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Fewer early neurologic complications with TAVR than SAVR
PARIS – Patients with severe aortic stenosis at intermediate operative risk have a significantly lower 30-day risk of stroke and other neurologic complications with transcatheter aortic valve replacement than with surgical replacement, according to new results from the landmark SURTAVI trial.
“This is the first time the stroke rate has been shown to be lower with TAVR than with surgery,” A. Pieter Kappetein, MD, noted in presenting the results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
It’s a finding that adds to the momentum for studying TAVR in low-surgical-risk patients, he added.
“As we move toward lower-risk patients it will become even more important to see whether there is a difference in stroke. Suppose the stroke rate in SURTAVI had been a little higher with TAVR than SAVR? It would really make us more cautious about moving toward lower-risk patients. Now that we see that in intermediate-risk patients the stroke rate is actually a little bit lower than with surgery, I think we’ll feel more comfortable moving toward lower-risk patients,” according to Dr. Kappetein, professor of cardiothoracic surgery at Erasmus University Medical Center in Rotterdam.
SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) involved randomization of 1,660 patients with severe symptomatic aortic stenosis to TAVR or SAVR. All participants were deemed to be at intermediate operative risk based upon a predicted surgical mortality of 3%-15%. The primary outcome -- a composite of all-cause mortality and disabling stroke at 2 years -- was presented at the 2017 meeting of the American College of Cardiology and simultaneously published (N Engl J Med. 2017 Apr 6;376(14):1321-1331). The rate was 12.6% with TAVR using the self-expanding CoreValve or Evolut R bioprosthesis and noninferior at 14% with SAVR.
Dr. Kappetein presented a prespecified secondary analysis of the 30-day rate of all neurologic complications, including nondisabling strokes and encephalopathy. He and the other SURTAVI organizers felt this was an important outcome because these early neurologic events have a major impact upon quality of life, including whether a patient will be discharged home or to a rehabilitation clinic or skilled nursing facility following aortic valve replacement.
The 30-day incidence of all stroke was 3.3% in the TAVR patients, significantly lower than the 5.4% rate in the SAVR group. By the 2-year mark, however, the difference was no longer statistically significant, with a rate of 6.3% in the TAVR group compared with 8.0% with SAVR.
Ninety-five percent of the early strokes were ischemic.
The 30-day incidence of disabling stroke was 1.2% with TAVR and 2.4% with SAVR, a difference that was not significant (P=0.057). The 2-year rate was 2.4% in the TAVR arm and 4.5% with SAVR, again not significantly different.
Half of the strokes in the TAVR group had a modified Rankin score of 0-1 at 30 days, meaning no or only minimal signs of stroke. In contrast, most of the strokes in the SAVR group were disabling, with a modified Rankin score of 2-6.
Only 36% of patients who had an early stroke were discharged home, compared with 87% of patients without a stroke. Not surprisingly, quality of life as assessed using the SF-36 physical summary was significantly worse in the early-stroke group. However, with or without stroke, TAVR patients recovered quality of life faster than SAVR patients.
He noted that the timing of the early strokes differed between the two groups. The great majority of both disabling and nondisabling strokes in the TAVR patients were periprocedural, occurring on the day of TAVR or the next day. Strokes in the SAVR group occurred then as well, but also on days 2-6.
One reason why SURTAVI is the first study to show a lower stroke risk with TAVR is that it was the first TAVR-versus-SAVR study to feature comprehensive neurologic testing pre- and post-procedure, along with evaluation of all suspected events by a neurologist or stroke specialist, according to Dr. Kappetein.
“As surgeons we all have said the stroke rate after SAVR is 1%-1.5%, but only when the patient wasn’t waving to us the next morning would we say, ‘Oh, that patient may have a stroke.’ Then we would call a neurologist. So there were many more subtle strokes that we never actually detected. If you do a proper examination of the patient before and after the procedure you’ll find many more strokes,” he said.
He and his coinvestigators systematically searched in vain for predictors of increased stroke risk among the TAVR and SAVR patients.
“Actually, the stroke risk is present for every patient we treat with TAVR or SAVR,” the surgeon continued.
However, discussant Adnan Kastrati, MD, chief physician at the German Heart Center in Munich, thought he spied in the SURTAVI data a potential opportunity to reduce early strokes in SAVR patients. He noted that new-onset atrial fibrillation is consistently more common in SAVR than TAVR patients, and that many of the strokes in the SAVR group occurred on days 2-6. When do heart surgeons typically start oral anticoagulation in their patients with postsurgical atrial fibrillation? he asked.
Not until after 48 hours, Dr. Kappetein replied.
“Those strokes on days 4, 5, and 6 might have to do with atrial fibrillation, and we may need to be more aggressive as surgeons in anticoagulating patients with atrial fibrillation after surgery,” he said.
Dr. Kappetein reported receiving research grant support from Medtronic, sponsor of SURTAVI.
This article was updated July 28, 2107.
PARIS – Patients with severe aortic stenosis at intermediate operative risk have a significantly lower 30-day risk of stroke and other neurologic complications with transcatheter aortic valve replacement than with surgical replacement, according to new results from the landmark SURTAVI trial.
“This is the first time the stroke rate has been shown to be lower with TAVR than with surgery,” A. Pieter Kappetein, MD, noted in presenting the results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
It’s a finding that adds to the momentum for studying TAVR in low-surgical-risk patients, he added.
“As we move toward lower-risk patients it will become even more important to see whether there is a difference in stroke. Suppose the stroke rate in SURTAVI had been a little higher with TAVR than SAVR? It would really make us more cautious about moving toward lower-risk patients. Now that we see that in intermediate-risk patients the stroke rate is actually a little bit lower than with surgery, I think we’ll feel more comfortable moving toward lower-risk patients,” according to Dr. Kappetein, professor of cardiothoracic surgery at Erasmus University Medical Center in Rotterdam.
SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) involved randomization of 1,660 patients with severe symptomatic aortic stenosis to TAVR or SAVR. All participants were deemed to be at intermediate operative risk based upon a predicted surgical mortality of 3%-15%. The primary outcome -- a composite of all-cause mortality and disabling stroke at 2 years -- was presented at the 2017 meeting of the American College of Cardiology and simultaneously published (N Engl J Med. 2017 Apr 6;376(14):1321-1331). The rate was 12.6% with TAVR using the self-expanding CoreValve or Evolut R bioprosthesis and noninferior at 14% with SAVR.
Dr. Kappetein presented a prespecified secondary analysis of the 30-day rate of all neurologic complications, including nondisabling strokes and encephalopathy. He and the other SURTAVI organizers felt this was an important outcome because these early neurologic events have a major impact upon quality of life, including whether a patient will be discharged home or to a rehabilitation clinic or skilled nursing facility following aortic valve replacement.
The 30-day incidence of all stroke was 3.3% in the TAVR patients, significantly lower than the 5.4% rate in the SAVR group. By the 2-year mark, however, the difference was no longer statistically significant, with a rate of 6.3% in the TAVR group compared with 8.0% with SAVR.
Ninety-five percent of the early strokes were ischemic.
The 30-day incidence of disabling stroke was 1.2% with TAVR and 2.4% with SAVR, a difference that was not significant (P=0.057). The 2-year rate was 2.4% in the TAVR arm and 4.5% with SAVR, again not significantly different.
Half of the strokes in the TAVR group had a modified Rankin score of 0-1 at 30 days, meaning no or only minimal signs of stroke. In contrast, most of the strokes in the SAVR group were disabling, with a modified Rankin score of 2-6.
Only 36% of patients who had an early stroke were discharged home, compared with 87% of patients without a stroke. Not surprisingly, quality of life as assessed using the SF-36 physical summary was significantly worse in the early-stroke group. However, with or without stroke, TAVR patients recovered quality of life faster than SAVR patients.
He noted that the timing of the early strokes differed between the two groups. The great majority of both disabling and nondisabling strokes in the TAVR patients were periprocedural, occurring on the day of TAVR or the next day. Strokes in the SAVR group occurred then as well, but also on days 2-6.
One reason why SURTAVI is the first study to show a lower stroke risk with TAVR is that it was the first TAVR-versus-SAVR study to feature comprehensive neurologic testing pre- and post-procedure, along with evaluation of all suspected events by a neurologist or stroke specialist, according to Dr. Kappetein.
“As surgeons we all have said the stroke rate after SAVR is 1%-1.5%, but only when the patient wasn’t waving to us the next morning would we say, ‘Oh, that patient may have a stroke.’ Then we would call a neurologist. So there were many more subtle strokes that we never actually detected. If you do a proper examination of the patient before and after the procedure you’ll find many more strokes,” he said.
He and his coinvestigators systematically searched in vain for predictors of increased stroke risk among the TAVR and SAVR patients.
“Actually, the stroke risk is present for every patient we treat with TAVR or SAVR,” the surgeon continued.
However, discussant Adnan Kastrati, MD, chief physician at the German Heart Center in Munich, thought he spied in the SURTAVI data a potential opportunity to reduce early strokes in SAVR patients. He noted that new-onset atrial fibrillation is consistently more common in SAVR than TAVR patients, and that many of the strokes in the SAVR group occurred on days 2-6. When do heart surgeons typically start oral anticoagulation in their patients with postsurgical atrial fibrillation? he asked.
Not until after 48 hours, Dr. Kappetein replied.
“Those strokes on days 4, 5, and 6 might have to do with atrial fibrillation, and we may need to be more aggressive as surgeons in anticoagulating patients with atrial fibrillation after surgery,” he said.
Dr. Kappetein reported receiving research grant support from Medtronic, sponsor of SURTAVI.
This article was updated July 28, 2107.
PARIS – Patients with severe aortic stenosis at intermediate operative risk have a significantly lower 30-day risk of stroke and other neurologic complications with transcatheter aortic valve replacement than with surgical replacement, according to new results from the landmark SURTAVI trial.
“This is the first time the stroke rate has been shown to be lower with TAVR than with surgery,” A. Pieter Kappetein, MD, noted in presenting the results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
It’s a finding that adds to the momentum for studying TAVR in low-surgical-risk patients, he added.
“As we move toward lower-risk patients it will become even more important to see whether there is a difference in stroke. Suppose the stroke rate in SURTAVI had been a little higher with TAVR than SAVR? It would really make us more cautious about moving toward lower-risk patients. Now that we see that in intermediate-risk patients the stroke rate is actually a little bit lower than with surgery, I think we’ll feel more comfortable moving toward lower-risk patients,” according to Dr. Kappetein, professor of cardiothoracic surgery at Erasmus University Medical Center in Rotterdam.
SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) involved randomization of 1,660 patients with severe symptomatic aortic stenosis to TAVR or SAVR. All participants were deemed to be at intermediate operative risk based upon a predicted surgical mortality of 3%-15%. The primary outcome -- a composite of all-cause mortality and disabling stroke at 2 years -- was presented at the 2017 meeting of the American College of Cardiology and simultaneously published (N Engl J Med. 2017 Apr 6;376(14):1321-1331). The rate was 12.6% with TAVR using the self-expanding CoreValve or Evolut R bioprosthesis and noninferior at 14% with SAVR.
Dr. Kappetein presented a prespecified secondary analysis of the 30-day rate of all neurologic complications, including nondisabling strokes and encephalopathy. He and the other SURTAVI organizers felt this was an important outcome because these early neurologic events have a major impact upon quality of life, including whether a patient will be discharged home or to a rehabilitation clinic or skilled nursing facility following aortic valve replacement.
The 30-day incidence of all stroke was 3.3% in the TAVR patients, significantly lower than the 5.4% rate in the SAVR group. By the 2-year mark, however, the difference was no longer statistically significant, with a rate of 6.3% in the TAVR group compared with 8.0% with SAVR.
Ninety-five percent of the early strokes were ischemic.
The 30-day incidence of disabling stroke was 1.2% with TAVR and 2.4% with SAVR, a difference that was not significant (P=0.057). The 2-year rate was 2.4% in the TAVR arm and 4.5% with SAVR, again not significantly different.
Half of the strokes in the TAVR group had a modified Rankin score of 0-1 at 30 days, meaning no or only minimal signs of stroke. In contrast, most of the strokes in the SAVR group were disabling, with a modified Rankin score of 2-6.
Only 36% of patients who had an early stroke were discharged home, compared with 87% of patients without a stroke. Not surprisingly, quality of life as assessed using the SF-36 physical summary was significantly worse in the early-stroke group. However, with or without stroke, TAVR patients recovered quality of life faster than SAVR patients.
He noted that the timing of the early strokes differed between the two groups. The great majority of both disabling and nondisabling strokes in the TAVR patients were periprocedural, occurring on the day of TAVR or the next day. Strokes in the SAVR group occurred then as well, but also on days 2-6.
One reason why SURTAVI is the first study to show a lower stroke risk with TAVR is that it was the first TAVR-versus-SAVR study to feature comprehensive neurologic testing pre- and post-procedure, along with evaluation of all suspected events by a neurologist or stroke specialist, according to Dr. Kappetein.
“As surgeons we all have said the stroke rate after SAVR is 1%-1.5%, but only when the patient wasn’t waving to us the next morning would we say, ‘Oh, that patient may have a stroke.’ Then we would call a neurologist. So there were many more subtle strokes that we never actually detected. If you do a proper examination of the patient before and after the procedure you’ll find many more strokes,” he said.
He and his coinvestigators systematically searched in vain for predictors of increased stroke risk among the TAVR and SAVR patients.
“Actually, the stroke risk is present for every patient we treat with TAVR or SAVR,” the surgeon continued.
However, discussant Adnan Kastrati, MD, chief physician at the German Heart Center in Munich, thought he spied in the SURTAVI data a potential opportunity to reduce early strokes in SAVR patients. He noted that new-onset atrial fibrillation is consistently more common in SAVR than TAVR patients, and that many of the strokes in the SAVR group occurred on days 2-6. When do heart surgeons typically start oral anticoagulation in their patients with postsurgical atrial fibrillation? he asked.
