JAMA news releases are made available to the public after 3 pm US Central time on the first 4 Tuesdays of each month. The Archives Journals news releases are made available to the public after 3 pm Central time on Mondays. We also provide a list of previous news releases.

JAMA NEWS RELEASES
(Embargoed for Release: 3 p.m. CT, Tuesday, May 17, 2005)

JAMA NEWS RELEASES

   TIMING OF INTRODUCTION OF GLUTEN INTO INFANT'S DIET ASSOCIATED WITH APPEARANCE OF CELIAC DISEASE IN CHILDREN AT RISK FOR THIS DISEASE

   SEVERAL FACTORS CAN INCREASE RISK FOR RECURRENT BLOOD CLOT

   BREAST CANCER CHEMOTHERAPY REGIMEN ASSOCIATED WITH LIFE-THREATENING COMPLICATIONS

JAMA REPORT (VIDEO NEWS RELEASE AND SCRIPT)

   VIDEO: Windows Media | Quicktime

   INFANT CEREAL LINKED TO INCREASED RISK OF CELIAC DISEASE — AGE OF INTRODUCTION IS CRITICAL FACTOR

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TV Note: This week's JAMA video news release is on the timing of introducing gluten into an infant's diet and risk of celiac disease. The release will be fed Tuesday, May 17, from 9:00 - 9:30 a.m. ET on Intelsat America 6 (formerly Telstar 6), Transponder 11 (C-Band) and from 2:00 - 2:30 p.m. ET on Intelsat America 6, Transponder 11 (C-Band). For more information, call 312/464-JAMA (5262).

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Embargoed for Release: 3 p.m. CT, TUESDAY, May 17, 2005
Media Advisory: To contact Jill M. Norris, M.P.H., Ph.D., call Tonya Ewers at 303-724-1524. To contact editorialist Richard J. Farrell, M.D., call Bonnie Prescott at 617-667-7306.

CHICAGO—Children with gluten exposure from cereal grains at 4 to 6 months of age have a lower risk of celiac disease than children with exposure before or after this time period, according to a study in the May 18 issue of JAMA.

Celiac disease, also called gluten-sensitive enteropathy (a disease of the intestinal tract), is characterized by chronic inflammation in the small intestine, induced by gluten (a protein substance) present in wheat, rye, or barley, according to background information in the article. The classic form of celiac disease typically presents in early childhood with abdominal pain and diarrhea, malabsorption, and nutrient deficiencies. Most patients with celiac disease carry the gene HLA-DRB1*03 (usually associated with HLA-DQ2) or HLA-DRB1*04 (associated with HLA-DQ8). These gene variations also confer increased risk for type 1 diabetes; thus, individuals with type 1 diabetes and their first-degree relatives have increased risk of celiac disease. However, few genetically susceptible individuals develop celiac disease, even though virtually all individuals in wheat-consuming populations are exposed to gluten. This suggests that additional factors play a role in disease risk.

Jill M. Norris, M.P.H., Ph.D., of the University of Colorado at Denver and Health Sciences Center, and colleagues investigated whether there was an association between timing of exposure to cereals and subsequent development of celiac disease autoimmunity (CDA) in children with a genetic predisposition for celiac disease. The study was conducted from 1994-2004 with 1,560 children at increased risk for celiac disease or type 1 diabetes, as defined by possession of either HLA-DR3 or DR4 gene variations, or having a first-degree relative with type 1 diabetes. The average follow-up was 4.8 years.

Fifty-one children developed CDA. The researchers found that findings adjusted for HLA-DR3 status indicated that children exposed to foods containing wheat, barley, or rye (gluten-containing foods) in the first 3 months of life (3 [6 percent] CDA positive vs. 40 [3 percent] CDA negative) had a 5-fold increased risk of CDA compared with children exposed to gluten-containing foods at 4 to 6 months (12 [23 percent] CDA positive vs. 574 [38 percent] CDA negative). Children not exposed to gluten until the seventh month or later (36 [71 percent] CDA positive vs. 895 [59 percent] CDA negative) had a marginally increased risk of CDA compared with those exposed at 4 to 6 months.

