPO.0000000000000879), awards points for the patient’s initial C-reactive protein level, the C-reactive protein levels on hospital days 2-3 and 4-5, the number of febrile days on antibiotic therapy, the band percentage of WBC, ICU admission, and disseminated disease such as endocarditis, septic pulmonary embolism, and deep venous thrombosis.
There is a dearth of long-term follow-up studies of pediatric osteomyelitis. To address this unmet need, he and his coinvestigators have enrolled 198 children with acute hematogenous osteomyelitis in an ongoing prospective study. All were treated with antibiotics until clinical and laboratory resolution of the infection and achievement of a normal erythrocyte sedimentation rate. All patients are being followed in a specialized multidisciplinary clinic at Texas Scottish Rite Hospital for Children directed by Dr. Copley. To date, 118 patients have been seen for their 2-year follow-up visit, which includes radiographs of the previous infection site, an orthopedic exam, and completion of the Pediatric Quality of Life Inventory and the Pediatric Outcomes Data Collection Instrument.
At follow-up, the children fell into three broad categories. Ten percent had severe radiographic and/or clinical sequelae such as limb length discrepancy, visible deformity, limited range of motion, osteonecrosis, physeal arrest, or joint destruction. Roughly 40% had complete resolution with normal function and no growth disturbance or other sequelae. And 50% had clinical resolution with a completely normal physical exam and excellent outcome measures, but minimal radiographic sequelae, mainly consisting of central physeal tenting.
“We think that they’re probably a low-risk group,” he said of that last group.
Children with severe sequelae had greater severity of illness at presentation and a more complicated course of initial therapy than those with complete resolution at 2 years of follow-up. Their mean severity of illness score was 4.9, compared with 1.8 in the 40% of children with complete resolution and 3.4 in those with mild radiographic sequelae.
In a univariate logistic regression analysis, each point increase in initial disease severity score was associated with a 20% bump in the risk of developing severe sequelae, with a predictive area under the curve of 0.67. A multivariate logistic regression analysis identified other independent predictors of severe sequelae: age below 6 years, being culture positive for methicillin-resistant Streptococcus aureus, and osteomyelitis contiguous with septic arthritis or abscess, which ultimately led to osteonecrosis and destruction. Incorporating these additional risk factors along with the initial severity of illness score improved the predictive area under the curve to 0.85.
About one-half of patients seen in the pediatric osteomyelitis clinic were bacteremic on admission, and of those, roughly half continued to be bacteremic despite antibiotic therapy. However, there was no difference in the prevalence of bacteremia between the groups with mild versus severe illness.
Asked how introduction of the severity-of-illness score has affected his surgical approach, Dr. Copley said he has become selectively more surgically aggressive.
“A lot of our children have abscesses that are pretty substantial,” he noted. “We’ve learned the hard way. I’ve been doing this for about 14 years now, and initially I used to do a lot of simple debridement of the infection. Now we’re much more extensive in our approach, so we do fewer surgeries, but those surgeries are more extensive.”
Dr. Copley reported having no financial conflicts regarding his study.
AT ESPID 2017
Key clinical point:
Major finding: Ninety percent of children with acute hematogenous osteomyelitis require no long-term follow-up after their initial antibiotic therapy.
Data source: An ongoing prospective study of 118 children followed for 2 years after initial treatment of acute hematogenous osteomyelitis.
Disclosures: The study presenter reported having no financial conflicts.
Female predisposition to anxiety disorders may have prenatal origin
SAN FRANCISCO – Why are anxiety disorders twice as prevalent in women as in men? As in Hawaiian hula dancing, the expressive hands may tell the tale.
The ratio of the length of the index finger to ring finger – known as the 2D:4D ratio – is a physical trait that remains stable across the lifetimes of males and females. It’s also a reliable indicator of prenatal exposure to androgens. In female college students, the higher the 2D:4D ratio, the greater their level of ruminative thinking, which is known to be both a risk factor and maintenance factor for anxiety, Ellie Shuo Jin reported at the annual conference of the Anxiety and Depression Association of America.
The findings shed new light on the relationship between testosterone and anxiety disorders, according to Ms. Jin, a doctoral student at the University of Texas, Austin. The hormone previously has been linked to reduced levels of anxiety, an observation consistent with the lower prevalence of anxiety disorders in men. However, it has been unclear whether prenatal exposure to testosterone, which encourages organizational effects, or the activational effects of postnatal exposure to the hormone is most protective against anxiety disorders.
Ms. Jin found that prenatal testosterone exposure as reflected in a low 2D:4D ratio was associated with a lower level of repetitive negative thinking as measured using the Perseverative Thinking Questionnaire but only in the female students.
She reported having no financial conflicts of interest regarding her study.
SAN FRANCISCO – Why are anxiety disorders twice as prevalent in women as in men? As in Hawaiian hula dancing, the expressive hands may tell the tale.
The ratio of the length of the index finger to ring finger – known as the 2D:4D ratio – is a physical trait that remains stable across the lifetimes of males and females. It’s also a reliable indicator of prenatal exposure to androgens. In female college students, the higher the 2D:4D ratio, the greater their level of ruminative thinking, which is known to be both a risk factor and maintenance factor for anxiety, Ellie Shuo Jin reported at the annual conference of the Anxiety and Depression Association of America.
The findings shed new light on the relationship between testosterone and anxiety disorders, according to Ms. Jin, a doctoral student at the University of Texas, Austin. The hormone previously has been linked to reduced levels of anxiety, an observation consistent with the lower prevalence of anxiety disorders in men. However, it has been unclear whether prenatal exposure to testosterone, which encourages organizational effects, or the activational effects of postnatal exposure to the hormone is most protective against anxiety disorders.
