Jane Salodof MacNeil

VERSAILLES, FRANCE — A preliminary report from a French registry collecting severe reactions to anti-tumor necrosis factor-? therapy suggests that patients may be at greater risk than realized of developing legionellosis and tuberculosis.

“What was most surprising was the 13 cases of legionellosis,” investigator Dr. Florence Tubach said at the 12th European Pediatric Rheumatology Congress. “[This] was quite unexpected.”

Dr. Tubach of Hôpital Bichat in Paris reported on the first 137 cases in the multidisciplinary RATIO (Recherche Anti-TNF Infections Opportunist) registry, which began accepting cases on Feb. 1, 2004. Four hundred eighty-six French centers have agreed to report severe infections and lymphomas in patients on TNF-? antagonists to the project, which is soliciting information quarterly.

The patients recorded so far have had 60 severe bacterial infections and 63 opportunistic infections (including 20 TB, 15 virosis, and 13 legionellosis). They also had 13 cases of lymphoma, and one of myeloma, Dr. Tubach said.

Rheumatoid arthritis was the most common underlying disease, occurring in 98 patients. The next most common underlying conditions were ankylosing spondylitis in 17 patients and Crohn's disease in 7 patients. Eight other diseases accounted for the remaining cases. Only two of the patients were children.

Dr. Tubach warned against making assumptions based on the number of patients who were taking infliximab, etanercept, or adalimumab. “We must be cautious with these numbers because we are in very small numbers, and infliximab has been available a long time, and adalimumab for only a short time,” she said.

The median duration of anti-TNF therapy when patients presented with TB was 26 weeks, with a range of 2–173 weeks, Dr. Tubach reported in a presentation on the first 13 cases of TB. “Despite preventive guidelines TB is a persistent risk, complicating anti-TNF therapy,” she said. “TB may occur later than previously reported.”

Before starting anti-TNF therapy, all but 2 of the 13 patients who became infected had intradermal tuberculin tests. The results were less than 5 mm in six patients, 5–10 mm in four patients, and more than 15 mm in one patient, Dr. Tubach said.

Though five patients had a history of exposure to TB, she said none had a personal history of TB, and no one received any chemoprophylaxis against TB. All had normal chest x-rays.

Based on these findings, she said France has decided to modify guidelines for prevention “to include in the definition of latent TB patients with a history of exposure to TB.” Authorities have also decreased the cut-off for positivity on the intradermal tuberculin test to 5 mm, she said.

The lymphoma cases included four Hodgkin's lymphomas, five diffuse large B-cell lymphomas, three T-cell lymphomas, and one mucosa-associated lymphoid tissue (MALT) B-cell lymphoma. Physicians detected Epstein-Barr virus in one Hodgkin's patient.

Dr. Tubach described the registry as “a good example of partnership between scientific societies, manufacturers, and the national authorities.” It is supported by a grant from the three manufacturers of anti-TNF-? drugs: Abbott, Schering-Plough, and Wyeth.

Since one of the goals is to identify risk factors for infection, Dr. Tubach said that the investigators plan to match each case in which infection is reported with two controls. One would be a patient who never received anti-TNF-? therapy. The other would be a patient who had taken one of the drugs, and stopped without becoming infected.

In response to an audience question, she said the registry is not prepared to give information on incidence of infection because it only collects information on patients who meet the inclusion criteria.

VERSAILLES, FRANCE — A preliminary report from a French registry collecting severe reactions to anti-tumor necrosis factor-? therapy suggests that patients may be at greater risk than realized of developing legionellosis and tuberculosis.

“What was most surprising was the 13 cases of legionellosis,” investigator Dr. Florence Tubach said at the 12th European Pediatric Rheumatology Congress. “[This] was quite unexpected.”

Dr. Tubach of Hôpital Bichat in Paris reported on the first 137 cases in the multidisciplinary RATIO (Recherche Anti-TNF Infections Opportunist) registry, which began accepting cases on Feb. 1, 2004. Four hundred eighty-six French centers have agreed to report severe infections and lymphomas in patients on TNF-? antagonists to the project, which is soliciting information quarterly.

The patients recorded so far have had 60 severe bacterial infections and 63 opportunistic infections (including 20 TB, 15 virosis, and 13 legionellosis). They also had 13 cases of lymphoma, and one of myeloma, Dr. Tubach said.

Rheumatoid arthritis was the most common underlying disease, occurring in 98 patients. The next most common underlying conditions were ankylosing spondylitis in 17 patients and Crohn's disease in 7 patients. Eight other diseases accounted for the remaining cases. Only two of the patients were children.

Dr. Tubach warned against making assumptions based on the number of patients who were taking infliximab, etanercept, or adalimumab. “We must be cautious with these numbers because we are in very small numbers, and infliximab has been available a long time, and adalimumab for only a short time,” she said.

The median duration of anti-TNF therapy when patients presented with TB was 26 weeks, with a range of 2–173 weeks, Dr. Tubach reported in a presentation on the first 13 cases of TB. “Despite preventive guidelines TB is a persistent risk, complicating anti-TNF therapy,” she said. “TB may occur later than previously reported.”

Before starting anti-TNF therapy, all but 2 of the 13 patients who became infected had intradermal tuberculin tests. The results were less than 5 mm in six patients, 5–10 mm in four patients, and more than 15 mm in one patient, Dr. Tubach said.

Though five patients had a history of exposure to TB, she said none had a personal history of TB, and no one received any chemoprophylaxis against TB. All had normal chest x-rays.

Based on these findings, she said France has decided to modify guidelines for prevention “to include in the definition of latent TB patients with a history of exposure to TB.” Authorities have also decreased the cut-off for positivity on the intradermal tuberculin test to 5 mm, she said.

The lymphoma cases included four Hodgkin's lymphomas, five diffuse large B-cell lymphomas, three T-cell lymphomas, and one mucosa-associated lymphoid tissue (MALT) B-cell lymphoma. Physicians detected Epstein-Barr virus in one Hodgkin's patient.

Dr. Tubach described the registry as “a good example of partnership between scientific societies, manufacturers, and the national authorities.” It is supported by a grant from the three manufacturers of anti-TNF-? drugs: Abbott, Schering-Plough, and Wyeth.

Since one of the goals is to identify risk factors for infection, Dr. Tubach said that the investigators plan to match each case in which infection is reported with two controls. One would be a patient who never received anti-TNF-? therapy. The other would be a patient who had taken one of the drugs, and stopped without becoming infected.

In response to an audience question, she said the registry is not prepared to give information on incidence of infection because it only collects information on patients who meet the inclusion criteria.

VERSAILLES, FRANCE — A preliminary report from a French registry collecting severe reactions to anti-tumor necrosis factor-? therapy suggests that patients may be at greater risk than realized of developing legionellosis and tuberculosis.

“What was most surprising was the 13 cases of legionellosis,” investigator Dr. Florence Tubach said at the 12th European Pediatric Rheumatology Congress. “[This] was quite unexpected.”

Dr. Tubach of Hôpital Bichat in Paris reported on the first 137 cases in the multidisciplinary RATIO (Recherche Anti-TNF Infections Opportunist) registry, which began accepting cases on Feb. 1, 2004. Four hundred eighty-six French centers have agreed to report severe infections and lymphomas in patients on TNF-? antagonists to the project, which is soliciting information quarterly.

The patients recorded so far have had 60 severe bacterial infections and 63 opportunistic infections (including 20 TB, 15 virosis, and 13 legionellosis). They also had 13 cases of lymphoma, and one of myeloma, Dr. Tubach said.

Rheumatoid arthritis was the most common underlying disease, occurring in 98 patients. The next most common underlying conditions were ankylosing spondylitis in 17 patients and Crohn's disease in 7 patients. Eight other diseases accounted for the remaining cases. Only two of the patients were children.

Dr. Tubach warned against making assumptions based on the number of patients who were taking infliximab, etanercept, or adalimumab. “We must be cautious with these numbers because we are in very small numbers, and infliximab has been available a long time, and adalimumab for only a short time,” she said.

The median duration of anti-TNF therapy when patients presented with TB was 26 weeks, with a range of 2–173 weeks, Dr. Tubach reported in a presentation on the first 13 cases of TB. “Despite preventive guidelines TB is a persistent risk, complicating anti-TNF therapy,” she said. “TB may occur later than previously reported.”

Before starting anti-TNF therapy, all but 2 of the 13 patients who became infected had intradermal tuberculin tests. The results were less than 5 mm in six patients, 5–10 mm in four patients, and more than 15 mm in one patient, Dr. Tubach said.

Though five patients had a history of exposure to TB, she said none had a personal history of TB, and no one received any chemoprophylaxis against TB. All had normal chest x-rays.

Based on these findings, she said France has decided to modify guidelines for prevention “to include in the definition of latent TB patients with a history of exposure to TB.” Authorities have also decreased the cut-off for positivity on the intradermal tuberculin test to 5 mm, she said.

The lymphoma cases included four Hodgkin's lymphomas, five diffuse large B-cell lymphomas, three T-cell lymphomas, and one mucosa-associated lymphoid tissue (MALT) B-cell lymphoma. Physicians detected Epstein-Barr virus in one Hodgkin's patient.

Dr. Tubach described the registry as “a good example of partnership between scientific societies, manufacturers, and the national authorities.” It is supported by a grant from the three manufacturers of anti-TNF-? drugs: Abbott, Schering-Plough, and Wyeth.

Since one of the goals is to identify risk factors for infection, Dr. Tubach said that the investigators plan to match each case in which infection is reported with two controls. One would be a patient who never received anti-TNF-? therapy. The other would be a patient who had taken one of the drugs, and stopped without becoming infected.

In response to an audience question, she said the registry is not prepared to give information on incidence of infection because it only collects information on patients who meet the inclusion criteria.

SANTA ANA PUEBLO, N.M. – Elderly people with depression and arthritis experienced significant pain relief with duloxetine in a placebo-controlled trial reported at the annual meeting of the Academy of Psychosomatic Medicine.

Conducted by investigators from Eli Lilly & Co., the research findings also documented significant improvement in cognitive functions, primarily verbal learning and memory, for depressed patients treated with duloxetine (Cymbalta) in the 8-week, multicenter study.

“I think (these findings are) very encouraging,” investigator Dr. Michael J. Robinson, a clinical research physician at Lilly's medical division in Indianapolis, said in an interview. “Duloxetine may be advantageous for those specific cognitive symptoms.”

The results suggest duloxetine can alleviate arthritis pain, a common comorbidity in depressed elderly patients. An inhibitor of serotonin and norepinephrine reuptake, duloxetine is known to have analgesic properties and is approved for treatment of peripheral neuropathic pain in patients with diabetes.

Cognition was a primary outcome in the trial, which randomized 207 depressed elderly patients to 60 mg daily of duloxetine and 104 to placebo. The two cohorts were similar, with an average age of 73 years, slightly more women than men, and more than three-fourths the population being white. All patients were at least 65 years old and had previous episodes of depression.

Similar proportions of patients withdrew because of adverse events. The most common in the duloxetine group were dry mouth, nausea, and constipation.

As could be expected, duloxetine produced faster and more significant reductions than placebo on the Geriatric Depression Scale (GDS) and the Hamilton Rating Scale for Depression (HAMD 17). On average, the GDS fell −4.07 in patients on duloxetine vs. -1.34 in the placebo cohort. HAMD 17 scores declined −6.49 with duloxetine and −3.72 with placebo.

The duloxetine cohort also demonstrated significantly greater improvement in a composite cognitive score based on four cognitive tests: a mean change of +1.95 vs. +0.76 for the placebo group. At baseline, the mean composite cognitive scores were 22.70 for the duloxetine group and 23.17 for the placebo group. Most of the improvement could be attributed to changes in scores on verbal learning and recall tests.

Visual analog scale scores for all 311 patients in the trial demonstrated greater improvement in back pain and “time in pain while awake” for the duloxetine cohort. In a subgroup analysis limited to patients with comorbid arthritis, 117 patients on duloxetine had significantly greater improvement in four of six pain measures, compared with scores of 55 patients on placebo.

At the outset, all patients with arthritis had significantly higher baseline scores on five of six pain categories assessed with visual analog scales. Overall severity was 38.3 for patients with arthritis vs. 22.5 in patients who did not have arthritis.

Over the course of the trial, arthritis patients in the duloxetine cohort had significantly greater improvements in overall pain, back pain, time in pain while awake, and interference with daily activities. Arthritis patients in the placebo group had more headache and shoulder pain, but the difference was not significant.

The mean change in overall pain scores was −6.70 for arthritis patients on duloxetine vs. −1.89 for arthritis patients on placebo. The most dramatic effect was for back pain, which fell by a mean of more than 20% with duloxetine while increasing more than 10% with placebo.

