Patrice Wendling

MIAMI BEACH — Rituximab treatment appears safe and efficacious for refractory systemic lupus erythematosus in children, Dr. Obioma Nwobi and colleagues reported in a poster at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Average SLE Disease Activity Index scores improved from 43 at baseline to 28 at 6 months post treatment in 16 children. Rituximab was well tolerated in 15 patients, but one died 20 days after starting rituximab of acute bacterial endocarditis.

Rituximab (Rituxan) has come under scrutiny after two patients treated with rituximab for SLE developed progressive multifocal leukoencephalopathy (PML), a viral infection of the central nervous system.

SLE is not an approved indication for rituximab, which selectively depletes CD20+ B cells. It is approved only for the treatment of non-Hodgkin's lymphoma and refractory rheumatoid arthritis.

The death in the current study was likely “related to the severe immune suppression imposed by the use of Cytoxan prior to the rituximab,” senior author Dr. Carolyn Abitbol said in an interview.

“Although Cytoxan has long been considered the 'standard of care' in treating SLE nephritis because of its efficacy, the primary cause of death in lupus patients is infection,” she said.

The safety and efficacy of rituximab has been established in at least three adult SLE trials, numerous rheumatoid arthritis trials, and in more than 300,000 patients treated for lymphomas, said Dr. Abitbol, professor of pediatrics and clinical director of pediatric dialysis, University of Miami.

Dr. Abitbol agreed with a recent statement that the reported deaths were the results of extreme immunosuppression, and were not attributable to rituximab (the statement can be located online at www.hopkins-arthritis.som.jhmi.edu/news-archive/2007/genentech-PML.html

Rituximab infusions were administered weekly at an initial dose of 188 mg/m

Six months after treatment, significant decreases were observed from baseline in average urine albumin:creatinine ratio (3,756 mg/g vs. 361 mg/g), urine protein:creatinine ratio in patients not on dialysis (4.2 mg/dL vs. 0.7 mg/dL), and serum creatinine (1.2 mg/dL vs. 0.6 mg/dL).

Significant increases were seen in serum albumin levels (2.6 mg/dL vs. 3.5 mg/dL) and CD4 T cells (344 vs. 556). An insignificant increase in CD8 T cells also was observed (332 vs. 590). CD 20+ B cells decreased significantly at 6 months from baseline (243 vs. 74). B-cell depletion, measured serially over 6–18 months, lasted an average of 6–8 months.

The authors said collaborative controlled trials are needed in children to develop protocols for rituximab as a component of induction and/or maintenance therapy for SLE.

MIAMI BEACH — Rituximab treatment appears safe and efficacious for refractory systemic lupus erythematosus in children, Dr. Obioma Nwobi and colleagues reported in a poster at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Average SLE Disease Activity Index scores improved from 43 at baseline to 28 at 6 months post treatment in 16 children. Rituximab was well tolerated in 15 patients, but one died 20 days after starting rituximab of acute bacterial endocarditis.

Rituximab (Rituxan) has come under scrutiny after two patients treated with rituximab for SLE developed progressive multifocal leukoencephalopathy (PML), a viral infection of the central nervous system.

SLE is not an approved indication for rituximab, which selectively depletes CD20+ B cells. It is approved only for the treatment of non-Hodgkin's lymphoma and refractory rheumatoid arthritis.

The death in the current study was likely “related to the severe immune suppression imposed by the use of Cytoxan prior to the rituximab,” senior author Dr. Carolyn Abitbol said in an interview.

“Although Cytoxan has long been considered the 'standard of care' in treating SLE nephritis because of its efficacy, the primary cause of death in lupus patients is infection,” she said.

The safety and efficacy of rituximab has been established in at least three adult SLE trials, numerous rheumatoid arthritis trials, and in more than 300,000 patients treated for lymphomas, said Dr. Abitbol, professor of pediatrics and clinical director of pediatric dialysis, University of Miami.

Dr. Abitbol agreed with a recent statement that the reported deaths were the results of extreme immunosuppression, and were not attributable to rituximab (the statement can be located online at www.hopkins-arthritis.som.jhmi.edu/news-archive/2007/genentech-PML.html

Rituximab infusions were administered weekly at an initial dose of 188 mg/m

Six months after treatment, significant decreases were observed from baseline in average urine albumin:creatinine ratio (3,756 mg/g vs. 361 mg/g), urine protein:creatinine ratio in patients not on dialysis (4.2 mg/dL vs. 0.7 mg/dL), and serum creatinine (1.2 mg/dL vs. 0.6 mg/dL).

Significant increases were seen in serum albumin levels (2.6 mg/dL vs. 3.5 mg/dL) and CD4 T cells (344 vs. 556). An insignificant increase in CD8 T cells also was observed (332 vs. 590). CD 20+ B cells decreased significantly at 6 months from baseline (243 vs. 74). B-cell depletion, measured serially over 6–18 months, lasted an average of 6–8 months.

The authors said collaborative controlled trials are needed in children to develop protocols for rituximab as a component of induction and/or maintenance therapy for SLE.

MIAMI BEACH — Rituximab treatment appears safe and efficacious for refractory systemic lupus erythematosus in children, Dr. Obioma Nwobi and colleagues reported in a poster at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Average SLE Disease Activity Index scores improved from 43 at baseline to 28 at 6 months post treatment in 16 children. Rituximab was well tolerated in 15 patients, but one died 20 days after starting rituximab of acute bacterial endocarditis.

Rituximab (Rituxan) has come under scrutiny after two patients treated with rituximab for SLE developed progressive multifocal leukoencephalopathy (PML), a viral infection of the central nervous system.

SLE is not an approved indication for rituximab, which selectively depletes CD20+ B cells. It is approved only for the treatment of non-Hodgkin's lymphoma and refractory rheumatoid arthritis.

The death in the current study was likely “related to the severe immune suppression imposed by the use of Cytoxan prior to the rituximab,” senior author Dr. Carolyn Abitbol said in an interview.

“Although Cytoxan has long been considered the 'standard of care' in treating SLE nephritis because of its efficacy, the primary cause of death in lupus patients is infection,” she said.

The safety and efficacy of rituximab has been established in at least three adult SLE trials, numerous rheumatoid arthritis trials, and in more than 300,000 patients treated for lymphomas, said Dr. Abitbol, professor of pediatrics and clinical director of pediatric dialysis, University of Miami.

Dr. Abitbol agreed with a recent statement that the reported deaths were the results of extreme immunosuppression, and were not attributable to rituximab (the statement can be located online at www.hopkins-arthritis.som.jhmi.edu/news-archive/2007/genentech-PML.html

Rituximab infusions were administered weekly at an initial dose of 188 mg/m

Six months after treatment, significant decreases were observed from baseline in average urine albumin:creatinine ratio (3,756 mg/g vs. 361 mg/g), urine protein:creatinine ratio in patients not on dialysis (4.2 mg/dL vs. 0.7 mg/dL), and serum creatinine (1.2 mg/dL vs. 0.6 mg/dL).

Significant increases were seen in serum albumin levels (2.6 mg/dL vs. 3.5 mg/dL) and CD4 T cells (344 vs. 556). An insignificant increase in CD8 T cells also was observed (332 vs. 590). CD 20+ B cells decreased significantly at 6 months from baseline (243 vs. 74). B-cell depletion, measured serially over 6–18 months, lasted an average of 6–8 months.

The authors said collaborative controlled trials are needed in children to develop protocols for rituximab as a component of induction and/or maintenance therapy for SLE.

CHICAGO — Fixed-dose combination therapy increased blood pressure control rates from 37% to 76% over 18 months in patients with high-risk hypertension in a large, multinational trial reported at the annual meeting of the American Society of Hypertension.

Control rates were even higher in the U.S. cohort, where 80.5% of patients achieved control to less than 140 mm Hg—an unprecedented rate for a U.S. trial, reported Dr. Kenneth Jamerson, who presented the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial. Significant reductions in systolic blood pressure were seen across all patient populations, including African Americans.

Dr. Jamerson and associates randomized 11,463 patients age 55 years or older with a systolic blood pressure of at least 160 mm Hg or currently on antihypertensive therapy to treatment with either Lotrel, which contains the ACE inhibitor benazepril and the calcium-channel blocker amlodipine, or to benazepril plus the diuretic hydrochlorothiazide (HCTZ).

At 18 months, patients achieved an average decline in blood pressure from 145/80 mm Hg to 132/74 mm Hg. Almost one-fifth of patients went on to achieve a systolic BP of less than 120 mm Hg. The study remains blinded, so blood pressure reductions were not stratified based on treatment. Cardiovascular morbidity and mortality outcomes, the study's primary end point, are anticipated after the trial ends in 2008.

Dr. Jamerson believes the current data will help shift the traditional approach to hypertension management in which clinicians initiate monotherapy then sequentially use additional medications as needed in order to achieve target blood pressure goals.

“For more than 2 decades, too many clinicians have chanted the mantra, 'start low, go slow,' despite having lots of data that multiple drugs are going to be necessary to achieve blood pressure control,” said Dr. Jamerson, professor in the department of internal medicine, division of cardiovascular medicine, University of Michigan, Ann Arbor.

“We think we provide substantial evidence to suggest that initial combination therapy is very effective, and think there is substantial evidence here to support broadening the use of combination therapy as an initial therapy.”

Although 97% of patients in the study were already taking antihypertensive medication, just 37.5% had their blood pressure controlled at baseline to 140/90 mm Hg—the currently recommended target in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Dosages were titrated at month 2 to a fixed dose of benazepril 40 mg/amlodipine 10 mg or benazepril 40 mg/HCTZ 25 mg, with the option of adding on other antihypertensive agents at month 3. Overall, 35% of patients used add-on medications, said Dr. Jamerson, who has received grant/research support from Novartis, which sponsored the study and markets Lotrel.

At 18 months, the average systolic BP declined from 153 mm Hg to 137 mm Hg among Nordic patients, from 142 mm Hg to 129 among the U.S. cohort, and from 145 mm Hg to 133 mm Hg among African Americans.

A bit more work needs to be done among patients with diabetes and chronic kidney disease, Dr. Jamerson said. Their respective mean systolic BPs decreased from 145 mm Hg to 131.5 mm Hg and from 149 mm Hg to 136 mm Hg—both short of the JNC 7 goal of 130 mm Hg for these difficult-to-treat populations. Overall, 60% of ACCOMPLISH participants have diabetes, and had a BP control rate of 15%.

ASH President Suzanne Oparil said in an interview that these are the highest overall control rates ever achieved, but at roughly 80% are only slightly higher than the 65% reported in previous hypertension trials. The low systolic BP rates reported in the U.S. cohort may reflect higher values at baseline in the Nordic cohort and a more cautious treatment approach typically used by European physicians.

Dr. Oparil, professor of medicine, physiology, and biophysics at the University of Alabama, Birmingham, took issue with the notion that these results will shift treatment patterns, as the VALUE, or Valsartan Antihypertensive Long-term Use Evaluation trial, already provided clinicians with the lesson that controlling blood pressure quickly is important. “It's not that paradigm shifting because that's what we're preaching anyway,” she said.

Some members of the audience suggested that the go-slow approach remains warranted in certain patients such as the elderly because of potential side effects including hypotension. Hypotension was reported in 207 or 2% of patients and 0.4% of these were hospitalized for the condition. Dizziness was reported in 2,144 (19%) patients, peripheral edema in 2,009 (17.6%), and chest pain in 159 (1.4%).

Dr. Jamerson responded by noting that the average age of the ACCOMPLISH cohort was 68 years, but added that the final data will be analyzed to determine exactly how many hypotensive events are drug-related.

