Jennie Smith

Major Finding: Serum levels of the inflammatory protein MRP8/14 were elevated in 96% of children with JIA who went on to respond well to methotrexate.

Data Source: Data from a Dutch register of 109 children with JIA.

Disclosures: Dr. Moncrieffe's study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children's Charity.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of 109 previously untreated children with JIA to assess predictors of success with methotrexate. The findings represent a step toward the “ambitious goal” of personalized medicine for JIA, said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Dr. Moncrieffe noted that serum MRP8/14 is “relatively easy to measure,” and that samples do not require cold storage.

High levels of MRP 8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an American College of Rheumatology score of 50 or higher at 6 months on methotrexate, with the likelihood of achieving ACR50 or better increasing with every 500-ng/mL serum increase. Of patients with MRP8/14 levels above 3,000 ng/mL at baseline, 96% went on to achieve an ACR50 or higher response to methotrexate. High serum levels were predictive of response to methotrexate regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam (the Netherlands) presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and her associates enrolled 262 patients who had never been prescribed a biologic agent to control their disease before starting etanercept. The patients had been enrolled in the Dutch Arthritis and Biologicals in Children register, which since 1999 has kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They collected baseline clinical data using the physician's global assessment of disease activity and children's health assessment questionnaire scores. The investigators' goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might predict adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

“It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal,” said Dr. Otten. “However, a still-substantial proportion of patients do not reach the goal of inactive disease.” About a third of the patients in Dr. Otten and colleagues' study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began etanercept treatment before trying disease-modifying antirheumatic drugs improved more than those who had been on them previously. This finding was “really important,” as it indicated “the earlier and more aggressively we treat, the better the patients get,” she said.

Major Finding: Serum levels of the inflammatory protein MRP8/14 were elevated in 96% of children with JIA who went on to respond well to methotrexate.

Data Source: Data from a Dutch register of 109 children with JIA.

Disclosures: Dr. Moncrieffe's study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children's Charity.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of 109 previously untreated children with JIA to assess predictors of success with methotrexate. The findings represent a step toward the “ambitious goal” of personalized medicine for JIA, said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Dr. Moncrieffe noted that serum MRP8/14 is “relatively easy to measure,” and that samples do not require cold storage.

High levels of MRP 8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an American College of Rheumatology score of 50 or higher at 6 months on methotrexate, with the likelihood of achieving ACR50 or better increasing with every 500-ng/mL serum increase. Of patients with MRP8/14 levels above 3,000 ng/mL at baseline, 96% went on to achieve an ACR50 or higher response to methotrexate. High serum levels were predictive of response to methotrexate regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam (the Netherlands) presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and her associates enrolled 262 patients who had never been prescribed a biologic agent to control their disease before starting etanercept. The patients had been enrolled in the Dutch Arthritis and Biologicals in Children register, which since 1999 has kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They collected baseline clinical data using the physician's global assessment of disease activity and children's health assessment questionnaire scores. The investigators' goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might predict adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

“It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal,” said Dr. Otten. “However, a still-substantial proportion of patients do not reach the goal of inactive disease.” About a third of the patients in Dr. Otten and colleagues' study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began etanercept treatment before trying disease-modifying antirheumatic drugs improved more than those who had been on them previously. This finding was “really important,” as it indicated “the earlier and more aggressively we treat, the better the patients get,” she said.

Major Finding: Serum levels of the inflammatory protein MRP8/14 were elevated in 96% of children with JIA who went on to respond well to methotrexate.

Data Source: Data from a Dutch register of 109 children with JIA.

Disclosures: Dr. Moncrieffe's study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children's Charity.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of 109 previously untreated children with JIA to assess predictors of success with methotrexate. The findings represent a step toward the “ambitious goal” of personalized medicine for JIA, said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Dr. Moncrieffe noted that serum MRP8/14 is “relatively easy to measure,” and that samples do not require cold storage.

High levels of MRP 8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an American College of Rheumatology score of 50 or higher at 6 months on methotrexate, with the likelihood of achieving ACR50 or better increasing with every 500-ng/mL serum increase. Of patients with MRP8/14 levels above 3,000 ng/mL at baseline, 96% went on to achieve an ACR50 or higher response to methotrexate. High serum levels were predictive of response to methotrexate regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam (the Netherlands) presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and her associates enrolled 262 patients who had never been prescribed a biologic agent to control their disease before starting etanercept. The patients had been enrolled in the Dutch Arthritis and Biologicals in Children register, which since 1999 has kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They collected baseline clinical data using the physician's global assessment of disease activity and children's health assessment questionnaire scores. The investigators' goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might predict adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

“It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal,” said Dr. Otten. “However, a still-substantial proportion of patients do not reach the goal of inactive disease.” About a third of the patients in Dr. Otten and colleagues' study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began etanercept treatment before trying disease-modifying antirheumatic drugs improved more than those who had been on them previously. This finding was “really important,” as it indicated “the earlier and more aggressively we treat, the better the patients get,” she said.

BRUGES, BELGIUM – Should children whose juvenile idiopathic arthritis has been diagnosed by ultrasound be treated as aggressively as those whose disease is diagnosed clinically?

Researchers presenting last week at the Pediatric Rheumatology European Society Congress in Bruges, Belgium, offered both cautious and enthusiastic perspectives on musculoskeletal ultrasound, the use of which has become ubiquitous in pediatric rheumatology.

Dr. Silvia Magni-Manzoni, of Fondazione San Matteo in Pavia, Italy, presented results from a recent Europe-wide survey that showed that ultrasound is now being used by more than 90% of pediatric rheumatologists in their practices, with 40% of them using the technology personally (Pediatr. Rheumatol. 2011;9[suppl. 1]:P47), according to Dr. Magni-Manzoni, who conducted the survey with her associates.

Their 10-question survey of nearly 400 pediatric rheumatologists achieved a 24% response rate, with answers from 37 countries. The investigators collected information about current use in daily practice, the clinical relevance of ultrasound, and areas for prospective development. Nearly three-quarters of respondents said that ultrasound allowed for the immediate improving of diagnosis of joint and soft tissue disease, and 70% said they considered ultrasound important for diagnosis, therapy monitoring, and research.

However, Dr. Magni-Manzoni further cautioned about using ultrasound to predict the course of disease and make treatment recommendations in juvenile idiopathic arthritis (JIA).

Ultrasound diagnoses have led to the reclassification of JIA patients’ disease subtypes; for example, patients considered by clinical exam to be oligoarthritic have been reclassified as polyarthritic after ultrasound. "Clinical and ultrasound examinations show different sensitivity in detecting synovitis, especially for peripheral joints," she noted.

Last fall, Dr. Magni-Manzoni presented findings at the annual meeting of the American College of Rheumatology that showed how pronounced the discrepancy between clinical and ultrasound-detected synovitis can be. Looking at 28 consecutive JIA patients (Arthritis Rheum. 2010;62[suppl. 10]:2220) determined by clinical exam to be in remission, Dr. Magni-Manzoni and colleagues found synovial hyperplasia in 75% of these patients following immediate referral for ultrasound examination.

But the decision to treat earlier or more aggressively in patients with ultrasound-detected symptoms depends on whether the ultrasound-detected synovitis, joint diffusion, or synovial hyperplasia will ultimately translate into disease flares, she said.

Dr. Magni-Manzoni said that her team has been exploring the question, following 39 consecutive JIA patients who had been diagnosed at baseline with clinically inactive disease, but after a separate ultrasound exam immediately afterward were found to have subclinical symptoms.

After 2 years’ follow up, Dr. Magni-Manzoni and colleagues found that subclinical, ultrasound-detected synovial symptoms were not predictive of disease flares. More than 60% of the study subjects still had clinically inactive disease, even though three-quarters of them had ultrasound-detected synovial hyperplasia, and two-thirds had joint diffusion, at baseline.

In a separate presentation in at the pediatric rheumatology congress, Dr. Athimalaipet V. Ramanan discussed his data showing that ultrasound can be used successfully in specific applications in JIA. Used as a visual guide, ultrasound can produce accurate and effective temporomandibular joint injections as evidenced from a small study (n = 39).

The study involved children with JIA that was complicated by temporomandibular joint (TMJ) involvement. TMJ arthritis symptoms resolved in 92% of children within 2 months after ultrasound-guided corticosteroid injection. However, Dr. Ramanan, of the Bristol Royal Hospital for Children in Bristol, U.K., also noted his group had not found ultrasound helpful in diagnosis (Pediatr. Rheumatol. 2011;9[suppl. 1]:P122).

Noting that data presented by other investigators at the congress showed that blind TMJ injections in children with JIA were as successful as ones that were guided radiologically, Dr. Ramanan told the congress that despite lingering uncertainties, "We think the possibility of problems will be a lot lower with guided rather than blind injections."

Dr. Magni-Manzoni told the congress that she agreed that ultrasound-guided joint injections, such as those investigated by Dr. Ramanan and colleagues, were "very useful" in clinical practice. She expressed the need for more guidelines and for better knowledge of ultrasound anatomy in healthy children as reference. "Ultrasound reference values are not known in healthy children," she said.

While ultrasound has considerable advantages for the pediatric rheumatologist, Dr. Magni-Manzoni said, "there are some challenges." Ultrasound is not sensitive in helping identify disease in all joints, such as TMJ, she pointed out; the quality of imaging depends on the type of machine used and the operator’s technique; and operators require constant practice.

Dr. Magni-Manzoni and Dr. Ramanan each reported that they had no disclosures related to their findings.

BRUGES, BELGIUM – Should children whose juvenile idiopathic arthritis has been diagnosed by ultrasound be treated as aggressively as those whose disease is diagnosed clinically?

Researchers presenting last week at the Pediatric Rheumatology European Society Congress in Bruges, Belgium, offered both cautious and enthusiastic perspectives on musculoskeletal ultrasound, the use of which has become ubiquitous in pediatric rheumatology.

Dr. Silvia Magni-Manzoni, of Fondazione San Matteo in Pavia, Italy, presented results from a recent Europe-wide survey that showed that ultrasound is now being used by more than 90% of pediatric rheumatologists in their practices, with 40% of them using the technology personally (Pediatr. Rheumatol. 2011;9[suppl. 1]:P47), according to Dr. Magni-Manzoni, who conducted the survey with her associates.

Their 10-question survey of nearly 400 pediatric rheumatologists achieved a 24% response rate, with answers from 37 countries. The investigators collected information about current use in daily practice, the clinical relevance of ultrasound, and areas for prospective development. Nearly three-quarters of respondents said that ultrasound allowed for the immediate improving of diagnosis of joint and soft tissue disease, and 70% said they considered ultrasound important for diagnosis, therapy monitoring, and research.

However, Dr. Magni-Manzoni further cautioned about using ultrasound to predict the course of disease and make treatment recommendations in juvenile idiopathic arthritis (JIA).

Ultrasound diagnoses have led to the reclassification of JIA patients’ disease subtypes; for example, patients considered by clinical exam to be oligoarthritic have been reclassified as polyarthritic after ultrasound. "Clinical and ultrasound examinations show different sensitivity in detecting synovitis, especially for peripheral joints," she noted.

Last fall, Dr. Magni-Manzoni presented findings at the annual meeting of the American College of Rheumatology that showed how pronounced the discrepancy between clinical and ultrasound-detected synovitis can be. Looking at 28 consecutive JIA patients (Arthritis Rheum. 2010;62[suppl. 10]:2220) determined by clinical exam to be in remission, Dr. Magni-Manzoni and colleagues found synovial hyperplasia in 75% of these patients following immediate referral for ultrasound examination.

But the decision to treat earlier or more aggressively in patients with ultrasound-detected symptoms depends on whether the ultrasound-detected synovitis, joint diffusion, or synovial hyperplasia will ultimately translate into disease flares, she said.

Dr. Magni-Manzoni said that her team has been exploring the question, following 39 consecutive JIA patients who had been diagnosed at baseline with clinically inactive disease, but after a separate ultrasound exam immediately afterward were found to have subclinical symptoms.

After 2 years’ follow up, Dr. Magni-Manzoni and colleagues found that subclinical, ultrasound-detected synovial symptoms were not predictive of disease flares. More than 60% of the study subjects still had clinically inactive disease, even though three-quarters of them had ultrasound-detected synovial hyperplasia, and two-thirds had joint diffusion, at baseline.