“We don't know if this is their pain due to arthritis or their pain due to depression,” Dr. Robinson said. “This is just looking at general pain outcomes.” Baseline scores for depression and improvements in mood were similar for arthritis patients in the two arms of the trial.

SANTA ANA PUEBLO, N.M. – Elderly people with depression and arthritis experienced significant pain relief with duloxetine in a placebo-controlled trial reported at the annual meeting of the Academy of Psychosomatic Medicine.

Conducted by investigators from Eli Lilly & Co., the research findings also documented significant improvement in cognitive functions, primarily verbal learning and memory, for depressed patients treated with duloxetine (Cymbalta) in the 8-week, multicenter study.

“I think (these findings are) very encouraging,” investigator Dr. Michael J. Robinson, a clinical research physician at Lilly's medical division in Indianapolis, said in an interview. “Duloxetine may be advantageous for those specific cognitive symptoms.”

The results suggest duloxetine can alleviate arthritis pain, a common comorbidity in depressed elderly patients. An inhibitor of serotonin and norepinephrine reuptake, duloxetine is known to have analgesic properties and is approved for treatment of peripheral neuropathic pain in patients with diabetes.

Cognition was a primary outcome in the trial, which randomized 207 depressed elderly patients to 60 mg daily of duloxetine and 104 to placebo. The two cohorts were similar, with an average age of 73 years, slightly more women than men, and more than three-fourths the population being white. All patients were at least 65 years old and had previous episodes of depression.

Similar proportions of patients withdrew because of adverse events. The most common in the duloxetine group were dry mouth, nausea, and constipation.

As could be expected, duloxetine produced faster and more significant reductions than placebo on the Geriatric Depression Scale (GDS) and the Hamilton Rating Scale for Depression (HAMD 17). On average, the GDS fell −4.07 in patients on duloxetine vs. -1.34 in the placebo cohort. HAMD 17 scores declined −6.49 with duloxetine and −3.72 with placebo.

The duloxetine cohort also demonstrated significantly greater improvement in a composite cognitive score based on four cognitive tests: a mean change of +1.95 vs. +0.76 for the placebo group. At baseline, the mean composite cognitive scores were 22.70 for the duloxetine group and 23.17 for the placebo group. Most of the improvement could be attributed to changes in scores on verbal learning and recall tests.

Visual analog scale scores for all 311 patients in the trial demonstrated greater improvement in back pain and “time in pain while awake” for the duloxetine cohort. In a subgroup analysis limited to patients with comorbid arthritis, 117 patients on duloxetine had significantly greater improvement in four of six pain measures, compared with scores of 55 patients on placebo.

At the outset, all patients with arthritis had significantly higher baseline scores on five of six pain categories assessed with visual analog scales. Overall severity was 38.3 for patients with arthritis vs. 22.5 in patients who did not have arthritis.

Over the course of the trial, arthritis patients in the duloxetine cohort had significantly greater improvements in overall pain, back pain, time in pain while awake, and interference with daily activities. Arthritis patients in the placebo group had more headache and shoulder pain, but the difference was not significant.

The mean change in overall pain scores was −6.70 for arthritis patients on duloxetine vs. −1.89 for arthritis patients on placebo. The most dramatic effect was for back pain, which fell by a mean of more than 20% with duloxetine while increasing more than 10% with placebo.

“We don't know if this is their pain due to arthritis or their pain due to depression,” Dr. Robinson said. “This is just looking at general pain outcomes.” Baseline scores for depression and improvements in mood were similar for arthritis patients in the two arms of the trial.

SANTA ANA PUEBLO, N.M. – Elderly people with depression and arthritis experienced significant pain relief with duloxetine in a placebo-controlled trial reported at the annual meeting of the Academy of Psychosomatic Medicine.

Conducted by investigators from Eli Lilly & Co., the research findings also documented significant improvement in cognitive functions, primarily verbal learning and memory, for depressed patients treated with duloxetine (Cymbalta) in the 8-week, multicenter study.

“I think (these findings are) very encouraging,” investigator Dr. Michael J. Robinson, a clinical research physician at Lilly's medical division in Indianapolis, said in an interview. “Duloxetine may be advantageous for those specific cognitive symptoms.”

The results suggest duloxetine can alleviate arthritis pain, a common comorbidity in depressed elderly patients. An inhibitor of serotonin and norepinephrine reuptake, duloxetine is known to have analgesic properties and is approved for treatment of peripheral neuropathic pain in patients with diabetes.

Cognition was a primary outcome in the trial, which randomized 207 depressed elderly patients to 60 mg daily of duloxetine and 104 to placebo. The two cohorts were similar, with an average age of 73 years, slightly more women than men, and more than three-fourths the population being white. All patients were at least 65 years old and had previous episodes of depression.

Similar proportions of patients withdrew because of adverse events. The most common in the duloxetine group were dry mouth, nausea, and constipation.

As could be expected, duloxetine produced faster and more significant reductions than placebo on the Geriatric Depression Scale (GDS) and the Hamilton Rating Scale for Depression (HAMD 17). On average, the GDS fell −4.07 in patients on duloxetine vs. -1.34 in the placebo cohort. HAMD 17 scores declined −6.49 with duloxetine and −3.72 with placebo.

The duloxetine cohort also demonstrated significantly greater improvement in a composite cognitive score based on four cognitive tests: a mean change of +1.95 vs. +0.76 for the placebo group. At baseline, the mean composite cognitive scores were 22.70 for the duloxetine group and 23.17 for the placebo group. Most of the improvement could be attributed to changes in scores on verbal learning and recall tests.

Visual analog scale scores for all 311 patients in the trial demonstrated greater improvement in back pain and “time in pain while awake” for the duloxetine cohort. In a subgroup analysis limited to patients with comorbid arthritis, 117 patients on duloxetine had significantly greater improvement in four of six pain measures, compared with scores of 55 patients on placebo.

At the outset, all patients with arthritis had significantly higher baseline scores on five of six pain categories assessed with visual analog scales. Overall severity was 38.3 for patients with arthritis vs. 22.5 in patients who did not have arthritis.

Over the course of the trial, arthritis patients in the duloxetine cohort had significantly greater improvements in overall pain, back pain, time in pain while awake, and interference with daily activities. Arthritis patients in the placebo group had more headache and shoulder pain, but the difference was not significant.

The mean change in overall pain scores was −6.70 for arthritis patients on duloxetine vs. −1.89 for arthritis patients on placebo. The most dramatic effect was for back pain, which fell by a mean of more than 20% with duloxetine while increasing more than 10% with placebo.

“We don't know if this is their pain due to arthritis or their pain due to depression,” Dr. Robinson said. “This is just looking at general pain outcomes.” Baseline scores for depression and improvements in mood were similar for arthritis patients in the two arms of the trial.

SCOTTSDALE, ARIZ. — Noninvasive genetic screening has a higher detection rate when done in the first trimester of pregnancy and should be offered with prompt disclosure of results, Joe Leigh Simpson, M.D., said at the annual meeting of the Central Association of Obstetricians and Gynecologists.

An offer of amniocentesis or chorionic villus sampling (CVS) to every pregnant woman regardless of age also should be considered, according to Dr. Simpson, chairman of obstetrics and gynecology at Baylor College of Medicine, Houston.

“I believe a good case could be made for universal invasive screening,” he said. “I believe amniocentesis and CVS are much safer than generally touted. The 1-in-200 [loss rate] figure we have told our patients is doing them a disservice, because it is not a valid figure in 2005.”

He predicted karyotyping will become obsolete as a diagnostic tool within the next 5–10 years. Chromosomal microarrays currently in development are more accurate than karyotypes, and should soon be able to detect many common Mendelian disorders, Dr. Simpson said after describing ongoing research at Baylor, where he also is a professor in the department of molecular and human genetics.

“I don't think there is any question the public will demand this approach and not karyotypes,” he said. “Karyotypes have a limited future in terms of the diagnostic field.”

The American College of Obstetricians and Gynecologists is reviewing the current guideline for invasive and noninvasive screening, adopted in 1996, according to Dr. Simpson. He predicted a revision with a “cafeteria of options” will be announced early next year.

Among the noninvasive options he listed are sequential first and second trimester screening with various serum analytes, nuchal translucency ultrasound, and nasal bone inspection.

“Noninvasive first-trimester screening shows clear improvement, 5%–10%, over second-trimester screening, and is more applicable to multiple gestations,” he said, citing recent results from a new analysis of data from the First and Second Trimester Evaluation of Risk for Aneuploidy (FASTER) trial. “Successful incorporation with nasal bone [screening] could yield over 90% detection.”

Dr. Simpson said nuchal translucency ultrasound in the first trimester is especially useful in women with multiple gestations, as it allows assessment of individual fetuses. With serum testing alone, he said, detection rates in this population can dip as low as 25% with second-trimester screening.

First-trimester screening for absence of nasal bone was not successful in a 2003 report from the FASTER trial, but other studies have reported Down syndrome detection rates as high as 73%, according to Dr. Simpson. He advocated using nasal bone inspection with other noninvasive tests rather than as the sole measure.

In two recent studies from the United Kingdom, he said 30,564 women and 15,822 women, respectively, were screened by four measures: pregnancy-associated plasma protein A (PAPP-A), human chorionic gonadotropin (hCG), nuchal translucency, and nasal bone inspection. The detection rates were 93% and 97%, respectively.

“Early is better for issues of privacy and access to management, but it is also [better] for sensitivity,” Dr. Simpson said.

Addressing the controversy over disclosure of first-trimester results before a woman returns for second-trimester screening, he warned of the potential for litigation if the patient fails to return or is somehow lost to follow-up without learning she is at high risk.

“What if you have someone who would have had a procedure if you told her the results in the first trimester, and she just did not get around to coming back to you, or there is a hurricane or whatever?” he said, adding that second-trimester detection rates have been shown not to decline as feared when high-risk women were advised of first-trimester results.

As for invasive procedures, Dr. Simpson said the fetal loss rates are “probably no more than 1 in 500.” He cited several large studies showing fetal loss rates as low as 1 in 667 amniocentesis procedures.

SCOTTSDALE, ARIZ. — Noninvasive genetic screening has a higher detection rate when done in the first trimester of pregnancy and should be offered with prompt disclosure of results, Joe Leigh Simpson, M.D., said at the annual meeting of the Central Association of Obstetricians and Gynecologists.

An offer of amniocentesis or chorionic villus sampling (CVS) to every pregnant woman regardless of age also should be considered, according to Dr. Simpson, chairman of obstetrics and gynecology at Baylor College of Medicine, Houston.

“I believe a good case could be made for universal invasive screening,” he said. “I believe amniocentesis and CVS are much safer than generally touted. The 1-in-200 [loss rate] figure we have told our patients is doing them a disservice, because it is not a valid figure in 2005.”

He predicted karyotyping will become obsolete as a diagnostic tool within the next 5–10 years. Chromosomal microarrays currently in development are more accurate than karyotypes, and should soon be able to detect many common Mendelian disorders, Dr. Simpson said after describing ongoing research at Baylor, where he also is a professor in the department of molecular and human genetics.

“I don't think there is any question the public will demand this approach and not karyotypes,” he said. “Karyotypes have a limited future in terms of the diagnostic field.”

The American College of Obstetricians and Gynecologists is reviewing the current guideline for invasive and noninvasive screening, adopted in 1996, according to Dr. Simpson. He predicted a revision with a “cafeteria of options” will be announced early next year.

Among the noninvasive options he listed are sequential first and second trimester screening with various serum analytes, nuchal translucency ultrasound, and nasal bone inspection.

“Noninvasive first-trimester screening shows clear improvement, 5%–10%, over second-trimester screening, and is more applicable to multiple gestations,” he said, citing recent results from a new analysis of data from the First and Second Trimester Evaluation of Risk for Aneuploidy (FASTER) trial. “Successful incorporation with nasal bone [screening] could yield over 90% detection.”

Dr. Simpson said nuchal translucency ultrasound in the first trimester is especially useful in women with multiple gestations, as it allows assessment of individual fetuses. With serum testing alone, he said, detection rates in this population can dip as low as 25% with second-trimester screening.

First-trimester screening for absence of nasal bone was not successful in a 2003 report from the FASTER trial, but other studies have reported Down syndrome detection rates as high as 73%, according to Dr. Simpson. He advocated using nasal bone inspection with other noninvasive tests rather than as the sole measure.

In two recent studies from the United Kingdom, he said 30,564 women and 15,822 women, respectively, were screened by four measures: pregnancy-associated plasma protein A (PAPP-A), human chorionic gonadotropin (hCG), nuchal translucency, and nasal bone inspection. The detection rates were 93% and 97%, respectively.

