Bruce Jancin

Topical timolol for the treatment of infantile hemangiomas is emerging as a safer, easier alternative to oral propranolol in selected patients, according to Dr. Sheila Fallon Friedlander.

"I think this [timolol] is something that’s very, very useful. You’re going to be seeing more of it around in use for this condition. We’ve seen encouraging results in the past 2½ years. It’s well tolerated, and I think there will come a day when even primary care physicians will be using topical timolol with comfort," she said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/IMNG Medical Media

Topical timolol works best for small, relatively thin hemangiomas, such as eyelid lesions, advised Dr. Friedlander, president of the Society for Pediatric Dermatology and a pediatric dermatologist at the University of California, San Diego.

"You don’t put timolol on big, thick lesions and expect it to work; it won’t," she said.

At this point, the evidence base for topical timolol is far smaller than for propranolol, which has become the clear drug of choice for children requiring systemic therapy. To date, there are at least 20 articles involving about 175 timolol-treated patients, with the single largest published series consisting of 73 children (Pediatr. Dermatol. 2012;29:28-31).

Topical timolol is outpatient therapy. Used judiciously, it doesn’t appear to result in significant systemic absorption. The dose most experts recommend is 1 drop of 0.5% timolol ophthalmic gel-forming solution applied twice daily to the lesion.

Dr. Friedlander and her colleagues at Rady Children’s Hospital in San Diego are about to embark on a large, prospective study of topical timolol for infantile hemangiomas to further define the treatment efficacy; the systemic risk, if any; and appropriate patient monitoring.

Meanwhile, now that the dust has settled, propranolol is the unequivocal drug of choice when systemic therapy is warranted. It has replaced corticosteroid therapy, which is what most dermatologists were trained to use.

"Propranolol for hemangiomas is the most important thing that’s happened in pediatric dermatology in the last few years. It’s a wonderful, wonderful agent that we now have available to help us," Dr. Friedlander said.

There are more than 2,000 publications on propranolol, including a new systematic review of nearly 1,300 patients treated by dermatologists at the University of California, San Francisco, who reported a 98% response rate and a low rate of side effects (Pediatr. Dermatol. 2013 Feb. 14 [doi:10.1111/pde.12089]).

In addition, recent expert consensus guidelines on the use of propranolol for the treatment of infantile hemangiomas (Pediatrics 2013;131:128-40) are "very helpful," Dr. Friedlander continued.

Today, inpatient propranolol therapy is reserved for very young infants of less than 8 weeks’ corrected gestational age, those with comorbid cardiac conditions or asthma, and kids who don’t have reliable family support. Most children are now treated as outpatients, typically beginning at about 6 months of age. The usual starting dose is 0.5 mg/kg per day, titrating up to about 2 mg/kg per day. Dr. Friedlander said she typically continues treatment for about 10 months; discontinuing too early can lead to rebound.

The recommended monitoring consists of heart rate and blood pressure measurements at baseline and 1 and 2 hours after the initial dose of propranolol, with repeat monitoring required only when the dose is increased by more than 0.5 mg/kg per day. Although routine blood glucose testing isn’t recommended, propranolol does lower the blood glucose level, so it’s essential that a treated child feeds often, and that the drug is stopped when a child has a gastrointestinal illness with vomiting or diarrhea, or is not feeding adequately for his or her age.

In addition to making sure an infant doesn’t have a cardiac condition or upper airway issues before starting the child on propranolol, check for a segmental hemangioma greater than about 5 cm on the face or neck, which is a red flag. A child with such a lesion is at risk for the PHACE syndrome and needs to undergo brain imaging to make sure the arterial vasculature is normal before propranolol therapy is started, Dr. Friedlander emphasized.

She reported having no relevant financial conflicts. SDEF and this news organization are owned by the same parent company.

b.jancin@elsevier.com

Topical timolol for the treatment of infantile hemangiomas is emerging as a safer, easier alternative to oral propranolol in selected patients, according to Dr. Sheila Fallon Friedlander.

"I think this [timolol] is something that’s very, very useful. You’re going to be seeing more of it around in use for this condition. We’ve seen encouraging results in the past 2½ years. It’s well tolerated, and I think there will come a day when even primary care physicians will be using topical timolol with comfort," she said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/IMNG Medical Media

Topical timolol works best for small, relatively thin hemangiomas, such as eyelid lesions, advised Dr. Friedlander, president of the Society for Pediatric Dermatology and a pediatric dermatologist at the University of California, San Diego.

"You don’t put timolol on big, thick lesions and expect it to work; it won’t," she said.

At this point, the evidence base for topical timolol is far smaller than for propranolol, which has become the clear drug of choice for children requiring systemic therapy. To date, there are at least 20 articles involving about 175 timolol-treated patients, with the single largest published series consisting of 73 children (Pediatr. Dermatol. 2012;29:28-31).

Topical timolol is outpatient therapy. Used judiciously, it doesn’t appear to result in significant systemic absorption. The dose most experts recommend is 1 drop of 0.5% timolol ophthalmic gel-forming solution applied twice daily to the lesion.

Dr. Friedlander and her colleagues at Rady Children’s Hospital in San Diego are about to embark on a large, prospective study of topical timolol for infantile hemangiomas to further define the treatment efficacy; the systemic risk, if any; and appropriate patient monitoring.

Meanwhile, now that the dust has settled, propranolol is the unequivocal drug of choice when systemic therapy is warranted. It has replaced corticosteroid therapy, which is what most dermatologists were trained to use.

"Propranolol for hemangiomas is the most important thing that’s happened in pediatric dermatology in the last few years. It’s a wonderful, wonderful agent that we now have available to help us," Dr. Friedlander said.

There are more than 2,000 publications on propranolol, including a new systematic review of nearly 1,300 patients treated by dermatologists at the University of California, San Francisco, who reported a 98% response rate and a low rate of side effects (Pediatr. Dermatol. 2013 Feb. 14 [doi:10.1111/pde.12089]).

In addition, recent expert consensus guidelines on the use of propranolol for the treatment of infantile hemangiomas (Pediatrics 2013;131:128-40) are "very helpful," Dr. Friedlander continued.

Today, inpatient propranolol therapy is reserved for very young infants of less than 8 weeks’ corrected gestational age, those with comorbid cardiac conditions or asthma, and kids who don’t have reliable family support. Most children are now treated as outpatients, typically beginning at about 6 months of age. The usual starting dose is 0.5 mg/kg per day, titrating up to about 2 mg/kg per day. Dr. Friedlander said she typically continues treatment for about 10 months; discontinuing too early can lead to rebound.

The recommended monitoring consists of heart rate and blood pressure measurements at baseline and 1 and 2 hours after the initial dose of propranolol, with repeat monitoring required only when the dose is increased by more than 0.5 mg/kg per day. Although routine blood glucose testing isn’t recommended, propranolol does lower the blood glucose level, so it’s essential that a treated child feeds often, and that the drug is stopped when a child has a gastrointestinal illness with vomiting or diarrhea, or is not feeding adequately for his or her age.

In addition to making sure an infant doesn’t have a cardiac condition or upper airway issues before starting the child on propranolol, check for a segmental hemangioma greater than about 5 cm on the face or neck, which is a red flag. A child with such a lesion is at risk for the PHACE syndrome and needs to undergo brain imaging to make sure the arterial vasculature is normal before propranolol therapy is started, Dr. Friedlander emphasized.

She reported having no relevant financial conflicts. SDEF and this news organization are owned by the same parent company.

b.jancin@elsevier.com

Topical timolol for the treatment of infantile hemangiomas is emerging as a safer, easier alternative to oral propranolol in selected patients, according to Dr. Sheila Fallon Friedlander.

"I think this [timolol] is something that’s very, very useful. You’re going to be seeing more of it around in use for this condition. We’ve seen encouraging results in the past 2½ years. It’s well tolerated, and I think there will come a day when even primary care physicians will be using topical timolol with comfort," she said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/IMNG Medical Media

Topical timolol works best for small, relatively thin hemangiomas, such as eyelid lesions, advised Dr. Friedlander, president of the Society for Pediatric Dermatology and a pediatric dermatologist at the University of California, San Diego.

"You don’t put timolol on big, thick lesions and expect it to work; it won’t," she said.

At this point, the evidence base for topical timolol is far smaller than for propranolol, which has become the clear drug of choice for children requiring systemic therapy. To date, there are at least 20 articles involving about 175 timolol-treated patients, with the single largest published series consisting of 73 children (Pediatr. Dermatol. 2012;29:28-31).

Topical timolol is outpatient therapy. Used judiciously, it doesn’t appear to result in significant systemic absorption. The dose most experts recommend is 1 drop of 0.5% timolol ophthalmic gel-forming solution applied twice daily to the lesion.

Dr. Friedlander and her colleagues at Rady Children’s Hospital in San Diego are about to embark on a large, prospective study of topical timolol for infantile hemangiomas to further define the treatment efficacy; the systemic risk, if any; and appropriate patient monitoring.

Meanwhile, now that the dust has settled, propranolol is the unequivocal drug of choice when systemic therapy is warranted. It has replaced corticosteroid therapy, which is what most dermatologists were trained to use.

"Propranolol for hemangiomas is the most important thing that’s happened in pediatric dermatology in the last few years. It’s a wonderful, wonderful agent that we now have available to help us," Dr. Friedlander said.

There are more than 2,000 publications on propranolol, including a new systematic review of nearly 1,300 patients treated by dermatologists at the University of California, San Francisco, who reported a 98% response rate and a low rate of side effects (Pediatr. Dermatol. 2013 Feb. 14 [doi:10.1111/pde.12089]).

In addition, recent expert consensus guidelines on the use of propranolol for the treatment of infantile hemangiomas (Pediatrics 2013;131:128-40) are "very helpful," Dr. Friedlander continued.

Today, inpatient propranolol therapy is reserved for very young infants of less than 8 weeks’ corrected gestational age, those with comorbid cardiac conditions or asthma, and kids who don’t have reliable family support. Most children are now treated as outpatients, typically beginning at about 6 months of age. The usual starting dose is 0.5 mg/kg per day, titrating up to about 2 mg/kg per day. Dr. Friedlander said she typically continues treatment for about 10 months; discontinuing too early can lead to rebound.

The recommended monitoring consists of heart rate and blood pressure measurements at baseline and 1 and 2 hours after the initial dose of propranolol, with repeat monitoring required only when the dose is increased by more than 0.5 mg/kg per day. Although routine blood glucose testing isn’t recommended, propranolol does lower the blood glucose level, so it’s essential that a treated child feeds often, and that the drug is stopped when a child has a gastrointestinal illness with vomiting or diarrhea, or is not feeding adequately for his or her age.

In addition to making sure an infant doesn’t have a cardiac condition or upper airway issues before starting the child on propranolol, check for a segmental hemangioma greater than about 5 cm on the face or neck, which is a red flag. A child with such a lesion is at risk for the PHACE syndrome and needs to undergo brain imaging to make sure the arterial vasculature is normal before propranolol therapy is started, Dr. Friedlander emphasized.

She reported having no relevant financial conflicts. SDEF and this news organization are owned by the same parent company.

b.jancin@elsevier.com

HONOLULU – Traditionally, acute ischemic stroke patients have been admitted to an ICU for administration of intravenous tissue plasminogen activator therapy. But it’s not necessary, according to Kisha C. Coleman.

Instead, these patients can safely undergo intravenous TPA therapy in a well-prepared stroke unit with excellent clinical outcomes – and big cost savings, said Ms. Coleman, a nurse at the University of Alabama at Birmingham comprehensive stroke center.

She presented what she and her coinvestigators said is the largest-ever series of non–ICU-managed stroke patients treated with intravenous TPA. The series consisted of 302 consecutive patients admitted from the emergency department to the university’s nine-bed intermediate-level stroke unit for intravenous TPA therapy during 2009-2011. During this 3-year period, another 31 acute ischemic stroke patients were sent from the ED to the ICU because of hemodynamic or pulmonary instability.

The stroke unit has flexible staffing, and the nurses have undergone extensive training. Their capabilities include management of intravenous TPA therapy, administration of nicardipine infusions when warranted for blood pressure control, management of bilevel positive airway pressure ventilation, and noninvasive or direct central arterial line and hardwired cardiac monitoring.