In a separate presentation in at the pediatric rheumatology congress, Dr. Athimalaipet V. Ramanan discussed his data showing that ultrasound can be used successfully in specific applications in JIA. Used as a visual guide, ultrasound can produce accurate and effective temporomandibular joint injections as evidenced from a small study (n = 39).

The study involved children with JIA that was complicated by temporomandibular joint (TMJ) involvement. TMJ arthritis symptoms resolved in 92% of children within 2 months after ultrasound-guided corticosteroid injection. However, Dr. Ramanan, of the Bristol Royal Hospital for Children in Bristol, U.K., also noted his group had not found ultrasound helpful in diagnosis (Pediatr. Rheumatol. 2011;9[suppl. 1]:P122).

Noting that data presented by other investigators at the congress showed that blind TMJ injections in children with JIA were as successful as ones that were guided radiologically, Dr. Ramanan told the congress that despite lingering uncertainties, "We think the possibility of problems will be a lot lower with guided rather than blind injections."

Dr. Magni-Manzoni told the congress that she agreed that ultrasound-guided joint injections, such as those investigated by Dr. Ramanan and colleagues, were "very useful" in clinical practice. She expressed the need for more guidelines and for better knowledge of ultrasound anatomy in healthy children as reference. "Ultrasound reference values are not known in healthy children," she said.

While ultrasound has considerable advantages for the pediatric rheumatologist, Dr. Magni-Manzoni said, "there are some challenges." Ultrasound is not sensitive in helping identify disease in all joints, such as TMJ, she pointed out; the quality of imaging depends on the type of machine used and the operator’s technique; and operators require constant practice.

Dr. Magni-Manzoni and Dr. Ramanan each reported that they had no disclosures related to their findings.

BRUGES, BELGIUM – Should children whose juvenile idiopathic arthritis has been diagnosed by ultrasound be treated as aggressively as those whose disease is diagnosed clinically?

Researchers presenting last week at the Pediatric Rheumatology European Society Congress in Bruges, Belgium, offered both cautious and enthusiastic perspectives on musculoskeletal ultrasound, the use of which has become ubiquitous in pediatric rheumatology.

Dr. Silvia Magni-Manzoni, of Fondazione San Matteo in Pavia, Italy, presented results from a recent Europe-wide survey that showed that ultrasound is now being used by more than 90% of pediatric rheumatologists in their practices, with 40% of them using the technology personally (Pediatr. Rheumatol. 2011;9[suppl. 1]:P47), according to Dr. Magni-Manzoni, who conducted the survey with her associates.

Their 10-question survey of nearly 400 pediatric rheumatologists achieved a 24% response rate, with answers from 37 countries. The investigators collected information about current use in daily practice, the clinical relevance of ultrasound, and areas for prospective development. Nearly three-quarters of respondents said that ultrasound allowed for the immediate improving of diagnosis of joint and soft tissue disease, and 70% said they considered ultrasound important for diagnosis, therapy monitoring, and research.

However, Dr. Magni-Manzoni further cautioned about using ultrasound to predict the course of disease and make treatment recommendations in juvenile idiopathic arthritis (JIA).

Ultrasound diagnoses have led to the reclassification of JIA patients’ disease subtypes; for example, patients considered by clinical exam to be oligoarthritic have been reclassified as polyarthritic after ultrasound. "Clinical and ultrasound examinations show different sensitivity in detecting synovitis, especially for peripheral joints," she noted.

Last fall, Dr. Magni-Manzoni presented findings at the annual meeting of the American College of Rheumatology that showed how pronounced the discrepancy between clinical and ultrasound-detected synovitis can be. Looking at 28 consecutive JIA patients (Arthritis Rheum. 2010;62[suppl. 10]:2220) determined by clinical exam to be in remission, Dr. Magni-Manzoni and colleagues found synovial hyperplasia in 75% of these patients following immediate referral for ultrasound examination.

But the decision to treat earlier or more aggressively in patients with ultrasound-detected symptoms depends on whether the ultrasound-detected synovitis, joint diffusion, or synovial hyperplasia will ultimately translate into disease flares, she said.

Dr. Magni-Manzoni said that her team has been exploring the question, following 39 consecutive JIA patients who had been diagnosed at baseline with clinically inactive disease, but after a separate ultrasound exam immediately afterward were found to have subclinical symptoms.

After 2 years’ follow up, Dr. Magni-Manzoni and colleagues found that subclinical, ultrasound-detected synovial symptoms were not predictive of disease flares. More than 60% of the study subjects still had clinically inactive disease, even though three-quarters of them had ultrasound-detected synovial hyperplasia, and two-thirds had joint diffusion, at baseline.

In a separate presentation in at the pediatric rheumatology congress, Dr. Athimalaipet V. Ramanan discussed his data showing that ultrasound can be used successfully in specific applications in JIA. Used as a visual guide, ultrasound can produce accurate and effective temporomandibular joint injections as evidenced from a small study (n = 39).

The study involved children with JIA that was complicated by temporomandibular joint (TMJ) involvement. TMJ arthritis symptoms resolved in 92% of children within 2 months after ultrasound-guided corticosteroid injection. However, Dr. Ramanan, of the Bristol Royal Hospital for Children in Bristol, U.K., also noted his group had not found ultrasound helpful in diagnosis (Pediatr. Rheumatol. 2011;9[suppl. 1]:P122).

Noting that data presented by other investigators at the congress showed that blind TMJ injections in children with JIA were as successful as ones that were guided radiologically, Dr. Ramanan told the congress that despite lingering uncertainties, "We think the possibility of problems will be a lot lower with guided rather than blind injections."

Dr. Magni-Manzoni told the congress that she agreed that ultrasound-guided joint injections, such as those investigated by Dr. Ramanan and colleagues, were "very useful" in clinical practice. She expressed the need for more guidelines and for better knowledge of ultrasound anatomy in healthy children as reference. "Ultrasound reference values are not known in healthy children," she said.

While ultrasound has considerable advantages for the pediatric rheumatologist, Dr. Magni-Manzoni said, "there are some challenges." Ultrasound is not sensitive in helping identify disease in all joints, such as TMJ, she pointed out; the quality of imaging depends on the type of machine used and the operator’s technique; and operators require constant practice.

Dr. Magni-Manzoni and Dr. Ramanan each reported that they had no disclosures related to their findings.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of previously untreated children with juvenile idiopathic arthritis (JIA) (n = 109) to assess predictors of success with methotrexate. The findings represent a step toward the "ambitious goal of personalized medicine for JIA," said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Using a blood sample, clinicians might be able to know "whether or not, when a child walks in, is methotrexate going to be appropriate," she noted.

Dr. Moncrieffe noted that serum MRP8/14 is "relatively easy to measure" and that samples do not require cold storage, making laboratory transport and processing easier. High levels of MRP8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an ACR score of 50 or higher at 6 months on methotrexate, the researchers found, with likelihood of achieving ACR 50 or better seen increasing with every 500 ng/ml serum increase.

Of patients with MRP8/14 levels above 3,000 ng/ml at baseline, 96% went on to achieve an ACR 50 or higher response to methotrexate. High serum levels were predictive of methotrexate success regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Investigator Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and colleagues enrolled 262 patients who had never been prescribed a biological agent to control their disease before starting etanercept. The patients had been enrolled as the Dutch Arthritis and Biologicals in Children register, which has since 1999 kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They then collected baseline clinical data using the physician’s global assessment of disease activity and children’s health assessment questionnaire scores. The investigators’ goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might be predictive of adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

"It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal," Dr. Otten said at the conference. "However, a still-substantial proportion of patients do not reach the goal of inactive disease."

About a third of the patients in Dr. Otten and colleagues’ study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR 50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR 50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began treatment with etanercept before trying disease-modifying anti-rheumatic drugs (DMARDs) saw more improvement than those who had been on them previously, the investigators learned. The finding that children who had taken fewer DMARDS did better was "really important," as it indicated "the earlier and more aggressively we treat, the better the patients get," she said.

Girls and children with systemic-onset JIA were more likely to fare poorly on etanercept, Dr. Otten and her colleagues found. However, about a quarter of children with systemic onset were able to achieve inactive disease after 15 months of treatment.

Dr. Moncrieffe’s study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children’s Charity. University College London has filed a patent relating to methods for predicting effectiveness of drug treatment for arthritis. Dr Moncrieffe is an inventor on this patent application.

Some funding for the study came from Abbott and Pfizer, Dr. Otten disclosed.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of previously untreated children with juvenile idiopathic arthritis (JIA) (n = 109) to assess predictors of success with methotrexate. The findings represent a step toward the "ambitious goal of personalized medicine for JIA," said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Using a blood sample, clinicians might be able to know "whether or not, when a child walks in, is methotrexate going to be appropriate," she noted.

Dr. Moncrieffe noted that serum MRP8/14 is "relatively easy to measure" and that samples do not require cold storage, making laboratory transport and processing easier. High levels of MRP8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an ACR score of 50 or higher at 6 months on methotrexate, the researchers found, with likelihood of achieving ACR 50 or better seen increasing with every 500 ng/ml serum increase.

Of patients with MRP8/14 levels above 3,000 ng/ml at baseline, 96% went on to achieve an ACR 50 or higher response to methotrexate. High serum levels were predictive of methotrexate success regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Investigator Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and colleagues enrolled 262 patients who had never been prescribed a biological agent to control their disease before starting etanercept. The patients had been enrolled as the Dutch Arthritis and Biologicals in Children register, which has since 1999 kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They then collected baseline clinical data using the physician’s global assessment of disease activity and children’s health assessment questionnaire scores. The investigators’ goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might be predictive of adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

"It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal," Dr. Otten said at the conference. "However, a still-substantial proportion of patients do not reach the goal of inactive disease."

About a third of the patients in Dr. Otten and colleagues’ study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR 50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR 50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began treatment with etanercept before trying disease-modifying anti-rheumatic drugs (DMARDs) saw more improvement than those who had been on them previously, the investigators learned. The finding that children who had taken fewer DMARDS did better was "really important," as it indicated "the earlier and more aggressively we treat, the better the patients get," she said.

Girls and children with systemic-onset JIA were more likely to fare poorly on etanercept, Dr. Otten and her colleagues found. However, about a quarter of children with systemic onset were able to achieve inactive disease after 15 months of treatment.

Dr. Moncrieffe’s study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children’s Charity. University College London has filed a patent relating to methods for predicting effectiveness of drug treatment for arthritis. Dr Moncrieffe is an inventor on this patent application.

Some funding for the study came from Abbott and Pfizer, Dr. Otten disclosed.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of previously untreated children with juvenile idiopathic arthritis (JIA) (n = 109) to assess predictors of success with methotrexate. The findings represent a step toward the "ambitious goal of personalized medicine for JIA," said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Using a blood sample, clinicians might be able to know "whether or not, when a child walks in, is methotrexate going to be appropriate," she noted.

Dr. Moncrieffe noted that serum MRP8/14 is "relatively easy to measure" and that samples do not require cold storage, making laboratory transport and processing easier. High levels of MRP8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an ACR score of 50 or higher at 6 months on methotrexate, the researchers found, with likelihood of achieving ACR 50 or better seen increasing with every 500 ng/ml serum increase.

Of patients with MRP8/14 levels above 3,000 ng/ml at baseline, 96% went on to achieve an ACR 50 or higher response to methotrexate. High serum levels were predictive of methotrexate success regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Investigator Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and colleagues enrolled 262 patients who had never been prescribed a biological agent to control their disease before starting etanercept. The patients had been enrolled as the Dutch Arthritis and Biologicals in Children register, which has since 1999 kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They then collected baseline clinical data using the physician’s global assessment of disease activity and children’s health assessment questionnaire scores. The investigators’ goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might be predictive of adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

"It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal," Dr. Otten said at the conference. "However, a still-substantial proportion of patients do not reach the goal of inactive disease."

About a third of the patients in Dr. Otten and colleagues’ study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR 50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR 50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began treatment with etanercept before trying disease-modifying anti-rheumatic drugs (DMARDs) saw more improvement than those who had been on them previously, the investigators learned. The finding that children who had taken fewer DMARDS did better was "really important," as it indicated "the earlier and more aggressively we treat, the better the patients get," she said.

Girls and children with systemic-onset JIA were more likely to fare poorly on etanercept, Dr. Otten and her colleagues found. However, about a quarter of children with systemic onset were able to achieve inactive disease after 15 months of treatment.