Not until after 48 hours, Dr. Kappetein replied.
“Those strokes on days 4, 5, and 6 might have to do with atrial fibrillation, and we may need to be more aggressive as surgeons in anticoagulating patients with atrial fibrillation after surgery,” he said.
Dr. Kappetein reported receiving research grant support from Medtronic, sponsor of SURTAVI.
This article was updated July 28, 2107.
AT EUROPCR
Key clinical point:
Major finding: The combined incidence of disabling and nondisabling stroke within 30 days of TAVR was 3.3%, significantly better than the 5.4% rate in patients who underwent SAVR.
Data source: SURTAVI was a multicenter trial which included 1,660 patients with severe aortic stenosis who were at intermediate operative risk and were randomized to TAVR or SAVR.
Disclosures: The study presenter reported receiving research grant support from Medtronic, sponsor of the SURTAVI trial.
Hypertonic saline for bronchiolitis found ineffective in large RCT study
MADRID – Giving nebulized hypertonic saline (NHS) to infants who present to pediatric emergency departments with a first episode of moderate to severe acute bronchiolitis did not reduce their hospitalization rate in the randomized, multicenter, double-blind GUERANDE trial.
Moreover, mild adverse events – mainly worsening cough – were significantly more frequent in the NHS recipients than in controls given nebulized normal saline, Christele Gras-le Guen, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Some previous studies have suggested a modest benefit, but they were underpowered to draw meaningful conclusions. GUERANDE, a 777-patient randomized trial conducted in 24 French pediatric emergency departments, was the first quality study large enough to determine whether the therapy results in fewer hospital admissions, she said.
In GUERANDE, infants with a first episode of acute bronchiolitis were given two 20-minute nebulizations of 3% hypertonic saline or 0.9% normal saline 20 minutes apart.
The primary outcome was the rate of hospital admission within 24 hours after enrollment. The rate was 48% in the NHS group and 52% in controls, a nonsignificant difference which shrunk even more after controlling for age, oxygen saturation, and respiratory syncytial virus infection status.
No serious adverse events occurred in GUERANDE. However, the rate of mild adverse events was 9% in the NHS group, significantly higher than the 4% rate in controls. Notably, cough without respiratory distress occurred 30 times in 26 infants in the NHS group, compared with 4 times in 3 control subjects.
Dr. Gras-le Guin reported having no financial conflicts regarding the GUERANDE study, funded by the French Health Ministry.
MADRID – Giving nebulized hypertonic saline (NHS) to infants who present to pediatric emergency departments with a first episode of moderate to severe acute bronchiolitis did not reduce their hospitalization rate in the randomized, multicenter, double-blind GUERANDE trial.
Moreover, mild adverse events – mainly worsening cough – were significantly more frequent in the NHS recipients than in controls given nebulized normal saline, Christele Gras-le Guen, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Some previous studies have suggested a modest benefit, but they were underpowered to draw meaningful conclusions. GUERANDE, a 777-patient randomized trial conducted in 24 French pediatric emergency departments, was the first quality study large enough to determine whether the therapy results in fewer hospital admissions, she said.
In GUERANDE, infants with a first episode of acute bronchiolitis were given two 20-minute nebulizations of 3% hypertonic saline or 0.9% normal saline 20 minutes apart.
The primary outcome was the rate of hospital admission within 24 hours after enrollment. The rate was 48% in the NHS group and 52% in controls, a nonsignificant difference which shrunk even more after controlling for age, oxygen saturation, and respiratory syncytial virus infection status.
No serious adverse events occurred in GUERANDE. However, the rate of mild adverse events was 9% in the NHS group, significantly higher than the 4% rate in controls. Notably, cough without respiratory distress occurred 30 times in 26 infants in the NHS group, compared with 4 times in 3 control subjects.
Dr. Gras-le Guin reported having no financial conflicts regarding the GUERANDE study, funded by the French Health Ministry.
MADRID – Giving nebulized hypertonic saline (NHS) to infants who present to pediatric emergency departments with a first episode of moderate to severe acute bronchiolitis did not reduce their hospitalization rate in the randomized, multicenter, double-blind GUERANDE trial.
Moreover, mild adverse events – mainly worsening cough – were significantly more frequent in the NHS recipients than in controls given nebulized normal saline, Christele Gras-le Guen, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
Some previous studies have suggested a modest benefit, but they were underpowered to draw meaningful conclusions. GUERANDE, a 777-patient randomized trial conducted in 24 French pediatric emergency departments, was the first quality study large enough to determine whether the therapy results in fewer hospital admissions, she said.
In GUERANDE, infants with a first episode of acute bronchiolitis were given two 20-minute nebulizations of 3% hypertonic saline or 0.9% normal saline 20 minutes apart.
The primary outcome was the rate of hospital admission within 24 hours after enrollment. The rate was 48% in the NHS group and 52% in controls, a nonsignificant difference which shrunk even more after controlling for age, oxygen saturation, and respiratory syncytial virus infection status.
No serious adverse events occurred in GUERANDE. However, the rate of mild adverse events was 9% in the NHS group, significantly higher than the 4% rate in controls. Notably, cough without respiratory distress occurred 30 times in 26 infants in the NHS group, compared with 4 times in 3 control subjects.
Dr. Gras-le Guin reported having no financial conflicts regarding the GUERANDE study, funded by the French Health Ministry.
AT ESPID 2017
Key clinical point:
Major finding: The rate of hospitalization following administration of nebulized hypertonic saline to infants with a first episode of acute bronchiolitis was 48%, not significantly different from the 52% rate in controls.
Data source: This was a randomized, multicenter, double-blind, controlled clinical trial including 777 infants with acute bronchiolitis.
Disclosures: The GUERANDE study was funded by the French Health Ministry. The presenter reported having no financial conflicts.
Measles immunization is a major challenge in HIV-infected children
MADRID – Impaired response to measles immunization is common in HIV-infected children, and revaccination – while an important strategy – helps only some of them, Ruth del Valle, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
The key predictor of an impaired response to measles immunization appears to be a CD4/CD8 cell ratio of less than 1.0, added Dr. del Valle of Infant Sofia University Hospital in Madrid.
Of note, 48% of the children had a CD4/CD8 ratio of less than 1.0 at baseline. This ratio is gaining credence as a predictor of HIV-positive patients’ immunologic response to a variety of vaccines: most recently, in Dr. del Valle’s study, to measles vaccine and, in two earlier studies published in 2016, to yellow fever vaccine (PLoS Negl Trop Dis. 2016 Dec 12;10[12]:e0005219) and hepatitis B vaccine (Vaccine. 2016 Apr 7;34[16]:1889-95).
In Dr. del Valle’s study, only 52% of HIV-positive children developed protective antibody levels following completion of the standard two-dose MMR schedule. In accord with current Paediatric European Network for Treatment of AIDS (PENTA) guidelines, 41 unresponsive patients then received a booster MMR dose (HIV Med. 2012 Jul;13[6]:333-6). Of the 41, 10 (24%) did not respond to the booster dose, either. Thus, the final measles protection rate in this study was only 77%.
These study findings highlight the importance of routinely testing measles vaccine response in HIV-infected children in clinical practice, she noted.
The CD4/CD8 ratio was 1.3 in good responders to measles immunization and 0.9 in nonresponders. In a multivariate analysis, a CD4/CD8 ratio of less than 1.0 conferred a 3.2 times increased risk of impaired response to the measles vaccine.
Dr. del Valle and her coinvestigators in CORISPES (the Spanish Cohort of HIV-infected Children) plan further studies to determine the duration of protection against measles in those patients who responded to the booster dose.
Session cochair Nigel Klein, MD, commented that Dr. del Valle’s study is “one of a number of reports that HIV-infected children, as they get older, are predisposed to getting infections that we should be able to prevent.”
“I think we don’t know best how to manage this population of patients. You can give more vaccinations, but, as Dr. del Valle has shown, not all of them will respond. And I think this study is further evidence that the better we can maintain our children’s immune systems by treating early, the better our chances of getting good responses when we vaccinate,” said Dr. Klein, professor of pediatric infectious diseases and immunology at Great Ormond Street Children’s Hospital and University College London.
Dr. del Valle reported having no relevant financial disclosures.
MADRID – Impaired response to measles immunization is common in HIV-infected children, and revaccination – while an important strategy – helps only some of them, Ruth del Valle, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
The key predictor of an impaired response to measles immunization appears to be a CD4/CD8 cell ratio of less than 1.0, added Dr. del Valle of Infant Sofia University Hospital in Madrid.
Of note, 48% of the children had a CD4/CD8 ratio of less than 1.0 at baseline. This ratio is gaining credence as a predictor of HIV-positive patients’ immunologic response to a variety of vaccines: most recently, in Dr. del Valle’s study, to measles vaccine and, in two earlier studies published in 2016, to yellow fever vaccine (PLoS Negl Trop Dis. 2016 Dec 12;10[12]:e0005219) and hepatitis B vaccine (Vaccine. 2016 Apr 7;34[16]:1889-95).
In Dr. del Valle’s study, only 52% of HIV-positive children developed protective antibody levels following completion of the standard two-dose MMR schedule. In accord with current Paediatric European Network for Treatment of AIDS (PENTA) guidelines, 41 unresponsive patients then received a booster MMR dose (HIV Med. 2012 Jul;13[6]:333-6). Of the 41, 10 (24%) did not respond to the booster dose, either. Thus, the final measles protection rate in this study was only 77%.
These study findings highlight the importance of routinely testing measles vaccine response in HIV-infected children in clinical practice, she noted.
The CD4/CD8 ratio was 1.3 in good responders to measles immunization and 0.9 in nonresponders. In a multivariate analysis, a CD4/CD8 ratio of less than 1.0 conferred a 3.2 times increased risk of impaired response to the measles vaccine.
Dr. del Valle and her coinvestigators in CORISPES (the Spanish Cohort of HIV-infected Children) plan further studies to determine the duration of protection against measles in those patients who responded to the booster dose.
Session cochair Nigel Klein, MD, commented that Dr. del Valle’s study is “one of a number of reports that HIV-infected children, as they get older, are predisposed to getting infections that we should be able to prevent.”
“I think we don’t know best how to manage this population of patients. You can give more vaccinations, but, as Dr. del Valle has shown, not all of them will respond. And I think this study is further evidence that the better we can maintain our children’s immune systems by treating early, the better our chances of getting good responses when we vaccinate,” said Dr. Klein, professor of pediatric infectious diseases and immunology at Great Ormond Street Children’s Hospital and University College London.
Dr. del Valle reported having no relevant financial disclosures.
MADRID – Impaired response to measles immunization is common in HIV-infected children, and revaccination – while an important strategy – helps only some of them, Ruth del Valle, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
The key predictor of an impaired response to measles immunization appears to be a CD4/CD8 cell ratio of less than 1.0, added Dr. del Valle of Infant Sofia University Hospital in Madrid.
Of note, 48% of the children had a CD4/CD8 ratio of less than 1.0 at baseline. This ratio is gaining credence as a predictor of HIV-positive patients’ immunologic response to a variety of vaccines: most recently, in Dr. del Valle’s study, to measles vaccine and, in two earlier studies published in 2016, to yellow fever vaccine (PLoS Negl Trop Dis. 2016 Dec 12;10[12]:e0005219) and hepatitis B vaccine (Vaccine. 2016 Apr 7;34[16]:1889-95).
In Dr. del Valle’s study, only 52% of HIV-positive children developed protective antibody levels following completion of the standard two-dose MMR schedule. In accord with current Paediatric European Network for Treatment of AIDS (PENTA) guidelines, 41 unresponsive patients then received a booster MMR dose (HIV Med. 2012 Jul;13[6]:333-6). Of the 41, 10 (24%) did not respond to the booster dose, either. Thus, the final measles protection rate in this study was only 77%.
These study findings highlight the importance of routinely testing measles vaccine response in HIV-infected children in clinical practice, she noted.
The CD4/CD8 ratio was 1.3 in good responders to measles immunization and 0.9 in nonresponders. In a multivariate analysis, a CD4/CD8 ratio of less than 1.0 conferred a 3.2 times increased risk of impaired response to the measles vaccine.
Dr. del Valle and her coinvestigators in CORISPES (the Spanish Cohort of HIV-infected Children) plan further studies to determine the duration of protection against measles in those patients who responded to the booster dose.
Session cochair Nigel Klein, MD, commented that Dr. del Valle’s study is “one of a number of reports that HIV-infected children, as they get older, are predisposed to getting infections that we should be able to prevent.”
“I think we don’t know best how to manage this population of patients. You can give more vaccinations, but, as Dr. del Valle has shown, not all of them will respond. And I think this study is further evidence that the better we can maintain our children’s immune systems by treating early, the better our chances of getting good responses when we vaccinate,” said Dr. Klein, professor of pediatric infectious diseases and immunology at Great Ormond Street Children’s Hospital and University College London.
Dr. del Valle reported having no relevant financial disclosures.
AT ESPID 2017
Key clinical point:
Major finding: After two doses of MMR and, if needed, a third booster dose, 23% of a group of HIV-infected children remained unprotected against measles.
Data source: This multicenter study included 120 HIV-infected Spanish children who received two doses of the MMR vaccine and, if still unprotected against measles, a booster dose.
Disclosures: Dr. del Valle reported having no relevant financial disclosures.
Tweaking CBT to boost outcomes in GAD
SAN FRANCISCO – The search is on for ways to refine cognitive-behavioral therapy for generalized anxiety disorder in order to improve upon current relatively modest success rates.
Cognitive-behavioral therapy (CBT) is less effective for generalized anxiety disorder (GAD) than for the other anxiety disorders. Only about one-half of patients are improved post-treatment, and less than one-third reach recovery, noted Richard E. Zinbarg, PhD, at the annual conference of the Anxiety and Depression Association of America.