The median National Institutes of Health Stroke Scale score at admission to the stroke unit was 9, with a median modified Rankin score of 3 at discharge. Ten percent of patients received nicardipine infusions.

The overall symptomatic intracranial hemorrhage rate was 3.3%, with a systemic hemorrhage rate of 2.9%. The volume of patients admitted to the stroke unit for intravenous TPA increased over time from 86 patients in 2009 to 107 in 2010 and 109 in 2011. Meanwhile, the incidence of symptomatic intracranial hemorrhage dropped from 4.7% the first year to 2.8% in each of the next 2 years.

"We attribute that to increased nurse efficiency over time in caring for these types of patients," Ms. Coleman said at the International Stroke Conference, sponsored by the American Heart Association.

No patients required a transfer from the stroke unit to the ICU for continued management. No TPA-related deaths occurred.

Hospital length of stay decreased from a median 9.8 days in 2009 to 6.4 in 2010 and 5.2 days in 2011, she continued.

The 31 patients admitted to the ICU from the emergency department during the study period and the 302 managed in the stroke unit had similar admission NIH Stroke Scale severity scores, symptomatic intracranial hemorrhage and systemic hemorrhage rates, and average lengths of stay.

A day in the ICU costs about $1,200 more than does a day in the stroke unit, she noted. The estimated cost savings resulting from avoided ICU days during this 3-year period was $362,400, even after adjustment for the expense of the additional training for nurses. And that figure is a conservative one that probably significantly underestimates the true savings, according to Ms. Coleman.

"Use of the ICU solely for management of TPA monitoring may constitute a significant overuse of system resources at an expense that is not associated with additional safety benefit," she concluded.

Beyond the sizable cost savings, another advantage of managing intravenous TPA therapy in the stroke unit rather than the ICU is continuity of care. These patients are admitted to and discharged from the stroke unit, she noted.

Ms. Coleman reported having no relevant financial conflicts.

b.jancin@elsevier.com

HONOLULU – Traditionally, acute ischemic stroke patients have been admitted to an ICU for administration of intravenous tissue plasminogen activator therapy. But it’s not necessary, according to Kisha C. Coleman.

Instead, these patients can safely undergo intravenous TPA therapy in a well-prepared stroke unit with excellent clinical outcomes – and big cost savings, said Ms. Coleman, a nurse at the University of Alabama at Birmingham comprehensive stroke center.

She presented what she and her coinvestigators said is the largest-ever series of non–ICU-managed stroke patients treated with intravenous TPA. The series consisted of 302 consecutive patients admitted from the emergency department to the university’s nine-bed intermediate-level stroke unit for intravenous TPA therapy during 2009-2011. During this 3-year period, another 31 acute ischemic stroke patients were sent from the ED to the ICU because of hemodynamic or pulmonary instability.

The stroke unit has flexible staffing, and the nurses have undergone extensive training. Their capabilities include management of intravenous TPA therapy, administration of nicardipine infusions when warranted for blood pressure control, management of bilevel positive airway pressure ventilation, and noninvasive or direct central arterial line and hardwired cardiac monitoring.

The median National Institutes of Health Stroke Scale score at admission to the stroke unit was 9, with a median modified Rankin score of 3 at discharge. Ten percent of patients received nicardipine infusions.

The overall symptomatic intracranial hemorrhage rate was 3.3%, with a systemic hemorrhage rate of 2.9%. The volume of patients admitted to the stroke unit for intravenous TPA increased over time from 86 patients in 2009 to 107 in 2010 and 109 in 2011. Meanwhile, the incidence of symptomatic intracranial hemorrhage dropped from 4.7% the first year to 2.8% in each of the next 2 years.

"We attribute that to increased nurse efficiency over time in caring for these types of patients," Ms. Coleman said at the International Stroke Conference, sponsored by the American Heart Association.

No patients required a transfer from the stroke unit to the ICU for continued management. No TPA-related deaths occurred.

Hospital length of stay decreased from a median 9.8 days in 2009 to 6.4 in 2010 and 5.2 days in 2011, she continued.

The 31 patients admitted to the ICU from the emergency department during the study period and the 302 managed in the stroke unit had similar admission NIH Stroke Scale severity scores, symptomatic intracranial hemorrhage and systemic hemorrhage rates, and average lengths of stay.

A day in the ICU costs about $1,200 more than does a day in the stroke unit, she noted. The estimated cost savings resulting from avoided ICU days during this 3-year period was $362,400, even after adjustment for the expense of the additional training for nurses. And that figure is a conservative one that probably significantly underestimates the true savings, according to Ms. Coleman.

"Use of the ICU solely for management of TPA monitoring may constitute a significant overuse of system resources at an expense that is not associated with additional safety benefit," she concluded.

Beyond the sizable cost savings, another advantage of managing intravenous TPA therapy in the stroke unit rather than the ICU is continuity of care. These patients are admitted to and discharged from the stroke unit, she noted.

Ms. Coleman reported having no relevant financial conflicts.

b.jancin@elsevier.com

HONOLULU – Traditionally, acute ischemic stroke patients have been admitted to an ICU for administration of intravenous tissue plasminogen activator therapy. But it’s not necessary, according to Kisha C. Coleman.

Instead, these patients can safely undergo intravenous TPA therapy in a well-prepared stroke unit with excellent clinical outcomes – and big cost savings, said Ms. Coleman, a nurse at the University of Alabama at Birmingham comprehensive stroke center.

She presented what she and her coinvestigators said is the largest-ever series of non–ICU-managed stroke patients treated with intravenous TPA. The series consisted of 302 consecutive patients admitted from the emergency department to the university’s nine-bed intermediate-level stroke unit for intravenous TPA therapy during 2009-2011. During this 3-year period, another 31 acute ischemic stroke patients were sent from the ED to the ICU because of hemodynamic or pulmonary instability.

The stroke unit has flexible staffing, and the nurses have undergone extensive training. Their capabilities include management of intravenous TPA therapy, administration of nicardipine infusions when warranted for blood pressure control, management of bilevel positive airway pressure ventilation, and noninvasive or direct central arterial line and hardwired cardiac monitoring.

The median National Institutes of Health Stroke Scale score at admission to the stroke unit was 9, with a median modified Rankin score of 3 at discharge. Ten percent of patients received nicardipine infusions.

The overall symptomatic intracranial hemorrhage rate was 3.3%, with a systemic hemorrhage rate of 2.9%. The volume of patients admitted to the stroke unit for intravenous TPA increased over time from 86 patients in 2009 to 107 in 2010 and 109 in 2011. Meanwhile, the incidence of symptomatic intracranial hemorrhage dropped from 4.7% the first year to 2.8% in each of the next 2 years.

"We attribute that to increased nurse efficiency over time in caring for these types of patients," Ms. Coleman said at the International Stroke Conference, sponsored by the American Heart Association.

No patients required a transfer from the stroke unit to the ICU for continued management. No TPA-related deaths occurred.

Hospital length of stay decreased from a median 9.8 days in 2009 to 6.4 in 2010 and 5.2 days in 2011, she continued.

The 31 patients admitted to the ICU from the emergency department during the study period and the 302 managed in the stroke unit had similar admission NIH Stroke Scale severity scores, symptomatic intracranial hemorrhage and systemic hemorrhage rates, and average lengths of stay.

A day in the ICU costs about $1,200 more than does a day in the stroke unit, she noted. The estimated cost savings resulting from avoided ICU days during this 3-year period was $362,400, even after adjustment for the expense of the additional training for nurses. And that figure is a conservative one that probably significantly underestimates the true savings, according to Ms. Coleman.

"Use of the ICU solely for management of TPA monitoring may constitute a significant overuse of system resources at an expense that is not associated with additional safety benefit," she concluded.

Beyond the sizable cost savings, another advantage of managing intravenous TPA therapy in the stroke unit rather than the ICU is continuity of care. These patients are admitted to and discharged from the stroke unit, she noted.

Ms. Coleman reported having no relevant financial conflicts.

b.jancin@elsevier.com

Emerging data strongly suggest that children with atopic dermatitis are at increased risk for attention-deficit/hyperactivity disorder.

"The first paper was actually a really good paper, but it was just one study and so we did not quite believe it. But now there’s a confirmatory study by a separate group with really big data," Dr. Lawrence K. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

In addition, the second study pointed to a possible higher risk of autism in children with atopic dermatitis, and it also confirmed other reports of increased rates of depression and anxiety, noted Dr. Eichenfield, professor of clinical pediatrics and medicine at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital, also in San Diego.

Atopic dermatitis is the most common chronic inflammatory condition in childhood. Attention-deficit/hyperactivity disorder is the most common psychiatric disorder. The first study to report an association between the two was a German, case-control, population-based study involving 1,436 atopic dermatitis patients aged 6-17 years and an equal number of age- and gender-matched controls without the skin disease.

The prevalence of diagnosed ADHD was 5.2% in the atopic dermatitis patients and 3.4% in controls (P = 0.02). In a multivariate logistic regression analysis, atopic dermatitis was an independent predictor of prevalent ADHD, with an associated 47% increased risk of the psychiatric disorder compared with youths without atopic dermatitis. Moreover, there was a suggestion that the more severe a patient’s atopic dermatitis, the greater the likelihood of comorbid ADHD, since the likelihood of ADHD increased with each additional physician visit for atopic dermatitis (JAMA 2009;301:724-6).

More recently, in a study presented at a major meeting but not yet published, Dr. Eric L. Simpson and his coinvestigators at Oregon Health and Science University, Portland, confirmed the initial German finding that pediatric atopic dermatitis is associated with ADHD, this time in a database of 90,000 U.S. children. Once again, the more severe the skin disease, the greater the risk of ADHD. In this study, atopic dermatitis was also associated with increased risks of depression, anxiety, and autism.

Possible mechanisms underlying the observed association between atopic dermatitis and comorbid psychiatric conditions include sleep disturbance – a prominent feature in atopic dermatitis – and systemic inflammation, according to Dr. Eichenfield.

The well-established atopic comorbidities associated with atopic dermatitis are asthma, allergic rhinitis, and food allergy. Dr. Eichenfield said that he welcomes the evolving evidence of psychologic comorbidities for the opportunity it provides to encourage treatment adherence. Like other treating physicians, he finds topical steroid phobia to be a huge problem.

"I actually use this information in my clinical practice as a way to get my families to adequately treat atopic dermatitis," he said. "If I have families that are very steroid phobic, I’ll say, ‘You know, you really want to treat your kid with appropriate topical therapy to minimize the disease impact: to minimize the sleep disturbance and potentially minimize the neurobehavioral impact of atopic dermatitis.’ I use that as a tool to stay with our regimens of care."

Steroid phobia is a problem worldwide, not just in the United States. For example, Dr. Eichenfield noted that when French dermatologists recently surveyed 208 consecutive atopic dermatitis patients or their parents using a detailed 69-item questionnaire, 81% reported having fears about topical corticosteroids – the mainstay of atopic dermatitis treatment – and 36% admitted to treatment nonadherence as a result of their worries. Fears did not correlate with disease severity (Br. J. Dermatol. 2011;165:808-14).

"I think that in all of dermatology there’s probably no greater chasm between where our families are at in terms of concerns about a medication and where we are as physicians in terms of not having concerns than in the area of topical steroids for atopic dermatitis," Dr. Eichenfield said.

He noted that he makes extensive use of parental educational handouts and written action plans in addition to face-to-face discussion of safety concerns at the time he prescribes topical steroids. One strategy that he’s recently realized makes a big difference in terms of adherence is to explain carefully that the midpotency topical steroids used in treating atopic dermatitis – as distinct from potent and superpotent topical steroids – do not have the side effects and systemic absorption issues steroid-phobic parents are worried about.

Another effective strategy is to be very specific about the quantity of topical medication he wants the patient to use for flare control.

"Instead of saying, ‘Twice a day application of a midstrength topical steroid for 2 weeks,’ now I’ll say, "I would like you to use up this 80-g tube in the next 2 weeks and then I’ll see you back – and it’s safe to use this amount for this particular length of time.’ I find that makes a huge difference in terms of outcomes if I explain it that way," Dr. Eichenfield said.