The study is powered to show that the combination of benazepril and amlodipine will reduce cardiovascular morbidity and mortality in patients with high-risk hypertension by 15%, compared with the combination of benazepril and HCTZ. Theoretical research suggests that a combination of ACE inhibitors and calcium-channel blockers might confer an additional benefit, as they have been shown independently to increase vascular nitric oxide production, Dr. Jamerson said.

'For more than 2 decades, too many clinicians have chanted the mantra, “start low, go slow.”' DR. JAMERSON

CHICAGO — Fixed-dose combination therapy increased blood pressure control rates from 37% to 76% over 18 months in patients with high-risk hypertension in a large, multinational trial reported at the annual meeting of the American Society of Hypertension.

Control rates were even higher in the U.S. cohort, where 80.5% of patients achieved control to less than 140 mm Hg—an unprecedented rate for a U.S. trial, reported Dr. Kenneth Jamerson, who presented the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial. Significant reductions in systolic blood pressure were seen across all patient populations, including African Americans.

Dr. Jamerson and associates randomized 11,463 patients age 55 years or older with a systolic blood pressure of at least 160 mm Hg or currently on antihypertensive therapy to treatment with either Lotrel, which contains the ACE inhibitor benazepril and the calcium-channel blocker amlodipine, or to benazepril plus the diuretic hydrochlorothiazide (HCTZ).

At 18 months, patients achieved an average decline in blood pressure from 145/80 mm Hg to 132/74 mm Hg. Almost one-fifth of patients went on to achieve a systolic BP of less than 120 mm Hg. The study remains blinded, so blood pressure reductions were not stratified based on treatment. Cardiovascular morbidity and mortality outcomes, the study's primary end point, are anticipated after the trial ends in 2008.

Dr. Jamerson believes the current data will help shift the traditional approach to hypertension management in which clinicians initiate monotherapy then sequentially use additional medications as needed in order to achieve target blood pressure goals.

“For more than 2 decades, too many clinicians have chanted the mantra, 'start low, go slow,' despite having lots of data that multiple drugs are going to be necessary to achieve blood pressure control,” said Dr. Jamerson, professor in the department of internal medicine, division of cardiovascular medicine, University of Michigan, Ann Arbor.

“We think we provide substantial evidence to suggest that initial combination therapy is very effective, and think there is substantial evidence here to support broadening the use of combination therapy as an initial therapy.”

Although 97% of patients in the study were already taking antihypertensive medication, just 37.5% had their blood pressure controlled at baseline to 140/90 mm Hg—the currently recommended target in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Dosages were titrated at month 2 to a fixed dose of benazepril 40 mg/amlodipine 10 mg or benazepril 40 mg/HCTZ 25 mg, with the option of adding on other antihypertensive agents at month 3. Overall, 35% of patients used add-on medications, said Dr. Jamerson, who has received grant/research support from Novartis, which sponsored the study and markets Lotrel.

At 18 months, the average systolic BP declined from 153 mm Hg to 137 mm Hg among Nordic patients, from 142 mm Hg to 129 among the U.S. cohort, and from 145 mm Hg to 133 mm Hg among African Americans.

A bit more work needs to be done among patients with diabetes and chronic kidney disease, Dr. Jamerson said. Their respective mean systolic BPs decreased from 145 mm Hg to 131.5 mm Hg and from 149 mm Hg to 136 mm Hg—both short of the JNC 7 goal of 130 mm Hg for these difficult-to-treat populations. Overall, 60% of ACCOMPLISH participants have diabetes, and had a BP control rate of 15%.

ASH President Suzanne Oparil said in an interview that these are the highest overall control rates ever achieved, but at roughly 80% are only slightly higher than the 65% reported in previous hypertension trials. The low systolic BP rates reported in the U.S. cohort may reflect higher values at baseline in the Nordic cohort and a more cautious treatment approach typically used by European physicians.

Dr. Oparil, professor of medicine, physiology, and biophysics at the University of Alabama, Birmingham, took issue with the notion that these results will shift treatment patterns, as the VALUE, or Valsartan Antihypertensive Long-term Use Evaluation trial, already provided clinicians with the lesson that controlling blood pressure quickly is important. “It's not that paradigm shifting because that's what we're preaching anyway,” she said.

Some members of the audience suggested that the go-slow approach remains warranted in certain patients such as the elderly because of potential side effects including hypotension. Hypotension was reported in 207 or 2% of patients and 0.4% of these were hospitalized for the condition. Dizziness was reported in 2,144 (19%) patients, peripheral edema in 2,009 (17.6%), and chest pain in 159 (1.4%).

Dr. Jamerson responded by noting that the average age of the ACCOMPLISH cohort was 68 years, but added that the final data will be analyzed to determine exactly how many hypotensive events are drug-related.

The study is powered to show that the combination of benazepril and amlodipine will reduce cardiovascular morbidity and mortality in patients with high-risk hypertension by 15%, compared with the combination of benazepril and HCTZ. Theoretical research suggests that a combination of ACE inhibitors and calcium-channel blockers might confer an additional benefit, as they have been shown independently to increase vascular nitric oxide production, Dr. Jamerson said.

'For more than 2 decades, too many clinicians have chanted the mantra, “start low, go slow.”' DR. JAMERSON

CHICAGO — Fixed-dose combination therapy increased blood pressure control rates from 37% to 76% over 18 months in patients with high-risk hypertension in a large, multinational trial reported at the annual meeting of the American Society of Hypertension.

Control rates were even higher in the U.S. cohort, where 80.5% of patients achieved control to less than 140 mm Hg—an unprecedented rate for a U.S. trial, reported Dr. Kenneth Jamerson, who presented the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial. Significant reductions in systolic blood pressure were seen across all patient populations, including African Americans.

Dr. Jamerson and associates randomized 11,463 patients age 55 years or older with a systolic blood pressure of at least 160 mm Hg or currently on antihypertensive therapy to treatment with either Lotrel, which contains the ACE inhibitor benazepril and the calcium-channel blocker amlodipine, or to benazepril plus the diuretic hydrochlorothiazide (HCTZ).

At 18 months, patients achieved an average decline in blood pressure from 145/80 mm Hg to 132/74 mm Hg. Almost one-fifth of patients went on to achieve a systolic BP of less than 120 mm Hg. The study remains blinded, so blood pressure reductions were not stratified based on treatment. Cardiovascular morbidity and mortality outcomes, the study's primary end point, are anticipated after the trial ends in 2008.

Dr. Jamerson believes the current data will help shift the traditional approach to hypertension management in which clinicians initiate monotherapy then sequentially use additional medications as needed in order to achieve target blood pressure goals.

“For more than 2 decades, too many clinicians have chanted the mantra, 'start low, go slow,' despite having lots of data that multiple drugs are going to be necessary to achieve blood pressure control,” said Dr. Jamerson, professor in the department of internal medicine, division of cardiovascular medicine, University of Michigan, Ann Arbor.

“We think we provide substantial evidence to suggest that initial combination therapy is very effective, and think there is substantial evidence here to support broadening the use of combination therapy as an initial therapy.”

Although 97% of patients in the study were already taking antihypertensive medication, just 37.5% had their blood pressure controlled at baseline to 140/90 mm Hg—the currently recommended target in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Dosages were titrated at month 2 to a fixed dose of benazepril 40 mg/amlodipine 10 mg or benazepril 40 mg/HCTZ 25 mg, with the option of adding on other antihypertensive agents at month 3. Overall, 35% of patients used add-on medications, said Dr. Jamerson, who has received grant/research support from Novartis, which sponsored the study and markets Lotrel.

At 18 months, the average systolic BP declined from 153 mm Hg to 137 mm Hg among Nordic patients, from 142 mm Hg to 129 among the U.S. cohort, and from 145 mm Hg to 133 mm Hg among African Americans.

A bit more work needs to be done among patients with diabetes and chronic kidney disease, Dr. Jamerson said. Their respective mean systolic BPs decreased from 145 mm Hg to 131.5 mm Hg and from 149 mm Hg to 136 mm Hg—both short of the JNC 7 goal of 130 mm Hg for these difficult-to-treat populations. Overall, 60% of ACCOMPLISH participants have diabetes, and had a BP control rate of 15%.

ASH President Suzanne Oparil said in an interview that these are the highest overall control rates ever achieved, but at roughly 80% are only slightly higher than the 65% reported in previous hypertension trials. The low systolic BP rates reported in the U.S. cohort may reflect higher values at baseline in the Nordic cohort and a more cautious treatment approach typically used by European physicians.

Dr. Oparil, professor of medicine, physiology, and biophysics at the University of Alabama, Birmingham, took issue with the notion that these results will shift treatment patterns, as the VALUE, or Valsartan Antihypertensive Long-term Use Evaluation trial, already provided clinicians with the lesson that controlling blood pressure quickly is important. “It's not that paradigm shifting because that's what we're preaching anyway,” she said.

Some members of the audience suggested that the go-slow approach remains warranted in certain patients such as the elderly because of potential side effects including hypotension. Hypotension was reported in 207 or 2% of patients and 0.4% of these were hospitalized for the condition. Dizziness was reported in 2,144 (19%) patients, peripheral edema in 2,009 (17.6%), and chest pain in 159 (1.4%).

Dr. Jamerson responded by noting that the average age of the ACCOMPLISH cohort was 68 years, but added that the final data will be analyzed to determine exactly how many hypotensive events are drug-related.

The study is powered to show that the combination of benazepril and amlodipine will reduce cardiovascular morbidity and mortality in patients with high-risk hypertension by 15%, compared with the combination of benazepril and HCTZ. Theoretical research suggests that a combination of ACE inhibitors and calcium-channel blockers might confer an additional benefit, as they have been shown independently to increase vascular nitric oxide production, Dr. Jamerson said.

'For more than 2 decades, too many clinicians have chanted the mantra, “start low, go slow.”' DR. JAMERSON

TORONTO — Bordetella pertussis polymerase chain reaction tests can be positive months after clinical illness, Dr. Bryan Stone reported in a poster presentation at the annual meeting of the Pediatric Academic Societies.

It took a full 7 months for patients who initially tested positive for B. pertussis by polymerase chain reaction (PCR) to convert to a negative status, according to data from a prospective cohort study of 36 patients.

Rapid PCR testing has a sensitivity of 94%–98%. But there are concerns the test may be overly sensitive and may produce clinically irrelevant positives.

Patients with pertussis are believed to be contagious through the first 21 days of illness or completion of 5 days of antibiotics. What hasn't been known is the length of time after reported onset of symptoms that PCR testing remains positive, said Dr. Stone, medical director of the neuroscience trauma unit and assistant professor of pediatrics at the University of Utah, Salt Lake City.

“What we usually do clinically is, once we test, we treat for 5 days in isolation and assume that they are no longer contagious and basically cured, and let them out of isolation,” Dr. Stone said in an interview. “This has some implications because these people are clearly still carrying this organism for weeks and months; and all of these patients were treated with antibiotics.”

The analysis was based on 36 participants providing 61 samples taken over a range of 4 days to 204 days from onset of symptoms. Thirteen “index” cases were PCR-positive infants admitted to a tertiary care center and 23 were in close contact with an infected infant and had a cough lasting 7 or more days. The mean age of the index cases was 78 days, and none had received any pertussis immunizations.

Testing occurred weekly for 3 weeks and then monthly or every other month for 12 months, or until the test became negative. Overall, 15 patients allowed serial sampling; 16 allowed only one sample; and 5 were initially negative, but remained ill for more than 21 days from onset of symptoms.

Antibiotics were started 4–136 days after onset of symptoms, and from 35 days prior to 1 day after enrollment. There was no difference in antibiotic exposure in patients who tested PCR positive or negative, Dr. Stone and his associates reported.

Half of the participants remained PCR positive between 60 and 150 days after onset of symptoms. Post-tussive emesis, cyanosis, and hypoxemia by pulse oximetry were more common in PCR-positive patients, while sore throat and rhinorrhea were more common in PCR-negative patients. But the sample numbers were insufficient for significance.