At a session on advances in treatment of GAD, investigators presented randomized clinical trials assessing a variety of specific strategies aimed at enhancing the effectiveness of CBT in evidence-based fashion. The trials included a study of the impact of having patients keep a worry outcome journal, an exploration of the potential deleterious effects of a phenomenon known as relaxation-induced anxiety, and a study of the effectiveness of emotion regulation therapy, a relatively recent form of psychotherapy that’s part of the so-called “third wave” of CBT.
Worry outcome journal
Lucas LaFreniere observed that while CBT has been broadly shown to be effective for GAD, the various forms of CBT are packages of components that often include psychoeducation, stimulus control, behavioral experiments, exposure, cognitive reframing, relaxation training, and other elements in various combinations and sequences. Almost none of these specific components has been evaluated formally to learn whether they are pulling their weight therapeutically and making a positive contribution to outcomes.
Mr. LaFreniere, a doctoral student in clinical psychology at Pennsylvania State University in Hershey, presented a randomized trial of one such component, worry outcome monitoring, which currently is incorporated in some but not all CBT programs for GAD. Mr. LaFreniere and his coinvestigators developed a version of worry outcome monitoring they dubbed the worry outcome journal, or WOJ, which he characterized as “a brief ecological momentary intervention for worry.”
The WOJ works like this: At four random times per day, WOJ users receive a phone message to drop what they’re doing and record on a chart what they’re currently worrying about. They briefly note the date and time, the content of their worry, the distress it’s causing on a 1-7 scale, how much time they’re spending thinking about it, and their prediction as to the likelihood that this negative event actually will come to pass, which by the nature of their illness generally is unrealistically sky high early on in treatment. Later, they return to record whether the worrisome outcome occurred. The WOJ data are often reviewed in session.
The hypothesis was that the WOJ would reduce worry by aiding GAD patients in attending to their worries more thoroughly and objectively, recognizing in the moment the high cost of their worrying in terms of distress and cognitive interference, forming more realistic predictions about the future, and changing their conviction that excessive worrying is a worthwhile use of their time.
“One thing that particularly motivates me as a treatment researcher is the idea that those with GAD could be making themselves chronically miserable in an effort to protect themselves from future catastrophes that likely are not even going to happen. That’s a lot of human suffering that isn’t necessary. What we can do to help with that, we should do,” Mr. LaFreniere said.
On the other hand, this was a matter that cried out for a controlled trial because of the possibility that attempts to reduce worry might have unintended harmful consequences.
“Those with GAD have positive beliefs about worry. They believe it’s useful: it motivates, buffers emotional shifts, facilitates problem solving, and marks you as caring and conscientious – good personality traits,” he explained.
His study included 51 GAD patients randomized to 10 days using the WOJ or to a thought log control condition in which prompted by their cell phone four times daily, they recorded whatever everyday thought was on their mind at the moment. An example drawn from personal experience, Mr. LaFreniere said, might be “I love enchiladas!”
Outcome measures evaluated at baseline, again at 10 days upon conclusion of the intervention, and finally at 30 days of follow-up were the Penn State Worry Questionnaire, the GAD Questionnaire for DSM-IV, and the Meta-Cognitions Questionnaire subscales for positive beliefs about worry, uncontrollability of one’s thoughts, and negative beliefs about worry.
“The big reveal was that 91% of their worries did not come true,” he reported.
The primary outcome was reduction in worries as measured by the Penn State Questionnaire. The WOJ group showed a significant reduction, compared with controls, immediately post-treatment – which remained significant, albeit attenuated to a moderate effect size, at 30 days.
At day 10, 18 of 29 WOJ users no longer met diagnostic criteria for GAD, compared with 6 of 22 controls. By day 30, however, there was no significant between-group difference on this secondary endpoint.
The WOJ group showed a significantly greater reduction than controls on the secondary endpoint of uncontrollability of beliefs at both days 10 and 30.
“The WOJ may be a viable ecological momentary intervention for reducing worry in GAD. Therapist-free use of WOJ led to decreased worrying after only 10 days. It’s quite possible that longer practice may yield even stronger results. After all, for a normal CBT protocol, we’re looking at 8-20 weeks of treatment,” Mr. LaFreniere observed.
“I’d like to underscore that there was no harm done: The WOJ didn’t increase detrimental beliefs about worry,” he added. “We had a worry ourselves as researchers – disconfirmed by the trial – that patients may take the non-occurrence of their worries as some kind of proof that worry prevented those bad things from happening.”
Mr. LaFreniere is interested in studying the WOJ for worry reduction in non-GAD populations.
“Worry can be very high in other anxiety disorders, major depressive disorder, bipolar disorders, and in insomnia. The WOJ is highly cost-effective and easy to disseminate. It could very easily be made into a smartphone app,” he said.
Relaxation-induced anxiety
Relaxation training often is incorporated in treatment packages for GAD. Yet, it’s possible that one reason CBT is only modestly effective for GAD is because of relaxation-induced anxiety (RIA), an understudied phenomenon defined as a paradoxical increase in the physiological, behavioral, and cognitive aspects of anxiety when a person tries to relax.
“It has been theorized that individuals who are especially concerned with maintaining control over physical and psychological processes find relaxation vulnerable, unpleasant, and activating. Thus, discomfort with perceived lack of control during relaxed moments – an inability to let go – may result in unsought increase in anxiety during therapeutic attempts at relaxation,” according to Michelle G. Newman, PhD, professor of psychology at Penn State.
She presented a secondary analysis of a published randomized clinical trial she coauthored (J Consult Clin Psychol. 2002 Apr;70[2]:288-98) in which 41 participants with GAD were assigned to CBT with relaxation therapy using standard progressive muscle relaxation techniques or to self-control desensitization. Relaxation therapy and relaxation-induced anxiety ratings were recorded at each session. Outcomes were assessed post-treatment and at 6, 12, and 24 months of follow-up using the Penn State Worry Questionnaire, the State-Trait Anxiety Inventory, the Hamilton Anxiety Rating Scale, and the Clinician Severity Rating for GAD symptoms. In addition, immediately after each in-session relaxation practice, patients were asked to rate on a 9-point scale how much they noticed an increase in anxiety during the relaxation session.
All subjects improved significantly, but those with a lower peak RIA – defined as the highest level of RIA experienced in any of the 14 treatment sessions – had significantly fewer GAD symptoms at the end of therapy as well as at 2-year follow-up. Peak RIA was unrelated to baseline GAD symptom severity or change over time in anxiety symptoms. However, patients whose peak RIA occurred during the last several treatment sessions showed less improvement in GAD symptoms at the conclusion of treatment than those whose peak came earlier.
The clinical implications of these findings are that therapists who use progressive muscle relaxation in the treatment of GAD should assess RIA at the conclusion of every session, and if a patient reports moderate or higher RIA, the duration of the relaxation training portion of therapy should not be shortened until after several consecutive sessions of lower RIA have been reported, according to Dr. Newman.
Emotion regulation therapy
Megan E. Renna brought attendees up to speed on emotion regulation therapy (ERT), a third wave variant of CBT that incorporates principles from more traditional CBT, such as skills training and exposure, supplemented by teaching emotion regulation skills. Those skills include the development of present moment awareness and cultivation of compassion. Both are grounded in research on motivational and regulatory learning mechanisms related to threat vs. safety and reward versus loss.
As detailed in a recent review article for which she was first author (Front Psychol. 2017 Feb 6;8:98), ERT is a manualized, mechanism-targeted treatment for what she termed “distress disorders”; namely, GAD and major depressive disorder, which are highly comorbid, share key underlying temperamental features, and for whom adequate therapeutic success is all too often elusive. ERT appears to be particularly useful during the emerging adulthood years and across a broad range of ethnic and racial patients, according to Ms. Renna, a PhD student in clinical psychology at Hunter College in New York.
The efficacy of the original 20-session, individual therapy version of ERT was established in a study of 20 GAD patients, half of whom also had major depression (Depress Anxiety. 2015 Aug;32[8]:614-23). But Ms. Renna said ERT’s developers – Douglas S. Mennin, PhD, of Hunter College, and David M. Fresco, PhD, of Kent State (Ohio) University, are interested in determining the minimum effective therapeutic dose of ERT. They have conducted an open randomized trial of a 16-session version of ERT in which the results proved similar to those seen with 20 sessions. Now they’re carrying out a study of 8 vs. 16 sessions. The study is ongoing, but at first look, the results with 8 sessions of ERT appear similar to 16, Ms. Renna said.
None of the speakers reported having any financial conflicts of interest.
SAN FRANCISCO – The search is on for ways to refine cognitive-behavioral therapy for generalized anxiety disorder in order to improve upon current relatively modest success rates.
Cognitive-behavioral therapy (CBT) is less effective for generalized anxiety disorder (GAD) than for the other anxiety disorders. Only about one-half of patients are improved post-treatment, and less than one-third reach recovery, noted Richard E. Zinbarg, PhD, at the annual conference of the Anxiety and Depression Association of America.
At a session on advances in treatment of GAD, investigators presented randomized clinical trials assessing a variety of specific strategies aimed at enhancing the effectiveness of CBT in evidence-based fashion. The trials included a study of the impact of having patients keep a worry outcome journal, an exploration of the potential deleterious effects of a phenomenon known as relaxation-induced anxiety, and a study of the effectiveness of emotion regulation therapy, a relatively recent form of psychotherapy that’s part of the so-called “third wave” of CBT.
Worry outcome journal
Lucas LaFreniere observed that while CBT has been broadly shown to be effective for GAD, the various forms of CBT are packages of components that often include psychoeducation, stimulus control, behavioral experiments, exposure, cognitive reframing, relaxation training, and other elements in various combinations and sequences. Almost none of these specific components has been evaluated formally to learn whether they are pulling their weight therapeutically and making a positive contribution to outcomes.
Mr. LaFreniere, a doctoral student in clinical psychology at Pennsylvania State University in Hershey, presented a randomized trial of one such component, worry outcome monitoring, which currently is incorporated in some but not all CBT programs for GAD. Mr. LaFreniere and his coinvestigators developed a version of worry outcome monitoring they dubbed the worry outcome journal, or WOJ, which he characterized as “a brief ecological momentary intervention for worry.”
The WOJ works like this: At four random times per day, WOJ users receive a phone message to drop what they’re doing and record on a chart what they’re currently worrying about. They briefly note the date and time, the content of their worry, the distress it’s causing on a 1-7 scale, how much time they’re spending thinking about it, and their prediction as to the likelihood that this negative event actually will come to pass, which by the nature of their illness generally is unrealistically sky high early on in treatment. Later, they return to record whether the worrisome outcome occurred. The WOJ data are often reviewed in session.
The hypothesis was that the WOJ would reduce worry by aiding GAD patients in attending to their worries more thoroughly and objectively, recognizing in the moment the high cost of their worrying in terms of distress and cognitive interference, forming more realistic predictions about the future, and changing their conviction that excessive worrying is a worthwhile use of their time.
“One thing that particularly motivates me as a treatment researcher is the idea that those with GAD could be making themselves chronically miserable in an effort to protect themselves from future catastrophes that likely are not even going to happen. That’s a lot of human suffering that isn’t necessary. What we can do to help with that, we should do,” Mr. LaFreniere said.
On the other hand, this was a matter that cried out for a controlled trial because of the possibility that attempts to reduce worry might have unintended harmful consequences.
“Those with GAD have positive beliefs about worry. They believe it’s useful: it motivates, buffers emotional shifts, facilitates problem solving, and marks you as caring and conscientious – good personality traits,” he explained.
His study included 51 GAD patients randomized to 10 days using the WOJ or to a thought log control condition in which prompted by their cell phone four times daily, they recorded whatever everyday thought was on their mind at the moment. An example drawn from personal experience, Mr. LaFreniere said, might be “I love enchiladas!”
Outcome measures evaluated at baseline, again at 10 days upon conclusion of the intervention, and finally at 30 days of follow-up were the Penn State Worry Questionnaire, the GAD Questionnaire for DSM-IV, and the Meta-Cognitions Questionnaire subscales for positive beliefs about worry, uncontrollability of one’s thoughts, and negative beliefs about worry.
“The big reveal was that 91% of their worries did not come true,” he reported.
The primary outcome was reduction in worries as measured by the Penn State Questionnaire. The WOJ group showed a significant reduction, compared with controls, immediately post-treatment – which remained significant, albeit attenuated to a moderate effect size, at 30 days.
At day 10, 18 of 29 WOJ users no longer met diagnostic criteria for GAD, compared with 6 of 22 controls. By day 30, however, there was no significant between-group difference on this secondary endpoint.
The WOJ group showed a significantly greater reduction than controls on the secondary endpoint of uncontrollability of beliefs at both days 10 and 30.
“The WOJ may be a viable ecological momentary intervention for reducing worry in GAD. Therapist-free use of WOJ led to decreased worrying after only 10 days. It’s quite possible that longer practice may yield even stronger results. After all, for a normal CBT protocol, we’re looking at 8-20 weeks of treatment,” Mr. LaFreniere observed.
“I’d like to underscore that there was no harm done: The WOJ didn’t increase detrimental beliefs about worry,” he added. “We had a worry ourselves as researchers – disconfirmed by the trial – that patients may take the non-occurrence of their worries as some kind of proof that worry prevented those bad things from happening.”
Mr. LaFreniere is interested in studying the WOJ for worry reduction in non-GAD populations.
“Worry can be very high in other anxiety disorders, major depressive disorder, bipolar disorders, and in insomnia. The WOJ is highly cost-effective and easy to disseminate. It could very easily be made into a smartphone app,” he said.
Relaxation-induced anxiety
Relaxation training often is incorporated in treatment packages for GAD. Yet, it’s possible that one reason CBT is only modestly effective for GAD is because of relaxation-induced anxiety (RIA), an understudied phenomenon defined as a paradoxical increase in the physiological, behavioral, and cognitive aspects of anxiety when a person tries to relax.
