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M. Alexander Otto began his reporting career early in 1999 covering the pharmaceutical industry for a national pharmacists' magazine and freelancing for the Washington Post and other newspapers. He then joined BNA, now part of Bloomberg News, covering health law and the protection of people and animals in medical research. Alex next worked for the McClatchy Company. Based on his work, Alex won a year-long Knight Science Journalism Fellowship to MIT in 2008-2009. He joined the company shortly thereafter. Alex has a newspaper journalism degree from Syracuse (N.Y.) University and a master's degree in medical science -- a physician assistant degree -- from George Washington University. Alex is based in Seattle.
AAAAI: EpiPen Jr Needles Too Long for Many Children Under 15 kg
LOS ANGELES – For about half of children under 15 kg, pediatric epinephrine autoinjector needles are too long – they’re likely to hit the femur.
If the drug is deposited at the periosteum, it won’t be absorbed properly. If the needle delivers it to the bone marrow, the results could be disastrous.
“I’ve had three patients where the needle came back bent, so this happens,” said Dr. Harold Kim, an allergist in Kitchener, Ont. “Fortunately, there’s a fairly simple workaround. I ask parents to squeeze the [thigh] muscle before they give the shot, so that the muscle doesn’t compress. If the muscle doesn’t compress, you won’t hit bone, and the kid is going to be fine. Parents are really grateful” to learn this, but “they have to be careful not to inject their fingers.”
The findings come from Dr. Kim’s ultrasound study of thigh tissue thickness in 53 children weighing 7.5-15 kg. He and his colleagues found that with 10 pounds of pressure to simulate autoinjector deployment, the mean skin-to-bone distance was 13.3 mm, plus or minus 2.1 mm (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.1167).
The needle length for EpiPen Jr is 12.7 mm, which was long enough to strike bone in 43% of the subjects.
“Epinephrine autoinjectors should be the mainstay of treatment for anaphylaxis, but our data suggest that the optimal needle length” for patients 7.5-15 kg “should be shorter than the needle length in current, commercially available” products. “There may be some modifications that need to be made in the way they are given. I actually ultrasound all the kids in my clinic to see if there will be problems,” Dr. Kim said at the American Academy of Allergy, Asthma, and Immunology annual meeting.
The study was done with an ultrasound probe in a housing that mimicked the footprint of Sanofi’s Auvi-Q, which is no longer on the U.S. and Canadian markets. If anything, the problem would be worse with EpiPen Jr because of its smaller footprint, Dr. Kim said.
On average, the subjects were 20 months old and 11 kg. Just over half were boys, and about 80% were white. The mean height was 79 cm and mean body mass index 19 kg/m2. About 60% of the subjects had injectors because of food allergies. Both transverse and longitudinal images of thigh tissue were used in the study, and distances were read by a blinded ultrasound expert.
Dr. Kim and his colleagues became interested after finding that needles may actually be too short to reach muscle in obese patients. While working on that issue, however, they also discovered “that 30% of kids less than 15 kg were at risk of the needle hitting the bone. We were surprised by those findings,” so looked into them further, he said.
EpiPen Jr is off label for children under 15 kg, but still often prescribed for them.
Sanofi funded the work. Dr. Kim is an advisor for the company, as well as for Pfizer, maker of EpiPen.
LOS ANGELES – For about half of children under 15 kg, pediatric epinephrine autoinjector needles are too long – they’re likely to hit the femur.
If the drug is deposited at the periosteum, it won’t be absorbed properly. If the needle delivers it to the bone marrow, the results could be disastrous.
“I’ve had three patients where the needle came back bent, so this happens,” said Dr. Harold Kim, an allergist in Kitchener, Ont. “Fortunately, there’s a fairly simple workaround. I ask parents to squeeze the [thigh] muscle before they give the shot, so that the muscle doesn’t compress. If the muscle doesn’t compress, you won’t hit bone, and the kid is going to be fine. Parents are really grateful” to learn this, but “they have to be careful not to inject their fingers.”
The findings come from Dr. Kim’s ultrasound study of thigh tissue thickness in 53 children weighing 7.5-15 kg. He and his colleagues found that with 10 pounds of pressure to simulate autoinjector deployment, the mean skin-to-bone distance was 13.3 mm, plus or minus 2.1 mm (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.1167).
The needle length for EpiPen Jr is 12.7 mm, which was long enough to strike bone in 43% of the subjects.
“Epinephrine autoinjectors should be the mainstay of treatment for anaphylaxis, but our data suggest that the optimal needle length” for patients 7.5-15 kg “should be shorter than the needle length in current, commercially available” products. “There may be some modifications that need to be made in the way they are given. I actually ultrasound all the kids in my clinic to see if there will be problems,” Dr. Kim said at the American Academy of Allergy, Asthma, and Immunology annual meeting.
The study was done with an ultrasound probe in a housing that mimicked the footprint of Sanofi’s Auvi-Q, which is no longer on the U.S. and Canadian markets. If anything, the problem would be worse with EpiPen Jr because of its smaller footprint, Dr. Kim said.
On average, the subjects were 20 months old and 11 kg. Just over half were boys, and about 80% were white. The mean height was 79 cm and mean body mass index 19 kg/m2. About 60% of the subjects had injectors because of food allergies. Both transverse and longitudinal images of thigh tissue were used in the study, and distances were read by a blinded ultrasound expert.
Dr. Kim and his colleagues became interested after finding that needles may actually be too short to reach muscle in obese patients. While working on that issue, however, they also discovered “that 30% of kids less than 15 kg were at risk of the needle hitting the bone. We were surprised by those findings,” so looked into them further, he said.
EpiPen Jr is off label for children under 15 kg, but still often prescribed for them.
Sanofi funded the work. Dr. Kim is an advisor for the company, as well as for Pfizer, maker of EpiPen.
LOS ANGELES – For about half of children under 15 kg, pediatric epinephrine autoinjector needles are too long – they’re likely to hit the femur.
If the drug is deposited at the periosteum, it won’t be absorbed properly. If the needle delivers it to the bone marrow, the results could be disastrous.
“I’ve had three patients where the needle came back bent, so this happens,” said Dr. Harold Kim, an allergist in Kitchener, Ont. “Fortunately, there’s a fairly simple workaround. I ask parents to squeeze the [thigh] muscle before they give the shot, so that the muscle doesn’t compress. If the muscle doesn’t compress, you won’t hit bone, and the kid is going to be fine. Parents are really grateful” to learn this, but “they have to be careful not to inject their fingers.”
The findings come from Dr. Kim’s ultrasound study of thigh tissue thickness in 53 children weighing 7.5-15 kg. He and his colleagues found that with 10 pounds of pressure to simulate autoinjector deployment, the mean skin-to-bone distance was 13.3 mm, plus or minus 2.1 mm (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.1167).
The needle length for EpiPen Jr is 12.7 mm, which was long enough to strike bone in 43% of the subjects.
“Epinephrine autoinjectors should be the mainstay of treatment for anaphylaxis, but our data suggest that the optimal needle length” for patients 7.5-15 kg “should be shorter than the needle length in current, commercially available” products. “There may be some modifications that need to be made in the way they are given. I actually ultrasound all the kids in my clinic to see if there will be problems,” Dr. Kim said at the American Academy of Allergy, Asthma, and Immunology annual meeting.
The study was done with an ultrasound probe in a housing that mimicked the footprint of Sanofi’s Auvi-Q, which is no longer on the U.S. and Canadian markets. If anything, the problem would be worse with EpiPen Jr because of its smaller footprint, Dr. Kim said.
On average, the subjects were 20 months old and 11 kg. Just over half were boys, and about 80% were white. The mean height was 79 cm and mean body mass index 19 kg/m2. About 60% of the subjects had injectors because of food allergies. Both transverse and longitudinal images of thigh tissue were used in the study, and distances were read by a blinded ultrasound expert.
Dr. Kim and his colleagues became interested after finding that needles may actually be too short to reach muscle in obese patients. While working on that issue, however, they also discovered “that 30% of kids less than 15 kg were at risk of the needle hitting the bone. We were surprised by those findings,” so looked into them further, he said.
EpiPen Jr is off label for children under 15 kg, but still often prescribed for them.
Sanofi funded the work. Dr. Kim is an advisor for the company, as well as for Pfizer, maker of EpiPen.
AT 2016 AAAAI ANNUAL MEETING
AAAAI: EpiPen Jr needles too long for many children under 15 kg
LOS ANGELES – For about half of children under 15 kg, pediatric epinephrine autoinjector needles are too long – they’re likely to hit the femur.
If the drug is deposited at the periosteum, it won’t be absorbed properly. If the needle delivers it to the bone marrow, the results could be disastrous.
“I’ve had three patients where the needle came back bent, so this happens,” said Dr. Harold Kim, an allergist in Kitchener, Ont. “Fortunately, there’s a fairly simple workaround. I ask parents to squeeze the [thigh] muscle before they give the shot, so that the muscle doesn’t compress. If the muscle doesn’t compress, you won’t hit bone, and the kid is going to be fine. Parents are really grateful” to learn this, but “they have to be careful not to inject their fingers.”
The findings come from Dr. Kim’s ultrasound study of thigh tissue thickness in 53 children weighing 7.5-15 kg. He and his colleagues found that with 10 pounds of pressure to simulate autoinjector deployment, the mean skin-to-bone distance was 13.3 mm, plus or minus 2.1 mm (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.1167).
The needle length for EpiPen Jr is 12.7 mm, which was long enough to strike bone in 43% of the subjects.
“Epinephrine autoinjectors should be the mainstay of treatment for anaphylaxis, but our data suggest that the optimal needle length” for patients 7.5-15 kg “should be shorter than the needle length in current, commercially available” products. “There may be some modifications that need to be made in the way they are given. I actually ultrasound all the kids in my clinic to see if there will be problems,” Dr. Kim said at the American Academy of Allergy, Asthma, and Immunology annual meeting.
The study was done with an ultrasound probe in a housing that mimicked the footprint of Sanofi’s Auvi-Q, which is no longer on the U.S. and Canadian markets. If anything, the problem would be worse with EpiPen Jr because of its smaller footprint, Dr. Kim said.
