Diana Mahoney

BOSTON — Screening asymptomatic diabetes patients for myocardial ischemia using advanced imaging does not improve their 5-year prognosis for coronary events, compared with standard care, results of a multicenter study have shown.

Of the 561 type 2 diabetes patients without symptomatic or previously diagnosed coronary artery disease who underwent screening with stress adenosine myocardial perfusion imaging (MPI) as part of the study, “only 22% had inducible ischemia, which was far less than we expected,” Dr. Frans J. Wackers of Yale University, said at the annual meeting of the American Society of Nuclear Cardiology.

During a mean follow-up of 4.8 years, the cumulative rate of cardiac events for both groups was about 3% among patients in the screening group and among the 562 patients in the standard care control group.

The study randomized 1,123 patients, aged 55–75 years, with a mean diabetes duration of 8.7 years to MPI single-photon emission computed tomography screening or standard care without screening.

Patients with normal MPI or small MPI defects had 5-year cumulative cardiac event rates of 2.1% and 2.0%, respectively. Among patients with moderate to large MPI defects, as well as those with nonperfusion abnormalities such as ischemic changes on electrocardiogram, rates were significantly higher, at 12.3% and 6.8%, respectively.

Predictors of cardiac events by Cox regression included male sex, peripheral vascular disease, creatinine level, and abnormal heart rate response to standing.

Clinical events and inducible ischemia both identify higher-risk patients with type 2 diabetes, “but overall rates of cardiac events are equivalent whether or not patients underwent initial screening,” said Dr. Wackers, who reported no financial conflicts of interest.

BOSTON — Screening asymptomatic diabetes patients for myocardial ischemia using advanced imaging does not improve their 5-year prognosis for coronary events, compared with standard care, results of a multicenter study have shown.

Of the 561 type 2 diabetes patients without symptomatic or previously diagnosed coronary artery disease who underwent screening with stress adenosine myocardial perfusion imaging (MPI) as part of the study, “only 22% had inducible ischemia, which was far less than we expected,” Dr. Frans J. Wackers of Yale University, said at the annual meeting of the American Society of Nuclear Cardiology.

During a mean follow-up of 4.8 years, the cumulative rate of cardiac events for both groups was about 3% among patients in the screening group and among the 562 patients in the standard care control group.

The study randomized 1,123 patients, aged 55–75 years, with a mean diabetes duration of 8.7 years to MPI single-photon emission computed tomography screening or standard care without screening.

Patients with normal MPI or small MPI defects had 5-year cumulative cardiac event rates of 2.1% and 2.0%, respectively. Among patients with moderate to large MPI defects, as well as those with nonperfusion abnormalities such as ischemic changes on electrocardiogram, rates were significantly higher, at 12.3% and 6.8%, respectively.

Predictors of cardiac events by Cox regression included male sex, peripheral vascular disease, creatinine level, and abnormal heart rate response to standing.

Clinical events and inducible ischemia both identify higher-risk patients with type 2 diabetes, “but overall rates of cardiac events are equivalent whether or not patients underwent initial screening,” said Dr. Wackers, who reported no financial conflicts of interest.

BOSTON — Screening asymptomatic diabetes patients for myocardial ischemia using advanced imaging does not improve their 5-year prognosis for coronary events, compared with standard care, results of a multicenter study have shown.

Of the 561 type 2 diabetes patients without symptomatic or previously diagnosed coronary artery disease who underwent screening with stress adenosine myocardial perfusion imaging (MPI) as part of the study, “only 22% had inducible ischemia, which was far less than we expected,” Dr. Frans J. Wackers of Yale University, said at the annual meeting of the American Society of Nuclear Cardiology.

During a mean follow-up of 4.8 years, the cumulative rate of cardiac events for both groups was about 3% among patients in the screening group and among the 562 patients in the standard care control group.

The study randomized 1,123 patients, aged 55–75 years, with a mean diabetes duration of 8.7 years to MPI single-photon emission computed tomography screening or standard care without screening.

Patients with normal MPI or small MPI defects had 5-year cumulative cardiac event rates of 2.1% and 2.0%, respectively. Among patients with moderate to large MPI defects, as well as those with nonperfusion abnormalities such as ischemic changes on electrocardiogram, rates were significantly higher, at 12.3% and 6.8%, respectively.

Predictors of cardiac events by Cox regression included male sex, peripheral vascular disease, creatinine level, and abnormal heart rate response to standing.

Clinical events and inducible ischemia both identify higher-risk patients with type 2 diabetes, “but overall rates of cardiac events are equivalent whether or not patients underwent initial screening,” said Dr. Wackers, who reported no financial conflicts of interest.

BOSTON — The prognostic performance of pharmacologic stress myocardial perfusion single-photon emission CT shown in academic studies generalizes to daily practice, a study has shown.

“The current prognostic literature indicates that [the imaging technology] is an effective tool for coronary artery disease risk stratification, but the majority of these studies come from single institutions using expert readers. We wanted to investigate the prognostic power of the perfusion imaging variables as read by local readers in many sites across the world,” Dr. James Udelson said at the annual meeting of the American Society of Nuclear Cardiology.

To do this, Dr. Udelson of Tufts University, Boston, along with lead investigator Dr. Rory Hachamovitch, who is in private practice in Los Angeles, and their colleagues, conducted a prospective study comprising 4,989 patients with known or suspected coronary artery disease recruited from 89 centers in eight countries during 20 consecutive work days. All of the patients had been referred for clinically indicated pharmacologic stress myocardial perfusion imaging by single-photon emission CT (PS SPECT MPI). Of the study population, 48% of the patients were tested in tertiary care centers, and 26% each underwent testing in private and community centers.

The investigators did not dictate the imaging protocol for the study; rather, “each center used its own standard protocol for stress isotope image acquisition,” said Dr. Udelson. “This was an effectiveness study of real life practices,” he added. Toward this end, approximately 150 local readers from the different sites interpreted the images and reported segmental scores using the 17-segment, 4-point scoring model from which nuclear variables were converted into percent myocardium ischemic and percent myocardium fixed, as has been done in the literature, he said.

The primary end point of the study was all-cause death, “with the simple goal of identifying the incremental value of perfusion imaging data over all other data,” said Dr. Udelson.

Using scripted phone calls to each site, the investigators followed the patients for revascularization and all-cause death for 1 year after the imaging study. Excluded from the study were 212 patients who had undergone early revascularization (within 90 days after testing) and thus were excluded from the final analysis. All-cause death was reported for 155 of the remaining patients, said Dr. Udelson. The all-cause death rate in patients with abnormal MPI was 3.7%, significantly higher than the 2.2% observed in patients with normal MPI, he said, noting that the risk of all-cause death was greatest in patients with both reversible and fixed perfusion defects (5.4%), compared with patients with fixed but no reversible defects (3.2%) and patients with reversible but no fixed defects (2.5%).

In addition to abnormal MPI, other predictors of all-cause death were history of heart failure, chronic obstructive pulmonary disease, and diabetes. Controlling for these clinical variables as well as for demographic and historical data, “the MPI results were highly predictive of 1-year all-cause death,” Dr. Udelson said.

In the final multivariate model, both the percent myocardium with reversible defects and percent with fixed defects had statistically significant increased hazard ratios, expressed per 1% change, Dr. Udelson explained. “For example, an increase in the percent myocardium reversible, or ischemic, of 3% would be associated with a 15% increased risk [of all-cause death].”

“The findings indicate that the perfusion imaging variables, as read by local readers from many sites across the world, have prognostic power incremental to all of the clinical data,” said Dr. Udelson. “This generalizability has not been shown for other imaging modalities.”

This study was funded by King Pharmaceuticals Research & Development Inc., for which Dr. Udelson and Dr. Hachamovitch are paid consultants.

The multicener, internationaltrial 'was an effectiveness study of real life practices.' DR. UDELSON

BOSTON — The prognostic performance of pharmacologic stress myocardial perfusion single-photon emission CT shown in academic studies generalizes to daily practice, a study has shown.

“The current prognostic literature indicates that [the imaging technology] is an effective tool for coronary artery disease risk stratification, but the majority of these studies come from single institutions using expert readers. We wanted to investigate the prognostic power of the perfusion imaging variables as read by local readers in many sites across the world,” Dr. James Udelson said at the annual meeting of the American Society of Nuclear Cardiology.

To do this, Dr. Udelson of Tufts University, Boston, along with lead investigator Dr. Rory Hachamovitch, who is in private practice in Los Angeles, and their colleagues, conducted a prospective study comprising 4,989 patients with known or suspected coronary artery disease recruited from 89 centers in eight countries during 20 consecutive work days. All of the patients had been referred for clinically indicated pharmacologic stress myocardial perfusion imaging by single-photon emission CT (PS SPECT MPI). Of the study population, 48% of the patients were tested in tertiary care centers, and 26% each underwent testing in private and community centers.

The investigators did not dictate the imaging protocol for the study; rather, “each center used its own standard protocol for stress isotope image acquisition,” said Dr. Udelson. “This was an effectiveness study of real life practices,” he added. Toward this end, approximately 150 local readers from the different sites interpreted the images and reported segmental scores using the 17-segment, 4-point scoring model from which nuclear variables were converted into percent myocardium ischemic and percent myocardium fixed, as has been done in the literature, he said.

The primary end point of the study was all-cause death, “with the simple goal of identifying the incremental value of perfusion imaging data over all other data,” said Dr. Udelson.

Using scripted phone calls to each site, the investigators followed the patients for revascularization and all-cause death for 1 year after the imaging study. Excluded from the study were 212 patients who had undergone early revascularization (within 90 days after testing) and thus were excluded from the final analysis. All-cause death was reported for 155 of the remaining patients, said Dr. Udelson. The all-cause death rate in patients with abnormal MPI was 3.7%, significantly higher than the 2.2% observed in patients with normal MPI, he said, noting that the risk of all-cause death was greatest in patients with both reversible and fixed perfusion defects (5.4%), compared with patients with fixed but no reversible defects (3.2%) and patients with reversible but no fixed defects (2.5%).

In addition to abnormal MPI, other predictors of all-cause death were history of heart failure, chronic obstructive pulmonary disease, and diabetes. Controlling for these clinical variables as well as for demographic and historical data, “the MPI results were highly predictive of 1-year all-cause death,” Dr. Udelson said.

In the final multivariate model, both the percent myocardium with reversible defects and percent with fixed defects had statistically significant increased hazard ratios, expressed per 1% change, Dr. Udelson explained. “For example, an increase in the percent myocardium reversible, or ischemic, of 3% would be associated with a 15% increased risk [of all-cause death].”

“The findings indicate that the perfusion imaging variables, as read by local readers from many sites across the world, have prognostic power incremental to all of the clinical data,” said Dr. Udelson. “This generalizability has not been shown for other imaging modalities.”

This study was funded by King Pharmaceuticals Research & Development Inc., for which Dr. Udelson and Dr. Hachamovitch are paid consultants.

The multicener, internationaltrial 'was an effectiveness study of real life practices.' DR. UDELSON

BOSTON — The prognostic performance of pharmacologic stress myocardial perfusion single-photon emission CT shown in academic studies generalizes to daily practice, a study has shown.

“The current prognostic literature indicates that [the imaging technology] is an effective tool for coronary artery disease risk stratification, but the majority of these studies come from single institutions using expert readers. We wanted to investigate the prognostic power of the perfusion imaging variables as read by local readers in many sites across the world,” Dr. James Udelson said at the annual meeting of the American Society of Nuclear Cardiology.

To do this, Dr. Udelson of Tufts University, Boston, along with lead investigator Dr. Rory Hachamovitch, who is in private practice in Los Angeles, and their colleagues, conducted a prospective study comprising 4,989 patients with known or suspected coronary artery disease recruited from 89 centers in eight countries during 20 consecutive work days. All of the patients had been referred for clinically indicated pharmacologic stress myocardial perfusion imaging by single-photon emission CT (PS SPECT MPI). Of the study population, 48% of the patients were tested in tertiary care centers, and 26% each underwent testing in private and community centers.

The investigators did not dictate the imaging protocol for the study; rather, “each center used its own standard protocol for stress isotope image acquisition,” said Dr. Udelson. “This was an effectiveness study of real life practices,” he added. Toward this end, approximately 150 local readers from the different sites interpreted the images and reported segmental scores using the 17-segment, 4-point scoring model from which nuclear variables were converted into percent myocardium ischemic and percent myocardium fixed, as has been done in the literature, he said.

The primary end point of the study was all-cause death, “with the simple goal of identifying the incremental value of perfusion imaging data over all other data,” said Dr. Udelson.

Using scripted phone calls to each site, the investigators followed the patients for revascularization and all-cause death for 1 year after the imaging study. Excluded from the study were 212 patients who had undergone early revascularization (within 90 days after testing) and thus were excluded from the final analysis. All-cause death was reported for 155 of the remaining patients, said Dr. Udelson. The all-cause death rate in patients with abnormal MPI was 3.7%, significantly higher than the 2.2% observed in patients with normal MPI, he said, noting that the risk of all-cause death was greatest in patients with both reversible and fixed perfusion defects (5.4%), compared with patients with fixed but no reversible defects (3.2%) and patients with reversible but no fixed defects (2.5%).

In addition to abnormal MPI, other predictors of all-cause death were history of heart failure, chronic obstructive pulmonary disease, and diabetes. Controlling for these clinical variables as well as for demographic and historical data, “the MPI results were highly predictive of 1-year all-cause death,” Dr. Udelson said.