He reported serving as a consultant to Bayer, Galderma, GlaxoSmithKline, and Valeant.

SDEF and this news organization are owned by the same parent company.

b.jancin@elsevier.com

Emerging data strongly suggest that children with atopic dermatitis are at increased risk for attention-deficit/hyperactivity disorder.

"The first paper was actually a really good paper, but it was just one study and so we did not quite believe it. But now there’s a confirmatory study by a separate group with really big data," Dr. Lawrence K. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

In addition, the second study pointed to a possible higher risk of autism in children with atopic dermatitis, and it also confirmed other reports of increased rates of depression and anxiety, noted Dr. Eichenfield, professor of clinical pediatrics and medicine at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital, also in San Diego.

Atopic dermatitis is the most common chronic inflammatory condition in childhood. Attention-deficit/hyperactivity disorder is the most common psychiatric disorder. The first study to report an association between the two was a German, case-control, population-based study involving 1,436 atopic dermatitis patients aged 6-17 years and an equal number of age- and gender-matched controls without the skin disease.

The prevalence of diagnosed ADHD was 5.2% in the atopic dermatitis patients and 3.4% in controls (P = 0.02). In a multivariate logistic regression analysis, atopic dermatitis was an independent predictor of prevalent ADHD, with an associated 47% increased risk of the psychiatric disorder compared with youths without atopic dermatitis. Moreover, there was a suggestion that the more severe a patient’s atopic dermatitis, the greater the likelihood of comorbid ADHD, since the likelihood of ADHD increased with each additional physician visit for atopic dermatitis (JAMA 2009;301:724-6).

More recently, in a study presented at a major meeting but not yet published, Dr. Eric L. Simpson and his coinvestigators at Oregon Health and Science University, Portland, confirmed the initial German finding that pediatric atopic dermatitis is associated with ADHD, this time in a database of 90,000 U.S. children. Once again, the more severe the skin disease, the greater the risk of ADHD. In this study, atopic dermatitis was also associated with increased risks of depression, anxiety, and autism.

Possible mechanisms underlying the observed association between atopic dermatitis and comorbid psychiatric conditions include sleep disturbance – a prominent feature in atopic dermatitis – and systemic inflammation, according to Dr. Eichenfield.

The well-established atopic comorbidities associated with atopic dermatitis are asthma, allergic rhinitis, and food allergy. Dr. Eichenfield said that he welcomes the evolving evidence of psychologic comorbidities for the opportunity it provides to encourage treatment adherence. Like other treating physicians, he finds topical steroid phobia to be a huge problem.

"I actually use this information in my clinical practice as a way to get my families to adequately treat atopic dermatitis," he said. "If I have families that are very steroid phobic, I’ll say, ‘You know, you really want to treat your kid with appropriate topical therapy to minimize the disease impact: to minimize the sleep disturbance and potentially minimize the neurobehavioral impact of atopic dermatitis.’ I use that as a tool to stay with our regimens of care."

Steroid phobia is a problem worldwide, not just in the United States. For example, Dr. Eichenfield noted that when French dermatologists recently surveyed 208 consecutive atopic dermatitis patients or their parents using a detailed 69-item questionnaire, 81% reported having fears about topical corticosteroids – the mainstay of atopic dermatitis treatment – and 36% admitted to treatment nonadherence as a result of their worries. Fears did not correlate with disease severity (Br. J. Dermatol. 2011;165:808-14).

"I think that in all of dermatology there’s probably no greater chasm between where our families are at in terms of concerns about a medication and where we are as physicians in terms of not having concerns than in the area of topical steroids for atopic dermatitis," Dr. Eichenfield said.

He noted that he makes extensive use of parental educational handouts and written action plans in addition to face-to-face discussion of safety concerns at the time he prescribes topical steroids. One strategy that he’s recently realized makes a big difference in terms of adherence is to explain carefully that the midpotency topical steroids used in treating atopic dermatitis – as distinct from potent and superpotent topical steroids – do not have the side effects and systemic absorption issues steroid-phobic parents are worried about.

Another effective strategy is to be very specific about the quantity of topical medication he wants the patient to use for flare control.

"Instead of saying, ‘Twice a day application of a midstrength topical steroid for 2 weeks,’ now I’ll say, "I would like you to use up this 80-g tube in the next 2 weeks and then I’ll see you back – and it’s safe to use this amount for this particular length of time.’ I find that makes a huge difference in terms of outcomes if I explain it that way," Dr. Eichenfield said.

He reported serving as a consultant to Bayer, Galderma, GlaxoSmithKline, and Valeant.

SDEF and this news organization are owned by the same parent company.

b.jancin@elsevier.com

Emerging data strongly suggest that children with atopic dermatitis are at increased risk for attention-deficit/hyperactivity disorder.

"The first paper was actually a really good paper, but it was just one study and so we did not quite believe it. But now there’s a confirmatory study by a separate group with really big data," Dr. Lawrence K. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

In addition, the second study pointed to a possible higher risk of autism in children with atopic dermatitis, and it also confirmed other reports of increased rates of depression and anxiety, noted Dr. Eichenfield, professor of clinical pediatrics and medicine at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital, also in San Diego.

Atopic dermatitis is the most common chronic inflammatory condition in childhood. Attention-deficit/hyperactivity disorder is the most common psychiatric disorder. The first study to report an association between the two was a German, case-control, population-based study involving 1,436 atopic dermatitis patients aged 6-17 years and an equal number of age- and gender-matched controls without the skin disease.

The prevalence of diagnosed ADHD was 5.2% in the atopic dermatitis patients and 3.4% in controls (P = 0.02). In a multivariate logistic regression analysis, atopic dermatitis was an independent predictor of prevalent ADHD, with an associated 47% increased risk of the psychiatric disorder compared with youths without atopic dermatitis. Moreover, there was a suggestion that the more severe a patient’s atopic dermatitis, the greater the likelihood of comorbid ADHD, since the likelihood of ADHD increased with each additional physician visit for atopic dermatitis (JAMA 2009;301:724-6).

More recently, in a study presented at a major meeting but not yet published, Dr. Eric L. Simpson and his coinvestigators at Oregon Health and Science University, Portland, confirmed the initial German finding that pediatric atopic dermatitis is associated with ADHD, this time in a database of 90,000 U.S. children. Once again, the more severe the skin disease, the greater the risk of ADHD. In this study, atopic dermatitis was also associated with increased risks of depression, anxiety, and autism.

Possible mechanisms underlying the observed association between atopic dermatitis and comorbid psychiatric conditions include sleep disturbance – a prominent feature in atopic dermatitis – and systemic inflammation, according to Dr. Eichenfield.

The well-established atopic comorbidities associated with atopic dermatitis are asthma, allergic rhinitis, and food allergy. Dr. Eichenfield said that he welcomes the evolving evidence of psychologic comorbidities for the opportunity it provides to encourage treatment adherence. Like other treating physicians, he finds topical steroid phobia to be a huge problem.

"I actually use this information in my clinical practice as a way to get my families to adequately treat atopic dermatitis," he said. "If I have families that are very steroid phobic, I’ll say, ‘You know, you really want to treat your kid with appropriate topical therapy to minimize the disease impact: to minimize the sleep disturbance and potentially minimize the neurobehavioral impact of atopic dermatitis.’ I use that as a tool to stay with our regimens of care."

Steroid phobia is a problem worldwide, not just in the United States. For example, Dr. Eichenfield noted that when French dermatologists recently surveyed 208 consecutive atopic dermatitis patients or their parents using a detailed 69-item questionnaire, 81% reported having fears about topical corticosteroids – the mainstay of atopic dermatitis treatment – and 36% admitted to treatment nonadherence as a result of their worries. Fears did not correlate with disease severity (Br. J. Dermatol. 2011;165:808-14).

"I think that in all of dermatology there’s probably no greater chasm between where our families are at in terms of concerns about a medication and where we are as physicians in terms of not having concerns than in the area of topical steroids for atopic dermatitis," Dr. Eichenfield said.

He noted that he makes extensive use of parental educational handouts and written action plans in addition to face-to-face discussion of safety concerns at the time he prescribes topical steroids. One strategy that he’s recently realized makes a big difference in terms of adherence is to explain carefully that the midpotency topical steroids used in treating atopic dermatitis – as distinct from potent and superpotent topical steroids – do not have the side effects and systemic absorption issues steroid-phobic parents are worried about.

Another effective strategy is to be very specific about the quantity of topical medication he wants the patient to use for flare control.

"Instead of saying, ‘Twice a day application of a midstrength topical steroid for 2 weeks,’ now I’ll say, "I would like you to use up this 80-g tube in the next 2 weeks and then I’ll see you back – and it’s safe to use this amount for this particular length of time.’ I find that makes a huge difference in terms of outcomes if I explain it that way," Dr. Eichenfield said.

He reported serving as a consultant to Bayer, Galderma, GlaxoSmithKline, and Valeant.

SDEF and this news organization are owned by the same parent company.

b.jancin@elsevier.com

One in three stroke survivors in the United States has undiagnosed prediabetes, a national survey has shown.

Black stroke survivors are more than twice as likely as whites to have undiagnosed prediabetes or diabetes mellitus, while Hispanics have an intermediate risk, Dr. Amytis Towfighi said at the International Stroke Conference sponsored by the American Heart Association.

She presented an analysis of 1,070 adult stroke survivors included in the National Health and Nutrition Examination Survey, a Centers for Disease Control and Prevention–sponsored cross-sectional survey weighted so as to be representative of the full U.S. population. Thus, the findings in the NHANES stroke survivors can be extrapolated to the estimated 5.1 million adult stroke survivors nationwide.

The overall prevalence of prediabetes among stroke survivors as defined by a hemoglobin A_1c level of 5.7%-6.4% was 32.3%. The figure was 37.8% in blacks, 31.6% in Hispanics, and 26.3% in whites. Only 2.5% of stroke survivors had physician-diagnosed prediabetes, reported Dr. Towfighi, who is chair of the neurology department and director of the acute neurology and acute stroke unit at Rancho Los Amigos National Rehabilitation Center, Downey, Calif.

The prevalence of undiagnosed diabetes mellitus was 3.7% overall. In contrast, 26.9% of stroke survivors had diagnosed diabetes, with rates ranging from 42.7% in Hispanics to 35.7% in blacks and 24.4% in whites.

Black stroke survivors with undiagnosed prediabetes or diabetes were significantly younger: a mean of 59 years old compared with 70 years in whites and 67 years in Hispanics. They were also significantly more likely to smoke and to be on antihypertensive medications. Of black stroke survivors, 58% were women compared with 42% of white stroke survivors.

Chronic hyperglycemia is a potent risk factor for vascular events. Thus, unrecognized prediabetes or diabetes may amplify an individual’s risk of recurrent stroke. Given that if left untreated, prediabetes will progress to diabetes, it makes sense to systematically screen patients for these metabolic abnormalities at the time of an index stroke as a means of improving clinical outcomes and reducing racial disparities, Dr. Towfighi said.

She reported having no relevant financial conflicts.

b.jancin@elsevier.com

One in three stroke survivors in the United States has undiagnosed prediabetes, a national survey has shown.

Black stroke survivors are more than twice as likely as whites to have undiagnosed prediabetes or diabetes mellitus, while Hispanics have an intermediate risk, Dr. Amytis Towfighi said at the International Stroke Conference sponsored by the American Heart Association.

She presented an analysis of 1,070 adult stroke survivors included in the National Health and Nutrition Examination Survey, a Centers for Disease Control and Prevention–sponsored cross-sectional survey weighted so as to be representative of the full U.S. population. Thus, the findings in the NHANES stroke survivors can be extrapolated to the estimated 5.1 million adult stroke survivors nationwide.

The overall prevalence of prediabetes among stroke survivors as defined by a hemoglobin A_1c level of 5.7%-6.4% was 32.3%. The figure was 37.8% in blacks, 31.6% in Hispanics, and 26.3% in whites. Only 2.5% of stroke survivors had physician-diagnosed prediabetes, reported Dr. Towfighi, who is chair of the neurology department and director of the acute neurology and acute stroke unit at Rancho Los Amigos National Rehabilitation Center, Downey, Calif.