“It has been theorized that individuals who are especially concerned with maintaining control over physical and psychological processes find relaxation vulnerable, unpleasant, and activating. Thus, discomfort with perceived lack of control during relaxed moments – an inability to let go – may result in unsought increase in anxiety during therapeutic attempts at relaxation,” according to Michelle G. Newman, PhD, professor of psychology at Penn State.
She presented a secondary analysis of a published randomized clinical trial she coauthored (J Consult Clin Psychol. 2002 Apr;70[2]:288-98) in which 41 participants with GAD were assigned to CBT with relaxation therapy using standard progressive muscle relaxation techniques or to self-control desensitization. Relaxation therapy and relaxation-induced anxiety ratings were recorded at each session. Outcomes were assessed post-treatment and at 6, 12, and 24 months of follow-up using the Penn State Worry Questionnaire, the State-Trait Anxiety Inventory, the Hamilton Anxiety Rating Scale, and the Clinician Severity Rating for GAD symptoms. In addition, immediately after each in-session relaxation practice, patients were asked to rate on a 9-point scale how much they noticed an increase in anxiety during the relaxation session.
All subjects improved significantly, but those with a lower peak RIA – defined as the highest level of RIA experienced in any of the 14 treatment sessions – had significantly fewer GAD symptoms at the end of therapy as well as at 2-year follow-up. Peak RIA was unrelated to baseline GAD symptom severity or change over time in anxiety symptoms. However, patients whose peak RIA occurred during the last several treatment sessions showed less improvement in GAD symptoms at the conclusion of treatment than those whose peak came earlier.
The clinical implications of these findings are that therapists who use progressive muscle relaxation in the treatment of GAD should assess RIA at the conclusion of every session, and if a patient reports moderate or higher RIA, the duration of the relaxation training portion of therapy should not be shortened until after several consecutive sessions of lower RIA have been reported, according to Dr. Newman.
Emotion regulation therapy
Megan E. Renna brought attendees up to speed on emotion regulation therapy (ERT), a third wave variant of CBT that incorporates principles from more traditional CBT, such as skills training and exposure, supplemented by teaching emotion regulation skills. Those skills include the development of present moment awareness and cultivation of compassion. Both are grounded in research on motivational and regulatory learning mechanisms related to threat vs. safety and reward versus loss.
As detailed in a recent review article for which she was first author (Front Psychol. 2017 Feb 6;8:98), ERT is a manualized, mechanism-targeted treatment for what she termed “distress disorders”; namely, GAD and major depressive disorder, which are highly comorbid, share key underlying temperamental features, and for whom adequate therapeutic success is all too often elusive. ERT appears to be particularly useful during the emerging adulthood years and across a broad range of ethnic and racial patients, according to Ms. Renna, a PhD student in clinical psychology at Hunter College in New York.
The efficacy of the original 20-session, individual therapy version of ERT was established in a study of 20 GAD patients, half of whom also had major depression (Depress Anxiety. 2015 Aug;32[8]:614-23). But Ms. Renna said ERT’s developers – Douglas S. Mennin, PhD, of Hunter College, and David M. Fresco, PhD, of Kent State (Ohio) University, are interested in determining the minimum effective therapeutic dose of ERT. They have conducted an open randomized trial of a 16-session version of ERT in which the results proved similar to those seen with 20 sessions. Now they’re carrying out a study of 8 vs. 16 sessions. The study is ongoing, but at first look, the results with 8 sessions of ERT appear similar to 16, Ms. Renna said.
None of the speakers reported having any financial conflicts of interest.
SAN FRANCISCO – The search is on for ways to refine cognitive-behavioral therapy for generalized anxiety disorder in order to improve upon current relatively modest success rates.
Cognitive-behavioral therapy (CBT) is less effective for generalized anxiety disorder (GAD) than for the other anxiety disorders. Only about one-half of patients are improved post-treatment, and less than one-third reach recovery, noted Richard E. Zinbarg, PhD, at the annual conference of the Anxiety and Depression Association of America.
At a session on advances in treatment of GAD, investigators presented randomized clinical trials assessing a variety of specific strategies aimed at enhancing the effectiveness of CBT in evidence-based fashion. The trials included a study of the impact of having patients keep a worry outcome journal, an exploration of the potential deleterious effects of a phenomenon known as relaxation-induced anxiety, and a study of the effectiveness of emotion regulation therapy, a relatively recent form of psychotherapy that’s part of the so-called “third wave” of CBT.
Worry outcome journal
Lucas LaFreniere observed that while CBT has been broadly shown to be effective for GAD, the various forms of CBT are packages of components that often include psychoeducation, stimulus control, behavioral experiments, exposure, cognitive reframing, relaxation training, and other elements in various combinations and sequences. Almost none of these specific components has been evaluated formally to learn whether they are pulling their weight therapeutically and making a positive contribution to outcomes.
Mr. LaFreniere, a doctoral student in clinical psychology at Pennsylvania State University in Hershey, presented a randomized trial of one such component, worry outcome monitoring, which currently is incorporated in some but not all CBT programs for GAD. Mr. LaFreniere and his coinvestigators developed a version of worry outcome monitoring they dubbed the worry outcome journal, or WOJ, which he characterized as “a brief ecological momentary intervention for worry.”
The WOJ works like this: At four random times per day, WOJ users receive a phone message to drop what they’re doing and record on a chart what they’re currently worrying about. They briefly note the date and time, the content of their worry, the distress it’s causing on a 1-7 scale, how much time they’re spending thinking about it, and their prediction as to the likelihood that this negative event actually will come to pass, which by the nature of their illness generally is unrealistically sky high early on in treatment. Later, they return to record whether the worrisome outcome occurred. The WOJ data are often reviewed in session.
The hypothesis was that the WOJ would reduce worry by aiding GAD patients in attending to their worries more thoroughly and objectively, recognizing in the moment the high cost of their worrying in terms of distress and cognitive interference, forming more realistic predictions about the future, and changing their conviction that excessive worrying is a worthwhile use of their time.
“One thing that particularly motivates me as a treatment researcher is the idea that those with GAD could be making themselves chronically miserable in an effort to protect themselves from future catastrophes that likely are not even going to happen. That’s a lot of human suffering that isn’t necessary. What we can do to help with that, we should do,” Mr. LaFreniere said.
On the other hand, this was a matter that cried out for a controlled trial because of the possibility that attempts to reduce worry might have unintended harmful consequences.
“Those with GAD have positive beliefs about worry. They believe it’s useful: it motivates, buffers emotional shifts, facilitates problem solving, and marks you as caring and conscientious – good personality traits,” he explained.
His study included 51 GAD patients randomized to 10 days using the WOJ or to a thought log control condition in which prompted by their cell phone four times daily, they recorded whatever everyday thought was on their mind at the moment. An example drawn from personal experience, Mr. LaFreniere said, might be “I love enchiladas!”
Outcome measures evaluated at baseline, again at 10 days upon conclusion of the intervention, and finally at 30 days of follow-up were the Penn State Worry Questionnaire, the GAD Questionnaire for DSM-IV, and the Meta-Cognitions Questionnaire subscales for positive beliefs about worry, uncontrollability of one’s thoughts, and negative beliefs about worry.
“The big reveal was that 91% of their worries did not come true,” he reported.
The primary outcome was reduction in worries as measured by the Penn State Questionnaire. The WOJ group showed a significant reduction, compared with controls, immediately post-treatment – which remained significant, albeit attenuated to a moderate effect size, at 30 days.
At day 10, 18 of 29 WOJ users no longer met diagnostic criteria for GAD, compared with 6 of 22 controls. By day 30, however, there was no significant between-group difference on this secondary endpoint.
The WOJ group showed a significantly greater reduction than controls on the secondary endpoint of uncontrollability of beliefs at both days 10 and 30.
“The WOJ may be a viable ecological momentary intervention for reducing worry in GAD. Therapist-free use of WOJ led to decreased worrying after only 10 days. It’s quite possible that longer practice may yield even stronger results. After all, for a normal CBT protocol, we’re looking at 8-20 weeks of treatment,” Mr. LaFreniere observed.
“I’d like to underscore that there was no harm done: The WOJ didn’t increase detrimental beliefs about worry,” he added. “We had a worry ourselves as researchers – disconfirmed by the trial – that patients may take the non-occurrence of their worries as some kind of proof that worry prevented those bad things from happening.”
Mr. LaFreniere is interested in studying the WOJ for worry reduction in non-GAD populations.
“Worry can be very high in other anxiety disorders, major depressive disorder, bipolar disorders, and in insomnia. The WOJ is highly cost-effective and easy to disseminate. It could very easily be made into a smartphone app,” he said.
Relaxation-induced anxiety
Relaxation training often is incorporated in treatment packages for GAD. Yet, it’s possible that one reason CBT is only modestly effective for GAD is because of relaxation-induced anxiety (RIA), an understudied phenomenon defined as a paradoxical increase in the physiological, behavioral, and cognitive aspects of anxiety when a person tries to relax.
“It has been theorized that individuals who are especially concerned with maintaining control over physical and psychological processes find relaxation vulnerable, unpleasant, and activating. Thus, discomfort with perceived lack of control during relaxed moments – an inability to let go – may result in unsought increase in anxiety during therapeutic attempts at relaxation,” according to Michelle G. Newman, PhD, professor of psychology at Penn State.
She presented a secondary analysis of a published randomized clinical trial she coauthored (J Consult Clin Psychol. 2002 Apr;70[2]:288-98) in which 41 participants with GAD were assigned to CBT with relaxation therapy using standard progressive muscle relaxation techniques or to self-control desensitization. Relaxation therapy and relaxation-induced anxiety ratings were recorded at each session. Outcomes were assessed post-treatment and at 6, 12, and 24 months of follow-up using the Penn State Worry Questionnaire, the State-Trait Anxiety Inventory, the Hamilton Anxiety Rating Scale, and the Clinician Severity Rating for GAD symptoms. In addition, immediately after each in-session relaxation practice, patients were asked to rate on a 9-point scale how much they noticed an increase in anxiety during the relaxation session.
All subjects improved significantly, but those with a lower peak RIA – defined as the highest level of RIA experienced in any of the 14 treatment sessions – had significantly fewer GAD symptoms at the end of therapy as well as at 2-year follow-up. Peak RIA was unrelated to baseline GAD symptom severity or change over time in anxiety symptoms. However, patients whose peak RIA occurred during the last several treatment sessions showed less improvement in GAD symptoms at the conclusion of treatment than those whose peak came earlier.
The clinical implications of these findings are that therapists who use progressive muscle relaxation in the treatment of GAD should assess RIA at the conclusion of every session, and if a patient reports moderate or higher RIA, the duration of the relaxation training portion of therapy should not be shortened until after several consecutive sessions of lower RIA have been reported, according to Dr. Newman.
Emotion regulation therapy
Megan E. Renna brought attendees up to speed on emotion regulation therapy (ERT), a third wave variant of CBT that incorporates principles from more traditional CBT, such as skills training and exposure, supplemented by teaching emotion regulation skills. Those skills include the development of present moment awareness and cultivation of compassion. Both are grounded in research on motivational and regulatory learning mechanisms related to threat vs. safety and reward versus loss.
As detailed in a recent review article for which she was first author (Front Psychol. 2017 Feb 6;8:98), ERT is a manualized, mechanism-targeted treatment for what she termed “distress disorders”; namely, GAD and major depressive disorder, which are highly comorbid, share key underlying temperamental features, and for whom adequate therapeutic success is all too often elusive. ERT appears to be particularly useful during the emerging adulthood years and across a broad range of ethnic and racial patients, according to Ms. Renna, a PhD student in clinical psychology at Hunter College in New York.
The efficacy of the original 20-session, individual therapy version of ERT was established in a study of 20 GAD patients, half of whom also had major depression (Depress Anxiety. 2015 Aug;32[8]:614-23). But Ms. Renna said ERT’s developers – Douglas S. Mennin, PhD, of Hunter College, and David M. Fresco, PhD, of Kent State (Ohio) University, are interested in determining the minimum effective therapeutic dose of ERT. They have conducted an open randomized trial of a 16-session version of ERT in which the results proved similar to those seen with 20 sessions. Now they’re carrying out a study of 8 vs. 16 sessions. The study is ongoing, but at first look, the results with 8 sessions of ERT appear similar to 16, Ms. Renna said.
None of the speakers reported having any financial conflicts of interest.
EXPERT ANALYSIS FROM THE ANXIETY AND DEPRESSION CONFERENCE 2017
All isn’t well with HIV-exposed uninfected infants
MADRID – Children who were HIV-exposed antenatally but not infected are at double the risk of hospitalization for infectious diseases during their first year of life, compared with HIV-unexposed controls, according to what’s believed to be the first prospective study examining the issue in a Western industrialized country.
That’s one key take-away message from the study conducted in Brussels. Another key finding was that the sharply increased risk of hospitalization for infection during infancy was erased if HIV-infected mothers started antiretroviral therapy prior to, rather than during, pregnancy, Catherine Adler, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a prospective study of 125 HIV-positive and 119 HIV-negative pregnant Belgian women of comparable ethnic and sociodemographic backgrounds. All of the HIV-positive mothers were on antiretroviral therapy, which they started either prior to or during pregnancy.
The two groups of women gave birth to 132 HEU and 123 HIV-unexposed babies, all born after 35 weeks’ gestation. The babies didn’t differ in terms of gender, prematurity rate, mode of delivery, or the use of antibiotics at delivery. However, 17% of the HEU babies had a birth weight below 2,500 g, compared with just 3% of the HIV-unexposed controls. Also, as a matter of policy, none of the HEU babies were breastfed, while 95% of the controls were, Dr. Adler explained.