The findings have not changed PCR testing at Dr. Stone's institution. But they have raised the index of suspicion in the clinical setting, as a PCR-positive result may confound the diagnosis of cough illness in patients who have had a pertussis infection in the prior 6 months, but are not currently infected, Dr. Stone said.

“I think it's going to have to be taken into clinical context a lot more strongly,” he said. “We can't just say, 'Oh this PCR was positive, this patient has pertussis.' We have to put it into clinical context.”

The study was prompted by a case in which a 7-week-old infant was admitted to the pediatric intensive care unit for respiratory failure and seizure with a prolonged 6-week hospital course, only to be readmitted with coughing paroxysm and classic whoop 17 days after discharge and 58 days after onset of symptoms and initiation of treatment. At both admissions, pertussis PCR was positive and direct fluorescent antibody culture negative. It was unclear whether she had pertussis again, a macrolide-resistant organism or simply a persisting positive PCR—raising the question as to the duration of PCR positivity, Dr. Stone explained.

A PCR-positive result may confound the diagnosis of cough illness in certain patients. DR. STONE

TORONTO — Bordetella pertussis polymerase chain reaction tests can be positive months after clinical illness, Dr. Bryan Stone reported in a poster presentation at the annual meeting of the Pediatric Academic Societies.

It took a full 7 months for patients who initially tested positive for B. pertussis by polymerase chain reaction (PCR) to convert to a negative status, according to data from a prospective cohort study of 36 patients.

Rapid PCR testing has a sensitivity of 94%–98%. But there are concerns the test may be overly sensitive and may produce clinically irrelevant positives.

Patients with pertussis are believed to be contagious through the first 21 days of illness or completion of 5 days of antibiotics. What hasn't been known is the length of time after reported onset of symptoms that PCR testing remains positive, said Dr. Stone, medical director of the neuroscience trauma unit and assistant professor of pediatrics at the University of Utah, Salt Lake City.

“What we usually do clinically is, once we test, we treat for 5 days in isolation and assume that they are no longer contagious and basically cured, and let them out of isolation,” Dr. Stone said in an interview. “This has some implications because these people are clearly still carrying this organism for weeks and months; and all of these patients were treated with antibiotics.”

The analysis was based on 36 participants providing 61 samples taken over a range of 4 days to 204 days from onset of symptoms. Thirteen “index” cases were PCR-positive infants admitted to a tertiary care center and 23 were in close contact with an infected infant and had a cough lasting 7 or more days. The mean age of the index cases was 78 days, and none had received any pertussis immunizations.

Testing occurred weekly for 3 weeks and then monthly or every other month for 12 months, or until the test became negative. Overall, 15 patients allowed serial sampling; 16 allowed only one sample; and 5 were initially negative, but remained ill for more than 21 days from onset of symptoms.

Antibiotics were started 4–136 days after onset of symptoms, and from 35 days prior to 1 day after enrollment. There was no difference in antibiotic exposure in patients who tested PCR positive or negative, Dr. Stone and his associates reported.

Half of the participants remained PCR positive between 60 and 150 days after onset of symptoms. Post-tussive emesis, cyanosis, and hypoxemia by pulse oximetry were more common in PCR-positive patients, while sore throat and rhinorrhea were more common in PCR-negative patients. But the sample numbers were insufficient for significance.

The findings have not changed PCR testing at Dr. Stone's institution. But they have raised the index of suspicion in the clinical setting, as a PCR-positive result may confound the diagnosis of cough illness in patients who have had a pertussis infection in the prior 6 months, but are not currently infected, Dr. Stone said.

“I think it's going to have to be taken into clinical context a lot more strongly,” he said. “We can't just say, 'Oh this PCR was positive, this patient has pertussis.' We have to put it into clinical context.”

The study was prompted by a case in which a 7-week-old infant was admitted to the pediatric intensive care unit for respiratory failure and seizure with a prolonged 6-week hospital course, only to be readmitted with coughing paroxysm and classic whoop 17 days after discharge and 58 days after onset of symptoms and initiation of treatment. At both admissions, pertussis PCR was positive and direct fluorescent antibody culture negative. It was unclear whether she had pertussis again, a macrolide-resistant organism or simply a persisting positive PCR—raising the question as to the duration of PCR positivity, Dr. Stone explained.

A PCR-positive result may confound the diagnosis of cough illness in certain patients. DR. STONE

TORONTO — Bordetella pertussis polymerase chain reaction tests can be positive months after clinical illness, Dr. Bryan Stone reported in a poster presentation at the annual meeting of the Pediatric Academic Societies.

It took a full 7 months for patients who initially tested positive for B. pertussis by polymerase chain reaction (PCR) to convert to a negative status, according to data from a prospective cohort study of 36 patients.

Rapid PCR testing has a sensitivity of 94%–98%. But there are concerns the test may be overly sensitive and may produce clinically irrelevant positives.

Patients with pertussis are believed to be contagious through the first 21 days of illness or completion of 5 days of antibiotics. What hasn't been known is the length of time after reported onset of symptoms that PCR testing remains positive, said Dr. Stone, medical director of the neuroscience trauma unit and assistant professor of pediatrics at the University of Utah, Salt Lake City.

“What we usually do clinically is, once we test, we treat for 5 days in isolation and assume that they are no longer contagious and basically cured, and let them out of isolation,” Dr. Stone said in an interview. “This has some implications because these people are clearly still carrying this organism for weeks and months; and all of these patients were treated with antibiotics.”

The analysis was based on 36 participants providing 61 samples taken over a range of 4 days to 204 days from onset of symptoms. Thirteen “index” cases were PCR-positive infants admitted to a tertiary care center and 23 were in close contact with an infected infant and had a cough lasting 7 or more days. The mean age of the index cases was 78 days, and none had received any pertussis immunizations.

Testing occurred weekly for 3 weeks and then monthly or every other month for 12 months, or until the test became negative. Overall, 15 patients allowed serial sampling; 16 allowed only one sample; and 5 were initially negative, but remained ill for more than 21 days from onset of symptoms.

Antibiotics were started 4–136 days after onset of symptoms, and from 35 days prior to 1 day after enrollment. There was no difference in antibiotic exposure in patients who tested PCR positive or negative, Dr. Stone and his associates reported.

Half of the participants remained PCR positive between 60 and 150 days after onset of symptoms. Post-tussive emesis, cyanosis, and hypoxemia by pulse oximetry were more common in PCR-positive patients, while sore throat and rhinorrhea were more common in PCR-negative patients. But the sample numbers were insufficient for significance.

The findings have not changed PCR testing at Dr. Stone's institution. But they have raised the index of suspicion in the clinical setting, as a PCR-positive result may confound the diagnosis of cough illness in patients who have had a pertussis infection in the prior 6 months, but are not currently infected, Dr. Stone said.

“I think it's going to have to be taken into clinical context a lot more strongly,” he said. “We can't just say, 'Oh this PCR was positive, this patient has pertussis.' We have to put it into clinical context.”

The study was prompted by a case in which a 7-week-old infant was admitted to the pediatric intensive care unit for respiratory failure and seizure with a prolonged 6-week hospital course, only to be readmitted with coughing paroxysm and classic whoop 17 days after discharge and 58 days after onset of symptoms and initiation of treatment. At both admissions, pertussis PCR was positive and direct fluorescent antibody culture negative. It was unclear whether she had pertussis again, a macrolide-resistant organism or simply a persisting positive PCR—raising the question as to the duration of PCR positivity, Dr. Stone explained.

A PCR-positive result may confound the diagnosis of cough illness in certain patients. DR. STONE

KANSAS CITY, MO. — Rotavirus G2 serotypes caused an unexpectedly high proportion of rotavirus dehydrating acute gastroenteritis in infants and children during the 2005–2006 epidemic season in Philadelphia, data from an industry-sponsored study show.

Serotype G1P1A[8] is the most common circulating human rotavirus during an epidemic, while G2 serotypes emerge sporadically. Overall, 45% of 2005–2006 rotavirus acute gastroenteritis (AGE) cases at Children's Hospital of Philadelphia (CHOP) were caused by non-G1 serotypes, predominantly G2, Diane Lawley, R.N., and her associates reported in a poster at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Annual surveillance at Children's Hospital of Philadelphia indicates a steady increase in the number of rotavirus AGE cases since the 1994–1995 season. In 2005–2006, there were 306 evaluable cases, compared with 92–185 cases during the preceding 11 consecutive seasons.

Final analysis of 275 community-acquired cases in 2005–2006, after 31 nosocomial cases were removed from analysis, indicated that G2 serotypes caused 101 (37%) cases of AGE, compared with just 1%–11% in the preceding 6 years in the study was conducted by Merck Research Laboratories in West Point, Pa., and CHOP's Clark Laboratory, which receives funding from Merck.

In addition, 21 (8%) serotype G9 cases were identified in 2005–2006.

Data were not available for the entire 11 seasons because only a limited number of samples were tested during the first 5 seasons, Ms. Lawley explained in an interview.

G2 serotypes caused proportionally more gastroenteritis in infants 5 months of age or less (34 cases) and in infants age 12–17 months (15 cases). G2 serotypes also were more common in black infants (80 cases), and in infants from urban versus nonurban homes (66 vs. 34), the authors reported.

The majority of samples in the study were obtained from CHOP inpatients (86%) or patients evaluated in the emergency department (10%), with a smaller percentage (4%) coming from outpatient clinics.

“Although untested, the inability to predict large non-G1 rotavirus outbreaks may favor the use of a multivalent vaccine that specifically protects against G2 infections, which usually do not coexpress P1A[8],” the authors concluded.

Merck's new oral pentavalent rotavirus vaccine (RotaTeq), licensed in the United States in 2006 for children aged 6–32 weeks, contains serotypes G1–4 and G1P1A[8].

GlaxoSmithKline's new monovalent vaccine (Rotarix), licensed in Mexico and numerous other countries, contains the G1P1A[8] serotype.

KANSAS CITY, MO. — Rotavirus G2 serotypes caused an unexpectedly high proportion of rotavirus dehydrating acute gastroenteritis in infants and children during the 2005–2006 epidemic season in Philadelphia, data from an industry-sponsored study show.

Serotype G1P1A[8] is the most common circulating human rotavirus during an epidemic, while G2 serotypes emerge sporadically. Overall, 45% of 2005–2006 rotavirus acute gastroenteritis (AGE) cases at Children's Hospital of Philadelphia (CHOP) were caused by non-G1 serotypes, predominantly G2, Diane Lawley, R.N., and her associates reported in a poster at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Annual surveillance at Children's Hospital of Philadelphia indicates a steady increase in the number of rotavirus AGE cases since the 1994–1995 season. In 2005–2006, there were 306 evaluable cases, compared with 92–185 cases during the preceding 11 consecutive seasons.

Final analysis of 275 community-acquired cases in 2005–2006, after 31 nosocomial cases were removed from analysis, indicated that G2 serotypes caused 101 (37%) cases of AGE, compared with just 1%–11% in the preceding 6 years in the study was conducted by Merck Research Laboratories in West Point, Pa., and CHOP's Clark Laboratory, which receives funding from Merck.

In addition, 21 (8%) serotype G9 cases were identified in 2005–2006.

Data were not available for the entire 11 seasons because only a limited number of samples were tested during the first 5 seasons, Ms. Lawley explained in an interview.

G2 serotypes caused proportionally more gastroenteritis in infants 5 months of age or less (34 cases) and in infants age 12–17 months (15 cases). G2 serotypes also were more common in black infants (80 cases), and in infants from urban versus nonurban homes (66 vs. 34), the authors reported.

The majority of samples in the study were obtained from CHOP inpatients (86%) or patients evaluated in the emergency department (10%), with a smaller percentage (4%) coming from outpatient clinics.