The prevalence of undiagnosed diabetes mellitus was 3.7% overall. In contrast, 26.9% of stroke survivors had diagnosed diabetes, with rates ranging from 42.7% in Hispanics to 35.7% in blacks and 24.4% in whites.

Black stroke survivors with undiagnosed prediabetes or diabetes were significantly younger: a mean of 59 years old compared with 70 years in whites and 67 years in Hispanics. They were also significantly more likely to smoke and to be on antihypertensive medications. Of black stroke survivors, 58% were women compared with 42% of white stroke survivors.

Chronic hyperglycemia is a potent risk factor for vascular events. Thus, unrecognized prediabetes or diabetes may amplify an individual’s risk of recurrent stroke. Given that if left untreated, prediabetes will progress to diabetes, it makes sense to systematically screen patients for these metabolic abnormalities at the time of an index stroke as a means of improving clinical outcomes and reducing racial disparities, Dr. Towfighi said.

She reported having no relevant financial conflicts.

b.jancin@elsevier.com

One in three stroke survivors in the United States has undiagnosed prediabetes, a national survey has shown.

Black stroke survivors are more than twice as likely as whites to have undiagnosed prediabetes or diabetes mellitus, while Hispanics have an intermediate risk, Dr. Amytis Towfighi said at the International Stroke Conference sponsored by the American Heart Association.

She presented an analysis of 1,070 adult stroke survivors included in the National Health and Nutrition Examination Survey, a Centers for Disease Control and Prevention–sponsored cross-sectional survey weighted so as to be representative of the full U.S. population. Thus, the findings in the NHANES stroke survivors can be extrapolated to the estimated 5.1 million adult stroke survivors nationwide.

The overall prevalence of prediabetes among stroke survivors as defined by a hemoglobin A_1c level of 5.7%-6.4% was 32.3%. The figure was 37.8% in blacks, 31.6% in Hispanics, and 26.3% in whites. Only 2.5% of stroke survivors had physician-diagnosed prediabetes, reported Dr. Towfighi, who is chair of the neurology department and director of the acute neurology and acute stroke unit at Rancho Los Amigos National Rehabilitation Center, Downey, Calif.

The prevalence of undiagnosed diabetes mellitus was 3.7% overall. In contrast, 26.9% of stroke survivors had diagnosed diabetes, with rates ranging from 42.7% in Hispanics to 35.7% in blacks and 24.4% in whites.

Black stroke survivors with undiagnosed prediabetes or diabetes were significantly younger: a mean of 59 years old compared with 70 years in whites and 67 years in Hispanics. They were also significantly more likely to smoke and to be on antihypertensive medications. Of black stroke survivors, 58% were women compared with 42% of white stroke survivors.

Chronic hyperglycemia is a potent risk factor for vascular events. Thus, unrecognized prediabetes or diabetes may amplify an individual’s risk of recurrent stroke. Given that if left untreated, prediabetes will progress to diabetes, it makes sense to systematically screen patients for these metabolic abnormalities at the time of an index stroke as a means of improving clinical outcomes and reducing racial disparities, Dr. Towfighi said.

She reported having no relevant financial conflicts.

b.jancin@elsevier.com

The relatively low U.S. rates of intravenous tissue plasminogen activator therapy for acute stroke may be due in substantial part to widespread use of additional eligibility restrictions beyond the product labeling, Fern Cudlip said at the International Stroke Conference sponsored by the American Heart Association.

Her national survey showed that 81% of U.S. certified stroke centers employ additional inclusion and exclusion criteria not contained in the TPA (Activase) labeling.

"The use of additional exclusion criteria is so common that it implies perhaps there’s a tendency to try to find a reason not to treat," observed Ms. Cudlip, a nurse practitioner who is stroke program coordinator at Eden Medical Center, Castro Valley, Calif.

Her proposed solution: Organizations that certify stroke centers should require adherence to the TPA-label–defined treatment criteria as a means of improving the nation’s low intravenous TPA treatment rates.

The impetus for the national survey presented by Ms. Cudlip was a sense of frustration that 16 years after Food and Drug Administration approval of intravenous TPA as the first and to date still the only proven therapy for acute stroke, treatment rates remain lower than in many other countries. That’s the case even though access to treatment is better than ever, since there are now more than 900 certified U.S. stroke centers.

In talking informally with colleagues around the country, Ms. Cudlip said she and her coinvestigators realized that many hospitals tack on additional nonstandard requirements for intravenous TPA beyond those specified in the labeling. The investigators decided to document these practices.

Representatives from 229 stroke centers in 43 states and Washington, D.C., completed the 15-minute survey. Sixty-nine percent of the stroke centers were located in community hospitals; the other 31%, in academic medical centers. The centers handled an average of 374 ischemic stroke patients per year, with an overall 8.7% intravenous TPA treatment rate. The rate was significantly higher in academic centers: 10.8%, compared with 8.0% in stroke centers in community hospitals.

The survey questions on nonlabel inclusion and exclusion criteria were restricted to patients who present within the 3-hour treatment window opening at stroke onset. For patients who present within 3 hours, 35% of stroke centers impose as an additional treatment criterion a National Institutes of Health Stroke Severity (NIHSS) score of at least 4, and 26% of centers will give intravenous TPA only if CT angiography shows an occlusion. Neither of these inclusion restrictions are part of the product labeling.

Numerous exclusion criteria beyond the TPA labeling are in use. For example, 44% of stroke centers won’t administer intravenous TPA to a patient who presents within 3 hours of stroke onset if the patient shows rapid improvement, even though a disabling deficit remains. Thirty percent exclude from treatment those patients with an NIHSS score greater than 22; a concurrent acute MI is a contraindication to intravenous TPA at 26% of stroke centers; 22% exclude patients on any form of anticoagulation, regardless of the coagulation laboratory results; 20% exclude patients with a suspected but unwitnessed seizure; 16% routinely exclude patients over age 80; 14% exclude patients with a large-vessel occlusion deemed amenable to intra-arterial therapy; 7% won’t treat a patient on nicardipine for blood pressure control; and 5% won’t treat an otherwise-qualified patient who is on dual-antiplatelet therapy.

The number of nonstandard inclusion and exclusion criteria in place at a stroke center showed a significant inverse relationship with the institutional intravenous TPA treatment rate. Smaller community hospitals with lower ischemic stroke admission volumes tended to have a longer list of nonstandard treatment criteria, according to Ms. Cudlip.

Several audience members rose to voice frustration at the list of off-label impediments to prompt intravenous TPA therapy at their home institutions. One physician, noting that institutional change can be difficult to achieve, asked Ms. Cudlip which two common nonlabel treatment criteria she’d make her top priority for elimination.

Ms. Cudlip answered without hesitation: The requirement that a patient has to have an NIHSS score of 4 or more, which according to her survey is in use at more than one-third of stroke centers, needs to go.

"I can have an NIHSS score of 3 and yet have completely lost my speech. That’s pretty disabling, right? I’d really want you to treat me. I need to speak," she said.

The other widely used nonlabel criterion Ms. Cudlip would target for elimination immediately is the treatment exclusion for patients with rapidly improving symptoms despite a remaining disabling deficit.

A physician audience member chimed in that he finds particularly disturbing the policy of not treating patients over age 80, which is in place at 16% of stroke centers. Ms. Cudlip was fully on board with getting rid of that restriction, as well.

"The oldest we’ve treated at our center is a woman who was 106, not that we do it all the time," she said, generating a vigorous round of applause.

She reported having no relevant financial conflicts.

b.jancin@elsevier.com

The relatively low U.S. rates of intravenous tissue plasminogen activator therapy for acute stroke may be due in substantial part to widespread use of additional eligibility restrictions beyond the product labeling, Fern Cudlip said at the International Stroke Conference sponsored by the American Heart Association.

Her national survey showed that 81% of U.S. certified stroke centers employ additional inclusion and exclusion criteria not contained in the TPA (Activase) labeling.

"The use of additional exclusion criteria is so common that it implies perhaps there’s a tendency to try to find a reason not to treat," observed Ms. Cudlip, a nurse practitioner who is stroke program coordinator at Eden Medical Center, Castro Valley, Calif.

Her proposed solution: Organizations that certify stroke centers should require adherence to the TPA-label–defined treatment criteria as a means of improving the nation’s low intravenous TPA treatment rates.

The impetus for the national survey presented by Ms. Cudlip was a sense of frustration that 16 years after Food and Drug Administration approval of intravenous TPA as the first and to date still the only proven therapy for acute stroke, treatment rates remain lower than in many other countries. That’s the case even though access to treatment is better than ever, since there are now more than 900 certified U.S. stroke centers.

In talking informally with colleagues around the country, Ms. Cudlip said she and her coinvestigators realized that many hospitals tack on additional nonstandard requirements for intravenous TPA beyond those specified in the labeling. The investigators decided to document these practices.

Representatives from 229 stroke centers in 43 states and Washington, D.C., completed the 15-minute survey. Sixty-nine percent of the stroke centers were located in community hospitals; the other 31%, in academic medical centers. The centers handled an average of 374 ischemic stroke patients per year, with an overall 8.7% intravenous TPA treatment rate. The rate was significantly higher in academic centers: 10.8%, compared with 8.0% in stroke centers in community hospitals.

The survey questions on nonlabel inclusion and exclusion criteria were restricted to patients who present within the 3-hour treatment window opening at stroke onset. For patients who present within 3 hours, 35% of stroke centers impose as an additional treatment criterion a National Institutes of Health Stroke Severity (NIHSS) score of at least 4, and 26% of centers will give intravenous TPA only if CT angiography shows an occlusion. Neither of these inclusion restrictions are part of the product labeling.

Numerous exclusion criteria beyond the TPA labeling are in use. For example, 44% of stroke centers won’t administer intravenous TPA to a patient who presents within 3 hours of stroke onset if the patient shows rapid improvement, even though a disabling deficit remains. Thirty percent exclude from treatment those patients with an NIHSS score greater than 22; a concurrent acute MI is a contraindication to intravenous TPA at 26% of stroke centers; 22% exclude patients on any form of anticoagulation, regardless of the coagulation laboratory results; 20% exclude patients with a suspected but unwitnessed seizure; 16% routinely exclude patients over age 80; 14% exclude patients with a large-vessel occlusion deemed amenable to intra-arterial therapy; 7% won’t treat a patient on nicardipine for blood pressure control; and 5% won’t treat an otherwise-qualified patient who is on dual-antiplatelet therapy.

The number of nonstandard inclusion and exclusion criteria in place at a stroke center showed a significant inverse relationship with the institutional intravenous TPA treatment rate. Smaller community hospitals with lower ischemic stroke admission volumes tended to have a longer list of nonstandard treatment criteria, according to Ms. Cudlip.

Several audience members rose to voice frustration at the list of off-label impediments to prompt intravenous TPA therapy at their home institutions. One physician, noting that institutional change can be difficult to achieve, asked Ms. Cudlip which two common nonlabel treatment criteria she’d make her top priority for elimination.

Ms. Cudlip answered without hesitation: The requirement that a patient has to have an NIHSS score of 4 or more, which according to her survey is in use at more than one-third of stroke centers, needs to go.

"I can have an NIHSS score of 3 and yet have completely lost my speech. That’s pretty disabling, right? I’d really want you to treat me. I need to speak," she said.

The other widely used nonlabel criterion Ms. Cudlip would target for elimination immediately is the treatment exclusion for patients with rapidly improving symptoms despite a remaining disabling deficit.

A physician audience member chimed in that he finds particularly disturbing the policy of not treating patients over age 80, which is in place at 16% of stroke centers. Ms. Cudlip was fully on board with getting rid of that restriction, as well.

"The oldest we’ve treated at our center is a woman who was 106, not that we do it all the time," she said, generating a vigorous round of applause.

She reported having no relevant financial conflicts.

b.jancin@elsevier.com

The relatively low U.S. rates of intravenous tissue plasminogen activator therapy for acute stroke may be due in substantial part to widespread use of additional eligibility restrictions beyond the product labeling, Fern Cudlip said at the International Stroke Conference sponsored by the American Heart Association.