Of the 25 children with biopsy-confirmed CDA-positive status, 3 (12 percent) were exposed to wheat, barley, or rye at 1 to 3 months, 3 (12 percent) at 4 to 6 months, and 19 (76 percent) at 7 months or later vs. 40 (3 percent), 583 (38 percent), and 912 (59 percent) of unaffected children, respectively. Initial exposure to wheat, barley, or rye in the first 3 months or in the seventh month or later significantly increased risk of biopsy-confirmed CDA compared with exposure at 4 to 6 months.

"Given that our study population was selected for specific genetic and family history characteristics, our findings are generalizable only to children at increased risk for celiac disease. We cannot exclude the possibility that earlier exposure to gluten simply leads to earlier appearance of CDA and that all exposed at-risk children will eventually develop CDA. Long-term follow-up of this cohort may be necessary to address this question. Given the small number of CDA-positive children and wide CIs [confidence intervals], we recommend that these results be confirmed in other prospective cohorts of children at risk for celiac disease before any interventions are implemented," the authors write.
(JAMA. 2005;293:2343-2351. Available post-embargo at jama.com)

Editor's Note: This research was supported by grants from the National Institutes of Health, Autoimmune Prevention Center, Diabetes Endocrine Research Center, Clinical Investigation & Bioinformatics Core, and the General Clinical Research Centers Program, National Center for Research Resources.

EDITORIAL: INFANT GLUTEN AND CELIAC DISEASE — TOO EARLY, TOO LATE, TOO MUCH, TOO MANY QUESTIONS

In an accompanying editorial, Richard J. Farrell, M.D., of Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, discusses the findings by Norris et al.

"Long-term follow-up of this cohort may help clarify whether earlier exposure to gluten results in a real increased risk of celiac disease, an earlier presentation of the disease, or neither. Longitudinal data may also clarify whether earlier exposure to gluten simply leads to earlier appearance of tTG [tissue transglutaminase, an autoantigen] or whether all exposed at-risk children will eventually develop tTG."

"Ultimately, much larger, international prospective studies are required to unravel the complex interplay between multiple infant diet factors and an immature immune system in a genetically predisposed individual at risk for celiac disease. Only then will it be possible to know the true effect of ...exclusive vs. partial breastfeeding, gluten amount vs. gluten timing, and infant cereal vs. follow-up infant formula on celiac disease risk and presentation," Dr. Farrell writes.
(JAMA. 2005;293:2410-2412. Available post-embargo at jama.com)

For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: mediarelations{at}jama-archives.org.

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Embargoed for Release: 3 p.m. CT, TUESDAY, May 17, 2005
Media Advisory: To contact corresponding author Frits R. Rosendaal, M.D., Ph.D., email: f.r.rosendaal{at}lumc.nl.

SEVERAL FACTORS CAN INCREASE RISK FOR RECURRENT BLOOD CLOT

CHICAGO—Patients who have a blood clot are at high risk of having another one, and men have more than twice the risk as women, according to a study in the May 18 issue of JAMA.

While estimates of the overall risk of a thrombotic (blood clot) event recurrence vary, reports on contributing factors are contradictory, according to background information in the article. Knowledge of the risk of a thrombotic event recurrence and its determinants is relevant for clinical policy regarding screening for thrombophilia (increased risk for blood clot), duration of anticoagulant treatment, and treatment strategies in circumstances of increased risk.

Sverre C. Christiansen, M.D., of the Leiden University Medical Center, Leiden, the Netherlands, and colleagues conducted a follow-up study of 474 patients aged 18 to 70 years who had a thrombotic event to determine the risk of recurrence and the effect of several thrombophilic risk factors on the risk of recurrence. The Leiden Thrombophilia Study (LETS) was conducted from 1988 through 1992 and patients were followed-up through 2000.

