Michele G. Sullivan

BOSTON — Drug changes—by the physician or the patient—and infections are the most likely culprits behind motor fluctuations that land a patient with Parkinson's disease in the emergency department.

“The first thing to do is look for infections or other medical issues, and check to see if there have been any medication changes,” said Dr. Stewart Factor said at the annual meeting of the American Academy of Neurology.

Urinary tract or upper respiratory infections can trigger dyskinesias by altering the sensitivity to medication, said Dr. Factor of Emory University, Atlanta.

He cited the case of a 60-year-old woman whose “off” periods confined her to a wheelchair. She had sudden rapid cycling from virtual immobility to severe dyskinesia that made it difficult to breathe, and reported a fever of 101° F for 3 days. In the ED, she displayed decreased breath sounds and crackles on the left side. A chest radiograph confirmed lower left lobe pneumonia. She responded well to intravenous antibiotics and fluids, but the dyskinetic cycling continued despite holding her carbidopa-levodopa and decreasing her pergolide by half. Only after 48 hours, when she became afebrile and the pneumonia had improved, was it possible to restart her medication, Dr. Factor said.

A second patient arrived at the ED short of breath, dehydrated, and diaphoretic, with a sudden, severe escalation of choreiform dyskinesia that had been going on for several hours. His leg movements were so extreme, he had severe bruising from hitting them against the bed rails in the ED. His creatine kinase was more than 21,000 U/L, and his white blood cell count was elevated. Questioning revealed he'd taken extra carbidopa-levodopa. “He had planned on going dancing that night and he didn't want to go 'off',” Dr. Factor said. In the ED, his medications were withheld for 12 hours, and he received intravenous fluids. He was discharged when his creatine kinase was normal, and restarted his drugs.

“People who self-medicate love to be 'on,' even if it increases their dyskinesia,” Dr. Factor said. “It's so much better than the alternative for them.” Patients may have run out of their drugs, or recently added a new drug that was increased too rapidly or stopped suddenly.

Psychiatric symptoms also cause patients to change their drug regimen, he added, citing the case of a woman with Parkinson's-related psychosis. She'd been prescribed 100 mg/day of quetiapine after a suicide attempt, but the dose was cut to 50 mg several years later. After the drop, “she heard the voice of God telling her to stop her medications, and became severely immobile,” Dr. Factor said. Psychiatric symptoms resolved after quetiapine was increased from 50 mg to 400 mg.

Abrupt stop of dopaminergic medications can lead to Parkinson's hyperpyrexia syndrome (PHS). Its clinical features are nearly identical to neuroleptic malignant syndrome: severe rigidity with tremor progressing to immobility. Within 72–96 hours, most patients develop fever (up to 107° F) and altered state of consciousness (from agitation and confusion to stupor and coma), plus autonomic dysregulation (tachycardia, tachypnea, labile blood pressure, urinary incontinence, or diaphoresis). There will always be leukocytosis and elevated creatine kinase. PHS is rare but serious—about 30% don't fully recover, and about 4% die.

PHS is usually tied to abrupt stop of drugs, including drug holidays, noncompliance, unsure diagnosis, or sudden alteration of drug regimen.

Tips for Calming Patients' Motor Fluctuations

The primary goal should always be to identify and treat any constitutional illness, said Dr. Stewart Factor. But if no underlying illness is present, drug therapy must be focused on breaking the motor cycle and then tailoring medical therapy to the patient's needs.

“Alteration in Parkinson's medications must be individualized with the goal of trying to maintain a more constant peripheral level of levodopa,” he said.

For prolonged “off” periods, consider the following approaches:

▸ Use more frequent carbidopa-levodopa (C/L) doses.

▸ Make quick-absorb C/L by dissolving tablets in tap water with ascorbic acid and dividing into hourly doses.

▸ Try adding a dopamine agonist.

▸ Use parenteral injection of apomorphine hydrochloride. “This drug when administered subcutaneously has a rapid onset, usually within 10 minutes, and a short duration of about 1 hour,” Dr. Factor said. “It has been used to rescue patients from intractable off periods, consistently improves off periods, and its effectiveness can be maintained for years.”

▸ Try controlled-release C/L.

For peak-dose choreiform dyskinesias, consider these strategies:

▸ Lower the dose of C/L or hold the medication until the symptoms improve.

▸ Try a mild sedative (lorazepam, alprazolam, or clonazepam) in the meantime. “This is particularly useful when dyskinesias are worse at night, and can be utilized in the ED while waiting for the dopaminergic medications to wear off,” he said.

▸ Controlled-release C/L may be a better choice, because its peak plasma level is lower than the standard formulation. This may worsen diphasic dyskinesias, however, especially if given in the evening.

▸ Do not give patients any of the typical neuroleptics such as haloperidol or prochlorperazine, because they can ultimately worsen Parkinson's.

BOSTON — Drug changes—by the physician or the patient—and infections are the most likely culprits behind motor fluctuations that land a patient with Parkinson's disease in the emergency department.

“The first thing to do is look for infections or other medical issues, and check to see if there have been any medication changes,” said Dr. Stewart Factor said at the annual meeting of the American Academy of Neurology.

Urinary tract or upper respiratory infections can trigger dyskinesias by altering the sensitivity to medication, said Dr. Factor of Emory University, Atlanta.

He cited the case of a 60-year-old woman whose “off” periods confined her to a wheelchair. She had sudden rapid cycling from virtual immobility to severe dyskinesia that made it difficult to breathe, and reported a fever of 101° F for 3 days. In the ED, she displayed decreased breath sounds and crackles on the left side. A chest radiograph confirmed lower left lobe pneumonia. She responded well to intravenous antibiotics and fluids, but the dyskinetic cycling continued despite holding her carbidopa-levodopa and decreasing her pergolide by half. Only after 48 hours, when she became afebrile and the pneumonia had improved, was it possible to restart her medication, Dr. Factor said.

A second patient arrived at the ED short of breath, dehydrated, and diaphoretic, with a sudden, severe escalation of choreiform dyskinesia that had been going on for several hours. His leg movements were so extreme, he had severe bruising from hitting them against the bed rails in the ED. His creatine kinase was more than 21,000 U/L, and his white blood cell count was elevated. Questioning revealed he'd taken extra carbidopa-levodopa. “He had planned on going dancing that night and he didn't want to go 'off',” Dr. Factor said. In the ED, his medications were withheld for 12 hours, and he received intravenous fluids. He was discharged when his creatine kinase was normal, and restarted his drugs.

“People who self-medicate love to be 'on,' even if it increases their dyskinesia,” Dr. Factor said. “It's so much better than the alternative for them.” Patients may have run out of their drugs, or recently added a new drug that was increased too rapidly or stopped suddenly.

Psychiatric symptoms also cause patients to change their drug regimen, he added, citing the case of a woman with Parkinson's-related psychosis. She'd been prescribed 100 mg/day of quetiapine after a suicide attempt, but the dose was cut to 50 mg several years later. After the drop, “she heard the voice of God telling her to stop her medications, and became severely immobile,” Dr. Factor said. Psychiatric symptoms resolved after quetiapine was increased from 50 mg to 400 mg.

Abrupt stop of dopaminergic medications can lead to Parkinson's hyperpyrexia syndrome (PHS). Its clinical features are nearly identical to neuroleptic malignant syndrome: severe rigidity with tremor progressing to immobility. Within 72–96 hours, most patients develop fever (up to 107° F) and altered state of consciousness (from agitation and confusion to stupor and coma), plus autonomic dysregulation (tachycardia, tachypnea, labile blood pressure, urinary incontinence, or diaphoresis). There will always be leukocytosis and elevated creatine kinase. PHS is rare but serious—about 30% don't fully recover, and about 4% die.

PHS is usually tied to abrupt stop of drugs, including drug holidays, noncompliance, unsure diagnosis, or sudden alteration of drug regimen.

Tips for Calming Patients' Motor Fluctuations

The primary goal should always be to identify and treat any constitutional illness, said Dr. Stewart Factor. But if no underlying illness is present, drug therapy must be focused on breaking the motor cycle and then tailoring medical therapy to the patient's needs.

“Alteration in Parkinson's medications must be individualized with the goal of trying to maintain a more constant peripheral level of levodopa,” he said.

For prolonged “off” periods, consider the following approaches:

▸ Use more frequent carbidopa-levodopa (C/L) doses.

▸ Make quick-absorb C/L by dissolving tablets in tap water with ascorbic acid and dividing into hourly doses.

▸ Try adding a dopamine agonist.

▸ Use parenteral injection of apomorphine hydrochloride. “This drug when administered subcutaneously has a rapid onset, usually within 10 minutes, and a short duration of about 1 hour,” Dr. Factor said. “It has been used to rescue patients from intractable off periods, consistently improves off periods, and its effectiveness can be maintained for years.”

▸ Try controlled-release C/L.

For peak-dose choreiform dyskinesias, consider these strategies:

▸ Lower the dose of C/L or hold the medication until the symptoms improve.

▸ Try a mild sedative (lorazepam, alprazolam, or clonazepam) in the meantime. “This is particularly useful when dyskinesias are worse at night, and can be utilized in the ED while waiting for the dopaminergic medications to wear off,” he said.

▸ Controlled-release C/L may be a better choice, because its peak plasma level is lower than the standard formulation. This may worsen diphasic dyskinesias, however, especially if given in the evening.

▸ Do not give patients any of the typical neuroleptics such as haloperidol or prochlorperazine, because they can ultimately worsen Parkinson's.

BOSTON — Drug changes—by the physician or the patient—and infections are the most likely culprits behind motor fluctuations that land a patient with Parkinson's disease in the emergency department.

“The first thing to do is look for infections or other medical issues, and check to see if there have been any medication changes,” said Dr. Stewart Factor said at the annual meeting of the American Academy of Neurology.

Urinary tract or upper respiratory infections can trigger dyskinesias by altering the sensitivity to medication, said Dr. Factor of Emory University, Atlanta.

He cited the case of a 60-year-old woman whose “off” periods confined her to a wheelchair. She had sudden rapid cycling from virtual immobility to severe dyskinesia that made it difficult to breathe, and reported a fever of 101° F for 3 days. In the ED, she displayed decreased breath sounds and crackles on the left side. A chest radiograph confirmed lower left lobe pneumonia. She responded well to intravenous antibiotics and fluids, but the dyskinetic cycling continued despite holding her carbidopa-levodopa and decreasing her pergolide by half. Only after 48 hours, when she became afebrile and the pneumonia had improved, was it possible to restart her medication, Dr. Factor said.

A second patient arrived at the ED short of breath, dehydrated, and diaphoretic, with a sudden, severe escalation of choreiform dyskinesia that had been going on for several hours. His leg movements were so extreme, he had severe bruising from hitting them against the bed rails in the ED. His creatine kinase was more than 21,000 U/L, and his white blood cell count was elevated. Questioning revealed he'd taken extra carbidopa-levodopa. “He had planned on going dancing that night and he didn't want to go 'off',” Dr. Factor said. In the ED, his medications were withheld for 12 hours, and he received intravenous fluids. He was discharged when his creatine kinase was normal, and restarted his drugs.

“People who self-medicate love to be 'on,' even if it increases their dyskinesia,” Dr. Factor said. “It's so much better than the alternative for them.” Patients may have run out of their drugs, or recently added a new drug that was increased too rapidly or stopped suddenly.

Psychiatric symptoms also cause patients to change their drug regimen, he added, citing the case of a woman with Parkinson's-related psychosis. She'd been prescribed 100 mg/day of quetiapine after a suicide attempt, but the dose was cut to 50 mg several years later. After the drop, “she heard the voice of God telling her to stop her medications, and became severely immobile,” Dr. Factor said. Psychiatric symptoms resolved after quetiapine was increased from 50 mg to 400 mg.

Abrupt stop of dopaminergic medications can lead to Parkinson's hyperpyrexia syndrome (PHS). Its clinical features are nearly identical to neuroleptic malignant syndrome: severe rigidity with tremor progressing to immobility. Within 72–96 hours, most patients develop fever (up to 107° F) and altered state of consciousness (from agitation and confusion to stupor and coma), plus autonomic dysregulation (tachycardia, tachypnea, labile blood pressure, urinary incontinence, or diaphoresis). There will always be leukocytosis and elevated creatine kinase. PHS is rare but serious—about 30% don't fully recover, and about 4% die.

PHS is usually tied to abrupt stop of drugs, including drug holidays, noncompliance, unsure diagnosis, or sudden alteration of drug regimen.

Tips for Calming Patients' Motor Fluctuations

The primary goal should always be to identify and treat any constitutional illness, said Dr. Stewart Factor. But if no underlying illness is present, drug therapy must be focused on breaking the motor cycle and then tailoring medical therapy to the patient's needs.

“Alteration in Parkinson's medications must be individualized with the goal of trying to maintain a more constant peripheral level of levodopa,” he said.

For prolonged “off” periods, consider the following approaches:

▸ Use more frequent carbidopa-levodopa (C/L) doses.

▸ Make quick-absorb C/L by dissolving tablets in tap water with ascorbic acid and dividing into hourly doses.

▸ Try adding a dopamine agonist.

▸ Use parenteral injection of apomorphine hydrochloride. “This drug when administered subcutaneously has a rapid onset, usually within 10 minutes, and a short duration of about 1 hour,” Dr. Factor said. “It has been used to rescue patients from intractable off periods, consistently improves off periods, and its effectiveness can be maintained for years.”

▸ Try controlled-release C/L.

For peak-dose choreiform dyskinesias, consider these strategies:

▸ Lower the dose of C/L or hold the medication until the symptoms improve.

▸ Try a mild sedative (lorazepam, alprazolam, or clonazepam) in the meantime. “This is particularly useful when dyskinesias are worse at night, and can be utilized in the ED while waiting for the dopaminergic medications to wear off,” he said.

▸ Controlled-release C/L may be a better choice, because its peak plasma level is lower than the standard formulation. This may worsen diphasic dyskinesias, however, especially if given in the evening.

▸ Do not give patients any of the typical neuroleptics such as haloperidol or prochlorperazine, because they can ultimately worsen Parkinson's.

BOSTON — Botulinum toxin injections are significantly more effective than oral tizanidine in reducing muscle tone and normalizing the appearance of spastic upper limbs in patients who have experienced a stroke or traumatic brain injury.