Dr. Moncrieffe’s study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children’s Charity. University College London has filed a patent relating to methods for predicting effectiveness of drug treatment for arthritis. Dr Moncrieffe is an inventor on this patent application.

Some funding for the study came from Abbott and Pfizer, Dr. Otten disclosed.

BRUGES, BELGIUM – Canakinumab, an investigational interleukin-1b antibody also known as ACZ885, has been shown to lessen symptoms of systemic juvenile idiopathic arthritis more than placebo.

The medication, which has yet to be licensed in any country, is administered once a month by subcutaneous injection, instead of intravenous infusion.

The endpoint of the study was a reduction in disease activity by 30% according to American College of Rheumatology Pediatric criteria (ACR Pedi 30), which were modified for the study to include absence of fever, according to Dr. Nicolino Ruperto of the Pediatric Rheumatology International Trials Organization (PRINTO) and Istituto G Gaslini in Genoa, Italy.

Results from a phase III, manufacturer-sponsored, randomized controlled trial (n = 84) of canakinumab showed that a single injection of 4 mg/kg lessened symptoms by 30% or more in 83.7% of patients in the treatment arm (n = 43), compared with 9.8% in the placebo arm (n = 41), at 15 days (Pediatr. Rheum. 2011;9[Suppl 1]:O21).

Patients enrolled in the study were between 2 and 19 years old, with active disease but no macrophage activation syndrome. For the study group as a whole, the mean disease duration was 3.4 years; mean CRP 200.6 mg/L, mean number of active joints was 14.1; and mean prednisone equivalent therapy was 0.3 mg/kg per day.

Dr. Ruperto told the conference that the study participants had spiking intermittent fever at enrollment lasting at least 3 days, and they were allowed to continue on methotrexate or corticosteroids during the trial, but no biological agents besides the study medication.

A majority of patients in the treatment arm (67.4%) achieved ACR Pedi 50 improvement, compared with 4.9% for placebo, and about a third (32.6%) in the study arm saw improvement of ACR Pedi 100, compared with none for placebo. Both ACR Pedi 30 and ACR Pedi 50 responses with canakinumab remained significantly higher than with placebo at day 29.

Adverse events occurred in 55.8% of canakinumab and 39% of placebo patients. Dr. Ruperto said that the most frequently reported adverse events in the study group were upper respiratory problems and gastrointestinal complaints. No patients discontinued the trial because of side effects; however, 6 patients in the treatment arm and 37 in the placebo arm discontinued because for lack of therapeutic effect.

Two deaths occurred in the study group after the completion of the trial, during the long-term follow-up period, Dr. Ruperto told the congress. Both deaths were due to macrophage activation syndrome; one complicated with sepsis and the other with pulmonary hypertension.

The study was funded by Novartis. Dr. Ruperto reported having no financial conflicts of interest. Two of his coinvestigators are Novartis shareholders and one is a Novartis employee.

BRUGES, BELGIUM – Canakinumab, an investigational interleukin-1b antibody also known as ACZ885, has been shown to lessen symptoms of systemic juvenile idiopathic arthritis more than placebo.

The medication, which has yet to be licensed in any country, is administered once a month by subcutaneous injection, instead of intravenous infusion.

The endpoint of the study was a reduction in disease activity by 30% according to American College of Rheumatology Pediatric criteria (ACR Pedi 30), which were modified for the study to include absence of fever, according to Dr. Nicolino Ruperto of the Pediatric Rheumatology International Trials Organization (PRINTO) and Istituto G Gaslini in Genoa, Italy.

Results from a phase III, manufacturer-sponsored, randomized controlled trial (n = 84) of canakinumab showed that a single injection of 4 mg/kg lessened symptoms by 30% or more in 83.7% of patients in the treatment arm (n = 43), compared with 9.8% in the placebo arm (n = 41), at 15 days (Pediatr. Rheum. 2011;9[Suppl 1]:O21).

Patients enrolled in the study were between 2 and 19 years old, with active disease but no macrophage activation syndrome. For the study group as a whole, the mean disease duration was 3.4 years; mean CRP 200.6 mg/L, mean number of active joints was 14.1; and mean prednisone equivalent therapy was 0.3 mg/kg per day.

Dr. Ruperto told the conference that the study participants had spiking intermittent fever at enrollment lasting at least 3 days, and they were allowed to continue on methotrexate or corticosteroids during the trial, but no biological agents besides the study medication.

A majority of patients in the treatment arm (67.4%) achieved ACR Pedi 50 improvement, compared with 4.9% for placebo, and about a third (32.6%) in the study arm saw improvement of ACR Pedi 100, compared with none for placebo. Both ACR Pedi 30 and ACR Pedi 50 responses with canakinumab remained significantly higher than with placebo at day 29.

Adverse events occurred in 55.8% of canakinumab and 39% of placebo patients. Dr. Ruperto said that the most frequently reported adverse events in the study group were upper respiratory problems and gastrointestinal complaints. No patients discontinued the trial because of side effects; however, 6 patients in the treatment arm and 37 in the placebo arm discontinued because for lack of therapeutic effect.

Two deaths occurred in the study group after the completion of the trial, during the long-term follow-up period, Dr. Ruperto told the congress. Both deaths were due to macrophage activation syndrome; one complicated with sepsis and the other with pulmonary hypertension.

The study was funded by Novartis. Dr. Ruperto reported having no financial conflicts of interest. Two of his coinvestigators are Novartis shareholders and one is a Novartis employee.

BRUGES, BELGIUM – Canakinumab, an investigational interleukin-1b antibody also known as ACZ885, has been shown to lessen symptoms of systemic juvenile idiopathic arthritis more than placebo.

The medication, which has yet to be licensed in any country, is administered once a month by subcutaneous injection, instead of intravenous infusion.

The endpoint of the study was a reduction in disease activity by 30% according to American College of Rheumatology Pediatric criteria (ACR Pedi 30), which were modified for the study to include absence of fever, according to Dr. Nicolino Ruperto of the Pediatric Rheumatology International Trials Organization (PRINTO) and Istituto G Gaslini in Genoa, Italy.

Results from a phase III, manufacturer-sponsored, randomized controlled trial (n = 84) of canakinumab showed that a single injection of 4 mg/kg lessened symptoms by 30% or more in 83.7% of patients in the treatment arm (n = 43), compared with 9.8% in the placebo arm (n = 41), at 15 days (Pediatr. Rheum. 2011;9[Suppl 1]:O21).

Patients enrolled in the study were between 2 and 19 years old, with active disease but no macrophage activation syndrome. For the study group as a whole, the mean disease duration was 3.4 years; mean CRP 200.6 mg/L, mean number of active joints was 14.1; and mean prednisone equivalent therapy was 0.3 mg/kg per day.

Dr. Ruperto told the conference that the study participants had spiking intermittent fever at enrollment lasting at least 3 days, and they were allowed to continue on methotrexate or corticosteroids during the trial, but no biological agents besides the study medication.

A majority of patients in the treatment arm (67.4%) achieved ACR Pedi 50 improvement, compared with 4.9% for placebo, and about a third (32.6%) in the study arm saw improvement of ACR Pedi 100, compared with none for placebo. Both ACR Pedi 30 and ACR Pedi 50 responses with canakinumab remained significantly higher than with placebo at day 29.

Adverse events occurred in 55.8% of canakinumab and 39% of placebo patients. Dr. Ruperto said that the most frequently reported adverse events in the study group were upper respiratory problems and gastrointestinal complaints. No patients discontinued the trial because of side effects; however, 6 patients in the treatment arm and 37 in the placebo arm discontinued because for lack of therapeutic effect.

Two deaths occurred in the study group after the completion of the trial, during the long-term follow-up period, Dr. Ruperto told the congress. Both deaths were due to macrophage activation syndrome; one complicated with sepsis and the other with pulmonary hypertension.

The study was funded by Novartis. Dr. Ruperto reported having no financial conflicts of interest. Two of his coinvestigators are Novartis shareholders and one is a Novartis employee.

BRUGES, BELGIUM – A vaccine to prevent human papilloma virus infection, thereby limiting the risk for cervical cancer, has been found to be safe and effective in girls with juvenile idiopathic arthritis.

No changes in disease activity or differences in the girls’ ability to mount healthy antibody titers compared with healthy controls occurred, according to investigator Dr. Marloes Heijstek.

However, while the vaccine was also shown not to influence disease activity in girls with systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM), these groups did not mount antibody titers comparable to those seen in girls with juvenile idiopathic arthritis (JIA) and healthy controls, suggesting that the vaccine may offer girls with SLE or JDM less protection against acquiring cancer-causing types of human papilloma virus (HPV).

Even in JIA, the duration of protection remains to be determined and may be shorter than in healthy controls, investigators cautioned.

These findings come from a Dutch study of 58 patients with rheumatic disease and 51 healthy controls (Pediatr. Rheumatol. 2011;9[suppl. 1]:O41 ). Dr. Heijstek of the University Medical Center Utrecht (the Netherlands) collaborated on the ongoing study with principal investigator Dr. Nico M. Wulffraat, also of UMC Utrecht. Dr. Heijstek and Dr. Wulffraat also collaborated on an earlier safety study of measles, mumps, and rubella vaccine in JIA patients (Ann. Rheum. Dis. 2007;66:1384-7).

Dr. Heijstek’s HPV vaccine study enrolled girls with rheumatic disease who had been immunized with the bivalent HPV 16/18 vaccine Cervarix as part of a national program in the Netherlands that aims to vaccinate starting at age 12, before the girls are likely to be sexually active, in three doses at 0, 1, and 6 months, and followed up a year after vaccination. Study subjects and controls were between the ages of 12 and 18. Patients enrolled had JIA (n = 45), JDM (n = 5), or SLE (n = 8). Some of the subjects were taking medication to manage their disease at the time of vaccination. Specifically, 42% of JIA patients and 40% of JDM patients were taking methotrexate; 24% of JIA patients were taking anti-TNF medications.

The percentage of patients able to mount an immunological response to vaccination was shown to be the same in patients and controls, but geometric mean antibody titers for HPV16 were found to be lower in JIA (5,119 LU/mL), SLE (1,461 LU/mL), and JDM patients (3,233 LU/mL) compared with controls.

Geometric mean antibody titers for HPV18 were seen as similar in JIA patients and controls (2,764 LU/mL vs. 2,522 LU/mL). However, SLE and JDM patients showed markedly lower geometric mean antibody titers. Methotrexate use did not lower vaccine responses. One JDM patient did not seroconvert, Dr. Heijstek said. That patient was on both methotrexate and anti-TNF for disease control.

The group as a whole had fairly low, stable disease activity, Dr. Heijstek explained. However, this was not part of the enrollment criteria. When patients have high disease activity, they or their parents often fear a flare of disease due to vaccination or they have the general feeling that it is better to postpone the vaccination until the disease is stable, she told attendees at the congress.

The median juvenile arthritis disease activity score (JADAS)-27 did change considerably between visits (1.9-2.5), but JADAS-27 was significantly elevated at 7 months (P = .001) due to one outlier. SLE and JDM disease activity remained similar.

Days before Dr. Heijstek’s presentation, Dr. Wulffraat provided a background discussion on vaccinations in children with rheumatic diseases. Dr. Wulffraat and Dr. Heijstek’s investigation of MMR vaccine in JIA patients had shown the vaccine not to cause rheumatic disease flare ups or viral disease, and methotrexate use did not appear to affect antibody response.

What is remains unknown is how durable any vaccine protection is in children with rheumatic disease, according to Dr. Wulffraat. Longer study will be required to determine how long the titers persist, and whether they are protective in children on biological therapies such as anti-TNF inhibitors.

Neither Dr. Wulffraat nor Dr. Heijstek disclosed conflicts of interest related to their findings.

BRUGES, BELGIUM – A vaccine to prevent human papilloma virus infection, thereby limiting the risk for cervical cancer, has been found to be safe and effective in girls with juvenile idiopathic arthritis.

No changes in disease activity or differences in the girls’ ability to mount healthy antibody titers compared with healthy controls occurred, according to investigator Dr. Marloes Heijstek.

However, while the vaccine was also shown not to influence disease activity in girls with systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM), these groups did not mount antibody titers comparable to those seen in girls with juvenile idiopathic arthritis (JIA) and healthy controls, suggesting that the vaccine may offer girls with SLE or JDM less protection against acquiring cancer-causing types of human papilloma virus (HPV).