Her national survey showed that 81% of U.S. certified stroke centers employ additional inclusion and exclusion criteria not contained in the TPA (Activase) labeling.

"The use of additional exclusion criteria is so common that it implies perhaps there’s a tendency to try to find a reason not to treat," observed Ms. Cudlip, a nurse practitioner who is stroke program coordinator at Eden Medical Center, Castro Valley, Calif.

Her proposed solution: Organizations that certify stroke centers should require adherence to the TPA-label–defined treatment criteria as a means of improving the nation’s low intravenous TPA treatment rates.

The impetus for the national survey presented by Ms. Cudlip was a sense of frustration that 16 years after Food and Drug Administration approval of intravenous TPA as the first and to date still the only proven therapy for acute stroke, treatment rates remain lower than in many other countries. That’s the case even though access to treatment is better than ever, since there are now more than 900 certified U.S. stroke centers.

In talking informally with colleagues around the country, Ms. Cudlip said she and her coinvestigators realized that many hospitals tack on additional nonstandard requirements for intravenous TPA beyond those specified in the labeling. The investigators decided to document these practices.

Representatives from 229 stroke centers in 43 states and Washington, D.C., completed the 15-minute survey. Sixty-nine percent of the stroke centers were located in community hospitals; the other 31%, in academic medical centers. The centers handled an average of 374 ischemic stroke patients per year, with an overall 8.7% intravenous TPA treatment rate. The rate was significantly higher in academic centers: 10.8%, compared with 8.0% in stroke centers in community hospitals.

The survey questions on nonlabel inclusion and exclusion criteria were restricted to patients who present within the 3-hour treatment window opening at stroke onset. For patients who present within 3 hours, 35% of stroke centers impose as an additional treatment criterion a National Institutes of Health Stroke Severity (NIHSS) score of at least 4, and 26% of centers will give intravenous TPA only if CT angiography shows an occlusion. Neither of these inclusion restrictions are part of the product labeling.

Numerous exclusion criteria beyond the TPA labeling are in use. For example, 44% of stroke centers won’t administer intravenous TPA to a patient who presents within 3 hours of stroke onset if the patient shows rapid improvement, even though a disabling deficit remains. Thirty percent exclude from treatment those patients with an NIHSS score greater than 22; a concurrent acute MI is a contraindication to intravenous TPA at 26% of stroke centers; 22% exclude patients on any form of anticoagulation, regardless of the coagulation laboratory results; 20% exclude patients with a suspected but unwitnessed seizure; 16% routinely exclude patients over age 80; 14% exclude patients with a large-vessel occlusion deemed amenable to intra-arterial therapy; 7% won’t treat a patient on nicardipine for blood pressure control; and 5% won’t treat an otherwise-qualified patient who is on dual-antiplatelet therapy.

The number of nonstandard inclusion and exclusion criteria in place at a stroke center showed a significant inverse relationship with the institutional intravenous TPA treatment rate. Smaller community hospitals with lower ischemic stroke admission volumes tended to have a longer list of nonstandard treatment criteria, according to Ms. Cudlip.

Several audience members rose to voice frustration at the list of off-label impediments to prompt intravenous TPA therapy at their home institutions. One physician, noting that institutional change can be difficult to achieve, asked Ms. Cudlip which two common nonlabel treatment criteria she’d make her top priority for elimination.

Ms. Cudlip answered without hesitation: The requirement that a patient has to have an NIHSS score of 4 or more, which according to her survey is in use at more than one-third of stroke centers, needs to go.

"I can have an NIHSS score of 3 and yet have completely lost my speech. That’s pretty disabling, right? I’d really want you to treat me. I need to speak," she said.

The other widely used nonlabel criterion Ms. Cudlip would target for elimination immediately is the treatment exclusion for patients with rapidly improving symptoms despite a remaining disabling deficit.

A physician audience member chimed in that he finds particularly disturbing the policy of not treating patients over age 80, which is in place at 16% of stroke centers. Ms. Cudlip was fully on board with getting rid of that restriction, as well.

"The oldest we’ve treated at our center is a woman who was 106, not that we do it all the time," she said, generating a vigorous round of applause.

She reported having no relevant financial conflicts.

b.jancin@elsevier.com

Diminished renal function is an independent risk factor for recurrent stroke within the first 6 months following hospitalization for an acute ischemic stroke, Dr. Abraham Thomas reported at the International Stroke Conference.

The short-term risk of recurrent stroke climbs in stepwise fashion with decreasing renal function. Even patients categorized as having stage 2 renal function by National Kidney Foundation criteria – those with an estimated glomerular filtration rate of 60-89 mL/min/1.73 m² – have a 60% increased risk compared with those who have an estimated GFR of 90 or greater, according to Dr. Thomas of the University of California, San Francisco.

He presented an observational study involving 2,882 patients admitted with acute ischemic stroke to 12 Northern California Kaiser Permanente hospitals during 2004-2007. Twenty-four percent had stage 1 renal function upon admission, with an eGFR of at least 90 mL/min/1.73 m². Forty-seven percent were stage 2, 25% were stage 3 as defined by an eGFR of 30-59, and the rest had stage 4 chronic kidney disease.

In a multivariate analysis, stage 2 renal function was independently associated with a 60% greater risk of recurrent stroke within 6 months compared with those who were stage 1. Patients with stage 3 renal function were at 70% greater risk than were those who were stage 1, while stage 4 patients were at 80% increased risk.

Renal dysfunction is an established risk factor for first-time cardiovascular events, including stroke. But the relationship between renal function and short-term risk of recurrent stroke has not previously been scrutinized.

One possible mechanism by which impaired renal function might predict an increased short-term risk of recurrent stroke involves poor blood pressure control, Dr. Thomas observed. The prevalence of hypertension was 19% with stage 1 renal function, 24% in those who were stage 2, and 26% in patients with stage 3 or 4 renal function. And at 6 months’ follow-up, blood pressure control was less than half as common among stage 4 patients than in those who were stages 1-3.

The conference was sponsored by the American Heart Association. Dr. Thomas reported having no financial conflicts.

b.jancin@elsevier.com

Diminished renal function is an independent risk factor for recurrent stroke within the first 6 months following hospitalization for an acute ischemic stroke, Dr. Abraham Thomas reported at the International Stroke Conference.

The short-term risk of recurrent stroke climbs in stepwise fashion with decreasing renal function. Even patients categorized as having stage 2 renal function by National Kidney Foundation criteria – those with an estimated glomerular filtration rate of 60-89 mL/min/1.73 m² – have a 60% increased risk compared with those who have an estimated GFR of 90 or greater, according to Dr. Thomas of the University of California, San Francisco.

He presented an observational study involving 2,882 patients admitted with acute ischemic stroke to 12 Northern California Kaiser Permanente hospitals during 2004-2007. Twenty-four percent had stage 1 renal function upon admission, with an eGFR of at least 90 mL/min/1.73 m². Forty-seven percent were stage 2, 25% were stage 3 as defined by an eGFR of 30-59, and the rest had stage 4 chronic kidney disease.

In a multivariate analysis, stage 2 renal function was independently associated with a 60% greater risk of recurrent stroke within 6 months compared with those who were stage 1. Patients with stage 3 renal function were at 70% greater risk than were those who were stage 1, while stage 4 patients were at 80% increased risk.

Renal dysfunction is an established risk factor for first-time cardiovascular events, including stroke. But the relationship between renal function and short-term risk of recurrent stroke has not previously been scrutinized.

One possible mechanism by which impaired renal function might predict an increased short-term risk of recurrent stroke involves poor blood pressure control, Dr. Thomas observed. The prevalence of hypertension was 19% with stage 1 renal function, 24% in those who were stage 2, and 26% in patients with stage 3 or 4 renal function. And at 6 months’ follow-up, blood pressure control was less than half as common among stage 4 patients than in those who were stages 1-3.

The conference was sponsored by the American Heart Association. Dr. Thomas reported having no financial conflicts.

b.jancin@elsevier.com

Diminished renal function is an independent risk factor for recurrent stroke within the first 6 months following hospitalization for an acute ischemic stroke, Dr. Abraham Thomas reported at the International Stroke Conference.

The short-term risk of recurrent stroke climbs in stepwise fashion with decreasing renal function. Even patients categorized as having stage 2 renal function by National Kidney Foundation criteria – those with an estimated glomerular filtration rate of 60-89 mL/min/1.73 m² – have a 60% increased risk compared with those who have an estimated GFR of 90 or greater, according to Dr. Thomas of the University of California, San Francisco.

He presented an observational study involving 2,882 patients admitted with acute ischemic stroke to 12 Northern California Kaiser Permanente hospitals during 2004-2007. Twenty-four percent had stage 1 renal function upon admission, with an eGFR of at least 90 mL/min/1.73 m². Forty-seven percent were stage 2, 25% were stage 3 as defined by an eGFR of 30-59, and the rest had stage 4 chronic kidney disease.

In a multivariate analysis, stage 2 renal function was independently associated with a 60% greater risk of recurrent stroke within 6 months compared with those who were stage 1. Patients with stage 3 renal function were at 70% greater risk than were those who were stage 1, while stage 4 patients were at 80% increased risk.

Renal dysfunction is an established risk factor for first-time cardiovascular events, including stroke. But the relationship between renal function and short-term risk of recurrent stroke has not previously been scrutinized.

One possible mechanism by which impaired renal function might predict an increased short-term risk of recurrent stroke involves poor blood pressure control, Dr. Thomas observed. The prevalence of hypertension was 19% with stage 1 renal function, 24% in those who were stage 2, and 26% in patients with stage 3 or 4 renal function. And at 6 months’ follow-up, blood pressure control was less than half as common among stage 4 patients than in those who were stages 1-3.

The conference was sponsored by the American Heart Association. Dr. Thomas reported having no financial conflicts.

b.jancin@elsevier.com

HONOLULU – Neurologists, internists, and emergency physicians with expertise in acute stroke care are wildly inaccurate in predicting key clinical outcomes in patients with acute ischemic stroke, a study has shown.

Indeed, in the JURASSIC (Clinician Judgment versus Risk Score to Predict Stroke Outcomes) trial, physician estimates as to whether patients would be dead or disabled at discharge were accurate in only 16.9% of cases, or one out of six times. In contrast, a validated predictive model of stroke mortality known as the iScore was on the mark 90% of the time, Dr. Gustavo Saposnik reported at the International Stroke Conference sponsored by the American Heart Association.

Dr. Saposnik and his coworkers developed the iScore because they saw the need for an objective, simple tool to stratify mortality risk in acute ischemic stroke patients. The ability to estimate prognosis with reasonable accuracy is essential to treatment decisions, discharge planning, counseling of patients and their families, and the accuracy of health care policy makers’ comparisons of outcomes between different hospitals.

For the JURASSIC trial, the investigators involved a convenience sample of 111 Ontario physicians with expertise in acute stroke care. Half were neurologists, and the rest were internists or emergency physicians. Their mean age was 40 years, and they each saw an average of 98 stroke patients annually.

Each physician was presented with case summaries for five acute ischemic stroke patients and asked to predict their likelihood of death or disability at discharge as well as 30-day mortality. The five cases were representative of the most common clinical scenarios extracted from a pool of more than 12,000 patients admitted to Ontario stroke centers, so there were no red herrings or tricks.

The 111 physicians collectively made 1,661 outcome predictions. Only 16.9% of their predictions regarding death or disability at discharge were within the 95% confidence interval for the actual observed outcomes. The physicians’ accuracy at predicting 30-day mortality was 46.9%. The iScore-based outcome estimates were within the 95% confidence interval in 90% of cases.

Only 1 of the 111 physicians was accurate in predicting clinical outcomes in four of the five cases. None got all five correct.

The iScore utilizes information easily obtainable within hours of hospital presentation without specialized lab tests or imaging. The variables incorporated into the iScore are age, sex, stroke severity and subtype, coronary artery disease, heart failure, smoking, cancer, hyperglycemia upon admission, history of atrial fibrillation, and renal disease requiring dialysis. Thus, the user-friendly iScore is suitable for use in community hospitals as well as tertiary centers, noted Dr. Saposnik of the University of Toronto.