In the final multivariate model, both the percent myocardium with reversible defects and percent with fixed defects had statistically significant increased hazard ratios, expressed per 1% change, Dr. Udelson explained. “For example, an increase in the percent myocardium reversible, or ischemic, of 3% would be associated with a 15% increased risk [of all-cause death].”

“The findings indicate that the perfusion imaging variables, as read by local readers from many sites across the world, have prognostic power incremental to all of the clinical data,” said Dr. Udelson. “This generalizability has not been shown for other imaging modalities.”

This study was funded by King Pharmaceuticals Research & Development Inc., for which Dr. Udelson and Dr. Hachamovitch are paid consultants.

The multicener, internationaltrial 'was an effectiveness study of real life practices.' DR. UDELSON

BOSTON — In the ongoing debate over whether patients with chronic, stable angina are better served by revascularization with percutaneous coronary intervention in addition to drug treatment or optimal medical therapy alone, the key variable appears to be ischemic burden, Dr. Daniel S. Berman reported at the annual meeting of the American Society of Nuclear Cardiology.

Last year, investigators in the Clinical Outcomes Using Revascularization and Aggressive Drug Evaluation (COURAGE) trial reported that adding percutaneous coronary intervention (PCI) to optimal medical therapy in patients with stable coronary artery disease did not improve clinical end points, compared with optimal medical therapy alone (N. Engl. J. Med. 2007;356:1503–16). The results sparked a controversy that led some experts to conclude that PCI is overused and unnecessary in stable coronary disease.

More recently, however, a substudy of the COURAGE trial comprising 314 patients equally distributed between groups treated with PCI plus optical medical therapy and optimal medical therapy alone showed that the PCI strategy produced a greater ischemia reduction than the optimal medical therapy-only (OMT-only) intervention—particularly among patients with moderate to severe ischemia at baseline.

“Importantly, patients in both groups who experienced ischemia reduction had a significantly lower risk for death or myocardial infarction than patients without ischemia reduction, and the magnitude of residual ischemia was proportional to the overall risk of subsequent cardiac event,” said Dr. Berman, chief of cardiac imaging and nuclear cardiology at Cedars-Sinai Heart Center in Los Angeles.

The main COURAGE trial included 2,287 patients, with a history of angina or documented myocardial ischemia and at least one significant coronary lesion, who were stable on medical therapy. Participants were randomized to continue their medication alone or with PCI, and the study's combined end points were death or nonfatal myocardial infarction. The composite rates of death or nonfatal myocardial infarction over 4.6 years of follow-up were statistically similar in both groups, at 19.0% for the PCI group and at in18.5%, the patients who received only optimal medical therapy, showing no benefit of PCI over optical medical therapy in stable coronary artery disease.

In the nuclear imaging substudy, the 314 patients were equally distributed between the PCI and OMT groups and they were well matched with respect to demographics and risk factors, said Dr. Berman.

All of the patients were on medication for a mean 374 days from baseline and all underwent serial myocardial perfusion single-photon emission computed tomography (SPECT-MPI) studies 6–18 months following the baseline examination to assess the extent and severity of the perfusion defect in the global myocardium, he said.

With myocardial ischemia defined as the total perfusion deficit at stress minus the perfusion deficit at rest, 33% of patients in the PCI group and 20% in the OMT-only group showed a 5% or greater reduction in ischemia.

Among the patients in the imaging substudy with moderate to severe pretreatment ischemia, defined as a perfusion defect involving 10% or more of myocardium, “78% of the PCI patients demonstrated 5% improvement or greater, compared to 52% of the [OMT-only] patients,” Dr. Berman reported.

In considering these changes in terms of their relationship to subsequent outcomes, “we looked at the myocardial infarction rates in patients with and without ischemia reduction and determined that patients in both groups with 5% improvement in ischemia had approximately 50% lower cardiac event rate,” he said.

A similarly reduced cardiac event rate was observed in the 105 patients from both groups with moderate to severe ischemia and a greater than 5% reduction in ischemia observed post treatment, he said.

Although the substudy was not sufficiently powered to generalize that reducing ischemia will prevent later cardiac events, “we did see a striking relationship between amount of residual ischemia and the subsequent death or myocardial infarction rate,” Dr. Berman stated.

This observation is “definitely a hypothesis generator,” warranting a controlled trial comparing the PCI-based strategy with optimal medical therapy alone in patients with chronic stable angina who would be randomized based on the presence of moderate to severe ischemia, he said.

“We should be studying patients with 10% or more ischemia to determine if there is a subset of patients who would have improved angina and quality-of-life outcomes with revascularization.” The findings would be especially important to those patients with documented large amounts of jeopardized myocardia in whom medical therapy does not provide adequate relief, he concluded.

The COURAGE nuclear imaging substudy was supported by Bristol-Myers Squibb Medical Imaging and Astellas Healthcare.

COURAGE patients with moderate to severe ischemia showed greater improvement after PCIthan after OMT only. DR. BERMAN

The above SPECT-MPIimage shows the first and second stress myocardial perfusion from a patient in the nuclear substudy of the COURAGE trial who received optimal medical therapy only. Total perfusion deficit was reduced from 16% to 6%. Patients in both the PCI and OMT-only groups with 5% improvement in ischemia had 50% lower cardiac event rates. Images courtesy Dr. Daniel S. Berman

BOSTON — In the ongoing debate over whether patients with chronic, stable angina are better served by revascularization with percutaneous coronary intervention in addition to drug treatment or optimal medical therapy alone, the key variable appears to be ischemic burden, Dr. Daniel S. Berman reported at the annual meeting of the American Society of Nuclear Cardiology.

Last year, investigators in the Clinical Outcomes Using Revascularization and Aggressive Drug Evaluation (COURAGE) trial reported that adding percutaneous coronary intervention (PCI) to optimal medical therapy in patients with stable coronary artery disease did not improve clinical end points, compared with optimal medical therapy alone (N. Engl. J. Med. 2007;356:1503–16). The results sparked a controversy that led some experts to conclude that PCI is overused and unnecessary in stable coronary disease.

More recently, however, a substudy of the COURAGE trial comprising 314 patients equally distributed between groups treated with PCI plus optical medical therapy and optimal medical therapy alone showed that the PCI strategy produced a greater ischemia reduction than the optimal medical therapy-only (OMT-only) intervention—particularly among patients with moderate to severe ischemia at baseline.

“Importantly, patients in both groups who experienced ischemia reduction had a significantly lower risk for death or myocardial infarction than patients without ischemia reduction, and the magnitude of residual ischemia was proportional to the overall risk of subsequent cardiac event,” said Dr. Berman, chief of cardiac imaging and nuclear cardiology at Cedars-Sinai Heart Center in Los Angeles.

The main COURAGE trial included 2,287 patients, with a history of angina or documented myocardial ischemia and at least one significant coronary lesion, who were stable on medical therapy. Participants were randomized to continue their medication alone or with PCI, and the study's combined end points were death or nonfatal myocardial infarction. The composite rates of death or nonfatal myocardial infarction over 4.6 years of follow-up were statistically similar in both groups, at 19.0% for the PCI group and at in18.5%, the patients who received only optimal medical therapy, showing no benefit of PCI over optical medical therapy in stable coronary artery disease.

In the nuclear imaging substudy, the 314 patients were equally distributed between the PCI and OMT groups and they were well matched with respect to demographics and risk factors, said Dr. Berman.

All of the patients were on medication for a mean 374 days from baseline and all underwent serial myocardial perfusion single-photon emission computed tomography (SPECT-MPI) studies 6–18 months following the baseline examination to assess the extent and severity of the perfusion defect in the global myocardium, he said.

With myocardial ischemia defined as the total perfusion deficit at stress minus the perfusion deficit at rest, 33% of patients in the PCI group and 20% in the OMT-only group showed a 5% or greater reduction in ischemia.

Among the patients in the imaging substudy with moderate to severe pretreatment ischemia, defined as a perfusion defect involving 10% or more of myocardium, “78% of the PCI patients demonstrated 5% improvement or greater, compared to 52% of the [OMT-only] patients,” Dr. Berman reported.

In considering these changes in terms of their relationship to subsequent outcomes, “we looked at the myocardial infarction rates in patients with and without ischemia reduction and determined that patients in both groups with 5% improvement in ischemia had approximately 50% lower cardiac event rate,” he said.

A similarly reduced cardiac event rate was observed in the 105 patients from both groups with moderate to severe ischemia and a greater than 5% reduction in ischemia observed post treatment, he said.

Although the substudy was not sufficiently powered to generalize that reducing ischemia will prevent later cardiac events, “we did see a striking relationship between amount of residual ischemia and the subsequent death or myocardial infarction rate,” Dr. Berman stated.

This observation is “definitely a hypothesis generator,” warranting a controlled trial comparing the PCI-based strategy with optimal medical therapy alone in patients with chronic stable angina who would be randomized based on the presence of moderate to severe ischemia, he said.

“We should be studying patients with 10% or more ischemia to determine if there is a subset of patients who would have improved angina and quality-of-life outcomes with revascularization.” The findings would be especially important to those patients with documented large amounts of jeopardized myocardia in whom medical therapy does not provide adequate relief, he concluded.

The COURAGE nuclear imaging substudy was supported by Bristol-Myers Squibb Medical Imaging and Astellas Healthcare.

COURAGE patients with moderate to severe ischemia showed greater improvement after PCIthan after OMT only. DR. BERMAN

The above SPECT-MPIimage shows the first and second stress myocardial perfusion from a patient in the nuclear substudy of the COURAGE trial who received optimal medical therapy only. Total perfusion deficit was reduced from 16% to 6%. Patients in both the PCI and OMT-only groups with 5% improvement in ischemia had 50% lower cardiac event rates. Images courtesy Dr. Daniel S. Berman

BOSTON — In the ongoing debate over whether patients with chronic, stable angina are better served by revascularization with percutaneous coronary intervention in addition to drug treatment or optimal medical therapy alone, the key variable appears to be ischemic burden, Dr. Daniel S. Berman reported at the annual meeting of the American Society of Nuclear Cardiology.

Last year, investigators in the Clinical Outcomes Using Revascularization and Aggressive Drug Evaluation (COURAGE) trial reported that adding percutaneous coronary intervention (PCI) to optimal medical therapy in patients with stable coronary artery disease did not improve clinical end points, compared with optimal medical therapy alone (N. Engl. J. Med. 2007;356:1503–16). The results sparked a controversy that led some experts to conclude that PCI is overused and unnecessary in stable coronary disease.

More recently, however, a substudy of the COURAGE trial comprising 314 patients equally distributed between groups treated with PCI plus optical medical therapy and optimal medical therapy alone showed that the PCI strategy produced a greater ischemia reduction than the optimal medical therapy-only (OMT-only) intervention—particularly among patients with moderate to severe ischemia at baseline.

“Importantly, patients in both groups who experienced ischemia reduction had a significantly lower risk for death or myocardial infarction than patients without ischemia reduction, and the magnitude of residual ischemia was proportional to the overall risk of subsequent cardiac event,” said Dr. Berman, chief of cardiac imaging and nuclear cardiology at Cedars-Sinai Heart Center in Los Angeles.

The main COURAGE trial included 2,287 patients, with a history of angina or documented myocardial ischemia and at least one significant coronary lesion, who were stable on medical therapy. Participants were randomized to continue their medication alone or with PCI, and the study's combined end points were death or nonfatal myocardial infarction. The composite rates of death or nonfatal myocardial infarction over 4.6 years of follow-up were statistically similar in both groups, at 19.0% for the PCI group and at in18.5%, the patients who received only optimal medical therapy, showing no benefit of PCI over optical medical therapy in stable coronary artery disease.

In the nuclear imaging substudy, the 314 patients were equally distributed between the PCI and OMT groups and they were well matched with respect to demographics and risk factors, said Dr. Berman.

All of the patients were on medication for a mean 374 days from baseline and all underwent serial myocardial perfusion single-photon emission computed tomography (SPECT-MPI) studies 6–18 months following the baseline examination to assess the extent and severity of the perfusion defect in the global myocardium, he said.

With myocardial ischemia defined as the total perfusion deficit at stress minus the perfusion deficit at rest, 33% of patients in the PCI group and 20% in the OMT-only group showed a 5% or greater reduction in ischemia.

Among the patients in the imaging substudy with moderate to severe pretreatment ischemia, defined as a perfusion defect involving 10% or more of myocardium, “78% of the PCI patients demonstrated 5% improvement or greater, compared to 52% of the [OMT-only] patients,” Dr. Berman reported.

In considering these changes in terms of their relationship to subsequent outcomes, “we looked at the myocardial infarction rates in patients with and without ischemia reduction and determined that patients in both groups with 5% improvement in ischemia had approximately 50% lower cardiac event rate,” he said.

A similarly reduced cardiac event rate was observed in the 105 patients from both groups with moderate to severe ischemia and a greater than 5% reduction in ischemia observed post treatment, he said.

Although the substudy was not sufficiently powered to generalize that reducing ischemia will prevent later cardiac events, “we did see a striking relationship between amount of residual ischemia and the subsequent death or myocardial infarction rate,” Dr. Berman stated.

This observation is “definitely a hypothesis generator,” warranting a controlled trial comparing the PCI-based strategy with optimal medical therapy alone in patients with chronic stable angina who would be randomized based on the presence of moderate to severe ischemia, he said.

“We should be studying patients with 10% or more ischemia to determine if there is a subset of patients who would have improved angina and quality-of-life outcomes with revascularization.” The findings would be especially important to those patients with documented large amounts of jeopardized myocardia in whom medical therapy does not provide adequate relief, he concluded.