In fact, Dr. David Simpson reported at the annual meeting of the American Academy of Neurology, tizanidine—a first-line therapy for cerebral spasticity—was significantly less effective than placebo, suggesting it's time for physicians “to reconsider our first-line treatment for these patients, “said Dr. Simpson, professor of neurology at the Mount Sinai School of Medicine, New York.

Allergan Inc. sponsored the trial; Dr. Simpson and some of his coinvestigators have received research support and personal compensation from the company.

He presented the initial results of an 18-week three-way study of botulinum toxin, tizanidine, and placebo in 60 patients with increased upper limb tone secondary to stroke or traumatic brain injury.

Patients were randomized to either botulinum toxin injection plus oral placebo; tizanidine plus placebo injections; or oral placebo-placebo injections. All botulinum toxin patients received a mandatory injection of 50 units in the wrist flexors; providers could also inject additional toxin in other upper limb muscles, at doses deemed therapeutic. The maximum botulinum exposure was 500 units. Dilutions above the elbow were 2 cm

Tizanidine was titrated according to the label indications: 4 mg/day, escalating 4 mg every 3–4 days based on frequent consultation and patient reaction, to a maximum of 36 mg/day. If adverse events occurred, patients were permitted to slow their titration.

At baseline, all patients had a modified Ashworth score of at least 3 (0 indicates normal tone, whereas 5 indicates rigidity). By week 3, patients receiving the toxin showed significantly more wrist flexor relaxation than the other groups (−1.25 vs. −0.25 for tizanidine and −0.67 for placebo). The results were similar at week 6. By week 18, the toxin group was moving back toward its baseline scores.

Finger tone was also significantly more improved in patients in the toxin group than in those in the tizanidine or placebo groups (−1.32 vs. −0.22 and −0.69).

“In fact, the placebo group did significantly better than the tizanidine group in both categories,” he said.

Only limb posture cosmesis was significantly improved in the Disability Assessment Score, he said. The greatest improvement occurred in the botulinum toxin group.

BOSTON — Botulinum toxin injections are significantly more effective than oral tizanidine in reducing muscle tone and normalizing the appearance of spastic upper limbs in patients who have experienced a stroke or traumatic brain injury.

In fact, Dr. David Simpson reported at the annual meeting of the American Academy of Neurology, tizanidine—a first-line therapy for cerebral spasticity—was significantly less effective than placebo, suggesting it's time for physicians “to reconsider our first-line treatment for these patients, “said Dr. Simpson, professor of neurology at the Mount Sinai School of Medicine, New York.

Allergan Inc. sponsored the trial; Dr. Simpson and some of his coinvestigators have received research support and personal compensation from the company.

He presented the initial results of an 18-week three-way study of botulinum toxin, tizanidine, and placebo in 60 patients with increased upper limb tone secondary to stroke or traumatic brain injury.

Patients were randomized to either botulinum toxin injection plus oral placebo; tizanidine plus placebo injections; or oral placebo-placebo injections. All botulinum toxin patients received a mandatory injection of 50 units in the wrist flexors; providers could also inject additional toxin in other upper limb muscles, at doses deemed therapeutic. The maximum botulinum exposure was 500 units. Dilutions above the elbow were 2 cm

Tizanidine was titrated according to the label indications: 4 mg/day, escalating 4 mg every 3–4 days based on frequent consultation and patient reaction, to a maximum of 36 mg/day. If adverse events occurred, patients were permitted to slow their titration.

At baseline, all patients had a modified Ashworth score of at least 3 (0 indicates normal tone, whereas 5 indicates rigidity). By week 3, patients receiving the toxin showed significantly more wrist flexor relaxation than the other groups (−1.25 vs. −0.25 for tizanidine and −0.67 for placebo). The results were similar at week 6. By week 18, the toxin group was moving back toward its baseline scores.

Finger tone was also significantly more improved in patients in the toxin group than in those in the tizanidine or placebo groups (−1.32 vs. −0.22 and −0.69).

“In fact, the placebo group did significantly better than the tizanidine group in both categories,” he said.

Only limb posture cosmesis was significantly improved in the Disability Assessment Score, he said. The greatest improvement occurred in the botulinum toxin group.

BOSTON — Botulinum toxin injections are significantly more effective than oral tizanidine in reducing muscle tone and normalizing the appearance of spastic upper limbs in patients who have experienced a stroke or traumatic brain injury.

In fact, Dr. David Simpson reported at the annual meeting of the American Academy of Neurology, tizanidine—a first-line therapy for cerebral spasticity—was significantly less effective than placebo, suggesting it's time for physicians “to reconsider our first-line treatment for these patients, “said Dr. Simpson, professor of neurology at the Mount Sinai School of Medicine, New York.

Allergan Inc. sponsored the trial; Dr. Simpson and some of his coinvestigators have received research support and personal compensation from the company.

He presented the initial results of an 18-week three-way study of botulinum toxin, tizanidine, and placebo in 60 patients with increased upper limb tone secondary to stroke or traumatic brain injury.

Patients were randomized to either botulinum toxin injection plus oral placebo; tizanidine plus placebo injections; or oral placebo-placebo injections. All botulinum toxin patients received a mandatory injection of 50 units in the wrist flexors; providers could also inject additional toxin in other upper limb muscles, at doses deemed therapeutic. The maximum botulinum exposure was 500 units. Dilutions above the elbow were 2 cm

Tizanidine was titrated according to the label indications: 4 mg/day, escalating 4 mg every 3–4 days based on frequent consultation and patient reaction, to a maximum of 36 mg/day. If adverse events occurred, patients were permitted to slow their titration.

At baseline, all patients had a modified Ashworth score of at least 3 (0 indicates normal tone, whereas 5 indicates rigidity). By week 3, patients receiving the toxin showed significantly more wrist flexor relaxation than the other groups (−1.25 vs. −0.25 for tizanidine and −0.67 for placebo). The results were similar at week 6. By week 18, the toxin group was moving back toward its baseline scores.

Finger tone was also significantly more improved in patients in the toxin group than in those in the tizanidine or placebo groups (−1.32 vs. −0.22 and −0.69).

“In fact, the placebo group did significantly better than the tizanidine group in both categories,” he said.

Only limb posture cosmesis was significantly improved in the Disability Assessment Score, he said. The greatest improvement occurred in the botulinum toxin group.

BOSTON — Two new data sets reinforce the recommendation to avoid valproate as a first-line therapy for any indication in women of childbearing years.

The findings, presented at the annual meeting of the American Academy of Neurology, strengthen evidence of a link between valproate and major congenital malformations as well as impaired cognitive development of children exposed in utero.

“Not only our study, but nine other studies on valproate's anatomical and behavioral effects, have shown similar signals of poor outcome with this drug,” Dr. Kimford J Meador said. “The drug should not be a first-line therapy for any indication in women of childbearing age. At the very minimum, women need to be aware of these risks if they are going to take this drug. We need to remember that half of U.S. pregnancies are unplanned.”

Dr. Meador, the Melvin Greer Professor of Neurology and director of the epilepsy program at the University of Florida, Gainesville, presented interim data from the ongoing Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study for which investigators enrolled 185 children whose mothers took carbamazepine (48), lamotrigine (66), phenytoin (42), or valproate (29) for epilepsy during pregnancy.

Dr. Meador presented data on patients' mental development at age 2 years; the prospective study will follow the cohort to age 6. Mean IQ scores based on the Mental Development Index (MDI) from the Bayley Scale were lowest for children in the valproate group (81), Dr. Meador said. A score below 85 is considered to be below normal limits. Mean scores in the other groups were 94 for lamotrigine, 95 for phenytoin, and 96 for carbamazepine.

In addition, he said, the percentage of children in the valproate group with an MDI of less than 70 (correlating with mental retardation) was 24%, about double that seen in any of the other groups (carbamazepine, 13%; lamotrigine, 11%; and phenytoin, 12%).

The study also found an inverse relationship between maternal valproate blood levels during pregnancy and MDI scores in the children, Dr. Meador noted. All of the valproate relationships remained constant even after maternal IQ—an important driver of childhood IQ—maternal epilepsy type, and past medical history were controlled for.

The mechanism of brain injury in the valproate group is probably third-trimester neuronal apoptosis, Dr. Meador said in an interview. “We think it's similar to what's seen in fetal alcohol syndrome, and the apoptosis appears to occur at a relatively lower dose than it would with other drugs, such as phenytoin. I think that's why we see such an increased signal.”

NEAD only includes children of women with epilepsy—the group that accounts for the smallest proportion of valproate prescriptions, he added. “Most of the prescriptions are written for other things. … [Fewer] than half are for epilepsy.”

In the third quarter of 2006, about 16% of women of childbearing age with epilepsy were taking the drug, making it the fourth leading antiepileptic in the United States for this group. Valproate sales jumped 28% last year, an increase “that has to include some portion of women of childbearing age,” Dr. Meador said.

The second study, GlaxoSmithKline's lamotrigine pregnancy registry, found that valproate in conjunction with lamotrigine significantly increases the risk of a major birth defect. The company produces lamotrigine. The registry, now in its 14th year, has prospectively enrolled 2,400 pregnancies occurring in 32 countries. There are known outcome data on 1,539 pregnancies, said Marianne Cunnington, Ph.D., of GlaxoSmithKline.

The risk of a major birth defect in the 908 first-trimester exposures to lamotrigine only was 2.9%, similar to the background population risk of 2%–3%. The risk associated with nonvalproate polytherapy was 2.6%. But when lamotrigine polytherapy included valproate, the risk of a major congenital malformation jumped to more than 11%. “We have a signal for an increased risk for polytherapy including valproate,” she said, although “it's unclear whether valproate is responsible for this increased risk.”

Dr. Meador noted, however, that six other studies have concluded that valproate significantly increases the risk of birth defects. “Each of these studies has different cohorts, but [investigators] all found similar rates.”

BOSTON — Two new data sets reinforce the recommendation to avoid valproate as a first-line therapy for any indication in women of childbearing years.

The findings, presented at the annual meeting of the American Academy of Neurology, strengthen evidence of a link between valproate and major congenital malformations as well as impaired cognitive development of children exposed in utero.

“Not only our study, but nine other studies on valproate's anatomical and behavioral effects, have shown similar signals of poor outcome with this drug,” Dr. Kimford J Meador said. “The drug should not be a first-line therapy for any indication in women of childbearing age. At the very minimum, women need to be aware of these risks if they are going to take this drug. We need to remember that half of U.S. pregnancies are unplanned.”

Dr. Meador, the Melvin Greer Professor of Neurology and director of the epilepsy program at the University of Florida, Gainesville, presented interim data from the ongoing Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study for which investigators enrolled 185 children whose mothers took carbamazepine (48), lamotrigine (66), phenytoin (42), or valproate (29) for epilepsy during pregnancy.

Dr. Meador presented data on patients' mental development at age 2 years; the prospective study will follow the cohort to age 6. Mean IQ scores based on the Mental Development Index (MDI) from the Bayley Scale were lowest for children in the valproate group (81), Dr. Meador said. A score below 85 is considered to be below normal limits. Mean scores in the other groups were 94 for lamotrigine, 95 for phenytoin, and 96 for carbamazepine.

In addition, he said, the percentage of children in the valproate group with an MDI of less than 70 (correlating with mental retardation) was 24%, about double that seen in any of the other groups (carbamazepine, 13%; lamotrigine, 11%; and phenytoin, 12%).

The study also found an inverse relationship between maternal valproate blood levels during pregnancy and MDI scores in the children, Dr. Meador noted. All of the valproate relationships remained constant even after maternal IQ—an important driver of childhood IQ—maternal epilepsy type, and past medical history were controlled for.

The mechanism of brain injury in the valproate group is probably third-trimester neuronal apoptosis, Dr. Meador said in an interview. “We think it's similar to what's seen in fetal alcohol syndrome, and the apoptosis appears to occur at a relatively lower dose than it would with other drugs, such as phenytoin. I think that's why we see such an increased signal.”

NEAD only includes children of women with epilepsy—the group that accounts for the smallest proportion of valproate prescriptions, he added. “Most of the prescriptions are written for other things. … [Fewer] than half are for epilepsy.”

In the third quarter of 2006, about 16% of women of childbearing age with epilepsy were taking the drug, making it the fourth leading antiepileptic in the United States for this group. Valproate sales jumped 28% last year, an increase “that has to include some portion of women of childbearing age,” Dr. Meador said.

The second study, GlaxoSmithKline's lamotrigine pregnancy registry, found that valproate in conjunction with lamotrigine significantly increases the risk of a major birth defect. The company produces lamotrigine. The registry, now in its 14th year, has prospectively enrolled 2,400 pregnancies occurring in 32 countries. There are known outcome data on 1,539 pregnancies, said Marianne Cunnington, Ph.D., of GlaxoSmithKline.

The risk of a major birth defect in the 908 first-trimester exposures to lamotrigine only was 2.9%, similar to the background population risk of 2%–3%. The risk associated with nonvalproate polytherapy was 2.6%. But when lamotrigine polytherapy included valproate, the risk of a major congenital malformation jumped to more than 11%. “We have a signal for an increased risk for polytherapy including valproate,” she said, although “it's unclear whether valproate is responsible for this increased risk.”

Dr. Meador noted, however, that six other studies have concluded that valproate significantly increases the risk of birth defects. “Each of these studies has different cohorts, but [investigators] all found similar rates.”

BOSTON — Two new data sets reinforce the recommendation to avoid valproate as a first-line therapy for any indication in women of childbearing years.

The findings, presented at the annual meeting of the American Academy of Neurology, strengthen evidence of a link between valproate and major congenital malformations as well as impaired cognitive development of children exposed in utero.

“Not only our study, but nine other studies on valproate's anatomical and behavioral effects, have shown similar signals of poor outcome with this drug,” Dr. Kimford J Meador said. “The drug should not be a first-line therapy for any indication in women of childbearing age. At the very minimum, women need to be aware of these risks if they are going to take this drug. We need to remember that half of U.S. pregnancies are unplanned.”

Dr. Meador, the Melvin Greer Professor of Neurology and director of the epilepsy program at the University of Florida, Gainesville, presented interim data from the ongoing Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study for which investigators enrolled 185 children whose mothers took carbamazepine (48), lamotrigine (66), phenytoin (42), or valproate (29) for epilepsy during pregnancy.