“Although untested, the inability to predict large non-G1 rotavirus outbreaks may favor the use of a multivalent vaccine that specifically protects against G2 infections, which usually do not coexpress P1A[8],” the authors concluded.

Merck's new oral pentavalent rotavirus vaccine (RotaTeq), licensed in the United States in 2006 for children aged 6–32 weeks, contains serotypes G1–4 and G1P1A[8].

GlaxoSmithKline's new monovalent vaccine (Rotarix), licensed in Mexico and numerous other countries, contains the G1P1A[8] serotype.

KANSAS CITY, MO. — Rotavirus G2 serotypes caused an unexpectedly high proportion of rotavirus dehydrating acute gastroenteritis in infants and children during the 2005–2006 epidemic season in Philadelphia, data from an industry-sponsored study show.

Serotype G1P1A[8] is the most common circulating human rotavirus during an epidemic, while G2 serotypes emerge sporadically. Overall, 45% of 2005–2006 rotavirus acute gastroenteritis (AGE) cases at Children's Hospital of Philadelphia (CHOP) were caused by non-G1 serotypes, predominantly G2, Diane Lawley, R.N., and her associates reported in a poster at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Annual surveillance at Children's Hospital of Philadelphia indicates a steady increase in the number of rotavirus AGE cases since the 1994–1995 season. In 2005–2006, there were 306 evaluable cases, compared with 92–185 cases during the preceding 11 consecutive seasons.

Final analysis of 275 community-acquired cases in 2005–2006, after 31 nosocomial cases were removed from analysis, indicated that G2 serotypes caused 101 (37%) cases of AGE, compared with just 1%–11% in the preceding 6 years in the study was conducted by Merck Research Laboratories in West Point, Pa., and CHOP's Clark Laboratory, which receives funding from Merck.

In addition, 21 (8%) serotype G9 cases were identified in 2005–2006.

Data were not available for the entire 11 seasons because only a limited number of samples were tested during the first 5 seasons, Ms. Lawley explained in an interview.

G2 serotypes caused proportionally more gastroenteritis in infants 5 months of age or less (34 cases) and in infants age 12–17 months (15 cases). G2 serotypes also were more common in black infants (80 cases), and in infants from urban versus nonurban homes (66 vs. 34), the authors reported.

The majority of samples in the study were obtained from CHOP inpatients (86%) or patients evaluated in the emergency department (10%), with a smaller percentage (4%) coming from outpatient clinics.

“Although untested, the inability to predict large non-G1 rotavirus outbreaks may favor the use of a multivalent vaccine that specifically protects against G2 infections, which usually do not coexpress P1A[8],” the authors concluded.

Merck's new oral pentavalent rotavirus vaccine (RotaTeq), licensed in the United States in 2006 for children aged 6–32 weeks, contains serotypes G1–4 and G1P1A[8].

GlaxoSmithKline's new monovalent vaccine (Rotarix), licensed in Mexico and numerous other countries, contains the G1P1A[8] serotype.

NEW YORK — Tourette's syndrome treatment should be targeted to improve comorbidities rather than on the characteristic vocal and motor tics, Dr. John T. Walkup said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“To enhance outcome, go for the comorbidity; don't go for the tics,” said Dr. Walkup of the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore.

“As tics are easy to spot, doctors have a tendency to treat tics first and then stop,” Dr. Walkup said at the meeting. “It's an impulse I would encourage everyone to restrain.”

As tics wax and wane even during treatment, treating physicians can get caught “chasing” tics by upping the dose, and adding or changing meds. Because tics wax and wane, doctors may falsely believe that the medication just delivered was responsible for the improvement, Dr. Walkup said.

Additionally, the comorbidity may not respond to tic-suppressing medications, and a few children with Tourette's will actually develop anxiety or depressive disorders on antipsychotics, Dr. Walkup said.

Tics can present in upward of 25% of school-aged children. Tourette's syndrome is associated with several coexisting conditions, including obsessive-compulsive disorder, attention-deficit hyperactivity disorder (ADHD), anxiety and depressive disorders, and other behavioral problems.

A small percentage of patients have a poor outcome from tics alone, Dr. Walkup said.

Taking a good family and social history is essential to identifying genetic and environmental factors for these conditions.

Children are at risk for specific comorbid conditions at certain ages. As a general rule, ADHD is more likely to occur in children at about ages 5–7 years, whereas anxiety tends to present between 8–10 years, depression between 10–14 years, and the classic version of bipolar disorder from age 14 years and up, Dr. Walkup said.

“If you've got a kid with a history of mild tics and who at age 9 deteriorates in his course, I'd be looking for an anxiety disorder as a potential cause of the deterioration, he said.

Many Tourette's syndrome patients also have behavioral problems, Dr. Walkup said.

Since Tourette's is considered a neurologic disorder, parents inadvertently may back off routine discipline strategies resulting in an increase in behavior problems, he explained.

Dr. Walkup recommends parent training for child behavioral problems, including emotional outbursts.

Data are expected at the end of 2007 from two large National Institutes of Health-funded studies evaluating behavioral strategies for tic suppression in children with Tourette's, he said.

NEW YORK — Tourette's syndrome treatment should be targeted to improve comorbidities rather than on the characteristic vocal and motor tics, Dr. John T. Walkup said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“To enhance outcome, go for the comorbidity; don't go for the tics,” said Dr. Walkup of the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore.

“As tics are easy to spot, doctors have a tendency to treat tics first and then stop,” Dr. Walkup said at the meeting. “It's an impulse I would encourage everyone to restrain.”

As tics wax and wane even during treatment, treating physicians can get caught “chasing” tics by upping the dose, and adding or changing meds. Because tics wax and wane, doctors may falsely believe that the medication just delivered was responsible for the improvement, Dr. Walkup said.

Additionally, the comorbidity may not respond to tic-suppressing medications, and a few children with Tourette's will actually develop anxiety or depressive disorders on antipsychotics, Dr. Walkup said.

Tics can present in upward of 25% of school-aged children. Tourette's syndrome is associated with several coexisting conditions, including obsessive-compulsive disorder, attention-deficit hyperactivity disorder (ADHD), anxiety and depressive disorders, and other behavioral problems.

A small percentage of patients have a poor outcome from tics alone, Dr. Walkup said.

Taking a good family and social history is essential to identifying genetic and environmental factors for these conditions.

Children are at risk for specific comorbid conditions at certain ages. As a general rule, ADHD is more likely to occur in children at about ages 5–7 years, whereas anxiety tends to present between 8–10 years, depression between 10–14 years, and the classic version of bipolar disorder from age 14 years and up, Dr. Walkup said.

“If you've got a kid with a history of mild tics and who at age 9 deteriorates in his course, I'd be looking for an anxiety disorder as a potential cause of the deterioration, he said.

Many Tourette's syndrome patients also have behavioral problems, Dr. Walkup said.

Since Tourette's is considered a neurologic disorder, parents inadvertently may back off routine discipline strategies resulting in an increase in behavior problems, he explained.

Dr. Walkup recommends parent training for child behavioral problems, including emotional outbursts.

Data are expected at the end of 2007 from two large National Institutes of Health-funded studies evaluating behavioral strategies for tic suppression in children with Tourette's, he said.

NEW YORK — Tourette's syndrome treatment should be targeted to improve comorbidities rather than on the characteristic vocal and motor tics, Dr. John T. Walkup said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“To enhance outcome, go for the comorbidity; don't go for the tics,” said Dr. Walkup of the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore.

“As tics are easy to spot, doctors have a tendency to treat tics first and then stop,” Dr. Walkup said at the meeting. “It's an impulse I would encourage everyone to restrain.”

As tics wax and wane even during treatment, treating physicians can get caught “chasing” tics by upping the dose, and adding or changing meds. Because tics wax and wane, doctors may falsely believe that the medication just delivered was responsible for the improvement, Dr. Walkup said.

Additionally, the comorbidity may not respond to tic-suppressing medications, and a few children with Tourette's will actually develop anxiety or depressive disorders on antipsychotics, Dr. Walkup said.

Tics can present in upward of 25% of school-aged children. Tourette's syndrome is associated with several coexisting conditions, including obsessive-compulsive disorder, attention-deficit hyperactivity disorder (ADHD), anxiety and depressive disorders, and other behavioral problems.

A small percentage of patients have a poor outcome from tics alone, Dr. Walkup said.

Taking a good family and social history is essential to identifying genetic and environmental factors for these conditions.

Children are at risk for specific comorbid conditions at certain ages. As a general rule, ADHD is more likely to occur in children at about ages 5–7 years, whereas anxiety tends to present between 8–10 years, depression between 10–14 years, and the classic version of bipolar disorder from age 14 years and up, Dr. Walkup said.

“If you've got a kid with a history of mild tics and who at age 9 deteriorates in his course, I'd be looking for an anxiety disorder as a potential cause of the deterioration, he said.

Many Tourette's syndrome patients also have behavioral problems, Dr. Walkup said.

Since Tourette's is considered a neurologic disorder, parents inadvertently may back off routine discipline strategies resulting in an increase in behavior problems, he explained.

Dr. Walkup recommends parent training for child behavioral problems, including emotional outbursts.

Data are expected at the end of 2007 from two large National Institutes of Health-funded studies evaluating behavioral strategies for tic suppression in children with Tourette's, he said.

KANSAS CITY, MO. — The strategy of immunizing all children at the 11- to 12-year preadolescent visit and those entering high school with the new meningococcal conjugate vaccine appears to be working, according to preliminary Centers for Disease Control and Prevention data.

Uptake of Menactra vaccine was higher in these target age groups compared with nontargeted 13- and 16-year-olds in a study of 619,371 adolescents, Dr. Pascale Wortley and associates reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Menactra (made by Sanofi Pasteur) was licensed in January 2005 for use in persons aged 11–55 years, and is recommended for all children at the 11- to 12-year preadolescent visit, those entering high school, college students living in dormitories, U.S. military recruits, and others who choose to be vaccinated.

The study also indicated that heavy demand during the summer months did cause a vaccine shortage.

“Even though the total number of teens vaccinated did not exceed the amount of vaccine available, because it was all concentrated over the space of a few months, it did create a shortage situation,” said Dr. Wortley of the CDC's Immunization Services Division in Atlanta.

The investigators analyzed data from 619,371 adolescents aged 11–16 years vaccinated with Menactra (MCV4) in 2005 at five of eight managed care organizations participating in the Vaccine Safety Datalink.

The five managed care organizations experienced a rapid increase in immunizations among the three age groups (11–12 years, 14–15 years, and 13- and 16-year-olds) between May and August, followed by a rapid decline to a relatively steady rate by Sept. 30. Overall, 73% of vaccinations were given between June and August, said Dr. Wortley, who presented the results on behalf of lead author Dr. Suchita Lorick, also of the CDC in Atlanta.

At the end of 2005, the cumulative coverage was 12% for ages 11–12 years, 11% for ages 14–15 years, and 8% for ages 13 and 16 years.

Compared with the group of 13- and 16-year-olds, the risk ratios for receiving Menactra for those aged 11–12 years and 14–15 years were 1.49 and 1.29, respectively.

Coverage among 11- to 12-year-olds reached nearly 35% at one of the HMO sites with an explicit policy targeting this age group, compared with less than 15% at two other larger HMO sites that reported experiencing some degree of vaccine shortage in 2005, she said.

Because of the strong summer usage, the investigators decided to compare Menactra uptake patterns with uptake for the old polysaccharide meningococcal formulation (Menomune, also made by Sanofi Pasteur) and the tetanus and diphtheria (Td) vaccine. They used data from the 2003–2004 Vaccine Safety Datalink and 2004 data from the MarketScan databases, representing 40 self-insured employers and more than 1 million 11- to 16-year-olds.