The COURAGE nuclear imaging substudy was supported by Bristol-Myers Squibb Medical Imaging and Astellas Healthcare.

COURAGE patients with moderate to severe ischemia showed greater improvement after PCIthan after OMT only. DR. BERMAN

The above SPECT-MPIimage shows the first and second stress myocardial perfusion from a patient in the nuclear substudy of the COURAGE trial who received optimal medical therapy only. Total perfusion deficit was reduced from 16% to 6%. Patients in both the PCI and OMT-only groups with 5% improvement in ischemia had 50% lower cardiac event rates. Images courtesy Dr. Daniel S. Berman

BOSTON — A recent study suggesting that prophylactic antibiotics for an initial urinary tract infection in children do not prevent recurrent infection and may, in fact, contribute to an increased risk of recurrent infection with a resistant bacteria has raised questions about the standard of care for these patients.

Dr. Ron Keren of the Children's Hospital of Philadelphia made this presentationat the annual meeting of the American Academy of Pediatrics.

The AAP 1999 practice parameter recommends that all children with a first urinary tract infection (UTI) undergo renal ultrasound to detect abnormalities such as hydronephrosis, bladder hypertrophy, and ureteroceles; and either a voiding cystourethrogram (VCUG) or direct radionuclide cystography (RNC) to evaluate the presence and degree of vesicoureteral reflux (VUR), Dr. Keren explained. Conventional wisdom has been that evidence of VUR, which is found in 30%–40% of children with UTI, warrants prophylactic antibiotic treatment to prevent recurrent infection and subsequent kidney damage, he said.

In an observational study, Dr. Keren and his colleagues reviewed the electronic health records of nearly 80,000 children with at least two pediatric care visits over a 5-year period and identified 611 children who had been diagnosed with a first UTI (JAMA 2007;298:179–86). “We then looked forward into the records to determine how many of these kids had recurrent [UTI], what the risk factors were, and whether the prescription of prophylactic antibiotics actually changed the risk,” he said.

Of those 611 children who'd had a UTI, 83 (14%) had been diagnosed with a recurrent infection. With use of a time-to-event analysis, “white children, older children, and children with high-grade VUR had a statistically significant increased risk of recurrent UTI, while having been prescribed prophylactic antibiotics had no relationship to recurrent infection,” he said, noting that children with low grade VUR, which is what the majority of kids have when there is evidence of VUR, were not at increased risk for reinfection. Additionally, “having been exposed to prophylactic antibiotics increased the odds of reinfection with a bug that was not pansensitive almost eightfold,” he said.

Multiple clinical trials also have failed to show a benefit of prophylactic antibiotics for the prevention of recurrent UTIs, and the authors of a 2006 systematic review of the available literature reported that the evidence to support the widespread use of antibiotics to prevent recurrent, symptomatic UTI is weak but stressed the need for large randomized, double-blinded clinical trials (Cochrane Database Syst. Rev. 2006; doi:10.1002/14651858.CD001534).

Given the apparent contradiction between the evidence and the standard of care, what is a pediatrician or parent to do? “Remember the old saying: 'The absence of evidence is not evidence of absence of benefit,'” Dr. Keren advised. “Right now, the AAP says we should be screening these kids, and we should probably be doing something about what we find. It's perfectly fine to take the conservative approach and continue to screen all kids for VUR after the first UTI and continue to prescribe prophylactic antibiotics for kids with VUR until the VUR resolves, until we get better evidence.”

But it's also okay to use clinical judgment with respect to individualizing care, Dr. Keren stressed. “There's a big difference between a 3-year-old girl with her first afebrile UTI concurrent with potty training vs. a 5-month-old girl with febrile UTI requiring hospitalization and a history of febrile illnesses that got better with antibiotics, and a sibling and mother with a history of dilating VUR,” he said. “These are two very different creatures. I would seriously consider screening the latter child for VUR but waiting for recurrent UTI before screening the older child.”

Interestingly, the AAP imaging recommendations as outlined in the practice parameter also have been the subject of controversy. “The guidelines were written for children from 2 to 24 months of age. There's no comment on what to do for older children, yet when you look at the epidemiology of UTI in kids, the majority of children are between 2 and 6 years old when they get their first UTI. Should we be doing the same for a 4-year-old as we do for a 2- to 24-month old?” asked Dr. Keren. And while the guidelines clearly spell out imaging recommendations, “they don't tell us what to do with the findings uncovered on imaging.”

Because of this, the current management model for VUR comes from the American Urological Association (AUA) guidelines, which indicate that treatment should be decided based the age of the child and the grade of VUR based on the International Classification System for vesicoureteral reflux. “With the exception of kids between 1 and 5 years with bilateral grade V VUR and kids 6–10 years with bilateral grade III or IV reflux or unilateral grade V reflux, for whom surgery is recommended, the AUG recommends prophylactic antibiotics for initial management of kids who don't have renal scarring at the time of diagnosis,” said Dr. Keren.

“Of course, a lot of sites are not doing DMSA [dimercaptosuccinic acid] renal flow scans up front, so they don't know whether there is scarring, but these recommendations stem from an empirical treatment model that's been in place for 20–30 years that suggests UTIs in the presence of reflux leads to scarring which can lead later in life to end-stage renal disease, hypertension, or preeclampsia in young women,” he said. “The idea was that if you could knock out either one of these arms—UTI or VUR—either by surgically correcting the reflux or preventing UTI with prophylactic antibiotics, you could prevent the march down this path.”

Multiple studies comparing the effectiveness of these interventions have failed to show that either approach is better than the other with respect to the development of new renal scars, “or whether any intervention does more good than harm for VUR,” said Dr. Keren.

Because of this, “there is a lot of skepticism about that empirical model as the basis for our management, which has led to calls for a 'top down' management approach, starting with the kidneys vs. the bladder.”

According to this approach, the kidneys of children with a UTI should be assessed by DMSA scan. “The absence of abnormalities on DMSA scan has a very good negative predictive value for high-grade VUR, which is most strongly associated with subsequent renal scarring and other effects of pyelonephritis,” said Dr. Keren. “With normal DMSA scan, you can reassure parents that the kidneys are normal and that the child is unlikely to have dilating VUR, and you might want to consider skipping the VCUG.” An abnormal scan warrants the VCUG and, depending on the degree of VUR, the consideration of antibiotics or surgery, he said.

Dr. Keren reported having no financial conflicts of interest with respect to his presentation.

Dysfunctional Voiding Often Causes UTIs

It's critical for general pediatricians to consider dysfunctional elimination as a cause of urinary tract infections in children, Dr. Keren said.

Dysfunctional elimination often goes undiagnosed and undertreated, despite the fact that approximately 40% of children with first UTI and 80% of children with recurrent UTI will have symptoms of the condition, Dr. Keren said. It is characterized by abnormal elimination patterns (frequent or infrequent voids, urgency, and constipation), bladder or bowel incontinence, and/or withholding maneuvers.

The possibility of dysfunctional elimination can be evaluated using the validated Dysfunctional Voiding Scoring System, which asks a series of simple questions about bowel and bladder practices (J. Urol. 2000;164:1011–5).

Once the condition has been diagnosed, parents should be encouraged to try some simple interventions, such as scheduling voiding times every 2 or 3 hours, treating constipation with laxatives and increased fluid intake, and avoiding bladder irritants such as caffeine, food coloring, chocolate, citrus, and carbonated beverages.

“If these interventions don't work, I would refer the child to a urologist for further evaluation. Often, some of the bigger academic hospitals will have dysfunctional voiding clinics, where a psychologist might work with the child using biofeedback to retrain the pelvic floor muscles. The urologist might also prescribe anticholinergics,” Dr. Keren said.

Studies have shown treatment of dysfunctional elimination can decrease UTI recurrences and can speed the resolution of VUR, he said. As such, “screening for [dysfunctional elimination] is an important first step in the management of pediatric UTI,” he said.

BOSTON — A recent study suggesting that prophylactic antibiotics for an initial urinary tract infection in children do not prevent recurrent infection and may, in fact, contribute to an increased risk of recurrent infection with a resistant bacteria has raised questions about the standard of care for these patients.

Dr. Ron Keren of the Children's Hospital of Philadelphia made this presentationat the annual meeting of the American Academy of Pediatrics.

The AAP 1999 practice parameter recommends that all children with a first urinary tract infection (UTI) undergo renal ultrasound to detect abnormalities such as hydronephrosis, bladder hypertrophy, and ureteroceles; and either a voiding cystourethrogram (VCUG) or direct radionuclide cystography (RNC) to evaluate the presence and degree of vesicoureteral reflux (VUR), Dr. Keren explained. Conventional wisdom has been that evidence of VUR, which is found in 30%–40% of children with UTI, warrants prophylactic antibiotic treatment to prevent recurrent infection and subsequent kidney damage, he said.

In an observational study, Dr. Keren and his colleagues reviewed the electronic health records of nearly 80,000 children with at least two pediatric care visits over a 5-year period and identified 611 children who had been diagnosed with a first UTI (JAMA 2007;298:179–86). “We then looked forward into the records to determine how many of these kids had recurrent [UTI], what the risk factors were, and whether the prescription of prophylactic antibiotics actually changed the risk,” he said.

Of those 611 children who'd had a UTI, 83 (14%) had been diagnosed with a recurrent infection. With use of a time-to-event analysis, “white children, older children, and children with high-grade VUR had a statistically significant increased risk of recurrent UTI, while having been prescribed prophylactic antibiotics had no relationship to recurrent infection,” he said, noting that children with low grade VUR, which is what the majority of kids have when there is evidence of VUR, were not at increased risk for reinfection. Additionally, “having been exposed to prophylactic antibiotics increased the odds of reinfection with a bug that was not pansensitive almost eightfold,” he said.

Multiple clinical trials also have failed to show a benefit of prophylactic antibiotics for the prevention of recurrent UTIs, and the authors of a 2006 systematic review of the available literature reported that the evidence to support the widespread use of antibiotics to prevent recurrent, symptomatic UTI is weak but stressed the need for large randomized, double-blinded clinical trials (Cochrane Database Syst. Rev. 2006; doi:10.1002/14651858.CD001534).

Given the apparent contradiction between the evidence and the standard of care, what is a pediatrician or parent to do? “Remember the old saying: 'The absence of evidence is not evidence of absence of benefit,'” Dr. Keren advised. “Right now, the AAP says we should be screening these kids, and we should probably be doing something about what we find. It's perfectly fine to take the conservative approach and continue to screen all kids for VUR after the first UTI and continue to prescribe prophylactic antibiotics for kids with VUR until the VUR resolves, until we get better evidence.”

But it's also okay to use clinical judgment with respect to individualizing care, Dr. Keren stressed. “There's a big difference between a 3-year-old girl with her first afebrile UTI concurrent with potty training vs. a 5-month-old girl with febrile UTI requiring hospitalization and a history of febrile illnesses that got better with antibiotics, and a sibling and mother with a history of dilating VUR,” he said. “These are two very different creatures. I would seriously consider screening the latter child for VUR but waiting for recurrent UTI before screening the older child.”

Interestingly, the AAP imaging recommendations as outlined in the practice parameter also have been the subject of controversy. “The guidelines were written for children from 2 to 24 months of age. There's no comment on what to do for older children, yet when you look at the epidemiology of UTI in kids, the majority of children are between 2 and 6 years old when they get their first UTI. Should we be doing the same for a 4-year-old as we do for a 2- to 24-month old?” asked Dr. Keren. And while the guidelines clearly spell out imaging recommendations, “they don't tell us what to do with the findings uncovered on imaging.”

Because of this, the current management model for VUR comes from the American Urological Association (AUA) guidelines, which indicate that treatment should be decided based the age of the child and the grade of VUR based on the International Classification System for vesicoureteral reflux. “With the exception of kids between 1 and 5 years with bilateral grade V VUR and kids 6–10 years with bilateral grade III or IV reflux or unilateral grade V reflux, for whom surgery is recommended, the AUG recommends prophylactic antibiotics for initial management of kids who don't have renal scarring at the time of diagnosis,” said Dr. Keren.

“Of course, a lot of sites are not doing DMSA [dimercaptosuccinic acid] renal flow scans up front, so they don't know whether there is scarring, but these recommendations stem from an empirical treatment model that's been in place for 20–30 years that suggests UTIs in the presence of reflux leads to scarring which can lead later in life to end-stage renal disease, hypertension, or preeclampsia in young women,” he said. “The idea was that if you could knock out either one of these arms—UTI or VUR—either by surgically correcting the reflux or preventing UTI with prophylactic antibiotics, you could prevent the march down this path.”

Multiple studies comparing the effectiveness of these interventions have failed to show that either approach is better than the other with respect to the development of new renal scars, “or whether any intervention does more good than harm for VUR,” said Dr. Keren.

Because of this, “there is a lot of skepticism about that empirical model as the basis for our management, which has led to calls for a 'top down' management approach, starting with the kidneys vs. the bladder.”

According to this approach, the kidneys of children with a UTI should be assessed by DMSA scan. “The absence of abnormalities on DMSA scan has a very good negative predictive value for high-grade VUR, which is most strongly associated with subsequent renal scarring and other effects of pyelonephritis,” said Dr. Keren. “With normal DMSA scan, you can reassure parents that the kidneys are normal and that the child is unlikely to have dilating VUR, and you might want to consider skipping the VCUG.” An abnormal scan warrants the VCUG and, depending on the degree of VUR, the consideration of antibiotics or surgery, he said.

Dr. Keren reported having no financial conflicts of interest with respect to his presentation.