On average, the subjects were 20 months old and 11 kg. Just over half were boys, and about 80% were white. The mean height was 79 cm and mean body mass index 19 kg/m2. About 60% of the subjects had injectors because of food allergies. Both transverse and longitudinal images of thigh tissue were used in the study, and distances were read by a blinded ultrasound expert.
Dr. Kim and his colleagues became interested after finding that needles may actually be too short to reach muscle in obese patients. While working on that issue, however, they also discovered “that 30% of kids less than 15 kg were at risk of the needle hitting the bone. We were surprised by those findings,” so looked into them further, he said.
EpiPen Jr is off label for children under 15 kg, but still often prescribed for them.
Sanofi funded the work. Dr. Kim is an advisor for the company, as well as for Pfizer, maker of EpiPen.
LOS ANGELES – For about half of children under 15 kg, pediatric epinephrine autoinjector needles are too long – they’re likely to hit the femur.
If the drug is deposited at the periosteum, it won’t be absorbed properly. If the needle delivers it to the bone marrow, the results could be disastrous.
“I’ve had three patients where the needle came back bent, so this happens,” said Dr. Harold Kim, an allergist in Kitchener, Ont. “Fortunately, there’s a fairly simple workaround. I ask parents to squeeze the [thigh] muscle before they give the shot, so that the muscle doesn’t compress. If the muscle doesn’t compress, you won’t hit bone, and the kid is going to be fine. Parents are really grateful” to learn this, but “they have to be careful not to inject their fingers.”
The findings come from Dr. Kim’s ultrasound study of thigh tissue thickness in 53 children weighing 7.5-15 kg. He and his colleagues found that with 10 pounds of pressure to simulate autoinjector deployment, the mean skin-to-bone distance was 13.3 mm, plus or minus 2.1 mm (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.1167).
The needle length for EpiPen Jr is 12.7 mm, which was long enough to strike bone in 43% of the subjects.
“Epinephrine autoinjectors should be the mainstay of treatment for anaphylaxis, but our data suggest that the optimal needle length” for patients 7.5-15 kg “should be shorter than the needle length in current, commercially available” products. “There may be some modifications that need to be made in the way they are given. I actually ultrasound all the kids in my clinic to see if there will be problems,” Dr. Kim said at the American Academy of Allergy, Asthma, and Immunology annual meeting.
The study was done with an ultrasound probe in a housing that mimicked the footprint of Sanofi’s Auvi-Q, which is no longer on the U.S. and Canadian markets. If anything, the problem would be worse with EpiPen Jr because of its smaller footprint, Dr. Kim said.
On average, the subjects were 20 months old and 11 kg. Just over half were boys, and about 80% were white. The mean height was 79 cm and mean body mass index 19 kg/m2. About 60% of the subjects had injectors because of food allergies. Both transverse and longitudinal images of thigh tissue were used in the study, and distances were read by a blinded ultrasound expert.
Dr. Kim and his colleagues became interested after finding that needles may actually be too short to reach muscle in obese patients. While working on that issue, however, they also discovered “that 30% of kids less than 15 kg were at risk of the needle hitting the bone. We were surprised by those findings,” so looked into them further, he said.
EpiPen Jr is off label for children under 15 kg, but still often prescribed for them.
Sanofi funded the work. Dr. Kim is an advisor for the company, as well as for Pfizer, maker of EpiPen.
LOS ANGELES – For about half of children under 15 kg, pediatric epinephrine autoinjector needles are too long – they’re likely to hit the femur.
If the drug is deposited at the periosteum, it won’t be absorbed properly. If the needle delivers it to the bone marrow, the results could be disastrous.
“I’ve had three patients where the needle came back bent, so this happens,” said Dr. Harold Kim, an allergist in Kitchener, Ont. “Fortunately, there’s a fairly simple workaround. I ask parents to squeeze the [thigh] muscle before they give the shot, so that the muscle doesn’t compress. If the muscle doesn’t compress, you won’t hit bone, and the kid is going to be fine. Parents are really grateful” to learn this, but “they have to be careful not to inject their fingers.”
The findings come from Dr. Kim’s ultrasound study of thigh tissue thickness in 53 children weighing 7.5-15 kg. He and his colleagues found that with 10 pounds of pressure to simulate autoinjector deployment, the mean skin-to-bone distance was 13.3 mm, plus or minus 2.1 mm (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.1167).
The needle length for EpiPen Jr is 12.7 mm, which was long enough to strike bone in 43% of the subjects.
“Epinephrine autoinjectors should be the mainstay of treatment for anaphylaxis, but our data suggest that the optimal needle length” for patients 7.5-15 kg “should be shorter than the needle length in current, commercially available” products. “There may be some modifications that need to be made in the way they are given. I actually ultrasound all the kids in my clinic to see if there will be problems,” Dr. Kim said at the American Academy of Allergy, Asthma, and Immunology annual meeting.
The study was done with an ultrasound probe in a housing that mimicked the footprint of Sanofi’s Auvi-Q, which is no longer on the U.S. and Canadian markets. If anything, the problem would be worse with EpiPen Jr because of its smaller footprint, Dr. Kim said.
On average, the subjects were 20 months old and 11 kg. Just over half were boys, and about 80% were white. The mean height was 79 cm and mean body mass index 19 kg/m2. About 60% of the subjects had injectors because of food allergies. Both transverse and longitudinal images of thigh tissue were used in the study, and distances were read by a blinded ultrasound expert.
Dr. Kim and his colleagues became interested after finding that needles may actually be too short to reach muscle in obese patients. While working on that issue, however, they also discovered “that 30% of kids less than 15 kg were at risk of the needle hitting the bone. We were surprised by those findings,” so looked into them further, he said.
EpiPen Jr is off label for children under 15 kg, but still often prescribed for them.
Sanofi funded the work. Dr. Kim is an advisor for the company, as well as for Pfizer, maker of EpiPen.
AT 2016 AAAAI ANNUAL MEETING
Key clinical point: EpiPen Jr needles are too long for many children under 15 kg.
Major finding: With 10 pounds of pressure to simulate autoinjector deployment, the mean skin-to-bone distance was 13.3 mm, plus or minus 2.1 mm. The needle length for EpiPen Jr is 12.7 mm, which was long enough to strike bone in 43% of the subjects.
Data source: Prospective investigation of 53 children weighing 7.5-15 kg.
Disclosures: Sanofi funded the work. The presenter is an adviser for the company, as well as for Pfizer.
AAAAI: Risks comparable in adult asthma patients given fluticasone and salmeterol plus fluticasone combo
LOS ANGELES – Fluticasone-salmeterol inhalers (Advair) are as safe as and more effective than fluticasone monotherapy inhalers are for patients with moderate to severe asthma, according to a large, randomized trial from its drug maker, GlaxoSmithKline, presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology and simultaneously published online March 6 in the New England Journal of Medicine.
The study is the first of several that the Food and Drug Administration required from Glaxo and other manufacturers in 2010 to evaluate the safety of long-acting beta-2 agonists (LABAs) such as salmeterol when used in combination with inhaled corticosteroids, after it became clear that LABAs, when used alone, increase the risk of serious asthma complications, including death (N Engl J Med. 2016 Mar 6. doi: 10.1056/NEJMoa1511049).
Current black box warnings on fluticasone-salmeterol (Advair), Merck’s mometasone-formoterol inhaler (Dulera), and AstraZeneca’s budesonide-formoterol combo (Symbicort)note that data are “inadequate to determine” if concomitant steroids mitigate the risk of LABAs.
Merck and AstraZeneca’s studies are ongoing, but Glaxo’s initial results seem reassuring. “I think what this study really does is provide evidence to answer the question that FDA was asking about safety. This is [also] the first really large study to show a decrease in exacerbations with [fluticasone-salmeterol],” principal investigator Dr. David Stempel, with Glaxo’s Respiratory Clinical Development program in Durham, N.C., said at the annual meeting.
However, because “patients with a history of life-threatening or unstable asthma” – including those who, at any point, had been intubated for asthma – “were excluded from the study, our results cannot be extrapolated to such patients,” the researchers wrote.
The inclusion criteria were otherwise broad: Adults and adolescents at least 12 years old, with a history of severe asthma exacerbations requiring the use of inhaled glucocorticoids or hospitalization in the previous year, but not in the month before enrollment, were included. There were 5,834 subjects randomized to fluticasone-salmeterol and 5,845 to fluticasone alone, both for 26 weeks. Adherence to the study medications was 95%.
There were 36 serious asthma-related events – endotracheal intubation or hospitalization – in 34 patients (0.58%) in the fluticasone-salmeterol group, and 38 events in 33 patients (0.56%) in the fluticasone-only group. The hazard ratio for serious asthma-related events with fluticasone-salmeterol was 1.03 (95% confidence interval, 0.64-1.66), indicating that the safety of the combination was comparable with that of fluticasone monotherapy (P = .003). There were no asthma-related deaths in the trial, and two intubations in the fluticasone-only group.
The risk of a severe asthma exacerbation was 21% lower with fluticasone-salmeterol (HR, 0.79; 95% CI 0.70-0.89). While 480 fluticasone-salmeterol patients (8%) had at least one severe asthma exacerbation, at least one severe exacerbation occurred in 597 fluticasone-only patients (10%; P less than 0.001). “The difference was most prominent among adolescents, in whom the risk was 35% lower,” the investigators wrote.
“We found that ... the risk of serious asthma-related events was no greater when salmeterol was delivered by inhaler in a fixed-dose combination with fluticasone propionate than when fluticasone was administered alone,” and the “clinical benefits of fluticasone-salmeterol were significant,” they concluded.
The trial, which was designed with FDA guidance, excluded patients with life-threatening or unstable asthma in order to “mimic the population in which the (original LABA safety) signal was seen” in earlier studies; “the signal wasn’t seen specifically in that population.” Even so, “very few patients were eliminated due to a history of life-threatening asthma,” Dr. Stempel said.