All three vaccines experienced increased usage during the summer, which comes as no surprise given the number of school physical examinations conducted at this time of year, Dr. Wortley said.

The September decline observed in Menactra usage likely was not related to the Food and Drug Administration's and CDC's notice in October 2005 that Guillain-Barré Syndrome could be associated with Menactra, she added.

“Clearly, vaccination had already decreased dramatically before that notice appeared,” Dr. Wortley said. “It looks like the uptick was related to the ACIP [Advisory Committee on Immunization Practices] recommendation, and potentially, the trend down was not related to the [Guillain-Barré Syndrome] notice.”

The CDC's Advisory Committee on Immunization Practices published its recommendations for Menactra in May 2005 after debating the age group or groups for which the vaccine should be recommended. Older adolescents (17–18 years) have the highest rates of meningococcal disease (1.7 per 100,000). But younger teens, who have somewhat lower rates of infection, are more likely to visit their physicians through the already established preadolescent health care visit and high school-entry physical examination.

KANSAS CITY, MO. — The strategy of immunizing all children at the 11- to 12-year preadolescent visit and those entering high school with the new meningococcal conjugate vaccine appears to be working, according to preliminary Centers for Disease Control and Prevention data.

Uptake of Menactra vaccine was higher in these target age groups compared with nontargeted 13- and 16-year-olds in a study of 619,371 adolescents, Dr. Pascale Wortley and associates reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Menactra (made by Sanofi Pasteur) was licensed in January 2005 for use in persons aged 11–55 years, and is recommended for all children at the 11- to 12-year preadolescent visit, those entering high school, college students living in dormitories, U.S. military recruits, and others who choose to be vaccinated.

The study also indicated that heavy demand during the summer months did cause a vaccine shortage.

“Even though the total number of teens vaccinated did not exceed the amount of vaccine available, because it was all concentrated over the space of a few months, it did create a shortage situation,” said Dr. Wortley of the CDC's Immunization Services Division in Atlanta.

The investigators analyzed data from 619,371 adolescents aged 11–16 years vaccinated with Menactra (MCV4) in 2005 at five of eight managed care organizations participating in the Vaccine Safety Datalink.

The five managed care organizations experienced a rapid increase in immunizations among the three age groups (11–12 years, 14–15 years, and 13- and 16-year-olds) between May and August, followed by a rapid decline to a relatively steady rate by Sept. 30. Overall, 73% of vaccinations were given between June and August, said Dr. Wortley, who presented the results on behalf of lead author Dr. Suchita Lorick, also of the CDC in Atlanta.

At the end of 2005, the cumulative coverage was 12% for ages 11–12 years, 11% for ages 14–15 years, and 8% for ages 13 and 16 years.

Compared with the group of 13- and 16-year-olds, the risk ratios for receiving Menactra for those aged 11–12 years and 14–15 years were 1.49 and 1.29, respectively.

Coverage among 11- to 12-year-olds reached nearly 35% at one of the HMO sites with an explicit policy targeting this age group, compared with less than 15% at two other larger HMO sites that reported experiencing some degree of vaccine shortage in 2005, she said.

Because of the strong summer usage, the investigators decided to compare Menactra uptake patterns with uptake for the old polysaccharide meningococcal formulation (Menomune, also made by Sanofi Pasteur) and the tetanus and diphtheria (Td) vaccine. They used data from the 2003–2004 Vaccine Safety Datalink and 2004 data from the MarketScan databases, representing 40 self-insured employers and more than 1 million 11- to 16-year-olds.

All three vaccines experienced increased usage during the summer, which comes as no surprise given the number of school physical examinations conducted at this time of year, Dr. Wortley said.

The September decline observed in Menactra usage likely was not related to the Food and Drug Administration's and CDC's notice in October 2005 that Guillain-Barré Syndrome could be associated with Menactra, she added.

“Clearly, vaccination had already decreased dramatically before that notice appeared,” Dr. Wortley said. “It looks like the uptick was related to the ACIP [Advisory Committee on Immunization Practices] recommendation, and potentially, the trend down was not related to the [Guillain-Barré Syndrome] notice.”

The CDC's Advisory Committee on Immunization Practices published its recommendations for Menactra in May 2005 after debating the age group or groups for which the vaccine should be recommended. Older adolescents (17–18 years) have the highest rates of meningococcal disease (1.7 per 100,000). But younger teens, who have somewhat lower rates of infection, are more likely to visit their physicians through the already established preadolescent health care visit and high school-entry physical examination.

KANSAS CITY, MO. — The strategy of immunizing all children at the 11- to 12-year preadolescent visit and those entering high school with the new meningococcal conjugate vaccine appears to be working, according to preliminary Centers for Disease Control and Prevention data.

Uptake of Menactra vaccine was higher in these target age groups compared with nontargeted 13- and 16-year-olds in a study of 619,371 adolescents, Dr. Pascale Wortley and associates reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Menactra (made by Sanofi Pasteur) was licensed in January 2005 for use in persons aged 11–55 years, and is recommended for all children at the 11- to 12-year preadolescent visit, those entering high school, college students living in dormitories, U.S. military recruits, and others who choose to be vaccinated.

The study also indicated that heavy demand during the summer months did cause a vaccine shortage.

“Even though the total number of teens vaccinated did not exceed the amount of vaccine available, because it was all concentrated over the space of a few months, it did create a shortage situation,” said Dr. Wortley of the CDC's Immunization Services Division in Atlanta.

The investigators analyzed data from 619,371 adolescents aged 11–16 years vaccinated with Menactra (MCV4) in 2005 at five of eight managed care organizations participating in the Vaccine Safety Datalink.

The five managed care organizations experienced a rapid increase in immunizations among the three age groups (11–12 years, 14–15 years, and 13- and 16-year-olds) between May and August, followed by a rapid decline to a relatively steady rate by Sept. 30. Overall, 73% of vaccinations were given between June and August, said Dr. Wortley, who presented the results on behalf of lead author Dr. Suchita Lorick, also of the CDC in Atlanta.

At the end of 2005, the cumulative coverage was 12% for ages 11–12 years, 11% for ages 14–15 years, and 8% for ages 13 and 16 years.

Compared with the group of 13- and 16-year-olds, the risk ratios for receiving Menactra for those aged 11–12 years and 14–15 years were 1.49 and 1.29, respectively.

Coverage among 11- to 12-year-olds reached nearly 35% at one of the HMO sites with an explicit policy targeting this age group, compared with less than 15% at two other larger HMO sites that reported experiencing some degree of vaccine shortage in 2005, she said.

Because of the strong summer usage, the investigators decided to compare Menactra uptake patterns with uptake for the old polysaccharide meningococcal formulation (Menomune, also made by Sanofi Pasteur) and the tetanus and diphtheria (Td) vaccine. They used data from the 2003–2004 Vaccine Safety Datalink and 2004 data from the MarketScan databases, representing 40 self-insured employers and more than 1 million 11- to 16-year-olds.

All three vaccines experienced increased usage during the summer, which comes as no surprise given the number of school physical examinations conducted at this time of year, Dr. Wortley said.

The September decline observed in Menactra usage likely was not related to the Food and Drug Administration's and CDC's notice in October 2005 that Guillain-Barré Syndrome could be associated with Menactra, she added.

“Clearly, vaccination had already decreased dramatically before that notice appeared,” Dr. Wortley said. “It looks like the uptick was related to the ACIP [Advisory Committee on Immunization Practices] recommendation, and potentially, the trend down was not related to the [Guillain-Barré Syndrome] notice.”

The CDC's Advisory Committee on Immunization Practices published its recommendations for Menactra in May 2005 after debating the age group or groups for which the vaccine should be recommended. Older adolescents (17–18 years) have the highest rates of meningococcal disease (1.7 per 100,000). But younger teens, who have somewhat lower rates of infection, are more likely to visit their physicians through the already established preadolescent health care visit and high school-entry physical examination.

NEW YORK – A 6-year-old girl with autism is treated with risperidone 0.5 mg twice daily, and after 2 months of treatment her behavior is improved, and there are no noted side effects. But her serum prolactin is clearly elevated for her age at 45 ng/mL. What should you do?

Nothing. In fact, her serum prolactin shouldn't have been measured in the first place, Dr. Harold E. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

Secretion of prolactin is primarily regulated by tonic inhibition by dopamine, which is secreted by the hypothalamus and acts on D2 dopamine (DA) receptors in the pituitary gland. Most antipsychotics have D2 DA antagonist activity and therefore raise serum prolactin.

Atypical antipsychotics vary in their affinity for the D2 DA receptor and in their propensity to cause hyperprolactinemia, which is characterized by amenorrhea and oligomenorrhea in women of reproductive age, breast enlargement or engorgement in women and men, galactorrhea, decreased libido, erectile dysfunction, osteoporosis, failure to enter or progress through puberty, and possibly hirsutism in women.

The young autism patient is prepubertal and has no ovarian function, so there is nothing for her prolactin to inhibit, said Dr. Carlson of the division of endocrinology at the State University of New York at Stony Brook. In the absence of estrogen priming, it is unlikely she will have breast enlargement or galactorrhea.

Moreover, prolactin levels often spontaneously decrease over time despite continued antipsychotic therapy, even at the same dosage. A post hoc analysis of data from five clinical trials in 700 children and adolescents, aged 5–15 years, reveals that prolactin levels in children receiving long-term risperidone (Risperdal) tend to peak within the first 2 months and then steadily decline to values within or very close to normal within 3–5 months (J. Clin. Psychiatry 2003;64:1362–9).

A similar trend in prolactin levels was identified in a large 52-week unpublished study involving 542 children conducted by Dr. Christoph U. Correll and his colleagues at the Zucker Hillside Hospital in Glen Oaks, N.Y., Dr. Carlson reported.

Risperidone is the most potent prolactin elevator, followed by haloperidol (Haldol), olanzapine (Zyprexa), ziprasidone (Geodon), and quetiapine (Seroquel). Clozapine (Clozaril) is relatively neutral, and aripiprazole (Abilify)–a partial D2 DA agonist–suppresses prolactin below baseline levels. It is sometimes useful to combine aripiprazole or a prolactin-neutral agent if discontinuation of a prolactin-raising antipsychotic is not an option, Dr. Carlson said.

First and foremost, inquire about menstruation, nipple discharge, sexual functioning, and pubertal development in all patients receiving antipsychotics; if they are normal, there is no need to measure serum prolactin, he said.

If prolactin is elevated in an asymptomatic patient, perform a pregnancy test and check thyroid-stimulating hormone and serum creatinine to rule out other causes of hyperprolactinemia. Because estrogen enhances prolactin responsiveness, women and postpubertal girls have greater drug-induced prolactin elevations than do men. In general, the higher the serum prolactin, the more likely it is for the patient to be symptomatic, Dr. Carlson said.

If serum prolactin is less than 200 ng/mL in patients with clinical features of hyperprolactinemia, try reducing the dose of the antipsychotic or switch to a more prolactin-sparing drug. If prolactin is greater than 200 ng/mL, or remains elevated after switching agents, that is the only time to perform an MRI scan of the sella turcica to look for a pituitary adenoma or parasellar tumor, Dr. Carlson said.

Some patients have been alarmed about recently reported surveillance data identifying 77 reports of pituitary tumors occurring in patients receiving antipsychotic agents–particularly risperidone–since 1968 (Pharmacotherapy 2006;26:748–58). The data raise obvious questions, said Dr. Carlson, but he added that the report provided no information on the type of tumor, response to changes in therapy, or patient outcomes.

In addition, the patients may have incidental pituitary tumors, which are found in roughly 10% of normal adults on routine MRI. “We really are awaiting a systematic and exhaustive study to determine if there is a causal or coincidental association,” he said. “I favor coincidental.”