The primary outcome in the study was the rate of hospitalization for infection during the first 12 months of life. The rate was 21% in the HEU babies, significantly greater than the 11% rate in HIV-unexposed babies. In a multivariate analysis adjusted for preterm birth, low birth weight, literacy, and maternal age, HEU status was associated with twofold increased risk of hospitalization for infection in infancy.
“The increased susceptibility of HEU infants to infectious disease is not restricted to children born in developing countries,” she declared.
The disparity in hospitalization rates was driven by hospitalization for viral infections, which occurred at a rate of 20% in the HEU group, versus 9% in controls. Particularly notable were the 10 hospitalizations for respiratory syncytial virus infection in the HEU patients, compared with just 1 in the controls.
Dr. Adler and her coinvestigators will continue following the children out to about 3 years of age. After age 12 months, the two groups no longer differed significantly in their risk of hospitalization for infection.
“The first year is a vulnerable period. Our data highlight the importance of a close follow-up of these infants,” she said.
The biggest risk factor for hospitalization for infectious illness in the HEU group was initiation of antiretroviral therapy during pregnancy. The hospitalization rate in HEU infants whose mothers began therapy prior to pregnancy was the same as in HIV-unexposed infants. The inference is that it’s not in utero exposure to antiretroviral drugs that is responsible for the increased risk of hospitalization during infancy.
“This observation supports the notion that it’s the activity of the maternal HIV infection – the exposure to a strongly proinflammatory state in the mother – that contributes to the risk of severe infection in HEU infants, probably by causing changes in innate immunity cells,” according to Dr. Adler.
Even though the increased risk of hospitalization for infectious illnesses in HEU children falls off after age 12 months, she continued, her group is following them out to about age 3 years because “we have the impression that they are at risk for neurodevelopmental problems, including language delay.”
Other researchers in the audience confirmed this risk, reporting that, as they follow HEU children through adolescence, they see an increased rate of attention deficits and associated comorbidities.
Dr. Adler called the administration of antiretroviral therapy to pregnant HIV-infected women in order to prevent maternal-to-child transmission of the disease “one of the major successes of the 21st century.”
“The number of new HIV infections among children has collapsed, leading to an increasing number of HIV-exposed but uninfected children. One million of them are born each year,” she said.
Dr. Adler reported having no financial conflicts of interest regarding her study.
*The article was updated 6/15/17.
MADRID – Children who were HIV-exposed antenatally but not infected are at double the risk of hospitalization for infectious diseases during their first year of life, compared with HIV-unexposed controls, according to what’s believed to be the first prospective study examining the issue in a Western industrialized country.
That’s one key take-away message from the study conducted in Brussels. Another key finding was that the sharply increased risk of hospitalization for infection during infancy was erased if HIV-infected mothers started antiretroviral therapy prior to, rather than during, pregnancy, Catherine Adler, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a prospective study of 125 HIV-positive and 119 HIV-negative pregnant Belgian women of comparable ethnic and sociodemographic backgrounds. All of the HIV-positive mothers were on antiretroviral therapy, which they started either prior to or during pregnancy.
The two groups of women gave birth to 132 HEU and 123 HIV-unexposed babies, all born after 35 weeks’ gestation. The babies didn’t differ in terms of gender, prematurity rate, mode of delivery, or the use of antibiotics at delivery. However, 17% of the HEU babies had a birth weight below 2,500 g, compared with just 3% of the HIV-unexposed controls. Also, as a matter of policy, none of the HEU babies were breastfed, while 95% of the controls were, Dr. Adler explained.
The primary outcome in the study was the rate of hospitalization for infection during the first 12 months of life. The rate was 21% in the HEU babies, significantly greater than the 11% rate in HIV-unexposed babies. In a multivariate analysis adjusted for preterm birth, low birth weight, literacy, and maternal age, HEU status was associated with twofold increased risk of hospitalization for infection in infancy.
“The increased susceptibility of HEU infants to infectious disease is not restricted to children born in developing countries,” she declared.
The disparity in hospitalization rates was driven by hospitalization for viral infections, which occurred at a rate of 20% in the HEU group, versus 9% in controls. Particularly notable were the 10 hospitalizations for respiratory syncytial virus infection in the HEU patients, compared with just 1 in the controls.
Dr. Adler and her coinvestigators will continue following the children out to about 3 years of age. After age 12 months, the two groups no longer differed significantly in their risk of hospitalization for infection.
“The first year is a vulnerable period. Our data highlight the importance of a close follow-up of these infants,” she said.
The biggest risk factor for hospitalization for infectious illness in the HEU group was initiation of antiretroviral therapy during pregnancy. The hospitalization rate in HEU infants whose mothers began therapy prior to pregnancy was the same as in HIV-unexposed infants. The inference is that it’s not in utero exposure to antiretroviral drugs that is responsible for the increased risk of hospitalization during infancy.
“This observation supports the notion that it’s the activity of the maternal HIV infection – the exposure to a strongly proinflammatory state in the mother – that contributes to the risk of severe infection in HEU infants, probably by causing changes in innate immunity cells,” according to Dr. Adler.
Even though the increased risk of hospitalization for infectious illnesses in HEU children falls off after age 12 months, she continued, her group is following them out to about age 3 years because “we have the impression that they are at risk for neurodevelopmental problems, including language delay.”
Other researchers in the audience confirmed this risk, reporting that, as they follow HEU children through adolescence, they see an increased rate of attention deficits and associated comorbidities.
Dr. Adler called the administration of antiretroviral therapy to pregnant HIV-infected women in order to prevent maternal-to-child transmission of the disease “one of the major successes of the 21st century.”
“The number of new HIV infections among children has collapsed, leading to an increasing number of HIV-exposed but uninfected children. One million of them are born each year,” she said.
Dr. Adler reported having no financial conflicts of interest regarding her study.
*The article was updated 6/15/17.
MADRID – Children who were HIV-exposed antenatally but not infected are at double the risk of hospitalization for infectious diseases during their first year of life, compared with HIV-unexposed controls, according to what’s believed to be the first prospective study examining the issue in a Western industrialized country.
That’s one key take-away message from the study conducted in Brussels. Another key finding was that the sharply increased risk of hospitalization for infection during infancy was erased if HIV-infected mothers started antiretroviral therapy prior to, rather than during, pregnancy, Catherine Adler, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a prospective study of 125 HIV-positive and 119 HIV-negative pregnant Belgian women of comparable ethnic and sociodemographic backgrounds. All of the HIV-positive mothers were on antiretroviral therapy, which they started either prior to or during pregnancy.
The two groups of women gave birth to 132 HEU and 123 HIV-unexposed babies, all born after 35 weeks’ gestation. The babies didn’t differ in terms of gender, prematurity rate, mode of delivery, or the use of antibiotics at delivery. However, 17% of the HEU babies had a birth weight below 2,500 g, compared with just 3% of the HIV-unexposed controls. Also, as a matter of policy, none of the HEU babies were breastfed, while 95% of the controls were, Dr. Adler explained.
The primary outcome in the study was the rate of hospitalization for infection during the first 12 months of life. The rate was 21% in the HEU babies, significantly greater than the 11% rate in HIV-unexposed babies. In a multivariate analysis adjusted for preterm birth, low birth weight, literacy, and maternal age, HEU status was associated with twofold increased risk of hospitalization for infection in infancy.
“The increased susceptibility of HEU infants to infectious disease is not restricted to children born in developing countries,” she declared.
The disparity in hospitalization rates was driven by hospitalization for viral infections, which occurred at a rate of 20% in the HEU group, versus 9% in controls. Particularly notable were the 10 hospitalizations for respiratory syncytial virus infection in the HEU patients, compared with just 1 in the controls.
Dr. Adler and her coinvestigators will continue following the children out to about 3 years of age. After age 12 months, the two groups no longer differed significantly in their risk of hospitalization for infection.
“The first year is a vulnerable period. Our data highlight the importance of a close follow-up of these infants,” she said.
The biggest risk factor for hospitalization for infectious illness in the HEU group was initiation of antiretroviral therapy during pregnancy. The hospitalization rate in HEU infants whose mothers began therapy prior to pregnancy was the same as in HIV-unexposed infants. The inference is that it’s not in utero exposure to antiretroviral drugs that is responsible for the increased risk of hospitalization during infancy.
“This observation supports the notion that it’s the activity of the maternal HIV infection – the exposure to a strongly proinflammatory state in the mother – that contributes to the risk of severe infection in HEU infants, probably by causing changes in innate immunity cells,” according to Dr. Adler.
Even though the increased risk of hospitalization for infectious illnesses in HEU children falls off after age 12 months, she continued, her group is following them out to about age 3 years because “we have the impression that they are at risk for neurodevelopmental problems, including language delay.”
Other researchers in the audience confirmed this risk, reporting that, as they follow HEU children through adolescence, they see an increased rate of attention deficits and associated comorbidities.
Dr. Adler called the administration of antiretroviral therapy to pregnant HIV-infected women in order to prevent maternal-to-child transmission of the disease “one of the major successes of the 21st century.”
“The number of new HIV infections among children has collapsed, leading to an increasing number of HIV-exposed but uninfected children. One million of them are born each year,” she said.
Dr. Adler reported having no financial conflicts of interest regarding her study.
*The article was updated 6/15/17.
AT ESPID 2017
Key clinical point:
Major finding: The rate of hospitalization for a serious infectious illness during the first 12 months of life was 21% in HIV-exposed uninfected children, significantly greater than the 11% rate in HIV-unexposed babies.
Data source: This prospective observational study included 125 HIV-positive and 119 HIV-negative pregnant Belgian women of comparable ethnic and sociodemographic backgrounds and their offspring, followed to date through the infants’ first birthday.
Disclosures: Dr. Adler reported having no financial conflicts of interest.
Whole blood PCR improves diagnosis of pediatric bacterial sepsis
MADRID – Whole blood multiplex polymerase chain reaction (PCR) holds considerable promise as a rapid noninvasive test to improve diagnosis of life-threatening bacterial infections in children with suspected sepsis yet negative blood cultures, Clare Thakker, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
There are several disadvantages with blood cultures – the current diagnostic standard. The turnaround time is 48 hours or longer. Moreover, false-negative culture results are common because of prior antibiotic therapy. And blood cultures require a considerable amount of blood, which becomes an issue in younger children with small blood volumes. Whole blood PCR is unfettered by these limitations, and it could reduce the need for invasive sampling, such as pleural or joint aspiration or CSF sampling, in blood culture–negative children, observed Dr. Thakker of Imperial College London.
The challenge posed by febrile children is that even though the vast majority will turn out to have a self-limited viral illness, a small proportion will have a life-threatening bacterial infection. And distinguishing between the two groups in timely fashion often remains difficult today, the pediatrician said.
Dr. Thakker reported on 504 EUCLIDS participants with suspected sepsis who had blood cultures and whole blood PCR testing done on the same day. The multiplex PCR, developed by Micropathology of Coventry, England, was set up to test simultaneously for five clinically important bacterial pathogens: Neisseria meningitidis, Streptococcus pneumoniae, S. pyogenes, Staphylococcus aureus, and Haemophilus influenzae. Prior to testing, the blood samples underwent lysozyme/lysostaphin digestion and silica bead disruption in order to break down cell walls and facilitate nucleic acid extraction.
Of the 504 children with suspected sepsis, 438 (87%) had negative blood cultures, among whom were 326 patients (74%) with clinically suspected or definite bacterial infection. The PCR test identified one of the five target pathogens in 25 of the 326 patients (8%) where physicians suspected bacterial sepsis despite negative cultures. Ten blood culture-negative patients (40%) were whole blood PCR positive for N. meningitidis, 6 (24%) for H. influenzae, 5 (20%) for S. pneumoniae, 3 (12%) for S. aureus, and 1 (4%) for S. pyogenes. Three of the 25 positive tests showed poor clinical correlation consistent with environmental contamination. The other 22 positive PCR results were consistent with the patient’s clinical syndrome – for example, N. meningitidis being found in the blood of a child with meningeal encephalitis – or concordant with the results of a culture obtained invasively at a sterile body site.
Ninety-two patients with negative blood cultures were culture positive for a causative bacterial pathogen obtained by invasive sampling of a sterile body site such as the CSF. In 68 of these 92 cases (74%), the pathogen was among those on the multiplex PCR panel.
“Our study results bring into question whether blood culture should be the gold standard; clearly, blood culture is not capturing everything. Our findings also highlight the need for developing additional diagnostic markers, maybe based upon the host inflammatory response, to delineate which of these detections are pathogens and which are passengers,” Dr. Thakker said.
She reported having no relevant financial conflicts regarding the European Union–sponsored study.
MADRID – Whole blood multiplex polymerase chain reaction (PCR) holds considerable promise as a rapid noninvasive test to improve diagnosis of life-threatening bacterial infections in children with suspected sepsis yet negative blood cultures, Clare Thakker, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
There are several disadvantages with blood cultures – the current diagnostic standard. The turnaround time is 48 hours or longer. Moreover, false-negative culture results are common because of prior antibiotic therapy. And blood cultures require a considerable amount of blood, which becomes an issue in younger children with small blood volumes. Whole blood PCR is unfettered by these limitations, and it could reduce the need for invasive sampling, such as pleural or joint aspiration or CSF sampling, in blood culture–negative children, observed Dr. Thakker of Imperial College London.
The challenge posed by febrile children is that even though the vast majority will turn out to have a self-limited viral illness, a small proportion will have a life-threatening bacterial infection. And distinguishing between the two groups in timely fashion often remains difficult today, the pediatrician said.
Dr. Thakker reported on 504 EUCLIDS participants with suspected sepsis who had blood cultures and whole blood PCR testing done on the same day. The multiplex PCR, developed by Micropathology of Coventry, England, was set up to test simultaneously for five clinically important bacterial pathogens: Neisseria meningitidis, Streptococcus pneumoniae, S. pyogenes, Staphylococcus aureus, and Haemophilus influenzae. Prior to testing, the blood samples underwent lysozyme/lysostaphin digestion and silica bead disruption in order to break down cell walls and facilitate nucleic acid extraction.