Dysfunctional Voiding Often Causes UTIs

It's critical for general pediatricians to consider dysfunctional elimination as a cause of urinary tract infections in children, Dr. Keren said.

Dysfunctional elimination often goes undiagnosed and undertreated, despite the fact that approximately 40% of children with first UTI and 80% of children with recurrent UTI will have symptoms of the condition, Dr. Keren said. It is characterized by abnormal elimination patterns (frequent or infrequent voids, urgency, and constipation), bladder or bowel incontinence, and/or withholding maneuvers.

The possibility of dysfunctional elimination can be evaluated using the validated Dysfunctional Voiding Scoring System, which asks a series of simple questions about bowel and bladder practices (J. Urol. 2000;164:1011–5).

Once the condition has been diagnosed, parents should be encouraged to try some simple interventions, such as scheduling voiding times every 2 or 3 hours, treating constipation with laxatives and increased fluid intake, and avoiding bladder irritants such as caffeine, food coloring, chocolate, citrus, and carbonated beverages.

“If these interventions don't work, I would refer the child to a urologist for further evaluation. Often, some of the bigger academic hospitals will have dysfunctional voiding clinics, where a psychologist might work with the child using biofeedback to retrain the pelvic floor muscles. The urologist might also prescribe anticholinergics,” Dr. Keren said.

Studies have shown treatment of dysfunctional elimination can decrease UTI recurrences and can speed the resolution of VUR, he said. As such, “screening for [dysfunctional elimination] is an important first step in the management of pediatric UTI,” he said.

BOSTON — A recent study suggesting that prophylactic antibiotics for an initial urinary tract infection in children do not prevent recurrent infection and may, in fact, contribute to an increased risk of recurrent infection with a resistant bacteria has raised questions about the standard of care for these patients.

Dr. Ron Keren of the Children's Hospital of Philadelphia made this presentationat the annual meeting of the American Academy of Pediatrics.

The AAP 1999 practice parameter recommends that all children with a first urinary tract infection (UTI) undergo renal ultrasound to detect abnormalities such as hydronephrosis, bladder hypertrophy, and ureteroceles; and either a voiding cystourethrogram (VCUG) or direct radionuclide cystography (RNC) to evaluate the presence and degree of vesicoureteral reflux (VUR), Dr. Keren explained. Conventional wisdom has been that evidence of VUR, which is found in 30%–40% of children with UTI, warrants prophylactic antibiotic treatment to prevent recurrent infection and subsequent kidney damage, he said.

In an observational study, Dr. Keren and his colleagues reviewed the electronic health records of nearly 80,000 children with at least two pediatric care visits over a 5-year period and identified 611 children who had been diagnosed with a first UTI (JAMA 2007;298:179–86). “We then looked forward into the records to determine how many of these kids had recurrent [UTI], what the risk factors were, and whether the prescription of prophylactic antibiotics actually changed the risk,” he said.

Of those 611 children who'd had a UTI, 83 (14%) had been diagnosed with a recurrent infection. With use of a time-to-event analysis, “white children, older children, and children with high-grade VUR had a statistically significant increased risk of recurrent UTI, while having been prescribed prophylactic antibiotics had no relationship to recurrent infection,” he said, noting that children with low grade VUR, which is what the majority of kids have when there is evidence of VUR, were not at increased risk for reinfection. Additionally, “having been exposed to prophylactic antibiotics increased the odds of reinfection with a bug that was not pansensitive almost eightfold,” he said.

Multiple clinical trials also have failed to show a benefit of prophylactic antibiotics for the prevention of recurrent UTIs, and the authors of a 2006 systematic review of the available literature reported that the evidence to support the widespread use of antibiotics to prevent recurrent, symptomatic UTI is weak but stressed the need for large randomized, double-blinded clinical trials (Cochrane Database Syst. Rev. 2006; doi:10.1002/14651858.CD001534).

Given the apparent contradiction between the evidence and the standard of care, what is a pediatrician or parent to do? “Remember the old saying: 'The absence of evidence is not evidence of absence of benefit,'” Dr. Keren advised. “Right now, the AAP says we should be screening these kids, and we should probably be doing something about what we find. It's perfectly fine to take the conservative approach and continue to screen all kids for VUR after the first UTI and continue to prescribe prophylactic antibiotics for kids with VUR until the VUR resolves, until we get better evidence.”

But it's also okay to use clinical judgment with respect to individualizing care, Dr. Keren stressed. “There's a big difference between a 3-year-old girl with her first afebrile UTI concurrent with potty training vs. a 5-month-old girl with febrile UTI requiring hospitalization and a history of febrile illnesses that got better with antibiotics, and a sibling and mother with a history of dilating VUR,” he said. “These are two very different creatures. I would seriously consider screening the latter child for VUR but waiting for recurrent UTI before screening the older child.”

Interestingly, the AAP imaging recommendations as outlined in the practice parameter also have been the subject of controversy. “The guidelines were written for children from 2 to 24 months of age. There's no comment on what to do for older children, yet when you look at the epidemiology of UTI in kids, the majority of children are between 2 and 6 years old when they get their first UTI. Should we be doing the same for a 4-year-old as we do for a 2- to 24-month old?” asked Dr. Keren. And while the guidelines clearly spell out imaging recommendations, “they don't tell us what to do with the findings uncovered on imaging.”

Because of this, the current management model for VUR comes from the American Urological Association (AUA) guidelines, which indicate that treatment should be decided based the age of the child and the grade of VUR based on the International Classification System for vesicoureteral reflux. “With the exception of kids between 1 and 5 years with bilateral grade V VUR and kids 6–10 years with bilateral grade III or IV reflux or unilateral grade V reflux, for whom surgery is recommended, the AUG recommends prophylactic antibiotics for initial management of kids who don't have renal scarring at the time of diagnosis,” said Dr. Keren.

“Of course, a lot of sites are not doing DMSA [dimercaptosuccinic acid] renal flow scans up front, so they don't know whether there is scarring, but these recommendations stem from an empirical treatment model that's been in place for 20–30 years that suggests UTIs in the presence of reflux leads to scarring which can lead later in life to end-stage renal disease, hypertension, or preeclampsia in young women,” he said. “The idea was that if you could knock out either one of these arms—UTI or VUR—either by surgically correcting the reflux or preventing UTI with prophylactic antibiotics, you could prevent the march down this path.”

Multiple studies comparing the effectiveness of these interventions have failed to show that either approach is better than the other with respect to the development of new renal scars, “or whether any intervention does more good than harm for VUR,” said Dr. Keren.

Because of this, “there is a lot of skepticism about that empirical model as the basis for our management, which has led to calls for a 'top down' management approach, starting with the kidneys vs. the bladder.”

According to this approach, the kidneys of children with a UTI should be assessed by DMSA scan. “The absence of abnormalities on DMSA scan has a very good negative predictive value for high-grade VUR, which is most strongly associated with subsequent renal scarring and other effects of pyelonephritis,” said Dr. Keren. “With normal DMSA scan, you can reassure parents that the kidneys are normal and that the child is unlikely to have dilating VUR, and you might want to consider skipping the VCUG.” An abnormal scan warrants the VCUG and, depending on the degree of VUR, the consideration of antibiotics or surgery, he said.

Dr. Keren reported having no financial conflicts of interest with respect to his presentation.

Dysfunctional Voiding Often Causes UTIs

It's critical for general pediatricians to consider dysfunctional elimination as a cause of urinary tract infections in children, Dr. Keren said.

Dysfunctional elimination often goes undiagnosed and undertreated, despite the fact that approximately 40% of children with first UTI and 80% of children with recurrent UTI will have symptoms of the condition, Dr. Keren said. It is characterized by abnormal elimination patterns (frequent or infrequent voids, urgency, and constipation), bladder or bowel incontinence, and/or withholding maneuvers.

The possibility of dysfunctional elimination can be evaluated using the validated Dysfunctional Voiding Scoring System, which asks a series of simple questions about bowel and bladder practices (J. Urol. 2000;164:1011–5).

Once the condition has been diagnosed, parents should be encouraged to try some simple interventions, such as scheduling voiding times every 2 or 3 hours, treating constipation with laxatives and increased fluid intake, and avoiding bladder irritants such as caffeine, food coloring, chocolate, citrus, and carbonated beverages.

“If these interventions don't work, I would refer the child to a urologist for further evaluation. Often, some of the bigger academic hospitals will have dysfunctional voiding clinics, where a psychologist might work with the child using biofeedback to retrain the pelvic floor muscles. The urologist might also prescribe anticholinergics,” Dr. Keren said.

Studies have shown treatment of dysfunctional elimination can decrease UTI recurrences and can speed the resolution of VUR, he said. As such, “screening for [dysfunctional elimination] is an important first step in the management of pediatric UTI,” he said.

BOSTON — All children should get at least 400 IU of vitamin D daily, either through dietary intake or supplementation, beginning within days of birth and continuing through adolescence.

New guidelines from the American Academy of Pediatrics double its 2003 vitamin D intake recommendation in an effort to prevent the development of rickets in specific pediatric populations and take advantage of the potential long-term health benefits associated with adequate intake of the fat-soluble nutrient, Dr. Frank Greer, chairman of the academy's National Committee on Nutrition and coauthor of the report, said at the AAP's annual meeting.

The new guidelines are “logical” amid continued reports of rickets in infants and adolescents in the United States and mounting clinical evidence that 200 IU a day may not sufficiently prevent deficiency-related conditions, said Dr. Greer, professor of pediatrics at the University of Wisconsin, Madison.

Increasing evidence in the adult literature has also implicated vitamin D in the prevention of infection; autoimmune diseases; some forms of cancer; osteoporosis; and type 2 diabetes.

The 2003 guidelines suggested vitamin D supplementation primarily for babies who were breastfed exclusively, with the belief that most other children would be able to meet the 200-IU/day recommendation through normal diet and milk consumption. But, Dr. Greer said, “now that we're at 400 IU, we are strongly recommending supplementation across the board because the presence of vitamin D as a natural ingredient in food in most diets is limited.”

Specific points in the guidelines include:

▸ Breastfed and partially breastfed babies should be supplemented with 400 IU of vitamin D daily beginning in the first few days of life.

▸ Infants and children who consume less than one quart of vitamin D-fortified formula or milk daily should receive a 400-IU supplement.

▸ Adolescents who do not get 400 IU of vitamin D through diet should take a daily supplement of that amount.

▸ Children at increased risk of vitamin D deficiency, such as those with chronic fat malabsorption and those taking certain antiseizure medications, may require higher doses of vitamin D.

African American babies are at particularly increased risk for vitamin D deficiency because dark skin pigmentation interferes with the penetration of ultraviolet light and with vitamin D production.

Adolescents, whose intake of vitamin D-fortified milk and vitamin D-rich foods such as fatty fish is generally insufficient, are also at risk. “It's not clear, especially in adolescents, whether 400 IU of vitamin D is enough … but we're concerned about recommending more than 400 IU because of the likelihood that vitamin D is going to start showing up in all sorts of foods, thanks to the [Food and Drug Administration's] allowance of qualified health care claims on food packaging,” Dr. Greer said, “Vitamin D is a prohormone that acts directly on cells to promote gene transcription. It's a powerful nutrient, so we have to be careful.”

The guidelines will be published in the November issue of Pediatrics (2008;122:1142-52).

Dr. Greer reported no conflicts of interest with respect to his presentation.

BOSTON — All children should get at least 400 IU of vitamin D daily, either through dietary intake or supplementation, beginning within days of birth and continuing through adolescence.

New guidelines from the American Academy of Pediatrics double its 2003 vitamin D intake recommendation in an effort to prevent the development of rickets in specific pediatric populations and take advantage of the potential long-term health benefits associated with adequate intake of the fat-soluble nutrient, Dr. Frank Greer, chairman of the academy's National Committee on Nutrition and coauthor of the report, said at the AAP's annual meeting.

The new guidelines are “logical” amid continued reports of rickets in infants and adolescents in the United States and mounting clinical evidence that 200 IU a day may not sufficiently prevent deficiency-related conditions, said Dr. Greer, professor of pediatrics at the University of Wisconsin, Madison.

Increasing evidence in the adult literature has also implicated vitamin D in the prevention of infection; autoimmune diseases; some forms of cancer; osteoporosis; and type 2 diabetes.

The 2003 guidelines suggested vitamin D supplementation primarily for babies who were breastfed exclusively, with the belief that most other children would be able to meet the 200-IU/day recommendation through normal diet and milk consumption. But, Dr. Greer said, “now that we're at 400 IU, we are strongly recommending supplementation across the board because the presence of vitamin D as a natural ingredient in food in most diets is limited.”

Specific points in the guidelines include:

▸ Breastfed and partially breastfed babies should be supplemented with 400 IU of vitamin D daily beginning in the first few days of life.

▸ Infants and children who consume less than one quart of vitamin D-fortified formula or milk daily should receive a 400-IU supplement.

▸ Adolescents who do not get 400 IU of vitamin D through diet should take a daily supplement of that amount.

▸ Children at increased risk of vitamin D deficiency, such as those with chronic fat malabsorption and those taking certain antiseizure medications, may require higher doses of vitamin D.

African American babies are at particularly increased risk for vitamin D deficiency because dark skin pigmentation interferes with the penetration of ultraviolet light and with vitamin D production.