“Early is better for issues of privacy and access to management, but it is also [better] for sensitivity,” Dr. Simpson said.

Addressing the controversy over disclosure of first-trimester results before a woman returns for second-trimester screening, he warned of the potential for litigation if the patient fails to return or is somehow lost to follow-up without learning she is at high risk.

“What if you have someone who would have had a procedure if you told her the results in the first trimester, and she just did not get around to coming back to you, or there is a hurricane or whatever?” he said, adding that second-trimester detection rates have been shown not to decline as feared when high-risk women were advised of first-trimester results.

As for invasive procedures, Dr. Simpson said the fetal loss rates are “probably no more than 1 in 500.” He cited several large studies showing fetal loss rates as low as 1 in 667 amniocentesis procedures.

SCOTTSDALE, ARIZ. — Noninvasive genetic screening has a higher detection rate when done in the first trimester of pregnancy and should be offered with prompt disclosure of results, Joe Leigh Simpson, M.D., said at the annual meeting of the Central Association of Obstetricians and Gynecologists.

An offer of amniocentesis or chorionic villus sampling (CVS) to every pregnant woman regardless of age also should be considered, according to Dr. Simpson, chairman of obstetrics and gynecology at Baylor College of Medicine, Houston.

“I believe a good case could be made for universal invasive screening,” he said. “I believe amniocentesis and CVS are much safer than generally touted. The 1-in-200 [loss rate] figure we have told our patients is doing them a disservice, because it is not a valid figure in 2005.”

He predicted karyotyping will become obsolete as a diagnostic tool within the next 5–10 years. Chromosomal microarrays currently in development are more accurate than karyotypes, and should soon be able to detect many common Mendelian disorders, Dr. Simpson said after describing ongoing research at Baylor, where he also is a professor in the department of molecular and human genetics.

“I don't think there is any question the public will demand this approach and not karyotypes,” he said. “Karyotypes have a limited future in terms of the diagnostic field.”

The American College of Obstetricians and Gynecologists is reviewing the current guideline for invasive and noninvasive screening, adopted in 1996, according to Dr. Simpson. He predicted a revision with a “cafeteria of options” will be announced early next year.

Among the noninvasive options he listed are sequential first and second trimester screening with various serum analytes, nuchal translucency ultrasound, and nasal bone inspection.

“Noninvasive first-trimester screening shows clear improvement, 5%–10%, over second-trimester screening, and is more applicable to multiple gestations,” he said, citing recent results from a new analysis of data from the First and Second Trimester Evaluation of Risk for Aneuploidy (FASTER) trial. “Successful incorporation with nasal bone [screening] could yield over 90% detection.”

Dr. Simpson said nuchal translucency ultrasound in the first trimester is especially useful in women with multiple gestations, as it allows assessment of individual fetuses. With serum testing alone, he said, detection rates in this population can dip as low as 25% with second-trimester screening.

First-trimester screening for absence of nasal bone was not successful in a 2003 report from the FASTER trial, but other studies have reported Down syndrome detection rates as high as 73%, according to Dr. Simpson. He advocated using nasal bone inspection with other noninvasive tests rather than as the sole measure.

In two recent studies from the United Kingdom, he said 30,564 women and 15,822 women, respectively, were screened by four measures: pregnancy-associated plasma protein A (PAPP-A), human chorionic gonadotropin (hCG), nuchal translucency, and nasal bone inspection. The detection rates were 93% and 97%, respectively.

“Early is better for issues of privacy and access to management, but it is also [better] for sensitivity,” Dr. Simpson said.

Addressing the controversy over disclosure of first-trimester results before a woman returns for second-trimester screening, he warned of the potential for litigation if the patient fails to return or is somehow lost to follow-up without learning she is at high risk.

“What if you have someone who would have had a procedure if you told her the results in the first trimester, and she just did not get around to coming back to you, or there is a hurricane or whatever?” he said, adding that second-trimester detection rates have been shown not to decline as feared when high-risk women were advised of first-trimester results.

As for invasive procedures, Dr. Simpson said the fetal loss rates are “probably no more than 1 in 500.” He cited several large studies showing fetal loss rates as low as 1 in 667 amniocentesis procedures.

SCOTTSDALE, ARIZ. — Physicians referring infertile couples for preimplantation genetic diagnosis need to be realistic with their patients and vigilant in assessing the center that will do the testing, according to Estil J. Strawn Jr., M.D.

“You cannot say [to the patient] with any assurance that the baby is going to be perfect and you are going to have a good outcome,” Dr. Strawn told practitioners at the annual meeting of the Central Association of Obstetricians and Gynecologists.

Preimplantation genetic diagnosis (PGD) has a proven track record with several thousand births worldwide over the past 15 years, said Dr. Strawn, director of the division of reproductive endocrinology and infertility at the Medical College of Wisconsin in Milwaukee.

Nonetheless, it does not lead to a successful pregnancy more often than not. Dr. Strawn described the U.S. experience as comparable with the 25% pregnancy rate per embryo transfer reported by the European Society for Human Reproduction and Embryology PGD Consortium. In women aged 39 and older, he noted, the rate drops to 12%.

The consortium represents 66 centers, including 10 in the United States, according to Dr. Strawn. He said it reported 4,055 cycles reached the egg retrieval stage from 1999 to 2002 and 70% of those cycles reached the embryo transfer stage.

Summarizing PGD results at his own center, he said 22 retrievals for 18 patients have produced 156 embryos, 124 of which could be biopsied. Of those, 96 (77%) could be diagnosed by PDG, and 56 of those were deemed to be normal embryos.

The process led to four pregnancies in women up to age 37, but one turned out to be a blighted ovum. Despite more retrievals, transfers, and embryos in women older than 37 years, the result also was four pregnancies, three of which ended in miscarriage.

Two cycles in the younger patients did not result in transfers because aneuploidy was diagnosed in all the embryos. Dr. Strawn said the two women were encouraged to consider egg donation, and both are now pregnant. Though the numbers are small, he said more couples likely will be helped as technology improves.

Currently, most centers are screening for 6–8 chromosomes (13, 15, 16, 18, 21, 22, X, and Y), Dr. Strawn said. “What about the other 15 pairs?” he asked, noting that an embryo could carry a genetic defect for which PGD screening is not yet available.

Commonly screened conditions include Duchenne's and Becker's muscular dystrophy, hemophilia A, X-linked mental retardation, cystic fibrosis, spinal muscular atrophy, thalassemia, myotonic dystrophy, Huntington's disease, and balanced translocations, according to a list he presented from the European consortium.

If a couple decides to try PGD after being advised of its limitations, Dr. Strawn urged physicians to investigate a center's resources and standards before making a referral. “You need to look at quality control in your center,” he said, emphasizing that no certifying body regulates PGD.

The process is complex and prone to pitfalls such as contamination, Dr. Strawn said. “PGD is limited by the extreme complexity of setting up appropriate standardized accurate assays for single gene disorders.” Even if the clinician is experienced, he warned that tests from a single cell can be difficult to interpret. He cited false-negative rates of 1%–2% in the medical literature and said false positives can be as high as 10% depending on the criteria used. In some cases, he said, uncertainty can lead to good embryos being discarded.

Express mailing of specimens is an unresolved issue for Dr. Strawn. About half of centers mail specimens to outside laboratories, according to a telephone survey he conducted of all U.S. centers performing at least 200 cycles of in vitro fertilization in 2001. Among 101 programs that responded, 65 offered PGD; only 30 of these did their own analyses on site.

Staffing is another issue he urged referring physicians to investigate. Citing his own center's experience in developing its PGD program, he estimated that 1–2 years of preparation go into offering the service.

“Our people practiced in mouse embryos before we went live,” he said, noting that a high level of expertise is required for those doing the procedure and analyzing the results.

Similarly, Dr. Strawn recommended asking not only whether the center offers genetic counseling, but also about the training of the person doing the counseling. “A lot of people are offering PGD because they want to compete,” he said, urging physicians to look for a team effort: “It's not just one doctor who says he can do … everything.”

SCOTTSDALE, ARIZ. — Physicians referring infertile couples for preimplantation genetic diagnosis need to be realistic with their patients and vigilant in assessing the center that will do the testing, according to Estil J. Strawn Jr., M.D.

“You cannot say [to the patient] with any assurance that the baby is going to be perfect and you are going to have a good outcome,” Dr. Strawn told practitioners at the annual meeting of the Central Association of Obstetricians and Gynecologists.

Preimplantation genetic diagnosis (PGD) has a proven track record with several thousand births worldwide over the past 15 years, said Dr. Strawn, director of the division of reproductive endocrinology and infertility at the Medical College of Wisconsin in Milwaukee.

Nonetheless, it does not lead to a successful pregnancy more often than not. Dr. Strawn described the U.S. experience as comparable with the 25% pregnancy rate per embryo transfer reported by the European Society for Human Reproduction and Embryology PGD Consortium. In women aged 39 and older, he noted, the rate drops to 12%.

The consortium represents 66 centers, including 10 in the United States, according to Dr. Strawn. He said it reported 4,055 cycles reached the egg retrieval stage from 1999 to 2002 and 70% of those cycles reached the embryo transfer stage.

Summarizing PGD results at his own center, he said 22 retrievals for 18 patients have produced 156 embryos, 124 of which could be biopsied. Of those, 96 (77%) could be diagnosed by PDG, and 56 of those were deemed to be normal embryos.

The process led to four pregnancies in women up to age 37, but one turned out to be a blighted ovum. Despite more retrievals, transfers, and embryos in women older than 37 years, the result also was four pregnancies, three of which ended in miscarriage.

Two cycles in the younger patients did not result in transfers because aneuploidy was diagnosed in all the embryos. Dr. Strawn said the two women were encouraged to consider egg donation, and both are now pregnant. Though the numbers are small, he said more couples likely will be helped as technology improves.

Currently, most centers are screening for 6–8 chromosomes (13, 15, 16, 18, 21, 22, X, and Y), Dr. Strawn said. “What about the other 15 pairs?” he asked, noting that an embryo could carry a genetic defect for which PGD screening is not yet available.

Commonly screened conditions include Duchenne's and Becker's muscular dystrophy, hemophilia A, X-linked mental retardation, cystic fibrosis, spinal muscular atrophy, thalassemia, myotonic dystrophy, Huntington's disease, and balanced translocations, according to a list he presented from the European consortium.

If a couple decides to try PGD after being advised of its limitations, Dr. Strawn urged physicians to investigate a center's resources and standards before making a referral. “You need to look at quality control in your center,” he said, emphasizing that no certifying body regulates PGD.

The process is complex and prone to pitfalls such as contamination, Dr. Strawn said. “PGD is limited by the extreme complexity of setting up appropriate standardized accurate assays for single gene disorders.” Even if the clinician is experienced, he warned that tests from a single cell can be difficult to interpret. He cited false-negative rates of 1%–2% in the medical literature and said false positives can be as high as 10% depending on the criteria used. In some cases, he said, uncertainty can lead to good embryos being discarded.

Express mailing of specimens is an unresolved issue for Dr. Strawn. About half of centers mail specimens to outside laboratories, according to a telephone survey he conducted of all U.S. centers performing at least 200 cycles of in vitro fertilization in 2001. Among 101 programs that responded, 65 offered PGD; only 30 of these did their own analyses on site.

Staffing is another issue he urged referring physicians to investigate. Citing his own center's experience in developing its PGD program, he estimated that 1–2 years of preparation go into offering the service.

“Our people practiced in mouse embryos before we went live,” he said, noting that a high level of expertise is required for those doing the procedure and analyzing the results.

Similarly, Dr. Strawn recommended asking not only whether the center offers genetic counseling, but also about the training of the person doing the counseling. “A lot of people are offering PGD because they want to compete,” he said, urging physicians to look for a team effort: “It's not just one doctor who says he can do … everything.”

SCOTTSDALE, ARIZ. — Physicians referring infertile couples for preimplantation genetic diagnosis need to be realistic with their patients and vigilant in assessing the center that will do the testing, according to Estil J. Strawn Jr., M.D.

“You cannot say [to the patient] with any assurance that the baby is going to be perfect and you are going to have a good outcome,” Dr. Strawn told practitioners at the annual meeting of the Central Association of Obstetricians and Gynecologists.

Preimplantation genetic diagnosis (PGD) has a proven track record with several thousand births worldwide over the past 15 years, said Dr. Strawn, director of the division of reproductive endocrinology and infertility at the Medical College of Wisconsin in Milwaukee.