The score enables patients to be classified into one of five categories based on the estimated risk of mortality. In a validation study (Circulation 2011;123:739-49), the 30-day mortality risk ranged from a low of 1.19% in group 1 to 41.57% in group 5.

The iScore is available as a Web-based tool.

Dr. Saposnik reported having no relevant financial conflicts.

b.jancin@elsevier.com

HONOLULU – Neurologists, internists, and emergency physicians with expertise in acute stroke care are wildly inaccurate in predicting key clinical outcomes in patients with acute ischemic stroke, a study has shown.

Indeed, in the JURASSIC (Clinician Judgment versus Risk Score to Predict Stroke Outcomes) trial, physician estimates as to whether patients would be dead or disabled at discharge were accurate in only 16.9% of cases, or one out of six times. In contrast, a validated predictive model of stroke mortality known as the iScore was on the mark 90% of the time, Dr. Gustavo Saposnik reported at the International Stroke Conference sponsored by the American Heart Association.

Dr. Saposnik and his coworkers developed the iScore because they saw the need for an objective, simple tool to stratify mortality risk in acute ischemic stroke patients. The ability to estimate prognosis with reasonable accuracy is essential to treatment decisions, discharge planning, counseling of patients and their families, and the accuracy of health care policy makers’ comparisons of outcomes between different hospitals.

For the JURASSIC trial, the investigators involved a convenience sample of 111 Ontario physicians with expertise in acute stroke care. Half were neurologists, and the rest were internists or emergency physicians. Their mean age was 40 years, and they each saw an average of 98 stroke patients annually.

Each physician was presented with case summaries for five acute ischemic stroke patients and asked to predict their likelihood of death or disability at discharge as well as 30-day mortality. The five cases were representative of the most common clinical scenarios extracted from a pool of more than 12,000 patients admitted to Ontario stroke centers, so there were no red herrings or tricks.

The 111 physicians collectively made 1,661 outcome predictions. Only 16.9% of their predictions regarding death or disability at discharge were within the 95% confidence interval for the actual observed outcomes. The physicians’ accuracy at predicting 30-day mortality was 46.9%. The iScore-based outcome estimates were within the 95% confidence interval in 90% of cases.

Only 1 of the 111 physicians was accurate in predicting clinical outcomes in four of the five cases. None got all five correct.

The iScore utilizes information easily obtainable within hours of hospital presentation without specialized lab tests or imaging. The variables incorporated into the iScore are age, sex, stroke severity and subtype, coronary artery disease, heart failure, smoking, cancer, hyperglycemia upon admission, history of atrial fibrillation, and renal disease requiring dialysis. Thus, the user-friendly iScore is suitable for use in community hospitals as well as tertiary centers, noted Dr. Saposnik of the University of Toronto.

The score enables patients to be classified into one of five categories based on the estimated risk of mortality. In a validation study (Circulation 2011;123:739-49), the 30-day mortality risk ranged from a low of 1.19% in group 1 to 41.57% in group 5.

The iScore is available as a Web-based tool.

Dr. Saposnik reported having no relevant financial conflicts.

b.jancin@elsevier.com

HONOLULU – Neurologists, internists, and emergency physicians with expertise in acute stroke care are wildly inaccurate in predicting key clinical outcomes in patients with acute ischemic stroke, a study has shown.

Indeed, in the JURASSIC (Clinician Judgment versus Risk Score to Predict Stroke Outcomes) trial, physician estimates as to whether patients would be dead or disabled at discharge were accurate in only 16.9% of cases, or one out of six times. In contrast, a validated predictive model of stroke mortality known as the iScore was on the mark 90% of the time, Dr. Gustavo Saposnik reported at the International Stroke Conference sponsored by the American Heart Association.

Dr. Saposnik and his coworkers developed the iScore because they saw the need for an objective, simple tool to stratify mortality risk in acute ischemic stroke patients. The ability to estimate prognosis with reasonable accuracy is essential to treatment decisions, discharge planning, counseling of patients and their families, and the accuracy of health care policy makers’ comparisons of outcomes between different hospitals.

For the JURASSIC trial, the investigators involved a convenience sample of 111 Ontario physicians with expertise in acute stroke care. Half were neurologists, and the rest were internists or emergency physicians. Their mean age was 40 years, and they each saw an average of 98 stroke patients annually.

Each physician was presented with case summaries for five acute ischemic stroke patients and asked to predict their likelihood of death or disability at discharge as well as 30-day mortality. The five cases were representative of the most common clinical scenarios extracted from a pool of more than 12,000 patients admitted to Ontario stroke centers, so there were no red herrings or tricks.

The 111 physicians collectively made 1,661 outcome predictions. Only 16.9% of their predictions regarding death or disability at discharge were within the 95% confidence interval for the actual observed outcomes. The physicians’ accuracy at predicting 30-day mortality was 46.9%. The iScore-based outcome estimates were within the 95% confidence interval in 90% of cases.

Only 1 of the 111 physicians was accurate in predicting clinical outcomes in four of the five cases. None got all five correct.

The iScore utilizes information easily obtainable within hours of hospital presentation without specialized lab tests or imaging. The variables incorporated into the iScore are age, sex, stroke severity and subtype, coronary artery disease, heart failure, smoking, cancer, hyperglycemia upon admission, history of atrial fibrillation, and renal disease requiring dialysis. Thus, the user-friendly iScore is suitable for use in community hospitals as well as tertiary centers, noted Dr. Saposnik of the University of Toronto.

The score enables patients to be classified into one of five categories based on the estimated risk of mortality. In a validation study (Circulation 2011;123:739-49), the 30-day mortality risk ranged from a low of 1.19% in group 1 to 41.57% in group 5.

The iScore is available as a Web-based tool.

Dr. Saposnik reported having no relevant financial conflicts.

b.jancin@elsevier.com

HONOLULU – One out of every five patients in the United States who receives thrombolytic therapy for an acute ischemic stroke gets it for a stroke occurring when they’re already hospitalized for another reason.

These thrombolytic-treated in-hospital strokes are associated with significantly increased complication and procedural intervention rates, longer length of stay, higher hospital charges, and greater risk of inpatient mortality, compared with out-of-hospital ischemic strokes in patients who get thrombolytic therapy upon presentation, Dr. Tenbit Emiru reported at the International Stroke Conference, which was sponsored by the American Heart Association.

Dr. Emiru’s study is also scheduled to be presented at the annual meeting of the American Academy of Neurology in San Diego on March 21.

She presented an analysis of data for the years 2002-2010 from the National Inpatient Sample, a large, nationally representative hospital database. During the 8-year study period, the database captured more than 24,000 patients who received thrombolytic therapy for an in-hospital acute ischemic stroke and 112,000 others who got a thrombolytic agent for an out-of-hospital ischemic stroke. Thus, 18% of all thrombolytic therapy for acute stroke was administered to patients whose stroke occurred in the hospital.

In-hospital mortality was 11% in thrombolytic-treated patients with in-hospital stroke and 10% in those treated for an out-of-hospital stroke. In a multivariate analysis adjusted for age, gender, and baseline risk factors, patients treated for in-hospital stroke had a statistically significant 10% increased risk of mortality, said Dr. Emiru of the Zeenat Qureshi Stroke Research Center at the University of Minnesota, Minneapolis.

The discharge rate with minimal or no disability was 36% for the in-hospital stroke group and 38% in those treated upon presentation with out-of-hospital stroke, a nonsignificant difference.

The mean length of stay was 8 days in the in-hospital stroke group and 7 days in the comparison group. The in-hospital stroke group had significantly higher rates of in-hospital pneumonia, deep venous thrombosis (DVT), sepsis, and pulmonary embolism, although the absolute differences were small. For example, pneumonia occurred in 5% of patients treated for in-hospital acute ischemic stroke, compared with 3% with out-of-hospital stroke, while DVT was a complication in 2% and 0.7%, respectively.

The disparity between in-hospital procedures for the two groups was more pronounced. For example, 31% of patients treated for in-hospital stroke underwent angiography, compared with 19% of out-of-hospital stroke patients. Those who got thrombolytic therapy for in-hospital stroke also had significantly higher rates of carotid angioplasty (5% vs. 2%) and carotid endarterectomy (3% vs. 1%), Dr. Emiru continued.

Hospital charges averaged $74,713 for patients with in-hospital stroke and $68,419 for those with out-of-hospital stroke.

Audience members indicated that they would have welcomed data on time to treatment from stroke onset for the two groups, as well as information on the reasons for hospitalization in the patients with in-hospital stroke. Neither issue was examined in the study. One audience member commented that the most obvious explanation for the worse outcomes in the thrombolytic-treated patients with in-hospital stroke is that they were sicker to begin with, as evidenced by the fact that were already hospitalized at the time of their ischemic stroke.

Dr. Emiru reported having no financial conflicts.

b.jancin@elsevier.com

HONOLULU – One out of every five patients in the United States who receives thrombolytic therapy for an acute ischemic stroke gets it for a stroke occurring when they’re already hospitalized for another reason.

These thrombolytic-treated in-hospital strokes are associated with significantly increased complication and procedural intervention rates, longer length of stay, higher hospital charges, and greater risk of inpatient mortality, compared with out-of-hospital ischemic strokes in patients who get thrombolytic therapy upon presentation, Dr. Tenbit Emiru reported at the International Stroke Conference, which was sponsored by the American Heart Association.

Dr. Emiru’s study is also scheduled to be presented at the annual meeting of the American Academy of Neurology in San Diego on March 21.

She presented an analysis of data for the years 2002-2010 from the National Inpatient Sample, a large, nationally representative hospital database. During the 8-year study period, the database captured more than 24,000 patients who received thrombolytic therapy for an in-hospital acute ischemic stroke and 112,000 others who got a thrombolytic agent for an out-of-hospital ischemic stroke. Thus, 18% of all thrombolytic therapy for acute stroke was administered to patients whose stroke occurred in the hospital.

In-hospital mortality was 11% in thrombolytic-treated patients with in-hospital stroke and 10% in those treated for an out-of-hospital stroke. In a multivariate analysis adjusted for age, gender, and baseline risk factors, patients treated for in-hospital stroke had a statistically significant 10% increased risk of mortality, said Dr. Emiru of the Zeenat Qureshi Stroke Research Center at the University of Minnesota, Minneapolis.

The discharge rate with minimal or no disability was 36% for the in-hospital stroke group and 38% in those treated upon presentation with out-of-hospital stroke, a nonsignificant difference.

The mean length of stay was 8 days in the in-hospital stroke group and 7 days in the comparison group. The in-hospital stroke group had significantly higher rates of in-hospital pneumonia, deep venous thrombosis (DVT), sepsis, and pulmonary embolism, although the absolute differences were small. For example, pneumonia occurred in 5% of patients treated for in-hospital acute ischemic stroke, compared with 3% with out-of-hospital stroke, while DVT was a complication in 2% and 0.7%, respectively.

The disparity between in-hospital procedures for the two groups was more pronounced. For example, 31% of patients treated for in-hospital stroke underwent angiography, compared with 19% of out-of-hospital stroke patients. Those who got thrombolytic therapy for in-hospital stroke also had significantly higher rates of carotid angioplasty (5% vs. 2%) and carotid endarterectomy (3% vs. 1%), Dr. Emiru continued.

Hospital charges averaged $74,713 for patients with in-hospital stroke and $68,419 for those with out-of-hospital stroke.

Audience members indicated that they would have welcomed data on time to treatment from stroke onset for the two groups, as well as information on the reasons for hospitalization in the patients with in-hospital stroke. Neither issue was examined in the study. One audience member commented that the most obvious explanation for the worse outcomes in the thrombolytic-treated patients with in-hospital stroke is that they were sicker to begin with, as evidenced by the fact that were already hospitalized at the time of their ischemic stroke.

Dr. Emiru reported having no financial conflicts.

b.jancin@elsevier.com

HONOLULU – One out of every five patients in the United States who receives thrombolytic therapy for an acute ischemic stroke gets it for a stroke occurring when they’re already hospitalized for another reason.