Even in JIA, the duration of protection remains to be determined and may be shorter than in healthy controls, investigators cautioned.

These findings come from a Dutch study of 58 patients with rheumatic disease and 51 healthy controls (Pediatr. Rheumatol. 2011;9[suppl. 1]:O41 ). Dr. Heijstek of the University Medical Center Utrecht (the Netherlands) collaborated on the ongoing study with principal investigator Dr. Nico M. Wulffraat, also of UMC Utrecht. Dr. Heijstek and Dr. Wulffraat also collaborated on an earlier safety study of measles, mumps, and rubella vaccine in JIA patients (Ann. Rheum. Dis. 2007;66:1384-7).

Dr. Heijstek’s HPV vaccine study enrolled girls with rheumatic disease who had been immunized with the bivalent HPV 16/18 vaccine Cervarix as part of a national program in the Netherlands that aims to vaccinate starting at age 12, before the girls are likely to be sexually active, in three doses at 0, 1, and 6 months, and followed up a year after vaccination. Study subjects and controls were between the ages of 12 and 18. Patients enrolled had JIA (n = 45), JDM (n = 5), or SLE (n = 8). Some of the subjects were taking medication to manage their disease at the time of vaccination. Specifically, 42% of JIA patients and 40% of JDM patients were taking methotrexate; 24% of JIA patients were taking anti-TNF medications.

The percentage of patients able to mount an immunological response to vaccination was shown to be the same in patients and controls, but geometric mean antibody titers for HPV16 were found to be lower in JIA (5,119 LU/mL), SLE (1,461 LU/mL), and JDM patients (3,233 LU/mL) compared with controls.

Geometric mean antibody titers for HPV18 were seen as similar in JIA patients and controls (2,764 LU/mL vs. 2,522 LU/mL). However, SLE and JDM patients showed markedly lower geometric mean antibody titers. Methotrexate use did not lower vaccine responses. One JDM patient did not seroconvert, Dr. Heijstek said. That patient was on both methotrexate and anti-TNF for disease control.

The group as a whole had fairly low, stable disease activity, Dr. Heijstek explained. However, this was not part of the enrollment criteria. When patients have high disease activity, they or their parents often fear a flare of disease due to vaccination or they have the general feeling that it is better to postpone the vaccination until the disease is stable, she told attendees at the congress.

The median juvenile arthritis disease activity score (JADAS)-27 did change considerably between visits (1.9-2.5), but JADAS-27 was significantly elevated at 7 months (P = .001) due to one outlier. SLE and JDM disease activity remained similar.

Days before Dr. Heijstek’s presentation, Dr. Wulffraat provided a background discussion on vaccinations in children with rheumatic diseases. Dr. Wulffraat and Dr. Heijstek’s investigation of MMR vaccine in JIA patients had shown the vaccine not to cause rheumatic disease flare ups or viral disease, and methotrexate use did not appear to affect antibody response.

What is remains unknown is how durable any vaccine protection is in children with rheumatic disease, according to Dr. Wulffraat. Longer study will be required to determine how long the titers persist, and whether they are protective in children on biological therapies such as anti-TNF inhibitors.

Neither Dr. Wulffraat nor Dr. Heijstek disclosed conflicts of interest related to their findings.

BRUGES, BELGIUM – A vaccine to prevent human papilloma virus infection, thereby limiting the risk for cervical cancer, has been found to be safe and effective in girls with juvenile idiopathic arthritis.

No changes in disease activity or differences in the girls’ ability to mount healthy antibody titers compared with healthy controls occurred, according to investigator Dr. Marloes Heijstek.

However, while the vaccine was also shown not to influence disease activity in girls with systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM), these groups did not mount antibody titers comparable to those seen in girls with juvenile idiopathic arthritis (JIA) and healthy controls, suggesting that the vaccine may offer girls with SLE or JDM less protection against acquiring cancer-causing types of human papilloma virus (HPV).

Even in JIA, the duration of protection remains to be determined and may be shorter than in healthy controls, investigators cautioned.

These findings come from a Dutch study of 58 patients with rheumatic disease and 51 healthy controls (Pediatr. Rheumatol. 2011;9[suppl. 1]:O41 ). Dr. Heijstek of the University Medical Center Utrecht (the Netherlands) collaborated on the ongoing study with principal investigator Dr. Nico M. Wulffraat, also of UMC Utrecht. Dr. Heijstek and Dr. Wulffraat also collaborated on an earlier safety study of measles, mumps, and rubella vaccine in JIA patients (Ann. Rheum. Dis. 2007;66:1384-7).

Dr. Heijstek’s HPV vaccine study enrolled girls with rheumatic disease who had been immunized with the bivalent HPV 16/18 vaccine Cervarix as part of a national program in the Netherlands that aims to vaccinate starting at age 12, before the girls are likely to be sexually active, in three doses at 0, 1, and 6 months, and followed up a year after vaccination. Study subjects and controls were between the ages of 12 and 18. Patients enrolled had JIA (n = 45), JDM (n = 5), or SLE (n = 8). Some of the subjects were taking medication to manage their disease at the time of vaccination. Specifically, 42% of JIA patients and 40% of JDM patients were taking methotrexate; 24% of JIA patients were taking anti-TNF medications.

The percentage of patients able to mount an immunological response to vaccination was shown to be the same in patients and controls, but geometric mean antibody titers for HPV16 were found to be lower in JIA (5,119 LU/mL), SLE (1,461 LU/mL), and JDM patients (3,233 LU/mL) compared with controls.

Geometric mean antibody titers for HPV18 were seen as similar in JIA patients and controls (2,764 LU/mL vs. 2,522 LU/mL). However, SLE and JDM patients showed markedly lower geometric mean antibody titers. Methotrexate use did not lower vaccine responses. One JDM patient did not seroconvert, Dr. Heijstek said. That patient was on both methotrexate and anti-TNF for disease control.

The group as a whole had fairly low, stable disease activity, Dr. Heijstek explained. However, this was not part of the enrollment criteria. When patients have high disease activity, they or their parents often fear a flare of disease due to vaccination or they have the general feeling that it is better to postpone the vaccination until the disease is stable, she told attendees at the congress.

The median juvenile arthritis disease activity score (JADAS)-27 did change considerably between visits (1.9-2.5), but JADAS-27 was significantly elevated at 7 months (P = .001) due to one outlier. SLE and JDM disease activity remained similar.

Days before Dr. Heijstek’s presentation, Dr. Wulffraat provided a background discussion on vaccinations in children with rheumatic diseases. Dr. Wulffraat and Dr. Heijstek’s investigation of MMR vaccine in JIA patients had shown the vaccine not to cause rheumatic disease flare ups or viral disease, and methotrexate use did not appear to affect antibody response.

What is remains unknown is how durable any vaccine protection is in children with rheumatic disease, according to Dr. Wulffraat. Longer study will be required to determine how long the titers persist, and whether they are protective in children on biological therapies such as anti-TNF inhibitors.

Neither Dr. Wulffraat nor Dr. Heijstek disclosed conflicts of interest related to their findings.

BRUGES, BELGIUM – A normal physical examination may be all that it takes to confirm inactive disease in a child with juvenile-onset systemic lupus erythematosus, according to new criteria.

Dr. Rina Mina of Cincinnati Children’s Medical Center said that she and her associated developed the criteria to determine clinical remission and clinically inactive disease in juvenile-onset systemic lupus erythematosus (JSLE), a complex disease. They used Delphi surveys of 210 pediatric rheumatologists. The senior author on the paper (Pediatr. Rheum. 2011;9[suppl. 1]:O17) was Dr. Hermine I. Brunner, also of Cincinnati Children’s.

The surveys achieved consensus on four descriptors: clinically inactive disease – which is defined without regard to medications used – and clinical remission on medication (including steroids and immunosuppressants), clinical remission on preventive medication, and clinical remission off medication. Consensus was lowest – only 86% – on what defined clinical remission off medication, while consensus for the other categories was between 94% and 96%.

According to the criteria, a JSLE patient with either inactive disease or clinical remission "should have no signs of disease activity on physical examination," Dr. Mina explained, adding that physical examination may ultimately prove to be enough to define inactivity. A patient with inactive disease or remission can have at most two nonlimiting symptoms such as headaches or fatigue.

Some select laboratory abnormalities can persist under either definition, she said, including a persistently positive antinuclear antibody test result, proteinuria from lupus-related kidney damage, or low levels of C4, for example. Members of the conference challenged Dr. Mina on the proteinuria, suggesting that it was dangerous to accept a patient with proteinuria as in remission; however, Dr. Mina argued that proteinuria was defined as a stable proteinuria as the result of damage, not a changing condition.

Use of preventive medication other than a steroid or immunosuppressant was defined as any medication to thwart disease progression or the development of disease-related damage. This category includes angiotensin-converting enzyme inhibitors, vitamin D, omega-3 acids, statins, and/or bisphosphonates. There was no consensus among the surveyed pediatric rheumatologists on whether nonsteroidal anti-inflammatory agents used daily could be considered preventive, Dr. Mina said at the meeting. Also lacking was any consensus on whether antimalarial drugs were to be considered preventive.

One of the key areas of consensus achieved by the surveys was that "inactive disease and clinical remission are distinct and should be differentiated from cure as well as from minimal disease activity," Dr. Mina said. What was "crucial" in differentiating between inactive disease and clinical remission was the time frame. Clinical remission on medication or with preventive medication is defined as requiring 6 continuous months. The criteria, she noted, are similar to current American College of Rheumatology/European League Against Rheumatism criteria for defining clinically inactive disease and remission in juvenile idiopathic arthritis.

Remission off medication was defined as disease inactivity for at least 12 continuous months. Patients could be considered "off medication" if they were not being treated with steroids, immunosuppressants, or preventive medications; however a patient could be treated with insulin to treat steroid-induced diabetes, for example, and still be included in this definition.

Dr. Mina reported that her group had validated the consensus definitions with a cohort of JSLE patients and had found the accuracy to be "outstanding" compared with scores from widely used disease indexes for JSLE. The new criteria surpassed both the SLE Disease Activity Index and the British Isles Lupus Assessment Group score in establishing inactive disease and remission. "All core parameters support the content validity of the consensus process," she said.

Dr. Mina said she had no relevant financial disclosures.

BRUGES, BELGIUM – A normal physical examination may be all that it takes to confirm inactive disease in a child with juvenile-onset systemic lupus erythematosus, according to new criteria.

Dr. Rina Mina of Cincinnati Children’s Medical Center said that she and her associated developed the criteria to determine clinical remission and clinically inactive disease in juvenile-onset systemic lupus erythematosus (JSLE), a complex disease. They used Delphi surveys of 210 pediatric rheumatologists. The senior author on the paper (Pediatr. Rheum. 2011;9[suppl. 1]:O17) was Dr. Hermine I. Brunner, also of Cincinnati Children’s.

The surveys achieved consensus on four descriptors: clinically inactive disease – which is defined without regard to medications used – and clinical remission on medication (including steroids and immunosuppressants), clinical remission on preventive medication, and clinical remission off medication. Consensus was lowest – only 86% – on what defined clinical remission off medication, while consensus for the other categories was between 94% and 96%.

According to the criteria, a JSLE patient with either inactive disease or clinical remission "should have no signs of disease activity on physical examination," Dr. Mina explained, adding that physical examination may ultimately prove to be enough to define inactivity. A patient with inactive disease or remission can have at most two nonlimiting symptoms such as headaches or fatigue.

Some select laboratory abnormalities can persist under either definition, she said, including a persistently positive antinuclear antibody test result, proteinuria from lupus-related kidney damage, or low levels of C4, for example. Members of the conference challenged Dr. Mina on the proteinuria, suggesting that it was dangerous to accept a patient with proteinuria as in remission; however, Dr. Mina argued that proteinuria was defined as a stable proteinuria as the result of damage, not a changing condition.

Use of preventive medication other than a steroid or immunosuppressant was defined as any medication to thwart disease progression or the development of disease-related damage. This category includes angiotensin-converting enzyme inhibitors, vitamin D, omega-3 acids, statins, and/or bisphosphonates. There was no consensus among the surveyed pediatric rheumatologists on whether nonsteroidal anti-inflammatory agents used daily could be considered preventive, Dr. Mina said at the meeting. Also lacking was any consensus on whether antimalarial drugs were to be considered preventive.