Ms. Jin found that prenatal testosterone exposure as reflected in a low 2D:4D ratio was associated with a lower level of repetitive negative thinking as measured using the Perseverative Thinking Questionnaire but only in the female students.
She reported having no financial conflicts of interest regarding her study.
SAN FRANCISCO – Why are anxiety disorders twice as prevalent in women as in men? As in Hawaiian hula dancing, the expressive hands may tell the tale.
The ratio of the length of the index finger to ring finger – known as the 2D:4D ratio – is a physical trait that remains stable across the lifetimes of males and females. It’s also a reliable indicator of prenatal exposure to androgens. In female college students, the higher the 2D:4D ratio, the greater their level of ruminative thinking, which is known to be both a risk factor and maintenance factor for anxiety, Ellie Shuo Jin reported at the annual conference of the Anxiety and Depression Association of America.
The findings shed new light on the relationship between testosterone and anxiety disorders, according to Ms. Jin, a doctoral student at the University of Texas, Austin. The hormone previously has been linked to reduced levels of anxiety, an observation consistent with the lower prevalence of anxiety disorders in men. However, it has been unclear whether prenatal exposure to testosterone, which encourages organizational effects, or the activational effects of postnatal exposure to the hormone is most protective against anxiety disorders.
Ms. Jin found that prenatal testosterone exposure as reflected in a low 2D:4D ratio was associated with a lower level of repetitive negative thinking as measured using the Perseverative Thinking Questionnaire but only in the female students.
She reported having no financial conflicts of interest regarding her study.
AT THE ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: The higher the ratio of the length of the index finger to the ring finger on the left hand, the greater the predisposition to repetitive negative thinking in women but not in men.
Data source: This cross-sectional study correlated the 2D:4D digit ratio to levels of repetitive negative thinking in 103 college students.
Disclosures: The presenter reported having no financial conflicts regarding her study.
Rapid lab test predicts pediatric pneumococcal pneumonia severity
MADRID – Thomsen-Friedenreich antigen activation is useful as a novel early predictor of empyema in pediatric community-acquired pneumonia, Chi-Jung Chang, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
In her retrospective study of 142 Taiwanese children and adolescents hospitalized for community-acquired pneumonia (CAP), Thomsen-Friedenreich antigen (TA) activation had 100% specificity, 100% positive predictive value, and 31% sensitivity for Streptococcus pneumoniae as the causative microorganism.
Moreover, the higher the TA activation titer, the more severe the pneumonia complications that followed, according to Dr. Chang of MacKay Children’s Hospital in Taipei, Taiwan.
The value of this lab test lies in its speed and accuracy for detection of S. pneumoniae CAP. Conventional culture methods are relatively slow and have poor sensitivity, because a child often already has been on empiric antimicrobial therapy and the culture specimen is unwittingly obtained from a sterile site, she explained.
Twenty-two of the 142 children and adolescents hospitalized for lobar CAP were TA activation positive at admission. They were considerably sicker than were the 120 patients who were TA activation negative. Their initial C-reactive protein level was 31.9 mg/dL, twice that of the negative group. Their peak CRP during the hospital stay was significantly higher as well, as was their peak WBC.
Hospital lengths of stay were longer in the TA activation–positive group. Eighteen of 22 TA activation–positive patients (82%) were admitted to the ICU for an average of 8 days, compared with 9% of the negative group.
All TA activation–positive patients had complicated pneumonia with parapneumonic effusions, empyema, necrotizing pneumonia, and/or lung abscesses, as did 36% of the negative group.
S. pneumoniae was the most common pathogen in this study of CAP. It was the responsible microbe in all 22 of the TA activation–positive patients and in 29% of the TA activation–negative ones. The most common serotype in the TA activation group was 19A, which accounted for 12 of the 22 cases. This also was the predominant serotype found in CAP across all Taiwan during the first half of this decade, when the study took place.
In a multivariate logistic regression analysis, TA activation was far and away the strongest independent predictor of empyema, with an associated 15.8-fold increased risk. The other two independent predictors – longer fever duration prior to hospitalization and a higher initial CRP level – were far less robust, according to Dr. Chang.
How TA activation works as a predictor
TA is present on the surface of erythrocytes, platelets, and glomeruli, but ordinarily it is covered by a layer of N-acetylneuraminic acid. Streptococcus pneumoniae produces circulating neuraminidases, which cleave the N-acetylneuraminic acid and expose the underlying TA. The TA then quickly becomes activated through interaction with the anti-TA antibodies, which are normally present in plasma. Once activated, the TA stays so for weeks to months.
Other neuraminidase-producing microorganisms include Clostridium perfringens, Escherichia coli, and Bacteroides.
Dr. Chang and her colleagues used the peanut lectin agglutination method in their TA activation testing.
She reported having no financial conflicts regarding her study.
MADRID – Thomsen-Friedenreich antigen activation is useful as a novel early predictor of empyema in pediatric community-acquired pneumonia, Chi-Jung Chang, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
In her retrospective study of 142 Taiwanese children and adolescents hospitalized for community-acquired pneumonia (CAP), Thomsen-Friedenreich antigen (TA) activation had 100% specificity, 100% positive predictive value, and 31% sensitivity for Streptococcus pneumoniae as the causative microorganism.
Moreover, the higher the TA activation titer, the more severe the pneumonia complications that followed, according to Dr. Chang of MacKay Children’s Hospital in Taipei, Taiwan.
The value of this lab test lies in its speed and accuracy for detection of S. pneumoniae CAP. Conventional culture methods are relatively slow and have poor sensitivity, because a child often already has been on empiric antimicrobial therapy and the culture specimen is unwittingly obtained from a sterile site, she explained.