These thrombolytic-treated in-hospital strokes are associated with significantly increased complication and procedural intervention rates, longer length of stay, higher hospital charges, and greater risk of inpatient mortality, compared with out-of-hospital ischemic strokes in patients who get thrombolytic therapy upon presentation, Dr. Tenbit Emiru reported at the International Stroke Conference, which was sponsored by the American Heart Association.

Dr. Emiru’s study is also scheduled to be presented at the annual meeting of the American Academy of Neurology in San Diego on March 21.

She presented an analysis of data for the years 2002-2010 from the National Inpatient Sample, a large, nationally representative hospital database. During the 8-year study period, the database captured more than 24,000 patients who received thrombolytic therapy for an in-hospital acute ischemic stroke and 112,000 others who got a thrombolytic agent for an out-of-hospital ischemic stroke. Thus, 18% of all thrombolytic therapy for acute stroke was administered to patients whose stroke occurred in the hospital.

In-hospital mortality was 11% in thrombolytic-treated patients with in-hospital stroke and 10% in those treated for an out-of-hospital stroke. In a multivariate analysis adjusted for age, gender, and baseline risk factors, patients treated for in-hospital stroke had a statistically significant 10% increased risk of mortality, said Dr. Emiru of the Zeenat Qureshi Stroke Research Center at the University of Minnesota, Minneapolis.

The discharge rate with minimal or no disability was 36% for the in-hospital stroke group and 38% in those treated upon presentation with out-of-hospital stroke, a nonsignificant difference.

The mean length of stay was 8 days in the in-hospital stroke group and 7 days in the comparison group. The in-hospital stroke group had significantly higher rates of in-hospital pneumonia, deep venous thrombosis (DVT), sepsis, and pulmonary embolism, although the absolute differences were small. For example, pneumonia occurred in 5% of patients treated for in-hospital acute ischemic stroke, compared with 3% with out-of-hospital stroke, while DVT was a complication in 2% and 0.7%, respectively.

The disparity between in-hospital procedures for the two groups was more pronounced. For example, 31% of patients treated for in-hospital stroke underwent angiography, compared with 19% of out-of-hospital stroke patients. Those who got thrombolytic therapy for in-hospital stroke also had significantly higher rates of carotid angioplasty (5% vs. 2%) and carotid endarterectomy (3% vs. 1%), Dr. Emiru continued.

Hospital charges averaged $74,713 for patients with in-hospital stroke and $68,419 for those with out-of-hospital stroke.

Audience members indicated that they would have welcomed data on time to treatment from stroke onset for the two groups, as well as information on the reasons for hospitalization in the patients with in-hospital stroke. Neither issue was examined in the study. One audience member commented that the most obvious explanation for the worse outcomes in the thrombolytic-treated patients with in-hospital stroke is that they were sicker to begin with, as evidenced by the fact that were already hospitalized at the time of their ischemic stroke.

Dr. Emiru reported having no financial conflicts.

b.jancin@elsevier.com

SNOWMASS, COLO. – Surgical aortic valve replacement is a mature operation with durable outcomes, but surgeons aren’t standing still in the face of competition posed by cardiologists’ transcatheter alternative.

Well along in clinical development is a minimally invasive surgical aortic valve replacement (SAVR), which utilizes a novel hybrid valve deployed via a 10-second balloon inflation, thereby avoiding the time-consuming suturing and knot-tying required when traditional surgical valves are sewn into place. This minimally invasive procedure involves a partial sternotomy so as to better maintain the skeletal integrity of the sternum, Dr. Michael J. Mack explained at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"I think this has the potential to cut surgical times in half. Indeed, the operations are now taking a total time of about 1 hour 45 minutes. This makes SAVR a better option for elderly patients who may not be TAVR candidates," said Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

A major clinical trial of the innovative hybrid no-suture valve, called the Edwards Lifesciences Intuity Valve System, has been completed in Europe, and another is underway in the United States. Other major medical device companies are also developing no-stitch surgical aortic valves.

"Now we can make SAVR better because there’s a less-invasive option. This never would have happened in surgery unless TAVR happened," Dr. Mack observed.

He reported receiving research grants from Edwards Lifesciences.

b.jancin@elsevier.com

SNOWMASS, COLO. – Surgical aortic valve replacement is a mature operation with durable outcomes, but surgeons aren’t standing still in the face of competition posed by cardiologists’ transcatheter alternative.

Well along in clinical development is a minimally invasive surgical aortic valve replacement (SAVR), which utilizes a novel hybrid valve deployed via a 10-second balloon inflation, thereby avoiding the time-consuming suturing and knot-tying required when traditional surgical valves are sewn into place. This minimally invasive procedure involves a partial sternotomy so as to better maintain the skeletal integrity of the sternum, Dr. Michael J. Mack explained at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"I think this has the potential to cut surgical times in half. Indeed, the operations are now taking a total time of about 1 hour 45 minutes. This makes SAVR a better option for elderly patients who may not be TAVR candidates," said Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

A major clinical trial of the innovative hybrid no-suture valve, called the Edwards Lifesciences Intuity Valve System, has been completed in Europe, and another is underway in the United States. Other major medical device companies are also developing no-stitch surgical aortic valves.

"Now we can make SAVR better because there’s a less-invasive option. This never would have happened in surgery unless TAVR happened," Dr. Mack observed.

He reported receiving research grants from Edwards Lifesciences.

b.jancin@elsevier.com

SNOWMASS, COLO. – Surgical aortic valve replacement is a mature operation with durable outcomes, but surgeons aren’t standing still in the face of competition posed by cardiologists’ transcatheter alternative.

Well along in clinical development is a minimally invasive surgical aortic valve replacement (SAVR), which utilizes a novel hybrid valve deployed via a 10-second balloon inflation, thereby avoiding the time-consuming suturing and knot-tying required when traditional surgical valves are sewn into place. This minimally invasive procedure involves a partial sternotomy so as to better maintain the skeletal integrity of the sternum, Dr. Michael J. Mack explained at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"I think this has the potential to cut surgical times in half. Indeed, the operations are now taking a total time of about 1 hour 45 minutes. This makes SAVR a better option for elderly patients who may not be TAVR candidates," said Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

A major clinical trial of the innovative hybrid no-suture valve, called the Edwards Lifesciences Intuity Valve System, has been completed in Europe, and another is underway in the United States. Other major medical device companies are also developing no-stitch surgical aortic valves.

"Now we can make SAVR better because there’s a less-invasive option. This never would have happened in surgery unless TAVR happened," Dr. Mack observed.

He reported receiving research grants from Edwards Lifesciences.

b.jancin@elsevier.com

SNOWMASS, COLO. – Fractional flow reserve measurement has rapidly emerged as the tool of choice for deciding in the catheterization laboratory whether to revascularize an intermediate 50%-70% stenosis in a patient with stable ischemic heart disease, according to Dr. E. Murat *Tuzcu.

The evidence is now compelling that fractional flow reserve (FFR) calculated invasively from coronary pressure measurement is superior to angiographic assessment, intravascular ultrasound, or optical coherence tomography for this purpose.

"When the question is, ‘What should we do with the borderline lesion?’ the answer is fractional flow reserve, even in the left main coronary artery," Dr. Tuzcu, professor of medicine at the Cleveland Clinic, asserted at the Annual Cardiovascular Conference at Snowmass.

FFR is the method par excellence for determining if an intermediate stenosis is hemodynamically significant; that is, whether the lesion is responsible for reversible ischemia. If it is, then coronary stenting will improve the patient’s functional status and reduce the likelihood of acute MI and all-cause mortality down the road. If FFR indicates that the stenosis is not responsible for reversible ischemia, however, then PCI won’t improve the patient’s prognosis. FFR has the additional virtues of being fast and simple, and it enables immediate decision-making in the cath lab, he explained.

For Dr. Tuzcu, the game changer for FFR was the DEFER study, which he considers to be one of the most important clinical trials in the field of interventional cardiology in the past decade. It showed that, by using FFR, cardiologists could be more selective in their use of PCI in the setting of stable ischemic heart disease.

DEFER was a multicenter Dutch/Belgian study in which 325 patients underwent FFR measurement just prior to planned PCI for an intermediate stenosis. If the FFR value was less than 0.75 – indicative of reversible ischemia – then PCI was performed as planned. If it was 0.75 or greater, patients were randomized to PCI or to deferred PCI.

At 5 years of follow-up, the rate of cardiac death or acute MI was 3.3% in the 91 patients with an FFR of 0.75 or more in the deferred PCI group – less than 1% per year. That wasn’t significantly different from the 7.9% rate among the 90 patients with an FFR of at least 0.75 who underwent prompt PCI. In contrast, the combined endpoint occurred in 15.7% of the 144 PCI-treated patients with FFR evidence of reversible ischemia due to the target lesion (J. Am. Coll. Cardiol. 2007;49:2105-11.)

DEFER was conducted in the bare metal–stent era. The next major clinical trial advancing FFR was the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study, in which 1,005 patients with multivessel CAD were randomized to PCI with drug-eluting stents guided by FFR or by angiography alone. The FFR definition of reversible ischemia used in FAME and subsequent trials was a value of 0.80 or less.

The 2-year rate of death or MI was 8.4% in the FFR-guided group, significantly less than the 12.9% rate in the angiography-guided patients. For patients with stenotic lesions deferred from PCI on the basis of an FFR greater than 0.80, the 2-year rate of MI was just 0.2%, with a revascularization rate of 3.2% (J. Am. Coll. Cardiol. 2010;56:177-84).

Nearly half of all stenoses were categorized angiographically as intermediate, 50%-70% lesions. FFR classified 35% of such lesions as functionally significant, while 65% were not associated with reversible ischemia (J. Am. Coll. Cardiol. 2010;55:2816-21).

In the FAME-2 trial, 888 patients with stable CAD and at least one functionally significant stenosis with an FFR of 0.80 or less were randomized to PCI plus optimal medical therapy or to optimal medical therapy alone. Recruitment was halted prematurely by the data safety monitoring board because the combined endpoint of death, MI, or urgent revascularization had occurred in 4.3% of the PCI group versus 12.7% of those assigned to optimal medical management alone (N. Engl. J. Med. 2012;367:991-1001).

Dr. Tuzcu noted that optical coherence tomography (OCT) has drawn much interest as a tool for identifying hemodynamically severe coronary stenoses. "It provides great pictures with tremendous resolution. For looking at stent strut coverage, OCT is a star tool. It’s almost like histology," he said.

It can’t, however, hold a candle to FFR for hemodynamic assessment of stenoses, he added, pointing to a recent Spanish study comparing FFR, OCT, and intravascular ultrasound (IVUS) for this purpose. OCT and IVUS displayed moderate diagnostic efficiency, with no clinically meaningful difference between them, but Dr. Tuzcu concurred with the investigators that the low specificity of OCT and IVUS precludes their use in lieu of FFR for functional assessment (J. Am. Coll. Cardiol. 2012;59:1080-9).

The most recent significant development on the FFR front was Dr. Gregg W. Stone’s presentation of the pooled results of the VERDICT and FIRST trials at the Transcatheter Cardiovascular Therapeutics conference in Miami last October. VERDICT and FIRST included 516 patients with 544 intermediate coronary stenoses evaluated by both FFR and IVUS at 24 centers in nine countries. The bottom line was that IVUS-determined minimum luminal cross-sectional area was only modestly correlated with FFR, according to Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University Medical Center/New York Presbyterian Hospital.

"I think this clearly showed – and probably conclusively showed – that, while IVUS is useful in many, many settings, it’s probably not the best tool when FFR is available for deciding which lesion is significant and which is not," Dr. Tuzcu said.

"IVUS is a pretty good tool, sometimes, for morphologic assessment. I like it when there’s an issue with the left main coronary artery. I can size the artery, I can understand an ostial lesion, and I can certainly understand better a bifurcation or trifurcation of the left main coronary artery," he added.

The current American College of Cardiology/American Heart Association guidelines give IVUS a class IIa rating as "reasonable" to assess angiographically intermediate stenoses of the left main coronary artery. FFR gets the same relatively tepid IIa rating for assessment of intermediate stenoses in any coronary arteries. In contrast, the latest European Society of Cardiology guidelines on coronary revascularization have bumped up FFR to a class Ia rating, making it the standard for this assessment.