Adolescents, whose intake of vitamin D-fortified milk and vitamin D-rich foods such as fatty fish is generally insufficient, are also at risk. “It's not clear, especially in adolescents, whether 400 IU of vitamin D is enough … but we're concerned about recommending more than 400 IU because of the likelihood that vitamin D is going to start showing up in all sorts of foods, thanks to the [Food and Drug Administration's] allowance of qualified health care claims on food packaging,” Dr. Greer said, “Vitamin D is a prohormone that acts directly on cells to promote gene transcription. It's a powerful nutrient, so we have to be careful.”

The guidelines will be published in the November issue of Pediatrics (2008;122:1142-52).

Dr. Greer reported no conflicts of interest with respect to his presentation.

BOSTON — All children should get at least 400 IU of vitamin D daily, either through dietary intake or supplementation, beginning within days of birth and continuing through adolescence.

New guidelines from the American Academy of Pediatrics double its 2003 vitamin D intake recommendation in an effort to prevent the development of rickets in specific pediatric populations and take advantage of the potential long-term health benefits associated with adequate intake of the fat-soluble nutrient, Dr. Frank Greer, chairman of the academy's National Committee on Nutrition and coauthor of the report, said at the AAP's annual meeting.

The new guidelines are “logical” amid continued reports of rickets in infants and adolescents in the United States and mounting clinical evidence that 200 IU a day may not sufficiently prevent deficiency-related conditions, said Dr. Greer, professor of pediatrics at the University of Wisconsin, Madison.

Increasing evidence in the adult literature has also implicated vitamin D in the prevention of infection; autoimmune diseases; some forms of cancer; osteoporosis; and type 2 diabetes.

The 2003 guidelines suggested vitamin D supplementation primarily for babies who were breastfed exclusively, with the belief that most other children would be able to meet the 200-IU/day recommendation through normal diet and milk consumption. But, Dr. Greer said, “now that we're at 400 IU, we are strongly recommending supplementation across the board because the presence of vitamin D as a natural ingredient in food in most diets is limited.”

Specific points in the guidelines include:

▸ Breastfed and partially breastfed babies should be supplemented with 400 IU of vitamin D daily beginning in the first few days of life.

▸ Infants and children who consume less than one quart of vitamin D-fortified formula or milk daily should receive a 400-IU supplement.

▸ Adolescents who do not get 400 IU of vitamin D through diet should take a daily supplement of that amount.

▸ Children at increased risk of vitamin D deficiency, such as those with chronic fat malabsorption and those taking certain antiseizure medications, may require higher doses of vitamin D.

African American babies are at particularly increased risk for vitamin D deficiency because dark skin pigmentation interferes with the penetration of ultraviolet light and with vitamin D production.

Adolescents, whose intake of vitamin D-fortified milk and vitamin D-rich foods such as fatty fish is generally insufficient, are also at risk. “It's not clear, especially in adolescents, whether 400 IU of vitamin D is enough … but we're concerned about recommending more than 400 IU because of the likelihood that vitamin D is going to start showing up in all sorts of foods, thanks to the [Food and Drug Administration's] allowance of qualified health care claims on food packaging,” Dr. Greer said, “Vitamin D is a prohormone that acts directly on cells to promote gene transcription. It's a powerful nutrient, so we have to be careful.”

The guidelines will be published in the November issue of Pediatrics (2008;122:1142-52).

Dr. Greer reported no conflicts of interest with respect to his presentation.

BOSTON — Screening asymptomatic diabetes patients for myocardial ischemia using advanced imaging does not improve their 5-year prognosis for coronary events, compared with standard care, study results have shown.

In addition, of the 561 type 2 diabetes patients without symptomatic or previously diagnosed coronary artery disease who underwent screening with stress adenosine myocardial perfusion imaging (MPI) as part of the study, “only 22% had inducible ischemia, which was far less than we expected,” Dr. Frans J. Wackers of Yale University, said at the annual meeting of the American Society of Nuclear Cardiology.

During a mean follow-up of 4.8 years, there was no difference in the rates of cardiac events between patients in the screening group and the 562 patients in the standard care control group, he said, noting that the cumulative rate of cardiac events for both groups was approximately 3%.

The multicenter study randomized 1,123 patients, aged 55–75 years, with a mean diabetes duration of 8.7 years to MPI single-photon emission computed tomography (SPECT) screening or standard care without screening.

Patients with normal MPI or small MPI defects had 5-year cumulative cardiac event rates of 2.1% and 2.0%, respectively. However, the cumulative rates among patients with moderate to large MPI defects, as well as those with nonperfusion abnormalities such as ischemic changes on electrocardiogram, were significantly higher, at 12.3% and 6.8%, respectively.

Predictors of cardiac events by Cox regression included male sex, peripheral vascular disease, creatinine level, and abnormal heart rate response to standing.

The findings indicate that clinical events and significant inducible ischemia both identify higher-risk patients with type 2 diabetes, “but overall rates of cardiac events are equivalent whether or not patients underwent initial screening,” said Dr. Wackers, who reported no financial conflicts of interest.

BOSTON — Screening asymptomatic diabetes patients for myocardial ischemia using advanced imaging does not improve their 5-year prognosis for coronary events, compared with standard care, study results have shown.

In addition, of the 561 type 2 diabetes patients without symptomatic or previously diagnosed coronary artery disease who underwent screening with stress adenosine myocardial perfusion imaging (MPI) as part of the study, “only 22% had inducible ischemia, which was far less than we expected,” Dr. Frans J. Wackers of Yale University, said at the annual meeting of the American Society of Nuclear Cardiology.

During a mean follow-up of 4.8 years, there was no difference in the rates of cardiac events between patients in the screening group and the 562 patients in the standard care control group, he said, noting that the cumulative rate of cardiac events for both groups was approximately 3%.

The multicenter study randomized 1,123 patients, aged 55–75 years, with a mean diabetes duration of 8.7 years to MPI single-photon emission computed tomography (SPECT) screening or standard care without screening.

Patients with normal MPI or small MPI defects had 5-year cumulative cardiac event rates of 2.1% and 2.0%, respectively. However, the cumulative rates among patients with moderate to large MPI defects, as well as those with nonperfusion abnormalities such as ischemic changes on electrocardiogram, were significantly higher, at 12.3% and 6.8%, respectively.

Predictors of cardiac events by Cox regression included male sex, peripheral vascular disease, creatinine level, and abnormal heart rate response to standing.

The findings indicate that clinical events and significant inducible ischemia both identify higher-risk patients with type 2 diabetes, “but overall rates of cardiac events are equivalent whether or not patients underwent initial screening,” said Dr. Wackers, who reported no financial conflicts of interest.

BOSTON — Screening asymptomatic diabetes patients for myocardial ischemia using advanced imaging does not improve their 5-year prognosis for coronary events, compared with standard care, study results have shown.

In addition, of the 561 type 2 diabetes patients without symptomatic or previously diagnosed coronary artery disease who underwent screening with stress adenosine myocardial perfusion imaging (MPI) as part of the study, “only 22% had inducible ischemia, which was far less than we expected,” Dr. Frans J. Wackers of Yale University, said at the annual meeting of the American Society of Nuclear Cardiology.

During a mean follow-up of 4.8 years, there was no difference in the rates of cardiac events between patients in the screening group and the 562 patients in the standard care control group, he said, noting that the cumulative rate of cardiac events for both groups was approximately 3%.

The multicenter study randomized 1,123 patients, aged 55–75 years, with a mean diabetes duration of 8.7 years to MPI single-photon emission computed tomography (SPECT) screening or standard care without screening.

Patients with normal MPI or small MPI defects had 5-year cumulative cardiac event rates of 2.1% and 2.0%, respectively. However, the cumulative rates among patients with moderate to large MPI defects, as well as those with nonperfusion abnormalities such as ischemic changes on electrocardiogram, were significantly higher, at 12.3% and 6.8%, respectively.

Predictors of cardiac events by Cox regression included male sex, peripheral vascular disease, creatinine level, and abnormal heart rate response to standing.

The findings indicate that clinical events and significant inducible ischemia both identify higher-risk patients with type 2 diabetes, “but overall rates of cardiac events are equivalent whether or not patients underwent initial screening,” said Dr. Wackers, who reported no financial conflicts of interest.

An awareness of lysosomal storage disorders as a cause of joint abnormalities in children is essential for identifying the genetic disorders and intervening before permanent musculoskeletal damage occurs.

“New therapies are available, but their effect on bone and connective tissue disease is slow, so they need to be applied early for maximal benefit,” Dr. J. Edmund Wraith said at the annual congress of the Paediatric Rheumatology European Society.

Lysosomal storage diseases (LSDs) are heterogenous, inherited disorders characterized by the absence or deficiency of specific enzymes involved in the breakdown of macromolecules within the lysosomes of human cells. The resulting cellular dysfunction leads to progressive physical and/or mental deterioration, and death in some cases.

“There are a number of classic presentations, including hydrops fetalis; enlargement of the liver and spleen; neurodegenerative disease; and, most relevant to rheumatologists, skeletal dysplasia known as dyostosis multiplex and connective tissue involvement leading to progressive joint stiffness,” said Dr. Wraith of the Royal Manchester (England) Children's Hospital. “The disorders most often seen by rheumatologists are the attenuated form of mucopolysaccharidosis type I [Hurler/Scheie and Scheie disease], [and] mucolipidosis type III [pseudo-Hurler polydystrophy], in which skeletal involvement is prominent.”

These conditions, as well as two additional storage diseases—Gaucher disease, caused by a glucocerebrosidase deficiency, and Fabry disease, caused by deficiency of α-galactosidase A—can lead to musculoskeletal symptoms that can be mistaken for rheumatoid diseases. Patients with attenuated phenotypes of the mucopolysaccharidosis type I (MPS-I) disorders, for example, “often present during the first decade of life with joint contractures or a decreased range of motion, which can easily be mistaken for some form of juvenile arthritis,” said Dr. Hartmut Michels of the Rheumatic Children's Hospital, Garmisch-Partenkirchen, Germany. The skeletal complications of Gaucher disease type I, which include polyarthralgia of large peripheral joints, widening of the distal femur, bone pain, and bone crisis accompanied by swelling, localized skin erythema, and a raised erythrocyte sedimentation rate “can lead to a misdiagnosis of acute arthritis if the bone crisis is located close to a joint.”

The musculoskeletal symptoms of some of the other LSDs include a progressive restriction of joint mobility in the early years of life in mucolipidosis type III, and generalized pain and pain attacks similar to those seen in systemic vasculitides, connective tissue disease, or pain syndromes in Fabry disease, Dr. Michels noted.

While the early musculoskeletal symptoms may mimic rheumatoid conditions, the full clinical picture often tells a different story, said Dr. Wraith. For example, in the autosomal recessive MPS-I disorders, the characteristic bone and soft tissue changes “are usually not accompanied by the swelling and redness of the joints that are seen in the inflammatory arthropathies. Also, stiffness rather than pain tends to be the primary symptom,” he said.

Anti-CCP antibodies or antinuclear antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are typically not present in the storage diseases, said Dr. Michels. “Gaucher disease type I is an exception, because ESR may be elevated and antinuclear antibodies may be detected.” Prominent features of Gaucher disease type I include marked hepatomegaly and splenomegaly.

The nonspecific nature of early Fabry disease in children makes it one of the more difficult LSDs to diagnose, and a misdiagnosis of this X-linked sphingolipidosis can have the most devastating consequences, according to Dr. Michels. Caused by a systemic overaccumulation of globotriaosylceramide and related glycosphingolipids in lysosomes through the body, Fabry disease is characterized by progressive tissue and organ damage and ultimate organ failure. It affects, in particular, the kidneys, cardiovascular system, and cerebrovascular system.

Although the early, nonspecific symptoms, such as generalized pain and heat and cold intolerance, can easily be mistaken for fibromyalgia or a systemic vasculitide, “a thoroughly performed family history is important in obtaining an early diagnosis,” Dr. Michels and his colleagues observed in a recent review article. In one evaluation, they wrote, “Family histories revealed that 92% [out of 1,555 patients] had additional family members suffering from Fabry disease, comparable to the results of another study which demonstrated 43% of pediatric patients whose correct diagnosis was reached through their family histories,” (Curr. Opin. Rheumatol. Jan. 2008 [20]:76–81).

An awareness of the typical clinical picture of the relevant LSDs is essential, said Dr. Michels. “For example, hepato-splenomegaly in a child assumed to have oligoarticular juvenile idiopathic arthritis probably indicates Gaucher disease type I; carpel tunnel syndrome in a child thought to have JIA could be a symptom of MPS I-Scheie; and a stroke in a young adult with symptoms of fibromyalgia could mean Fabry disease,” he said. When an LSD is suspected, laboratory tests including lysosomal enzyme assays, can unequivocally diagnose or exclude the relevant disorders, he said.

“Until recently, rheumatologists did not have storage diseases on their differential diagnostic menu because the diseases were rare and not treatable,” said Dr. Bernhard Manger of the University of Erlangen-Nuremberg, Germany. “Now there is no excuse. … There are treatments.”

Enzyme replacement therapy via intravenous injection of recombinant proteins is the most common, Dr. Wraith said. The intravenous infusion of recombinant proteins effectively slows disease progression; thus, optimal efficacy requires early intervention, he said. The treatment is not a cure, however, and must be continued for life.

Other strategies include substrate reduction therapy and chemical chaperone therapy, which involve the application of small molecules that either inhibit the enzyme responsible for substrate synthesis or act as a chaperone to increase the residual activity of the lysosomal enzyme, said Dr. Michael Beck of the University of Mainz (Germany). In addition, “various in vivo and ex vivo gene therapeutic techniques have been developed, but are not yet available,” he said. “[These] administer the gene that is defective in a patient to the bloodstream or directly to the brain in order to overcome the blood-brain barrier.”