If a patient's MRI is normal, estrogen and testosterone could be replaced to treat hypogonadism, or medication could be given for osteoporosis, if needed. A few patients with antipsychotic-induced hyperprolactinemia have been concurrently treated with dopamine agonists with partial resolution of the hyperprolactinemia. But Dr. Carlson cautioned that in some patients, psychosis is occasionally worsened.

A prepubertal patient has no ovarian function, so there is nothing for her prolactin to inhibit. DR. CARLSON

NEW YORK – A 6-year-old girl with autism is treated with risperidone 0.5 mg twice daily, and after 2 months of treatment her behavior is improved, and there are no noted side effects. But her serum prolactin is clearly elevated for her age at 45 ng/mL. What should you do?

Nothing. In fact, her serum prolactin shouldn't have been measured in the first place, Dr. Harold E. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

Secretion of prolactin is primarily regulated by tonic inhibition by dopamine, which is secreted by the hypothalamus and acts on D2 dopamine (DA) receptors in the pituitary gland. Most antipsychotics have D2 DA antagonist activity and therefore raise serum prolactin.

Atypical antipsychotics vary in their affinity for the D2 DA receptor and in their propensity to cause hyperprolactinemia, which is characterized by amenorrhea and oligomenorrhea in women of reproductive age, breast enlargement or engorgement in women and men, galactorrhea, decreased libido, erectile dysfunction, osteoporosis, failure to enter or progress through puberty, and possibly hirsutism in women.

The young autism patient is prepubertal and has no ovarian function, so there is nothing for her prolactin to inhibit, said Dr. Carlson of the division of endocrinology at the State University of New York at Stony Brook. In the absence of estrogen priming, it is unlikely she will have breast enlargement or galactorrhea.

Moreover, prolactin levels often spontaneously decrease over time despite continued antipsychotic therapy, even at the same dosage. A post hoc analysis of data from five clinical trials in 700 children and adolescents, aged 5–15 years, reveals that prolactin levels in children receiving long-term risperidone (Risperdal) tend to peak within the first 2 months and then steadily decline to values within or very close to normal within 3–5 months (J. Clin. Psychiatry 2003;64:1362–9).

A similar trend in prolactin levels was identified in a large 52-week unpublished study involving 542 children conducted by Dr. Christoph U. Correll and his colleagues at the Zucker Hillside Hospital in Glen Oaks, N.Y., Dr. Carlson reported.

Risperidone is the most potent prolactin elevator, followed by haloperidol (Haldol), olanzapine (Zyprexa), ziprasidone (Geodon), and quetiapine (Seroquel). Clozapine (Clozaril) is relatively neutral, and aripiprazole (Abilify)–a partial D2 DA agonist–suppresses prolactin below baseline levels. It is sometimes useful to combine aripiprazole or a prolactin-neutral agent if discontinuation of a prolactin-raising antipsychotic is not an option, Dr. Carlson said.

First and foremost, inquire about menstruation, nipple discharge, sexual functioning, and pubertal development in all patients receiving antipsychotics; if they are normal, there is no need to measure serum prolactin, he said.

If prolactin is elevated in an asymptomatic patient, perform a pregnancy test and check thyroid-stimulating hormone and serum creatinine to rule out other causes of hyperprolactinemia. Because estrogen enhances prolactin responsiveness, women and postpubertal girls have greater drug-induced prolactin elevations than do men. In general, the higher the serum prolactin, the more likely it is for the patient to be symptomatic, Dr. Carlson said.

If serum prolactin is less than 200 ng/mL in patients with clinical features of hyperprolactinemia, try reducing the dose of the antipsychotic or switch to a more prolactin-sparing drug. If prolactin is greater than 200 ng/mL, or remains elevated after switching agents, that is the only time to perform an MRI scan of the sella turcica to look for a pituitary adenoma or parasellar tumor, Dr. Carlson said.

Some patients have been alarmed about recently reported surveillance data identifying 77 reports of pituitary tumors occurring in patients receiving antipsychotic agents–particularly risperidone–since 1968 (Pharmacotherapy 2006;26:748–58). The data raise obvious questions, said Dr. Carlson, but he added that the report provided no information on the type of tumor, response to changes in therapy, or patient outcomes.

In addition, the patients may have incidental pituitary tumors, which are found in roughly 10% of normal adults on routine MRI. “We really are awaiting a systematic and exhaustive study to determine if there is a causal or coincidental association,” he said. “I favor coincidental.”

If a patient's MRI is normal, estrogen and testosterone could be replaced to treat hypogonadism, or medication could be given for osteoporosis, if needed. A few patients with antipsychotic-induced hyperprolactinemia have been concurrently treated with dopamine agonists with partial resolution of the hyperprolactinemia. But Dr. Carlson cautioned that in some patients, psychosis is occasionally worsened.

A prepubertal patient has no ovarian function, so there is nothing for her prolactin to inhibit. DR. CARLSON

NEW YORK – A 6-year-old girl with autism is treated with risperidone 0.5 mg twice daily, and after 2 months of treatment her behavior is improved, and there are no noted side effects. But her serum prolactin is clearly elevated for her age at 45 ng/mL. What should you do?

Nothing. In fact, her serum prolactin shouldn't have been measured in the first place, Dr. Harold E. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

Secretion of prolactin is primarily regulated by tonic inhibition by dopamine, which is secreted by the hypothalamus and acts on D2 dopamine (DA) receptors in the pituitary gland. Most antipsychotics have D2 DA antagonist activity and therefore raise serum prolactin.

Atypical antipsychotics vary in their affinity for the D2 DA receptor and in their propensity to cause hyperprolactinemia, which is characterized by amenorrhea and oligomenorrhea in women of reproductive age, breast enlargement or engorgement in women and men, galactorrhea, decreased libido, erectile dysfunction, osteoporosis, failure to enter or progress through puberty, and possibly hirsutism in women.

The young autism patient is prepubertal and has no ovarian function, so there is nothing for her prolactin to inhibit, said Dr. Carlson of the division of endocrinology at the State University of New York at Stony Brook. In the absence of estrogen priming, it is unlikely she will have breast enlargement or galactorrhea.

Moreover, prolactin levels often spontaneously decrease over time despite continued antipsychotic therapy, even at the same dosage. A post hoc analysis of data from five clinical trials in 700 children and adolescents, aged 5–15 years, reveals that prolactin levels in children receiving long-term risperidone (Risperdal) tend to peak within the first 2 months and then steadily decline to values within or very close to normal within 3–5 months (J. Clin. Psychiatry 2003;64:1362–9).

A similar trend in prolactin levels was identified in a large 52-week unpublished study involving 542 children conducted by Dr. Christoph U. Correll and his colleagues at the Zucker Hillside Hospital in Glen Oaks, N.Y., Dr. Carlson reported.

Risperidone is the most potent prolactin elevator, followed by haloperidol (Haldol), olanzapine (Zyprexa), ziprasidone (Geodon), and quetiapine (Seroquel). Clozapine (Clozaril) is relatively neutral, and aripiprazole (Abilify)–a partial D2 DA agonist–suppresses prolactin below baseline levels. It is sometimes useful to combine aripiprazole or a prolactin-neutral agent if discontinuation of a prolactin-raising antipsychotic is not an option, Dr. Carlson said.

First and foremost, inquire about menstruation, nipple discharge, sexual functioning, and pubertal development in all patients receiving antipsychotics; if they are normal, there is no need to measure serum prolactin, he said.

If prolactin is elevated in an asymptomatic patient, perform a pregnancy test and check thyroid-stimulating hormone and serum creatinine to rule out other causes of hyperprolactinemia. Because estrogen enhances prolactin responsiveness, women and postpubertal girls have greater drug-induced prolactin elevations than do men. In general, the higher the serum prolactin, the more likely it is for the patient to be symptomatic, Dr. Carlson said.

If serum prolactin is less than 200 ng/mL in patients with clinical features of hyperprolactinemia, try reducing the dose of the antipsychotic or switch to a more prolactin-sparing drug. If prolactin is greater than 200 ng/mL, or remains elevated after switching agents, that is the only time to perform an MRI scan of the sella turcica to look for a pituitary adenoma or parasellar tumor, Dr. Carlson said.

Some patients have been alarmed about recently reported surveillance data identifying 77 reports of pituitary tumors occurring in patients receiving antipsychotic agents–particularly risperidone–since 1968 (Pharmacotherapy 2006;26:748–58). The data raise obvious questions, said Dr. Carlson, but he added that the report provided no information on the type of tumor, response to changes in therapy, or patient outcomes.

In addition, the patients may have incidental pituitary tumors, which are found in roughly 10% of normal adults on routine MRI. “We really are awaiting a systematic and exhaustive study to determine if there is a causal or coincidental association,” he said. “I favor coincidental.”

If a patient's MRI is normal, estrogen and testosterone could be replaced to treat hypogonadism, or medication could be given for osteoporosis, if needed. A few patients with antipsychotic-induced hyperprolactinemia have been concurrently treated with dopamine agonists with partial resolution of the hyperprolactinemia. But Dr. Carlson cautioned that in some patients, psychosis is occasionally worsened.

A prepubertal patient has no ovarian function, so there is nothing for her prolactin to inhibit. DR. CARLSON

MIAMI BEACH — Inadvertent misadministration can occur with several new vaccines that are commonly used, Dr. Larry Pickering said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

One potential source of confusion involves the two new tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccines licensed in 2005 for adolescents and adults, and the diphtheria, tetanus, and pertussis (DTaP) vaccine licensed in 1991 for children 6 weeks to 6 years of age.

One of the reasons for the confusion is that the labeling and packaging are very similar for Adacel (Tdap) and Daptacel (DTaP), Dr. Pickering said.

Sanofi Pasteur, maker of Adacel and Daptacel, confirms it has received reports of misadministration, more commonly involving adults being given the pediatric formulation, Donna K. Cary, director of public relations for Sanofi, said in an interview.

“For many years, DTaP was just a pediatric product, and it wasn't until just recently that we had Adacel for adults and adolescents, and GlaxoSmithKline has Boostrix,” Ms. Cary said. “I think it's that there is a new vaccine. The packaging is actually quite different.”

The company has started tracking reports of misadministration and is looking at ways to make the two products more distinct, such as noting on the label that Daptacel is for infants, she said. The Adacel label already states it is for adolescents and adults.

Until such changes are made, Dr. Pickering said, he keeps the two vaccines straight in his mind by remembering that Adacel and adult both begin with the letter A.

Dr. Pickering is unaware of any reports of mix-ups occurring with GlaxoSmithKline's Boostrix (Tdap) and Infanrix (DTaP) vaccines. No reports of misadministration of its products have been reported to GlaxoSmithKline, spokeswoman Liad Diamond said in an interview.

If an adolescent or adult inadvertently receives DTaP, the vaccine doesn't have to be repeated, although the patient may have increased reactions because the antigen contents are higher, Dr. Pickering said. If Tdap is given to an infant or child, the antigen contents are much lower and the dose will have to be repeated.

A second kind of vaccine mix-up has been reported involving the meningococcal polysaccharide vaccine that has been used subcutaneously for decades in the United States. The newer tetravalent meningococcal conjugate (MCV4) vaccine, licensed in the United States in January 2005, is for intramuscular use only.

The different routes of administration create an “automatic opportunity for confusion,” said Dr. Pickering, professor of pediatrics at Emory University and senior advisor to the director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, both in Atlanta.

Indeed, 101 people in seven states have reportedly received subcutaneous administration of the MCV4 vaccine, according to an investigation by the CDC (MMWR 2006;55:1016–17).

There were 12 nonserious adverse events, including 11 local reactions and a report of fever for 1 day among 54 people queried by providers as a result of the investigation. Serology results from 38 people vaccinated by the subcutaneous route indicate that although their titers were lower than those of patients vaccinated by the intramuscular route, the subcutaneously vaccinated patients were sufficiently protected and didn't need revaccination.