Nonetheless, it does not lead to a successful pregnancy more often than not. Dr. Strawn described the U.S. experience as comparable with the 25% pregnancy rate per embryo transfer reported by the European Society for Human Reproduction and Embryology PGD Consortium. In women aged 39 and older, he noted, the rate drops to 12%.

The consortium represents 66 centers, including 10 in the United States, according to Dr. Strawn. He said it reported 4,055 cycles reached the egg retrieval stage from 1999 to 2002 and 70% of those cycles reached the embryo transfer stage.

Summarizing PGD results at his own center, he said 22 retrievals for 18 patients have produced 156 embryos, 124 of which could be biopsied. Of those, 96 (77%) could be diagnosed by PDG, and 56 of those were deemed to be normal embryos.

The process led to four pregnancies in women up to age 37, but one turned out to be a blighted ovum. Despite more retrievals, transfers, and embryos in women older than 37 years, the result also was four pregnancies, three of which ended in miscarriage.

Two cycles in the younger patients did not result in transfers because aneuploidy was diagnosed in all the embryos. Dr. Strawn said the two women were encouraged to consider egg donation, and both are now pregnant. Though the numbers are small, he said more couples likely will be helped as technology improves.

Currently, most centers are screening for 6–8 chromosomes (13, 15, 16, 18, 21, 22, X, and Y), Dr. Strawn said. “What about the other 15 pairs?” he asked, noting that an embryo could carry a genetic defect for which PGD screening is not yet available.

Commonly screened conditions include Duchenne's and Becker's muscular dystrophy, hemophilia A, X-linked mental retardation, cystic fibrosis, spinal muscular atrophy, thalassemia, myotonic dystrophy, Huntington's disease, and balanced translocations, according to a list he presented from the European consortium.

If a couple decides to try PGD after being advised of its limitations, Dr. Strawn urged physicians to investigate a center's resources and standards before making a referral. “You need to look at quality control in your center,” he said, emphasizing that no certifying body regulates PGD.

The process is complex and prone to pitfalls such as contamination, Dr. Strawn said. “PGD is limited by the extreme complexity of setting up appropriate standardized accurate assays for single gene disorders.” Even if the clinician is experienced, he warned that tests from a single cell can be difficult to interpret. He cited false-negative rates of 1%–2% in the medical literature and said false positives can be as high as 10% depending on the criteria used. In some cases, he said, uncertainty can lead to good embryos being discarded.

Express mailing of specimens is an unresolved issue for Dr. Strawn. About half of centers mail specimens to outside laboratories, according to a telephone survey he conducted of all U.S. centers performing at least 200 cycles of in vitro fertilization in 2001. Among 101 programs that responded, 65 offered PGD; only 30 of these did their own analyses on site.

Staffing is another issue he urged referring physicians to investigate. Citing his own center's experience in developing its PGD program, he estimated that 1–2 years of preparation go into offering the service.

“Our people practiced in mouse embryos before we went live,” he said, noting that a high level of expertise is required for those doing the procedure and analyzing the results.

Similarly, Dr. Strawn recommended asking not only whether the center offers genetic counseling, but also about the training of the person doing the counseling. “A lot of people are offering PGD because they want to compete,” he said, urging physicians to look for a team effort: “It's not just one doctor who says he can do … everything.”

NICE, FRANCE — Advocates of endovascular aneurysm repair had high hopes that three large randomized, controlled trials conducted in Europe—EVAR I, EVAR II, and DREAM—would establish the procedure's superiority over open repair. Recently published results have been equivocal, however, and the closest an expert speakers' panel could come to consensus was that informed patient preference should be the deciding factor for the time being.

“I think today it's too close to call,” Jim A. Reekers, M.D., Ph.D., concluded after presentations by the principal investigators and a heated audience discussion at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe.

“The patient can make up his own mind because we don't have a definite answer yet,” said Dr. Reekers, a radiology professor at the University of Amsterdam, who discussed implications at the special session.

The three multicenter studies focused on abdominal aortic aneurysm repair.

British investigators led by Roger Greenhalgh, M.D., conducted the Endovascular Aneurysm Repair (EVAR) I trial at 34 centers in the United Kingdom. They enrolled patients who had aneurysms at least 5.5 cm in diameter and were fit for either endovascular or open repair.

EVAR I randomized 543 patients to stenting and 539 to open repair. Early results favored stenting, as its 30-day mortality rate of 1.7% was two-thirds less than the 4.7% reported for patients who had open repair (Lancet 2004;364:843–8).

By 4 years, however, all-cause mortality had leveled off at about 28% for both groups. The stenting cohort had fewer aneurysm-related deaths (4% vs. 7%), but more postoperative complications (41% vs. 9%).

The Dutch Randomized Endovascular Aneurysm Management (DREAM) trial group led by Jan D. Blankensteijn, M.D., enrolled patients with aneurysms at least 5 cm in length at 28 centers in the Netherlands and Belgium. It randomized 171 to stenting and 174 to open repair.

Again the early results favored stenting, which had an operative mortality rate of 1.2% vs. 4.6% in the open-repair group. Severe complications were fewer (N. Engl. J. Med. 2004;351:1607–18).

Once more, the results were not sustained. Two years after randomization, both cohorts had cumulative survival rates approaching 90%. Though open repair had more aneurysm-related deaths (5.7% vs. 2.1% for stenting), the investigators attributed the difference to the perioperative period. Aneurysm-related mortality was similar after the first 30 days. About two-thirds of both groups were free of moderate to severe complications (N. Engl. J. Med. 2005;352:2398–405).

Only unfit patients who were not candidates for surgery entered the EVAR II trial at 31 hospitals in the United Kingdom. The investigators assigned 166 to stenting and 172 to no intervention.

All told, 197 patients (including 47 who had been assigned to no intervention) underwent some form of aneurysm repair. During the follow-up period, 142 patients died; in 42 cases the deaths were related to aneurysms.

There were no significant differences in overall mortality or aneurysm-related survival (Lancet 2005;365:2187–92).

All three studies reported higher costs with stenting. The investigators attributed this, in part, to mandates for intensive follow-up in patients undergoing a new procedure.

The Dutch investigators similarly found costs to be about 4,500 euros higher with stenting, according to Dr. Blankensteijn, a professor of vascular surgery at the Radboud University Nijmegen (the Netherlands) Medical Center.

Dr. Greenhalgh, head of the department of vascular surgery at the Imperial College School of Medicine and Charing Cross Hospital in London, rejected a suggestion from the audience that the results favored open repair. “If open repair were clearly superior I would say EVAR is dead. If EVAR and open repair are neck and neck, then it is possible that EVAR is ahead,” he said. “At the 4-year point, there is a small but significant benefit of EVAR. Therefore EVAR is close to open repair or better.”

From a patient's perspective, he added, improved short-term risk with EVAR could be the deciding factor. For a man who is going to become a grandfather in 6 months, the early advantage could be more important than comparable survival at 4 years or the higher cost to society.

“But you have to say it comes at a cost, that [the patient] will be chained to your institution for period of time and might need repeat interventions,” Dr. Greenhalgh advised, adding that increased complications with stenting did not increase mortality. Most of the complications were minor.

NICE, FRANCE — Advocates of endovascular aneurysm repair had high hopes that three large randomized, controlled trials conducted in Europe—EVAR I, EVAR II, and DREAM—would establish the procedure's superiority over open repair. Recently published results have been equivocal, however, and the closest an expert speakers' panel could come to consensus was that informed patient preference should be the deciding factor for the time being.

“I think today it's too close to call,” Jim A. Reekers, M.D., Ph.D., concluded after presentations by the principal investigators and a heated audience discussion at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe.

“The patient can make up his own mind because we don't have a definite answer yet,” said Dr. Reekers, a radiology professor at the University of Amsterdam, who discussed implications at the special session.

The three multicenter studies focused on abdominal aortic aneurysm repair.

British investigators led by Roger Greenhalgh, M.D., conducted the Endovascular Aneurysm Repair (EVAR) I trial at 34 centers in the United Kingdom. They enrolled patients who had aneurysms at least 5.5 cm in diameter and were fit for either endovascular or open repair.

EVAR I randomized 543 patients to stenting and 539 to open repair. Early results favored stenting, as its 30-day mortality rate of 1.7% was two-thirds less than the 4.7% reported for patients who had open repair (Lancet 2004;364:843–8).

By 4 years, however, all-cause mortality had leveled off at about 28% for both groups. The stenting cohort had fewer aneurysm-related deaths (4% vs. 7%), but more postoperative complications (41% vs. 9%).

The Dutch Randomized Endovascular Aneurysm Management (DREAM) trial group led by Jan D. Blankensteijn, M.D., enrolled patients with aneurysms at least 5 cm in length at 28 centers in the Netherlands and Belgium. It randomized 171 to stenting and 174 to open repair.

Again the early results favored stenting, which had an operative mortality rate of 1.2% vs. 4.6% in the open-repair group. Severe complications were fewer (N. Engl. J. Med. 2004;351:1607–18).

Once more, the results were not sustained. Two years after randomization, both cohorts had cumulative survival rates approaching 90%. Though open repair had more aneurysm-related deaths (5.7% vs. 2.1% for stenting), the investigators attributed the difference to the perioperative period. Aneurysm-related mortality was similar after the first 30 days. About two-thirds of both groups were free of moderate to severe complications (N. Engl. J. Med. 2005;352:2398–405).

Only unfit patients who were not candidates for surgery entered the EVAR II trial at 31 hospitals in the United Kingdom. The investigators assigned 166 to stenting and 172 to no intervention.

All told, 197 patients (including 47 who had been assigned to no intervention) underwent some form of aneurysm repair. During the follow-up period, 142 patients died; in 42 cases the deaths were related to aneurysms.

There were no significant differences in overall mortality or aneurysm-related survival (Lancet 2005;365:2187–92).

All three studies reported higher costs with stenting. The investigators attributed this, in part, to mandates for intensive follow-up in patients undergoing a new procedure.

The Dutch investigators similarly found costs to be about 4,500 euros higher with stenting, according to Dr. Blankensteijn, a professor of vascular surgery at the Radboud University Nijmegen (the Netherlands) Medical Center.

Dr. Greenhalgh, head of the department of vascular surgery at the Imperial College School of Medicine and Charing Cross Hospital in London, rejected a suggestion from the audience that the results favored open repair. “If open repair were clearly superior I would say EVAR is dead. If EVAR and open repair are neck and neck, then it is possible that EVAR is ahead,” he said. “At the 4-year point, there is a small but significant benefit of EVAR. Therefore EVAR is close to open repair or better.”

From a patient's perspective, he added, improved short-term risk with EVAR could be the deciding factor. For a man who is going to become a grandfather in 6 months, the early advantage could be more important than comparable survival at 4 years or the higher cost to society.

“But you have to say it comes at a cost, that [the patient] will be chained to your institution for period of time and might need repeat interventions,” Dr. Greenhalgh advised, adding that increased complications with stenting did not increase mortality. Most of the complications were minor.

NICE, FRANCE — Advocates of endovascular aneurysm repair had high hopes that three large randomized, controlled trials conducted in Europe—EVAR I, EVAR II, and DREAM—would establish the procedure's superiority over open repair. Recently published results have been equivocal, however, and the closest an expert speakers' panel could come to consensus was that informed patient preference should be the deciding factor for the time being.

“I think today it's too close to call,” Jim A. Reekers, M.D., Ph.D., concluded after presentations by the principal investigators and a heated audience discussion at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe.

“The patient can make up his own mind because we don't have a definite answer yet,” said Dr. Reekers, a radiology professor at the University of Amsterdam, who discussed implications at the special session.

The three multicenter studies focused on abdominal aortic aneurysm repair.

British investigators led by Roger Greenhalgh, M.D., conducted the Endovascular Aneurysm Repair (EVAR) I trial at 34 centers in the United Kingdom. They enrolled patients who had aneurysms at least 5.5 cm in diameter and were fit for either endovascular or open repair.

EVAR I randomized 543 patients to stenting and 539 to open repair. Early results favored stenting, as its 30-day mortality rate of 1.7% was two-thirds less than the 4.7% reported for patients who had open repair (Lancet 2004;364:843–8).

By 4 years, however, all-cause mortality had leveled off at about 28% for both groups. The stenting cohort had fewer aneurysm-related deaths (4% vs. 7%), but more postoperative complications (41% vs. 9%).

The Dutch Randomized Endovascular Aneurysm Management (DREAM) trial group led by Jan D. Blankensteijn, M.D., enrolled patients with aneurysms at least 5 cm in length at 28 centers in the Netherlands and Belgium. It randomized 171 to stenting and 174 to open repair.

Again the early results favored stenting, which had an operative mortality rate of 1.2% vs. 4.6% in the open-repair group. Severe complications were fewer (N. Engl. J. Med. 2004;351:1607–18).