An awareness of lysosomal storage disorders as a cause of joint abnormalities in children is essential for identifying the genetic disorders and intervening before permanent musculoskeletal damage occurs.

“New therapies are available, but their effect on bone and connective tissue disease is slow, so they need to be applied early for maximal benefit,” Dr. J. Edmund Wraith said at the annual congress of the Paediatric Rheumatology European Society.

Lysosomal storage diseases (LSDs) are heterogenous, inherited disorders characterized by the absence or deficiency of specific enzymes involved in the breakdown of macromolecules within the lysosomes of human cells. The resulting cellular dysfunction leads to progressive physical and/or mental deterioration, and death in some cases.

“There are a number of classic presentations, including hydrops fetalis; enlargement of the liver and spleen; neurodegenerative disease; and, most relevant to rheumatologists, skeletal dysplasia known as dyostosis multiplex and connective tissue involvement leading to progressive joint stiffness,” said Dr. Wraith of the Royal Manchester (England) Children's Hospital. “The disorders most often seen by rheumatologists are the attenuated form of mucopolysaccharidosis type I [Hurler/Scheie and Scheie disease], [and] mucolipidosis type III [pseudo-Hurler polydystrophy], in which skeletal involvement is prominent.”

These conditions, as well as two additional storage diseases—Gaucher disease, caused by a glucocerebrosidase deficiency, and Fabry disease, caused by deficiency of α-galactosidase A—can lead to musculoskeletal symptoms that can be mistaken for rheumatoid diseases. Patients with attenuated phenotypes of the mucopolysaccharidosis type I (MPS-I) disorders, for example, “often present during the first decade of life with joint contractures or a decreased range of motion, which can easily be mistaken for some form of juvenile arthritis,” said Dr. Hartmut Michels of the Rheumatic Children's Hospital, Garmisch-Partenkirchen, Germany. The skeletal complications of Gaucher disease type I, which include polyarthralgia of large peripheral joints, widening of the distal femur, bone pain, and bone crisis accompanied by swelling, localized skin erythema, and a raised erythrocyte sedimentation rate “can lead to a misdiagnosis of acute arthritis if the bone crisis is located close to a joint.”

The musculoskeletal symptoms of some of the other LSDs include a progressive restriction of joint mobility in the early years of life in mucolipidosis type III, and generalized pain and pain attacks similar to those seen in systemic vasculitides, connective tissue disease, or pain syndromes in Fabry disease, Dr. Michels noted.

While the early musculoskeletal symptoms may mimic rheumatoid conditions, the full clinical picture often tells a different story, said Dr. Wraith. For example, in the autosomal recessive MPS-I disorders, the characteristic bone and soft tissue changes “are usually not accompanied by the swelling and redness of the joints that are seen in the inflammatory arthropathies. Also, stiffness rather than pain tends to be the primary symptom,” he said.

Anti-CCP antibodies or antinuclear antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are typically not present in the storage diseases, said Dr. Michels. “Gaucher disease type I is an exception, because ESR may be elevated and antinuclear antibodies may be detected.” Prominent features of Gaucher disease type I include marked hepatomegaly and splenomegaly.

The nonspecific nature of early Fabry disease in children makes it one of the more difficult LSDs to diagnose, and a misdiagnosis of this X-linked sphingolipidosis can have the most devastating consequences, according to Dr. Michels. Caused by a systemic overaccumulation of globotriaosylceramide and related glycosphingolipids in lysosomes through the body, Fabry disease is characterized by progressive tissue and organ damage and ultimate organ failure. It affects, in particular, the kidneys, cardiovascular system, and cerebrovascular system.

Although the early, nonspecific symptoms, such as generalized pain and heat and cold intolerance, can easily be mistaken for fibromyalgia or a systemic vasculitide, “a thoroughly performed family history is important in obtaining an early diagnosis,” Dr. Michels and his colleagues observed in a recent review article. In one evaluation, they wrote, “Family histories revealed that 92% [out of 1,555 patients] had additional family members suffering from Fabry disease, comparable to the results of another study which demonstrated 43% of pediatric patients whose correct diagnosis was reached through their family histories,” (Curr. Opin. Rheumatol. Jan. 2008 [20]:76–81).

An awareness of the typical clinical picture of the relevant LSDs is essential, said Dr. Michels. “For example, hepato-splenomegaly in a child assumed to have oligoarticular juvenile idiopathic arthritis probably indicates Gaucher disease type I; carpel tunnel syndrome in a child thought to have JIA could be a symptom of MPS I-Scheie; and a stroke in a young adult with symptoms of fibromyalgia could mean Fabry disease,” he said. When an LSD is suspected, laboratory tests including lysosomal enzyme assays, can unequivocally diagnose or exclude the relevant disorders, he said.

“Until recently, rheumatologists did not have storage diseases on their differential diagnostic menu because the diseases were rare and not treatable,” said Dr. Bernhard Manger of the University of Erlangen-Nuremberg, Germany. “Now there is no excuse. … There are treatments.”

Enzyme replacement therapy via intravenous injection of recombinant proteins is the most common, Dr. Wraith said. The intravenous infusion of recombinant proteins effectively slows disease progression; thus, optimal efficacy requires early intervention, he said. The treatment is not a cure, however, and must be continued for life.

Other strategies include substrate reduction therapy and chemical chaperone therapy, which involve the application of small molecules that either inhibit the enzyme responsible for substrate synthesis or act as a chaperone to increase the residual activity of the lysosomal enzyme, said Dr. Michael Beck of the University of Mainz (Germany). In addition, “various in vivo and ex vivo gene therapeutic techniques have been developed, but are not yet available,” he said. “[These] administer the gene that is defective in a patient to the bloodstream or directly to the brain in order to overcome the blood-brain barrier.”

An awareness of lysosomal storage disorders as a cause of joint abnormalities in children is essential for identifying the genetic disorders and intervening before permanent musculoskeletal damage occurs.

“New therapies are available, but their effect on bone and connective tissue disease is slow, so they need to be applied early for maximal benefit,” Dr. J. Edmund Wraith said at the annual congress of the Paediatric Rheumatology European Society.

Lysosomal storage diseases (LSDs) are heterogenous, inherited disorders characterized by the absence or deficiency of specific enzymes involved in the breakdown of macromolecules within the lysosomes of human cells. The resulting cellular dysfunction leads to progressive physical and/or mental deterioration, and death in some cases.

“There are a number of classic presentations, including hydrops fetalis; enlargement of the liver and spleen; neurodegenerative disease; and, most relevant to rheumatologists, skeletal dysplasia known as dyostosis multiplex and connective tissue involvement leading to progressive joint stiffness,” said Dr. Wraith of the Royal Manchester (England) Children's Hospital. “The disorders most often seen by rheumatologists are the attenuated form of mucopolysaccharidosis type I [Hurler/Scheie and Scheie disease], [and] mucolipidosis type III [pseudo-Hurler polydystrophy], in which skeletal involvement is prominent.”

These conditions, as well as two additional storage diseases—Gaucher disease, caused by a glucocerebrosidase deficiency, and Fabry disease, caused by deficiency of α-galactosidase A—can lead to musculoskeletal symptoms that can be mistaken for rheumatoid diseases. Patients with attenuated phenotypes of the mucopolysaccharidosis type I (MPS-I) disorders, for example, “often present during the first decade of life with joint contractures or a decreased range of motion, which can easily be mistaken for some form of juvenile arthritis,” said Dr. Hartmut Michels of the Rheumatic Children's Hospital, Garmisch-Partenkirchen, Germany. The skeletal complications of Gaucher disease type I, which include polyarthralgia of large peripheral joints, widening of the distal femur, bone pain, and bone crisis accompanied by swelling, localized skin erythema, and a raised erythrocyte sedimentation rate “can lead to a misdiagnosis of acute arthritis if the bone crisis is located close to a joint.”

The musculoskeletal symptoms of some of the other LSDs include a progressive restriction of joint mobility in the early years of life in mucolipidosis type III, and generalized pain and pain attacks similar to those seen in systemic vasculitides, connective tissue disease, or pain syndromes in Fabry disease, Dr. Michels noted.

While the early musculoskeletal symptoms may mimic rheumatoid conditions, the full clinical picture often tells a different story, said Dr. Wraith. For example, in the autosomal recessive MPS-I disorders, the characteristic bone and soft tissue changes “are usually not accompanied by the swelling and redness of the joints that are seen in the inflammatory arthropathies. Also, stiffness rather than pain tends to be the primary symptom,” he said.

Anti-CCP antibodies or antinuclear antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are typically not present in the storage diseases, said Dr. Michels. “Gaucher disease type I is an exception, because ESR may be elevated and antinuclear antibodies may be detected.” Prominent features of Gaucher disease type I include marked hepatomegaly and splenomegaly.

The nonspecific nature of early Fabry disease in children makes it one of the more difficult LSDs to diagnose, and a misdiagnosis of this X-linked sphingolipidosis can have the most devastating consequences, according to Dr. Michels. Caused by a systemic overaccumulation of globotriaosylceramide and related glycosphingolipids in lysosomes through the body, Fabry disease is characterized by progressive tissue and organ damage and ultimate organ failure. It affects, in particular, the kidneys, cardiovascular system, and cerebrovascular system.

Although the early, nonspecific symptoms, such as generalized pain and heat and cold intolerance, can easily be mistaken for fibromyalgia or a systemic vasculitide, “a thoroughly performed family history is important in obtaining an early diagnosis,” Dr. Michels and his colleagues observed in a recent review article. In one evaluation, they wrote, “Family histories revealed that 92% [out of 1,555 patients] had additional family members suffering from Fabry disease, comparable to the results of another study which demonstrated 43% of pediatric patients whose correct diagnosis was reached through their family histories,” (Curr. Opin. Rheumatol. Jan. 2008 [20]:76–81).

An awareness of the typical clinical picture of the relevant LSDs is essential, said Dr. Michels. “For example, hepato-splenomegaly in a child assumed to have oligoarticular juvenile idiopathic arthritis probably indicates Gaucher disease type I; carpel tunnel syndrome in a child thought to have JIA could be a symptom of MPS I-Scheie; and a stroke in a young adult with symptoms of fibromyalgia could mean Fabry disease,” he said. When an LSD is suspected, laboratory tests including lysosomal enzyme assays, can unequivocally diagnose or exclude the relevant disorders, he said.

“Until recently, rheumatologists did not have storage diseases on their differential diagnostic menu because the diseases were rare and not treatable,” said Dr. Bernhard Manger of the University of Erlangen-Nuremberg, Germany. “Now there is no excuse. … There are treatments.”

Enzyme replacement therapy via intravenous injection of recombinant proteins is the most common, Dr. Wraith said. The intravenous infusion of recombinant proteins effectively slows disease progression; thus, optimal efficacy requires early intervention, he said. The treatment is not a cure, however, and must be continued for life.

Other strategies include substrate reduction therapy and chemical chaperone therapy, which involve the application of small molecules that either inhibit the enzyme responsible for substrate synthesis or act as a chaperone to increase the residual activity of the lysosomal enzyme, said Dr. Michael Beck of the University of Mainz (Germany). In addition, “various in vivo and ex vivo gene therapeutic techniques have been developed, but are not yet available,” he said. “[These] administer the gene that is defective in a patient to the bloodstream or directly to the brain in order to overcome the blood-brain barrier.”

BOSTON — Screening asymptomatic diabetes patients for myocardial ischemia using advanced imaging does not improve their 5-year prognosis for coronary events, compared with standard care, study results have shown.

In addition to this “unexpected” finding from the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, a surprisingly low rate of ischemia was uncovered by the screening protocol in this population of patients who are considered to be at high risk for coronary disease, Dr. Frans J. Wackers reported at the annual meeting of the American Society of Nuclear Cardiology.

Of 561 type 2 diabetes patients without symptomatic or previously diagnosed coronary artery disease who underwent screening with stress adenosine myocardial perfusion imaging (MPI) as part of the study, “only 22% had inducible ischemia, which was far less than we expected,” said Dr. Wackers of Yale University, New Haven, Conn.

During a mean follow-up of 4.8 years, there was no difference in the rates of cardiac events between patients in the screening group and the 562 patients in the standard care control group, he said, noting that the cumulative rate of cardiac events for both groups was approximately 3%.

The goal of the DIAD study was to determine the prevalence of silent myocardial ischemia in adults with type 2 diabetes without evidence of coronary artery disease, as well as the cost-effectiveness of screening all diabetes patients for ischemia using MPI single-photon emission computed tomography (SPECT).

The multicenter study randomized 1,123 patients, aged 55-75 years, with a mean diabetes duration of 8.7 years to MPI SPECT screening or to standard care without screening. Subsequent diagnostic testing in both groups was performed at the discretion of patients' primary caregivers, even among those patients identified as having silent myocardial ischemia.

“When we gave the results to the physicians, we did not recommend treatment or referral to cardiologists because we didn't know if the results were [clinically relevant],” said Dr. Wackers.

All of the patients in the study were called at 6-month intervals to assess their cardiovascular health and treatment status.

In both the screening and standard care groups, 7% of the patients underwent coronary artery bypass grafting surgery during the course of the study. Additionally, the use of aspirin, statin drugs, and angiotensin-converting enzyme inhibitors increased significantly over the 5-year period, which probably explains why patients in both groups did so well, Dr. Wackers said.

With respect to the imaging findings in the screened population, patients with normal MPI results or with small MPI defects had 5-year cumulative cardiac event rates of 2.1% and 2.0%, respectively.