One of the key areas of consensus achieved by the surveys was that "inactive disease and clinical remission are distinct and should be differentiated from cure as well as from minimal disease activity," Dr. Mina said. What was "crucial" in differentiating between inactive disease and clinical remission was the time frame. Clinical remission on medication or with preventive medication is defined as requiring 6 continuous months. The criteria, she noted, are similar to current American College of Rheumatology/European League Against Rheumatism criteria for defining clinically inactive disease and remission in juvenile idiopathic arthritis.

Remission off medication was defined as disease inactivity for at least 12 continuous months. Patients could be considered "off medication" if they were not being treated with steroids, immunosuppressants, or preventive medications; however a patient could be treated with insulin to treat steroid-induced diabetes, for example, and still be included in this definition.

Dr. Mina reported that her group had validated the consensus definitions with a cohort of JSLE patients and had found the accuracy to be "outstanding" compared with scores from widely used disease indexes for JSLE. The new criteria surpassed both the SLE Disease Activity Index and the British Isles Lupus Assessment Group score in establishing inactive disease and remission. "All core parameters support the content validity of the consensus process," she said.

Dr. Mina said she had no relevant financial disclosures.

BRUGES, BELGIUM – A normal physical examination may be all that it takes to confirm inactive disease in a child with juvenile-onset systemic lupus erythematosus, according to new criteria.

Dr. Rina Mina of Cincinnati Children’s Medical Center said that she and her associated developed the criteria to determine clinical remission and clinically inactive disease in juvenile-onset systemic lupus erythematosus (JSLE), a complex disease. They used Delphi surveys of 210 pediatric rheumatologists. The senior author on the paper (Pediatr. Rheum. 2011;9[suppl. 1]:O17) was Dr. Hermine I. Brunner, also of Cincinnati Children’s.

The surveys achieved consensus on four descriptors: clinically inactive disease – which is defined without regard to medications used – and clinical remission on medication (including steroids and immunosuppressants), clinical remission on preventive medication, and clinical remission off medication. Consensus was lowest – only 86% – on what defined clinical remission off medication, while consensus for the other categories was between 94% and 96%.

According to the criteria, a JSLE patient with either inactive disease or clinical remission "should have no signs of disease activity on physical examination," Dr. Mina explained, adding that physical examination may ultimately prove to be enough to define inactivity. A patient with inactive disease or remission can have at most two nonlimiting symptoms such as headaches or fatigue.

Some select laboratory abnormalities can persist under either definition, she said, including a persistently positive antinuclear antibody test result, proteinuria from lupus-related kidney damage, or low levels of C4, for example. Members of the conference challenged Dr. Mina on the proteinuria, suggesting that it was dangerous to accept a patient with proteinuria as in remission; however, Dr. Mina argued that proteinuria was defined as a stable proteinuria as the result of damage, not a changing condition.

Use of preventive medication other than a steroid or immunosuppressant was defined as any medication to thwart disease progression or the development of disease-related damage. This category includes angiotensin-converting enzyme inhibitors, vitamin D, omega-3 acids, statins, and/or bisphosphonates. There was no consensus among the surveyed pediatric rheumatologists on whether nonsteroidal anti-inflammatory agents used daily could be considered preventive, Dr. Mina said at the meeting. Also lacking was any consensus on whether antimalarial drugs were to be considered preventive.

One of the key areas of consensus achieved by the surveys was that "inactive disease and clinical remission are distinct and should be differentiated from cure as well as from minimal disease activity," Dr. Mina said. What was "crucial" in differentiating between inactive disease and clinical remission was the time frame. Clinical remission on medication or with preventive medication is defined as requiring 6 continuous months. The criteria, she noted, are similar to current American College of Rheumatology/European League Against Rheumatism criteria for defining clinically inactive disease and remission in juvenile idiopathic arthritis.

Remission off medication was defined as disease inactivity for at least 12 continuous months. Patients could be considered "off medication" if they were not being treated with steroids, immunosuppressants, or preventive medications; however a patient could be treated with insulin to treat steroid-induced diabetes, for example, and still be included in this definition.

Dr. Mina reported that her group had validated the consensus definitions with a cohort of JSLE patients and had found the accuracy to be "outstanding" compared with scores from widely used disease indexes for JSLE. The new criteria surpassed both the SLE Disease Activity Index and the British Isles Lupus Assessment Group score in establishing inactive disease and remission. "All core parameters support the content validity of the consensus process," she said.

Dr. Mina said she had no relevant financial disclosures.

People exposed to the protozoan Giardia lamblia are at increased risk of having irritable bowel syndrome and chronic fatigue years after their gastrointestinal infections have been treated, a team of Norwegian researchers has found.

Although other types of acute gastrointestinal infections have been associated with ongoing disorders including both fatigue and irritable bowel syndrome (IBS), the finding challenges the assumption that acute giardiasis, once treated, does not cause long-term complications.

Among a cohort of people who became ill during a 2004 outbreak of giardiasis in the Norwegian city of Bergen, nearly half reported having chronic fatigue, IBS, or both 3 years later. Prescription data from the time of the outbreak, which was traced to a contaminated reservoir, suggested that the vast majority of those affected had been treated with metronidazole. Giardiasis is not endemic in Norway.

For their research, published online Sept. 12 in the journal Gut (doi:10.1136/gutjnl-2011-300220), Dr. Knut-Arne Wensaas of the University of Bergen and Uni Health in Bergen, and his colleagues, collected data using validated questionnaires from 817 patients who had laboratory-confirmed G. lamblia infection in 2004, and 1,128 age- and sex-matched controls (mean age, 36; about 66% female) not infected in that outbreak.

Of the exposed cases, 46.1% reported IBS at 3 years, compared with 14% in the control group, for a relative risk of 3.4 (95% CI, 2.9-3.8) after adjustment for potential confounding factors. The same percentage – 46.1% – of the exposed group reported chronic fatigue, compared with 12% of controls (adjusted RR, 4.0; 95% CI, 3.5-4.5).

Despite the study’s observational design, the association between prior infection and the two disorders was seen as so strong, Dr. Wensaas said in an interview, that "it suggests a causal relationship" that warrants further investigation.

In the exposed group, 62.6% of those with IBS had chronic fatigue, as did 30.6% of those without IBS, compared with 32% and 9% for controls. That the two disorders, IBS and chronic fatigue, were found to occur together more frequently among those with previous giardiasis suggested that there could be commonalities in the pathogenesis of giardiasis, IBS, and chronic fatigue. One possible link, the researchers hypothesized, is an immune response involving T lymphocytes.

While a majority of cases were women, sex was not seen as an effect modifier for IBS or for chronic fatigue. The prevalence of IBS was higher among women than men in both the exposed group (48.9% vs. 40.8%) and the control group (15.9% vs. 10.4%).

The authors noted that their definition of IBS was based on the Rome III criteria: "recurrent abdominal pain or discomfort at least 3 days a month in the past 3 months and associated with at least two of three criteria related to defecation (onset associated with a change in frequency or form of stool, or improvement with defecation)."

Dr. Wensaas said that the idea for the study came in part from his and his colleagues’ clinical observations treating patients in Bergen in the years following the outbreak. A previous study, by another research team, had also looked at the same outbreak and outcomes at a 2-year end point (Trans. R. Soc. Trop. Med. Hyg. 2009;103:530-2).

Dr. Wensaas, a general practitioner, said that not only had a large number of patients presented with fatigue and/or IBS following their giardiasis infections, but that they continued to have these symptoms well past the 3-year end point of the study, suggesting that the effects could continue even longer. Dr. Wensaas pointed to one Canadian study that found an elevated risk for IBS at 8 years after acute bacterial gastroenteritis (Gut 2010;59:605-11).

The investigators acknowledged as a weakness of their study the potential for selection bias inherent in its observational design and use of questionnaires. "There is a possibility that those having had acute giardiasis will be more aware of symptoms and more likely to find them abnormal than the controls, and thus report more complaints," they wrote, noting also that the city of Bergen had originally compensated those affected by the outbreak, potentially encouraging exaggerated complaints.

An additional weakness reported was that chronic giardiasis could not be ruled out among respondents.

Dr. Wensaas and his colleagues received funding for their study from the city of Bergen and the Norwegian Medical Association’s Funds for Research in General Practice; none of the study authors said they had relevant financial disclosures.

People exposed to the protozoan Giardia lamblia are at increased risk of having irritable bowel syndrome and chronic fatigue years after their gastrointestinal infections have been treated, a team of Norwegian researchers has found.

Although other types of acute gastrointestinal infections have been associated with ongoing disorders including both fatigue and irritable bowel syndrome (IBS), the finding challenges the assumption that acute giardiasis, once treated, does not cause long-term complications.

Among a cohort of people who became ill during a 2004 outbreak of giardiasis in the Norwegian city of Bergen, nearly half reported having chronic fatigue, IBS, or both 3 years later. Prescription data from the time of the outbreak, which was traced to a contaminated reservoir, suggested that the vast majority of those affected had been treated with metronidazole. Giardiasis is not endemic in Norway.

For their research, published online Sept. 12 in the journal Gut (doi:10.1136/gutjnl-2011-300220), Dr. Knut-Arne Wensaas of the University of Bergen and Uni Health in Bergen, and his colleagues, collected data using validated questionnaires from 817 patients who had laboratory-confirmed G. lamblia infection in 2004, and 1,128 age- and sex-matched controls (mean age, 36; about 66% female) not infected in that outbreak.

Of the exposed cases, 46.1% reported IBS at 3 years, compared with 14% in the control group, for a relative risk of 3.4 (95% CI, 2.9-3.8) after adjustment for potential confounding factors. The same percentage – 46.1% – of the exposed group reported chronic fatigue, compared with 12% of controls (adjusted RR, 4.0; 95% CI, 3.5-4.5).

Despite the study’s observational design, the association between prior infection and the two disorders was seen as so strong, Dr. Wensaas said in an interview, that "it suggests a causal relationship" that warrants further investigation.

In the exposed group, 62.6% of those with IBS had chronic fatigue, as did 30.6% of those without IBS, compared with 32% and 9% for controls. That the two disorders, IBS and chronic fatigue, were found to occur together more frequently among those with previous giardiasis suggested that there could be commonalities in the pathogenesis of giardiasis, IBS, and chronic fatigue. One possible link, the researchers hypothesized, is an immune response involving T lymphocytes.

While a majority of cases were women, sex was not seen as an effect modifier for IBS or for chronic fatigue. The prevalence of IBS was higher among women than men in both the exposed group (48.9% vs. 40.8%) and the control group (15.9% vs. 10.4%).

The authors noted that their definition of IBS was based on the Rome III criteria: "recurrent abdominal pain or discomfort at least 3 days a month in the past 3 months and associated with at least two of three criteria related to defecation (onset associated with a change in frequency or form of stool, or improvement with defecation)."

Dr. Wensaas said that the idea for the study came in part from his and his colleagues’ clinical observations treating patients in Bergen in the years following the outbreak. A previous study, by another research team, had also looked at the same outbreak and outcomes at a 2-year end point (Trans. R. Soc. Trop. Med. Hyg. 2009;103:530-2).

Dr. Wensaas, a general practitioner, said that not only had a large number of patients presented with fatigue and/or IBS following their giardiasis infections, but that they continued to have these symptoms well past the 3-year end point of the study, suggesting that the effects could continue even longer. Dr. Wensaas pointed to one Canadian study that found an elevated risk for IBS at 8 years after acute bacterial gastroenteritis (Gut 2010;59:605-11).

The investigators acknowledged as a weakness of their study the potential for selection bias inherent in its observational design and use of questionnaires. "There is a possibility that those having had acute giardiasis will be more aware of symptoms and more likely to find them abnormal than the controls, and thus report more complaints," they wrote, noting also that the city of Bergen had originally compensated those affected by the outbreak, potentially encouraging exaggerated complaints.

An additional weakness reported was that chronic giardiasis could not be ruled out among respondents.

Dr. Wensaas and his colleagues received funding for their study from the city of Bergen and the Norwegian Medical Association’s Funds for Research in General Practice; none of the study authors said they had relevant financial disclosures.

People exposed to the protozoan Giardia lamblia are at increased risk of having irritable bowel syndrome and chronic fatigue years after their gastrointestinal infections have been treated, a team of Norwegian researchers has found.