It’s unclear why concomitant steroids reduce the risk. “LABA monotherapy may mask underlying disease by providing a temporary reduction in symptoms but ultimately placing patients at risk for serious exacerbations. When you give short- or long-acting bronchodilators, patients feel better, but you’re not treating the underlying disease; corticosteroids treat the underlying inflammatory component,” he said
The company will soon publish results from a similar fluticasone-salmeterol safety trial in children 4-11 years old. “I hope were finished” after that, “but we have to have a discussion with FDA to see what’s next.” The agency might want to pool data from the incoming trials to look at LABA-containing inhalers as a class. “It’s too premature to know where we’ll go with the box warning, but there’s a lot more information now than was available when the box first appeared in 2003,” Dr. Stempel said.
The work was funded by GlaxoSmithKline, and the authors are current or former employees.
At first glance, these results appear to be quite reassuring. However, patients were excluded from the trial if they had a history of life-threatening or unstable asthma. Why this decision was made is never explained, but it is bewildering that the patients at highest risk for the composite primary outcome were purposely left out. Thus, it is not surprising that only two patients in the trial had life-threatening asthma and that adherence to study medication was 95%, a rate of success unheard of in clinical practice and even in well-controlled clinical trials. The exclusion of patients with unstable asthma probably selected those who were prone to be highly adherent to their usual therapy.
What practical conclusions can be drawn from this study? It is clear that among patients with asthma who have not had life-threatening episodes in the past and are highly adherent to their drug regimen, it is likely that the use of salmeterol together with fluticasone in a single inhaler is safe. For these patients and this combination, the black-box warning should be lifted. This is an important result, and it stresses once again that most patients with asthma, and especially those without serious episodes, can reach high levels of symptom control and avoid frequent exacerbations by simply using their inhalers every day.
What remains unanswered is whether this conclusion applies to patients who have the most severe and unstable disease, since these are the patients for whom all guidelines still recommend the use of LABAs [long-acting beta-2 agonists], combined with inhaled glucocorticoids, as first-line treatment. For these patients, the safe clinical approach is to maintain the same precautions in using fluticasone-salmeterol that have been recommended until now for all patients with asthma.
Dr. Fernando Martinez is a professor of pediatrics and director of the Asthma/Airway Disease Research Center at the University of Arizona, Tucson. He made his comments in an editorial (N Engl J Med. 2016 Mar 2016. doi: 10.1056/NEJMe1601040).
At first glance, these results appear to be quite reassuring. However, patients were excluded from the trial if they had a history of life-threatening or unstable asthma. Why this decision was made is never explained, but it is bewildering that the patients at highest risk for the composite primary outcome were purposely left out. Thus, it is not surprising that only two patients in the trial had life-threatening asthma and that adherence to study medication was 95%, a rate of success unheard of in clinical practice and even in well-controlled clinical trials. The exclusion of patients with unstable asthma probably selected those who were prone to be highly adherent to their usual therapy.
What practical conclusions can be drawn from this study? It is clear that among patients with asthma who have not had life-threatening episodes in the past and are highly adherent to their drug regimen, it is likely that the use of salmeterol together with fluticasone in a single inhaler is safe. For these patients and this combination, the black-box warning should be lifted. This is an important result, and it stresses once again that most patients with asthma, and especially those without serious episodes, can reach high levels of symptom control and avoid frequent exacerbations by simply using their inhalers every day.
What remains unanswered is whether this conclusion applies to patients who have the most severe and unstable disease, since these are the patients for whom all guidelines still recommend the use of LABAs [long-acting beta-2 agonists], combined with inhaled glucocorticoids, as first-line treatment. For these patients, the safe clinical approach is to maintain the same precautions in using fluticasone-salmeterol that have been recommended until now for all patients with asthma.
Dr. Fernando Martinez is a professor of pediatrics and director of the Asthma/Airway Disease Research Center at the University of Arizona, Tucson. He made his comments in an editorial (N Engl J Med. 2016 Mar 2016. doi: 10.1056/NEJMe1601040).
At first glance, these results appear to be quite reassuring. However, patients were excluded from the trial if they had a history of life-threatening or unstable asthma. Why this decision was made is never explained, but it is bewildering that the patients at highest risk for the composite primary outcome were purposely left out. Thus, it is not surprising that only two patients in the trial had life-threatening asthma and that adherence to study medication was 95%, a rate of success unheard of in clinical practice and even in well-controlled clinical trials. The exclusion of patients with unstable asthma probably selected those who were prone to be highly adherent to their usual therapy.
What practical conclusions can be drawn from this study? It is clear that among patients with asthma who have not had life-threatening episodes in the past and are highly adherent to their drug regimen, it is likely that the use of salmeterol together with fluticasone in a single inhaler is safe. For these patients and this combination, the black-box warning should be lifted. This is an important result, and it stresses once again that most patients with asthma, and especially those without serious episodes, can reach high levels of symptom control and avoid frequent exacerbations by simply using their inhalers every day.
What remains unanswered is whether this conclusion applies to patients who have the most severe and unstable disease, since these are the patients for whom all guidelines still recommend the use of LABAs [long-acting beta-2 agonists], combined with inhaled glucocorticoids, as first-line treatment. For these patients, the safe clinical approach is to maintain the same precautions in using fluticasone-salmeterol that have been recommended until now for all patients with asthma.
Dr. Fernando Martinez is a professor of pediatrics and director of the Asthma/Airway Disease Research Center at the University of Arizona, Tucson. He made his comments in an editorial (N Engl J Med. 2016 Mar 2016. doi: 10.1056/NEJMe1601040).
LOS ANGELES – Fluticasone-salmeterol inhalers (Advair) are as safe as and more effective than fluticasone monotherapy inhalers are for patients with moderate to severe asthma, according to a large, randomized trial from its drug maker, GlaxoSmithKline, presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology and simultaneously published online March 6 in the New England Journal of Medicine.
The study is the first of several that the Food and Drug Administration required from Glaxo and other manufacturers in 2010 to evaluate the safety of long-acting beta-2 agonists (LABAs) such as salmeterol when used in combination with inhaled corticosteroids, after it became clear that LABAs, when used alone, increase the risk of serious asthma complications, including death (N Engl J Med. 2016 Mar 6. doi: 10.1056/NEJMoa1511049).
Current black box warnings on fluticasone-salmeterol (Advair), Merck’s mometasone-formoterol inhaler (Dulera), and AstraZeneca’s budesonide-formoterol combo (Symbicort)note that data are “inadequate to determine” if concomitant steroids mitigate the risk of LABAs.
Merck and AstraZeneca’s studies are ongoing, but Glaxo’s initial results seem reassuring. “I think what this study really does is provide evidence to answer the question that FDA was asking about safety. This is [also] the first really large study to show a decrease in exacerbations with [fluticasone-salmeterol],” principal investigator Dr. David Stempel, with Glaxo’s Respiratory Clinical Development program in Durham, N.C., said at the annual meeting.
However, because “patients with a history of life-threatening or unstable asthma” – including those who, at any point, had been intubated for asthma – “were excluded from the study, our results cannot be extrapolated to such patients,” the researchers wrote.
The inclusion criteria were otherwise broad: Adults and adolescents at least 12 years old, with a history of severe asthma exacerbations requiring the use of inhaled glucocorticoids or hospitalization in the previous year, but not in the month before enrollment, were included. There were 5,834 subjects randomized to fluticasone-salmeterol and 5,845 to fluticasone alone, both for 26 weeks. Adherence to the study medications was 95%.
There were 36 serious asthma-related events – endotracheal intubation or hospitalization – in 34 patients (0.58%) in the fluticasone-salmeterol group, and 38 events in 33 patients (0.56%) in the fluticasone-only group. The hazard ratio for serious asthma-related events with fluticasone-salmeterol was 1.03 (95% confidence interval, 0.64-1.66), indicating that the safety of the combination was comparable with that of fluticasone monotherapy (P = .003). There were no asthma-related deaths in the trial, and two intubations in the fluticasone-only group.
The risk of a severe asthma exacerbation was 21% lower with fluticasone-salmeterol (HR, 0.79; 95% CI 0.70-0.89). While 480 fluticasone-salmeterol patients (8%) had at least one severe asthma exacerbation, at least one severe exacerbation occurred in 597 fluticasone-only patients (10%; P less than 0.001). “The difference was most prominent among adolescents, in whom the risk was 35% lower,” the investigators wrote.
“We found that ... the risk of serious asthma-related events was no greater when salmeterol was delivered by inhaler in a fixed-dose combination with fluticasone propionate than when fluticasone was administered alone,” and the “clinical benefits of fluticasone-salmeterol were significant,” they concluded.
The trial, which was designed with FDA guidance, excluded patients with life-threatening or unstable asthma in order to “mimic the population in which the (original LABA safety) signal was seen” in earlier studies; “the signal wasn’t seen specifically in that population.” Even so, “very few patients were eliminated due to a history of life-threatening asthma,” Dr. Stempel said.
It’s unclear why concomitant steroids reduce the risk. “LABA monotherapy may mask underlying disease by providing a temporary reduction in symptoms but ultimately placing patients at risk for serious exacerbations. When you give short- or long-acting bronchodilators, patients feel better, but you’re not treating the underlying disease; corticosteroids treat the underlying inflammatory component,” he said
The company will soon publish results from a similar fluticasone-salmeterol safety trial in children 4-11 years old. “I hope were finished” after that, “but we have to have a discussion with FDA to see what’s next.” The agency might want to pool data from the incoming trials to look at LABA-containing inhalers as a class. “It’s too premature to know where we’ll go with the box warning, but there’s a lot more information now than was available when the box first appeared in 2003,” Dr. Stempel said.
The work was funded by GlaxoSmithKline, and the authors are current or former employees.
LOS ANGELES – Fluticasone-salmeterol inhalers (Advair) are as safe as and more effective than fluticasone monotherapy inhalers are for patients with moderate to severe asthma, according to a large, randomized trial from its drug maker, GlaxoSmithKline, presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology and simultaneously published online March 6 in the New England Journal of Medicine.