However, the cumulative cardiac event rates among patients who had moderate to large MPI defects, as well as those found to have nonperfusion abnormalities such as ischemic changes on electrocardiogram, were significantly higher, at 12.3% and 6.8%, respectively, Dr. Wackers reported.

In addition to moderate/large MPI defects and nonperfusion abnormalities, the investigators found that predictors of cardiac events by Cox regression included male sex, peripheral vascular disease, creatinine level, and abnormal heart rate response to standing.

The findings indicate that clinical events and significant inducible ischemia both identify higher-risk patients with type 2 diabetes, “but overall rates of cardiac events are equivalent whether or not patients undergo initial screening,” Dr. Wackers stated.

Dr. Wackers reported no financial conflicts of interest related to this presentation.

'Overall rates of cardiac events are equivalent whether or not patients undergo initial screening.' DR. WACKERS

BOSTON — Screening asymptomatic diabetes patients for myocardial ischemia using advanced imaging does not improve their 5-year prognosis for coronary events, compared with standard care, study results have shown.

In addition to this “unexpected” finding from the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, a surprisingly low rate of ischemia was uncovered by the screening protocol in this population of patients who are considered to be at high risk for coronary disease, Dr. Frans J. Wackers reported at the annual meeting of the American Society of Nuclear Cardiology.

Of 561 type 2 diabetes patients without symptomatic or previously diagnosed coronary artery disease who underwent screening with stress adenosine myocardial perfusion imaging (MPI) as part of the study, “only 22% had inducible ischemia, which was far less than we expected,” said Dr. Wackers of Yale University, New Haven, Conn.

During a mean follow-up of 4.8 years, there was no difference in the rates of cardiac events between patients in the screening group and the 562 patients in the standard care control group, he said, noting that the cumulative rate of cardiac events for both groups was approximately 3%.

The goal of the DIAD study was to determine the prevalence of silent myocardial ischemia in adults with type 2 diabetes without evidence of coronary artery disease, as well as the cost-effectiveness of screening all diabetes patients for ischemia using MPI single-photon emission computed tomography (SPECT).

The multicenter study randomized 1,123 patients, aged 55-75 years, with a mean diabetes duration of 8.7 years to MPI SPECT screening or to standard care without screening. Subsequent diagnostic testing in both groups was performed at the discretion of patients' primary caregivers, even among those patients identified as having silent myocardial ischemia.

“When we gave the results to the physicians, we did not recommend treatment or referral to cardiologists because we didn't know if the results were [clinically relevant],” said Dr. Wackers.

All of the patients in the study were called at 6-month intervals to assess their cardiovascular health and treatment status.

In both the screening and standard care groups, 7% of the patients underwent coronary artery bypass grafting surgery during the course of the study. Additionally, the use of aspirin, statin drugs, and angiotensin-converting enzyme inhibitors increased significantly over the 5-year period, which probably explains why patients in both groups did so well, Dr. Wackers said.

With respect to the imaging findings in the screened population, patients with normal MPI results or with small MPI defects had 5-year cumulative cardiac event rates of 2.1% and 2.0%, respectively.

However, the cumulative cardiac event rates among patients who had moderate to large MPI defects, as well as those found to have nonperfusion abnormalities such as ischemic changes on electrocardiogram, were significantly higher, at 12.3% and 6.8%, respectively, Dr. Wackers reported.

In addition to moderate/large MPI defects and nonperfusion abnormalities, the investigators found that predictors of cardiac events by Cox regression included male sex, peripheral vascular disease, creatinine level, and abnormal heart rate response to standing.

The findings indicate that clinical events and significant inducible ischemia both identify higher-risk patients with type 2 diabetes, “but overall rates of cardiac events are equivalent whether or not patients undergo initial screening,” Dr. Wackers stated.

Dr. Wackers reported no financial conflicts of interest related to this presentation.

'Overall rates of cardiac events are equivalent whether or not patients undergo initial screening.' DR. WACKERS

BOSTON — Screening asymptomatic diabetes patients for myocardial ischemia using advanced imaging does not improve their 5-year prognosis for coronary events, compared with standard care, study results have shown.

In addition to this “unexpected” finding from the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, a surprisingly low rate of ischemia was uncovered by the screening protocol in this population of patients who are considered to be at high risk for coronary disease, Dr. Frans J. Wackers reported at the annual meeting of the American Society of Nuclear Cardiology.

Of 561 type 2 diabetes patients without symptomatic or previously diagnosed coronary artery disease who underwent screening with stress adenosine myocardial perfusion imaging (MPI) as part of the study, “only 22% had inducible ischemia, which was far less than we expected,” said Dr. Wackers of Yale University, New Haven, Conn.

During a mean follow-up of 4.8 years, there was no difference in the rates of cardiac events between patients in the screening group and the 562 patients in the standard care control group, he said, noting that the cumulative rate of cardiac events for both groups was approximately 3%.

The goal of the DIAD study was to determine the prevalence of silent myocardial ischemia in adults with type 2 diabetes without evidence of coronary artery disease, as well as the cost-effectiveness of screening all diabetes patients for ischemia using MPI single-photon emission computed tomography (SPECT).

The multicenter study randomized 1,123 patients, aged 55-75 years, with a mean diabetes duration of 8.7 years to MPI SPECT screening or to standard care without screening. Subsequent diagnostic testing in both groups was performed at the discretion of patients' primary caregivers, even among those patients identified as having silent myocardial ischemia.

“When we gave the results to the physicians, we did not recommend treatment or referral to cardiologists because we didn't know if the results were [clinically relevant],” said Dr. Wackers.

All of the patients in the study were called at 6-month intervals to assess their cardiovascular health and treatment status.

In both the screening and standard care groups, 7% of the patients underwent coronary artery bypass grafting surgery during the course of the study. Additionally, the use of aspirin, statin drugs, and angiotensin-converting enzyme inhibitors increased significantly over the 5-year period, which probably explains why patients in both groups did so well, Dr. Wackers said.

With respect to the imaging findings in the screened population, patients with normal MPI results or with small MPI defects had 5-year cumulative cardiac event rates of 2.1% and 2.0%, respectively.

However, the cumulative cardiac event rates among patients who had moderate to large MPI defects, as well as those found to have nonperfusion abnormalities such as ischemic changes on electrocardiogram, were significantly higher, at 12.3% and 6.8%, respectively, Dr. Wackers reported.

In addition to moderate/large MPI defects and nonperfusion abnormalities, the investigators found that predictors of cardiac events by Cox regression included male sex, peripheral vascular disease, creatinine level, and abnormal heart rate response to standing.

The findings indicate that clinical events and significant inducible ischemia both identify higher-risk patients with type 2 diabetes, “but overall rates of cardiac events are equivalent whether or not patients undergo initial screening,” Dr. Wackers stated.

Dr. Wackers reported no financial conflicts of interest related to this presentation.

'Overall rates of cardiac events are equivalent whether or not patients undergo initial screening.' DR. WACKERS

More than three-quarters of the nation's young children have been immunized with the full series of childhood vaccines recommended by the Centers for Disease Control and Prevention, according to data from the CDC's 2007 National Immunization Survey.

The survey provides coverage estimates for the 4:3:1:3:3:1 immunization series for children aged 19–35 months that includes vaccines for diphtheria, tetanus, and acellular pertussis (DTaP); poliovirus; measles, mumps, and rubella (MMR); Haemophilus influenzae type B; hepatitis B; and varicella.

All but one vaccine in the recommended series—the fourth dose of the DTaP vaccine—reached 90% coverage in 2007, including for the first time the varicella vaccine and the third dose of the seven-valent pneumococcal conjugate vaccine (PCV7), Dr. Julie Gerberding, director of the CDC, reported in a media briefing on the survey results. Additionally, less than 1% of the more than 17,000 children born between January 2004 and July 2006 represented in the survey had not received any vaccines in the recommended series by ages 19–35 months, and there were no statistically significant decreases in individual vaccine coverage from 2006 to 2007 (MMWR 2008;57:961-6).

The coverage rates are indicative of the “ongoing success” of the country's immunization program, said Dr. Gerberding. “This annual report card is very good. The survey indicates that we are at or above our Healthy People 2010 goal of 90% coverage for each of the vaccines [in the 4:3:1:3:3:1 series], and at 77.4%, we are close to the target of 80% for the combined series.” These numbers are a reflection of “the trust that parents have in the safety of the vaccines and in the health care providers who administer them,” she said.

Relative to the 2006 survey data, coverage levels in 2007 for one dose of the varicella vaccine increased from 89% to 90%, and coverage levels for three or more doses of the PCV7 increased from 87% to 90%, Dr. Gerberding reported.

As in previous years, the estimated vaccine coverage rates for the 4:3:1:3:3:1 series varied substantially among states, ranging from a low of 63% in Nevada to a high of 91% in Maryland. Similarly, there was substantial variation among 14 local areas surveyed, ranging from 70% in San Bernardino County, Calif., to 82% in Philadelphia, she said.

Despite regional coverage gaps, said Dr. Gerberding, “vaccine coverage levels were similar across all racial and ethnic groups for the complete series, and there were some important gains.” Specifically, among Native American and Alaska Native children, both varicella and fourth-dose PCV7 coverage increased significantly, from 85% in 2006 to 95% in 2007 for varicella and from 63% in 2006 to 80% for PCV7 in 2007, she noted.

Belying the apparent successes in the immunization program is the recently reported surge in U.S. measles outbreaks (MMWR 2008;57:893-6), which is “a sobering aspect in our failure to protect some children from vaccine-preventable diseases,” said Dr. Gerberding. “Many of the children affected in these outbreaks were not adequately protected. Some were too young to be fully immunized, and some parents chose not to immunize their children.”

The measles outbreaks serve as an important reminder to maintain heightened vigilance “and not take the benefits of immunizations for granted,” said Dr. Anne Schuchat, director of the CDC's National Center for Immunization and Respiratory Diseases. “We're doing well, but we're not finished. Achieving high [coverage] levels is important for preventing major resurgences in diseases like measles.”

The measles outbreaks also point to some of the limitations of the National Immunization Survey data, Dr. Schuchat said during the briefing.

The survey estimates state and national coverage levels and provides information on specific local areas, “but we don't have information for every local area,” she said.

ELSEVIER GLOBAL MEDICAL NEWS

More than three-quarters of the nation's young children have been immunized with the full series of childhood vaccines recommended by the Centers for Disease Control and Prevention, according to data from the CDC's 2007 National Immunization Survey.

The survey provides coverage estimates for the 4:3:1:3:3:1 immunization series for children aged 19–35 months that includes vaccines for diphtheria, tetanus, and acellular pertussis (DTaP); poliovirus; measles, mumps, and rubella (MMR); Haemophilus influenzae type B; hepatitis B; and varicella.

All but one vaccine in the recommended series—the fourth dose of the DTaP vaccine—reached 90% coverage in 2007, including for the first time the varicella vaccine and the third dose of the seven-valent pneumococcal conjugate vaccine (PCV7), Dr. Julie Gerberding, director of the CDC, reported in a media briefing on the survey results. Additionally, less than 1% of the more than 17,000 children born between January 2004 and July 2006 represented in the survey had not received any vaccines in the recommended series by ages 19–35 months, and there were no statistically significant decreases in individual vaccine coverage from 2006 to 2007 (MMWR 2008;57:961-6).

The coverage rates are indicative of the “ongoing success” of the country's immunization program, said Dr. Gerberding. “This annual report card is very good. The survey indicates that we are at or above our Healthy People 2010 goal of 90% coverage for each of the vaccines [in the 4:3:1:3:3:1 series], and at 77.4%, we are close to the target of 80% for the combined series.” These numbers are a reflection of “the trust that parents have in the safety of the vaccines and in the health care providers who administer them,” she said.

Relative to the 2006 survey data, coverage levels in 2007 for one dose of the varicella vaccine increased from 89% to 90%, and coverage levels for three or more doses of the PCV7 increased from 87% to 90%, Dr. Gerberding reported.

As in previous years, the estimated vaccine coverage rates for the 4:3:1:3:3:1 series varied substantially among states, ranging from a low of 63% in Nevada to a high of 91% in Maryland. Similarly, there was substantial variation among 14 local areas surveyed, ranging from 70% in San Bernardino County, Calif., to 82% in Philadelphia, she said.

Despite regional coverage gaps, said Dr. Gerberding, “vaccine coverage levels were similar across all racial and ethnic groups for the complete series, and there were some important gains.” Specifically, among Native American and Alaska Native children, both varicella and fourth-dose PCV7 coverage increased significantly, from 85% in 2006 to 95% in 2007 for varicella and from 63% in 2006 to 80% for PCV7 in 2007, she noted.

Belying the apparent successes in the immunization program is the recently reported surge in U.S. measles outbreaks (MMWR 2008;57:893-6), which is “a sobering aspect in our failure to protect some children from vaccine-preventable diseases,” said Dr. Gerberding. “Many of the children affected in these outbreaks were not adequately protected. Some were too young to be fully immunized, and some parents chose not to immunize their children.”

The measles outbreaks serve as an important reminder to maintain heightened vigilance “and not take the benefits of immunizations for granted,” said Dr. Anne Schuchat, director of the CDC's National Center for Immunization and Respiratory Diseases. “We're doing well, but we're not finished. Achieving high [coverage] levels is important for preventing major resurgences in diseases like measles.”

The measles outbreaks also point to some of the limitations of the National Immunization Survey data, Dr. Schuchat said during the briefing.

The survey estimates state and national coverage levels and provides information on specific local areas, “but we don't have information for every local area,” she said.