Twenty-two of the 142 children and adolescents hospitalized for lobar CAP were TA activation positive at admission. They were considerably sicker than were the 120 patients who were TA activation negative. Their initial C-reactive protein level was 31.9 mg/dL, twice that of the negative group. Their peak CRP during the hospital stay was significantly higher as well, as was their peak WBC.
Hospital lengths of stay were longer in the TA activation–positive group. Eighteen of 22 TA activation–positive patients (82%) were admitted to the ICU for an average of 8 days, compared with 9% of the negative group.
All TA activation–positive patients had complicated pneumonia with parapneumonic effusions, empyema, necrotizing pneumonia, and/or lung abscesses, as did 36% of the negative group.
S. pneumoniae was the most common pathogen in this study of CAP. It was the responsible microbe in all 22 of the TA activation–positive patients and in 29% of the TA activation–negative ones. The most common serotype in the TA activation group was 19A, which accounted for 12 of the 22 cases. This also was the predominant serotype found in CAP across all Taiwan during the first half of this decade, when the study took place.
In a multivariate logistic regression analysis, TA activation was far and away the strongest independent predictor of empyema, with an associated 15.8-fold increased risk. The other two independent predictors – longer fever duration prior to hospitalization and a higher initial CRP level – were far less robust, according to Dr. Chang.
How TA activation works as a predictor
TA is present on the surface of erythrocytes, platelets, and glomeruli, but ordinarily it is covered by a layer of N-acetylneuraminic acid. Streptococcus pneumoniae produces circulating neuraminidases, which cleave the N-acetylneuraminic acid and expose the underlying TA. The TA then quickly becomes activated through interaction with the anti-TA antibodies, which are normally present in plasma. Once activated, the TA stays so for weeks to months.
Other neuraminidase-producing microorganisms include Clostridium perfringens, Escherichia coli, and Bacteroides.
Dr. Chang and her colleagues used the peanut lectin agglutination method in their TA activation testing.
She reported having no financial conflicts regarding her study.
MADRID – Thomsen-Friedenreich antigen activation is useful as a novel early predictor of empyema in pediatric community-acquired pneumonia, Chi-Jung Chang, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
In her retrospective study of 142 Taiwanese children and adolescents hospitalized for community-acquired pneumonia (CAP), Thomsen-Friedenreich antigen (TA) activation had 100% specificity, 100% positive predictive value, and 31% sensitivity for Streptococcus pneumoniae as the causative microorganism.
Moreover, the higher the TA activation titer, the more severe the pneumonia complications that followed, according to Dr. Chang of MacKay Children’s Hospital in Taipei, Taiwan.
The value of this lab test lies in its speed and accuracy for detection of S. pneumoniae CAP. Conventional culture methods are relatively slow and have poor sensitivity, because a child often already has been on empiric antimicrobial therapy and the culture specimen is unwittingly obtained from a sterile site, she explained.
Twenty-two of the 142 children and adolescents hospitalized for lobar CAP were TA activation positive at admission. They were considerably sicker than were the 120 patients who were TA activation negative. Their initial C-reactive protein level was 31.9 mg/dL, twice that of the negative group. Their peak CRP during the hospital stay was significantly higher as well, as was their peak WBC.
Hospital lengths of stay were longer in the TA activation–positive group. Eighteen of 22 TA activation–positive patients (82%) were admitted to the ICU for an average of 8 days, compared with 9% of the negative group.
All TA activation–positive patients had complicated pneumonia with parapneumonic effusions, empyema, necrotizing pneumonia, and/or lung abscesses, as did 36% of the negative group.
S. pneumoniae was the most common pathogen in this study of CAP. It was the responsible microbe in all 22 of the TA activation–positive patients and in 29% of the TA activation–negative ones. The most common serotype in the TA activation group was 19A, which accounted for 12 of the 22 cases. This also was the predominant serotype found in CAP across all Taiwan during the first half of this decade, when the study took place.
In a multivariate logistic regression analysis, TA activation was far and away the strongest independent predictor of empyema, with an associated 15.8-fold increased risk. The other two independent predictors – longer fever duration prior to hospitalization and a higher initial CRP level – were far less robust, according to Dr. Chang.
How TA activation works as a predictor
TA is present on the surface of erythrocytes, platelets, and glomeruli, but ordinarily it is covered by a layer of N-acetylneuraminic acid. Streptococcus pneumoniae produces circulating neuraminidases, which cleave the N-acetylneuraminic acid and expose the underlying TA. The TA then quickly becomes activated through interaction with the anti-TA antibodies, which are normally present in plasma. Once activated, the TA stays so for weeks to months.
Other neuraminidase-producing microorganisms include Clostridium perfringens, Escherichia coli, and Bacteroides.
Dr. Chang and her colleagues used the peanut lectin agglutination method in their TA activation testing.
She reported having no financial conflicts regarding her study.
AT ESPID 2017
Key clinical point:
Major finding: A positive Thomsen-Friedenreich antigen activation test in pediatric community-acquired pneumonia had 100% specificity, 100% positive predictive value, and 31% sensitivity for S. pneumoniae as the causative microorganism.
Data source: A retrospective study of 142 Taiwanese children and teens hospitalized for lobular community-acquired pneumonia.
Disclosures: The study presenter reported having no financial conflicts of interest.