Dr. Meador presented data on patients' mental development at age 2 years; the prospective study will follow the cohort to age 6. Mean IQ scores based on the Mental Development Index (MDI) from the Bayley Scale were lowest for children in the valproate group (81), Dr. Meador said. A score below 85 is considered to be below normal limits. Mean scores in the other groups were 94 for lamotrigine, 95 for phenytoin, and 96 for carbamazepine.

In addition, he said, the percentage of children in the valproate group with an MDI of less than 70 (correlating with mental retardation) was 24%, about double that seen in any of the other groups (carbamazepine, 13%; lamotrigine, 11%; and phenytoin, 12%).

The study also found an inverse relationship between maternal valproate blood levels during pregnancy and MDI scores in the children, Dr. Meador noted. All of the valproate relationships remained constant even after maternal IQ—an important driver of childhood IQ—maternal epilepsy type, and past medical history were controlled for.

The mechanism of brain injury in the valproate group is probably third-trimester neuronal apoptosis, Dr. Meador said in an interview. “We think it's similar to what's seen in fetal alcohol syndrome, and the apoptosis appears to occur at a relatively lower dose than it would with other drugs, such as phenytoin. I think that's why we see such an increased signal.”

NEAD only includes children of women with epilepsy—the group that accounts for the smallest proportion of valproate prescriptions, he added. “Most of the prescriptions are written for other things. … [Fewer] than half are for epilepsy.”

In the third quarter of 2006, about 16% of women of childbearing age with epilepsy were taking the drug, making it the fourth leading antiepileptic in the United States for this group. Valproate sales jumped 28% last year, an increase “that has to include some portion of women of childbearing age,” Dr. Meador said.

The second study, GlaxoSmithKline's lamotrigine pregnancy registry, found that valproate in conjunction with lamotrigine significantly increases the risk of a major birth defect. The company produces lamotrigine. The registry, now in its 14th year, has prospectively enrolled 2,400 pregnancies occurring in 32 countries. There are known outcome data on 1,539 pregnancies, said Marianne Cunnington, Ph.D., of GlaxoSmithKline.

The risk of a major birth defect in the 908 first-trimester exposures to lamotrigine only was 2.9%, similar to the background population risk of 2%–3%. The risk associated with nonvalproate polytherapy was 2.6%. But when lamotrigine polytherapy included valproate, the risk of a major congenital malformation jumped to more than 11%. “We have a signal for an increased risk for polytherapy including valproate,” she said, although “it's unclear whether valproate is responsible for this increased risk.”

Dr. Meador noted, however, that six other studies have concluded that valproate significantly increases the risk of birth defects. “Each of these studies has different cohorts, but [investigators] all found similar rates.”

BOSTON — Despite high hopes for success, a phase III trial of the first medical therapy for intracerebral hemorrhage showed that the drug was no better than placebo in improving rates of death or disability 3 months after the bleed occurred.

Although recombinant activated factor VII (rFVIIa) reduced hematoma growth by up to 50% more than placebo, neither of the doses tested in the Recombinant Factor VII in Acute Intracerebral Hemorrhage Trial (FAST) improved rates of mortality or severe disability, Dr. Stephan Mayer said at the annual meeting of the American Academy of Neurology.

The results are an enormous disappointment to researchers and clinicians who felt that the drug's stellar phase IIB trial results showcased its potential to stop intracerebral bleeding and improve the dismal chances of patients who experience such an event. “In its phase IIB study, the drug created such a tremendous improvement that it almost seemed too good to be true,” with those in the active groups 38% less likely to die than those taking placebo, Dr. Mayer said. “And in fact, in this larger phase III trial, we found out that it was.”

The phase III FAST trial was conducted in 26 countries and randomized 841 patients to placebo or rFVIIa in doses of 20 or 80 mcg/kg. As in the earlier trial, patients had to receive the drugs no more than 4 hours after the onset of symptoms. The FAST demographics were fairly well matched, Dr. Mayer said, with two notable exceptions. There were significantly fewer intraventricular hemorrhages in the placebo group (29% vs. 35% in the 20-mcg and 41% in the 80-mcg groups). Left ventricular hypertrophy was also more prevalent in the treatment groups than in the placebo group, said Dr. Mayer, director of the neurologic intensive care unit at the Columbia-Presbyterian campus of the New York Presbyterian Hospital, and a principal investigator in the FAST study.

However, the mean time from symptom onset to treatment was identical in all groups (109 minutes), and almost all patients were treated within the 4-hour time frame (20% within 2 hours and 75% within 3 hours of symptom onset).

Safety was good, he said. The overall prevalence of thromboembolic events was no different among the groups (11% in placebo and the 20-mcg group, and 13% in the 80-mcg group). The frequency of venous thromboembolic events was similar (6% in placebo and 5% in each of the active groups), but arterial events were slightly more common in the 80-mcg group (10% vs. 6% in the 20-mcg group and 5% in the placebo group).

The increase in arterial events in the 80-mcg group was driven by a slight increase in myocardial ischemia and cerebral infarction during the first few days of dosing, Dr. Mayer said. “However, the total number of deaths among these patients was similar between groups, with two in the placebo group, four in the 20-mcg group, and five in the 80-mcg group.”

Thromboembolic events occurred slightly sooner in the 80-mcg group as well, he said.

The drug successfully decreased bleeding by 24 hours in the active groups. The placebo group had a mean increase of 26% in hematoma volume, whereas the increase was 18% in the 20-mcg group and 11% in the 80-mcg group. The absolute increase in hematoma volume by 24 hours was 7.6 mL in the placebo group, 4.7 mL in the 20-mcg group, and 3.8 mL in the 80-mcg group. “In terms of bleeding we essentially replicated our findings from the earlier trial,” Dr. Mayer said. “There was a highly statistically significant difference between placebo and the 80-mcg/kg group.” The study also determined that patients treated earlier experienced greater reductions in hematoma volume growth than those treated later.

However, the changes in bleeding did not translate into any significant improvements in clinical outcome. At 3 months, mortality was 19% in the placebo group, 18% in the 20-mcg group, and 21% in the 80-mcg group.

The combined end point of death or severe disability (a score of 5 or 6 on the Modified Rankin Scale) was not different among groups (24% in the placebo group, 26% in the 20-mcg group, and 29% in the 80-mcg group). “Actually, the 80-mcg group had slightly, but not statistically significant, higher odds of having a bad outcome than the placebo group did,” Dr. Mayer pointed out.

At the end of the trial, only 20% of the patients in each group were free from disability.

“In the first 2 weeks (of the phase III study), we did see greater mortality in the placebo group, but by the completion of the study, this effect was lost. The early deaths were directly tied to the neurologic event, including withdrawal of life support and brain death. After 15 days, the deaths we saw were more often related to comorbid illnesses, and they occurred mostly in our more elderly patients.”

BOSTON — Despite high hopes for success, a phase III trial of the first medical therapy for intracerebral hemorrhage showed that the drug was no better than placebo in improving rates of death or disability 3 months after the bleed occurred.

Although recombinant activated factor VII (rFVIIa) reduced hematoma growth by up to 50% more than placebo, neither of the doses tested in the Recombinant Factor VII in Acute Intracerebral Hemorrhage Trial (FAST) improved rates of mortality or severe disability, Dr. Stephan Mayer said at the annual meeting of the American Academy of Neurology.

The results are an enormous disappointment to researchers and clinicians who felt that the drug's stellar phase IIB trial results showcased its potential to stop intracerebral bleeding and improve the dismal chances of patients who experience such an event. “In its phase IIB study, the drug created such a tremendous improvement that it almost seemed too good to be true,” with those in the active groups 38% less likely to die than those taking placebo, Dr. Mayer said. “And in fact, in this larger phase III trial, we found out that it was.”

The phase III FAST trial was conducted in 26 countries and randomized 841 patients to placebo or rFVIIa in doses of 20 or 80 mcg/kg. As in the earlier trial, patients had to receive the drugs no more than 4 hours after the onset of symptoms. The FAST demographics were fairly well matched, Dr. Mayer said, with two notable exceptions. There were significantly fewer intraventricular hemorrhages in the placebo group (29% vs. 35% in the 20-mcg and 41% in the 80-mcg groups). Left ventricular hypertrophy was also more prevalent in the treatment groups than in the placebo group, said Dr. Mayer, director of the neurologic intensive care unit at the Columbia-Presbyterian campus of the New York Presbyterian Hospital, and a principal investigator in the FAST study.

However, the mean time from symptom onset to treatment was identical in all groups (109 minutes), and almost all patients were treated within the 4-hour time frame (20% within 2 hours and 75% within 3 hours of symptom onset).

Safety was good, he said. The overall prevalence of thromboembolic events was no different among the groups (11% in placebo and the 20-mcg group, and 13% in the 80-mcg group). The frequency of venous thromboembolic events was similar (6% in placebo and 5% in each of the active groups), but arterial events were slightly more common in the 80-mcg group (10% vs. 6% in the 20-mcg group and 5% in the placebo group).

The increase in arterial events in the 80-mcg group was driven by a slight increase in myocardial ischemia and cerebral infarction during the first few days of dosing, Dr. Mayer said. “However, the total number of deaths among these patients was similar between groups, with two in the placebo group, four in the 20-mcg group, and five in the 80-mcg group.”

Thromboembolic events occurred slightly sooner in the 80-mcg group as well, he said.

The drug successfully decreased bleeding by 24 hours in the active groups. The placebo group had a mean increase of 26% in hematoma volume, whereas the increase was 18% in the 20-mcg group and 11% in the 80-mcg group. The absolute increase in hematoma volume by 24 hours was 7.6 mL in the placebo group, 4.7 mL in the 20-mcg group, and 3.8 mL in the 80-mcg group. “In terms of bleeding we essentially replicated our findings from the earlier trial,” Dr. Mayer said. “There was a highly statistically significant difference between placebo and the 80-mcg/kg group.” The study also determined that patients treated earlier experienced greater reductions in hematoma volume growth than those treated later.

However, the changes in bleeding did not translate into any significant improvements in clinical outcome. At 3 months, mortality was 19% in the placebo group, 18% in the 20-mcg group, and 21% in the 80-mcg group.

The combined end point of death or severe disability (a score of 5 or 6 on the Modified Rankin Scale) was not different among groups (24% in the placebo group, 26% in the 20-mcg group, and 29% in the 80-mcg group). “Actually, the 80-mcg group had slightly, but not statistically significant, higher odds of having a bad outcome than the placebo group did,” Dr. Mayer pointed out.

At the end of the trial, only 20% of the patients in each group were free from disability.

“In the first 2 weeks (of the phase III study), we did see greater mortality in the placebo group, but by the completion of the study, this effect was lost. The early deaths were directly tied to the neurologic event, including withdrawal of life support and brain death. After 15 days, the deaths we saw were more often related to comorbid illnesses, and they occurred mostly in our more elderly patients.”

BOSTON — Despite high hopes for success, a phase III trial of the first medical therapy for intracerebral hemorrhage showed that the drug was no better than placebo in improving rates of death or disability 3 months after the bleed occurred.

Although recombinant activated factor VII (rFVIIa) reduced hematoma growth by up to 50% more than placebo, neither of the doses tested in the Recombinant Factor VII in Acute Intracerebral Hemorrhage Trial (FAST) improved rates of mortality or severe disability, Dr. Stephan Mayer said at the annual meeting of the American Academy of Neurology.

The results are an enormous disappointment to researchers and clinicians who felt that the drug's stellar phase IIB trial results showcased its potential to stop intracerebral bleeding and improve the dismal chances of patients who experience such an event. “In its phase IIB study, the drug created such a tremendous improvement that it almost seemed too good to be true,” with those in the active groups 38% less likely to die than those taking placebo, Dr. Mayer said. “And in fact, in this larger phase III trial, we found out that it was.”

The phase III FAST trial was conducted in 26 countries and randomized 841 patients to placebo or rFVIIa in doses of 20 or 80 mcg/kg. As in the earlier trial, patients had to receive the drugs no more than 4 hours after the onset of symptoms. The FAST demographics were fairly well matched, Dr. Mayer said, with two notable exceptions. There were significantly fewer intraventricular hemorrhages in the placebo group (29% vs. 35% in the 20-mcg and 41% in the 80-mcg groups). Left ventricular hypertrophy was also more prevalent in the treatment groups than in the placebo group, said Dr. Mayer, director of the neurologic intensive care unit at the Columbia-Presbyterian campus of the New York Presbyterian Hospital, and a principal investigator in the FAST study.

However, the mean time from symptom onset to treatment was identical in all groups (109 minutes), and almost all patients were treated within the 4-hour time frame (20% within 2 hours and 75% within 3 hours of symptom onset).

Safety was good, he said. The overall prevalence of thromboembolic events was no different among the groups (11% in placebo and the 20-mcg group, and 13% in the 80-mcg group). The frequency of venous thromboembolic events was similar (6% in placebo and 5% in each of the active groups), but arterial events were slightly more common in the 80-mcg group (10% vs. 6% in the 20-mcg group and 5% in the placebo group).

The increase in arterial events in the 80-mcg group was driven by a slight increase in myocardial ischemia and cerebral infarction during the first few days of dosing, Dr. Mayer said. “However, the total number of deaths among these patients was similar between groups, with two in the placebo group, four in the 20-mcg group, and five in the 80-mcg group.”

Thromboembolic events occurred slightly sooner in the 80-mcg group as well, he said.

The drug successfully decreased bleeding by 24 hours in the active groups. The placebo group had a mean increase of 26% in hematoma volume, whereas the increase was 18% in the 20-mcg group and 11% in the 80-mcg group. The absolute increase in hematoma volume by 24 hours was 7.6 mL in the placebo group, 4.7 mL in the 20-mcg group, and 3.8 mL in the 80-mcg group. “In terms of bleeding we essentially replicated our findings from the earlier trial,” Dr. Mayer said. “There was a highly statistically significant difference between placebo and the 80-mcg/kg group.” The study also determined that patients treated earlier experienced greater reductions in hematoma volume growth than those treated later.

However, the changes in bleeding did not translate into any significant improvements in clinical outcome. At 3 months, mortality was 19% in the placebo group, 18% in the 20-mcg group, and 21% in the 80-mcg group.

The combined end point of death or severe disability (a score of 5 or 6 on the Modified Rankin Scale) was not different among groups (24% in the placebo group, 26% in the 20-mcg group, and 29% in the 80-mcg group). “Actually, the 80-mcg group had slightly, but not statistically significant, higher odds of having a bad outcome than the placebo group did,” Dr. Mayer pointed out.

At the end of the trial, only 20% of the patients in each group were free from disability.