The study is the first of several that the Food and Drug Administration required from Glaxo and other manufacturers in 2010 to evaluate the safety of long-acting beta-2 agonists (LABAs) such as salmeterol when used in combination with inhaled corticosteroids, after it became clear that LABAs, when used alone, increase the risk of serious asthma complications, including death (N Engl J Med. 2016 Mar 6. doi: 10.1056/NEJMoa1511049).
Current black box warnings on fluticasone-salmeterol (Advair), Merck’s mometasone-formoterol inhaler (Dulera), and AstraZeneca’s budesonide-formoterol combo (Symbicort)note that data are “inadequate to determine” if concomitant steroids mitigate the risk of LABAs.
Merck and AstraZeneca’s studies are ongoing, but Glaxo’s initial results seem reassuring. “I think what this study really does is provide evidence to answer the question that FDA was asking about safety. This is [also] the first really large study to show a decrease in exacerbations with [fluticasone-salmeterol],” principal investigator Dr. David Stempel, with Glaxo’s Respiratory Clinical Development program in Durham, N.C., said at the annual meeting.
However, because “patients with a history of life-threatening or unstable asthma” – including those who, at any point, had been intubated for asthma – “were excluded from the study, our results cannot be extrapolated to such patients,” the researchers wrote.
The inclusion criteria were otherwise broad: Adults and adolescents at least 12 years old, with a history of severe asthma exacerbations requiring the use of inhaled glucocorticoids or hospitalization in the previous year, but not in the month before enrollment, were included. There were 5,834 subjects randomized to fluticasone-salmeterol and 5,845 to fluticasone alone, both for 26 weeks. Adherence to the study medications was 95%.
There were 36 serious asthma-related events – endotracheal intubation or hospitalization – in 34 patients (0.58%) in the fluticasone-salmeterol group, and 38 events in 33 patients (0.56%) in the fluticasone-only group. The hazard ratio for serious asthma-related events with fluticasone-salmeterol was 1.03 (95% confidence interval, 0.64-1.66), indicating that the safety of the combination was comparable with that of fluticasone monotherapy (P = .003). There were no asthma-related deaths in the trial, and two intubations in the fluticasone-only group.
The risk of a severe asthma exacerbation was 21% lower with fluticasone-salmeterol (HR, 0.79; 95% CI 0.70-0.89). While 480 fluticasone-salmeterol patients (8%) had at least one severe asthma exacerbation, at least one severe exacerbation occurred in 597 fluticasone-only patients (10%; P less than 0.001). “The difference was most prominent among adolescents, in whom the risk was 35% lower,” the investigators wrote.
“We found that ... the risk of serious asthma-related events was no greater when salmeterol was delivered by inhaler in a fixed-dose combination with fluticasone propionate than when fluticasone was administered alone,” and the “clinical benefits of fluticasone-salmeterol were significant,” they concluded.
The trial, which was designed with FDA guidance, excluded patients with life-threatening or unstable asthma in order to “mimic the population in which the (original LABA safety) signal was seen” in earlier studies; “the signal wasn’t seen specifically in that population.” Even so, “very few patients were eliminated due to a history of life-threatening asthma,” Dr. Stempel said.
It’s unclear why concomitant steroids reduce the risk. “LABA monotherapy may mask underlying disease by providing a temporary reduction in symptoms but ultimately placing patients at risk for serious exacerbations. When you give short- or long-acting bronchodilators, patients feel better, but you’re not treating the underlying disease; corticosteroids treat the underlying inflammatory component,” he said
The company will soon publish results from a similar fluticasone-salmeterol safety trial in children 4-11 years old. “I hope were finished” after that, “but we have to have a discussion with FDA to see what’s next.” The agency might want to pool data from the incoming trials to look at LABA-containing inhalers as a class. “It’s too premature to know where we’ll go with the box warning, but there’s a lot more information now than was available when the box first appeared in 2003,” Dr. Stempel said.
The work was funded by GlaxoSmithKline, and the authors are current or former employees.
AT 2016 AAAAI ANNUAL MEETING
Key clinical point: A long-standing theory in asthma medicine is starting to be confirmed: Long-acting beta-agonists appear to be safe when used with concomitant corticosteroids.
Major finding: Among more than 11,500 adults and adolescents, there were 36 serious asthma-related events – (endotracheal intubation or hospitalization) in 34 patients (0.58%) in the fluticasone-salmeterol group, and 38 events in 33 patients (0.56%) in the fluticasone-only group.
Data source: Multicenter, randomized, double-blind trial involving 11,679 adolescent and adult asthma patients.
Disclosures: The work was funded by GlaxoSmithKline, and the authors are current or former employees.
ISC: Cryptogenic stroke linked to PSVT in absence of atrial fibrillation
LOS ANGELES – Paroxysmal supraventricular tachycardia is associated with subsequent ischemic stroke in patients without documented atrial fibrillation, according to a claims analysis of 42,152 Medicare enrollees at least 66 years old.
Atrial fibrillation accounts for perhaps 30% of cryptogenic strokes, “so clearly there’s something more to the story than just atrial fibrillation in” the other 70%, said investigator Dr. Hooman Kamel, a neurologist at Weill Cornell Medical College, New York. “Most cryptogenic strokes seem like they are embolic. The question is what are the undiscovered sources of embolism?”
Dr. Kamel and his colleagues focused on paroxysmal supraventricular tachycardia (PSVT) even though it’s generally considered benign. But “PSVT is increasingly recognized as a marker for underlying atrial dysfunction, especially in older patients. In some cases, the abnormal atrial substrate could cause thromboembolism even before atrial fibrillation [AF] appears,” he said at the International Stroke Conference.
To ensure regular heart rhythm monitoring, the study was limited to patients with implanted pacemakers or defibrillators. Patients with AF or stroke before or at the time of device implantation were excluded.
After a median of 1.8 years of follow-up, 2,245 patients (5.3%) were diagnosed with PSVT, and 1,007 (2.4%) had an ischemic stroke. The incidence of stroke without PSVT diagnosis was 0.95% per year, but 2.17% per year with a preceding PSVT diagnosis (P less than .001). Adjusting for age, gender, income, hypertension, diabetes, heart failure, and other potential confounders, the team found that a diagnosis of PSVT was associated with a doubling of ischemic stroke risk (HR, 2.0; 95% CI, 1.3-3.0), and an almost quadrupling of the risk for embolic stroke (HR, 3.6; 95% CI, 1.1-11.8).
“A lot more work needs to be done to nail this down, but potentially we are broadening the pool of atrial markers for stroke risk. These results build on recent findings that disturbances of atrial rhythm and function other than AF may” lead to stroke, Dr. Kamel said.
It’s way too soon to consider atrial ablation for PSVT to reduce stroke risk, he said, but his team is interrogating its administrative data for clues of its utility. “The idea of ablation for stroke is really interesting. I think ablation should help reduce the risk of stroke. It’s a really important question, and we don’t know the answer yet. There’s a lot more to be learned, [but] there does seem to be a definite progression from PSVT to AF,” Dr. Kamel said.
The National Institutes of Health funded the work. Dr. Kamel is a speaker for Genentech.
LOS ANGELES – Paroxysmal supraventricular tachycardia is associated with subsequent ischemic stroke in patients without documented atrial fibrillation, according to a claims analysis of 42,152 Medicare enrollees at least 66 years old.
Atrial fibrillation accounts for perhaps 30% of cryptogenic strokes, “so clearly there’s something more to the story than just atrial fibrillation in” the other 70%, said investigator Dr. Hooman Kamel, a neurologist at Weill Cornell Medical College, New York. “Most cryptogenic strokes seem like they are embolic. The question is what are the undiscovered sources of embolism?”
Dr. Kamel and his colleagues focused on paroxysmal supraventricular tachycardia (PSVT) even though it’s generally considered benign. But “PSVT is increasingly recognized as a marker for underlying atrial dysfunction, especially in older patients. In some cases, the abnormal atrial substrate could cause thromboembolism even before atrial fibrillation [AF] appears,” he said at the International Stroke Conference.
To ensure regular heart rhythm monitoring, the study was limited to patients with implanted pacemakers or defibrillators. Patients with AF or stroke before or at the time of device implantation were excluded.
After a median of 1.8 years of follow-up, 2,245 patients (5.3%) were diagnosed with PSVT, and 1,007 (2.4%) had an ischemic stroke. The incidence of stroke without PSVT diagnosis was 0.95% per year, but 2.17% per year with a preceding PSVT diagnosis (P less than .001). Adjusting for age, gender, income, hypertension, diabetes, heart failure, and other potential confounders, the team found that a diagnosis of PSVT was associated with a doubling of ischemic stroke risk (HR, 2.0; 95% CI, 1.3-3.0), and an almost quadrupling of the risk for embolic stroke (HR, 3.6; 95% CI, 1.1-11.8).
“A lot more work needs to be done to nail this down, but potentially we are broadening the pool of atrial markers for stroke risk. These results build on recent findings that disturbances of atrial rhythm and function other than AF may” lead to stroke, Dr. Kamel said.
It’s way too soon to consider atrial ablation for PSVT to reduce stroke risk, he said, but his team is interrogating its administrative data for clues of its utility. “The idea of ablation for stroke is really interesting. I think ablation should help reduce the risk of stroke. It’s a really important question, and we don’t know the answer yet. There’s a lot more to be learned, [but] there does seem to be a definite progression from PSVT to AF,” Dr. Kamel said.
The National Institutes of Health funded the work. Dr. Kamel is a speaker for Genentech.
LOS ANGELES – Paroxysmal supraventricular tachycardia is associated with subsequent ischemic stroke in patients without documented atrial fibrillation, according to a claims analysis of 42,152 Medicare enrollees at least 66 years old.
Atrial fibrillation accounts for perhaps 30% of cryptogenic strokes, “so clearly there’s something more to the story than just atrial fibrillation in” the other 70%, said investigator Dr. Hooman Kamel, a neurologist at Weill Cornell Medical College, New York. “Most cryptogenic strokes seem like they are embolic. The question is what are the undiscovered sources of embolism?”