Once more, the results were not sustained. Two years after randomization, both cohorts had cumulative survival rates approaching 90%. Though open repair had more aneurysm-related deaths (5.7% vs. 2.1% for stenting), the investigators attributed the difference to the perioperative period. Aneurysm-related mortality was similar after the first 30 days. About two-thirds of both groups were free of moderate to severe complications (N. Engl. J. Med. 2005;352:2398–405).

Only unfit patients who were not candidates for surgery entered the EVAR II trial at 31 hospitals in the United Kingdom. The investigators assigned 166 to stenting and 172 to no intervention.

All told, 197 patients (including 47 who had been assigned to no intervention) underwent some form of aneurysm repair. During the follow-up period, 142 patients died; in 42 cases the deaths were related to aneurysms.

There were no significant differences in overall mortality or aneurysm-related survival (Lancet 2005;365:2187–92).

All three studies reported higher costs with stenting. The investigators attributed this, in part, to mandates for intensive follow-up in patients undergoing a new procedure.

The Dutch investigators similarly found costs to be about 4,500 euros higher with stenting, according to Dr. Blankensteijn, a professor of vascular surgery at the Radboud University Nijmegen (the Netherlands) Medical Center.

Dr. Greenhalgh, head of the department of vascular surgery at the Imperial College School of Medicine and Charing Cross Hospital in London, rejected a suggestion from the audience that the results favored open repair. “If open repair were clearly superior I would say EVAR is dead. If EVAR and open repair are neck and neck, then it is possible that EVAR is ahead,” he said. “At the 4-year point, there is a small but significant benefit of EVAR. Therefore EVAR is close to open repair or better.”

From a patient's perspective, he added, improved short-term risk with EVAR could be the deciding factor. For a man who is going to become a grandfather in 6 months, the early advantage could be more important than comparable survival at 4 years or the higher cost to society.

“But you have to say it comes at a cost, that [the patient] will be chained to your institution for period of time and might need repeat interventions,” Dr. Greenhalgh advised, adding that increased complications with stenting did not increase mortality. Most of the complications were minor.

NICE, FRANCE — A study of 77,000 Swedish cardiac patients found rates of renal failure were about twice as high following the use of iodixanol, an iso-osmolar contrast medium promoted as less toxic to the kidneys than competing low-osmolar products, Pontus B. Persson, M.D., Ph.D., reported at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe.

“From these data we conclude there is absolutely no indication that iodixanol is less harmful for kidney function than ioxaglate or iohexol,” Dr. Persson said.

“Actually, the contrary may be the case, but further studies are required to test if the contrary really may hold true,” concluded Dr. Persson, a renal physiologist at Humboldt University's Campus Charité Mitte in Berlin.

Dr. Persson and colleagues in Sweden compared patients in the Swedish Coronary Angiography and Angioplasty Registry to rehospitalizations with a diagnosis of renal failure in a Swedish hospital discharge register. The follow-up stretched as long as 12–14 years after percutaneous coronary interventions (PCI) and coronary angiography.

Within 1 year of coronary angiography or PCI, 70 of 5,728 patients given iohexol (Omnipaque) and 291 of 24,577 patients given ioxaglate (Hexabrix) returned to a hospital with a renal failure diagnosis. For both agents the proportion was 1.2%, Dr. Persson reported.

Among 47,543 patients for whom iodixanol (Visipaque) was used, rehospitalization with renal failure was about twice as common: 1,108 patients or 2.3%. The difference was statistically significant.

With attribution of a hazard ratio of 1 to the diagnosis of primary or secondary renal failure with iodixanol, the investigators calculated hazard ratios of 0.84 for iohexol and 0.77 for ioxaglate. These varied only slightly in subgroup analyses for patients with and without a prior history of renal failure, Dr. Persson said.

Two-thirds of the Swedish market is now using iodixanol, according to Dr. Persson, so the investigators also did a subgroup analysis of patients treated during the last 4 years to rule out a “time effect” on the findings.

“Again the data are rather clear,” he said. “Again we see a much higher risk for developing renal failure in the iodixanol group.”

In an interview at the meeting, he said that iodixanol is gaining a large share of the global market because it is thought to be less harmful to the kidneys. Low-osmolar contrast media were developed, he said, in an attempt to reduce significant side effects with the first generation of high-osmolar media. The low-osmolar media were much better tolerated, so biotechnology companies sought to reduce the osmolarity even further.

The strategy did not make sense to Dr. Persson for two reasons. First, he did not believe osmolarity was a problem. “Actually we [have been] giving diuretics with high osmolarity for decades, and nothing has happened,” he said.

Second, in reducing osmolarity, the new products increased the viscosity, “so it's more like syrup and not like water,” he said.

The higher viscosity can cause severe damage to the kidney because it clots the tubules, Dr. Persson said.

As a result of the changes, he contended, “Those contrast media that today are thought to be [safer] for the kidney lead to a twofold higher increase in renal failure diagnosis.”

Representatives of iodixanol's parent company, GE Healthcare Ltd. in Buckinghamshire, England, disputed Dr. Persson's findings in an interview after attending his presentation.

European medical director Hervé Lemaignen, M.D., and European brand manager Pamela McCord questioned whether nephropathy that was diagnosed long after use of iodixanol could be attributed to the dye.

They emphasized that the evidence in support of iodixanol being less neurotoxic comes from a randomized, double-blind, prospective, multicenter study (N. Engl. J. Med. 2003;348:491–9). It found that serum creatinine levels increased significantly less 3 days after angiography with iodixanol, compared with iohexol.

Dr. Persson said creatinine levels are only a surrogate measure for renal damage. He also contended that the published study was flawed because the patients in the iohexol group had diabetes for a mean of 18 years and therefore likely had more kidney damage than the iodixanol group, for whom the mean duration of diabetes was only 12.8 years.

The GE Healthcare officials maintained in turn that Dr. Persson's study was flawed, as the original database did not specify which contrast medium was used. “What they did was send out a questionnaire asking, 'Which contrast medium did you use in this year in your hospital?' So it is stretching it quite a little bit,” Ms. McCord said.

Dr. Lemaignen also challenged Dr. Persson's argument that increased viscosity makes iodixanol harmful to the kidneys. It is more viscous in the vial, he said, but it becomes thinner when mixed with blood.

NICE, FRANCE — A study of 77,000 Swedish cardiac patients found rates of renal failure were about twice as high following the use of iodixanol, an iso-osmolar contrast medium promoted as less toxic to the kidneys than competing low-osmolar products, Pontus B. Persson, M.D., Ph.D., reported at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe.

“From these data we conclude there is absolutely no indication that iodixanol is less harmful for kidney function than ioxaglate or iohexol,” Dr. Persson said.

“Actually, the contrary may be the case, but further studies are required to test if the contrary really may hold true,” concluded Dr. Persson, a renal physiologist at Humboldt University's Campus Charité Mitte in Berlin.

Dr. Persson and colleagues in Sweden compared patients in the Swedish Coronary Angiography and Angioplasty Registry to rehospitalizations with a diagnosis of renal failure in a Swedish hospital discharge register. The follow-up stretched as long as 12–14 years after percutaneous coronary interventions (PCI) and coronary angiography.

Within 1 year of coronary angiography or PCI, 70 of 5,728 patients given iohexol (Omnipaque) and 291 of 24,577 patients given ioxaglate (Hexabrix) returned to a hospital with a renal failure diagnosis. For both agents the proportion was 1.2%, Dr. Persson reported.

Among 47,543 patients for whom iodixanol (Visipaque) was used, rehospitalization with renal failure was about twice as common: 1,108 patients or 2.3%. The difference was statistically significant.

With attribution of a hazard ratio of 1 to the diagnosis of primary or secondary renal failure with iodixanol, the investigators calculated hazard ratios of 0.84 for iohexol and 0.77 for ioxaglate. These varied only slightly in subgroup analyses for patients with and without a prior history of renal failure, Dr. Persson said.

Two-thirds of the Swedish market is now using iodixanol, according to Dr. Persson, so the investigators also did a subgroup analysis of patients treated during the last 4 years to rule out a “time effect” on the findings.

“Again the data are rather clear,” he said. “Again we see a much higher risk for developing renal failure in the iodixanol group.”

In an interview at the meeting, he said that iodixanol is gaining a large share of the global market because it is thought to be less harmful to the kidneys. Low-osmolar contrast media were developed, he said, in an attempt to reduce significant side effects with the first generation of high-osmolar media. The low-osmolar media were much better tolerated, so biotechnology companies sought to reduce the osmolarity even further.

The strategy did not make sense to Dr. Persson for two reasons. First, he did not believe osmolarity was a problem. “Actually we [have been] giving diuretics with high osmolarity for decades, and nothing has happened,” he said.

Second, in reducing osmolarity, the new products increased the viscosity, “so it's more like syrup and not like water,” he said.

The higher viscosity can cause severe damage to the kidney because it clots the tubules, Dr. Persson said.

As a result of the changes, he contended, “Those contrast media that today are thought to be [safer] for the kidney lead to a twofold higher increase in renal failure diagnosis.”

Representatives of iodixanol's parent company, GE Healthcare Ltd. in Buckinghamshire, England, disputed Dr. Persson's findings in an interview after attending his presentation.

European medical director Hervé Lemaignen, M.D., and European brand manager Pamela McCord questioned whether nephropathy that was diagnosed long after use of iodixanol could be attributed to the dye.

They emphasized that the evidence in support of iodixanol being less neurotoxic comes from a randomized, double-blind, prospective, multicenter study (N. Engl. J. Med. 2003;348:491–9). It found that serum creatinine levels increased significantly less 3 days after angiography with iodixanol, compared with iohexol.

Dr. Persson said creatinine levels are only a surrogate measure for renal damage. He also contended that the published study was flawed because the patients in the iohexol group had diabetes for a mean of 18 years and therefore likely had more kidney damage than the iodixanol group, for whom the mean duration of diabetes was only 12.8 years.

The GE Healthcare officials maintained in turn that Dr. Persson's study was flawed, as the original database did not specify which contrast medium was used. “What they did was send out a questionnaire asking, 'Which contrast medium did you use in this year in your hospital?' So it is stretching it quite a little bit,” Ms. McCord said.

Dr. Lemaignen also challenged Dr. Persson's argument that increased viscosity makes iodixanol harmful to the kidneys. It is more viscous in the vial, he said, but it becomes thinner when mixed with blood.

NICE, FRANCE — A study of 77,000 Swedish cardiac patients found rates of renal failure were about twice as high following the use of iodixanol, an iso-osmolar contrast medium promoted as less toxic to the kidneys than competing low-osmolar products, Pontus B. Persson, M.D., Ph.D., reported at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe.

“From these data we conclude there is absolutely no indication that iodixanol is less harmful for kidney function than ioxaglate or iohexol,” Dr. Persson said.

“Actually, the contrary may be the case, but further studies are required to test if the contrary really may hold true,” concluded Dr. Persson, a renal physiologist at Humboldt University's Campus Charité Mitte in Berlin.

Dr. Persson and colleagues in Sweden compared patients in the Swedish Coronary Angiography and Angioplasty Registry to rehospitalizations with a diagnosis of renal failure in a Swedish hospital discharge register. The follow-up stretched as long as 12–14 years after percutaneous coronary interventions (PCI) and coronary angiography.

Within 1 year of coronary angiography or PCI, 70 of 5,728 patients given iohexol (Omnipaque) and 291 of 24,577 patients given ioxaglate (Hexabrix) returned to a hospital with a renal failure diagnosis. For both agents the proportion was 1.2%, Dr. Persson reported.

Among 47,543 patients for whom iodixanol (Visipaque) was used, rehospitalization with renal failure was about twice as common: 1,108 patients or 2.3%. The difference was statistically significant.

With attribution of a hazard ratio of 1 to the diagnosis of primary or secondary renal failure with iodixanol, the investigators calculated hazard ratios of 0.84 for iohexol and 0.77 for ioxaglate. These varied only slightly in subgroup analyses for patients with and without a prior history of renal failure, Dr. Persson said.

Two-thirds of the Swedish market is now using iodixanol, according to Dr. Persson, so the investigators also did a subgroup analysis of patients treated during the last 4 years to rule out a “time effect” on the findings.

“Again the data are rather clear,” he said. “Again we see a much higher risk for developing renal failure in the iodixanol group.”

In an interview at the meeting, he said that iodixanol is gaining a large share of the global market because it is thought to be less harmful to the kidneys. Low-osmolar contrast media were developed, he said, in an attempt to reduce significant side effects with the first generation of high-osmolar media. The low-osmolar media were much better tolerated, so biotechnology companies sought to reduce the osmolarity even further.