“In the first 2 weeks (of the phase III study), we did see greater mortality in the placebo group, but by the completion of the study, this effect was lost. The early deaths were directly tied to the neurologic event, including withdrawal of life support and brain death. After 15 days, the deaths we saw were more often related to comorbid illnesses, and they occurred mostly in our more elderly patients.”

WASHINGTON — Door-to-balloon times are significantly longer for those whose heart attacks land them in the emergency department after regular working hours than if they arrive during a weekday, Dr. Nowwar Mustafa said at a conference sponsored by the American Heart Association.

Despite presenting at a hospital with a round-the-clock cardiac catheterization lab, night and weekend patients still experienced significant delays in receiving percutaneous coronary intervention (PCI), compared with weekday patients, said Dr. Mustafa, of Christiana Hospital, Newark, Del.

Dr. Mustafa identified three periods of crucial delay in assessing and treating patients who arrived from 7 p.m. to 7 a.m. on a weeknight or from 7 p.m. on a Friday to 7 a.m. the following Monday. “The only time in which there was no significant delay compared to weekday patients was their time to first EKG,” he said. “At every other time interval the differences were significantly longer.”

He retrospectively analyzed time delays for 893 consecutive patients who presented to the hospital's emergency department with ST-segment elevation myocardial infarction during 2002–2006. All received emergent PCI. The mean door-to balloon time was 85 minutes, and 67% of the group fell within the recommended 90-minute treatment window.

He measured four time intervals: door to first ECG; first ECG to treatment decision; treatment decision to leaving the emergency department (ED); and leaving the ED to balloon inflation.

The time to first ECG was not significantly different between those who arrived during regular hours and those who did not (9.5 minutes vs. 8 minutes). At all other intervals, patients who arrived after-hours were significantly delayed: ECG to decision, 20 vs. 16 minutes; decision to leaving the ED, 15 vs. 10 minutes; and leaving the ED to balloon inflation, 48 vs. 42 minutes.

Those delays added up, Dr. Mustafa said. The mean door-to-balloon time was significantly longer in the off-hours group (92 vs. 78 minutes). The portion of those who fell within the 90-minute treatment window was also significantly smaller (58% vs. 76%).

The hang-up appeared to be the time it took to get a cardiologist consult, he said. “During regular working hours the cath lab staff is in-house, and after working hours, the staff is on-call and ready to start the case within 30 minutes of notification. But the decision to take the patient to cath lab is made by the on-call cardiologist. During regular working hours, we have a cardiologist in-house, but this is not necessarily the case after hours.”

Dr. Mustafa will evaluate patient outcomes in these groups to determine whether the delays affected mortality.

But in a recent, separate study, delays in door-to-balloon time were associated with an increase of up to 60% in mortality (N. Engl. J. Med. 2007;356:1099–109). “The curves separated early, on the second day of hospitalization, and persisted for an entire year,” he said.

The after-hours hang-up appeared to be the time it took to get a cardiologist consult. DR. MUSTAFA

WASHINGTON — Door-to-balloon times are significantly longer for those whose heart attacks land them in the emergency department after regular working hours than if they arrive during a weekday, Dr. Nowwar Mustafa said at a conference sponsored by the American Heart Association.

Despite presenting at a hospital with a round-the-clock cardiac catheterization lab, night and weekend patients still experienced significant delays in receiving percutaneous coronary intervention (PCI), compared with weekday patients, said Dr. Mustafa, of Christiana Hospital, Newark, Del.

Dr. Mustafa identified three periods of crucial delay in assessing and treating patients who arrived from 7 p.m. to 7 a.m. on a weeknight or from 7 p.m. on a Friday to 7 a.m. the following Monday. “The only time in which there was no significant delay compared to weekday patients was their time to first EKG,” he said. “At every other time interval the differences were significantly longer.”

He retrospectively analyzed time delays for 893 consecutive patients who presented to the hospital's emergency department with ST-segment elevation myocardial infarction during 2002–2006. All received emergent PCI. The mean door-to balloon time was 85 minutes, and 67% of the group fell within the recommended 90-minute treatment window.

He measured four time intervals: door to first ECG; first ECG to treatment decision; treatment decision to leaving the emergency department (ED); and leaving the ED to balloon inflation.

The time to first ECG was not significantly different between those who arrived during regular hours and those who did not (9.5 minutes vs. 8 minutes). At all other intervals, patients who arrived after-hours were significantly delayed: ECG to decision, 20 vs. 16 minutes; decision to leaving the ED, 15 vs. 10 minutes; and leaving the ED to balloon inflation, 48 vs. 42 minutes.

Those delays added up, Dr. Mustafa said. The mean door-to-balloon time was significantly longer in the off-hours group (92 vs. 78 minutes). The portion of those who fell within the 90-minute treatment window was also significantly smaller (58% vs. 76%).

The hang-up appeared to be the time it took to get a cardiologist consult, he said. “During regular working hours the cath lab staff is in-house, and after working hours, the staff is on-call and ready to start the case within 30 minutes of notification. But the decision to take the patient to cath lab is made by the on-call cardiologist. During regular working hours, we have a cardiologist in-house, but this is not necessarily the case after hours.”

Dr. Mustafa will evaluate patient outcomes in these groups to determine whether the delays affected mortality.

But in a recent, separate study, delays in door-to-balloon time were associated with an increase of up to 60% in mortality (N. Engl. J. Med. 2007;356:1099–109). “The curves separated early, on the second day of hospitalization, and persisted for an entire year,” he said.

The after-hours hang-up appeared to be the time it took to get a cardiologist consult. DR. MUSTAFA

WASHINGTON — Door-to-balloon times are significantly longer for those whose heart attacks land them in the emergency department after regular working hours than if they arrive during a weekday, Dr. Nowwar Mustafa said at a conference sponsored by the American Heart Association.

Despite presenting at a hospital with a round-the-clock cardiac catheterization lab, night and weekend patients still experienced significant delays in receiving percutaneous coronary intervention (PCI), compared with weekday patients, said Dr. Mustafa, of Christiana Hospital, Newark, Del.

Dr. Mustafa identified three periods of crucial delay in assessing and treating patients who arrived from 7 p.m. to 7 a.m. on a weeknight or from 7 p.m. on a Friday to 7 a.m. the following Monday. “The only time in which there was no significant delay compared to weekday patients was their time to first EKG,” he said. “At every other time interval the differences were significantly longer.”

He retrospectively analyzed time delays for 893 consecutive patients who presented to the hospital's emergency department with ST-segment elevation myocardial infarction during 2002–2006. All received emergent PCI. The mean door-to balloon time was 85 minutes, and 67% of the group fell within the recommended 90-minute treatment window.

He measured four time intervals: door to first ECG; first ECG to treatment decision; treatment decision to leaving the emergency department (ED); and leaving the ED to balloon inflation.

The time to first ECG was not significantly different between those who arrived during regular hours and those who did not (9.5 minutes vs. 8 minutes). At all other intervals, patients who arrived after-hours were significantly delayed: ECG to decision, 20 vs. 16 minutes; decision to leaving the ED, 15 vs. 10 minutes; and leaving the ED to balloon inflation, 48 vs. 42 minutes.

Those delays added up, Dr. Mustafa said. The mean door-to-balloon time was significantly longer in the off-hours group (92 vs. 78 minutes). The portion of those who fell within the 90-minute treatment window was also significantly smaller (58% vs. 76%).

The hang-up appeared to be the time it took to get a cardiologist consult, he said. “During regular working hours the cath lab staff is in-house, and after working hours, the staff is on-call and ready to start the case within 30 minutes of notification. But the decision to take the patient to cath lab is made by the on-call cardiologist. During regular working hours, we have a cardiologist in-house, but this is not necessarily the case after hours.”

Dr. Mustafa will evaluate patient outcomes in these groups to determine whether the delays affected mortality.

But in a recent, separate study, delays in door-to-balloon time were associated with an increase of up to 60% in mortality (N. Engl. J. Med. 2007;356:1099–109). “The curves separated early, on the second day of hospitalization, and persisted for an entire year,” he said.

The after-hours hang-up appeared to be the time it took to get a cardiologist consult. DR. MUSTAFA

WASHINGTON — When it comes to recommending angioplasty for stable coronary artery disease, evidence can take a backseat to worry, guilt, and the fear of legal liability.

“It appears that both cardiologists and primary care physicians [PCPs] have trouble balancing these psychological and emotional factors with scientific evidence in decision making, and this leads them to recommending more tests and procedures,” which eventually culminate in a trip to the cardiac catheterization lab, Dr. Grace Lin said at a conference sponsored by the American Heart Association. Once there, if any lesions at all are identified, “the die is cast” for percutaneous coronary intervention (PCI), she said.

Dr. Lin drew these conclusions from a series of six focus-group meetings she held with 28 primary care providers and 20 cardiologists (13 interventional and 7 noninterventional). She presented each group with three case scenarios based on actual patients with symptoms of stable coronary artery disease (CAD), and asked the participants to describe how they would arrive at a treatment recommendation.

All of the physicians lived in California; their mean duration of practice was 17 years. To help identify any regional differences, she drew one-third from San Francisco, one-third from the city's suburbs, and one-third from a rural county.

“We also interviewed PCPs and cardiologists separately, to encourage frank discussion,” said Dr. Lin of the University of California, San Francisco.

Group discussions were set around three case scenarios representing minimally symptomatic or asymptomatic patients for whom the current evidence shows no benefit of PCI over optimal medical therapy. She described one of the cases: a 45-year-old male with a family history of myocardial infarction. The patient worked out three times each week and was asymptomatic. His wife, however, was worried about his family history and bought him a coronary calcium scan for his birthday. The scan showed a calcium score of 745.

His stress test showed ST-segment depressions of 1–2 mm. A catheterization revealed a tight lesion in the left anterior descending artery.

Dr. Lin asked the group to discuss a range of recommendations, from reassurance and risk reduction interventions to medical therapy, PCI, and coronary artery bypass grafting.

All of the physicians in each group ended up recommending PCI for all three of the hypothetical patients, Dr. Lin said—despite their acknowledgement that no clinical evidence supported the procedure as more beneficial than medical therapy in either the short or long term.

Several major themes emerged from the physician discussions: guilt over the possibility of missing a potentially lethal lesion, patient expectation of testing and intervention, and liability fears.

The fear of guilt arising from a missed lesion was a particularly strong motivator for more tests and interventions. One primary care physician spoke quite eloquently of this, said Dr. Lin. “I had a healthy 42-year-old who dropped dead while jogging. I'm always afraid of missing that widow-maker lesion.”

A cardiologist expressed a similar view. Despite the data suggesting that PCI is no better than medical therapy for these patients, “I don't think you can ignore a lesion, because then, if something happens, it's your fault.”

“This belief was shared by most of the physicians in our groups,” Dr. Lin said. “I think it demonstrates the tendency of physicians to look for solutions based on action.”

Interestingly, the participants stuck to their recommendations despite their intellectual understanding of the clinical evidence. According to one cardiologist, “I think we know we are not necessarily preventing heart attacks by treating asymptomatic stenosis with PCI. We are going to prevent future heart attacks with lipid-lowering drugs, aspirin, and ACE inhibitors. But nonetheless, when that patient leaves with an open artery—that is the best that my interventional partners can deliver.”

Physicians aren't alone in wanting some concrete action in these cases, Dr Lin said. “Patient expectations are a frequent reason for testing. Both our PCPs and cardiologists said their patients expected testing regardless of what they themselves thought of it.”

One cardiologist put it this way: “If the patient is worried enough to come in and see me, we need to do this testing to reassure him.”

Concerns about medicolegal liability also strongly influenced the decision making. A PCP noted, “We all would feel more comfortable treating more patients medically if we weren't afraid of being sued. With a jury of laypeople, it's hard to justify not stenting despite the evidence, and because of that it's hard to just treat medically and not be afraid of a lawsuit.”

Again, Dr Lin observed, physicians felt very strongly about this despite evidence to the contrary. “There are no data linking additional testing with fewer lawsuits.”

All of these factors “culminate in a cascade effect where screening leads to more testing and eventually to the cath lab,” she said, citing a PCP who referred to the hypothetical patient's elevated calcium load. “This guy's wife has bought him much more than a scan—she has bought him an entrée to the whole garden path of testing. Any equivocal test and he's ending up in the cath lab.”

“This demonstrates that once a patient has any positive screen, it's very difficult to prevent a referral to a cardiologist and eventually, to the cath lab,” Dr. Lin said. “Once he reaches there, the cardiologists told us that if any amenable lesion is found, that person is almost certain to get a PCI.”

The culture of the catheterization lab also plays into this inevitable progression. A cardiologist explained, “By this time the die is cast. In our practice, where we don't get paid per procedure, we would have difficulty getting out of the lab because the cath lab staff wouldn't let us out unless we did something with that lesion.”

The cascade of emotion and worry is what appears to drive the patient with stable CAD to a PCI, Dr. Lin said. Even balancing the possible complications of the procedure with the evidence that it probably yields no additional benefit wasn't enough to sway physicians to medical therapy alone.

“One cardiologist put it like this,” she said. “'If you do the procedure and there's a complication, that's a complication. But if you don't do it and there's an event—that's a mistake.'”

The study “demonstrates the tendency of physicians to look for solutions based on action,” said Dr. Grace Lin. Michele G. Sullivan/Elsevier Global Medical News

WASHINGTON — When it comes to recommending angioplasty for stable coronary artery disease, evidence can take a backseat to worry, guilt, and the fear of legal liability.

“It appears that both cardiologists and primary care physicians [PCPs] have trouble balancing these psychological and emotional factors with scientific evidence in decision making, and this leads them to recommending more tests and procedures,” which eventually culminate in a trip to the cardiac catheterization lab, Dr. Grace Lin said at a conference sponsored by the American Heart Association. Once there, if any lesions at all are identified, “the die is cast” for percutaneous coronary intervention (PCI), she said.

Dr. Lin drew these conclusions from a series of six focus-group meetings she held with 28 primary care providers and 20 cardiologists (13 interventional and 7 noninterventional). She presented each group with three case scenarios based on actual patients with symptoms of stable coronary artery disease (CAD), and asked the participants to describe how they would arrive at a treatment recommendation.

All of the physicians lived in California; their mean duration of practice was 17 years. To help identify any regional differences, she drew one-third from San Francisco, one-third from the city's suburbs, and one-third from a rural county.