Adolescent HCV may be on the cusp of a revolution
MADRID – One hundred percent of adolescents with chronic hepatitis C virus genotypes 1 or 4 had no detectable viral RNA present 12 weeks after completing a course of direct-acting antiviral therapy in the phase III ZIRCON study, Stefan Wirth, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Direct-acting antiviral therapy has revolutionized the treatment of chronic hepatitis C virus (HCV) in adults over the past several years as a result of its unprecedented efficacy, safety, brevity, and ease of use. The Study to Evaluate Treatment of Hepatitis C Virus Infection in Pediatric Subjects, also known as ZIRCON, is the first clinical trial to report treatment results in adolescents, noted Dr. Wirth, a pediatric hepatologist at the University of Witten/Herdecke in Germany.
The trial is an ongoing international open-label study of 12 or 24 weeks of ombitasvir/paritaprevir/ritonavir (Viekira) with or without dasabuvir (Exviera) and with or without ribavirin in 3- to 17-year-olds infected with HCV genotypes 1 or 4. Dr. Wirth presented short-term efficacy, safety, and pharmacokinetic results in 38 adolescents, one-third of whom previously had undergone unsuccessful pegylated interferon-based treatment.
The primary efficacy outcome was a sustained virologic response – that is, no detectable virus – 12 weeks after completing the course of treatment. This was achieved in all patients.
The multidrug regimens were well tolerated. There were no serious adverse events, no grade 3 or 4 laboratory abnormalities, and no study discontinuations tied to adverse events.
Dosing was the same as in adults: ombitasvir/paritaprevir/ritonavir at 25 mg/150 mg/100 mg once daily, dasabuvir at 250 mg twice daily, and weight-based ribavirin. The pharmacokinetic endpoints – maximum plasma concentration, trough concentration, and the area under the plasma concentration-time curve – were comparable to those seen in adults.
“That’s an important thing, because it means there doesn’t need to be dosage adjustment in treating adolescents,” Dr. Wirth said.
The seven patients with HCV genotype 4 infection with or without cirrhosis received 12 weeks of ombitasvir/paritaprevir/ritonavir and ribavirin. The 10 teens with genotype 1b infection with or without cirrhosis got 12 weeks of ombitasvir/paritaprevir/ritonavir with dasabuvir, as did 12 with genotype 1a or 1b disease without cirrhosis. Eight patients with genotype 1a disease without cirrhosis received ombitasvir/paritaprevir/ritonavir with dasabuvir and ribavirin.
Asked whether he would recommend that physicians begin treating HCV-infected teens with direct-acting antivirals, Dr. Wirth urged his colleagues to refrain.
“I don’t recommend any treatment now. We have to wait for approval of this new therapy in the adolescents. We should no longer use pegylated interferon with ribavirin, because it’s obsolete. There’s no harm in waiting for the next 1 or 2 years for the adolescent patients to be able to have an indication for the new direct-acting antiviral therapies,” he said.
ZIRCON outcomes in HCV-infected children aged 3-8 and 9-11 years will be reported later. All study participants will be followed for about 3.5 years after completion of treatment.
Dr. Wirth reported receiving research grants from AbbVie, which is funding the ZIRCON study.
MADRID – One hundred percent of adolescents with chronic hepatitis C virus genotypes 1 or 4 had no detectable viral RNA present 12 weeks after completing a course of direct-acting antiviral therapy in the phase III ZIRCON study, Stefan Wirth, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Direct-acting antiviral therapy has revolutionized the treatment of chronic hepatitis C virus (HCV) in adults over the past several years as a result of its unprecedented efficacy, safety, brevity, and ease of use. The Study to Evaluate Treatment of Hepatitis C Virus Infection in Pediatric Subjects, also known as ZIRCON, is the first clinical trial to report treatment results in adolescents, noted Dr. Wirth, a pediatric hepatologist at the University of Witten/Herdecke in Germany.
The trial is an ongoing international open-label study of 12 or 24 weeks of ombitasvir/paritaprevir/ritonavir (Viekira) with or without dasabuvir (Exviera) and with or without ribavirin in 3- to 17-year-olds infected with HCV genotypes 1 or 4. Dr. Wirth presented short-term efficacy, safety, and pharmacokinetic results in 38 adolescents, one-third of whom previously had undergone unsuccessful pegylated interferon-based treatment.
The primary efficacy outcome was a sustained virologic response – that is, no detectable virus – 12 weeks after completing the course of treatment. This was achieved in all patients.
The multidrug regimens were well tolerated. There were no serious adverse events, no grade 3 or 4 laboratory abnormalities, and no study discontinuations tied to adverse events.
Dosing was the same as in adults: ombitasvir/paritaprevir/ritonavir at 25 mg/150 mg/100 mg once daily, dasabuvir at 250 mg twice daily, and weight-based ribavirin. The pharmacokinetic endpoints – maximum plasma concentration, trough concentration, and the area under the plasma concentration-time curve – were comparable to those seen in adults.
“That’s an important thing, because it means there doesn’t need to be dosage adjustment in treating adolescents,” Dr. Wirth said.
The seven patients with HCV genotype 4 infection with or without cirrhosis received 12 weeks of ombitasvir/paritaprevir/ritonavir and ribavirin. The 10 teens with genotype 1b infection with or without cirrhosis got 12 weeks of ombitasvir/paritaprevir/ritonavir with dasabuvir, as did 12 with genotype 1a or 1b disease without cirrhosis. Eight patients with genotype 1a disease without cirrhosis received ombitasvir/paritaprevir/ritonavir with dasabuvir and ribavirin.
Asked whether he would recommend that physicians begin treating HCV-infected teens with direct-acting antivirals, Dr. Wirth urged his colleagues to refrain.
“I don’t recommend any treatment now. We have to wait for approval of this new therapy in the adolescents. We should no longer use pegylated interferon with ribavirin, because it’s obsolete. There’s no harm in waiting for the next 1 or 2 years for the adolescent patients to be able to have an indication for the new direct-acting antiviral therapies,” he said.