The strategy did not make sense to Dr. Persson for two reasons. First, he did not believe osmolarity was a problem. “Actually we [have been] giving diuretics with high osmolarity for decades, and nothing has happened,” he said.

Second, in reducing osmolarity, the new products increased the viscosity, “so it's more like syrup and not like water,” he said.

The higher viscosity can cause severe damage to the kidney because it clots the tubules, Dr. Persson said.

As a result of the changes, he contended, “Those contrast media that today are thought to be [safer] for the kidney lead to a twofold higher increase in renal failure diagnosis.”

Representatives of iodixanol's parent company, GE Healthcare Ltd. in Buckinghamshire, England, disputed Dr. Persson's findings in an interview after attending his presentation.

European medical director Hervé Lemaignen, M.D., and European brand manager Pamela McCord questioned whether nephropathy that was diagnosed long after use of iodixanol could be attributed to the dye.

They emphasized that the evidence in support of iodixanol being less neurotoxic comes from a randomized, double-blind, prospective, multicenter study (N. Engl. J. Med. 2003;348:491–9). It found that serum creatinine levels increased significantly less 3 days after angiography with iodixanol, compared with iohexol.

Dr. Persson said creatinine levels are only a surrogate measure for renal damage. He also contended that the published study was flawed because the patients in the iohexol group had diabetes for a mean of 18 years and therefore likely had more kidney damage than the iodixanol group, for whom the mean duration of diabetes was only 12.8 years.

The GE Healthcare officials maintained in turn that Dr. Persson's study was flawed, as the original database did not specify which contrast medium was used. “What they did was send out a questionnaire asking, 'Which contrast medium did you use in this year in your hospital?' So it is stretching it quite a little bit,” Ms. McCord said.

Dr. Lemaignen also challenged Dr. Persson's argument that increased viscosity makes iodixanol harmful to the kidneys. It is more viscous in the vial, he said, but it becomes thinner when mixed with blood.

SCOTTSDALE, ARIZ. — A prospective observational study of 1,656 cesarean deliveries has produced a detailed portrait of factors leading to longer than usual operating times and the effects of long procedures on pregnancy outcomes.

Cesarean delivery is likely to be prolonged when a woman is older or overweight, according to data presented by investigator Everett F. Magann, M.D., at the annual meeting of the Central Association of Obstetricians and Gynecologists.

Dr. Magann reported that maternal age above 35 years and a body mass index of 30 kg/m

Dr. Magann suggested that obstetricians may want to consider requesting stronger backup when they perform a cesarean delivery on a woman who is older and overweight.

“Maybe call a partner in and get more experienced help,” he said, noting that longer procedures had negative effects on pregnancy outcomes.

“The most significant is that blood loss was increased, so you want to do your operation in a timely manner,” Dr. Magann of the Naval Medical Center in Portsmouth, Va., said in an interview.

He and his associates were surprised by two factors that turned out not to prolong cesarean delivery. “Surprisingly, endometriosis and wound separation were unrelated to the operation time,” they reported in a list of conclusions on the poster.

In the interview, Dr. Magann mentioned that the review also brought another surprise: “We didn't find [that] the longer you operate, the greater your risk of infection,” he said, noting that increased risk of infection is often assumed in this situation.

Women with preexisting hypertension or a low segment transverse scar from a previous cesarean operation were more likely to have longer procedures.

Other factors that contributed significantly to added time in the operating room were a uterus incision other than a transverse incision, having a first-year resident as the primary physician, and performance of a sterilization procedure during the operation.

Blood loss in excess of 1,000 mL was more than twice as likely (odds ratio 2.16) in operations lasting 30–60 minutes, compared with those lasting 30 minutes or less. The odds ratio rose to 6.93 in operations that lasted longer.

Patients whose cesarean delivery lasted longer than 60 minutes also were nearly three times more likely to have their umbilical artery pH level register below 7.1. In addition, their babies were nearly three times more likely to have Apgar scores below 7 at 5 minutes.

Risk of respiratory distress syndrome also increased with longer operating time; the odds ratio became 2.43 at 30–60 minutes and 4.07 after 60 minutes.

Nearly three-quarters (1,207/1,656) of women in the study were African American. Another 19% (315/1,656) were white. The women, more than half of whom were nulliparous, were 24.8 years old on average.

The investigators reported that 693 women had a previous cesarean delivery. About a third of this group (232 women) had at least two prior cesarean deliveries.

Complications occurred in 728 pregnancies (44%). Preeclampsia was the most common, occurring in 337 women. It was followed by gestational diabetes in 134 women, preterm premature rupture of membranes (76), congenital abnormalities (53), and intrauterine growth restriction (28).

Forty minutes was the median operative time in the study, which divided the women into three cohorts for the analysis. Only 386 deliveries (23%) were completed in 30 minutes or less. Nearly two-thirds (1,070 deliveries) took 31–60 minutes. The remaining 200 deliveries lasted longer than 60 minutes.

The study showed that the only factors associated with shortened delivery time were maternal age less than 18 years and fetal distress.

SCOTTSDALE, ARIZ. — A prospective observational study of 1,656 cesarean deliveries has produced a detailed portrait of factors leading to longer than usual operating times and the effects of long procedures on pregnancy outcomes.

Cesarean delivery is likely to be prolonged when a woman is older or overweight, according to data presented by investigator Everett F. Magann, M.D., at the annual meeting of the Central Association of Obstetricians and Gynecologists.

Dr. Magann reported that maternal age above 35 years and a body mass index of 30 kg/m

Dr. Magann suggested that obstetricians may want to consider requesting stronger backup when they perform a cesarean delivery on a woman who is older and overweight.

“Maybe call a partner in and get more experienced help,” he said, noting that longer procedures had negative effects on pregnancy outcomes.

“The most significant is that blood loss was increased, so you want to do your operation in a timely manner,” Dr. Magann of the Naval Medical Center in Portsmouth, Va., said in an interview.

He and his associates were surprised by two factors that turned out not to prolong cesarean delivery. “Surprisingly, endometriosis and wound separation were unrelated to the operation time,” they reported in a list of conclusions on the poster.

In the interview, Dr. Magann mentioned that the review also brought another surprise: “We didn't find [that] the longer you operate, the greater your risk of infection,” he said, noting that increased risk of infection is often assumed in this situation.

Women with preexisting hypertension or a low segment transverse scar from a previous cesarean operation were more likely to have longer procedures.

Other factors that contributed significantly to added time in the operating room were a uterus incision other than a transverse incision, having a first-year resident as the primary physician, and performance of a sterilization procedure during the operation.

Blood loss in excess of 1,000 mL was more than twice as likely (odds ratio 2.16) in operations lasting 30–60 minutes, compared with those lasting 30 minutes or less. The odds ratio rose to 6.93 in operations that lasted longer.

Patients whose cesarean delivery lasted longer than 60 minutes also were nearly three times more likely to have their umbilical artery pH level register below 7.1. In addition, their babies were nearly three times more likely to have Apgar scores below 7 at 5 minutes.

Risk of respiratory distress syndrome also increased with longer operating time; the odds ratio became 2.43 at 30–60 minutes and 4.07 after 60 minutes.

Nearly three-quarters (1,207/1,656) of women in the study were African American. Another 19% (315/1,656) were white. The women, more than half of whom were nulliparous, were 24.8 years old on average.

The investigators reported that 693 women had a previous cesarean delivery. About a third of this group (232 women) had at least two prior cesarean deliveries.

Complications occurred in 728 pregnancies (44%). Preeclampsia was the most common, occurring in 337 women. It was followed by gestational diabetes in 134 women, preterm premature rupture of membranes (76), congenital abnormalities (53), and intrauterine growth restriction (28).

Forty minutes was the median operative time in the study, which divided the women into three cohorts for the analysis. Only 386 deliveries (23%) were completed in 30 minutes or less. Nearly two-thirds (1,070 deliveries) took 31–60 minutes. The remaining 200 deliveries lasted longer than 60 minutes.

The study showed that the only factors associated with shortened delivery time were maternal age less than 18 years and fetal distress.

SCOTTSDALE, ARIZ. — A prospective observational study of 1,656 cesarean deliveries has produced a detailed portrait of factors leading to longer than usual operating times and the effects of long procedures on pregnancy outcomes.

Cesarean delivery is likely to be prolonged when a woman is older or overweight, according to data presented by investigator Everett F. Magann, M.D., at the annual meeting of the Central Association of Obstetricians and Gynecologists.

Dr. Magann reported that maternal age above 35 years and a body mass index of 30 kg/m

Dr. Magann suggested that obstetricians may want to consider requesting stronger backup when they perform a cesarean delivery on a woman who is older and overweight.

“Maybe call a partner in and get more experienced help,” he said, noting that longer procedures had negative effects on pregnancy outcomes.

“The most significant is that blood loss was increased, so you want to do your operation in a timely manner,” Dr. Magann of the Naval Medical Center in Portsmouth, Va., said in an interview.

He and his associates were surprised by two factors that turned out not to prolong cesarean delivery. “Surprisingly, endometriosis and wound separation were unrelated to the operation time,” they reported in a list of conclusions on the poster.

In the interview, Dr. Magann mentioned that the review also brought another surprise: “We didn't find [that] the longer you operate, the greater your risk of infection,” he said, noting that increased risk of infection is often assumed in this situation.

Women with preexisting hypertension or a low segment transverse scar from a previous cesarean operation were more likely to have longer procedures.

Other factors that contributed significantly to added time in the operating room were a uterus incision other than a transverse incision, having a first-year resident as the primary physician, and performance of a sterilization procedure during the operation.

Blood loss in excess of 1,000 mL was more than twice as likely (odds ratio 2.16) in operations lasting 30–60 minutes, compared with those lasting 30 minutes or less. The odds ratio rose to 6.93 in operations that lasted longer.

Patients whose cesarean delivery lasted longer than 60 minutes also were nearly three times more likely to have their umbilical artery pH level register below 7.1. In addition, their babies were nearly three times more likely to have Apgar scores below 7 at 5 minutes.

Risk of respiratory distress syndrome also increased with longer operating time; the odds ratio became 2.43 at 30–60 minutes and 4.07 after 60 minutes.

Nearly three-quarters (1,207/1,656) of women in the study were African American. Another 19% (315/1,656) were white. The women, more than half of whom were nulliparous, were 24.8 years old on average.

The investigators reported that 693 women had a previous cesarean delivery. About a third of this group (232 women) had at least two prior cesarean deliveries.

Complications occurred in 728 pregnancies (44%). Preeclampsia was the most common, occurring in 337 women. It was followed by gestational diabetes in 134 women, preterm premature rupture of membranes (76), congenital abnormalities (53), and intrauterine growth restriction (28).

Forty minutes was the median operative time in the study, which divided the women into three cohorts for the analysis. Only 386 deliveries (23%) were completed in 30 minutes or less. Nearly two-thirds (1,070 deliveries) took 31–60 minutes. The remaining 200 deliveries lasted longer than 60 minutes.

The study showed that the only factors associated with shortened delivery time were maternal age less than 18 years and fetal distress.

SCOTTSDALE, ARIZ. — Perioperative use of magnesium sulfate during cesarean delivery did not relieve short- or long-term pain for women in a double-blind, randomized controlled trial of 120 women.

Neither high nor low doses produced any benefit in pain control or satisfaction compared with saline solution in the intent-to-treat analysis.

Other than the expected variation in serum concentrations of magnesium, the only significant differences were slightly greater blood loss and longer time to solid foods for the women given magnesium sulfate, study investigator Everett F. Magann, M.D., reported at the annual meeting of the Central Association of Obstetricians and Gynecologists.

“Given the absence of any apparent analgesic benefit and the apparent increase in blood loss, we do not believe that the perioperative administration is clinically useful,” said Dr. Magann, a captain in the U.S. Naval Reserve who currently practices at Naval Medical Center Portsmouth (Va.).

The investigators wanted to test magnesium sulfate because it has been used successfully to control pain from cancer and some surgical procedures in other fields of medicine, according to Dr. Magann. He said they had found one abstract reporting that preeclamptic women undergoing cesarean deliveries had less pain than did matched controls.

“The use of magnesium is very familiar to obstetricians,” he said. “It is used in pregnancies complicated by preeclampsia and in pregnancies complicated by preterm labor to delay delivery until corticosteroids have been administered to accelerate fetal lung maturity and lessen neonatal morbidity.”

Magnesium is believed to alter pain processing, because it acts as an antagonist to receptors in the spinal cord.

“There is experimental evidence that magnesium may modulate acute pain [and] reduce postsurgical pain intensity and/or the dosage of analgesics,” Dr. Magann said.