Although other types of acute gastrointestinal infections have been associated with ongoing disorders including both fatigue and irritable bowel syndrome (IBS), the finding challenges the assumption that acute giardiasis, once treated, does not cause long-term complications.

Among a cohort of people who became ill during a 2004 outbreak of giardiasis in the Norwegian city of Bergen, nearly half reported having chronic fatigue, IBS, or both 3 years later. Prescription data from the time of the outbreak, which was traced to a contaminated reservoir, suggested that the vast majority of those affected had been treated with metronidazole. Giardiasis is not endemic in Norway.

For their research, published online Sept. 12 in the journal Gut (doi:10.1136/gutjnl-2011-300220), Dr. Knut-Arne Wensaas of the University of Bergen and Uni Health in Bergen, and his colleagues, collected data using validated questionnaires from 817 patients who had laboratory-confirmed G. lamblia infection in 2004, and 1,128 age- and sex-matched controls (mean age, 36; about 66% female) not infected in that outbreak.

Of the exposed cases, 46.1% reported IBS at 3 years, compared with 14% in the control group, for a relative risk of 3.4 (95% CI, 2.9-3.8) after adjustment for potential confounding factors. The same percentage – 46.1% – of the exposed group reported chronic fatigue, compared with 12% of controls (adjusted RR, 4.0; 95% CI, 3.5-4.5).

Despite the study’s observational design, the association between prior infection and the two disorders was seen as so strong, Dr. Wensaas said in an interview, that "it suggests a causal relationship" that warrants further investigation.

In the exposed group, 62.6% of those with IBS had chronic fatigue, as did 30.6% of those without IBS, compared with 32% and 9% for controls. That the two disorders, IBS and chronic fatigue, were found to occur together more frequently among those with previous giardiasis suggested that there could be commonalities in the pathogenesis of giardiasis, IBS, and chronic fatigue. One possible link, the researchers hypothesized, is an immune response involving T lymphocytes.

While a majority of cases were women, sex was not seen as an effect modifier for IBS or for chronic fatigue. The prevalence of IBS was higher among women than men in both the exposed group (48.9% vs. 40.8%) and the control group (15.9% vs. 10.4%).

The authors noted that their definition of IBS was based on the Rome III criteria: "recurrent abdominal pain or discomfort at least 3 days a month in the past 3 months and associated with at least two of three criteria related to defecation (onset associated with a change in frequency or form of stool, or improvement with defecation)."

Dr. Wensaas said that the idea for the study came in part from his and his colleagues’ clinical observations treating patients in Bergen in the years following the outbreak. A previous study, by another research team, had also looked at the same outbreak and outcomes at a 2-year end point (Trans. R. Soc. Trop. Med. Hyg. 2009;103:530-2).

Dr. Wensaas, a general practitioner, said that not only had a large number of patients presented with fatigue and/or IBS following their giardiasis infections, but that they continued to have these symptoms well past the 3-year end point of the study, suggesting that the effects could continue even longer. Dr. Wensaas pointed to one Canadian study that found an elevated risk for IBS at 8 years after acute bacterial gastroenteritis (Gut 2010;59:605-11).

The investigators acknowledged as a weakness of their study the potential for selection bias inherent in its observational design and use of questionnaires. "There is a possibility that those having had acute giardiasis will be more aware of symptoms and more likely to find them abnormal than the controls, and thus report more complaints," they wrote, noting also that the city of Bergen had originally compensated those affected by the outbreak, potentially encouraging exaggerated complaints.

An additional weakness reported was that chronic giardiasis could not be ruled out among respondents.

Dr. Wensaas and his colleagues received funding for their study from the city of Bergen and the Norwegian Medical Association’s Funds for Research in General Practice; none of the study authors said they had relevant financial disclosures.

Two doses of vaccine – and possibly a single dose – may offer as much protection against infection with cancer-causing forms of human papillomavirus as the standard three-dose series, according to results from a large study in Costa Rica published online Sept. 9 in the Journal of the National Cancer Institute .

The finding, the first clinical evidence suggesting that two doses or even one dose may be as effective as three, is a very hopeful one for women in resource-poor countries and may have important implications for women in relatively rich countries, such has the United States, where vaccine uptake has proven difficult to achieve, and where fewer than a third of girls receiving HPV vaccine are estimated to get a full three doses (MMWR 2011;60:1117-23).

Cervical cancer affects an estimated 530,000 women and causes 275,000 deaths annually, according to the International Agency for Research on Cancer, with more than 85% of the burden in less-developed regions of Africa, Asia, and Latin America. Certain types of HPV are the major cause of cervical cancer.

In the Costa Rican study, 7,466 women aged 18-25 years, most of them sexually active, were randomized to receive three doses of the HPV16/18 vaccine Cervarix (GlaxoSmithKline), or a hepatitis A control vaccine, as part of an ongoing phase III randomized controlled trial (J. Natl. Cancer Inst. 2011 [doi: 10.1093/jnci/djr319]).

All women in the study were supposed to receive three doses of either HPV vaccine or control; however, some of the women received fewer doses, largely because of pregnancy and referral to colposcopy.

The fact that many women did not complete the series allowed researchers, led by epidemiologist Aimée R. Kreimer, Ph.D., of the U.S. National Cancer Institute, to conduct an analysis comparing the efficacy of fewer than three doses of this HPV vaccine with the standard regimen in preventing newly detected persistent HPV16 and HPV18 infections.

Persistent infections were defined as evident in visits 10 or more months apart; all women in the study were seen annually during 4 years of follow-up.

After excluding women who had no follow-up or who were HPV16 and HPV18 positive at enrollment, 5,967 women who received three doses of HPV or hepatitis vaccine (2,957 received HPV vaccine or 50%), 802 who received two doses (422 HPV or 53%), and 384 who received one dose (196 HPV or 51%) were entered into analysis, for a total of 7,153.

Vaccine efficacy was 80.9% for three doses of HPV vaccine (25 and 133 1-year persistent HPV16/18 HPV infections in the HPV and control arms, respectively), 84.1% for two doses (3 and 17 infections), and 100% for one dose (0 and 10 infections). Persistent HPV16 or HPV18 infections were found to be unrelated to dosage of the control vaccine.

Dr. Kreimer and colleagues noted that although the study used data from a large randomized trial, their analysis was not randomized. However, they wrote, "the attack rates of new infections were essentially equal among women who received one, two, and three doses of the control vaccine. Equal attack rates in the control arm suggested that risks of infection were the same regardless of number of doses received. Furthermore, pregnancy, the most common reason that women received a reduced number of doses, was unrelated to vaccine assignment," and therefore unlikely to bias the findings.

They also acknowledged that while the benefit appeared to be the same for two and three doses, the duration of that benefit beyond 4 years was uncertain and would have to be established through further research.

Additionally, Dr. Kreimer and colleagues cautioned that their findings from the bivalent vaccine trial could not be extrapolated to the widely used quadrivalent HPV vaccine Gardasil, which is also administered in a three-dose series. Nor could they be considered relevant to populations with a greater incidence of comorbidities, particularly diseases affecting the immune system.

In an editorial comment accompanying Dr. Kreimer and colleagues’ study (J. Natl. Cancer Inst. 2011 [doi: 10.1093/jnci/djr354]), epidemiologist Cosette Marie Wheeler, Ph.D., of the University of New Mexico Health Sciences Center in Albuquerque, praised the study as having important public health implications.

If two doses of vaccine are indeed as effective as three, she wrote, this could be "an important step on the road to more effective and sustainable cervical cancer prevention programs," as more women could be vaccinated for the same cost.

However, Dr. Wheeler also cautioned that longer-term evidence was needed to determine whether clinically meaningful protection was achievable with two doses, noting also that there was biological evidence to suggest that three doses would provide greater cross-protection against heterologous HPV types. The finding of protection with a single dose, Dr. Wheeler wrote, was "unexpected" and should be viewed with caution.

Finally, Dr. Wheeler wrote, "it is important to consider that the findings reported by Kreimer et al. are limited to end points of persistent HPV infection. It remains unknown whether these observations will translate, over the long term, to the prevention of disease end points such as cervical intraepithelial neoplasia grade 3 and higher (CIN3+) and whether HPV vaccine protection, with fewer than three doses, will be sustainable even for homologous HPV vaccine types 16 and 18."

The study was sponsored by the National Cancer Institute (NCI) and the U.S. National Institutes of Health Office of Research on Women’s Health, with vaccine donated by the manufacturer. The manufacturer also provided financial support related to regulatory submission. Two coauthors on Dr. Kreimer and colleagues’ study, John T. Schiller and Douglas R. Lowy, disclosed being named inventors on U.S. government–owned HPV vaccine patents licensed to GlaxoSmithKline and Merck, and for which the NCI receives licensing fees. No other financial disclosures were reported. Dr. Wheeler did not report any relevant financial disclosures.

Two doses of vaccine – and possibly a single dose – may offer as much protection against infection with cancer-causing forms of human papillomavirus as the standard three-dose series, according to results from a large study in Costa Rica published online Sept. 9 in the Journal of the National Cancer Institute .

The finding, the first clinical evidence suggesting that two doses or even one dose may be as effective as three, is a very hopeful one for women in resource-poor countries and may have important implications for women in relatively rich countries, such has the United States, where vaccine uptake has proven difficult to achieve, and where fewer than a third of girls receiving HPV vaccine are estimated to get a full three doses (MMWR 2011;60:1117-23).

Cervical cancer affects an estimated 530,000 women and causes 275,000 deaths annually, according to the International Agency for Research on Cancer, with more than 85% of the burden in less-developed regions of Africa, Asia, and Latin America. Certain types of HPV are the major cause of cervical cancer.

In the Costa Rican study, 7,466 women aged 18-25 years, most of them sexually active, were randomized to receive three doses of the HPV16/18 vaccine Cervarix (GlaxoSmithKline), or a hepatitis A control vaccine, as part of an ongoing phase III randomized controlled trial (J. Natl. Cancer Inst. 2011 [doi: 10.1093/jnci/djr319]).

All women in the study were supposed to receive three doses of either HPV vaccine or control; however, some of the women received fewer doses, largely because of pregnancy and referral to colposcopy.

The fact that many women did not complete the series allowed researchers, led by epidemiologist Aimée R. Kreimer, Ph.D., of the U.S. National Cancer Institute, to conduct an analysis comparing the efficacy of fewer than three doses of this HPV vaccine with the standard regimen in preventing newly detected persistent HPV16 and HPV18 infections.

Persistent infections were defined as evident in visits 10 or more months apart; all women in the study were seen annually during 4 years of follow-up.

After excluding women who had no follow-up or who were HPV16 and HPV18 positive at enrollment, 5,967 women who received three doses of HPV or hepatitis vaccine (2,957 received HPV vaccine or 50%), 802 who received two doses (422 HPV or 53%), and 384 who received one dose (196 HPV or 51%) were entered into analysis, for a total of 7,153.

Vaccine efficacy was 80.9% for three doses of HPV vaccine (25 and 133 1-year persistent HPV16/18 HPV infections in the HPV and control arms, respectively), 84.1% for two doses (3 and 17 infections), and 100% for one dose (0 and 10 infections). Persistent HPV16 or HPV18 infections were found to be unrelated to dosage of the control vaccine.

Dr. Kreimer and colleagues noted that although the study used data from a large randomized trial, their analysis was not randomized. However, they wrote, "the attack rates of new infections were essentially equal among women who received one, two, and three doses of the control vaccine. Equal attack rates in the control arm suggested that risks of infection were the same regardless of number of doses received. Furthermore, pregnancy, the most common reason that women received a reduced number of doses, was unrelated to vaccine assignment," and therefore unlikely to bias the findings.

They also acknowledged that while the benefit appeared to be the same for two and three doses, the duration of that benefit beyond 4 years was uncertain and would have to be established through further research.

Additionally, Dr. Kreimer and colleagues cautioned that their findings from the bivalent vaccine trial could not be extrapolated to the widely used quadrivalent HPV vaccine Gardasil, which is also administered in a three-dose series. Nor could they be considered relevant to populations with a greater incidence of comorbidities, particularly diseases affecting the immune system.

In an editorial comment accompanying Dr. Kreimer and colleagues’ study (J. Natl. Cancer Inst. 2011 [doi: 10.1093/jnci/djr354]), epidemiologist Cosette Marie Wheeler, Ph.D., of the University of New Mexico Health Sciences Center in Albuquerque, praised the study as having important public health implications.