Of the 504 children with suspected sepsis, 438 (87%) had negative blood cultures, among whom were 326 patients (74%) with clinically suspected or definite bacterial infection. The PCR test identified one of the five target pathogens in 25 of the 326 patients (8%) where physicians suspected bacterial sepsis despite negative cultures. Ten blood culture-negative patients (40%) were whole blood PCR positive for N. meningitidis, 6 (24%) for H. influenzae, 5 (20%) for S. pneumoniae, 3 (12%) for S. aureus, and 1 (4%) for S. pyogenes. Three of the 25 positive tests showed poor clinical correlation consistent with environmental contamination. The other 22 positive PCR results were consistent with the patient’s clinical syndrome – for example, N. meningitidis being found in the blood of a child with meningeal encephalitis – or concordant with the results of a culture obtained invasively at a sterile body site.
Ninety-two patients with negative blood cultures were culture positive for a causative bacterial pathogen obtained by invasive sampling of a sterile body site such as the CSF. In 68 of these 92 cases (74%), the pathogen was among those on the multiplex PCR panel.
“Our study results bring into question whether blood culture should be the gold standard; clearly, blood culture is not capturing everything. Our findings also highlight the need for developing additional diagnostic markers, maybe based upon the host inflammatory response, to delineate which of these detections are pathogens and which are passengers,” Dr. Thakker said.
She reported having no relevant financial conflicts regarding the European Union–sponsored study.
MADRID – Whole blood multiplex polymerase chain reaction (PCR) holds considerable promise as a rapid noninvasive test to improve diagnosis of life-threatening bacterial infections in children with suspected sepsis yet negative blood cultures, Clare Thakker, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
There are several disadvantages with blood cultures – the current diagnostic standard. The turnaround time is 48 hours or longer. Moreover, false-negative culture results are common because of prior antibiotic therapy. And blood cultures require a considerable amount of blood, which becomes an issue in younger children with small blood volumes. Whole blood PCR is unfettered by these limitations, and it could reduce the need for invasive sampling, such as pleural or joint aspiration or CSF sampling, in blood culture–negative children, observed Dr. Thakker of Imperial College London.
The challenge posed by febrile children is that even though the vast majority will turn out to have a self-limited viral illness, a small proportion will have a life-threatening bacterial infection. And distinguishing between the two groups in timely fashion often remains difficult today, the pediatrician said.
Dr. Thakker reported on 504 EUCLIDS participants with suspected sepsis who had blood cultures and whole blood PCR testing done on the same day. The multiplex PCR, developed by Micropathology of Coventry, England, was set up to test simultaneously for five clinically important bacterial pathogens: Neisseria meningitidis, Streptococcus pneumoniae, S. pyogenes, Staphylococcus aureus, and Haemophilus influenzae. Prior to testing, the blood samples underwent lysozyme/lysostaphin digestion and silica bead disruption in order to break down cell walls and facilitate nucleic acid extraction.
Of the 504 children with suspected sepsis, 438 (87%) had negative blood cultures, among whom were 326 patients (74%) with clinically suspected or definite bacterial infection. The PCR test identified one of the five target pathogens in 25 of the 326 patients (8%) where physicians suspected bacterial sepsis despite negative cultures. Ten blood culture-negative patients (40%) were whole blood PCR positive for N. meningitidis, 6 (24%) for H. influenzae, 5 (20%) for S. pneumoniae, 3 (12%) for S. aureus, and 1 (4%) for S. pyogenes. Three of the 25 positive tests showed poor clinical correlation consistent with environmental contamination. The other 22 positive PCR results were consistent with the patient’s clinical syndrome – for example, N. meningitidis being found in the blood of a child with meningeal encephalitis – or concordant with the results of a culture obtained invasively at a sterile body site.
Ninety-two patients with negative blood cultures were culture positive for a causative bacterial pathogen obtained by invasive sampling of a sterile body site such as the CSF. In 68 of these 92 cases (74%), the pathogen was among those on the multiplex PCR panel.
“Our study results bring into question whether blood culture should be the gold standard; clearly, blood culture is not capturing everything. Our findings also highlight the need for developing additional diagnostic markers, maybe based upon the host inflammatory response, to delineate which of these detections are pathogens and which are passengers,” Dr. Thakker said.
She reported having no relevant financial conflicts regarding the European Union–sponsored study.
AT ESPID 2017
Key clinical point:
Major finding: Twenty-five of 326 children (8%) clinically suspected of having bacterial sepsis despite negative blood cultures proved positive for one of five important bacterial pathogens upon whole blood multiplex PCR testing .
Data source: EUCLIDS, a large, ongoing, 5-year international genomic study aimed at learning why some children with a bacterial infection develop serious illness while others do not.
Disclosures: The European Union sponsored the study. Dr. Thakker reported having no relevant financial conflicts.
Transcranial magnetic stimulation shows more promise in refractory OCD
SAN FRANCISCO – Mounting evidence suggests that transcranial magnetic stimulation is an effective noninvasive therapy for obsessive-compulsive disorder refractory to first-line medications, Eric Hollander, MD, said at the annual conference of the Anxiety and Depression Association of America.
A novel treatment for obsessive-compulsive disorder (OCD) would be most welcome. This is a disorder that’s common – affecting 2%-3% of the population – debilitating, and notoriously tough to treat. Roughly half of patients with OCD don’t respond to first-line therapy, which is selective serotonin reuptake inhibitors, cognitive-behavioral therapy, or both, according to Dr. Hollander, director of the autism and obsessive-compulsive spectrum program as well as the anxiety and depression program at Albert Einstein College of Medicine in New York.
Four companies now have FDA-cleared TMS devices indicated for treatment of major depression: Brainsway, which markets a dTMS device, and Neuronetics, MagVenture, and Magstim, which sell repetitive TMS (rTMS) devices that do not penetrate as deeply beneath the skull as dTMS and therefore target different brain structures.
TMS for OCD is, at present, off-label therapy. Yet, there is now sufficient experience derived from formal clinical trials and off-label use in clinical practice to be able to state that the standard target area for rTMS is the supplementary motor area (SMA), according to Dr. Hollander.
He was senior author of a randomized open-label pilot study involving 50 consecutive OCD patients refractory to SSRIs. Half were assigned to a popular second-line strategy: augmentation with antipsychotic agents. The other half received five 20-minute-long rTMS sessions per week for 3 weeks using low-frequency 1 Hz bilateral stimulation of the SMA.
At 3 weeks, the treatment response rate as defined by at least a 25% reduction from baseline on the Yale-Brown Obsessive-Compulsive Scale (YBOCS) was 68% in the rTMS group, compared with 24% in the control arm. Thus, rTMS was better than treatment as usual (J Psychopharmacol. 2016 Jun;30[6]:568-78).
“That’s considerable improvement after only 3 weeks of stimulation, which is a very short time, compared to other OCD treatments,” the psychiatrist noted.
In another study, Dr. Hollander and his coinvestigators used the same rTMS regimen targeting the SMA in 22 SSRI-refractory OCD patients. After 3 weeks of rTMS, 12 of the 22 were treatment responders and 3 patients were in remission.
Moreover, these effects were long-lasting. At 6 months, 13 patients were responders and 4 were in remission, and, at 12 months – nearly a year after their relatively brief course of rTMS – there were 12 responders and 3 remitters.
Participants also showed significant reductions on both the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A), effects that were sustained during follow-up, although the improvement in OCD symptoms was more impressive, he said.
Other investigators also have reported positive results using rTMS for OCD, with the first publication coming from Italian investigators more than a decade ago (Int J Neuropsychopharmacol. 2006 Feb;9[1]:95-100).
Studies of dTMS for OCD are a more recent development. In 2016, investigators reported on 40 OCD patients treated double-blind with either high-stimulation dTMS at 20 Hz, low-stimulation at 1 Hz, or a sham magnetic coil daily for 5 weeks. The target areas were the medial prefrontal and anterior cingulate cortices, areas too deep to be reached using rTMS. At the 5-week mark, the patients who received high-stimulation dTMS showed a mean 26% improvement in YBOCS scores, compared with a 6% reduction in the low-stimulation and sham-treatment arms.
In this study, electroencephalogram evoked potential responses over the anterior cingulate cortex correlated with clinical response, thus providing a welcome biomarker of treatment efficacy.
How TMS works in OCD
TMS involves placing a coil on the scalp to create a magnetic pulse that passes through the skull and achieves predictable changes in neuronal activity in brain tissue, either exciting or deactivating target regions depending upon whether high- or low-frequency TMS is applied.
Brain imaging studies show that OCD is characterized by hyperactivation of the medial frontal cortex and the SMA. The dysfunctional circuitry of OCD has been worked out. It’s striatally based, involving frontal-striatal-thalamic circuits. The SMA sits right above the anterior cingulate cortex and provides access to these key pathways. Basically, increased neuronal activity in the frontal lobes of OCD patients results in miscommunication with the striatal and thalamic regions, with resultant thalamic hyperactivity. This failure of cortical inhibition leads to persistent intrusive thoughts and behaviors, Dr. Hollander explained.
The neural circuitry of OCD is distinct from that of other anxiety disorders, and it appears that TMS is not as effective in those disorders as in OCD, he added.
The anterior cingulate is one step closer than the SMA to the frontal-striatal-thalamic circuits, which are of particular therapeutic interest in OCD, and it’s accessible by dTMS. Anterior cingulate activity is decreased in OCD. When high-frequency dTMS revs up that activity, the result is symptomatic improvement. Of note, the anterior cingulate also is the target for cingulotomy, an established surgical treatment for OCD.
Dr. Hollander reported receiving research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. He serves as a consultant to a number of pharmaceutical companies.
SAN FRANCISCO – Mounting evidence suggests that transcranial magnetic stimulation is an effective noninvasive therapy for obsessive-compulsive disorder refractory to first-line medications, Eric Hollander, MD, said at the annual conference of the Anxiety and Depression Association of America.
A novel treatment for obsessive-compulsive disorder (OCD) would be most welcome. This is a disorder that’s common – affecting 2%-3% of the population – debilitating, and notoriously tough to treat. Roughly half of patients with OCD don’t respond to first-line therapy, which is selective serotonin reuptake inhibitors, cognitive-behavioral therapy, or both, according to Dr. Hollander, director of the autism and obsessive-compulsive spectrum program as well as the anxiety and depression program at Albert Einstein College of Medicine in New York.
Four companies now have FDA-cleared TMS devices indicated for treatment of major depression: Brainsway, which markets a dTMS device, and Neuronetics, MagVenture, and Magstim, which sell repetitive TMS (rTMS) devices that do not penetrate as deeply beneath the skull as dTMS and therefore target different brain structures.
TMS for OCD is, at present, off-label therapy. Yet, there is now sufficient experience derived from formal clinical trials and off-label use in clinical practice to be able to state that the standard target area for rTMS is the supplementary motor area (SMA), according to Dr. Hollander.
He was senior author of a randomized open-label pilot study involving 50 consecutive OCD patients refractory to SSRIs. Half were assigned to a popular second-line strategy: augmentation with antipsychotic agents. The other half received five 20-minute-long rTMS sessions per week for 3 weeks using low-frequency 1 Hz bilateral stimulation of the SMA.
At 3 weeks, the treatment response rate as defined by at least a 25% reduction from baseline on the Yale-Brown Obsessive-Compulsive Scale (YBOCS) was 68% in the rTMS group, compared with 24% in the control arm. Thus, rTMS was better than treatment as usual (J Psychopharmacol. 2016 Jun;30[6]:568-78).
“That’s considerable improvement after only 3 weeks of stimulation, which is a very short time, compared to other OCD treatments,” the psychiatrist noted.
In another study, Dr. Hollander and his coinvestigators used the same rTMS regimen targeting the SMA in 22 SSRI-refractory OCD patients. After 3 weeks of rTMS, 12 of the 22 were treatment responders and 3 patients were in remission.
Moreover, these effects were long-lasting. At 6 months, 13 patients were responders and 4 were in remission, and, at 12 months – nearly a year after their relatively brief course of rTMS – there were 12 responders and 3 remitters.
Participants also showed significant reductions on both the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A), effects that were sustained during follow-up, although the improvement in OCD symptoms was more impressive, he said.
Other investigators also have reported positive results using rTMS for OCD, with the first publication coming from Italian investigators more than a decade ago (Int J Neuropsychopharmacol. 2006 Feb;9[1]:95-100).
Studies of dTMS for OCD are a more recent development. In 2016, investigators reported on 40 OCD patients treated double-blind with either high-stimulation dTMS at 20 Hz, low-stimulation at 1 Hz, or a sham magnetic coil daily for 5 weeks. The target areas were the medial prefrontal and anterior cingulate cortices, areas too deep to be reached using rTMS. At the 5-week mark, the patients who received high-stimulation dTMS showed a mean 26% improvement in YBOCS scores, compared with a 6% reduction in the low-stimulation and sham-treatment arms.
In this study, electroencephalogram evoked potential responses over the anterior cingulate cortex correlated with clinical response, thus providing a welcome biomarker of treatment efficacy.
How TMS works in OCD
TMS involves placing a coil on the scalp to create a magnetic pulse that passes through the skull and achieves predictable changes in neuronal activity in brain tissue, either exciting or deactivating target regions depending upon whether high- or low-frequency TMS is applied.
Brain imaging studies show that OCD is characterized by hyperactivation of the medial frontal cortex and the SMA. The dysfunctional circuitry of OCD has been worked out. It’s striatally based, involving frontal-striatal-thalamic circuits. The SMA sits right above the anterior cingulate cortex and provides access to these key pathways. Basically, increased neuronal activity in the frontal lobes of OCD patients results in miscommunication with the striatal and thalamic regions, with resultant thalamic hyperactivity. This failure of cortical inhibition leads to persistent intrusive thoughts and behaviors, Dr. Hollander explained.