He conducted the study at King Edward Memorial Hospital for Women, Perth, Western Australia, with colleagues from the hospital and the University of Western Australia.

From October 2002 to June 2004, they enrolled 131 women aged 18 years or older who were undergoing a planned cesarean delivery of a single infant, had no contraindication to magnesium sulfate, and consented to a combined spinal-epidural anesthetic.

Patients and health care providers were blinded to the randomization of the women. Eleven women withdrew consent or did not proceed to cesarean delivery. Although 15 women did not receive a full 24-hour infusion of magnesium sulfate and 9 did not adhere to analgesic protocol, these patients were included in the intent-to-treat analysis.

The high-dose group of 42 patients was given 50 mg/kg of magnesium sulfate an hour before surgery and 2 g/hour afterward.

A low-dose cohort of 38 women received a 25 mg/kg loading dose followed by 1 g/hour after surgery.

Forty women in a control group received a saline solution.

There were no significant differences between groups in baseline characteristics such as age and weight.

Although none of the women had serious complications requiring transfusions, Dr. Magann reported blood loss as 400 mL for the control group, 475 mL for the low-dose patients, and 500 mL in women at the higher dose.

Time to solid foods was 3 hours in the control group and 6 hours in the two cohorts on magnesium sulfate.

At 6 weeks, none of the women were using analgesic drugs. They also did not have any wound pain with movement or pressure.

Discussant Paul Ogburn, M.D., said the paper answered “fairly definitively no” to the question of whether magnesium sulfate would relieve cesarean pain.

Dr. Ogburn, director of maternal-fetal medicine at the State University of New York at Stony Brook, also suggested that the incidental findings of increased blood loss and delay until solid food is consumed may be important clinically.

SCOTTSDALE, ARIZ. — Perioperative use of magnesium sulfate during cesarean delivery did not relieve short- or long-term pain for women in a double-blind, randomized controlled trial of 120 women.

Neither high nor low doses produced any benefit in pain control or satisfaction compared with saline solution in the intent-to-treat analysis.

Other than the expected variation in serum concentrations of magnesium, the only significant differences were slightly greater blood loss and longer time to solid foods for the women given magnesium sulfate, study investigator Everett F. Magann, M.D., reported at the annual meeting of the Central Association of Obstetricians and Gynecologists.

“Given the absence of any apparent analgesic benefit and the apparent increase in blood loss, we do not believe that the perioperative administration is clinically useful,” said Dr. Magann, a captain in the U.S. Naval Reserve who currently practices at Naval Medical Center Portsmouth (Va.).

The investigators wanted to test magnesium sulfate because it has been used successfully to control pain from cancer and some surgical procedures in other fields of medicine, according to Dr. Magann. He said they had found one abstract reporting that preeclamptic women undergoing cesarean deliveries had less pain than did matched controls.

“The use of magnesium is very familiar to obstetricians,” he said. “It is used in pregnancies complicated by preeclampsia and in pregnancies complicated by preterm labor to delay delivery until corticosteroids have been administered to accelerate fetal lung maturity and lessen neonatal morbidity.”

Magnesium is believed to alter pain processing, because it acts as an antagonist to receptors in the spinal cord.

“There is experimental evidence that magnesium may modulate acute pain [and] reduce postsurgical pain intensity and/or the dosage of analgesics,” Dr. Magann said.

He conducted the study at King Edward Memorial Hospital for Women, Perth, Western Australia, with colleagues from the hospital and the University of Western Australia.

From October 2002 to June 2004, they enrolled 131 women aged 18 years or older who were undergoing a planned cesarean delivery of a single infant, had no contraindication to magnesium sulfate, and consented to a combined spinal-epidural anesthetic.

Patients and health care providers were blinded to the randomization of the women. Eleven women withdrew consent or did not proceed to cesarean delivery. Although 15 women did not receive a full 24-hour infusion of magnesium sulfate and 9 did not adhere to analgesic protocol, these patients were included in the intent-to-treat analysis.

The high-dose group of 42 patients was given 50 mg/kg of magnesium sulfate an hour before surgery and 2 g/hour afterward.

A low-dose cohort of 38 women received a 25 mg/kg loading dose followed by 1 g/hour after surgery.

Forty women in a control group received a saline solution.

There were no significant differences between groups in baseline characteristics such as age and weight.

Although none of the women had serious complications requiring transfusions, Dr. Magann reported blood loss as 400 mL for the control group, 475 mL for the low-dose patients, and 500 mL in women at the higher dose.

Time to solid foods was 3 hours in the control group and 6 hours in the two cohorts on magnesium sulfate.

At 6 weeks, none of the women were using analgesic drugs. They also did not have any wound pain with movement or pressure.

Discussant Paul Ogburn, M.D., said the paper answered “fairly definitively no” to the question of whether magnesium sulfate would relieve cesarean pain.

Dr. Ogburn, director of maternal-fetal medicine at the State University of New York at Stony Brook, also suggested that the incidental findings of increased blood loss and delay until solid food is consumed may be important clinically.

SCOTTSDALE, ARIZ. — Perioperative use of magnesium sulfate during cesarean delivery did not relieve short- or long-term pain for women in a double-blind, randomized controlled trial of 120 women.

Neither high nor low doses produced any benefit in pain control or satisfaction compared with saline solution in the intent-to-treat analysis.

Other than the expected variation in serum concentrations of magnesium, the only significant differences were slightly greater blood loss and longer time to solid foods for the women given magnesium sulfate, study investigator Everett F. Magann, M.D., reported at the annual meeting of the Central Association of Obstetricians and Gynecologists.

“Given the absence of any apparent analgesic benefit and the apparent increase in blood loss, we do not believe that the perioperative administration is clinically useful,” said Dr. Magann, a captain in the U.S. Naval Reserve who currently practices at Naval Medical Center Portsmouth (Va.).

The investigators wanted to test magnesium sulfate because it has been used successfully to control pain from cancer and some surgical procedures in other fields of medicine, according to Dr. Magann. He said they had found one abstract reporting that preeclamptic women undergoing cesarean deliveries had less pain than did matched controls.

“The use of magnesium is very familiar to obstetricians,” he said. “It is used in pregnancies complicated by preeclampsia and in pregnancies complicated by preterm labor to delay delivery until corticosteroids have been administered to accelerate fetal lung maturity and lessen neonatal morbidity.”

Magnesium is believed to alter pain processing, because it acts as an antagonist to receptors in the spinal cord.

“There is experimental evidence that magnesium may modulate acute pain [and] reduce postsurgical pain intensity and/or the dosage of analgesics,” Dr. Magann said.

He conducted the study at King Edward Memorial Hospital for Women, Perth, Western Australia, with colleagues from the hospital and the University of Western Australia.

From October 2002 to June 2004, they enrolled 131 women aged 18 years or older who were undergoing a planned cesarean delivery of a single infant, had no contraindication to magnesium sulfate, and consented to a combined spinal-epidural anesthetic.

Patients and health care providers were blinded to the randomization of the women. Eleven women withdrew consent or did not proceed to cesarean delivery. Although 15 women did not receive a full 24-hour infusion of magnesium sulfate and 9 did not adhere to analgesic protocol, these patients were included in the intent-to-treat analysis.

The high-dose group of 42 patients was given 50 mg/kg of magnesium sulfate an hour before surgery and 2 g/hour afterward.

A low-dose cohort of 38 women received a 25 mg/kg loading dose followed by 1 g/hour after surgery.

Forty women in a control group received a saline solution.

There were no significant differences between groups in baseline characteristics such as age and weight.

Although none of the women had serious complications requiring transfusions, Dr. Magann reported blood loss as 400 mL for the control group, 475 mL for the low-dose patients, and 500 mL in women at the higher dose.

Time to solid foods was 3 hours in the control group and 6 hours in the two cohorts on magnesium sulfate.

At 6 weeks, none of the women were using analgesic drugs. They also did not have any wound pain with movement or pressure.

Discussant Paul Ogburn, M.D., said the paper answered “fairly definitively no” to the question of whether magnesium sulfate would relieve cesarean pain.

Dr. Ogburn, director of maternal-fetal medicine at the State University of New York at Stony Brook, also suggested that the incidental findings of increased blood loss and delay until solid food is consumed may be important clinically.

SCOTTSDALE, ARIZ. — Researchers stopped a randomized, controlled trial comparing strategies to prevent postpartum hemorrhage when they found a 20-minute delay in delivery of the placenta to be much rarer than reported in the medical literature.

The investigators, who had expected 8% of women to take longer than 20 minutes, concluded that the third stage of labor exceeds this time frame in just 0.5% of pregnancies. Only 8 of the first 1,607 women recruited for the study took longer than 20 minutes to deliver the placenta, Everett F. Magann, M.D., reported in a poster at the annual meeting of the Central Association of Obstetricians and Gynecologists.

The multicenter trial was designed to determine whether 20 minutes would be a more optimal cutoff than 30 minutes for manually removing a placenta that had not delivered spontaneously. It also assessed risk factors for postpartum hemorrhage.

The investigators concluded that the new information from the aborted study “suggests that placental delivery should be considered earlier, perhaps at 10 minutes.”

Dr. Magann of the Naval Medical Center in Portsmouth, Va., said in an interview that they are redesigning the study to consider a cutoff of 10 minutes. “We think that is an appropriate place to look next,” he said.

Meanwhile, he and his colleagues stopped recruitment in the United States and Australia, as the original 7,300-woman goal could not produce statistically significant results on the study's primary end points with so few women reaching 20 or 30 minutes. “We saw we would need 110,000 women to get sample size,” he said.

Guidelines for manual delivery of the placenta are based on studies that are 15–20 years old, according to Dr. Magann. He noted that some practice guidelines are based on just one study, and others were never tested in clinical trials. He said, “I like to look at it again and say, 'Is that right?'”

When to intervene in the third stage of labor is an important issue in the Third World, he added. About 515,000 women die in childbirth each year, he said; the World Health Organization attributes a quarter of these deaths to postpartum hemorrhage.

More than half the women enrolled in the aborted study (56%) were Caucasian. Another 32% were African American. Their average age was 25.3 years, and their babies had reached a median gestational age of 39 weeks when delivered.

The median duration of labor was 7.2 hours for the first stage, 0.6 hours for the second stage, and 4 minutes for the third stage. A total of 1,431 placentas (89%) were delivered spontaneously within 10 minutes of birth. Another 168 placentas (10.5%) took 10–20 minutes for spontaneous delivery.

Older maternal age and duration of the second stage of labor beyond 2 hours were predictive of a prolonged third stage of labor.

Dr. Magann reported 42 women (3%) had postpartum hemorrhages. Duration of the third stage of labor beyond 10 minutes was a significant risk factor, with the odds ratios increasing from 2.68 for 10–15 minutes to 7.88 for durations longer than 15 minutes. Incidence of postpartum hemorrhage was 7% and 12%, respectively, in these time frames.

For women who delivered their placentas spontaneously within 5–10 minutes, however, the risk of postpartum hemorrhage was similar to the experience in women who delivered in less than 5 minutes (OR 1.16).

Chorioamnionitis at time of delivery was another significant simultaneous risk factor (OR 6.44) for postpartum hemorrhage within 24 hours of delivery. An overextended uterus also increased risk significantly (OR 2.85), whether due to a fetus weighing more than 4,000 g or to hydramnios.

Risk of postpartum hemorrhage was significantly less, however, in nulliparous women (OR 0.42).

SCOTTSDALE, ARIZ. — Researchers stopped a randomized, controlled trial comparing strategies to prevent postpartum hemorrhage when they found a 20-minute delay in delivery of the placenta to be much rarer than reported in the medical literature.

The investigators, who had expected 8% of women to take longer than 20 minutes, concluded that the third stage of labor exceeds this time frame in just 0.5% of pregnancies. Only 8 of the first 1,607 women recruited for the study took longer than 20 minutes to deliver the placenta, Everett F. Magann, M.D., reported in a poster at the annual meeting of the Central Association of Obstetricians and Gynecologists.

The multicenter trial was designed to determine whether 20 minutes would be a more optimal cutoff than 30 minutes for manually removing a placenta that had not delivered spontaneously. It also assessed risk factors for postpartum hemorrhage.

The investigators concluded that the new information from the aborted study “suggests that placental delivery should be considered earlier, perhaps at 10 minutes.”

Dr. Magann of the Naval Medical Center in Portsmouth, Va., said in an interview that they are redesigning the study to consider a cutoff of 10 minutes. “We think that is an appropriate place to look next,” he said.