If two doses of vaccine are indeed as effective as three, she wrote, this could be "an important step on the road to more effective and sustainable cervical cancer prevention programs," as more women could be vaccinated for the same cost.

However, Dr. Wheeler also cautioned that longer-term evidence was needed to determine whether clinically meaningful protection was achievable with two doses, noting also that there was biological evidence to suggest that three doses would provide greater cross-protection against heterologous HPV types. The finding of protection with a single dose, Dr. Wheeler wrote, was "unexpected" and should be viewed with caution.

Finally, Dr. Wheeler wrote, "it is important to consider that the findings reported by Kreimer et al. are limited to end points of persistent HPV infection. It remains unknown whether these observations will translate, over the long term, to the prevention of disease end points such as cervical intraepithelial neoplasia grade 3 and higher (CIN3+) and whether HPV vaccine protection, with fewer than three doses, will be sustainable even for homologous HPV vaccine types 16 and 18."

The study was sponsored by the National Cancer Institute (NCI) and the U.S. National Institutes of Health Office of Research on Women’s Health, with vaccine donated by the manufacturer. The manufacturer also provided financial support related to regulatory submission. Two coauthors on Dr. Kreimer and colleagues’ study, John T. Schiller and Douglas R. Lowy, disclosed being named inventors on U.S. government–owned HPV vaccine patents licensed to GlaxoSmithKline and Merck, and for which the NCI receives licensing fees. No other financial disclosures were reported. Dr. Wheeler did not report any relevant financial disclosures.

Two doses of vaccine – and possibly a single dose – may offer as much protection against infection with cancer-causing forms of human papillomavirus as the standard three-dose series, according to results from a large study in Costa Rica published online Sept. 9 in the Journal of the National Cancer Institute .

The finding, the first clinical evidence suggesting that two doses or even one dose may be as effective as three, is a very hopeful one for women in resource-poor countries and may have important implications for women in relatively rich countries, such has the United States, where vaccine uptake has proven difficult to achieve, and where fewer than a third of girls receiving HPV vaccine are estimated to get a full three doses (MMWR 2011;60:1117-23).

Cervical cancer affects an estimated 530,000 women and causes 275,000 deaths annually, according to the International Agency for Research on Cancer, with more than 85% of the burden in less-developed regions of Africa, Asia, and Latin America. Certain types of HPV are the major cause of cervical cancer.

In the Costa Rican study, 7,466 women aged 18-25 years, most of them sexually active, were randomized to receive three doses of the HPV16/18 vaccine Cervarix (GlaxoSmithKline), or a hepatitis A control vaccine, as part of an ongoing phase III randomized controlled trial (J. Natl. Cancer Inst. 2011 [doi: 10.1093/jnci/djr319]).

All women in the study were supposed to receive three doses of either HPV vaccine or control; however, some of the women received fewer doses, largely because of pregnancy and referral to colposcopy.

The fact that many women did not complete the series allowed researchers, led by epidemiologist Aimée R. Kreimer, Ph.D., of the U.S. National Cancer Institute, to conduct an analysis comparing the efficacy of fewer than three doses of this HPV vaccine with the standard regimen in preventing newly detected persistent HPV16 and HPV18 infections.

Persistent infections were defined as evident in visits 10 or more months apart; all women in the study were seen annually during 4 years of follow-up.

After excluding women who had no follow-up or who were HPV16 and HPV18 positive at enrollment, 5,967 women who received three doses of HPV or hepatitis vaccine (2,957 received HPV vaccine or 50%), 802 who received two doses (422 HPV or 53%), and 384 who received one dose (196 HPV or 51%) were entered into analysis, for a total of 7,153.

Vaccine efficacy was 80.9% for three doses of HPV vaccine (25 and 133 1-year persistent HPV16/18 HPV infections in the HPV and control arms, respectively), 84.1% for two doses (3 and 17 infections), and 100% for one dose (0 and 10 infections). Persistent HPV16 or HPV18 infections were found to be unrelated to dosage of the control vaccine.

Dr. Kreimer and colleagues noted that although the study used data from a large randomized trial, their analysis was not randomized. However, they wrote, "the attack rates of new infections were essentially equal among women who received one, two, and three doses of the control vaccine. Equal attack rates in the control arm suggested that risks of infection were the same regardless of number of doses received. Furthermore, pregnancy, the most common reason that women received a reduced number of doses, was unrelated to vaccine assignment," and therefore unlikely to bias the findings.

They also acknowledged that while the benefit appeared to be the same for two and three doses, the duration of that benefit beyond 4 years was uncertain and would have to be established through further research.

Additionally, Dr. Kreimer and colleagues cautioned that their findings from the bivalent vaccine trial could not be extrapolated to the widely used quadrivalent HPV vaccine Gardasil, which is also administered in a three-dose series. Nor could they be considered relevant to populations with a greater incidence of comorbidities, particularly diseases affecting the immune system.

In an editorial comment accompanying Dr. Kreimer and colleagues’ study (J. Natl. Cancer Inst. 2011 [doi: 10.1093/jnci/djr354]), epidemiologist Cosette Marie Wheeler, Ph.D., of the University of New Mexico Health Sciences Center in Albuquerque, praised the study as having important public health implications.

If two doses of vaccine are indeed as effective as three, she wrote, this could be "an important step on the road to more effective and sustainable cervical cancer prevention programs," as more women could be vaccinated for the same cost.

However, Dr. Wheeler also cautioned that longer-term evidence was needed to determine whether clinically meaningful protection was achievable with two doses, noting also that there was biological evidence to suggest that three doses would provide greater cross-protection against heterologous HPV types. The finding of protection with a single dose, Dr. Wheeler wrote, was "unexpected" and should be viewed with caution.

Finally, Dr. Wheeler wrote, "it is important to consider that the findings reported by Kreimer et al. are limited to end points of persistent HPV infection. It remains unknown whether these observations will translate, over the long term, to the prevention of disease end points such as cervical intraepithelial neoplasia grade 3 and higher (CIN3+) and whether HPV vaccine protection, with fewer than three doses, will be sustainable even for homologous HPV vaccine types 16 and 18."

The study was sponsored by the National Cancer Institute (NCI) and the U.S. National Institutes of Health Office of Research on Women’s Health, with vaccine donated by the manufacturer. The manufacturer also provided financial support related to regulatory submission. Two coauthors on Dr. Kreimer and colleagues’ study, John T. Schiller and Douglas R. Lowy, disclosed being named inventors on U.S. government–owned HPV vaccine patents licensed to GlaxoSmithKline and Merck, and for which the NCI receives licensing fees. No other financial disclosures were reported. Dr. Wheeler did not report any relevant financial disclosures.

Suicide bombs have now killed 200 coalition soldiers and more than 12,000 civilians in Iraq, say the authors of a new report focusing on the high number of civilian deaths – particularly child deaths – and injuries from such attacks.

The report, published online Sept. 1 in the Lancet, shows that while U.S.-led coalition forces have adopted successful strategies for avoiding suicide bomb attacks and for treating its own members exposed to them, the noncombatant, civilian population of Iraq has borne a remarkably heavy burden (Lancet 2011;378: 906-14).

Some 30,644 noncombatant civilians were injured and 12,284 killed in more than 1,000 suicide bombings between March 2003, when the Iraq war began, through the end of December 2010 – a ratio of 2.5 injured for every 1 killed, investigators found. Some 19% of all Iraqi civilian casualties and 11% of Iraqi civilian deaths in this period were caused by suicide bombs, with car bombs proving more lethal than those detonated by bombers on foot.

Courtesy U.S. Army/Pfc. Charles Probst

"I think everyone knows that civilians are more exposed to suicide bombs, but the extent to which that’s true was surprising," the study’s lead author, Dr. Madelyn Hsiao-Rei Hicks of King’s College London, said in an interview.

The study by Dr. Hicks and her colleagues also revealed Iraqi children to be particularly vulnerable. Children comprised 14% of suicide bomb fatalities during the study period – a share greater than the 9% dying in all forms of armed violence – and 51% of child casualties from suicide bombs were fatal.

Contributing factors may have included malnutrition, a scarcity of pediatric experts and supplies in clinics, more severe injuries, and greater physiological vulnerability to the type of injuries caused by suicide bombs, Dr. Hicks and her colleagues wrote.

While earlier, smaller studies have suggested that children are more vulnerable to suicide bombs, "I hadn’t seen that before in larger sets of data on children and adults," Dr. Hicks said. "It makes sense anatomically, as their heads and torsos are proportionately larger than adults’, and a bomb is more likely to hit a vital organ."

Why Suicide Attacks Focus on Iraqi Civilians

In an editorial comment accompanying the article, Dr. Gilbert Burnham of Johns Hopkins Bloomberg School of Public Health, Baltimore, offered a broader perspective on why Iraq’s civilian population would bear such a disproportionate brunt of such attacks, and what might be done about it (Lancet 2011;378:855-7).

"Prevention of suicide attacks is difficult because of their complex origins," Dr. Burnham wrote. "The military’s approach of controlling access and attacking suspicious targets has protected coalition forces in Iraq, but the resulting deaths of innocent civilians have alienated many Iraqis. This action has played a part in shifting suicide attacks towards civilian targets."

Attempts to stop bombers are often futile, Dr. Burnham continued. "Most effective is the elimination of conditions that cause popular support for terrorist groups," and targeting of extremist networks.

Dr. Burnham declared that he had no conflicts of interest. Dr. Hicks and colleagues declared that they had no financial conflicts of interest; however, their study, which had no outside funding, used data from Iraq Body Count, an organization founded by three of Dr. Hicks’ coauthors. Dr. Hicks serves as an unpaid director for IBC.

Dr. Hicks said that she had become involved with IBC after discovering that its database contained valuable public health information gotten through exacting methods. Moreover, she said, IBC distinguished between civilians and combatants, which many data sources do not, and had information on specific types of weapons involved in the injuries. "It's the kind of detail that’s very difficult to obtain in clinical settings," she said.

IBC has documented violent deaths of Iraqi civilians since 2003, using media, hospital, government and nongovernmental organization reports. Dr. Hicks and her colleagues also used data from iCasualties, a separate group that tracks coalition military casualties in Iraq and Afghanistan.

While the investigators acknowledged that one potential weakness of their study was its use of a database reliant on media reports, they noted that all IBC’s reports had been cross-checked and represented "documented, verifiable, individual casualties and suicide bomb events," not estimates or extrapolations.

The study appeared as part of a group of articles in the Lancet highlighting the health consequences of actions and conflicts in the decade following the terrorist attacks of Sept. 11, 2001.

How the War Impacts Noncombatants

The effects of the Iraq war on noncombatants was addressed further in separate study led by Dr. Christopher H. Warner of the U.S. Command and General Staff College in Fort Leavenworth, Kan. (Lancet 2011; 378: 915-24).

Dr. Warner and colleagues’ study showed that an Army ethics training program had improved troops’ self-reported behavior toward noncombatants, and increased troops’ stated willingness to report fellow unit members committing misconduct.

Soldiers from an infantry brigade team participated in the program, which used clips from popular movies and other unconventional teaching methods to highlight dilemmas involving noncombatants, and instruct on legal and ethical ways of resolving them.

The training, which lasted between 60 and 90 minutes, occurred during a 15-month deployment in Iraq that lasted until 2008. Randomly selected members of the brigade (n=421) completed anonymous surveys 3 months after the training, and their results were compared with anonymous surveys from randomly chosen members (n=397) completed before the training.

Only 5% of troops who had completed training reported having damaged or destroyed private property, compared with 14% before. A majority – 59% – reported being willing to report a unit member for mistreating a noncombatant, compared with 36% before. Combat frequency and intensity was the strongest predictor of unethical behavior, the investigators found, and posttraumatic stress disorder was not seen as predictive of unethical behavior after controlling for combat experiences.

In an editorial comment accompanying Dr. Warner and colleagues’ article, Dr. Jennifer Leaning of Harvard School of Public Health, Boston, and Michael Lappi, Ph.D., of Harvard Medical School, praised the design of both the training program, which can be used in a war zone, and the study (Lancet 2011;378:857-9). The study’s weaknesses, they wrote, "derive in some measure from its strengths, in that frequent entries and exits of soldiers from the deployment zone introduced sampling issues ... and concerns about self-report."