Dr. Tuzcu reported having no financial conflicts.

b.jancin@elsevier.com

*CORRECTION, 3/1/2013: In an earlier version of this story, the name of Dr. E. Murat Tuzcu was spelled incorrectly. This version has been updated.

SNOWMASS, COLO. – Fractional flow reserve measurement has rapidly emerged as the tool of choice for deciding in the catheterization laboratory whether to revascularize an intermediate 50%-70% stenosis in a patient with stable ischemic heart disease, according to Dr. E. Murat *Tuzcu.

The evidence is now compelling that fractional flow reserve (FFR) calculated invasively from coronary pressure measurement is superior to angiographic assessment, intravascular ultrasound, or optical coherence tomography for this purpose.

"When the question is, ‘What should we do with the borderline lesion?’ the answer is fractional flow reserve, even in the left main coronary artery," Dr. Tuzcu, professor of medicine at the Cleveland Clinic, asserted at the Annual Cardiovascular Conference at Snowmass.

FFR is the method par excellence for determining if an intermediate stenosis is hemodynamically significant; that is, whether the lesion is responsible for reversible ischemia. If it is, then coronary stenting will improve the patient’s functional status and reduce the likelihood of acute MI and all-cause mortality down the road. If FFR indicates that the stenosis is not responsible for reversible ischemia, however, then PCI won’t improve the patient’s prognosis. FFR has the additional virtues of being fast and simple, and it enables immediate decision-making in the cath lab, he explained.

For Dr. Tuzcu, the game changer for FFR was the DEFER study, which he considers to be one of the most important clinical trials in the field of interventional cardiology in the past decade. It showed that, by using FFR, cardiologists could be more selective in their use of PCI in the setting of stable ischemic heart disease.

DEFER was a multicenter Dutch/Belgian study in which 325 patients underwent FFR measurement just prior to planned PCI for an intermediate stenosis. If the FFR value was less than 0.75 – indicative of reversible ischemia – then PCI was performed as planned. If it was 0.75 or greater, patients were randomized to PCI or to deferred PCI.

At 5 years of follow-up, the rate of cardiac death or acute MI was 3.3% in the 91 patients with an FFR of 0.75 or more in the deferred PCI group – less than 1% per year. That wasn’t significantly different from the 7.9% rate among the 90 patients with an FFR of at least 0.75 who underwent prompt PCI. In contrast, the combined endpoint occurred in 15.7% of the 144 PCI-treated patients with FFR evidence of reversible ischemia due to the target lesion (J. Am. Coll. Cardiol. 2007;49:2105-11.)

DEFER was conducted in the bare metal–stent era. The next major clinical trial advancing FFR was the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study, in which 1,005 patients with multivessel CAD were randomized to PCI with drug-eluting stents guided by FFR or by angiography alone. The FFR definition of reversible ischemia used in FAME and subsequent trials was a value of 0.80 or less.

The 2-year rate of death or MI was 8.4% in the FFR-guided group, significantly less than the 12.9% rate in the angiography-guided patients. For patients with stenotic lesions deferred from PCI on the basis of an FFR greater than 0.80, the 2-year rate of MI was just 0.2%, with a revascularization rate of 3.2% (J. Am. Coll. Cardiol. 2010;56:177-84).

Nearly half of all stenoses were categorized angiographically as intermediate, 50%-70% lesions. FFR classified 35% of such lesions as functionally significant, while 65% were not associated with reversible ischemia (J. Am. Coll. Cardiol. 2010;55:2816-21).

In the FAME-2 trial, 888 patients with stable CAD and at least one functionally significant stenosis with an FFR of 0.80 or less were randomized to PCI plus optimal medical therapy or to optimal medical therapy alone. Recruitment was halted prematurely by the data safety monitoring board because the combined endpoint of death, MI, or urgent revascularization had occurred in 4.3% of the PCI group versus 12.7% of those assigned to optimal medical management alone (N. Engl. J. Med. 2012;367:991-1001).

Dr. Tuzcu noted that optical coherence tomography (OCT) has drawn much interest as a tool for identifying hemodynamically severe coronary stenoses. "It provides great pictures with tremendous resolution. For looking at stent strut coverage, OCT is a star tool. It’s almost like histology," he said.

It can’t, however, hold a candle to FFR for hemodynamic assessment of stenoses, he added, pointing to a recent Spanish study comparing FFR, OCT, and intravascular ultrasound (IVUS) for this purpose. OCT and IVUS displayed moderate diagnostic efficiency, with no clinically meaningful difference between them, but Dr. Tuzcu concurred with the investigators that the low specificity of OCT and IVUS precludes their use in lieu of FFR for functional assessment (J. Am. Coll. Cardiol. 2012;59:1080-9).

The most recent significant development on the FFR front was Dr. Gregg W. Stone’s presentation of the pooled results of the VERDICT and FIRST trials at the Transcatheter Cardiovascular Therapeutics conference in Miami last October. VERDICT and FIRST included 516 patients with 544 intermediate coronary stenoses evaluated by both FFR and IVUS at 24 centers in nine countries. The bottom line was that IVUS-determined minimum luminal cross-sectional area was only modestly correlated with FFR, according to Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University Medical Center/New York Presbyterian Hospital.

"I think this clearly showed – and probably conclusively showed – that, while IVUS is useful in many, many settings, it’s probably not the best tool when FFR is available for deciding which lesion is significant and which is not," Dr. Tuzcu said.

"IVUS is a pretty good tool, sometimes, for morphologic assessment. I like it when there’s an issue with the left main coronary artery. I can size the artery, I can understand an ostial lesion, and I can certainly understand better a bifurcation or trifurcation of the left main coronary artery," he added.

The current American College of Cardiology/American Heart Association guidelines give IVUS a class IIa rating as "reasonable" to assess angiographically intermediate stenoses of the left main coronary artery. FFR gets the same relatively tepid IIa rating for assessment of intermediate stenoses in any coronary arteries. In contrast, the latest European Society of Cardiology guidelines on coronary revascularization have bumped up FFR to a class Ia rating, making it the standard for this assessment.

Dr. Tuzcu reported having no financial conflicts.

b.jancin@elsevier.com

*CORRECTION, 3/1/2013: In an earlier version of this story, the name of Dr. E. Murat Tuzcu was spelled incorrectly. This version has been updated.

SNOWMASS, COLO. – Fractional flow reserve measurement has rapidly emerged as the tool of choice for deciding in the catheterization laboratory whether to revascularize an intermediate 50%-70% stenosis in a patient with stable ischemic heart disease, according to Dr. E. Murat *Tuzcu.

The evidence is now compelling that fractional flow reserve (FFR) calculated invasively from coronary pressure measurement is superior to angiographic assessment, intravascular ultrasound, or optical coherence tomography for this purpose.

"When the question is, ‘What should we do with the borderline lesion?’ the answer is fractional flow reserve, even in the left main coronary artery," Dr. Tuzcu, professor of medicine at the Cleveland Clinic, asserted at the Annual Cardiovascular Conference at Snowmass.

FFR is the method par excellence for determining if an intermediate stenosis is hemodynamically significant; that is, whether the lesion is responsible for reversible ischemia. If it is, then coronary stenting will improve the patient’s functional status and reduce the likelihood of acute MI and all-cause mortality down the road. If FFR indicates that the stenosis is not responsible for reversible ischemia, however, then PCI won’t improve the patient’s prognosis. FFR has the additional virtues of being fast and simple, and it enables immediate decision-making in the cath lab, he explained.

For Dr. Tuzcu, the game changer for FFR was the DEFER study, which he considers to be one of the most important clinical trials in the field of interventional cardiology in the past decade. It showed that, by using FFR, cardiologists could be more selective in their use of PCI in the setting of stable ischemic heart disease.

DEFER was a multicenter Dutch/Belgian study in which 325 patients underwent FFR measurement just prior to planned PCI for an intermediate stenosis. If the FFR value was less than 0.75 – indicative of reversible ischemia – then PCI was performed as planned. If it was 0.75 or greater, patients were randomized to PCI or to deferred PCI.

At 5 years of follow-up, the rate of cardiac death or acute MI was 3.3% in the 91 patients with an FFR of 0.75 or more in the deferred PCI group – less than 1% per year. That wasn’t significantly different from the 7.9% rate among the 90 patients with an FFR of at least 0.75 who underwent prompt PCI. In contrast, the combined endpoint occurred in 15.7% of the 144 PCI-treated patients with FFR evidence of reversible ischemia due to the target lesion (J. Am. Coll. Cardiol. 2007;49:2105-11.)

DEFER was conducted in the bare metal–stent era. The next major clinical trial advancing FFR was the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study, in which 1,005 patients with multivessel CAD were randomized to PCI with drug-eluting stents guided by FFR or by angiography alone. The FFR definition of reversible ischemia used in FAME and subsequent trials was a value of 0.80 or less.

The 2-year rate of death or MI was 8.4% in the FFR-guided group, significantly less than the 12.9% rate in the angiography-guided patients. For patients with stenotic lesions deferred from PCI on the basis of an FFR greater than 0.80, the 2-year rate of MI was just 0.2%, with a revascularization rate of 3.2% (J. Am. Coll. Cardiol. 2010;56:177-84).

Nearly half of all stenoses were categorized angiographically as intermediate, 50%-70% lesions. FFR classified 35% of such lesions as functionally significant, while 65% were not associated with reversible ischemia (J. Am. Coll. Cardiol. 2010;55:2816-21).

In the FAME-2 trial, 888 patients with stable CAD and at least one functionally significant stenosis with an FFR of 0.80 or less were randomized to PCI plus optimal medical therapy or to optimal medical therapy alone. Recruitment was halted prematurely by the data safety monitoring board because the combined endpoint of death, MI, or urgent revascularization had occurred in 4.3% of the PCI group versus 12.7% of those assigned to optimal medical management alone (N. Engl. J. Med. 2012;367:991-1001).

Dr. Tuzcu noted that optical coherence tomography (OCT) has drawn much interest as a tool for identifying hemodynamically severe coronary stenoses. "It provides great pictures with tremendous resolution. For looking at stent strut coverage, OCT is a star tool. It’s almost like histology," he said.

It can’t, however, hold a candle to FFR for hemodynamic assessment of stenoses, he added, pointing to a recent Spanish study comparing FFR, OCT, and intravascular ultrasound (IVUS) for this purpose. OCT and IVUS displayed moderate diagnostic efficiency, with no clinically meaningful difference between them, but Dr. Tuzcu concurred with the investigators that the low specificity of OCT and IVUS precludes their use in lieu of FFR for functional assessment (J. Am. Coll. Cardiol. 2012;59:1080-9).

The most recent significant development on the FFR front was Dr. Gregg W. Stone’s presentation of the pooled results of the VERDICT and FIRST trials at the Transcatheter Cardiovascular Therapeutics conference in Miami last October. VERDICT and FIRST included 516 patients with 544 intermediate coronary stenoses evaluated by both FFR and IVUS at 24 centers in nine countries. The bottom line was that IVUS-determined minimum luminal cross-sectional area was only modestly correlated with FFR, according to Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University Medical Center/New York Presbyterian Hospital.

"I think this clearly showed – and probably conclusively showed – that, while IVUS is useful in many, many settings, it’s probably not the best tool when FFR is available for deciding which lesion is significant and which is not," Dr. Tuzcu said.

"IVUS is a pretty good tool, sometimes, for morphologic assessment. I like it when there’s an issue with the left main coronary artery. I can size the artery, I can understand an ostial lesion, and I can certainly understand better a bifurcation or trifurcation of the left main coronary artery," he added.

The current American College of Cardiology/American Heart Association guidelines give IVUS a class IIa rating as "reasonable" to assess angiographically intermediate stenoses of the left main coronary artery. FFR gets the same relatively tepid IIa rating for assessment of intermediate stenoses in any coronary arteries. In contrast, the latest European Society of Cardiology guidelines on coronary revascularization have bumped up FFR to a class Ia rating, making it the standard for this assessment.

Dr. Tuzcu reported having no financial conflicts.

b.jancin@elsevier.com

*CORRECTION, 3/1/2013: In an earlier version of this story, the name of Dr. E. Murat Tuzcu was spelled incorrectly. This version has been updated.