“We also interviewed PCPs and cardiologists separately, to encourage frank discussion,” said Dr. Lin of the University of California, San Francisco.

Group discussions were set around three case scenarios representing minimally symptomatic or asymptomatic patients for whom the current evidence shows no benefit of PCI over optimal medical therapy. She described one of the cases: a 45-year-old male with a family history of myocardial infarction. The patient worked out three times each week and was asymptomatic. His wife, however, was worried about his family history and bought him a coronary calcium scan for his birthday. The scan showed a calcium score of 745.

His stress test showed ST-segment depressions of 1–2 mm. A catheterization revealed a tight lesion in the left anterior descending artery.

Dr. Lin asked the group to discuss a range of recommendations, from reassurance and risk reduction interventions to medical therapy, PCI, and coronary artery bypass grafting.

All of the physicians in each group ended up recommending PCI for all three of the hypothetical patients, Dr. Lin said—despite their acknowledgement that no clinical evidence supported the procedure as more beneficial than medical therapy in either the short or long term.

Several major themes emerged from the physician discussions: guilt over the possibility of missing a potentially lethal lesion, patient expectation of testing and intervention, and liability fears.

The fear of guilt arising from a missed lesion was a particularly strong motivator for more tests and interventions. One primary care physician spoke quite eloquently of this, said Dr. Lin. “I had a healthy 42-year-old who dropped dead while jogging. I'm always afraid of missing that widow-maker lesion.”

A cardiologist expressed a similar view. Despite the data suggesting that PCI is no better than medical therapy for these patients, “I don't think you can ignore a lesion, because then, if something happens, it's your fault.”

“This belief was shared by most of the physicians in our groups,” Dr. Lin said. “I think it demonstrates the tendency of physicians to look for solutions based on action.”

Interestingly, the participants stuck to their recommendations despite their intellectual understanding of the clinical evidence. According to one cardiologist, “I think we know we are not necessarily preventing heart attacks by treating asymptomatic stenosis with PCI. We are going to prevent future heart attacks with lipid-lowering drugs, aspirin, and ACE inhibitors. But nonetheless, when that patient leaves with an open artery—that is the best that my interventional partners can deliver.”

Physicians aren't alone in wanting some concrete action in these cases, Dr Lin said. “Patient expectations are a frequent reason for testing. Both our PCPs and cardiologists said their patients expected testing regardless of what they themselves thought of it.”

One cardiologist put it this way: “If the patient is worried enough to come in and see me, we need to do this testing to reassure him.”

Concerns about medicolegal liability also strongly influenced the decision making. A PCP noted, “We all would feel more comfortable treating more patients medically if we weren't afraid of being sued. With a jury of laypeople, it's hard to justify not stenting despite the evidence, and because of that it's hard to just treat medically and not be afraid of a lawsuit.”

Again, Dr Lin observed, physicians felt very strongly about this despite evidence to the contrary. “There are no data linking additional testing with fewer lawsuits.”

All of these factors “culminate in a cascade effect where screening leads to more testing and eventually to the cath lab,” she said, citing a PCP who referred to the hypothetical patient's elevated calcium load. “This guy's wife has bought him much more than a scan—she has bought him an entrée to the whole garden path of testing. Any equivocal test and he's ending up in the cath lab.”

“This demonstrates that once a patient has any positive screen, it's very difficult to prevent a referral to a cardiologist and eventually, to the cath lab,” Dr. Lin said. “Once he reaches there, the cardiologists told us that if any amenable lesion is found, that person is almost certain to get a PCI.”

The culture of the catheterization lab also plays into this inevitable progression. A cardiologist explained, “By this time the die is cast. In our practice, where we don't get paid per procedure, we would have difficulty getting out of the lab because the cath lab staff wouldn't let us out unless we did something with that lesion.”

The cascade of emotion and worry is what appears to drive the patient with stable CAD to a PCI, Dr. Lin said. Even balancing the possible complications of the procedure with the evidence that it probably yields no additional benefit wasn't enough to sway physicians to medical therapy alone.

“One cardiologist put it like this,” she said. “'If you do the procedure and there's a complication, that's a complication. But if you don't do it and there's an event—that's a mistake.'”

The study “demonstrates the tendency of physicians to look for solutions based on action,” said Dr. Grace Lin. Michele G. Sullivan/Elsevier Global Medical News

WASHINGTON — When it comes to recommending angioplasty for stable coronary artery disease, evidence can take a backseat to worry, guilt, and the fear of legal liability.

“It appears that both cardiologists and primary care physicians [PCPs] have trouble balancing these psychological and emotional factors with scientific evidence in decision making, and this leads them to recommending more tests and procedures,” which eventually culminate in a trip to the cardiac catheterization lab, Dr. Grace Lin said at a conference sponsored by the American Heart Association. Once there, if any lesions at all are identified, “the die is cast” for percutaneous coronary intervention (PCI), she said.

Dr. Lin drew these conclusions from a series of six focus-group meetings she held with 28 primary care providers and 20 cardiologists (13 interventional and 7 noninterventional). She presented each group with three case scenarios based on actual patients with symptoms of stable coronary artery disease (CAD), and asked the participants to describe how they would arrive at a treatment recommendation.

All of the physicians lived in California; their mean duration of practice was 17 years. To help identify any regional differences, she drew one-third from San Francisco, one-third from the city's suburbs, and one-third from a rural county.

“We also interviewed PCPs and cardiologists separately, to encourage frank discussion,” said Dr. Lin of the University of California, San Francisco.

Group discussions were set around three case scenarios representing minimally symptomatic or asymptomatic patients for whom the current evidence shows no benefit of PCI over optimal medical therapy. She described one of the cases: a 45-year-old male with a family history of myocardial infarction. The patient worked out three times each week and was asymptomatic. His wife, however, was worried about his family history and bought him a coronary calcium scan for his birthday. The scan showed a calcium score of 745.

His stress test showed ST-segment depressions of 1–2 mm. A catheterization revealed a tight lesion in the left anterior descending artery.

Dr. Lin asked the group to discuss a range of recommendations, from reassurance and risk reduction interventions to medical therapy, PCI, and coronary artery bypass grafting.

All of the physicians in each group ended up recommending PCI for all three of the hypothetical patients, Dr. Lin said—despite their acknowledgement that no clinical evidence supported the procedure as more beneficial than medical therapy in either the short or long term.

Several major themes emerged from the physician discussions: guilt over the possibility of missing a potentially lethal lesion, patient expectation of testing and intervention, and liability fears.

The fear of guilt arising from a missed lesion was a particularly strong motivator for more tests and interventions. One primary care physician spoke quite eloquently of this, said Dr. Lin. “I had a healthy 42-year-old who dropped dead while jogging. I'm always afraid of missing that widow-maker lesion.”

A cardiologist expressed a similar view. Despite the data suggesting that PCI is no better than medical therapy for these patients, “I don't think you can ignore a lesion, because then, if something happens, it's your fault.”

“This belief was shared by most of the physicians in our groups,” Dr. Lin said. “I think it demonstrates the tendency of physicians to look for solutions based on action.”

Interestingly, the participants stuck to their recommendations despite their intellectual understanding of the clinical evidence. According to one cardiologist, “I think we know we are not necessarily preventing heart attacks by treating asymptomatic stenosis with PCI. We are going to prevent future heart attacks with lipid-lowering drugs, aspirin, and ACE inhibitors. But nonetheless, when that patient leaves with an open artery—that is the best that my interventional partners can deliver.”

Physicians aren't alone in wanting some concrete action in these cases, Dr Lin said. “Patient expectations are a frequent reason for testing. Both our PCPs and cardiologists said their patients expected testing regardless of what they themselves thought of it.”

One cardiologist put it this way: “If the patient is worried enough to come in and see me, we need to do this testing to reassure him.”

Concerns about medicolegal liability also strongly influenced the decision making. A PCP noted, “We all would feel more comfortable treating more patients medically if we weren't afraid of being sued. With a jury of laypeople, it's hard to justify not stenting despite the evidence, and because of that it's hard to just treat medically and not be afraid of a lawsuit.”

Again, Dr Lin observed, physicians felt very strongly about this despite evidence to the contrary. “There are no data linking additional testing with fewer lawsuits.”

All of these factors “culminate in a cascade effect where screening leads to more testing and eventually to the cath lab,” she said, citing a PCP who referred to the hypothetical patient's elevated calcium load. “This guy's wife has bought him much more than a scan—she has bought him an entrée to the whole garden path of testing. Any equivocal test and he's ending up in the cath lab.”

“This demonstrates that once a patient has any positive screen, it's very difficult to prevent a referral to a cardiologist and eventually, to the cath lab,” Dr. Lin said. “Once he reaches there, the cardiologists told us that if any amenable lesion is found, that person is almost certain to get a PCI.”

The culture of the catheterization lab also plays into this inevitable progression. A cardiologist explained, “By this time the die is cast. In our practice, where we don't get paid per procedure, we would have difficulty getting out of the lab because the cath lab staff wouldn't let us out unless we did something with that lesion.”

The cascade of emotion and worry is what appears to drive the patient with stable CAD to a PCI, Dr. Lin said. Even balancing the possible complications of the procedure with the evidence that it probably yields no additional benefit wasn't enough to sway physicians to medical therapy alone.

“One cardiologist put it like this,” she said. “'If you do the procedure and there's a complication, that's a complication. But if you don't do it and there's an event—that's a mistake.'”

The study “demonstrates the tendency of physicians to look for solutions based on action,” said Dr. Grace Lin. Michele G. Sullivan/Elsevier Global Medical News

PHILADELPHIA — An “ah-ha!” moment can be the key to teen weight loss.

Adolescents who experience a “transformative event”—an experience that changes their self-concept with regard to weight or exercise—are apparently more likely to lose weight than are those who never undergo such a moment, Dr. Alexis Lieberman said at the annual meeting of the Eastern Society for Pediatric Research.

For some teens, the experience comes during a serious talk with a physician; for others, athletics is the motivating factor. But whatever the force behind the transformative event, she said, it appears to be a vital part of the weight loss experience.

Dr. Lieberman presented the results of a qualitative study of 22 teens, all black, inner city residents with a mean age of 16 years. All the teens had either gained or lost at least 2 kg/m

They participated in a series of structured interviews and focus group meetings, during which Dr. Lieberman and her colleagues explored important contributors to their weight change, including dietary habits, knowledge of healthy eating, finances and the impact of poverty, psychology, exercise, and home-school environment. The group included 10 weight increasers (six males and four females) with an average body mass index (BMI) of 38 kg/m

The groups had similarly poor dietary habits, she said. Both tended to skip breakfast, eat junk food instead of meals, and buy snacks at local convenience stores. Interestingly, they did have a good basic knowledge of what constitutes a healthy diet.

Poverty did not play as large a role as the researchers anticipated. While a lack of money did increase a teen's tendency to buy cheap, low-quality foods, it also forced many into the subsidized food programs at their schools. “Not having money meant they couldn't buy french fries in the cafeteria, and instead had to go to the free lunch line, where the food was supposedly healthier,” said Dr. Lieberman, a pediatrician at Albert Einstein Medical Center, Philadelphia.

Several important thematic differences emerged between the groups.

A transformative experience occurred in six of the weight decreasers and only two of the weight increasers. For several of the decreasers, the moment was a meeting with a physician, especially being told they were at risk of developing diabetes. Some related that prognosis to the same illness in a relative, and made a decision to change their own future.

For others, Dr. Lieberman said, the moment had to do with athletics. One teen was recruited from his recreation center basketball team to a traveling city team, and had to lose weight to stay on the team. Another girl joined the track team. Her coach advised her to improve her eating habits and lose weight because she had the potential to be a fast runner.

A violent experience changed the life of the final weight decreaser. He was almost “jumped,” and his grandfather then signed him up for a martial arts program at the local gym.

Transformative experiences also occurred in two teens who gained weight. One said his religious conversion allowed him to accept himself “as a big person.” Another teen learned she was a prediabetic, but wasn't able to make the changes necessary to lose weight.

Eight of the decreasers consistently engaged in intense physical activity (at least 2 hours each day of team sports or weight lifting), compared with only one of the increasers. “The one increaser who exercised was on a dance team that served doughnuts after practice.”

The decreasing group reported that family members tried to positively influence their diet. The teens who increased their weight, however, reported that they received support to accept their weight, with their family using euphemisms (“You're thick, not fat”) and telling them they “looked fine just as they were.”

Not having money meant they couldn't buy french fries, and instead had to go to the free lunch line. DR. LIEBERMAN

PHILADELPHIA — An “ah-ha!” moment can be the key to teen weight loss.

Adolescents who experience a “transformative event”—an experience that changes their self-concept with regard to weight or exercise—are apparently more likely to lose weight than are those who never undergo such a moment, Dr. Alexis Lieberman said at the annual meeting of the Eastern Society for Pediatric Research.

For some teens, the experience comes during a serious talk with a physician; for others, athletics is the motivating factor. But whatever the force behind the transformative event, she said, it appears to be a vital part of the weight loss experience.

Dr. Lieberman presented the results of a qualitative study of 22 teens, all black, inner city residents with a mean age of 16 years. All the teens had either gained or lost at least 2 kg/m

They participated in a series of structured interviews and focus group meetings, during which Dr. Lieberman and her colleagues explored important contributors to their weight change, including dietary habits, knowledge of healthy eating, finances and the impact of poverty, psychology, exercise, and home-school environment. The group included 10 weight increasers (six males and four females) with an average body mass index (BMI) of 38 kg/m

The groups had similarly poor dietary habits, she said. Both tended to skip breakfast, eat junk food instead of meals, and buy snacks at local convenience stores. Interestingly, they did have a good basic knowledge of what constitutes a healthy diet.

Poverty did not play as large a role as the researchers anticipated. While a lack of money did increase a teen's tendency to buy cheap, low-quality foods, it also forced many into the subsidized food programs at their schools. “Not having money meant they couldn't buy french fries in the cafeteria, and instead had to go to the free lunch line, where the food was supposedly healthier,” said Dr. Lieberman, a pediatrician at Albert Einstein Medical Center, Philadelphia.

Several important thematic differences emerged between the groups.

A transformative experience occurred in six of the weight decreasers and only two of the weight increasers. For several of the decreasers, the moment was a meeting with a physician, especially being told they were at risk of developing diabetes. Some related that prognosis to the same illness in a relative, and made a decision to change their own future.