Dr. Kamel and his colleagues focused on paroxysmal supraventricular tachycardia (PSVT) even though it’s generally considered benign. But “PSVT is increasingly recognized as a marker for underlying atrial dysfunction, especially in older patients. In some cases, the abnormal atrial substrate could cause thromboembolism even before atrial fibrillation [AF] appears,” he said at the International Stroke Conference.
To ensure regular heart rhythm monitoring, the study was limited to patients with implanted pacemakers or defibrillators. Patients with AF or stroke before or at the time of device implantation were excluded.
After a median of 1.8 years of follow-up, 2,245 patients (5.3%) were diagnosed with PSVT, and 1,007 (2.4%) had an ischemic stroke. The incidence of stroke without PSVT diagnosis was 0.95% per year, but 2.17% per year with a preceding PSVT diagnosis (P less than .001). Adjusting for age, gender, income, hypertension, diabetes, heart failure, and other potential confounders, the team found that a diagnosis of PSVT was associated with a doubling of ischemic stroke risk (HR, 2.0; 95% CI, 1.3-3.0), and an almost quadrupling of the risk for embolic stroke (HR, 3.6; 95% CI, 1.1-11.8).
“A lot more work needs to be done to nail this down, but potentially we are broadening the pool of atrial markers for stroke risk. These results build on recent findings that disturbances of atrial rhythm and function other than AF may” lead to stroke, Dr. Kamel said.
It’s way too soon to consider atrial ablation for PSVT to reduce stroke risk, he said, but his team is interrogating its administrative data for clues of its utility. “The idea of ablation for stroke is really interesting. I think ablation should help reduce the risk of stroke. It’s a really important question, and we don’t know the answer yet. There’s a lot more to be learned, [but] there does seem to be a definite progression from PSVT to AF,” Dr. Kamel said.
The National Institutes of Health funded the work. Dr. Kamel is a speaker for Genentech.
AT THE INTERNATIONAL STROKE CONFERENCE
Key clinical point: Paroxysmal supraventricular tachycardia could be an atrial marker for increased stroke risk when atrial fibrillation is not present, but additional research needs to confirm the finding.
Major finding: The incidence of stroke without PSVT diagnosis was 0.95% per year, but 2.17% per year with a preceding PSVT diagnosis (P less than .001).
Data source: Retrospective cohort of 42,152 Medicare enrollees.
Disclosures: The National Institutes of Health funded the work. The presenter is a speaker for Genentech.
ISC: Pick up Extra AF With Extended Holter Monitoring
LOS ANGELES – Atrial fibrillation is three times more likely to be detected within 6 months of an ischemic stroke if, instead of the usual 24 or so hours of Holter ECG monitoring, patients are monitored for 10 days poststroke, and then again for 10 days at 3 and 6 months, according to German investigators.
“Enhanced and prolonged monitoring should be considered for all stroke patients to improve the detection of atrial fibrillation,” said investigator Dr. Rolf Wachter, a cardiologist at the University of Göttingen (Germany).
Patients in the trial had no history of atrial fibrillation (AF) and were at least 60 years old; 200 were randomized to the extended-monitoring protocol, and 198 to standard of care, which included a median of 24 hours of Holter monitoring. The median time from symptom onset to randomization was 3 days. All patients were enrolled by day 5.
The study wasn’t limited to cryptogenic strokes; although the first stroke may not have been related to atrial fibrillation, a recurrent stroke could be, so “our approach was to look for AF in all stroke patients irrespective of etiology,” Dr. Wachter said at the International Stroke Conference.
By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002). The findings were largely the same when results were broken down by age, sex, National Institutes of Health Stroke Scale scores, and other metrics. AF was detected in the majority of both groups within a month.
Dr. Wachter did not elaborate on the frequency and duration of AF, but inclusion criteria required at least one episode lasting 30 seconds or longer.
The work touches on key issues facing neurologists and cardiologists today: How aggressive should post-stroke AF monitoring be, and when should treatment start?
Every AF patient in the study was orally anticoagulated, and almost all remained on their anticoagulant at 1 year. Their oral anticoagulant wasn’t reported, and the study wasn’t powered to detect differences in clinical outcomes. Even so, “we saw very positive trends in the right direction” for prolonged monitoring, he said.
Five patients in the intervention arm (2.5%) had a recurrent stroke and three (1.5%) had transient ischemic events at 1 year, versus nine (4.5%) recurrent strokes and five (2.5%) TIAs in the control arm. Six intervention patients (3%) and nine (4.5%) in the control group, had died.
A total of 60% of the subjects were men, and the mean age in the study was 73 years. The mean NIH Stroke Scale score was 3 in the intervention group and 2 in the control group. The mean CHADS2 (heart failure, hypertension, age, diabetes, stroke) score – a marker of thromboembolic risk – was 3.5 in both. Patients in the extended-monitoring group wore their Holter monitors for a median of 9.5 days at all three time points, but the initial compliance of 100% dropped to about 75% by the third session.
The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). Dr. Wachter is a speaker and consultant for the company.
There is widespread belief among most stroke neurologists that when you have a stroke that looks embolic and you don’t have a source, you need to monitor for longer than we have done traditionally. The nuances are really how to do that. This is a great approach; it’s a lot easier than wearing a 30-day Holter monitor or having an implanted device, but we have to compare it to other approaches and see what the heart endpoints really are to know if it’s the best approach.
I think everybody in the stroke community appreciates that the more you monitor, the more you are likely to find AF. How long you should monitor, by what technique, and whether monitoring should be continuous or intermittent are unanswered questions. The other question is how much AF is significant. Is a 30-second run significant, or does it need to be minutes at a time? These questions need to be answered before there’s a wholesale buy-in for this kind of monitoring for every patient.
Dr. Kyra Becker is a professor in the departments of neurology and neurological surgery, and director of Vascular Neurology Services at the University of Washington’s Comprehensive Stroke Center in Seattle. She was not involved in the study.
There is widespread belief among most stroke neurologists that when you have a stroke that looks embolic and you don’t have a source, you need to monitor for longer than we have done traditionally. The nuances are really how to do that. This is a great approach; it’s a lot easier than wearing a 30-day Holter monitor or having an implanted device, but we have to compare it to other approaches and see what the heart endpoints really are to know if it’s the best approach.
I think everybody in the stroke community appreciates that the more you monitor, the more you are likely to find AF. How long you should monitor, by what technique, and whether monitoring should be continuous or intermittent are unanswered questions. The other question is how much AF is significant. Is a 30-second run significant, or does it need to be minutes at a time? These questions need to be answered before there’s a wholesale buy-in for this kind of monitoring for every patient.
Dr. Kyra Becker is a professor in the departments of neurology and neurological surgery, and director of Vascular Neurology Services at the University of Washington’s Comprehensive Stroke Center in Seattle. She was not involved in the study.
There is widespread belief among most stroke neurologists that when you have a stroke that looks embolic and you don’t have a source, you need to monitor for longer than we have done traditionally. The nuances are really how to do that. This is a great approach; it’s a lot easier than wearing a 30-day Holter monitor or having an implanted device, but we have to compare it to other approaches and see what the heart endpoints really are to know if it’s the best approach.
I think everybody in the stroke community appreciates that the more you monitor, the more you are likely to find AF. How long you should monitor, by what technique, and whether monitoring should be continuous or intermittent are unanswered questions. The other question is how much AF is significant. Is a 30-second run significant, or does it need to be minutes at a time? These questions need to be answered before there’s a wholesale buy-in for this kind of monitoring for every patient.
Dr. Kyra Becker is a professor in the departments of neurology and neurological surgery, and director of Vascular Neurology Services at the University of Washington’s Comprehensive Stroke Center in Seattle. She was not involved in the study.
LOS ANGELES – Atrial fibrillation is three times more likely to be detected within 6 months of an ischemic stroke if, instead of the usual 24 or so hours of Holter ECG monitoring, patients are monitored for 10 days poststroke, and then again for 10 days at 3 and 6 months, according to German investigators.
“Enhanced and prolonged monitoring should be considered for all stroke patients to improve the detection of atrial fibrillation,” said investigator Dr. Rolf Wachter, a cardiologist at the University of Göttingen (Germany).
Patients in the trial had no history of atrial fibrillation (AF) and were at least 60 years old; 200 were randomized to the extended-monitoring protocol, and 198 to standard of care, which included a median of 24 hours of Holter monitoring. The median time from symptom onset to randomization was 3 days. All patients were enrolled by day 5.
The study wasn’t limited to cryptogenic strokes; although the first stroke may not have been related to atrial fibrillation, a recurrent stroke could be, so “our approach was to look for AF in all stroke patients irrespective of etiology,” Dr. Wachter said at the International Stroke Conference.
By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002). The findings were largely the same when results were broken down by age, sex, National Institutes of Health Stroke Scale scores, and other metrics. AF was detected in the majority of both groups within a month.
Dr. Wachter did not elaborate on the frequency and duration of AF, but inclusion criteria required at least one episode lasting 30 seconds or longer.
The work touches on key issues facing neurologists and cardiologists today: How aggressive should post-stroke AF monitoring be, and when should treatment start?
Every AF patient in the study was orally anticoagulated, and almost all remained on their anticoagulant at 1 year. Their oral anticoagulant wasn’t reported, and the study wasn’t powered to detect differences in clinical outcomes. Even so, “we saw very positive trends in the right direction” for prolonged monitoring, he said.
Five patients in the intervention arm (2.5%) had a recurrent stroke and three (1.5%) had transient ischemic events at 1 year, versus nine (4.5%) recurrent strokes and five (2.5%) TIAs in the control arm. Six intervention patients (3%) and nine (4.5%) in the control group, had died.
A total of 60% of the subjects were men, and the mean age in the study was 73 years. The mean NIH Stroke Scale score was 3 in the intervention group and 2 in the control group. The mean CHADS2 (heart failure, hypertension, age, diabetes, stroke) score – a marker of thromboembolic risk – was 3.5 in both. Patients in the extended-monitoring group wore their Holter monitors for a median of 9.5 days at all three time points, but the initial compliance of 100% dropped to about 75% by the third session.