ZIRCON outcomes in HCV-infected children aged 3-8 and 9-11 years will be reported later. All study participants will be followed for about 3.5 years after completion of treatment.
Dr. Wirth reported receiving research grants from AbbVie, which is funding the ZIRCON study.
MADRID – One hundred percent of adolescents with chronic hepatitis C virus genotypes 1 or 4 had no detectable viral RNA present 12 weeks after completing a course of direct-acting antiviral therapy in the phase III ZIRCON study, Stefan Wirth, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Direct-acting antiviral therapy has revolutionized the treatment of chronic hepatitis C virus (HCV) in adults over the past several years as a result of its unprecedented efficacy, safety, brevity, and ease of use. The Study to Evaluate Treatment of Hepatitis C Virus Infection in Pediatric Subjects, also known as ZIRCON, is the first clinical trial to report treatment results in adolescents, noted Dr. Wirth, a pediatric hepatologist at the University of Witten/Herdecke in Germany.
The trial is an ongoing international open-label study of 12 or 24 weeks of ombitasvir/paritaprevir/ritonavir (Viekira) with or without dasabuvir (Exviera) and with or without ribavirin in 3- to 17-year-olds infected with HCV genotypes 1 or 4. Dr. Wirth presented short-term efficacy, safety, and pharmacokinetic results in 38 adolescents, one-third of whom previously had undergone unsuccessful pegylated interferon-based treatment.
The primary efficacy outcome was a sustained virologic response – that is, no detectable virus – 12 weeks after completing the course of treatment. This was achieved in all patients.
The multidrug regimens were well tolerated. There were no serious adverse events, no grade 3 or 4 laboratory abnormalities, and no study discontinuations tied to adverse events.
Dosing was the same as in adults: ombitasvir/paritaprevir/ritonavir at 25 mg/150 mg/100 mg once daily, dasabuvir at 250 mg twice daily, and weight-based ribavirin. The pharmacokinetic endpoints – maximum plasma concentration, trough concentration, and the area under the plasma concentration-time curve – were comparable to those seen in adults.
“That’s an important thing, because it means there doesn’t need to be dosage adjustment in treating adolescents,” Dr. Wirth said.
The seven patients with HCV genotype 4 infection with or without cirrhosis received 12 weeks of ombitasvir/paritaprevir/ritonavir and ribavirin. The 10 teens with genotype 1b infection with or without cirrhosis got 12 weeks of ombitasvir/paritaprevir/ritonavir with dasabuvir, as did 12 with genotype 1a or 1b disease without cirrhosis. Eight patients with genotype 1a disease without cirrhosis received ombitasvir/paritaprevir/ritonavir with dasabuvir and ribavirin.
Asked whether he would recommend that physicians begin treating HCV-infected teens with direct-acting antivirals, Dr. Wirth urged his colleagues to refrain.
“I don’t recommend any treatment now. We have to wait for approval of this new therapy in the adolescents. We should no longer use pegylated interferon with ribavirin, because it’s obsolete. There’s no harm in waiting for the next 1 or 2 years for the adolescent patients to be able to have an indication for the new direct-acting antiviral therapies,” he said.
ZIRCON outcomes in HCV-infected children aged 3-8 and 9-11 years will be reported later. All study participants will be followed for about 3.5 years after completion of treatment.
Dr. Wirth reported receiving research grants from AbbVie, which is funding the ZIRCON study.
AT ESPID 2017
Key clinical point:
Major finding: Twelve weeks after adolescents with hepatitis C genotype 1 or 4 virus infection completed a course of direct-acting antiviral therapy, none had any detectable virus.
Data source: Interim report from an ongoing international open-label phase III study of 38 adolescents with chronic hepatitis C infection treated with direct-acting antiviral agents.
Disclosures: The study presenter reported receiving research grants from AbbVie, which is funding the ongoing ZIRCON study.
Biomarker predicts prolonged depression in breast cancer patients
SAN FRANCISCO – Nearly 40% of breast cancer patients experience prolonged depression lasting for at least 16 months after diagnosis of their malignancy; those at increased risk may be identifiable in a timely way by their exaggerated cortisol awakening response when measured after surgery but before adjuvant therapy, according to Kate R. Kuhlman, PhD.
“There are several psychological interventions that mitigate depressive symptoms and psychologic distress in women with breast cancer. This time period immediately following cancer diagnosis and surgery may be the optimal time to intervene,” said Dr. Kuhlman, a psychologist at the University of California, Los Angeles.
She presented a prospective study of 135 women with breast cancer who collected saliva samples for analysis of hypothalamic-pituitary-adrenal axis functioning on 3 consecutive days after their primary surgery but prior to starting adjuvant therapy. Samples were obtained on each of the 3 days upon awakening, 30 minutes later, 8 hours later, and at bedtime. The women also completed the Center for Epidemiologic Studies Depression Scale (CES-D) then and again 6 months after completing their breast cancer treatment.
At baseline, 45 of the 135 women scored 16 points or higher out of a possible 60 on the 20-question CES-D, indicative of clinically significant depression. Hypothalamic-pituitary-adrenal axis functioning wasn’t associated with depressive symptoms at that time. Importantly, however, one measure of baseline HPA axis functioning – the cortisol awakening response – proved to be associated with an increase in depressive symptoms over time, Dr. Kuhlman reported.
In a multivariate analysis adjusted for age, breast cancer stage, type of surgery, and forms of adjuvant therapy, a 1-standard-deviation increase above the mean in baseline cortisol awakening response was associated with a 6-point increase in CES-D score at follow-up 6 months after completion of breast cancer therapy. This association was seen only in the 90 women without significant depressive symptoms at baseline. And that’s exactly the population where a predictive biologic marker for future depression is most needed, Dr. Kuhlman said at the annual conference of the Anxiety and Depression Association of America.