For others, Dr. Lieberman said, the moment had to do with athletics. One teen was recruited from his recreation center basketball team to a traveling city team, and had to lose weight to stay on the team. Another girl joined the track team. Her coach advised her to improve her eating habits and lose weight because she had the potential to be a fast runner.

A violent experience changed the life of the final weight decreaser. He was almost “jumped,” and his grandfather then signed him up for a martial arts program at the local gym.

Transformative experiences also occurred in two teens who gained weight. One said his religious conversion allowed him to accept himself “as a big person.” Another teen learned she was a prediabetic, but wasn't able to make the changes necessary to lose weight.

Eight of the decreasers consistently engaged in intense physical activity (at least 2 hours each day of team sports or weight lifting), compared with only one of the increasers. “The one increaser who exercised was on a dance team that served doughnuts after practice.”

The decreasing group reported that family members tried to positively influence their diet. The teens who increased their weight, however, reported that they received support to accept their weight, with their family using euphemisms (“You're thick, not fat”) and telling them they “looked fine just as they were.”

Not having money meant they couldn't buy french fries, and instead had to go to the free lunch line. DR. LIEBERMAN

PHILADELPHIA — An “ah-ha!” moment can be the key to teen weight loss.

Adolescents who experience a “transformative event”—an experience that changes their self-concept with regard to weight or exercise—are apparently more likely to lose weight than are those who never undergo such a moment, Dr. Alexis Lieberman said at the annual meeting of the Eastern Society for Pediatric Research.

For some teens, the experience comes during a serious talk with a physician; for others, athletics is the motivating factor. But whatever the force behind the transformative event, she said, it appears to be a vital part of the weight loss experience.

Dr. Lieberman presented the results of a qualitative study of 22 teens, all black, inner city residents with a mean age of 16 years. All the teens had either gained or lost at least 2 kg/m

They participated in a series of structured interviews and focus group meetings, during which Dr. Lieberman and her colleagues explored important contributors to their weight change, including dietary habits, knowledge of healthy eating, finances and the impact of poverty, psychology, exercise, and home-school environment. The group included 10 weight increasers (six males and four females) with an average body mass index (BMI) of 38 kg/m

The groups had similarly poor dietary habits, she said. Both tended to skip breakfast, eat junk food instead of meals, and buy snacks at local convenience stores. Interestingly, they did have a good basic knowledge of what constitutes a healthy diet.

Poverty did not play as large a role as the researchers anticipated. While a lack of money did increase a teen's tendency to buy cheap, low-quality foods, it also forced many into the subsidized food programs at their schools. “Not having money meant they couldn't buy french fries in the cafeteria, and instead had to go to the free lunch line, where the food was supposedly healthier,” said Dr. Lieberman, a pediatrician at Albert Einstein Medical Center, Philadelphia.

Several important thematic differences emerged between the groups.

A transformative experience occurred in six of the weight decreasers and only two of the weight increasers. For several of the decreasers, the moment was a meeting with a physician, especially being told they were at risk of developing diabetes. Some related that prognosis to the same illness in a relative, and made a decision to change their own future.

For others, Dr. Lieberman said, the moment had to do with athletics. One teen was recruited from his recreation center basketball team to a traveling city team, and had to lose weight to stay on the team. Another girl joined the track team. Her coach advised her to improve her eating habits and lose weight because she had the potential to be a fast runner.

A violent experience changed the life of the final weight decreaser. He was almost “jumped,” and his grandfather then signed him up for a martial arts program at the local gym.

Transformative experiences also occurred in two teens who gained weight. One said his religious conversion allowed him to accept himself “as a big person.” Another teen learned she was a prediabetic, but wasn't able to make the changes necessary to lose weight.

Eight of the decreasers consistently engaged in intense physical activity (at least 2 hours each day of team sports or weight lifting), compared with only one of the increasers. “The one increaser who exercised was on a dance team that served doughnuts after practice.”

The decreasing group reported that family members tried to positively influence their diet. The teens who increased their weight, however, reported that they received support to accept their weight, with their family using euphemisms (“You're thick, not fat”) and telling them they “looked fine just as they were.”

Not having money meant they couldn't buy french fries, and instead had to go to the free lunch line. DR. LIEBERMAN

Small steps can lead to big changes when physicians use the power of a prescription pad to get patients up and exercising, experts say.

“There's nothing more frustrating to a patient than to be told bluntly, 'You need to exercise every day and lose 60 pounds,'” said Dr. Michael Fleming, past president of the American Academy of Family Physicians and someone who has struggled with obesity since childhood. “When someone told me that, I knew I was doomed. There was no way I could do it.”

Physicians share that defeatist attitude, he said in an interview. “It's incredibly frustrating to try to take care of someone who won't make lifestyle changes. And the frustration coming from both sides turns the patient off to whatever the doctor is trying to say.”

But change is possible, he said, and a recently published paper offers a valuable model for physicians who want to help their patients achieve it. “Helping Sedentary Patients Become More Active,” a case study and commentary by Dr. Caroline Richardson and her colleague Dr. Thomas Schwenk focuses on the power of incremental change (J. Clin. Outcomes Manage. 2007;14:161–71).

“The key to success, which this paper stresses, is the concept of taking small steps,” said Dr. Fleming, a former member of the advisory panel for the group Americans in Motion, an AAFP program that helps physicians promote fitness. “I can't start walking 10,000 steps a day tomorrow. But if someone suggests that I increase my walking by 2,500 steps a day, that's doable. I don't have to climb a mountain. Instead, I can go one hill at a time.”

Although patients may express frustration with their weight and exercise habits, most realize that they could benefit from change. At the same time, they doubt their ability to succeed. A pep talk about exercise and some vague dietary advice won't be strong enough to counteract that doubt. Instead, Dr. Richardson asserts, inactivity should be regarded as a potentially harmful condition that needs treatment. That treatment should include a physical exam with an assessment of the patient's current activity level, counseling that addresses barriers to change, and a prescription for addressing the problem.

The activity assessment should include questions about the frequency, duration, and intensity of daily activity. However, it is not always easy to get accurate answers, Dr. Richardson admitted in an interview. “People will say what they think you want to hear.” Patients also often incorrectly describe their activity level because they don't understand the difference between activity and structured exercise. “People might overestimate their activity because they feel as if they run around all day, [and] they're stressed and busy and exhausted at night. But this isn't the kind of activity that gives you any health points,” said Dr. Richardson. Conversely, people who walk constantly during their daily work might say they live a very sedentary life because they never visit the gym. “These perceived discrepancies are part of the reason people aren't successful in starting an exercise program.”

A baseline pedometer assessment can shed some light on how much exercise a person is getting. “It's a simple tool that gives patients an accurate reflection of what they are really doing and a way to set a concrete goal,” she said.

After the activity assessment is complete—and it could take two visits to get the full picture—you can begin setting goals. During the discussion, most patients will identify at least a few barriers to change, such as work, or having a busy schedule, or health issues.

“Physicians have played a big role” in enabling patients to use medical problems as an excuse, Dr. Richardson said. “We have a history of telling people to take it easy, not to exert themselves when they're in pain or don't feel good, especially people with chronic illness or the elderly. But this culture is actually making people sick. The truth is that it's not safe to remain sedentary.”

After the patient agrees that more exercise is necessary, the physician should formalize the recommendation by writing a prescription for a specific regimen, usually a walking program.

“Giving an exercise recommendation the authority of the prescription pad can make a big difference. The patients can look back on it as a reminder and as a trigger for action,” said Dr. Richardson.

The prescription should be specific, with goals that are easily attainable. The first step might be small, such as a 10-minute walk every day during lunch. But success in that small way might help bolster the patient's belief that change is possible.

Dr. Fleming admitted, it can be time consuming to persuade patients to be more active. The time factor, combined with the residual frustration because advice is frequently ignored, might be enough to discourage some physicians from broaching the issue.

“The argument that primary care physicians can't take up this issue because they already have too much to do in an appointment is spurious. If we are to take primary prevention seriously, then we have to believe that a large part of treating our patients is talking about lifestyle changes. This is just as much a part of our job as checking cholesterol and writing prescriptions for controlling diabetes,” he said.

'Physicians have played a big role' in enabling patients to use medical problems as an excuse. DR. RICHARDSON

Small steps can lead to big changes when physicians use the power of a prescription pad to get patients up and exercising, experts say.

“There's nothing more frustrating to a patient than to be told bluntly, 'You need to exercise every day and lose 60 pounds,'” said Dr. Michael Fleming, past president of the American Academy of Family Physicians and someone who has struggled with obesity since childhood. “When someone told me that, I knew I was doomed. There was no way I could do it.”

Physicians share that defeatist attitude, he said in an interview. “It's incredibly frustrating to try to take care of someone who won't make lifestyle changes. And the frustration coming from both sides turns the patient off to whatever the doctor is trying to say.”

But change is possible, he said, and a recently published paper offers a valuable model for physicians who want to help their patients achieve it. “Helping Sedentary Patients Become More Active,” a case study and commentary by Dr. Caroline Richardson and her colleague Dr. Thomas Schwenk focuses on the power of incremental change (J. Clin. Outcomes Manage. 2007;14:161–71).

“The key to success, which this paper stresses, is the concept of taking small steps,” said Dr. Fleming, a former member of the advisory panel for the group Americans in Motion, an AAFP program that helps physicians promote fitness. “I can't start walking 10,000 steps a day tomorrow. But if someone suggests that I increase my walking by 2,500 steps a day, that's doable. I don't have to climb a mountain. Instead, I can go one hill at a time.”

Although patients may express frustration with their weight and exercise habits, most realize that they could benefit from change. At the same time, they doubt their ability to succeed. A pep talk about exercise and some vague dietary advice won't be strong enough to counteract that doubt. Instead, Dr. Richardson asserts, inactivity should be regarded as a potentially harmful condition that needs treatment. That treatment should include a physical exam with an assessment of the patient's current activity level, counseling that addresses barriers to change, and a prescription for addressing the problem.

The activity assessment should include questions about the frequency, duration, and intensity of daily activity. However, it is not always easy to get accurate answers, Dr. Richardson admitted in an interview. “People will say what they think you want to hear.” Patients also often incorrectly describe their activity level because they don't understand the difference between activity and structured exercise. “People might overestimate their activity because they feel as if they run around all day, [and] they're stressed and busy and exhausted at night. But this isn't the kind of activity that gives you any health points,” said Dr. Richardson. Conversely, people who walk constantly during their daily work might say they live a very sedentary life because they never visit the gym. “These perceived discrepancies are part of the reason people aren't successful in starting an exercise program.”

A baseline pedometer assessment can shed some light on how much exercise a person is getting. “It's a simple tool that gives patients an accurate reflection of what they are really doing and a way to set a concrete goal,” she said.

After the activity assessment is complete—and it could take two visits to get the full picture—you can begin setting goals. During the discussion, most patients will identify at least a few barriers to change, such as work, or having a busy schedule, or health issues.

“Physicians have played a big role” in enabling patients to use medical problems as an excuse, Dr. Richardson said. “We have a history of telling people to take it easy, not to exert themselves when they're in pain or don't feel good, especially people with chronic illness or the elderly. But this culture is actually making people sick. The truth is that it's not safe to remain sedentary.”

After the patient agrees that more exercise is necessary, the physician should formalize the recommendation by writing a prescription for a specific regimen, usually a walking program.

“Giving an exercise recommendation the authority of the prescription pad can make a big difference. The patients can look back on it as a reminder and as a trigger for action,” said Dr. Richardson.

The prescription should be specific, with goals that are easily attainable. The first step might be small, such as a 10-minute walk every day during lunch. But success in that small way might help bolster the patient's belief that change is possible.

Dr. Fleming admitted, it can be time consuming to persuade patients to be more active. The time factor, combined with the residual frustration because advice is frequently ignored, might be enough to discourage some physicians from broaching the issue.

“The argument that primary care physicians can't take up this issue because they already have too much to do in an appointment is spurious. If we are to take primary prevention seriously, then we have to believe that a large part of treating our patients is talking about lifestyle changes. This is just as much a part of our job as checking cholesterol and writing prescriptions for controlling diabetes,” he said.

'Physicians have played a big role' in enabling patients to use medical problems as an excuse. DR. RICHARDSON

Small steps can lead to big changes when physicians use the power of a prescription pad to get patients up and exercising, experts say.

“There's nothing more frustrating to a patient than to be told bluntly, 'You need to exercise every day and lose 60 pounds,'” said Dr. Michael Fleming, past president of the American Academy of Family Physicians and someone who has struggled with obesity since childhood. “When someone told me that, I knew I was doomed. There was no way I could do it.”

Physicians share that defeatist attitude, he said in an interview. “It's incredibly frustrating to try to take care of someone who won't make lifestyle changes. And the frustration coming from both sides turns the patient off to whatever the doctor is trying to say.”

But change is possible, he said, and a recently published paper offers a valuable model for physicians who want to help their patients achieve it. “Helping Sedentary Patients Become More Active,” a case study and commentary by Dr. Caroline Richardson and her colleague Dr. Thomas Schwenk focuses on the power of incremental change (J. Clin. Outcomes Manage. 2007;14:161–71).

“The key to success, which this paper stresses, is the concept of taking small steps,” said Dr. Fleming, a former member of the advisory panel for the group Americans in Motion, an AAFP program that helps physicians promote fitness. “I can't start walking 10,000 steps a day tomorrow. But if someone suggests that I increase my walking by 2,500 steps a day, that's doable. I don't have to climb a mountain. Instead, I can go one hill at a time.”

Although patients may express frustration with their weight and exercise habits, most realize that they could benefit from change. At the same time, they doubt their ability to succeed. A pep talk about exercise and some vague dietary advice won't be strong enough to counteract that doubt. Instead, Dr. Richardson asserts, inactivity should be regarded as a potentially harmful condition that needs treatment. That treatment should include a physical exam with an assessment of the patient's current activity level, counseling that addresses barriers to change, and a prescription for addressing the problem.

The activity assessment should include questions about the frequency, duration, and intensity of daily activity. However, it is not always easy to get accurate answers, Dr. Richardson admitted in an interview. “People will say what they think you want to hear.” Patients also often incorrectly describe their activity level because they don't understand the difference between activity and structured exercise. “People might overestimate their activity because they feel as if they run around all day, [and] they're stressed and busy and exhausted at night. But this isn't the kind of activity that gives you any health points,” said Dr. Richardson. Conversely, people who walk constantly during their daily work might say they live a very sedentary life because they never visit the gym. “These perceived discrepancies are part of the reason people aren't successful in starting an exercise program.”