The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). Dr. Wachter is a speaker and consultant for the company.
LOS ANGELES – Atrial fibrillation is three times more likely to be detected within 6 months of an ischemic stroke if, instead of the usual 24 or so hours of Holter ECG monitoring, patients are monitored for 10 days poststroke, and then again for 10 days at 3 and 6 months, according to German investigators.
“Enhanced and prolonged monitoring should be considered for all stroke patients to improve the detection of atrial fibrillation,” said investigator Dr. Rolf Wachter, a cardiologist at the University of Göttingen (Germany).
Patients in the trial had no history of atrial fibrillation (AF) and were at least 60 years old; 200 were randomized to the extended-monitoring protocol, and 198 to standard of care, which included a median of 24 hours of Holter monitoring. The median time from symptom onset to randomization was 3 days. All patients were enrolled by day 5.
The study wasn’t limited to cryptogenic strokes; although the first stroke may not have been related to atrial fibrillation, a recurrent stroke could be, so “our approach was to look for AF in all stroke patients irrespective of etiology,” Dr. Wachter said at the International Stroke Conference.
By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002). The findings were largely the same when results were broken down by age, sex, National Institutes of Health Stroke Scale scores, and other metrics. AF was detected in the majority of both groups within a month.
Dr. Wachter did not elaborate on the frequency and duration of AF, but inclusion criteria required at least one episode lasting 30 seconds or longer.
The work touches on key issues facing neurologists and cardiologists today: How aggressive should post-stroke AF monitoring be, and when should treatment start?
Every AF patient in the study was orally anticoagulated, and almost all remained on their anticoagulant at 1 year. Their oral anticoagulant wasn’t reported, and the study wasn’t powered to detect differences in clinical outcomes. Even so, “we saw very positive trends in the right direction” for prolonged monitoring, he said.
Five patients in the intervention arm (2.5%) had a recurrent stroke and three (1.5%) had transient ischemic events at 1 year, versus nine (4.5%) recurrent strokes and five (2.5%) TIAs in the control arm. Six intervention patients (3%) and nine (4.5%) in the control group, had died.
A total of 60% of the subjects were men, and the mean age in the study was 73 years. The mean NIH Stroke Scale score was 3 in the intervention group and 2 in the control group. The mean CHADS2 (heart failure, hypertension, age, diabetes, stroke) score – a marker of thromboembolic risk – was 3.5 in both. Patients in the extended-monitoring group wore their Holter monitors for a median of 9.5 days at all three time points, but the initial compliance of 100% dropped to about 75% by the third session.
The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). Dr. Wachter is a speaker and consultant for the company.
AT THE INTERNATIONAL STROKE CONFERENCE
ISC: Pick up extra AF with extended Holter monitoring
LOS ANGELES – Atrial fibrillation is three times more likely to be detected within 6 months of an ischemic stroke if, instead of the usual 24 or so hours of Holter ECG monitoring, patients are monitored for 10 days poststroke, and then again for 10 days at 3 and 6 months, according to German investigators.
“Enhanced and prolonged monitoring should be considered for all stroke patients to improve the detection of atrial fibrillation,” said investigator Dr. Rolf Wachter, a cardiologist at the University of Göttingen (Germany).
Patients in the trial had no history of atrial fibrillation (AF) and were at least 60 years old; 200 were randomized to the extended-monitoring protocol, and 198 to standard of care, which included a median of 24 hours of Holter monitoring. The median time from symptom onset to randomization was 3 days. All patients were enrolled by day 5.
The study wasn’t limited to cryptogenic strokes; although the first stroke may not have been related to atrial fibrillation, a recurrent stroke could be, so “our approach was to look for AF in all stroke patients irrespective of etiology,” Dr. Wachter said at the International Stroke Conference.
By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002). The findings were largely the same when results were broken down by age, sex, National Institutes of Health Stroke Scale scores, and other metrics. AF was detected in the majority of both groups within a month.
Dr. Wachter did not elaborate on the frequency and duration of AF, but inclusion criteria required at least one episode lasting 30 seconds or longer.
The work touches on key issues facing neurologists and cardiologists today: How aggressive should post-stroke AF monitoring be, and when should treatment start?
Every AF patient in the study was orally anticoagulated, and almost all remained on their anticoagulant at 1 year. Their oral anticoagulant wasn’t reported, and the study wasn’t powered to detect differences in clinical outcomes. Even so, “we saw very positive trends in the right direction” for prolonged monitoring, he said.
Five patients in the intervention arm (2.5%) had a recurrent stroke and three (1.5%) had transient ischemic events at 1 year, versus nine (4.5%) recurrent strokes and five (2.5%) TIAs in the control arm. Six intervention patients (3%) and nine (4.5%) in the control group, had died.
A total of 60% of the subjects were men, and the mean age in the study was 73 years. The mean NIH Stroke Scale score was 3 in the intervention group and 2 in the control group. The mean CHADS2 (heart failure, hypertension, age, diabetes, stroke) score – a marker of thromboembolic risk – was 3.5 in both. Patients in the extended-monitoring group wore their Holter monitors for a median of 9.5 days at all three time points, but the initial compliance of 100% dropped to about 75% by the third session.
The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). Dr. Wachter is a speaker and consultant for the company.
There is widespread belief among most stroke neurologists that when you have a stroke that looks embolic and you don’t have a source, you need to monitor for longer than we have done traditionally. The nuances are really how to do that. This is a great approach; it’s a lot easier than wearing a 30-day Holter monitor or having an implanted device, but we have to compare it to other approaches and see what the heart endpoints really are to know if it’s the best approach.
I think everybody in the stroke community appreciates that the more you monitor, the more you are likely to find AF. How long you should monitor, by what technique, and whether monitoring should be continuous or intermittent are unanswered questions. The other question is how much AF is significant. Is a 30-second run significant, or does it need to be minutes at a time? These questions need to be answered before there’s a wholesale buy-in for this kind of monitoring for every patient.
Dr. Kyra Becker is a professor in the departments of neurology and neurological surgery, and director of Vascular Neurology Services at the University of Washington’s Comprehensive Stroke Center in Seattle. She was not involved in the study.
There is widespread belief among most stroke neurologists that when you have a stroke that looks embolic and you don’t have a source, you need to monitor for longer than we have done traditionally. The nuances are really how to do that. This is a great approach; it’s a lot easier than wearing a 30-day Holter monitor or having an implanted device, but we have to compare it to other approaches and see what the heart endpoints really are to know if it’s the best approach.
I think everybody in the stroke community appreciates that the more you monitor, the more you are likely to find AF. How long you should monitor, by what technique, and whether monitoring should be continuous or intermittent are unanswered questions. The other question is how much AF is significant. Is a 30-second run significant, or does it need to be minutes at a time? These questions need to be answered before there’s a wholesale buy-in for this kind of monitoring for every patient.
Dr. Kyra Becker is a professor in the departments of neurology and neurological surgery, and director of Vascular Neurology Services at the University of Washington’s Comprehensive Stroke Center in Seattle. She was not involved in the study.
There is widespread belief among most stroke neurologists that when you have a stroke that looks embolic and you don’t have a source, you need to monitor for longer than we have done traditionally. The nuances are really how to do that. This is a great approach; it’s a lot easier than wearing a 30-day Holter monitor or having an implanted device, but we have to compare it to other approaches and see what the heart endpoints really are to know if it’s the best approach.
I think everybody in the stroke community appreciates that the more you monitor, the more you are likely to find AF. How long you should monitor, by what technique, and whether monitoring should be continuous or intermittent are unanswered questions. The other question is how much AF is significant. Is a 30-second run significant, or does it need to be minutes at a time? These questions need to be answered before there’s a wholesale buy-in for this kind of monitoring for every patient.
Dr. Kyra Becker is a professor in the departments of neurology and neurological surgery, and director of Vascular Neurology Services at the University of Washington’s Comprehensive Stroke Center in Seattle. She was not involved in the study.
LOS ANGELES – Atrial fibrillation is three times more likely to be detected within 6 months of an ischemic stroke if, instead of the usual 24 or so hours of Holter ECG monitoring, patients are monitored for 10 days poststroke, and then again for 10 days at 3 and 6 months, according to German investigators.
“Enhanced and prolonged monitoring should be considered for all stroke patients to improve the detection of atrial fibrillation,” said investigator Dr. Rolf Wachter, a cardiologist at the University of Göttingen (Germany).
Patients in the trial had no history of atrial fibrillation (AF) and were at least 60 years old; 200 were randomized to the extended-monitoring protocol, and 198 to standard of care, which included a median of 24 hours of Holter monitoring. The median time from symptom onset to randomization was 3 days. All patients were enrolled by day 5.
The study wasn’t limited to cryptogenic strokes; although the first stroke may not have been related to atrial fibrillation, a recurrent stroke could be, so “our approach was to look for AF in all stroke patients irrespective of etiology,” Dr. Wachter said at the International Stroke Conference.
By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002). The findings were largely the same when results were broken down by age, sex, National Institutes of Health Stroke Scale scores, and other metrics. AF was detected in the majority of both groups within a month.
Dr. Wachter did not elaborate on the frequency and duration of AF, but inclusion criteria required at least one episode lasting 30 seconds or longer.
The work touches on key issues facing neurologists and cardiologists today: How aggressive should post-stroke AF monitoring be, and when should treatment start?
Every AF patient in the study was orally anticoagulated, and almost all remained on their anticoagulant at 1 year. Their oral anticoagulant wasn’t reported, and the study wasn’t powered to detect differences in clinical outcomes. Even so, “we saw very positive trends in the right direction” for prolonged monitoring, he said.
Five patients in the intervention arm (2.5%) had a recurrent stroke and three (1.5%) had transient ischemic events at 1 year, versus nine (4.5%) recurrent strokes and five (2.5%) TIAs in the control arm. Six intervention patients (3%) and nine (4.5%) in the control group, had died.