The neural circuitry of OCD is distinct from that of other anxiety disorders, and it appears that TMS is not as effective in those disorders as in OCD, he added.
The anterior cingulate is one step closer than the SMA to the frontal-striatal-thalamic circuits, which are of particular therapeutic interest in OCD, and it’s accessible by dTMS. Anterior cingulate activity is decreased in OCD. When high-frequency dTMS revs up that activity, the result is symptomatic improvement. Of note, the anterior cingulate also is the target for cingulotomy, an established surgical treatment for OCD.
Dr. Hollander reported receiving research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. He serves as a consultant to a number of pharmaceutical companies.
SAN FRANCISCO – Mounting evidence suggests that transcranial magnetic stimulation is an effective noninvasive therapy for obsessive-compulsive disorder refractory to first-line medications, Eric Hollander, MD, said at the annual conference of the Anxiety and Depression Association of America.
A novel treatment for obsessive-compulsive disorder (OCD) would be most welcome. This is a disorder that’s common – affecting 2%-3% of the population – debilitating, and notoriously tough to treat. Roughly half of patients with OCD don’t respond to first-line therapy, which is selective serotonin reuptake inhibitors, cognitive-behavioral therapy, or both, according to Dr. Hollander, director of the autism and obsessive-compulsive spectrum program as well as the anxiety and depression program at Albert Einstein College of Medicine in New York.
Four companies now have FDA-cleared TMS devices indicated for treatment of major depression: Brainsway, which markets a dTMS device, and Neuronetics, MagVenture, and Magstim, which sell repetitive TMS (rTMS) devices that do not penetrate as deeply beneath the skull as dTMS and therefore target different brain structures.
TMS for OCD is, at present, off-label therapy. Yet, there is now sufficient experience derived from formal clinical trials and off-label use in clinical practice to be able to state that the standard target area for rTMS is the supplementary motor area (SMA), according to Dr. Hollander.
He was senior author of a randomized open-label pilot study involving 50 consecutive OCD patients refractory to SSRIs. Half were assigned to a popular second-line strategy: augmentation with antipsychotic agents. The other half received five 20-minute-long rTMS sessions per week for 3 weeks using low-frequency 1 Hz bilateral stimulation of the SMA.
At 3 weeks, the treatment response rate as defined by at least a 25% reduction from baseline on the Yale-Brown Obsessive-Compulsive Scale (YBOCS) was 68% in the rTMS group, compared with 24% in the control arm. Thus, rTMS was better than treatment as usual (J Psychopharmacol. 2016 Jun;30[6]:568-78).
“That’s considerable improvement after only 3 weeks of stimulation, which is a very short time, compared to other OCD treatments,” the psychiatrist noted.
In another study, Dr. Hollander and his coinvestigators used the same rTMS regimen targeting the SMA in 22 SSRI-refractory OCD patients. After 3 weeks of rTMS, 12 of the 22 were treatment responders and 3 patients were in remission.
Moreover, these effects were long-lasting. At 6 months, 13 patients were responders and 4 were in remission, and, at 12 months – nearly a year after their relatively brief course of rTMS – there were 12 responders and 3 remitters.
Participants also showed significant reductions on both the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A), effects that were sustained during follow-up, although the improvement in OCD symptoms was more impressive, he said.
Other investigators also have reported positive results using rTMS for OCD, with the first publication coming from Italian investigators more than a decade ago (Int J Neuropsychopharmacol. 2006 Feb;9[1]:95-100).
Studies of dTMS for OCD are a more recent development. In 2016, investigators reported on 40 OCD patients treated double-blind with either high-stimulation dTMS at 20 Hz, low-stimulation at 1 Hz, or a sham magnetic coil daily for 5 weeks. The target areas were the medial prefrontal and anterior cingulate cortices, areas too deep to be reached using rTMS. At the 5-week mark, the patients who received high-stimulation dTMS showed a mean 26% improvement in YBOCS scores, compared with a 6% reduction in the low-stimulation and sham-treatment arms.
In this study, electroencephalogram evoked potential responses over the anterior cingulate cortex correlated with clinical response, thus providing a welcome biomarker of treatment efficacy.
How TMS works in OCD
TMS involves placing a coil on the scalp to create a magnetic pulse that passes through the skull and achieves predictable changes in neuronal activity in brain tissue, either exciting or deactivating target regions depending upon whether high- or low-frequency TMS is applied.
Brain imaging studies show that OCD is characterized by hyperactivation of the medial frontal cortex and the SMA. The dysfunctional circuitry of OCD has been worked out. It’s striatally based, involving frontal-striatal-thalamic circuits. The SMA sits right above the anterior cingulate cortex and provides access to these key pathways. Basically, increased neuronal activity in the frontal lobes of OCD patients results in miscommunication with the striatal and thalamic regions, with resultant thalamic hyperactivity. This failure of cortical inhibition leads to persistent intrusive thoughts and behaviors, Dr. Hollander explained.
The neural circuitry of OCD is distinct from that of other anxiety disorders, and it appears that TMS is not as effective in those disorders as in OCD, he added.
The anterior cingulate is one step closer than the SMA to the frontal-striatal-thalamic circuits, which are of particular therapeutic interest in OCD, and it’s accessible by dTMS. Anterior cingulate activity is decreased in OCD. When high-frequency dTMS revs up that activity, the result is symptomatic improvement. Of note, the anterior cingulate also is the target for cingulotomy, an established surgical treatment for OCD.
Dr. Hollander reported receiving research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. He serves as a consultant to a number of pharmaceutical companies.
EXPERT ANALYSIS FROM THE ANXIETY AND DEPRESSION CONFERENCE 2017
Who’s best suited for Internet-based CBT?
SAN FRANCISCO – Nearly 6% of patients deteriorated during Internet-based cognitive-behavioral therapy (iCBT) in an individual patient data meta-analysis totaling 2,866 participants in 29 published clinical trials, Alexander Rozental, PhD, reported at the annual conference of the Anxiety and Depression Association of America.
On the other hand, the meta-analysis also highlighted the hazards of doing nothing for patients experiencing mental distress: 17.4% of patients deteriorated while in wait-list control groups in the 29 trials, a rate of harm triple the 5.8% deterioration rate in patients during iCBT, added Dr. Rozental, a clinical psychologist at Stockholm University.
This meta-analysis is one of the very few studies to look at the negative effects of a psychologic treatment. Psychotherapy research has focused almost entirely on the positive effects. That’s at odds with the way pharmacologic research is conducted, in which reporting of adverse events is mandatory, he noted.
Of patients in the meta-analysis, 61% sought treatment for anxiety disorders, 20% for depression, and the rest for erectile dysfunction, pathological gambling, or relationship problems.
iCBT is particularly popular in Sweden, where it was developed two decades ago as a means of disseminating evidence-based, manualized therapy to a broad population in a highly cost-effective manner. This form of psychotherapy typically entails 8 to 12 weekly treatment modules, with weekly assignments, predetermined deadlines, texts and exercises, and regular, albeit relatively brief, contact with a therapist via secure email.
Dr. Rozental and his coinvestigators reviewed individual patient data in search of predictors of treatment success or deterioration. A profile emerged of the patients least likely to deteriorate while on iCBT: older age, university-educated, in a stable relationship, and with a higher level of symptoms pretreatment.
“You might interpret the findings as an indicator for matching the right type of treatment to the right patient. Perhaps those [who] are younger, have less than a university degree, and are not in a relationship might be better off in a face to face treatment, at least in terms of preventing deterioration,” he observed in an interview. “This makes sense if you think about the amount of work you have to do on your own in Internet-based psychological treatments, which include limited access to a therapist and require reading a lot of text material.”
Patients participating in iCBT who fit that profile might need extra support from a therapist in order to improve, Dr. Rozental added.
He reported having no financial conflicts regarding his study, which was funded by the Swedish Research Council for Health, Working Life, and Welfare.
SAN FRANCISCO – Nearly 6% of patients deteriorated during Internet-based cognitive-behavioral therapy (iCBT) in an individual patient data meta-analysis totaling 2,866 participants in 29 published clinical trials, Alexander Rozental, PhD, reported at the annual conference of the Anxiety and Depression Association of America.
On the other hand, the meta-analysis also highlighted the hazards of doing nothing for patients experiencing mental distress: 17.4% of patients deteriorated while in wait-list control groups in the 29 trials, a rate of harm triple the 5.8% deterioration rate in patients during iCBT, added Dr. Rozental, a clinical psychologist at Stockholm University.
This meta-analysis is one of the very few studies to look at the negative effects of a psychologic treatment. Psychotherapy research has focused almost entirely on the positive effects. That’s at odds with the way pharmacologic research is conducted, in which reporting of adverse events is mandatory, he noted.
Of patients in the meta-analysis, 61% sought treatment for anxiety disorders, 20% for depression, and the rest for erectile dysfunction, pathological gambling, or relationship problems.
iCBT is particularly popular in Sweden, where it was developed two decades ago as a means of disseminating evidence-based, manualized therapy to a broad population in a highly cost-effective manner. This form of psychotherapy typically entails 8 to 12 weekly treatment modules, with weekly assignments, predetermined deadlines, texts and exercises, and regular, albeit relatively brief, contact with a therapist via secure email.
Dr. Rozental and his coinvestigators reviewed individual patient data in search of predictors of treatment success or deterioration. A profile emerged of the patients least likely to deteriorate while on iCBT: older age, university-educated, in a stable relationship, and with a higher level of symptoms pretreatment.
“You might interpret the findings as an indicator for matching the right type of treatment to the right patient. Perhaps those [who] are younger, have less than a university degree, and are not in a relationship might be better off in a face to face treatment, at least in terms of preventing deterioration,” he observed in an interview. “This makes sense if you think about the amount of work you have to do on your own in Internet-based psychological treatments, which include limited access to a therapist and require reading a lot of text material.”
Patients participating in iCBT who fit that profile might need extra support from a therapist in order to improve, Dr. Rozental added.
He reported having no financial conflicts regarding his study, which was funded by the Swedish Research Council for Health, Working Life, and Welfare.
SAN FRANCISCO – Nearly 6% of patients deteriorated during Internet-based cognitive-behavioral therapy (iCBT) in an individual patient data meta-analysis totaling 2,866 participants in 29 published clinical trials, Alexander Rozental, PhD, reported at the annual conference of the Anxiety and Depression Association of America.
On the other hand, the meta-analysis also highlighted the hazards of doing nothing for patients experiencing mental distress: 17.4% of patients deteriorated while in wait-list control groups in the 29 trials, a rate of harm triple the 5.8% deterioration rate in patients during iCBT, added Dr. Rozental, a clinical psychologist at Stockholm University.
This meta-analysis is one of the very few studies to look at the negative effects of a psychologic treatment. Psychotherapy research has focused almost entirely on the positive effects. That’s at odds with the way pharmacologic research is conducted, in which reporting of adverse events is mandatory, he noted.
Of patients in the meta-analysis, 61% sought treatment for anxiety disorders, 20% for depression, and the rest for erectile dysfunction, pathological gambling, or relationship problems.
iCBT is particularly popular in Sweden, where it was developed two decades ago as a means of disseminating evidence-based, manualized therapy to a broad population in a highly cost-effective manner. This form of psychotherapy typically entails 8 to 12 weekly treatment modules, with weekly assignments, predetermined deadlines, texts and exercises, and regular, albeit relatively brief, contact with a therapist via secure email.
Dr. Rozental and his coinvestigators reviewed individual patient data in search of predictors of treatment success or deterioration. A profile emerged of the patients least likely to deteriorate while on iCBT: older age, university-educated, in a stable relationship, and with a higher level of symptoms pretreatment.
“You might interpret the findings as an indicator for matching the right type of treatment to the right patient. Perhaps those [who] are younger, have less than a university degree, and are not in a relationship might be better off in a face to face treatment, at least in terms of preventing deterioration,” he observed in an interview. “This makes sense if you think about the amount of work you have to do on your own in Internet-based psychological treatments, which include limited access to a therapist and require reading a lot of text material.”
Patients participating in iCBT who fit that profile might need extra support from a therapist in order to improve, Dr. Rozental added.
He reported having no financial conflicts regarding his study, which was funded by the Swedish Research Council for Health, Working Life, and Welfare.
AT THE ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: Slightly less than 6% of patients deteriorated while participating in Internet-based cognitive-behavioral therapy, mostly for anxiety disorders or depression.
Data source: This individual patient data meta-analysis involved 2,866 participants in 29 published clinical trials of internet-based cognitive-behavioral therapy.
Disclosures: The study was funded by the Swedish Research Council for Health, Working Life, and Welfare. The presenter reported having no financial conflicts.
Almost one-third of Syrian refugees in U.S. met PTSD criteria
SAN FRANCISCO – Nearly one-third of adult Syrian civil war refugees who have resettled in the Detroit area meet diagnostic criteria for posttraumatic stress disorder, according to preliminary results of an ongoing study presented by Arash Javanbakht, MD, at the annual conference of the Anxiety and Depression Association of America.
That’s comparable to PTSD rates documented in Vietnam War combat veterans.
“Based on these data, mental health care for Syrian refugees resettling in the U.S. is highly needed,” he observed.
Michigan has a large population of Syrian war refugees. All who settle in southeastern Michigan undergo an initial health examination at Arab American and Chaldean Council primary care clinics staffed by bilingual teams. More than 90% of eligible adult refugees who have been invited to join Dr. Javanbakht’s mental health screening study have opted to participate. This extraordinarily high recruitment rate suggests that the findings are generalizable to the broader Syrian refugee community throughout the United States in his view.
The screening tools employed in the study are the PTSD Checklist, DSM-IV version (PCL), and the Hopkins Symptom Checklist (HSCL-25), which contains 10 anxiety questions and 15 depression questions.