Still, Dr. Leaning and Dr. Lappi wrote, "soldiers deployed in counter-insurgency operations will always need to fall back on their own capacity, buttressed by sound training, for resilient and nuanced legal and moral choice."

Dr. Warner reported no conflicts of interest related to the study, and Dr. Leaning and Dr. Lappi also reported no conflicts of interest.

Suicide bombs have now killed 200 coalition soldiers and more than 12,000 civilians in Iraq, say the authors of a new report focusing on the high number of civilian deaths – particularly child deaths – and injuries from such attacks.

The report, published online Sept. 1 in the Lancet, shows that while U.S.-led coalition forces have adopted successful strategies for avoiding suicide bomb attacks and for treating its own members exposed to them, the noncombatant, civilian population of Iraq has borne a remarkably heavy burden (Lancet 2011;378: 906-14).

Some 30,644 noncombatant civilians were injured and 12,284 killed in more than 1,000 suicide bombings between March 2003, when the Iraq war began, through the end of December 2010 – a ratio of 2.5 injured for every 1 killed, investigators found. Some 19% of all Iraqi civilian casualties and 11% of Iraqi civilian deaths in this period were caused by suicide bombs, with car bombs proving more lethal than those detonated by bombers on foot.

Courtesy U.S. Army/Pfc. Charles Probst

"I think everyone knows that civilians are more exposed to suicide bombs, but the extent to which that’s true was surprising," the study’s lead author, Dr. Madelyn Hsiao-Rei Hicks of King’s College London, said in an interview.

The study by Dr. Hicks and her colleagues also revealed Iraqi children to be particularly vulnerable. Children comprised 14% of suicide bomb fatalities during the study period – a share greater than the 9% dying in all forms of armed violence – and 51% of child casualties from suicide bombs were fatal.

Contributing factors may have included malnutrition, a scarcity of pediatric experts and supplies in clinics, more severe injuries, and greater physiological vulnerability to the type of injuries caused by suicide bombs, Dr. Hicks and her colleagues wrote.

While earlier, smaller studies have suggested that children are more vulnerable to suicide bombs, "I hadn’t seen that before in larger sets of data on children and adults," Dr. Hicks said. "It makes sense anatomically, as their heads and torsos are proportionately larger than adults’, and a bomb is more likely to hit a vital organ."

Why Suicide Attacks Focus on Iraqi Civilians

In an editorial comment accompanying the article, Dr. Gilbert Burnham of Johns Hopkins Bloomberg School of Public Health, Baltimore, offered a broader perspective on why Iraq’s civilian population would bear such a disproportionate brunt of such attacks, and what might be done about it (Lancet 2011;378:855-7).

"Prevention of suicide attacks is difficult because of their complex origins," Dr. Burnham wrote. "The military’s approach of controlling access and attacking suspicious targets has protected coalition forces in Iraq, but the resulting deaths of innocent civilians have alienated many Iraqis. This action has played a part in shifting suicide attacks towards civilian targets."

Attempts to stop bombers are often futile, Dr. Burnham continued. "Most effective is the elimination of conditions that cause popular support for terrorist groups," and targeting of extremist networks.

Dr. Burnham declared that he had no conflicts of interest. Dr. Hicks and colleagues declared that they had no financial conflicts of interest; however, their study, which had no outside funding, used data from Iraq Body Count, an organization founded by three of Dr. Hicks’ coauthors. Dr. Hicks serves as an unpaid director for IBC.

Dr. Hicks said that she had become involved with IBC after discovering that its database contained valuable public health information gotten through exacting methods. Moreover, she said, IBC distinguished between civilians and combatants, which many data sources do not, and had information on specific types of weapons involved in the injuries. "It's the kind of detail that’s very difficult to obtain in clinical settings," she said.

IBC has documented violent deaths of Iraqi civilians since 2003, using media, hospital, government and nongovernmental organization reports. Dr. Hicks and her colleagues also used data from iCasualties, a separate group that tracks coalition military casualties in Iraq and Afghanistan.

While the investigators acknowledged that one potential weakness of their study was its use of a database reliant on media reports, they noted that all IBC’s reports had been cross-checked and represented "documented, verifiable, individual casualties and suicide bomb events," not estimates or extrapolations.

The study appeared as part of a group of articles in the Lancet highlighting the health consequences of actions and conflicts in the decade following the terrorist attacks of Sept. 11, 2001.

How the War Impacts Noncombatants

The effects of the Iraq war on noncombatants was addressed further in separate study led by Dr. Christopher H. Warner of the U.S. Command and General Staff College in Fort Leavenworth, Kan. (Lancet 2011; 378: 915-24).

Dr. Warner and colleagues’ study showed that an Army ethics training program had improved troops’ self-reported behavior toward noncombatants, and increased troops’ stated willingness to report fellow unit members committing misconduct.

Soldiers from an infantry brigade team participated in the program, which used clips from popular movies and other unconventional teaching methods to highlight dilemmas involving noncombatants, and instruct on legal and ethical ways of resolving them.

The training, which lasted between 60 and 90 minutes, occurred during a 15-month deployment in Iraq that lasted until 2008. Randomly selected members of the brigade (n=421) completed anonymous surveys 3 months after the training, and their results were compared with anonymous surveys from randomly chosen members (n=397) completed before the training.

Only 5% of troops who had completed training reported having damaged or destroyed private property, compared with 14% before. A majority – 59% – reported being willing to report a unit member for mistreating a noncombatant, compared with 36% before. Combat frequency and intensity was the strongest predictor of unethical behavior, the investigators found, and posttraumatic stress disorder was not seen as predictive of unethical behavior after controlling for combat experiences.

In an editorial comment accompanying Dr. Warner and colleagues’ article, Dr. Jennifer Leaning of Harvard School of Public Health, Boston, and Michael Lappi, Ph.D., of Harvard Medical School, praised the design of both the training program, which can be used in a war zone, and the study (Lancet 2011;378:857-9). The study’s weaknesses, they wrote, "derive in some measure from its strengths, in that frequent entries and exits of soldiers from the deployment zone introduced sampling issues ... and concerns about self-report."

Still, Dr. Leaning and Dr. Lappi wrote, "soldiers deployed in counter-insurgency operations will always need to fall back on their own capacity, buttressed by sound training, for resilient and nuanced legal and moral choice."

Dr. Warner reported no conflicts of interest related to the study, and Dr. Leaning and Dr. Lappi also reported no conflicts of interest.

Suicide bombs have now killed 200 coalition soldiers and more than 12,000 civilians in Iraq, say the authors of a new report focusing on the high number of civilian deaths – particularly child deaths – and injuries from such attacks.

The report, published online Sept. 1 in the Lancet, shows that while U.S.-led coalition forces have adopted successful strategies for avoiding suicide bomb attacks and for treating its own members exposed to them, the noncombatant, civilian population of Iraq has borne a remarkably heavy burden (Lancet 2011;378: 906-14).

Some 30,644 noncombatant civilians were injured and 12,284 killed in more than 1,000 suicide bombings between March 2003, when the Iraq war began, through the end of December 2010 – a ratio of 2.5 injured for every 1 killed, investigators found. Some 19% of all Iraqi civilian casualties and 11% of Iraqi civilian deaths in this period were caused by suicide bombs, with car bombs proving more lethal than those detonated by bombers on foot.

Courtesy U.S. Army/Pfc. Charles Probst

"I think everyone knows that civilians are more exposed to suicide bombs, but the extent to which that’s true was surprising," the study’s lead author, Dr. Madelyn Hsiao-Rei Hicks of King’s College London, said in an interview.

The study by Dr. Hicks and her colleagues also revealed Iraqi children to be particularly vulnerable. Children comprised 14% of suicide bomb fatalities during the study period – a share greater than the 9% dying in all forms of armed violence – and 51% of child casualties from suicide bombs were fatal.

Contributing factors may have included malnutrition, a scarcity of pediatric experts and supplies in clinics, more severe injuries, and greater physiological vulnerability to the type of injuries caused by suicide bombs, Dr. Hicks and her colleagues wrote.

While earlier, smaller studies have suggested that children are more vulnerable to suicide bombs, "I hadn’t seen that before in larger sets of data on children and adults," Dr. Hicks said. "It makes sense anatomically, as their heads and torsos are proportionately larger than adults’, and a bomb is more likely to hit a vital organ."

Why Suicide Attacks Focus on Iraqi Civilians

In an editorial comment accompanying the article, Dr. Gilbert Burnham of Johns Hopkins Bloomberg School of Public Health, Baltimore, offered a broader perspective on why Iraq’s civilian population would bear such a disproportionate brunt of such attacks, and what might be done about it (Lancet 2011;378:855-7).

"Prevention of suicide attacks is difficult because of their complex origins," Dr. Burnham wrote. "The military’s approach of controlling access and attacking suspicious targets has protected coalition forces in Iraq, but the resulting deaths of innocent civilians have alienated many Iraqis. This action has played a part in shifting suicide attacks towards civilian targets."

Attempts to stop bombers are often futile, Dr. Burnham continued. "Most effective is the elimination of conditions that cause popular support for terrorist groups," and targeting of extremist networks.

Dr. Burnham declared that he had no conflicts of interest. Dr. Hicks and colleagues declared that they had no financial conflicts of interest; however, their study, which had no outside funding, used data from Iraq Body Count, an organization founded by three of Dr. Hicks’ coauthors. Dr. Hicks serves as an unpaid director for IBC.

Dr. Hicks said that she had become involved with IBC after discovering that its database contained valuable public health information gotten through exacting methods. Moreover, she said, IBC distinguished between civilians and combatants, which many data sources do not, and had information on specific types of weapons involved in the injuries. "It's the kind of detail that’s very difficult to obtain in clinical settings," she said.

IBC has documented violent deaths of Iraqi civilians since 2003, using media, hospital, government and nongovernmental organization reports. Dr. Hicks and her colleagues also used data from iCasualties, a separate group that tracks coalition military casualties in Iraq and Afghanistan.

While the investigators acknowledged that one potential weakness of their study was its use of a database reliant on media reports, they noted that all IBC’s reports had been cross-checked and represented "documented, verifiable, individual casualties and suicide bomb events," not estimates or extrapolations.

The study appeared as part of a group of articles in the Lancet highlighting the health consequences of actions and conflicts in the decade following the terrorist attacks of Sept. 11, 2001.

How the War Impacts Noncombatants

The effects of the Iraq war on noncombatants was addressed further in separate study led by Dr. Christopher H. Warner of the U.S. Command and General Staff College in Fort Leavenworth, Kan. (Lancet 2011; 378: 915-24).

Dr. Warner and colleagues’ study showed that an Army ethics training program had improved troops’ self-reported behavior toward noncombatants, and increased troops’ stated willingness to report fellow unit members committing misconduct.

Soldiers from an infantry brigade team participated in the program, which used clips from popular movies and other unconventional teaching methods to highlight dilemmas involving noncombatants, and instruct on legal and ethical ways of resolving them.

The training, which lasted between 60 and 90 minutes, occurred during a 15-month deployment in Iraq that lasted until 2008. Randomly selected members of the brigade (n=421) completed anonymous surveys 3 months after the training, and their results were compared with anonymous surveys from randomly chosen members (n=397) completed before the training.

Only 5% of troops who had completed training reported having damaged or destroyed private property, compared with 14% before. A majority – 59% – reported being willing to report a unit member for mistreating a noncombatant, compared with 36% before. Combat frequency and intensity was the strongest predictor of unethical behavior, the investigators found, and posttraumatic stress disorder was not seen as predictive of unethical behavior after controlling for combat experiences.

In an editorial comment accompanying Dr. Warner and colleagues’ article, Dr. Jennifer Leaning of Harvard School of Public Health, Boston, and Michael Lappi, Ph.D., of Harvard Medical School, praised the design of both the training program, which can be used in a war zone, and the study (Lancet 2011;378:857-9). The study’s weaknesses, they wrote, "derive in some measure from its strengths, in that frequent entries and exits of soldiers from the deployment zone introduced sampling issues ... and concerns about self-report."

Still, Dr. Leaning and Dr. Lappi wrote, "soldiers deployed in counter-insurgency operations will always need to fall back on their own capacity, buttressed by sound training, for resilient and nuanced legal and moral choice."

Dr. Warner reported no conflicts of interest related to the study, and Dr. Leaning and Dr. Lappi also reported no conflicts of interest.