A total of 60% of the subjects were men, and the mean age in the study was 73 years. The mean NIH Stroke Scale score was 3 in the intervention group and 2 in the control group. The mean CHADS2 (heart failure, hypertension, age, diabetes, stroke) score – a marker of thromboembolic risk – was 3.5 in both. Patients in the extended-monitoring group wore their Holter monitors for a median of 9.5 days at all three time points, but the initial compliance of 100% dropped to about 75% by the third session.
The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). Dr. Wachter is a speaker and consultant for the company.
LOS ANGELES – Atrial fibrillation is three times more likely to be detected within 6 months of an ischemic stroke if, instead of the usual 24 or so hours of Holter ECG monitoring, patients are monitored for 10 days poststroke, and then again for 10 days at 3 and 6 months, according to German investigators.
“Enhanced and prolonged monitoring should be considered for all stroke patients to improve the detection of atrial fibrillation,” said investigator Dr. Rolf Wachter, a cardiologist at the University of Göttingen (Germany).
Patients in the trial had no history of atrial fibrillation (AF) and were at least 60 years old; 200 were randomized to the extended-monitoring protocol, and 198 to standard of care, which included a median of 24 hours of Holter monitoring. The median time from symptom onset to randomization was 3 days. All patients were enrolled by day 5.
The study wasn’t limited to cryptogenic strokes; although the first stroke may not have been related to atrial fibrillation, a recurrent stroke could be, so “our approach was to look for AF in all stroke patients irrespective of etiology,” Dr. Wachter said at the International Stroke Conference.
By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002). The findings were largely the same when results were broken down by age, sex, National Institutes of Health Stroke Scale scores, and other metrics. AF was detected in the majority of both groups within a month.
Dr. Wachter did not elaborate on the frequency and duration of AF, but inclusion criteria required at least one episode lasting 30 seconds or longer.
The work touches on key issues facing neurologists and cardiologists today: How aggressive should post-stroke AF monitoring be, and when should treatment start?
Every AF patient in the study was orally anticoagulated, and almost all remained on their anticoagulant at 1 year. Their oral anticoagulant wasn’t reported, and the study wasn’t powered to detect differences in clinical outcomes. Even so, “we saw very positive trends in the right direction” for prolonged monitoring, he said.
Five patients in the intervention arm (2.5%) had a recurrent stroke and three (1.5%) had transient ischemic events at 1 year, versus nine (4.5%) recurrent strokes and five (2.5%) TIAs in the control arm. Six intervention patients (3%) and nine (4.5%) in the control group, had died.
A total of 60% of the subjects were men, and the mean age in the study was 73 years. The mean NIH Stroke Scale score was 3 in the intervention group and 2 in the control group. The mean CHADS2 (heart failure, hypertension, age, diabetes, stroke) score – a marker of thromboembolic risk – was 3.5 in both. Patients in the extended-monitoring group wore their Holter monitors for a median of 9.5 days at all three time points, but the initial compliance of 100% dropped to about 75% by the third session.
The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). Dr. Wachter is a speaker and consultant for the company.
AT THE INTERNATIONAL STROKE CONFERENCE
Key clinical point: Repeated Holter monitoring over 6 months catches more atrial fibrillation than one-time, poststroke monitoring.
Major finding: By 6 months, AF was detected in 27 patients (13.5 %) in the extended-monitoring group, versus 9 (4.5 %) in the control group (absolute difference, 9%; 95% confidence interval, 3.5%-14.6%; P = .002).
Data source: Randomized trial with 398 ischemic stroke patients.
Disclosures: The work was funded by Boehringer Ingelheim, maker of the oral anticoagulant dabigatran (Pradaxa). The presenter is a speaker and consultant for the company.
VIDEO: A better way to treat large intraventricular hemorrhages
LOS ANGELES – For intraventricular hemorrhages of at least 20 mL, alteplase (Activase – Genentech) delivered directly into the clot by external ventricular drain almost doubles the odds of achieving a modified Rankin Score of 0-3 by 6 months.
More clot is removed – and patients with large intraventricular hemorrhages (IVHs) do better – with more vigorous alteplase dosing and when more than one drain is used.
The findings come from the Clot Lysis Evaluation of Accelerated Resolution (CLEAR III) trial, which randomized 249 IVH patients to 1 mg alteplase every 8 hours for up to 12 doses, and 251 to saline on the same schedule, delivered by external ventricular drain. The intervention didn’t make much difference with small hemorrhages.
In a video interview at the International Stroke Conference, investigator Dr. Issam Awad, a professor of surgery and neurology and director of neurovascular surgery at the University of Chicago, explained how to do the technique correctly for larger clots, and the expected benefits.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LOS ANGELES – For intraventricular hemorrhages of at least 20 mL, alteplase (Activase – Genentech) delivered directly into the clot by external ventricular drain almost doubles the odds of achieving a modified Rankin Score of 0-3 by 6 months.
More clot is removed – and patients with large intraventricular hemorrhages (IVHs) do better – with more vigorous alteplase dosing and when more than one drain is used.
The findings come from the Clot Lysis Evaluation of Accelerated Resolution (CLEAR III) trial, which randomized 249 IVH patients to 1 mg alteplase every 8 hours for up to 12 doses, and 251 to saline on the same schedule, delivered by external ventricular drain. The intervention didn’t make much difference with small hemorrhages.
In a video interview at the International Stroke Conference, investigator Dr. Issam Awad, a professor of surgery and neurology and director of neurovascular surgery at the University of Chicago, explained how to do the technique correctly for larger clots, and the expected benefits.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LOS ANGELES – For intraventricular hemorrhages of at least 20 mL, alteplase (Activase – Genentech) delivered directly into the clot by external ventricular drain almost doubles the odds of achieving a modified Rankin Score of 0-3 by 6 months.
More clot is removed – and patients with large intraventricular hemorrhages (IVHs) do better – with more vigorous alteplase dosing and when more than one drain is used.
The findings come from the Clot Lysis Evaluation of Accelerated Resolution (CLEAR III) trial, which randomized 249 IVH patients to 1 mg alteplase every 8 hours for up to 12 doses, and 251 to saline on the same schedule, delivered by external ventricular drain. The intervention didn’t make much difference with small hemorrhages.
In a video interview at the International Stroke Conference, investigator Dr. Issam Awad, a professor of surgery and neurology and director of neurovascular surgery at the University of Chicago, explained how to do the technique correctly for larger clots, and the expected benefits.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE INTERNATIONAL STROKE CONFERENCE
VIDEO: Intracranial warfarin bleeds smaller with prothrombin complex instead of FFP
LOS ANGELES – The international normalized ratio fell to 1.2 or less within 3 hours among 18 of 27 (67%) patients who received four-factor prothrombin complex concentrate (octaplex [Octapharma]) for warfarin-related intracranial hemorrhages, but only 2 of 23 (9%) who received fresh frozen plasma, according to a randomized trial from Germany.
Hematoma expansion was reduced by 16.9 mL (P = .026) at 3 hours and 16.4 mL (P = .018) at 24 hours in the prothrombin complex concentrate (PCC) group.
All the patients presented within 12 hours of symptom onset with an INR of at least 2; they received fresh frozen plasma (FFP) or four-factor PCC within an hour of their cerebral CT. There were eight deaths in the FFP group, including five due to hematoma expansion. The five deaths in the PCC group occurred after day 5, and one was thought to be because of hematoma expansion. Patients were 76 years old, on average, and the majority were men; both groups received vitamin K.
The findings make a case for PCC at a time when it’s unclear how best to handle warfarin-related intracranial bleeds, and whether the extra cost of PCC is worth it. Investigator Dr. Thorsten Steiner, a professor of neurology at the University of Heidelberg (Germany), addressed the relevant issues, including PCC safety, in a video interview at the International Stroke Conference sponsored by the American Heart Association. The investigator-initiated trial was funded by Octapharma, and Dr. Steiner reported receiving a research grant from the company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LOS ANGELES – The international normalized ratio fell to 1.2 or less within 3 hours among 18 of 27 (67%) patients who received four-factor prothrombin complex concentrate (octaplex [Octapharma]) for warfarin-related intracranial hemorrhages, but only 2 of 23 (9%) who received fresh frozen plasma, according to a randomized trial from Germany.
Hematoma expansion was reduced by 16.9 mL (P = .026) at 3 hours and 16.4 mL (P = .018) at 24 hours in the prothrombin complex concentrate (PCC) group.
All the patients presented within 12 hours of symptom onset with an INR of at least 2; they received fresh frozen plasma (FFP) or four-factor PCC within an hour of their cerebral CT. There were eight deaths in the FFP group, including five due to hematoma expansion. The five deaths in the PCC group occurred after day 5, and one was thought to be because of hematoma expansion. Patients were 76 years old, on average, and the majority were men; both groups received vitamin K.
The findings make a case for PCC at a time when it’s unclear how best to handle warfarin-related intracranial bleeds, and whether the extra cost of PCC is worth it. Investigator Dr. Thorsten Steiner, a professor of neurology at the University of Heidelberg (Germany), addressed the relevant issues, including PCC safety, in a video interview at the International Stroke Conference sponsored by the American Heart Association. The investigator-initiated trial was funded by Octapharma, and Dr. Steiner reported receiving a research grant from the company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LOS ANGELES – The international normalized ratio fell to 1.2 or less within 3 hours among 18 of 27 (67%) patients who received four-factor prothrombin complex concentrate (octaplex [Octapharma]) for warfarin-related intracranial hemorrhages, but only 2 of 23 (9%) who received fresh frozen plasma, according to a randomized trial from Germany.
Hematoma expansion was reduced by 16.9 mL (P = .026) at 3 hours and 16.4 mL (P = .018) at 24 hours in the prothrombin complex concentrate (PCC) group.
All the patients presented within 12 hours of symptom onset with an INR of at least 2; they received fresh frozen plasma (FFP) or four-factor PCC within an hour of their cerebral CT. There were eight deaths in the FFP group, including five due to hematoma expansion. The five deaths in the PCC group occurred after day 5, and one was thought to be because of hematoma expansion. Patients were 76 years old, on average, and the majority were men; both groups received vitamin K.