“The people at highest risk of depressive symptoms in the future are the ones who have the most symptoms now. They’re easy to identify. We have good reliable measures. But then there are also people at risk whom we would miss by using those measures because they don’t have high symptoms right now,” the psychologist explained.
She and her coinvestigators zeroed in on cortisol awakening response as a potential biomarker of increased future risk of depression because it reflects the adrenal gland’s sensitivity to adrenocorticotropic hormone and the gland’s ability to signal the pituitary to produce cortisol. This action is triggered when people go from sleep to awakening.
The next steps in this research are to confirm these novel findings and hunt for an alternative marker of adrenal sensitivity to adrenocorticotropic hormone that’s simpler than sending a waking saliva sample off to a laboratory.
This ongoing longitudinal study is funded by the National Cancer Institute. Dr. Kuhlman reported having no relevant financial conflicts.
SAN FRANCISCO – Nearly 40% of breast cancer patients experience prolonged depression lasting for at least 16 months after diagnosis of their malignancy; those at increased risk may be identifiable in a timely way by their exaggerated cortisol awakening response when measured after surgery but before adjuvant therapy, according to Kate R. Kuhlman, PhD.
“There are several psychological interventions that mitigate depressive symptoms and psychologic distress in women with breast cancer. This time period immediately following cancer diagnosis and surgery may be the optimal time to intervene,” said Dr. Kuhlman, a psychologist at the University of California, Los Angeles.
She presented a prospective study of 135 women with breast cancer who collected saliva samples for analysis of hypothalamic-pituitary-adrenal axis functioning on 3 consecutive days after their primary surgery but prior to starting adjuvant therapy. Samples were obtained on each of the 3 days upon awakening, 30 minutes later, 8 hours later, and at bedtime. The women also completed the Center for Epidemiologic Studies Depression Scale (CES-D) then and again 6 months after completing their breast cancer treatment.
At baseline, 45 of the 135 women scored 16 points or higher out of a possible 60 on the 20-question CES-D, indicative of clinically significant depression. Hypothalamic-pituitary-adrenal axis functioning wasn’t associated with depressive symptoms at that time. Importantly, however, one measure of baseline HPA axis functioning – the cortisol awakening response – proved to be associated with an increase in depressive symptoms over time, Dr. Kuhlman reported.
In a multivariate analysis adjusted for age, breast cancer stage, type of surgery, and forms of adjuvant therapy, a 1-standard-deviation increase above the mean in baseline cortisol awakening response was associated with a 6-point increase in CES-D score at follow-up 6 months after completion of breast cancer therapy. This association was seen only in the 90 women without significant depressive symptoms at baseline. And that’s exactly the population where a predictive biologic marker for future depression is most needed, Dr. Kuhlman said at the annual conference of the Anxiety and Depression Association of America.
“The people at highest risk of depressive symptoms in the future are the ones who have the most symptoms now. They’re easy to identify. We have good reliable measures. But then there are also people at risk whom we would miss by using those measures because they don’t have high symptoms right now,” the psychologist explained.
She and her coinvestigators zeroed in on cortisol awakening response as a potential biomarker of increased future risk of depression because it reflects the adrenal gland’s sensitivity to adrenocorticotropic hormone and the gland’s ability to signal the pituitary to produce cortisol. This action is triggered when people go from sleep to awakening.
The next steps in this research are to confirm these novel findings and hunt for an alternative marker of adrenal sensitivity to adrenocorticotropic hormone that’s simpler than sending a waking saliva sample off to a laboratory.
This ongoing longitudinal study is funded by the National Cancer Institute. Dr. Kuhlman reported having no relevant financial conflicts.
SAN FRANCISCO – Nearly 40% of breast cancer patients experience prolonged depression lasting for at least 16 months after diagnosis of their malignancy; those at increased risk may be identifiable in a timely way by their exaggerated cortisol awakening response when measured after surgery but before adjuvant therapy, according to Kate R. Kuhlman, PhD.
“There are several psychological interventions that mitigate depressive symptoms and psychologic distress in women with breast cancer. This time period immediately following cancer diagnosis and surgery may be the optimal time to intervene,” said Dr. Kuhlman, a psychologist at the University of California, Los Angeles.
She presented a prospective study of 135 women with breast cancer who collected saliva samples for analysis of hypothalamic-pituitary-adrenal axis functioning on 3 consecutive days after their primary surgery but prior to starting adjuvant therapy. Samples were obtained on each of the 3 days upon awakening, 30 minutes later, 8 hours later, and at bedtime. The women also completed the Center for Epidemiologic Studies Depression Scale (CES-D) then and again 6 months after completing their breast cancer treatment.
At baseline, 45 of the 135 women scored 16 points or higher out of a possible 60 on the 20-question CES-D, indicative of clinically significant depression. Hypothalamic-pituitary-adrenal axis functioning wasn’t associated with depressive symptoms at that time. Importantly, however, one measure of baseline HPA axis functioning – the cortisol awakening response – proved to be associated with an increase in depressive symptoms over time, Dr. Kuhlman reported.
In a multivariate analysis adjusted for age, breast cancer stage, type of surgery, and forms of adjuvant therapy, a 1-standard-deviation increase above the mean in baseline cortisol awakening response was associated with a 6-point increase in CES-D score at follow-up 6 months after completion of breast cancer therapy. This association was seen only in the 90 women without significant depressive symptoms at baseline. And that’s exactly the population where a predictive biologic marker for future depression is most needed, Dr. Kuhlman said at the annual conference of the Anxiety and Depression Association of America.