A baseline pedometer assessment can shed some light on how much exercise a person is getting. “It's a simple tool that gives patients an accurate reflection of what they are really doing and a way to set a concrete goal,” she said.

After the activity assessment is complete—and it could take two visits to get the full picture—you can begin setting goals. During the discussion, most patients will identify at least a few barriers to change, such as work, or having a busy schedule, or health issues.

“Physicians have played a big role” in enabling patients to use medical problems as an excuse, Dr. Richardson said. “We have a history of telling people to take it easy, not to exert themselves when they're in pain or don't feel good, especially people with chronic illness or the elderly. But this culture is actually making people sick. The truth is that it's not safe to remain sedentary.”

After the patient agrees that more exercise is necessary, the physician should formalize the recommendation by writing a prescription for a specific regimen, usually a walking program.

“Giving an exercise recommendation the authority of the prescription pad can make a big difference. The patients can look back on it as a reminder and as a trigger for action,” said Dr. Richardson.

The prescription should be specific, with goals that are easily attainable. The first step might be small, such as a 10-minute walk every day during lunch. But success in that small way might help bolster the patient's belief that change is possible.

Dr. Fleming admitted, it can be time consuming to persuade patients to be more active. The time factor, combined with the residual frustration because advice is frequently ignored, might be enough to discourage some physicians from broaching the issue.

“The argument that primary care physicians can't take up this issue because they already have too much to do in an appointment is spurious. If we are to take primary prevention seriously, then we have to believe that a large part of treating our patients is talking about lifestyle changes. This is just as much a part of our job as checking cholesterol and writing prescriptions for controlling diabetes,” he said.

'Physicians have played a big role' in enabling patients to use medical problems as an excuse. DR. RICHARDSON

The rates of new acute hepatitis A and B infections in the United States have plummeted to the lowest levels ever recorded, and may herald the eventual elimination of the diseases in this country.

New infections from both viruses declined in 2005 to more than 80% below the previously recorded nadir, according to a new report issued by the Centers for Disease Control and Prevention.

The incidence of hepatitis A for 2005—the latest year for which full data are available—was just 1.5/100,000, and the incidence of hepatitis B was only 1.8/100,000. Both were the lowest rates ever recorded in the United States, the report noted (MMWR 2007;56:[No. SS-3]).

“The trend has been very impressive,” Dr. Emmet B. Keeffe, professor of medicine and chief of hepatology at Stanford (Calif.) University Medical Center, told this news organization. “We are having a significant impact on this disease in the United States, and we could see its eradication.”

Dr. Hua Chen of University of Houston agreed. “I'm very optimistic about it. I really believe these diseases could be eliminated within 10 or 20 years,” said Dr. Chen, an expert on hepatitis vaccine research.

CDC epidemiologist Annemarie Wasley, Sc.D., who prepared the report, expressed a more cautious outlook, but said the numbers illustrate the beneficial impact of a national vaccine strategy aimed at eradicating hepatitis.

“While it's difficult to predict the future, we feel that if we keep applying these recommendations, strengthening them where they are weak, and reaching out to high-risk groups, we can continue this downward trend to an even lower incidence of new infection,” she said in an interview.

The decrease in new infections is related directly to recent expansions in the recommendations for routine hepatitis A vaccination in young children and to ongoing hepatitis B vaccination strategies, Dr. Wasley said.

“The significant progress we're seeing in the reduction of new infections is concentrated primarily in younger age groups, and most probably reflects the impact of our universal vaccination strategies,” she said.

Only 4,488 acute symptomatic cases of hepatitis A were reported to the National Notifiable Diseases Surveillance System in 2005, according to the report. The disease incidence peaked in 1995, when more than 31,500 cases (12/100,000) were reported.

Rates have declined steadily since then, reflecting the 1996 recommendation to vaccinate those at increased risk of infection (international travelers, men who have sex with men, drug users, and children living in communities with high rates of disease). A 1999 recommendation to implement routine vaccination for children in 11 states with high infection rates contributed to the effect: New infections dropped from more than 17,000 in 1999 to fewer than 9,000 in 2002.

The 2005 recommendation to include hepatitis A as part of the routine childhood vaccination schedule probably will help to perpetuate the downward trend. That recommendation will “provide the foundation for eventual consideration of elimination of indigenous hepatitis A virus transmission in the U.S.,” the report noted.

Hepatitis A has shown a cyclical pattern in the United States since record keeping began in 1966, the report said. The 2005 rate of new infection is more than 80% lower than any previously recorded low in that cycle.

Hepatitis B also showed a similarly dramatic decline in 2005, with 5,494 acute symptomatic cases. This amounted to an 80% decline since 1991, when more than 24,000 cases were reported.

The decline in this disease is associated with the national four-step program to eliminate transmission of hepatitis B, launched in 1991.

The key elements of that program were universal vaccination of all newborns, routine screening of all pregnant women with prenatal treatment of those infected, routine vaccination of all unvaccinated children and adolescents, and vaccination of all at-risk adults.

The report also notes a significant decline in hepatitis C. This finding is probably because of risk-reduction behaviors and the decline in needle sharing among injectable drug users, Dr. Wasley said.

Hepatitis C continued the decline it has shown since its peak in 1985, when almost 27,000 new cases occurred. In 2005, only 671 cases were reported, for an overall national rate of just 0.2/100,000.

But despite the good news, challenges remain. Unfortunately, Dr. Wasley said, rates of hepatitis B among 24- to 44-year-olds remain unacceptably high. Most of the occurrences in this age group are associated with high-risk behaviors, including intravenous drug use, male/male sex, and multiple sexual partners. “The vaccine has always been recommended for people with these risk factors, but the challenge is getting it to them.”

The problem is not vaccine availability, said Dr. Chen, but instead it is an issue of education and accessibility. “Adults with sexually transmitted disease and illegal drug users are the two biggest populations at risk right now. These are precisely the adults who don't self-identify as a high-risk population. They remain unaware of their risk and do not communicate this with their physicians—if they even have a physician. It's a huge challenge to public health to effectively reach them and get them vaccinated.”

Her recent review of more than 6,000 respondents to the National Health and Nutrition Examination Survey examined factors affecting hepatitis vaccination rates (Curr. Med. Res. Opin. 2006;22:2489–96). Among those with high-risk behaviors, being single, male, and uninsured had significant negative associations with hepatitis vaccination. “The people who need it most are the ones who don't have it,” said Dr. Chen.

Dr. Keeffe agreed. “These are hard populations to penetrate and elicit compliance from. Doctors who work in these environments, such as STD clinics or inner cities with large indigent populations, need to try and increase the delivery of vaccine to these patients.”

But even if new hepatitis infections become a relic of the past, Dr. Wasley said, physicians will be dealing with the existing chronic infections for years and years to come. “We can't forget that there are more than 3 million people in this country who have chronic hepatitis, and that is an enormous health care burden,” she said.

ELSEVIER GLOBAL MEDICAL NEWS

The rates of new acute hepatitis A and B infections in the United States have plummeted to the lowest levels ever recorded, and may herald the eventual elimination of the diseases in this country.

New infections from both viruses declined in 2005 to more than 80% below the previously recorded nadir, according to a new report issued by the Centers for Disease Control and Prevention.

The incidence of hepatitis A for 2005—the latest year for which full data are available—was just 1.5/100,000, and the incidence of hepatitis B was only 1.8/100,000. Both were the lowest rates ever recorded in the United States, the report noted (MMWR 2007;56:[No. SS-3]).

“The trend has been very impressive,” Dr. Emmet B. Keeffe, professor of medicine and chief of hepatology at Stanford (Calif.) University Medical Center, told this news organization. “We are having a significant impact on this disease in the United States, and we could see its eradication.”

Dr. Hua Chen of University of Houston agreed. “I'm very optimistic about it. I really believe these diseases could be eliminated within 10 or 20 years,” said Dr. Chen, an expert on hepatitis vaccine research.

CDC epidemiologist Annemarie Wasley, Sc.D., who prepared the report, expressed a more cautious outlook, but said the numbers illustrate the beneficial impact of a national vaccine strategy aimed at eradicating hepatitis.

“While it's difficult to predict the future, we feel that if we keep applying these recommendations, strengthening them where they are weak, and reaching out to high-risk groups, we can continue this downward trend to an even lower incidence of new infection,” she said in an interview.

The decrease in new infections is related directly to recent expansions in the recommendations for routine hepatitis A vaccination in young children and to ongoing hepatitis B vaccination strategies, Dr. Wasley said.

“The significant progress we're seeing in the reduction of new infections is concentrated primarily in younger age groups, and most probably reflects the impact of our universal vaccination strategies,” she said.

Only 4,488 acute symptomatic cases of hepatitis A were reported to the National Notifiable Diseases Surveillance System in 2005, according to the report. The disease incidence peaked in 1995, when more than 31,500 cases (12/100,000) were reported.

Rates have declined steadily since then, reflecting the 1996 recommendation to vaccinate those at increased risk of infection (international travelers, men who have sex with men, drug users, and children living in communities with high rates of disease). A 1999 recommendation to implement routine vaccination for children in 11 states with high infection rates contributed to the effect: New infections dropped from more than 17,000 in 1999 to fewer than 9,000 in 2002.

The 2005 recommendation to include hepatitis A as part of the routine childhood vaccination schedule probably will help to perpetuate the downward trend. That recommendation will “provide the foundation for eventual consideration of elimination of indigenous hepatitis A virus transmission in the U.S.,” the report noted.

Hepatitis A has shown a cyclical pattern in the United States since record keeping began in 1966, the report said. The 2005 rate of new infection is more than 80% lower than any previously recorded low in that cycle.

Hepatitis B also showed a similarly dramatic decline in 2005, with 5,494 acute symptomatic cases. This amounted to an 80% decline since 1991, when more than 24,000 cases were reported.

The decline in this disease is associated with the national four-step program to eliminate transmission of hepatitis B, launched in 1991.

The key elements of that program were universal vaccination of all newborns, routine screening of all pregnant women with prenatal treatment of those infected, routine vaccination of all unvaccinated children and adolescents, and vaccination of all at-risk adults.

The report also notes a significant decline in hepatitis C. This finding is probably because of risk-reduction behaviors and the decline in needle sharing among injectable drug users, Dr. Wasley said.

Hepatitis C continued the decline it has shown since its peak in 1985, when almost 27,000 new cases occurred. In 2005, only 671 cases were reported, for an overall national rate of just 0.2/100,000.

But despite the good news, challenges remain. Unfortunately, Dr. Wasley said, rates of hepatitis B among 24- to 44-year-olds remain unacceptably high. Most of the occurrences in this age group are associated with high-risk behaviors, including intravenous drug use, male/male sex, and multiple sexual partners. “The vaccine has always been recommended for people with these risk factors, but the challenge is getting it to them.”

The problem is not vaccine availability, said Dr. Chen, but instead it is an issue of education and accessibility. “Adults with sexually transmitted disease and illegal drug users are the two biggest populations at risk right now. These are precisely the adults who don't self-identify as a high-risk population. They remain unaware of their risk and do not communicate this with their physicians—if they even have a physician. It's a huge challenge to public health to effectively reach them and get them vaccinated.”

Her recent review of more than 6,000 respondents to the National Health and Nutrition Examination Survey examined factors affecting hepatitis vaccination rates (Curr. Med. Res. Opin. 2006;22:2489–96). Among those with high-risk behaviors, being single, male, and uninsured had significant negative associations with hepatitis vaccination. “The people who need it most are the ones who don't have it,” said Dr. Chen.

Dr. Keeffe agreed. “These are hard populations to penetrate and elicit compliance from. Doctors who work in these environments, such as STD clinics or inner cities with large indigent populations, need to try and increase the delivery of vaccine to these patients.”

But even if new hepatitis infections become a relic of the past, Dr. Wasley said, physicians will be dealing with the existing chronic infections for years and years to come. “We can't forget that there are more than 3 million people in this country who have chronic hepatitis, and that is an enormous health care burden,” she said.

ELSEVIER GLOBAL MEDICAL NEWS

The rates of new acute hepatitis A and B infections in the United States have plummeted to the lowest levels ever recorded, and may herald the eventual elimination of the diseases in this country.

New infections from both viruses declined in 2005 to more than 80% below the previously recorded nadir, according to a new report issued by the Centers for Disease Control and Prevention.

The incidence of hepatitis A for 2005—the latest year for which full data are available—was just 1.5/100,000, and the incidence of hepatitis B was only 1.8/100,000. Both were the lowest rates ever recorded in the United States, the report noted (MMWR 2007;56:[No. SS-3]).

“The trend has been very impressive,” Dr. Emmet B. Keeffe, professor of medicine and chief of hepatology at Stanford (Calif.) University Medical Center, told this news organization. “We are having a significant impact on this disease in the United States, and we could see its eradication.”

Dr. Hua Chen of University of Houston agreed. “I'm very optimistic about it. I really believe these diseases could be eliminated within 10 or 20 years,” said Dr. Chen, an expert on hepatitis vaccine research.

CDC epidemiologist Annemarie Wasley, Sc.D., who prepared the report, expressed a more cautious outlook, but said the numbers illustrate the beneficial impact of a national vaccine strategy aimed at eradicating hepatitis.

“While it's difficult to predict the future, we feel that if we keep applying these recommendations, strengthening them where they are weak, and reaching out to high-risk groups, we can continue this downward trend to an even lower incidence of new infection,” she said in an interview.

The decrease in new infections is related directly to recent expansions in the recommendations for routine hepatitis A vaccination in young children and to ongoing hepatitis B vaccination strategies, Dr. Wasley said.

“The significant progress we're seeing in the reduction of new infections is concentrated primarily in younger age groups, and most probably reflects the impact of our universal vaccination strategies,” she said.

Only 4,488 acute symptomatic cases of hepatitis A were reported to the National Notifiable Diseases Surveillance System in 2005, according to the report. The disease incidence peaked in 1995, when more than 31,500 cases (12/100,000) were reported.

Rates have declined steadily since then, reflecting the 1996 recommendation to vaccinate those at increased risk of infection (international travelers, men who have sex with men, drug users, and children living in communities with high rates of disease). A 1999 recommendation to implement routine vaccination for children in 11 states with high infection rates contributed to the effect: New infections dropped from more than 17,000 in 1999 to fewer than 9,000 in 2002.