The findings make a case for PCC at a time when it’s unclear how best to handle warfarin-related intracranial bleeds, and whether the extra cost of PCC is worth it. Investigator Dr. Thorsten Steiner, a professor of neurology at the University of Heidelberg (Germany), addressed the relevant issues, including PCC safety, in a video interview at the International Stroke Conference sponsored by the American Heart Association. The investigator-initiated trial was funded by Octapharma, and Dr. Steiner reported receiving a research grant from the company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE INTERNATIONAL STROKE CONFERENCE
Zika diagnostic test available from CDC to certified labs
As concern about Zika virus mounts, the Food and Drug Administration on Feb. 26 authorized use of an investigational test from the Centers for Disease Control and Prevention to detect antibodies in sera and cerebrospinal fluid.
Known as the Zika Immunoglobulin M Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), the test is available under an FDA Emergency Use Authorization to labs certified by CDC for high-complexity tests.
If infection is suspected, “the Zika MAC-ELISA may be ordered. Please contact your state or local health department to facilitate testing,” FDA said in a fact sheet for health care providers.
“At this time, there are no FDA approved/cleared tests available that can detect Zika virus in clinical specimens in the United States. Therefore, CDC has developed this test to detect evidence of Zika virus infections.” Positive and inconclusive results must be confirmed by CDC or authorized laboratories, the FDA noted.
Testing is appropriate in patients with signs and symptoms of Zika virus infection who recently traveled to areas with active transmissions. Anti-Zika IgM can usually be detected after about 4 days of symptoms, and remains detectable for about 3 months.
Most who are infected with the Zika virus don’t know they have it. For others, symptoms set in after a few days, tend to be mild, last about a week, and can include fever, rash, joint pain, and conjunctivitis. The virus has, however, been associated in Brazil with Guillain-Barre syndrome and microcephaly, although detection in pregnant women does not necessarily mean the fetus has been harmed.
So far, there have been more than 90 confirmed cases of Zika infection in the United States, most, but not all, in people who had recently traveled to endemic areas.
The FDA did not report sensitivity and specificity figures, but it’s clear from what it did say that reliability is an issue. Closely-related flavivirus infections, such as dengue fever, can trigger false positives, and in patients vaccinated against yellow fever or Japanese encephalitis, cross-reactive antibodies can also “make it difficult to identify which flavivirus is causing the patient’s current illness,” the fact sheet noted.
False negatives should be considered when “recent exposures or clinical presentation are consistent with Zika virus infection and diagnostic tests for other causes of illness are negative. Conversely, a negative result in an asymptomatic patient with a lower likelihood of exposure (e.g., a short term traveler to an affected area) may suggest the patient is not infected,” the FDA noted.
Zika MAC-ELISA labeling, fact sheets for patients, and other materials are available on the FDA’s Emergency Use Authorizations webpage. The CDC has a Zika virus site for health care providers, as well.
As concern about Zika virus mounts, the Food and Drug Administration on Feb. 26 authorized use of an investigational test from the Centers for Disease Control and Prevention to detect antibodies in sera and cerebrospinal fluid.
Known as the Zika Immunoglobulin M Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), the test is available under an FDA Emergency Use Authorization to labs certified by CDC for high-complexity tests.
If infection is suspected, “the Zika MAC-ELISA may be ordered. Please contact your state or local health department to facilitate testing,” FDA said in a fact sheet for health care providers.
“At this time, there are no FDA approved/cleared tests available that can detect Zika virus in clinical specimens in the United States. Therefore, CDC has developed this test to detect evidence of Zika virus infections.” Positive and inconclusive results must be confirmed by CDC or authorized laboratories, the FDA noted.
Testing is appropriate in patients with signs and symptoms of Zika virus infection who recently traveled to areas with active transmissions. Anti-Zika IgM can usually be detected after about 4 days of symptoms, and remains detectable for about 3 months.
Most who are infected with the Zika virus don’t know they have it. For others, symptoms set in after a few days, tend to be mild, last about a week, and can include fever, rash, joint pain, and conjunctivitis. The virus has, however, been associated in Brazil with Guillain-Barre syndrome and microcephaly, although detection in pregnant women does not necessarily mean the fetus has been harmed.
So far, there have been more than 90 confirmed cases of Zika infection in the United States, most, but not all, in people who had recently traveled to endemic areas.
The FDA did not report sensitivity and specificity figures, but it’s clear from what it did say that reliability is an issue. Closely-related flavivirus infections, such as dengue fever, can trigger false positives, and in patients vaccinated against yellow fever or Japanese encephalitis, cross-reactive antibodies can also “make it difficult to identify which flavivirus is causing the patient’s current illness,” the fact sheet noted.
False negatives should be considered when “recent exposures or clinical presentation are consistent with Zika virus infection and diagnostic tests for other causes of illness are negative. Conversely, a negative result in an asymptomatic patient with a lower likelihood of exposure (e.g., a short term traveler to an affected area) may suggest the patient is not infected,” the FDA noted.
Zika MAC-ELISA labeling, fact sheets for patients, and other materials are available on the FDA’s Emergency Use Authorizations webpage. The CDC has a Zika virus site for health care providers, as well.
As concern about Zika virus mounts, the Food and Drug Administration on Feb. 26 authorized use of an investigational test from the Centers for Disease Control and Prevention to detect antibodies in sera and cerebrospinal fluid.
Known as the Zika Immunoglobulin M Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), the test is available under an FDA Emergency Use Authorization to labs certified by CDC for high-complexity tests.
If infection is suspected, “the Zika MAC-ELISA may be ordered. Please contact your state or local health department to facilitate testing,” FDA said in a fact sheet for health care providers.
“At this time, there are no FDA approved/cleared tests available that can detect Zika virus in clinical specimens in the United States. Therefore, CDC has developed this test to detect evidence of Zika virus infections.” Positive and inconclusive results must be confirmed by CDC or authorized laboratories, the FDA noted.
Testing is appropriate in patients with signs and symptoms of Zika virus infection who recently traveled to areas with active transmissions. Anti-Zika IgM can usually be detected after about 4 days of symptoms, and remains detectable for about 3 months.
Most who are infected with the Zika virus don’t know they have it. For others, symptoms set in after a few days, tend to be mild, last about a week, and can include fever, rash, joint pain, and conjunctivitis. The virus has, however, been associated in Brazil with Guillain-Barre syndrome and microcephaly, although detection in pregnant women does not necessarily mean the fetus has been harmed.
So far, there have been more than 90 confirmed cases of Zika infection in the United States, most, but not all, in people who had recently traveled to endemic areas.
The FDA did not report sensitivity and specificity figures, but it’s clear from what it did say that reliability is an issue. Closely-related flavivirus infections, such as dengue fever, can trigger false positives, and in patients vaccinated against yellow fever or Japanese encephalitis, cross-reactive antibodies can also “make it difficult to identify which flavivirus is causing the patient’s current illness,” the fact sheet noted.
False negatives should be considered when “recent exposures or clinical presentation are consistent with Zika virus infection and diagnostic tests for other causes of illness are negative. Conversely, a negative result in an asymptomatic patient with a lower likelihood of exposure (e.g., a short term traveler to an affected area) may suggest the patient is not infected,” the FDA noted.
Zika MAC-ELISA labeling, fact sheets for patients, and other materials are available on the FDA’s Emergency Use Authorizations webpage. The CDC has a Zika virus site for health care providers, as well.
VIDEO: Rapidly improving stroke patients still at risk for bad outcomes
LOS ANGELES – Stroke patients might seem to improve on their way to the hospital, but it’s hard to know if they really are.
Investigators at State University of New York, Brooklyn, have taken a step toward identifying risk factors for poor outcomes when patients seem to be getting better. In a post hoc analysis of the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial, they found that in general, clinical outcomes were better with rapid neurologic improvement on the Los Angeles Motor Scale, but about half who had improved 2 points by the time they reached the hospital – and more than a third who improved 4 points – were not discharged home.
Investigator Dr. Steven Levine, a professor of neurology and emergency medicine at SUNY Brooklyn, is working on the risk factors, and he shared what’s known so far in an interview at the International Stroke Conference, sponsored by the American Heart Association. The work is part of Genentech’s efforts to identify patients who benefit from the company’s tissue plasminogen activator, alteplase, despite arriving with low stroke scale scores. Dr. Levine is an adviser to Genentech.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LOS ANGELES – Stroke patients might seem to improve on their way to the hospital, but it’s hard to know if they really are.
Investigators at State University of New York, Brooklyn, have taken a step toward identifying risk factors for poor outcomes when patients seem to be getting better. In a post hoc analysis of the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial, they found that in general, clinical outcomes were better with rapid neurologic improvement on the Los Angeles Motor Scale, but about half who had improved 2 points by the time they reached the hospital – and more than a third who improved 4 points – were not discharged home.
Investigator Dr. Steven Levine, a professor of neurology and emergency medicine at SUNY Brooklyn, is working on the risk factors, and he shared what’s known so far in an interview at the International Stroke Conference, sponsored by the American Heart Association. The work is part of Genentech’s efforts to identify patients who benefit from the company’s tissue plasminogen activator, alteplase, despite arriving with low stroke scale scores. Dr. Levine is an adviser to Genentech.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
LOS ANGELES – Stroke patients might seem to improve on their way to the hospital, but it’s hard to know if they really are.
Investigators at State University of New York, Brooklyn, have taken a step toward identifying risk factors for poor outcomes when patients seem to be getting better. In a post hoc analysis of the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial, they found that in general, clinical outcomes were better with rapid neurologic improvement on the Los Angeles Motor Scale, but about half who had improved 2 points by the time they reached the hospital – and more than a third who improved 4 points – were not discharged home.
Investigator Dr. Steven Levine, a professor of neurology and emergency medicine at SUNY Brooklyn, is working on the risk factors, and he shared what’s known so far in an interview at the International Stroke Conference, sponsored by the American Heart Association. The work is part of Genentech’s efforts to identify patients who benefit from the company’s tissue plasminogen activator, alteplase, despite arriving with low stroke scale scores. Dr. Levine is an adviser to Genentech.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE INTERNATIONAL STROKE CONFERENCE