Finally, the Advisory Committee on Immunization Practices recently received reports of adults accidentally receiving the new adult zoster (Varivax) vaccine used to prevent the varicella zoster virus in patients 12 months of age and older, and of infants receiving the Zostavax vaccine used to prevent herpes zoster in adults 60 years of age or older.

Even though all varicella products are made from the same varicella-zoster bulk lots, the zoster vaccine concentration is 14 times higher than the varicella vaccine concentration, Dr. Pickering noted.

If the varicella vaccine is given to an adult, it might not work because of the lower vaccine content, he said. In case of such a mix-up, an adult should then receive the correct zoster vaccine.

If zoster vaccine is inadvertently given to a small child, the dose should count, but reactions might be greater and could include local skin reactions, low-grade fever, and the development of vesicular lesions around the injection site.

MIAMI BEACH — Inadvertent misadministration can occur with several new vaccines that are commonly used, Dr. Larry Pickering said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

One potential source of confusion involves the two new tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccines licensed in 2005 for adolescents and adults, and the diphtheria, tetanus, and pertussis (DTaP) vaccine licensed in 1991 for children 6 weeks to 6 years of age.

One of the reasons for the confusion is that the labeling and packaging are very similar for Adacel (Tdap) and Daptacel (DTaP), Dr. Pickering said.

Sanofi Pasteur, maker of Adacel and Daptacel, confirms it has received reports of misadministration, more commonly involving adults being given the pediatric formulation, Donna K. Cary, director of public relations for Sanofi, said in an interview.

“For many years, DTaP was just a pediatric product, and it wasn't until just recently that we had Adacel for adults and adolescents, and GlaxoSmithKline has Boostrix,” Ms. Cary said. “I think it's that there is a new vaccine. The packaging is actually quite different.”

The company has started tracking reports of misadministration and is looking at ways to make the two products more distinct, such as noting on the label that Daptacel is for infants, she said. The Adacel label already states it is for adolescents and adults.

Until such changes are made, Dr. Pickering said, he keeps the two vaccines straight in his mind by remembering that Adacel and adult both begin with the letter A.

Dr. Pickering is unaware of any reports of mix-ups occurring with GlaxoSmithKline's Boostrix (Tdap) and Infanrix (DTaP) vaccines. No reports of misadministration of its products have been reported to GlaxoSmithKline, spokeswoman Liad Diamond said in an interview.

If an adolescent or adult inadvertently receives DTaP, the vaccine doesn't have to be repeated, although the patient may have increased reactions because the antigen contents are higher, Dr. Pickering said. If Tdap is given to an infant or child, the antigen contents are much lower and the dose will have to be repeated.

A second kind of vaccine mix-up has been reported involving the meningococcal polysaccharide vaccine that has been used subcutaneously for decades in the United States. The newer tetravalent meningococcal conjugate (MCV4) vaccine, licensed in the United States in January 2005, is for intramuscular use only.

The different routes of administration create an “automatic opportunity for confusion,” said Dr. Pickering, professor of pediatrics at Emory University and senior advisor to the director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, both in Atlanta.

Indeed, 101 people in seven states have reportedly received subcutaneous administration of the MCV4 vaccine, according to an investigation by the CDC (MMWR 2006;55:1016–17).

There were 12 nonserious adverse events, including 11 local reactions and a report of fever for 1 day among 54 people queried by providers as a result of the investigation. Serology results from 38 people vaccinated by the subcutaneous route indicate that although their titers were lower than those of patients vaccinated by the intramuscular route, the subcutaneously vaccinated patients were sufficiently protected and didn't need revaccination.

Finally, the Advisory Committee on Immunization Practices recently received reports of adults accidentally receiving the new adult zoster (Varivax) vaccine used to prevent the varicella zoster virus in patients 12 months of age and older, and of infants receiving the Zostavax vaccine used to prevent herpes zoster in adults 60 years of age or older.

Even though all varicella products are made from the same varicella-zoster bulk lots, the zoster vaccine concentration is 14 times higher than the varicella vaccine concentration, Dr. Pickering noted.

If the varicella vaccine is given to an adult, it might not work because of the lower vaccine content, he said. In case of such a mix-up, an adult should then receive the correct zoster vaccine.

If zoster vaccine is inadvertently given to a small child, the dose should count, but reactions might be greater and could include local skin reactions, low-grade fever, and the development of vesicular lesions around the injection site.

MIAMI BEACH — Inadvertent misadministration can occur with several new vaccines that are commonly used, Dr. Larry Pickering said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

One potential source of confusion involves the two new tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccines licensed in 2005 for adolescents and adults, and the diphtheria, tetanus, and pertussis (DTaP) vaccine licensed in 1991 for children 6 weeks to 6 years of age.

One of the reasons for the confusion is that the labeling and packaging are very similar for Adacel (Tdap) and Daptacel (DTaP), Dr. Pickering said.

Sanofi Pasteur, maker of Adacel and Daptacel, confirms it has received reports of misadministration, more commonly involving adults being given the pediatric formulation, Donna K. Cary, director of public relations for Sanofi, said in an interview.

“For many years, DTaP was just a pediatric product, and it wasn't until just recently that we had Adacel for adults and adolescents, and GlaxoSmithKline has Boostrix,” Ms. Cary said. “I think it's that there is a new vaccine. The packaging is actually quite different.”

The company has started tracking reports of misadministration and is looking at ways to make the two products more distinct, such as noting on the label that Daptacel is for infants, she said. The Adacel label already states it is for adolescents and adults.

Until such changes are made, Dr. Pickering said, he keeps the two vaccines straight in his mind by remembering that Adacel and adult both begin with the letter A.

Dr. Pickering is unaware of any reports of mix-ups occurring with GlaxoSmithKline's Boostrix (Tdap) and Infanrix (DTaP) vaccines. No reports of misadministration of its products have been reported to GlaxoSmithKline, spokeswoman Liad Diamond said in an interview.

If an adolescent or adult inadvertently receives DTaP, the vaccine doesn't have to be repeated, although the patient may have increased reactions because the antigen contents are higher, Dr. Pickering said. If Tdap is given to an infant or child, the antigen contents are much lower and the dose will have to be repeated.

A second kind of vaccine mix-up has been reported involving the meningococcal polysaccharide vaccine that has been used subcutaneously for decades in the United States. The newer tetravalent meningococcal conjugate (MCV4) vaccine, licensed in the United States in January 2005, is for intramuscular use only.

The different routes of administration create an “automatic opportunity for confusion,” said Dr. Pickering, professor of pediatrics at Emory University and senior advisor to the director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, both in Atlanta.

Indeed, 101 people in seven states have reportedly received subcutaneous administration of the MCV4 vaccine, according to an investigation by the CDC (MMWR 2006;55:1016–17).

There were 12 nonserious adverse events, including 11 local reactions and a report of fever for 1 day among 54 people queried by providers as a result of the investigation. Serology results from 38 people vaccinated by the subcutaneous route indicate that although their titers were lower than those of patients vaccinated by the intramuscular route, the subcutaneously vaccinated patients were sufficiently protected and didn't need revaccination.

Finally, the Advisory Committee on Immunization Practices recently received reports of adults accidentally receiving the new adult zoster (Varivax) vaccine used to prevent the varicella zoster virus in patients 12 months of age and older, and of infants receiving the Zostavax vaccine used to prevent herpes zoster in adults 60 years of age or older.

Even though all varicella products are made from the same varicella-zoster bulk lots, the zoster vaccine concentration is 14 times higher than the varicella vaccine concentration, Dr. Pickering noted.

If the varicella vaccine is given to an adult, it might not work because of the lower vaccine content, he said. In case of such a mix-up, an adult should then receive the correct zoster vaccine.

If zoster vaccine is inadvertently given to a small child, the dose should count, but reactions might be greater and could include local skin reactions, low-grade fever, and the development of vesicular lesions around the injection site.

MIAMI BEACH — Laser surgery with intravenous deep sedation can be performed safely in a pediatric procedure room rather than an operating room when treating congenital vascular stains, Dr. Elizabeth Alvarez Connelly said in a poster presentation at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Pulsed dye lasers are considered the standard for the treatment of congenital vascular stains in young children, but one of the greatest challenges in their use is maintaining an adequate comfort level throughout the multiple treatment sessions needed.

Children are traditionally treated under gas anesthesia in the OR, but repeat sessions can be costly for all parties and stressful to the patient and family, said Dr. Connelly, a pediatric dermatologist at the University of Miami.

Laser surgery in pediatric procedure rooms does not require a sterile environment or a clearance visit by a pediatrician or anesthesiologist and allows clinicians to treat a large surface area during one laser session. The average time from start to patient release is about 2 hours, compared with 4–6 hours for OR-based treatments.

"For new parents, it's wonderful because they can come in to the procedure room and are there during the [intravenous line placement] and when they leave they can see that the child is asleep and comfortable," she said in an interview. "For the child, they don't even notice the parent was gone. It's just so much easier on everyone."

Dr. Connelly and colleagues presented a case series of 15 children with port-wine stains larger than 10 cm2 who received laser surgery in a pediatric procedure room separate from the main operating suite, with sedation provided by a nurse practitioner and pediatric intensivist. Ethyl chloride spray was used prior to intravenous line insertion and intravenous propofol (Diprivan)/fentanyl or ketamine was dosed based on weight.

The patients received an average of three to four treatments with a 595-nm pulsed dye laser (Candela VBeam) at a fluence of 7.5–9.5 J/cm2, pulse duration of 1.5 milliseconds, and 7-mm spot size.

Lightening of individual port wine stains was observed in all patients after each treatment. The only side effect, purpura, developed in all of the children treated and lasted for 10–14 days, which is the natural course following laser therapy, Dr. Connelly said.

There were no adverse reactions to the anesthesia. No intubations or overnight hospitalizations were required.

Without expensive OR costs, there was a 50%-70% cost savings per laser procedure, said Dr. Connelly, who acknowledged that a formal cost analysis was not performed.

When moving laser treatments from the OR to a pediatric procedure room, ensure that preoperative fluids are restricted based on age; properly sized safety equipment is readily available; and all patients are watched carefully for signs of nausea, vomiting, or fever prior to discharge, she said.

Dr. Connelly added that she has no relevant financial relationship with Candela Corp.

MIAMI BEACH — Laser surgery with intravenous deep sedation can be performed safely in a pediatric procedure room rather than an operating room when treating congenital vascular stains, Dr. Elizabeth Alvarez Connelly said in a poster presentation at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Pulsed dye lasers are considered the standard for the treatment of congenital vascular stains in young children, but one of the greatest challenges in their use is maintaining an adequate comfort level throughout the multiple treatment sessions needed.

Children are traditionally treated under gas anesthesia in the OR, but repeat sessions can be costly for all parties and stressful to the patient and family, said Dr. Connelly, a pediatric dermatologist at the University of Miami.

Laser surgery in pediatric procedure rooms does not require a sterile environment or a clearance visit by a pediatrician or anesthesiologist and allows clinicians to treat a large surface area during one laser session. The average time from start to patient release is about 2 hours, compared with 4–6 hours for OR-based treatments.

"For new parents, it's wonderful because they can come in to the procedure room and are there during the [intravenous line placement] and when they leave they can see that the child is asleep and comfortable," she said in an interview. "For the child, they don't even notice the parent was gone. It's just so much easier on everyone."

Dr. Connelly and colleagues presented a case series of 15 children with port-wine stains larger than 10 cm2 who received laser surgery in a pediatric procedure room separate from the main operating suite, with sedation provided by a nurse practitioner and pediatric intensivist. Ethyl chloride spray was used prior to intravenous line insertion and intravenous propofol (Diprivan)/fentanyl or ketamine was dosed based on weight.