The 2005 recommendation to include hepatitis A as part of the routine childhood vaccination schedule probably will help to perpetuate the downward trend. That recommendation will “provide the foundation for eventual consideration of elimination of indigenous hepatitis A virus transmission in the U.S.,” the report noted.

Hepatitis A has shown a cyclical pattern in the United States since record keeping began in 1966, the report said. The 2005 rate of new infection is more than 80% lower than any previously recorded low in that cycle.

Hepatitis B also showed a similarly dramatic decline in 2005, with 5,494 acute symptomatic cases. This amounted to an 80% decline since 1991, when more than 24,000 cases were reported.

The decline in this disease is associated with the national four-step program to eliminate transmission of hepatitis B, launched in 1991.

The key elements of that program were universal vaccination of all newborns, routine screening of all pregnant women with prenatal treatment of those infected, routine vaccination of all unvaccinated children and adolescents, and vaccination of all at-risk adults.

The report also notes a significant decline in hepatitis C. This finding is probably because of risk-reduction behaviors and the decline in needle sharing among injectable drug users, Dr. Wasley said.

Hepatitis C continued the decline it has shown since its peak in 1985, when almost 27,000 new cases occurred. In 2005, only 671 cases were reported, for an overall national rate of just 0.2/100,000.

But despite the good news, challenges remain. Unfortunately, Dr. Wasley said, rates of hepatitis B among 24- to 44-year-olds remain unacceptably high. Most of the occurrences in this age group are associated with high-risk behaviors, including intravenous drug use, male/male sex, and multiple sexual partners. “The vaccine has always been recommended for people with these risk factors, but the challenge is getting it to them.”

The problem is not vaccine availability, said Dr. Chen, but instead it is an issue of education and accessibility. “Adults with sexually transmitted disease and illegal drug users are the two biggest populations at risk right now. These are precisely the adults who don't self-identify as a high-risk population. They remain unaware of their risk and do not communicate this with their physicians—if they even have a physician. It's a huge challenge to public health to effectively reach them and get them vaccinated.”

Her recent review of more than 6,000 respondents to the National Health and Nutrition Examination Survey examined factors affecting hepatitis vaccination rates (Curr. Med. Res. Opin. 2006;22:2489–96). Among those with high-risk behaviors, being single, male, and uninsured had significant negative associations with hepatitis vaccination. “The people who need it most are the ones who don't have it,” said Dr. Chen.

Dr. Keeffe agreed. “These are hard populations to penetrate and elicit compliance from. Doctors who work in these environments, such as STD clinics or inner cities with large indigent populations, need to try and increase the delivery of vaccine to these patients.”

But even if new hepatitis infections become a relic of the past, Dr. Wasley said, physicians will be dealing with the existing chronic infections for years and years to come. “We can't forget that there are more than 3 million people in this country who have chronic hepatitis, and that is an enormous health care burden,” she said.

ELSEVIER GLOBAL MEDICAL NEWS

Ibuprofen may increase the risk of heart attack, stroke, and congestive heart failure in osteoarthritis patients who also take low-dose aspirin because of a high risk of cardiovascular disease, according to the findings of a post hoc analysis.

Although the absolute number of events was small, these patients were nine times more likely to experience a heart attack or stroke than were those who took lumiracoxib with the preventive aspirin therapy, Dr. Michael E. Farkouh and colleagues have reported (Ann. Rheum. Dis. 2007 [Epub doi:10.1136/and.2006.066001]).

The post hoc analysis findings of the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) are strong enough to warrant vigilance when prescribing pain relievers for this group of arthritis patients, wrote Dr. Farkouh and his coauthors. “Owing to the over-the-counter availability of ibuprofen and naproxen, coupled with the scarcity of long-term NSAID clinical trials in high-risk patients, the findings of this study have immediate relevance to patients with arthritis at increased cardiovascular risk. … Caution is advised for high-risk patients prescribed COX-2 inhibitors and nonselective NSAIDs, particularly ibuprofen.”

TARGET, a Novartis-funded study, tested the cardiovascular and gastrointestinal safety of the firm's investigational drug, lumiracoxib. More than 18,000 osteoarthritis patients were enrolled and randomized to high doses of lumiracoxib (400 mg/day), naproxen (1,000 mg/day), or ibuprofen (2,400 mg/day) for 52 weeks. The study drug was found to be as safe as the comparators in the incidence of nonfatal and silent myocardial infarction, stroke, or cardiovascular death (Lancet 2004;364:675–84).

However, critics pointed out that the TARGET population “purposefully excluded patients with known and significant preexisting coronary artery disease” and was not adequately powered to detect significant differences in rates of myocardial infarction (Lancet 2004;364:639–40).

In the new post hoc analysis, the TARGET population was stratified into low- and high-risk groups according to use of low-dose aspirin, said Dr. Farkouh of the Mt. Sinai Cardiovascular Institute in New York.

TARGET involved 3,042 patients who were considered at high risk of cardiovascular disease, based on prior events including silent MI, a high Framingham risk profile, or the presence of diabetes and more than one cardiovascular risk factor. Of this group, 60% were taking low-dose aspirin.

High-risk patients who took naproxen and aspirin were not at increased risk of adverse cardiovascular outcomes, compared with those taking lumiracoxib and aspirin. But those who took ibuprofen and aspirin were nine times more likely to experience a heart attack or stroke than were those who took the lumiracoxib/aspirin combination (8 vs. 1, or 2% vs. 0.25%).

Among high-risk patients who were not taking aspirin, naproxen was the safest choice, with no events occurring in the naproxen group compared with five events (1.57%) in the lumiracoxib group.

The ibuprofen/aspirin combination was also associated with a trend toward more congestive heart failure, compared with the lumiracoxib/aspirin combination (6 vs. 1, or 1.6% vs. 0.25%). This difference was not statistically significant, but was the primary driver of a 10-fold increase in the risk of heart failure in all the patients taking ibuprofen, compared with all of those taking lumiracoxib (8 vs. 1, or 1.28% vs. 0.14%).

Among low-risk patients, there were no significant associations between increased cardiovascular events or heart failure and any of the regimens.

The findings of increased heart attack and stroke seem to support the theory that ibuprofen might block aspirin's beneficial effect on platelet aggregation, the authors said. The drug might also negatively affect fluid balance and blood pressure, leading to the increased incidence of congestive heart failure in aspirin/ibuprofen users.

The hazard ratios may seem large, but it's important to keep the overall numbers in mind before drawing any firm conclusions, said Dr. Roy Altman, professor of medicine in the division of rheumatology at the University of California, Los Angeles. “Cardiovascular events were not the primary objective of the TARGET study. The total number of events was relatively small, and TARGET was smaller than a cardiovascular event study, which usually contains about 30,000 patients. These factors make this a hypothesis-generating study.”

Ibuprofen may increase the risk of heart attack, stroke, and congestive heart failure in osteoarthritis patients who also take low-dose aspirin because of a high risk of cardiovascular disease, according to the findings of a post hoc analysis.

Although the absolute number of events was small, these patients were nine times more likely to experience a heart attack or stroke than were those who took lumiracoxib with the preventive aspirin therapy, Dr. Michael E. Farkouh and colleagues have reported (Ann. Rheum. Dis. 2007 [Epub doi:10.1136/and.2006.066001]).

The post hoc analysis findings of the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) are strong enough to warrant vigilance when prescribing pain relievers for this group of arthritis patients, wrote Dr. Farkouh and his coauthors. “Owing to the over-the-counter availability of ibuprofen and naproxen, coupled with the scarcity of long-term NSAID clinical trials in high-risk patients, the findings of this study have immediate relevance to patients with arthritis at increased cardiovascular risk. … Caution is advised for high-risk patients prescribed COX-2 inhibitors and nonselective NSAIDs, particularly ibuprofen.”

TARGET, a Novartis-funded study, tested the cardiovascular and gastrointestinal safety of the firm's investigational drug, lumiracoxib. More than 18,000 osteoarthritis patients were enrolled and randomized to high doses of lumiracoxib (400 mg/day), naproxen (1,000 mg/day), or ibuprofen (2,400 mg/day) for 52 weeks. The study drug was found to be as safe as the comparators in the incidence of nonfatal and silent myocardial infarction, stroke, or cardiovascular death (Lancet 2004;364:675–84).

However, critics pointed out that the TARGET population “purposefully excluded patients with known and significant preexisting coronary artery disease” and was not adequately powered to detect significant differences in rates of myocardial infarction (Lancet 2004;364:639–40).

In the new post hoc analysis, the TARGET population was stratified into low- and high-risk groups according to use of low-dose aspirin, said Dr. Farkouh of the Mt. Sinai Cardiovascular Institute in New York.

TARGET involved 3,042 patients who were considered at high risk of cardiovascular disease, based on prior events including silent MI, a high Framingham risk profile, or the presence of diabetes and more than one cardiovascular risk factor. Of this group, 60% were taking low-dose aspirin.

High-risk patients who took naproxen and aspirin were not at increased risk of adverse cardiovascular outcomes, compared with those taking lumiracoxib and aspirin. But those who took ibuprofen and aspirin were nine times more likely to experience a heart attack or stroke than were those who took the lumiracoxib/aspirin combination (8 vs. 1, or 2% vs. 0.25%).

Among high-risk patients who were not taking aspirin, naproxen was the safest choice, with no events occurring in the naproxen group compared with five events (1.57%) in the lumiracoxib group.

The ibuprofen/aspirin combination was also associated with a trend toward more congestive heart failure, compared with the lumiracoxib/aspirin combination (6 vs. 1, or 1.6% vs. 0.25%). This difference was not statistically significant, but was the primary driver of a 10-fold increase in the risk of heart failure in all the patients taking ibuprofen, compared with all of those taking lumiracoxib (8 vs. 1, or 1.28% vs. 0.14%).

Among low-risk patients, there were no significant associations between increased cardiovascular events or heart failure and any of the regimens.

The findings of increased heart attack and stroke seem to support the theory that ibuprofen might block aspirin's beneficial effect on platelet aggregation, the authors said. The drug might also negatively affect fluid balance and blood pressure, leading to the increased incidence of congestive heart failure in aspirin/ibuprofen users.

The hazard ratios may seem large, but it's important to keep the overall numbers in mind before drawing any firm conclusions, said Dr. Roy Altman, professor of medicine in the division of rheumatology at the University of California, Los Angeles. “Cardiovascular events were not the primary objective of the TARGET study. The total number of events was relatively small, and TARGET was smaller than a cardiovascular event study, which usually contains about 30,000 patients. These factors make this a hypothesis-generating study.”

Ibuprofen may increase the risk of heart attack, stroke, and congestive heart failure in osteoarthritis patients who also take low-dose aspirin because of a high risk of cardiovascular disease, according to the findings of a post hoc analysis.

Although the absolute number of events was small, these patients were nine times more likely to experience a heart attack or stroke than were those who took lumiracoxib with the preventive aspirin therapy, Dr. Michael E. Farkouh and colleagues have reported (Ann. Rheum. Dis. 2007 [Epub doi:10.1136/and.2006.066001]).

The post hoc analysis findings of the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) are strong enough to warrant vigilance when prescribing pain relievers for this group of arthritis patients, wrote Dr. Farkouh and his coauthors. “Owing to the over-the-counter availability of ibuprofen and naproxen, coupled with the scarcity of long-term NSAID clinical trials in high-risk patients, the findings of this study have immediate relevance to patients with arthritis at increased cardiovascular risk. … Caution is advised for high-risk patients prescribed COX-2 inhibitors and nonselective NSAIDs, particularly ibuprofen.”

TARGET, a Novartis-funded study, tested the cardiovascular and gastrointestinal safety of the firm's investigational drug, lumiracoxib. More than 18,000 osteoarthritis patients were enrolled and randomized to high doses of lumiracoxib (400 mg/day), naproxen (1,000 mg/day), or ibuprofen (2,400 mg/day) for 52 weeks. The study drug was found to be as safe as the comparators in the incidence of nonfatal and silent myocardial infarction, stroke, or cardiovascular death (Lancet 2004;364:675–84).

However, critics pointed out that the TARGET population “purposefully excluded patients with known and significant preexisting coronary artery disease” and was not adequately powered to detect significant differences in rates of myocardial infarction (Lancet 2004;364:639–40).

In the new post hoc analysis, the TARGET population was stratified into low- and high-risk groups according to use of low-dose aspirin, said Dr. Farkouh of the Mt. Sinai Cardiovascular Institute in New York.

TARGET involved 3,042 patients who were considered at high risk of cardiovascular disease, based on prior events including silent MI, a high Framingham risk profile, or the presence of diabetes and more than one cardiovascular risk factor. Of this group, 60% were taking low-dose aspirin.

High-risk patients who took naproxen and aspirin were not at increased risk of adverse cardiovascular outcomes, compared with those taking lumiracoxib and aspirin. But those who took ibuprofen and aspirin were nine times more likely to experience a heart attack or stroke than were those who took the lumiracoxib/aspirin combination (8 vs. 1, or 2% vs. 0.25%).

Among high-risk patients who were not taking aspirin, naproxen was the safest choice, with no events occurring in the naproxen group compared with five events (1.57%) in the lumiracoxib group.

The ibuprofen/aspirin combination was also associated with a trend toward more congestive heart failure, compared with the lumiracoxib/aspirin combination (6 vs. 1, or 1.6% vs. 0.25%). This difference was not statistically significant, but was the primary driver of a 10-fold increase in the risk of heart failure in all the patients taking ibuprofen, compared with all of those taking lumiracoxib (8 vs. 1, or 1.28% vs. 0.14%).

Among low-risk patients, there were no significant associations between increased cardiovascular events or heart failure and any of the regimens.

The findings of increased heart attack and stroke seem to support the theory that ibuprofen might block aspirin's beneficial effect on platelet aggregation, the authors said. The drug might also negatively affect fluid balance and blood pressure, leading to the increased incidence of congestive heart failure in aspirin/ibuprofen users.

The hazard ratios may seem large, but it's important to keep the overall numbers in mind before drawing any firm conclusions, said Dr. Roy Altman, professor of medicine in the division of rheumatology at the University of California, Los Angeles. “Cardiovascular events were not the primary objective of the TARGET study. The total number of events was relatively small, and TARGET was smaller than a cardiovascular event study, which usually contains about 30,000 patients. These factors make this a hypothesis-generating study.”