“The people at highest risk of depressive symptoms in the future are the ones who have the most symptoms now. They’re easy to identify. We have good reliable measures. But then there are also people at risk whom we would miss by using those measures because they don’t have high symptoms right now,” the psychologist explained.
She and her coinvestigators zeroed in on cortisol awakening response as a potential biomarker of increased future risk of depression because it reflects the adrenal gland’s sensitivity to adrenocorticotropic hormone and the gland’s ability to signal the pituitary to produce cortisol. This action is triggered when people go from sleep to awakening.
The next steps in this research are to confirm these novel findings and hunt for an alternative marker of adrenal sensitivity to adrenocorticotropic hormone that’s simpler than sending a waking saliva sample off to a laboratory.
This ongoing longitudinal study is funded by the National Cancer Institute. Dr. Kuhlman reported having no relevant financial conflicts.
AT ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: Nondepressed breast cancer patients whose saliva samples show an exaggerated cortisol awakening response when measured after surgery but before adjuvant therapy are at increased risk for developing prolonged depression as treatment progresses.
Data source: A prospective longitudinal study of 135 women with breast cancer.
Disclosures: This ongoing study is funded by the National Cancer Institute. The presenter reported having no relevant financial conflicts.
Complicated grief treatment gets better results than interpersonal psychotherapy
SAN FRANCISCO – The effectiveness of complicated grief treatment (CGT) rests, to a significant extent, on its capacity to reduce the grieving patient’s level of avoidance of reminders of the loss, Kim Glickman, PhD, said at the annual conference of the Anxiety and Depression Association of America.
Her psychotherapeutic mechanism-of-action study identified two other mediators of improvement in response to CGT: guilt related to the death and negative thoughts about the future. Patients who experienced significant reductions in levels of those variables during CGT were much more likely to ultimately be treatment responders.
The clinical implication of these findings is that psychotherapists should focus on reducing grief complications, such as avoidance behaviors and maladaptive thoughts, including blaming oneself or others for how the person died and seeing a hopeless future, according to Dr. Glickman, of City University of New York.
Complicated grief affects about 7% of bereaved individuals. It is characterized by prolonged emotional pain, intense sorrow, preoccupation with thoughts of the loved one, and persistent yearning. It is typically resistant to antidepressant therapy. In the DSM-5, it is called “persistent complex bereavement disorder” and is described in a chapter on provisional conditions for further study. Since it doesn’t have the status of a formal diagnostic entity, insurers typically will not pay for treatment of complicated grief reactions.
CGT has been shown to be effective in three randomized clinical trials. It is a manualized 16-session therapy that can be considered a form of cognitive-behavioral therapy with added elements of interpersonal psychotherapy and motivational interviewing. The focus is on encouraging adaptation to the loss by keeping grief center stage, honoring the person who died, and envisioning a future with possibilities for happiness, Dr. Glickman explained.
The mechanisms of action of CGT haven’t been well-characterized. This was the impetus for Dr. Glickman’s study, in which she analyzed data from the first randomized trial to demonstrate CGT’s effectiveness more than a decade ago (JAMA. 2005 Jun 1;293[21]:2601-8).
Among the 69 patients with complicated grief who completed 16 sessions of psychotherapy, the clinical response rate was 51% in the CGT group, compared with 28% in patients randomized to interpersonal psychotherapy. The number needed to treat with CGT was 4.3 in order to achieve a clinical response, defined as either a Clinical Global Impression–Improvement score of 1 or 2 or at least a 20-point improvement pre to post treatment on the self-rated Inventory of Complicated Grief.
In order to more closely examine potential mediators of clinical response, Dr. Glickman chose as her measure of change in feelings of guilt the study participants’ scores on the Structured Clinical Interview for Complicated Grief. To assess negative thoughts about the future, she relied on item two from the Beck Depression Inventory and, for avoidance behaviors, she used scores on the 15-item Grief-Related Avoidance Questionnaire.
CGT proved significantly more effective than interpersonal therapy at improving scores on all three of these instruments. The mediating effect was most robust for improvement in avoidance behaviors.
Dr. Glickman’s future research plans include looking at additional possible mediators of CGT’s efficacy, including change in emotion regulation, ideally assessed on a weekly basis during the course of treatment.
Complicated grief therapy was pioneered by therapists at Columbia University in New York. Dr. Glickman noted that more information about complicated grief and training in CGT is available at www.complicatedgrief.columbia.edu.
The randomized trial on which her analysis was based was funded by the National Institute of Mental Health. Dr. Glickman reported having no financial conflicts regarding her study.
SAN FRANCISCO – The effectiveness of complicated grief treatment (CGT) rests, to a significant extent, on its capacity to reduce the grieving patient’s level of avoidance of reminders of the loss, Kim Glickman, PhD, said at the annual conference of the Anxiety and Depression Association of America.
Her psychotherapeutic mechanism-of-action study identified two other mediators of improvement in response to CGT: guilt related to the death and negative thoughts about the future. Patients who experienced significant reductions in levels of those variables during CGT were much more likely to ultimately be treatment responders.
The clinical implication of these findings is that psychotherapists should focus on reducing grief complications, such as avoidance behaviors and maladaptive thoughts, including blaming oneself or others for how the person died and seeing a hopeless future, according to Dr. Glickman, of City University of New York.
Complicated grief affects about 7% of bereaved individuals. It is characterized by prolonged emotional pain, intense sorrow, preoccupation with thoughts of the loved one, and persistent yearning. It is typically resistant to antidepressant therapy. In the DSM-5, it is called “persistent complex bereavement disorder” and is described in a chapter on provisional conditions for further study. Since it doesn’t have the status of a formal diagnostic entity, insurers typically will not pay for treatment of complicated grief reactions.