Meanwhile, he and his colleagues stopped recruitment in the United States and Australia, as the original 7,300-woman goal could not produce statistically significant results on the study's primary end points with so few women reaching 20 or 30 minutes. “We saw we would need 110,000 women to get sample size,” he said.

Guidelines for manual delivery of the placenta are based on studies that are 15–20 years old, according to Dr. Magann. He noted that some practice guidelines are based on just one study, and others were never tested in clinical trials. He said, “I like to look at it again and say, 'Is that right?'”

When to intervene in the third stage of labor is an important issue in the Third World, he added. About 515,000 women die in childbirth each year, he said; the World Health Organization attributes a quarter of these deaths to postpartum hemorrhage.

More than half the women enrolled in the aborted study (56%) were Caucasian. Another 32% were African American. Their average age was 25.3 years, and their babies had reached a median gestational age of 39 weeks when delivered.

The median duration of labor was 7.2 hours for the first stage, 0.6 hours for the second stage, and 4 minutes for the third stage. A total of 1,431 placentas (89%) were delivered spontaneously within 10 minutes of birth. Another 168 placentas (10.5%) took 10–20 minutes for spontaneous delivery.

Older maternal age and duration of the second stage of labor beyond 2 hours were predictive of a prolonged third stage of labor.

Dr. Magann reported 42 women (3%) had postpartum hemorrhages. Duration of the third stage of labor beyond 10 minutes was a significant risk factor, with the odds ratios increasing from 2.68 for 10–15 minutes to 7.88 for durations longer than 15 minutes. Incidence of postpartum hemorrhage was 7% and 12%, respectively, in these time frames.

For women who delivered their placentas spontaneously within 5–10 minutes, however, the risk of postpartum hemorrhage was similar to the experience in women who delivered in less than 5 minutes (OR 1.16).

Chorioamnionitis at time of delivery was another significant simultaneous risk factor (OR 6.44) for postpartum hemorrhage within 24 hours of delivery. An overextended uterus also increased risk significantly (OR 2.85), whether due to a fetus weighing more than 4,000 g or to hydramnios.

Risk of postpartum hemorrhage was significantly less, however, in nulliparous women (OR 0.42).

SCOTTSDALE, ARIZ. — Researchers stopped a randomized, controlled trial comparing strategies to prevent postpartum hemorrhage when they found a 20-minute delay in delivery of the placenta to be much rarer than reported in the medical literature.

The investigators, who had expected 8% of women to take longer than 20 minutes, concluded that the third stage of labor exceeds this time frame in just 0.5% of pregnancies. Only 8 of the first 1,607 women recruited for the study took longer than 20 minutes to deliver the placenta, Everett F. Magann, M.D., reported in a poster at the annual meeting of the Central Association of Obstetricians and Gynecologists.

The multicenter trial was designed to determine whether 20 minutes would be a more optimal cutoff than 30 minutes for manually removing a placenta that had not delivered spontaneously. It also assessed risk factors for postpartum hemorrhage.

The investigators concluded that the new information from the aborted study “suggests that placental delivery should be considered earlier, perhaps at 10 minutes.”

Dr. Magann of the Naval Medical Center in Portsmouth, Va., said in an interview that they are redesigning the study to consider a cutoff of 10 minutes. “We think that is an appropriate place to look next,” he said.

Meanwhile, he and his colleagues stopped recruitment in the United States and Australia, as the original 7,300-woman goal could not produce statistically significant results on the study's primary end points with so few women reaching 20 or 30 minutes. “We saw we would need 110,000 women to get sample size,” he said.

Guidelines for manual delivery of the placenta are based on studies that are 15–20 years old, according to Dr. Magann. He noted that some practice guidelines are based on just one study, and others were never tested in clinical trials. He said, “I like to look at it again and say, 'Is that right?'”

When to intervene in the third stage of labor is an important issue in the Third World, he added. About 515,000 women die in childbirth each year, he said; the World Health Organization attributes a quarter of these deaths to postpartum hemorrhage.

More than half the women enrolled in the aborted study (56%) were Caucasian. Another 32% were African American. Their average age was 25.3 years, and their babies had reached a median gestational age of 39 weeks when delivered.

The median duration of labor was 7.2 hours for the first stage, 0.6 hours for the second stage, and 4 minutes for the third stage. A total of 1,431 placentas (89%) were delivered spontaneously within 10 minutes of birth. Another 168 placentas (10.5%) took 10–20 minutes for spontaneous delivery.

Older maternal age and duration of the second stage of labor beyond 2 hours were predictive of a prolonged third stage of labor.

Dr. Magann reported 42 women (3%) had postpartum hemorrhages. Duration of the third stage of labor beyond 10 minutes was a significant risk factor, with the odds ratios increasing from 2.68 for 10–15 minutes to 7.88 for durations longer than 15 minutes. Incidence of postpartum hemorrhage was 7% and 12%, respectively, in these time frames.

For women who delivered their placentas spontaneously within 5–10 minutes, however, the risk of postpartum hemorrhage was similar to the experience in women who delivered in less than 5 minutes (OR 1.16).

Chorioamnionitis at time of delivery was another significant simultaneous risk factor (OR 6.44) for postpartum hemorrhage within 24 hours of delivery. An overextended uterus also increased risk significantly (OR 2.85), whether due to a fetus weighing more than 4,000 g or to hydramnios.

Risk of postpartum hemorrhage was significantly less, however, in nulliparous women (OR 0.42).

VERSAILLES, FRANCE — The presence of sclerosis/induration is the cornerstone criterion for confirming the diagnosis of juvenile systemic sclerosis, according to conclusions drawn from an international consensus conference.

In addition, Francesco Zulian, M.D., explained at the 12th European Pediatric Rheumatology Congress, that the diagnosis also requires that patients have at least two of the following minor criteria:

Skin: Sclerodactyly.

Vascular: Raynaud's phenomenon, digital ulcers, nailfold capillary changes.

Gastrointestinal: Gastrointestinal reflux, dysphasia.

Respiratory: Lung fibrosis, pulmonary hypertension, diffuse lung capacity for carbon monoxide.

Renal: Renal crisis, new-onset hypertension.

Cardiac: Heart failure, arrhythmias.

Neurologic: Carpal tunnel syndrome, peripheral neuropathy.

Musculoskeletal: Arthritis, myositis, tendon friction rubs.

Serology: Antinuclear antibodies, systemic sclerosis-selective autoantibodies.

Dr. Zulian of the University of Padua (Italy) emphasized that these criteria are in the draft stage. The next step will be to validate the classification with trials in adult and juvenile patients. Although the system is based on childhood cases, he suggested it might also improve the rate of diagnosing the disease accurately in adults.

An added benefit of the project is that “we [now] have an international database we are going to open up and use for future research,” he told this newspaper in an interview. “This is a very rare disease, and we need cooperation between different countries. It is a devastating disease, and the mortality is high.”

Fifty-five centers in 24 countries contributed data on 205 patients. The cases included 153 patients with systemic sclerosis, 26 patients with overlap syndrome, and another 26 patients with mixed connective tissue disease.

The project, which began in 2002, initially identified 86 preliminary classification criteria, including the three major criteria: sclerosis/induration, Raynaud's phenomenon, and sclerodactyly.

A group of 16 adult and pediatric rheumatologist experts then used the criteria to diagnose 160 patients from records presented at a consensus conference. The case files included children with systemic sclerosis and the confounding diseases.

The experts were able to reach consensus on 127 patients (79%): 70 with juvenile systemic sclerosis and 57 without the condition. They were unable to reach a consensus on 33 patients (21%), Dr. Zulian reported.

As a result of that concensus process, the 86 possible diagnostic factors were narrowed down to a short list. The objectives were “to propose classification criteria that mimic as much as possible the evaluation of physicians attending the consensus conference,” and to evaluate how well the criteria distinguish patients who have juvenile systemic sclerosis from those who do not, he said.

VERSAILLES, FRANCE — The presence of sclerosis/induration is the cornerstone criterion for confirming the diagnosis of juvenile systemic sclerosis, according to conclusions drawn from an international consensus conference.

In addition, Francesco Zulian, M.D., explained at the 12th European Pediatric Rheumatology Congress, that the diagnosis also requires that patients have at least two of the following minor criteria:

Skin: Sclerodactyly.

Vascular: Raynaud's phenomenon, digital ulcers, nailfold capillary changes.

Gastrointestinal: Gastrointestinal reflux, dysphasia.

Respiratory: Lung fibrosis, pulmonary hypertension, diffuse lung capacity for carbon monoxide.

Renal: Renal crisis, new-onset hypertension.

Cardiac: Heart failure, arrhythmias.

Neurologic: Carpal tunnel syndrome, peripheral neuropathy.

Musculoskeletal: Arthritis, myositis, tendon friction rubs.

Serology: Antinuclear antibodies, systemic sclerosis-selective autoantibodies.

Dr. Zulian of the University of Padua (Italy) emphasized that these criteria are in the draft stage. The next step will be to validate the classification with trials in adult and juvenile patients. Although the system is based on childhood cases, he suggested it might also improve the rate of diagnosing the disease accurately in adults.

An added benefit of the project is that “we [now] have an international database we are going to open up and use for future research,” he told this newspaper in an interview. “This is a very rare disease, and we need cooperation between different countries. It is a devastating disease, and the mortality is high.”

Fifty-five centers in 24 countries contributed data on 205 patients. The cases included 153 patients with systemic sclerosis, 26 patients with overlap syndrome, and another 26 patients with mixed connective tissue disease.

The project, which began in 2002, initially identified 86 preliminary classification criteria, including the three major criteria: sclerosis/induration, Raynaud's phenomenon, and sclerodactyly.

A group of 16 adult and pediatric rheumatologist experts then used the criteria to diagnose 160 patients from records presented at a consensus conference. The case files included children with systemic sclerosis and the confounding diseases.

The experts were able to reach consensus on 127 patients (79%): 70 with juvenile systemic sclerosis and 57 without the condition. They were unable to reach a consensus on 33 patients (21%), Dr. Zulian reported.

As a result of that concensus process, the 86 possible diagnostic factors were narrowed down to a short list. The objectives were “to propose classification criteria that mimic as much as possible the evaluation of physicians attending the consensus conference,” and to evaluate how well the criteria distinguish patients who have juvenile systemic sclerosis from those who do not, he said.

VERSAILLES, FRANCE — The presence of sclerosis/induration is the cornerstone criterion for confirming the diagnosis of juvenile systemic sclerosis, according to conclusions drawn from an international consensus conference.

In addition, Francesco Zulian, M.D., explained at the 12th European Pediatric Rheumatology Congress, that the diagnosis also requires that patients have at least two of the following minor criteria:

Skin: Sclerodactyly.

Vascular: Raynaud's phenomenon, digital ulcers, nailfold capillary changes.

Gastrointestinal: Gastrointestinal reflux, dysphasia.

Respiratory: Lung fibrosis, pulmonary hypertension, diffuse lung capacity for carbon monoxide.

Renal: Renal crisis, new-onset hypertension.

Cardiac: Heart failure, arrhythmias.

Neurologic: Carpal tunnel syndrome, peripheral neuropathy.

Musculoskeletal: Arthritis, myositis, tendon friction rubs.

Serology: Antinuclear antibodies, systemic sclerosis-selective autoantibodies.

Dr. Zulian of the University of Padua (Italy) emphasized that these criteria are in the draft stage. The next step will be to validate the classification with trials in adult and juvenile patients. Although the system is based on childhood cases, he suggested it might also improve the rate of diagnosing the disease accurately in adults.

An added benefit of the project is that “we [now] have an international database we are going to open up and use for future research,” he told this newspaper in an interview. “This is a very rare disease, and we need cooperation between different countries. It is a devastating disease, and the mortality is high.”

Fifty-five centers in 24 countries contributed data on 205 patients. The cases included 153 patients with systemic sclerosis, 26 patients with overlap syndrome, and another 26 patients with mixed connective tissue disease.

The project, which began in 2002, initially identified 86 preliminary classification criteria, including the three major criteria: sclerosis/induration, Raynaud's phenomenon, and sclerodactyly.

A group of 16 adult and pediatric rheumatologist experts then used the criteria to diagnose 160 patients from records presented at a consensus conference. The case files included children with systemic sclerosis and the confounding diseases.

The experts were able to reach consensus on 127 patients (79%): 70 with juvenile systemic sclerosis and 57 without the condition. They were unable to reach a consensus on 33 patients (21%), Dr. Zulian reported.

As a result of that concensus process, the 86 possible diagnostic factors were narrowed down to a short list. The objectives were “to propose classification criteria that mimic as much as possible the evaluation of physicians attending the consensus conference,” and to evaluate how well the criteria distinguish patients who have juvenile systemic sclerosis from those who do not, he said.