Of the first 82 adult Syrian refugees evaluated, 26 (31.5%) were diagnosed as having PTSD on the basis of a PCL total score of 40 or more plus fulfillment of the DSM-IV diagnostic criteria for the disorder. In fact, this subgroup had a mean PCL score of 62.3. The prevalence of PTSD was twice as great in women, compared with men (see graphic).
Clinically impactful anxiety symptoms as defined by an HSCL-25 anxiety score greater than 1.79 was present in 38 refugees (47%), and clinically meaningful depressive symptoms were present in 47 (58%).
Anxiety, depression, and PTSD all were tightly correlated, complicating the clinical challenges, the psychiatrist noted.
Enrollment in the study is ongoing, but a first pass examination of a participant population that’s now twice the size of that in his presentation at the conference continues to show similar results, according to Dr. Javanbakht.
Dr. Javanbakht reported having no financial conflicts of interest regarding the study, which was funded by the state of Michigan and the Detroit Wayne Mental Health Authority.
SAN FRANCISCO – Nearly one-third of adult Syrian civil war refugees who have resettled in the Detroit area meet diagnostic criteria for posttraumatic stress disorder, according to preliminary results of an ongoing study presented by Arash Javanbakht, MD, at the annual conference of the Anxiety and Depression Association of America.
That’s comparable to PTSD rates documented in Vietnam War combat veterans.
“Based on these data, mental health care for Syrian refugees resettling in the U.S. is highly needed,” he observed.
Michigan has a large population of Syrian war refugees. All who settle in southeastern Michigan undergo an initial health examination at Arab American and Chaldean Council primary care clinics staffed by bilingual teams. More than 90% of eligible adult refugees who have been invited to join Dr. Javanbakht’s mental health screening study have opted to participate. This extraordinarily high recruitment rate suggests that the findings are generalizable to the broader Syrian refugee community throughout the United States in his view.
The screening tools employed in the study are the PTSD Checklist, DSM-IV version (PCL), and the Hopkins Symptom Checklist (HSCL-25), which contains 10 anxiety questions and 15 depression questions.
Of the first 82 adult Syrian refugees evaluated, 26 (31.5%) were diagnosed as having PTSD on the basis of a PCL total score of 40 or more plus fulfillment of the DSM-IV diagnostic criteria for the disorder. In fact, this subgroup had a mean PCL score of 62.3. The prevalence of PTSD was twice as great in women, compared with men (see graphic).
Clinically impactful anxiety symptoms as defined by an HSCL-25 anxiety score greater than 1.79 was present in 38 refugees (47%), and clinically meaningful depressive symptoms were present in 47 (58%).
Anxiety, depression, and PTSD all were tightly correlated, complicating the clinical challenges, the psychiatrist noted.
Enrollment in the study is ongoing, but a first pass examination of a participant population that’s now twice the size of that in his presentation at the conference continues to show similar results, according to Dr. Javanbakht.
Dr. Javanbakht reported having no financial conflicts of interest regarding the study, which was funded by the state of Michigan and the Detroit Wayne Mental Health Authority.
SAN FRANCISCO – Nearly one-third of adult Syrian civil war refugees who have resettled in the Detroit area meet diagnostic criteria for posttraumatic stress disorder, according to preliminary results of an ongoing study presented by Arash Javanbakht, MD, at the annual conference of the Anxiety and Depression Association of America.
That’s comparable to PTSD rates documented in Vietnam War combat veterans.
“Based on these data, mental health care for Syrian refugees resettling in the U.S. is highly needed,” he observed.
Michigan has a large population of Syrian war refugees. All who settle in southeastern Michigan undergo an initial health examination at Arab American and Chaldean Council primary care clinics staffed by bilingual teams. More than 90% of eligible adult refugees who have been invited to join Dr. Javanbakht’s mental health screening study have opted to participate. This extraordinarily high recruitment rate suggests that the findings are generalizable to the broader Syrian refugee community throughout the United States in his view.
The screening tools employed in the study are the PTSD Checklist, DSM-IV version (PCL), and the Hopkins Symptom Checklist (HSCL-25), which contains 10 anxiety questions and 15 depression questions.
Of the first 82 adult Syrian refugees evaluated, 26 (31.5%) were diagnosed as having PTSD on the basis of a PCL total score of 40 or more plus fulfillment of the DSM-IV diagnostic criteria for the disorder. In fact, this subgroup had a mean PCL score of 62.3. The prevalence of PTSD was twice as great in women, compared with men (see graphic).
Clinically impactful anxiety symptoms as defined by an HSCL-25 anxiety score greater than 1.79 was present in 38 refugees (47%), and clinically meaningful depressive symptoms were present in 47 (58%).
Anxiety, depression, and PTSD all were tightly correlated, complicating the clinical challenges, the psychiatrist noted.
Enrollment in the study is ongoing, but a first pass examination of a participant population that’s now twice the size of that in his presentation at the conference continues to show similar results, according to Dr. Javanbakht.
Dr. Javanbakht reported having no financial conflicts of interest regarding the study, which was funded by the state of Michigan and the Detroit Wayne Mental Health Authority.
AT THE ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: One-third of adult Syrian war refugees who have resettled in Michigan have posttraumatic stress disorder.
Data source: This ongoing cross-sectional study initially screened 82 adult Syrian civil war refugees for PTSD, anxiety, and depression.
Disclosures: This ongoing study is funded by the state of Michigan and the Detroit Wayne Mental Health Authority. The presenter reported having no financial conflicts of interest.
Low-dose aspirin bests dual-antiplatelet therapy in TAVR
PARIS – Single-antiplatelet therapy with low-dose aspirin following transcatheter aortic valve replacement (TAVR) reduced the occurrence of major adverse events, compared with guideline-recommended dual-antiplatelet therapy (DAPT), in the randomized ARTE trial.
The TAVR guideline recommendation for DAPT with low-dose aspirin plus clopidogrel is not based on evidence. It relies on expert opinion. ARTE (Aspirin Versus Aspirin + Clopidogrel Following TAVR) is the first sizable randomized trial to address the safety and efficacy of aspirin alone versus DAPT in the setting of TAVR, Josep Rodés-Cabau, MD, noted in presenting the ARTE results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
ARTE was a multicenter, prospective, international open-label study of 222 TAVR patients who were randomized to 3 months of single-antiplatelet therapy (SAPT) with aspirin at 80-100 mg/day or to DAPT with aspirin at 80-100 mg/day plus clopidogrel at 75 mg/day after a single 300-mg loading dose. Participants had a mean Society of Thoracic Surgery Predicted Risk of Mortality score of 6.3%. The vast majority of participants received the balloon-expandable Edwards Lifesciences Sapien XT valve. The remainder got the Sapien 3 valve.
The primary outcome was the 3-month composite of death, MI, major or life-threatening bleeding, or stroke or transient ischemic attack. It occurred in 15.3% of the DAPT group and 7.2% on SAPT, a difference that didn’t reach statistical significance (P = .065) because of small patient numbers.
All subjects were on a proton pump inhibitor. The type, timing, and severity of bleeding events differed between the two study arms. All 4 bleeding events in the SAPT group were vascular in nature, while 5 of the 12 in the DAPT group were gastrointestinal. All the bleeding events in the SAPT group occurred within 72 hours after TAVR, whereas 5 of 12 in the DAPT recipients occurred later. Only one patient on SAPT experienced life-threatening bleeding, compared with seven DAPT patients who did.
“There were two prior smaller studies before ours,” according to Dr. Rodés-Cabau of Laval University in Quebec City. “One showed no differences, and an Italian one showed a tendency toward more bleeding with DAPT. So, I think there has been no sign to date that adding clopidogrel protects this group of patients from anything.”
Discussant Luis Nombela-Franco, MD, an interventional cardiologist at San Carlos Hospital in Madrid, pronounced the ARTE trial guideline-changing despite its limitations.
ARTE was supported by grants from Edwards Lifesciences and the Quebec Heart and Lung Institute.
Simultaneous with Dr. Rodés-Cabau’s presentation in Paris, the ARTE trial was published online (JACC Cardiovasc Interv. 2017 May 11. pii: S1936-8798[17]30812-9).
PARIS – Single-antiplatelet therapy with low-dose aspirin following transcatheter aortic valve replacement (TAVR) reduced the occurrence of major adverse events, compared with guideline-recommended dual-antiplatelet therapy (DAPT), in the randomized ARTE trial.
The TAVR guideline recommendation for DAPT with low-dose aspirin plus clopidogrel is not based on evidence. It relies on expert opinion. ARTE (Aspirin Versus Aspirin + Clopidogrel Following TAVR) is the first sizable randomized trial to address the safety and efficacy of aspirin alone versus DAPT in the setting of TAVR, Josep Rodés-Cabau, MD, noted in presenting the ARTE results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
ARTE was a multicenter, prospective, international open-label study of 222 TAVR patients who were randomized to 3 months of single-antiplatelet therapy (SAPT) with aspirin at 80-100 mg/day or to DAPT with aspirin at 80-100 mg/day plus clopidogrel at 75 mg/day after a single 300-mg loading dose. Participants had a mean Society of Thoracic Surgery Predicted Risk of Mortality score of 6.3%. The vast majority of participants received the balloon-expandable Edwards Lifesciences Sapien XT valve. The remainder got the Sapien 3 valve.
The primary outcome was the 3-month composite of death, MI, major or life-threatening bleeding, or stroke or transient ischemic attack. It occurred in 15.3% of the DAPT group and 7.2% on SAPT, a difference that didn’t reach statistical significance (P = .065) because of small patient numbers.
All subjects were on a proton pump inhibitor. The type, timing, and severity of bleeding events differed between the two study arms. All 4 bleeding events in the SAPT group were vascular in nature, while 5 of the 12 in the DAPT group were gastrointestinal. All the bleeding events in the SAPT group occurred within 72 hours after TAVR, whereas 5 of 12 in the DAPT recipients occurred later. Only one patient on SAPT experienced life-threatening bleeding, compared with seven DAPT patients who did.
“There were two prior smaller studies before ours,” according to Dr. Rodés-Cabau of Laval University in Quebec City. “One showed no differences, and an Italian one showed a tendency toward more bleeding with DAPT. So, I think there has been no sign to date that adding clopidogrel protects this group of patients from anything.”
Discussant Luis Nombela-Franco, MD, an interventional cardiologist at San Carlos Hospital in Madrid, pronounced the ARTE trial guideline-changing despite its limitations.
ARTE was supported by grants from Edwards Lifesciences and the Quebec Heart and Lung Institute.
Simultaneous with Dr. Rodés-Cabau’s presentation in Paris, the ARTE trial was published online (JACC Cardiovasc Interv. 2017 May 11. pii: S1936-8798[17]30812-9).
PARIS – Single-antiplatelet therapy with low-dose aspirin following transcatheter aortic valve replacement (TAVR) reduced the occurrence of major adverse events, compared with guideline-recommended dual-antiplatelet therapy (DAPT), in the randomized ARTE trial.
The TAVR guideline recommendation for DAPT with low-dose aspirin plus clopidogrel is not based on evidence. It relies on expert opinion. ARTE (Aspirin Versus Aspirin + Clopidogrel Following TAVR) is the first sizable randomized trial to address the safety and efficacy of aspirin alone versus DAPT in the setting of TAVR, Josep Rodés-Cabau, MD, noted in presenting the ARTE results at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
ARTE was a multicenter, prospective, international open-label study of 222 TAVR patients who were randomized to 3 months of single-antiplatelet therapy (SAPT) with aspirin at 80-100 mg/day or to DAPT with aspirin at 80-100 mg/day plus clopidogrel at 75 mg/day after a single 300-mg loading dose. Participants had a mean Society of Thoracic Surgery Predicted Risk of Mortality score of 6.3%. The vast majority of participants received the balloon-expandable Edwards Lifesciences Sapien XT valve. The remainder got the Sapien 3 valve.
The primary outcome was the 3-month composite of death, MI, major or life-threatening bleeding, or stroke or transient ischemic attack. It occurred in 15.3% of the DAPT group and 7.2% on SAPT, a difference that didn’t reach statistical significance (P = .065) because of small patient numbers.
All subjects were on a proton pump inhibitor. The type, timing, and severity of bleeding events differed between the two study arms. All 4 bleeding events in the SAPT group were vascular in nature, while 5 of the 12 in the DAPT group were gastrointestinal. All the bleeding events in the SAPT group occurred within 72 hours after TAVR, whereas 5 of 12 in the DAPT recipients occurred later. Only one patient on SAPT experienced life-threatening bleeding, compared with seven DAPT patients who did.
“There were two prior smaller studies before ours,” according to Dr. Rodés-Cabau of Laval University in Quebec City. “One showed no differences, and an Italian one showed a tendency toward more bleeding with DAPT. So, I think there has been no sign to date that adding clopidogrel protects this group of patients from anything.”
Discussant Luis Nombela-Franco, MD, an interventional cardiologist at San Carlos Hospital in Madrid, pronounced the ARTE trial guideline-changing despite its limitations.
ARTE was supported by grants from Edwards Lifesciences and the Quebec Heart and Lung Institute.
Simultaneous with Dr. Rodés-Cabau’s presentation in Paris, the ARTE trial was published online (JACC Cardiovasc Interv. 2017 May 11. pii: S1936-8798[17]30812-9).
AT EUROPCR
Key clinical point:
Major finding: The 3-month composite of death, MI, major or life-threatening bleeding, or stroke or transient ischemic attack occurred in 15.3% of TAVR patients randomized to DAPT with low-dose aspirin plus clopidogrel, compared with 7.2% on aspirin only.
Data source: A randomized, multicenter, international, prospective open-label trial in 222 TAVR patients.
Disclosures: The presenter reported receiving research grants from Edwards Lifesciences and the Quebec Heart and Lung Institute, which supported the ARTE trial.