CGT has been shown to be effective in three randomized clinical trials. It is a manualized 16-session therapy that can be considered a form of cognitive-behavioral therapy with added elements of interpersonal psychotherapy and motivational interviewing. The focus is on encouraging adaptation to the loss by keeping grief center stage, honoring the person who died, and envisioning a future with possibilities for happiness, Dr. Glickman explained.
The mechanisms of action of CGT haven’t been well-characterized. This was the impetus for Dr. Glickman’s study, in which she analyzed data from the first randomized trial to demonstrate CGT’s effectiveness more than a decade ago (JAMA. 2005 Jun 1;293[21]:2601-8).
Among the 69 patients with complicated grief who completed 16 sessions of psychotherapy, the clinical response rate was 51% in the CGT group, compared with 28% in patients randomized to interpersonal psychotherapy. The number needed to treat with CGT was 4.3 in order to achieve a clinical response, defined as either a Clinical Global Impression–Improvement score of 1 or 2 or at least a 20-point improvement pre to post treatment on the self-rated Inventory of Complicated Grief.
In order to more closely examine potential mediators of clinical response, Dr. Glickman chose as her measure of change in feelings of guilt the study participants’ scores on the Structured Clinical Interview for Complicated Grief. To assess negative thoughts about the future, she relied on item two from the Beck Depression Inventory and, for avoidance behaviors, she used scores on the 15-item Grief-Related Avoidance Questionnaire.
CGT proved significantly more effective than interpersonal therapy at improving scores on all three of these instruments. The mediating effect was most robust for improvement in avoidance behaviors.
Dr. Glickman’s future research plans include looking at additional possible mediators of CGT’s efficacy, including change in emotion regulation, ideally assessed on a weekly basis during the course of treatment.
Complicated grief therapy was pioneered by therapists at Columbia University in New York. Dr. Glickman noted that more information about complicated grief and training in CGT is available at www.complicatedgrief.columbia.edu.
The randomized trial on which her analysis was based was funded by the National Institute of Mental Health. Dr. Glickman reported having no financial conflicts regarding her study.
SAN FRANCISCO – The effectiveness of complicated grief treatment (CGT) rests, to a significant extent, on its capacity to reduce the grieving patient’s level of avoidance of reminders of the loss, Kim Glickman, PhD, said at the annual conference of the Anxiety and Depression Association of America.
Her psychotherapeutic mechanism-of-action study identified two other mediators of improvement in response to CGT: guilt related to the death and negative thoughts about the future. Patients who experienced significant reductions in levels of those variables during CGT were much more likely to ultimately be treatment responders.
The clinical implication of these findings is that psychotherapists should focus on reducing grief complications, such as avoidance behaviors and maladaptive thoughts, including blaming oneself or others for how the person died and seeing a hopeless future, according to Dr. Glickman, of City University of New York.
Complicated grief affects about 7% of bereaved individuals. It is characterized by prolonged emotional pain, intense sorrow, preoccupation with thoughts of the loved one, and persistent yearning. It is typically resistant to antidepressant therapy. In the DSM-5, it is called “persistent complex bereavement disorder” and is described in a chapter on provisional conditions for further study. Since it doesn’t have the status of a formal diagnostic entity, insurers typically will not pay for treatment of complicated grief reactions.
CGT has been shown to be effective in three randomized clinical trials. It is a manualized 16-session therapy that can be considered a form of cognitive-behavioral therapy with added elements of interpersonal psychotherapy and motivational interviewing. The focus is on encouraging adaptation to the loss by keeping grief center stage, honoring the person who died, and envisioning a future with possibilities for happiness, Dr. Glickman explained.
The mechanisms of action of CGT haven’t been well-characterized. This was the impetus for Dr. Glickman’s study, in which she analyzed data from the first randomized trial to demonstrate CGT’s effectiveness more than a decade ago (JAMA. 2005 Jun 1;293[21]:2601-8).
Among the 69 patients with complicated grief who completed 16 sessions of psychotherapy, the clinical response rate was 51% in the CGT group, compared with 28% in patients randomized to interpersonal psychotherapy. The number needed to treat with CGT was 4.3 in order to achieve a clinical response, defined as either a Clinical Global Impression–Improvement score of 1 or 2 or at least a 20-point improvement pre to post treatment on the self-rated Inventory of Complicated Grief.
In order to more closely examine potential mediators of clinical response, Dr. Glickman chose as her measure of change in feelings of guilt the study participants’ scores on the Structured Clinical Interview for Complicated Grief. To assess negative thoughts about the future, she relied on item two from the Beck Depression Inventory and, for avoidance behaviors, she used scores on the 15-item Grief-Related Avoidance Questionnaire.
CGT proved significantly more effective than interpersonal therapy at improving scores on all three of these instruments. The mediating effect was most robust for improvement in avoidance behaviors.
Dr. Glickman’s future research plans include looking at additional possible mediators of CGT’s efficacy, including change in emotion regulation, ideally assessed on a weekly basis during the course of treatment.
Complicated grief therapy was pioneered by therapists at Columbia University in New York. Dr. Glickman noted that more information about complicated grief and training in CGT is available at www.complicatedgrief.columbia.edu.
The randomized trial on which her analysis was based was funded by the National Institute of Mental Health. Dr. Glickman reported having no financial conflicts regarding her study.
AT THE ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: A key mediator of clinical improvement in response to cognitive grief treatment is a reduction in avoidance behaviors.
Data source: A secondary analysis of a randomized trial of complicated grief treatment versus interpersonal psychotherapy in 69 patients with complicated grief.
Disclosures: The study presenter reported having no financial conflicts.