The patients received an average of three to four treatments with a 595-nm pulsed dye laser (Candela VBeam) at a fluence of 7.5–9.5 J/cm2, pulse duration of 1.5 milliseconds, and 7-mm spot size.

Lightening of individual port wine stains was observed in all patients after each treatment. The only side effect, purpura, developed in all of the children treated and lasted for 10–14 days, which is the natural course following laser therapy, Dr. Connelly said.

There were no adverse reactions to the anesthesia. No intubations or overnight hospitalizations were required.

Without expensive OR costs, there was a 50%-70% cost savings per laser procedure, said Dr. Connelly, who acknowledged that a formal cost analysis was not performed.

When moving laser treatments from the OR to a pediatric procedure room, ensure that preoperative fluids are restricted based on age; properly sized safety equipment is readily available; and all patients are watched carefully for signs of nausea, vomiting, or fever prior to discharge, she said.

Dr. Connelly added that she has no relevant financial relationship with Candela Corp.

MIAMI BEACH — Laser surgery with intravenous deep sedation can be performed safely in a pediatric procedure room rather than an operating room when treating congenital vascular stains, Dr. Elizabeth Alvarez Connelly said in a poster presentation at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Pulsed dye lasers are considered the standard for the treatment of congenital vascular stains in young children, but one of the greatest challenges in their use is maintaining an adequate comfort level throughout the multiple treatment sessions needed.

Children are traditionally treated under gas anesthesia in the OR, but repeat sessions can be costly for all parties and stressful to the patient and family, said Dr. Connelly, a pediatric dermatologist at the University of Miami.

Laser surgery in pediatric procedure rooms does not require a sterile environment or a clearance visit by a pediatrician or anesthesiologist and allows clinicians to treat a large surface area during one laser session. The average time from start to patient release is about 2 hours, compared with 4–6 hours for OR-based treatments.

"For new parents, it's wonderful because they can come in to the procedure room and are there during the [intravenous line placement] and when they leave they can see that the child is asleep and comfortable," she said in an interview. "For the child, they don't even notice the parent was gone. It's just so much easier on everyone."

Dr. Connelly and colleagues presented a case series of 15 children with port-wine stains larger than 10 cm2 who received laser surgery in a pediatric procedure room separate from the main operating suite, with sedation provided by a nurse practitioner and pediatric intensivist. Ethyl chloride spray was used prior to intravenous line insertion and intravenous propofol (Diprivan)/fentanyl or ketamine was dosed based on weight.

The patients received an average of three to four treatments with a 595-nm pulsed dye laser (Candela VBeam) at a fluence of 7.5–9.5 J/cm2, pulse duration of 1.5 milliseconds, and 7-mm spot size.

Lightening of individual port wine stains was observed in all patients after each treatment. The only side effect, purpura, developed in all of the children treated and lasted for 10–14 days, which is the natural course following laser therapy, Dr. Connelly said.

There were no adverse reactions to the anesthesia. No intubations or overnight hospitalizations were required.

Without expensive OR costs, there was a 50%-70% cost savings per laser procedure, said Dr. Connelly, who acknowledged that a formal cost analysis was not performed.

When moving laser treatments from the OR to a pediatric procedure room, ensure that preoperative fluids are restricted based on age; properly sized safety equipment is readily available; and all patients are watched carefully for signs of nausea, vomiting, or fever prior to discharge, she said.

Dr. Connelly added that she has no relevant financial relationship with Candela Corp.

KANSAS CITY, MO. — Physicians support using risk-based standing orders for adult hepatitis B vaccinations, but see clear barriers to their implementation, results of a national survey show.

Prior studies show that age- and risk-based standing orders that authorize health care personnel to vaccinate by protocol without physician involvement have increased adult pneumococcal and influenza vaccination rates by 16%–97%, when done as part of a multicomponent strategy.

But unlike assessing adults for pneumococcal disease or influenza, using standing orders to assess for hepatitis B virus (HBV) risk factors requires obtaining potentially sensitive information, Dr. Allison Kempe and her associates reported in a poster at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention. Like HIV, HBV can be transmitted through unprotected sex with an infected person or through shared needles.

“This is a debate because some people think that risk-based criteria are far less effective than age-based criteria, and the CDC has decided to go with risk based,” Dr. Kempe, of the Children's Hospital in Denver, said in an interview.

In December 2006, the CDC's Advisory Committee on Immunization Practices recommended that practitioners in primary care settings implement standing orders to identify and vaccinate adults with HBV risk factors.

In September and October 2006, Dr. Kempe and her associates used a mail- or Internet-based questionnaire to survey family medicine and general internal medicine physicians on the feasibility of implementing HBV risk-based standing orders. Surveys were completed by 65% (282 of 433) of family physicians and 79% (332 of 420) general internists. Responses generally did not differ by specialty, so data were combined.

Overall, 47% of respondents reported being “very supportive” and 37% “somewhat supportive” of risk-based standing orders.

“However, physicians reported significant barriers to risk-based approaches, suggesting that alternative strategies might be needed for hepatitis B vaccination to be successfully implemented,” the authors wrote.

Factors identified as “definite barriers” or “somewhat of a barrier” to standing orders included patients not disclosing sensitive information (definite 36%, somewhat 38%); nurses and medical assistants (MAs) being too pressed for time to assess risk (30%, 37%); risk screening negatively impacting patient flow (20%, 27%); risk screening requiring more knowledge than nurses or MAs have (16%, 30%); and the fact that because of the complexity of the standing orders, nurses and MAs would still have questions about who should be immunized (15%, 31%).

The investigators did not perform a head-to-head comparison between risk- and age-based criteria, but feasibility was thought to be higher for age-based criteria, Dr. Kempe said. Just 25% of family physicians and 27% of internists thought risk-based criteria would be “very feasible” versus 38% and 37% for age-based criteria.

In a second analysis, most physicians reported that HBV vaccination was a “moderate priority” (42% of the family medicine physicians, 45% of the internists) or a “low priority” (39%, 28%) in their practices, Dr. Matthew Daley and his associates reported in a separate poster at the meeting.

A minority (37%) of respondents routinely use written questionnaires at an initial inpatient visit to assess sexual behavior or drug use, reported Dr. Daley, also of the Children's Hospital.

KANSAS CITY, MO. — Physicians support using risk-based standing orders for adult hepatitis B vaccinations, but see clear barriers to their implementation, results of a national survey show.

Prior studies show that age- and risk-based standing orders that authorize health care personnel to vaccinate by protocol without physician involvement have increased adult pneumococcal and influenza vaccination rates by 16%–97%, when done as part of a multicomponent strategy.

But unlike assessing adults for pneumococcal disease or influenza, using standing orders to assess for hepatitis B virus (HBV) risk factors requires obtaining potentially sensitive information, Dr. Allison Kempe and her associates reported in a poster at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention. Like HIV, HBV can be transmitted through unprotected sex with an infected person or through shared needles.

“This is a debate because some people think that risk-based criteria are far less effective than age-based criteria, and the CDC has decided to go with risk based,” Dr. Kempe, of the Children's Hospital in Denver, said in an interview.

In December 2006, the CDC's Advisory Committee on Immunization Practices recommended that practitioners in primary care settings implement standing orders to identify and vaccinate adults with HBV risk factors.

In September and October 2006, Dr. Kempe and her associates used a mail- or Internet-based questionnaire to survey family medicine and general internal medicine physicians on the feasibility of implementing HBV risk-based standing orders. Surveys were completed by 65% (282 of 433) of family physicians and 79% (332 of 420) general internists. Responses generally did not differ by specialty, so data were combined.

Overall, 47% of respondents reported being “very supportive” and 37% “somewhat supportive” of risk-based standing orders.

“However, physicians reported significant barriers to risk-based approaches, suggesting that alternative strategies might be needed for hepatitis B vaccination to be successfully implemented,” the authors wrote.

Factors identified as “definite barriers” or “somewhat of a barrier” to standing orders included patients not disclosing sensitive information (definite 36%, somewhat 38%); nurses and medical assistants (MAs) being too pressed for time to assess risk (30%, 37%); risk screening negatively impacting patient flow (20%, 27%); risk screening requiring more knowledge than nurses or MAs have (16%, 30%); and the fact that because of the complexity of the standing orders, nurses and MAs would still have questions about who should be immunized (15%, 31%).

The investigators did not perform a head-to-head comparison between risk- and age-based criteria, but feasibility was thought to be higher for age-based criteria, Dr. Kempe said. Just 25% of family physicians and 27% of internists thought risk-based criteria would be “very feasible” versus 38% and 37% for age-based criteria.

In a second analysis, most physicians reported that HBV vaccination was a “moderate priority” (42% of the family medicine physicians, 45% of the internists) or a “low priority” (39%, 28%) in their practices, Dr. Matthew Daley and his associates reported in a separate poster at the meeting.

A minority (37%) of respondents routinely use written questionnaires at an initial inpatient visit to assess sexual behavior or drug use, reported Dr. Daley, also of the Children's Hospital.

KANSAS CITY, MO. — Physicians support using risk-based standing orders for adult hepatitis B vaccinations, but see clear barriers to their implementation, results of a national survey show.

Prior studies show that age- and risk-based standing orders that authorize health care personnel to vaccinate by protocol without physician involvement have increased adult pneumococcal and influenza vaccination rates by 16%–97%, when done as part of a multicomponent strategy.

But unlike assessing adults for pneumococcal disease or influenza, using standing orders to assess for hepatitis B virus (HBV) risk factors requires obtaining potentially sensitive information, Dr. Allison Kempe and her associates reported in a poster at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention. Like HIV, HBV can be transmitted through unprotected sex with an infected person or through shared needles.

“This is a debate because some people think that risk-based criteria are far less effective than age-based criteria, and the CDC has decided to go with risk based,” Dr. Kempe, of the Children's Hospital in Denver, said in an interview.

In December 2006, the CDC's Advisory Committee on Immunization Practices recommended that practitioners in primary care settings implement standing orders to identify and vaccinate adults with HBV risk factors.

In September and October 2006, Dr. Kempe and her associates used a mail- or Internet-based questionnaire to survey family medicine and general internal medicine physicians on the feasibility of implementing HBV risk-based standing orders. Surveys were completed by 65% (282 of 433) of family physicians and 79% (332 of 420) general internists. Responses generally did not differ by specialty, so data were combined.

Overall, 47% of respondents reported being “very supportive” and 37% “somewhat supportive” of risk-based standing orders.

“However, physicians reported significant barriers to risk-based approaches, suggesting that alternative strategies might be needed for hepatitis B vaccination to be successfully implemented,” the authors wrote.

Factors identified as “definite barriers” or “somewhat of a barrier” to standing orders included patients not disclosing sensitive information (definite 36%, somewhat 38%); nurses and medical assistants (MAs) being too pressed for time to assess risk (30%, 37%); risk screening negatively impacting patient flow (20%, 27%); risk screening requiring more knowledge than nurses or MAs have (16%, 30%); and the fact that because of the complexity of the standing orders, nurses and MAs would still have questions about who should be immunized (15%, 31%).

The investigators did not perform a head-to-head comparison between risk- and age-based criteria, but feasibility was thought to be higher for age-based criteria, Dr. Kempe said. Just 25% of family physicians and 27% of internists thought risk-based criteria would be “very feasible” versus 38% and 37% for age-based criteria.

In a second analysis, most physicians reported that HBV vaccination was a “moderate priority” (42% of the family medicine physicians, 45% of the internists) or a “low priority” (39%, 28%) in their practices, Dr. Matthew Daley and his associates reported in a separate poster at the meeting.

A minority (37%) of respondents routinely use written questionnaires at an initial inpatient visit to assess sexual behavior or drug use, reported Dr. Daley, also of the Children's Hospital.