ELSEVIER GLOBAL MEDICAL NEWS

More than three-quarters of the nation's young children have been immunized with the full series of childhood vaccines recommended by the Centers for Disease Control and Prevention, according to data from the CDC's 2007 National Immunization Survey.

The survey provides coverage estimates for the 4:3:1:3:3:1 immunization series for children aged 19–35 months that includes vaccines for diphtheria, tetanus, and acellular pertussis (DTaP); poliovirus; measles, mumps, and rubella (MMR); Haemophilus influenzae type B; hepatitis B; and varicella.

All but one vaccine in the recommended series—the fourth dose of the DTaP vaccine—reached 90% coverage in 2007, including for the first time the varicella vaccine and the third dose of the seven-valent pneumococcal conjugate vaccine (PCV7), Dr. Julie Gerberding, director of the CDC, reported in a media briefing on the survey results. Additionally, less than 1% of the more than 17,000 children born between January 2004 and July 2006 represented in the survey had not received any vaccines in the recommended series by ages 19–35 months, and there were no statistically significant decreases in individual vaccine coverage from 2006 to 2007 (MMWR 2008;57:961-6).

The coverage rates are indicative of the “ongoing success” of the country's immunization program, said Dr. Gerberding. “This annual report card is very good. The survey indicates that we are at or above our Healthy People 2010 goal of 90% coverage for each of the vaccines [in the 4:3:1:3:3:1 series], and at 77.4%, we are close to the target of 80% for the combined series.” These numbers are a reflection of “the trust that parents have in the safety of the vaccines and in the health care providers who administer them,” she said.

Relative to the 2006 survey data, coverage levels in 2007 for one dose of the varicella vaccine increased from 89% to 90%, and coverage levels for three or more doses of the PCV7 increased from 87% to 90%, Dr. Gerberding reported.

As in previous years, the estimated vaccine coverage rates for the 4:3:1:3:3:1 series varied substantially among states, ranging from a low of 63% in Nevada to a high of 91% in Maryland. Similarly, there was substantial variation among 14 local areas surveyed, ranging from 70% in San Bernardino County, Calif., to 82% in Philadelphia, she said.

Despite regional coverage gaps, said Dr. Gerberding, “vaccine coverage levels were similar across all racial and ethnic groups for the complete series, and there were some important gains.” Specifically, among Native American and Alaska Native children, both varicella and fourth-dose PCV7 coverage increased significantly, from 85% in 2006 to 95% in 2007 for varicella and from 63% in 2006 to 80% for PCV7 in 2007, she noted.

Belying the apparent successes in the immunization program is the recently reported surge in U.S. measles outbreaks (MMWR 2008;57:893-6), which is “a sobering aspect in our failure to protect some children from vaccine-preventable diseases,” said Dr. Gerberding. “Many of the children affected in these outbreaks were not adequately protected. Some were too young to be fully immunized, and some parents chose not to immunize their children.”

The measles outbreaks serve as an important reminder to maintain heightened vigilance “and not take the benefits of immunizations for granted,” said Dr. Anne Schuchat, director of the CDC's National Center for Immunization and Respiratory Diseases. “We're doing well, but we're not finished. Achieving high [coverage] levels is important for preventing major resurgences in diseases like measles.”

The measles outbreaks also point to some of the limitations of the National Immunization Survey data, Dr. Schuchat said during the briefing.

The survey estimates state and national coverage levels and provides information on specific local areas, “but we don't have information for every local area,” she said.

ELSEVIER GLOBAL MEDICAL NEWS

Most patients with a history of suspected vaccine allergy can be vaccinated safely against other diseases and some can receive additional doses of the vaccines to which they previously reacted, according to a report.

Careful monitoring and standard precautions are the keys to successful revaccination in patients who might have experienced hypersensitivity reactions after previous vaccines, wrote Dr. Robert Wood, chief of pediatric allergy and immunology at Johns Hopkins Children's Center, Baltimore (Pediatrics, Sept. 2008 122:e771-7).

Dr. Wood and his colleagues in the hypersensitivity working group of the Clinical Immunization Safety Assessment (CISA) network have developed a detailed algorithm for the evaluation and treatment of patients with suspected hypersensitivity.

According to the algorithm, physicians should take a detailed history to determine whether the symptoms of the prior reaction were consistent with an immediate-type reaction, and if so, whether the reaction might be IgE-mediated. Important considerations include the timing of onset of the symptoms, exposure to other allergens, duration of symptoms, vaccine history, history of atopic disease, and the specific vaccine that was administered, the authors wrote.

On an individual patient basis, there is a relatively low risk of true IgE-mediated type-1 hypersensitivity reactions—those that typically occur within minutes of exposure to the allergen and can potentially progress to anaphylaxis—as well as the more benign delayed-type hypersensitivity reactions. In medical settings, however, because vaccines are so widely administered, this is a “relatively common clinical problem,” according to the authors.

In the absence of symptoms of a true hypersensitivity reaction, patients can be revaccinated “in appropriate settings, with a waiting period of at least 15 minutes as per the guidelines of the Advisory Committee on Immunization Practices,” according to the algorithm.

In an individual with a history of an IgE-mediated reaction, referral for allergy testing is warranted, especially if additional doses of the vaccine are required.

“Both skin testing and testing for specific IgE antibodies in serum have been used for the diagnosis of allergic reactions related to MMR, influenza, DTP, varicella, and pneumococcal polysaccharide vaccines, as well as for the diagnosis of egg and gelatin sensitivity,” the authors wrote. Whenever possible, “skin testing should be done by using the specific vaccine, from the same manufacturer, that is suspected of causing the reaction,” they added.

Based on a case-by-case risk-benefit analysis per the algorithm, options for revaccination include:

▸ Withholding further doses of the vaccine in patients at risk for life-threatening complications from the vaccine, as well as in those with serologic evidence of immunity and those who are at low risk for the disease or disease complications.

▸ Revaccination and physician supervision for patients without evidence of immediate hypersensitivity.

▸ Revaccination using an alternative form of the vaccine that doesn't contain the offending allergen.

▸ Revaccination using special precautions, as outlined in the report, in patients with incomplete immunity to the disease who might be at risk for the disease.

“By use of a careful history and appropriate testing, most patients can be safely vaccinated or assured ongoing protection by the assessment of antibody titers,” the authors wrote.

Although the algorithm and guidelines are designed as a framework to help providers manage patients with suspected vaccine allergies, “the treatment of patients with suspected vaccine allergy is clearly an area in need of additional study,” they stated.

To accurately estimate the true burden of vaccine hypersensitivity reactions, the authors stressed that all suspected immediate and delayed reactions should be reported to the Vaccine Adverse Event Reporting System (www.vaers.hhs.gov

One of the working group members and report coauthors, Dr. Neal A. Halsey of Johns Hopkins University, and two additional working group members, reported receiving research support from multiple vaccine manufacturers.

Most patients with a history of suspected vaccine allergy can be vaccinated safely against other diseases and some can receive additional doses of the vaccines to which they previously reacted, according to a report.

Careful monitoring and standard precautions are the keys to successful revaccination in patients who might have experienced hypersensitivity reactions after previous vaccines, wrote Dr. Robert Wood, chief of pediatric allergy and immunology at Johns Hopkins Children's Center, Baltimore (Pediatrics, Sept. 2008 122:e771-7).

Dr. Wood and his colleagues in the hypersensitivity working group of the Clinical Immunization Safety Assessment (CISA) network have developed a detailed algorithm for the evaluation and treatment of patients with suspected hypersensitivity.

According to the algorithm, physicians should take a detailed history to determine whether the symptoms of the prior reaction were consistent with an immediate-type reaction, and if so, whether the reaction might be IgE-mediated. Important considerations include the timing of onset of the symptoms, exposure to other allergens, duration of symptoms, vaccine history, history of atopic disease, and the specific vaccine that was administered, the authors wrote.

On an individual patient basis, there is a relatively low risk of true IgE-mediated type-1 hypersensitivity reactions—those that typically occur within minutes of exposure to the allergen and can potentially progress to anaphylaxis—as well as the more benign delayed-type hypersensitivity reactions. In medical settings, however, because vaccines are so widely administered, this is a “relatively common clinical problem,” according to the authors.

In the absence of symptoms of a true hypersensitivity reaction, patients can be revaccinated “in appropriate settings, with a waiting period of at least 15 minutes as per the guidelines of the Advisory Committee on Immunization Practices,” according to the algorithm.

In an individual with a history of an IgE-mediated reaction, referral for allergy testing is warranted, especially if additional doses of the vaccine are required.

“Both skin testing and testing for specific IgE antibodies in serum have been used for the diagnosis of allergic reactions related to MMR, influenza, DTP, varicella, and pneumococcal polysaccharide vaccines, as well as for the diagnosis of egg and gelatin sensitivity,” the authors wrote. Whenever possible, “skin testing should be done by using the specific vaccine, from the same manufacturer, that is suspected of causing the reaction,” they added.

Based on a case-by-case risk-benefit analysis per the algorithm, options for revaccination include:

▸ Withholding further doses of the vaccine in patients at risk for life-threatening complications from the vaccine, as well as in those with serologic evidence of immunity and those who are at low risk for the disease or disease complications.

▸ Revaccination and physician supervision for patients without evidence of immediate hypersensitivity.

▸ Revaccination using an alternative form of the vaccine that doesn't contain the offending allergen.

▸ Revaccination using special precautions, as outlined in the report, in patients with incomplete immunity to the disease who might be at risk for the disease.

“By use of a careful history and appropriate testing, most patients can be safely vaccinated or assured ongoing protection by the assessment of antibody titers,” the authors wrote.

Although the algorithm and guidelines are designed as a framework to help providers manage patients with suspected vaccine allergies, “the treatment of patients with suspected vaccine allergy is clearly an area in need of additional study,” they stated.

To accurately estimate the true burden of vaccine hypersensitivity reactions, the authors stressed that all suspected immediate and delayed reactions should be reported to the Vaccine Adverse Event Reporting System (www.vaers.hhs.gov

One of the working group members and report coauthors, Dr. Neal A. Halsey of Johns Hopkins University, and two additional working group members, reported receiving research support from multiple vaccine manufacturers.

Most patients with a history of suspected vaccine allergy can be vaccinated safely against other diseases and some can receive additional doses of the vaccines to which they previously reacted, according to a report.

Careful monitoring and standard precautions are the keys to successful revaccination in patients who might have experienced hypersensitivity reactions after previous vaccines, wrote Dr. Robert Wood, chief of pediatric allergy and immunology at Johns Hopkins Children's Center, Baltimore (Pediatrics, Sept. 2008 122:e771-7).

Dr. Wood and his colleagues in the hypersensitivity working group of the Clinical Immunization Safety Assessment (CISA) network have developed a detailed algorithm for the evaluation and treatment of patients with suspected hypersensitivity.

According to the algorithm, physicians should take a detailed history to determine whether the symptoms of the prior reaction were consistent with an immediate-type reaction, and if so, whether the reaction might be IgE-mediated. Important considerations include the timing of onset of the symptoms, exposure to other allergens, duration of symptoms, vaccine history, history of atopic disease, and the specific vaccine that was administered, the authors wrote.

On an individual patient basis, there is a relatively low risk of true IgE-mediated type-1 hypersensitivity reactions—those that typically occur within minutes of exposure to the allergen and can potentially progress to anaphylaxis—as well as the more benign delayed-type hypersensitivity reactions. In medical settings, however, because vaccines are so widely administered, this is a “relatively common clinical problem,” according to the authors.

In the absence of symptoms of a true hypersensitivity reaction, patients can be revaccinated “in appropriate settings, with a waiting period of at least 15 minutes as per the guidelines of the Advisory Committee on Immunization Practices,” according to the algorithm.

In an individual with a history of an IgE-mediated reaction, referral for allergy testing is warranted, especially if additional doses of the vaccine are required.

“Both skin testing and testing for specific IgE antibodies in serum have been used for the diagnosis of allergic reactions related to MMR, influenza, DTP, varicella, and pneumococcal polysaccharide vaccines, as well as for the diagnosis of egg and gelatin sensitivity,” the authors wrote. Whenever possible, “skin testing should be done by using the specific vaccine, from the same manufacturer, that is suspected of causing the reaction,” they added.

Based on a case-by-case risk-benefit analysis per the algorithm, options for revaccination include:

▸ Withholding further doses of the vaccine in patients at risk for life-threatening complications from the vaccine, as well as in those with serologic evidence of immunity and those who are at low risk for the disease or disease complications.

▸ Revaccination and physician supervision for patients without evidence of immediate hypersensitivity.

▸ Revaccination using an alternative form of the vaccine that doesn't contain the offending allergen.

▸ Revaccination using special precautions, as outlined in the report, in patients with incomplete immunity to the disease who might be at risk for the disease.

“By use of a careful history and appropriate testing, most patients can be safely vaccinated or assured ongoing protection by the assessment of antibody titers,” the authors wrote.

Although the algorithm and guidelines are designed as a framework to help providers manage patients with suspected vaccine allergies, “the treatment of patients with suspected vaccine allergy is clearly an area in need of additional study,” they stated.

To accurately estimate the true burden of vaccine hypersensitivity reactions, the authors stressed that all suspected immediate and delayed reactions should be reported to the Vaccine Adverse Event Reporting System (www.vaers.hhs.gov

One of the working group members and report coauthors, Dr. Neal A. Halsey of Johns Hopkins University, and two additional working group members, reported receiving research support from multiple vaccine manufacturers.