A total of 474 patients were followed up an average of 7.3 years and recurrent thrombotic events occurred in 90 patients. The researchers "found an annual risk of thrombotic event recurrence of 2.6 percent. The cumulative risk of recurrence was 12.4 percent after 5 years and 16.5 percent after 7 years of follow-up. Although the incidence rate was slightly higher in the first 2 years, at an annual rate of 3.2 percent, the risk of thrombotic event recurrence persisted at a high level of more than 2 percent during the following years."

The risk of thrombotic event recurrence was 2.7 times higher in men than in women. Patients whose initial thrombotic event was idiopathic (unknown cause) had nearly two times the risk of a thrombotic event recurrence than patients whose initial event was provoked. Women who used oral contraceptives during follow-up had a higher thrombotic event recurrence rate than those who did not.

"Solitary laboratory abnormalities appear not to predict the risk of recurrence. Therefore, extensive, if any, thrombophilic work-up after a first thrombotic event is not likely to confer a clinical benefit to the patient. Similarly, a differential treatment with regard to duration of oral anticoagulation in patients with prothrombotic abnormalities does not seem to be rational based on these data. Adequate prophylactic anticoagulation during risk situations for all patients with a history of a thrombotic event may be the most important measure to reduce the risk of a recurrent event. Women using oral contraceptives should be advised to refrain from further use. The decision on optimal duration of anticoagulation therapy after a first thrombotic event will probably need to be based on clinical factors (male sex, oral contraceptive use, and idiopathic first thrombotic event) rather than laboratory abnormalities," the authors conclude.
(JAMA. 2005;293:2352-2361. Available post-embargo at jama.com)

Editor's Note: The LETS study was funded by a grant from the Netherlands Heart Foundation and the follow-up study was funded by a grant from the Prevention Fund/ZonMW.

For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: mediarelations{at}jama-archives.org.

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Embargoed for Release: 3 p.m. CT, TUESDAY, May 17, 2005
Media Advisory: To contact Etienne G. C. Brain, M.D., email: e.brain{at}stcloud-huguenin.org.

BREAST CANCER CHEMOTHERAPY REGIMEN ASSOCIATED WITH LIFE-THREATENING COMPLICATIONS

CHICAGO—The chemotherapy regimen of doxorubicin plus docetaxel, used to treat breast cancer in a clinical trial, was associated with an increased risk of serious complications, resulting in the premature termination of the trial, according to a study in the May 18 issue of JAMA.

Combinations of certain breast cancer drug classes have proven superior to some single classes alone in advanced or metastatic breast cancer, according to background information in the article. Uncertainties remain regarding the optimal schedule of administration of combination regimens, as well as safety and cost issues, and whether some drugs should be used outside of clinical trials.

Etienne G. C. Brain, M.D., of the René Huguenin Cancer Centre, Saint-Cloud, France and colleagues describe the adverse events associated with the chemotherapy in a breast cancer trial. The randomized multicenter study (Reposant sur des Arguments Pronostiques et Prédictifs [RAPP]-01) compared the effectiveness of 2 chemotherapy regimens. The trial included 627 women aged 18-70 years, who had primary unilateral breast cancer and either a moderate number of positive axillary lymph nodes (3 or less) or no positive axillary lymph nodes, but were at a high risk of relapse. Patients were treated at 11 French cancer referral centers from June 1999 through January 2003. Patients received doxorubicin plus docetaxel, or doxorubicin plus cyclophosphamide, given postoperatively for 4 courses.

The trial was terminated prematurely when 2 deaths related to drug toxicity and 1 case of bowel perforation with peritonitis (inflammation of the membrane of the abdomen) occurred among patients with febrile neutropenia (very low level of white blood cells accompanied by fever, a condition that indicates the patient may have a potentially life-threatening infection), all in the doxorubicin-docetaxel group. The incidence of febrile neutropenia was significantly higher with the doxorubicin-docetaxel regimen (40.8 percent) than with the doxorubicin-cyclophosphamide regimen (7.1 percent). The follow-up has been too short (24 months) to analyze the primary end point, which was the disease-free survival rate at 5 years.

"The rate of toxic death has decreased far below 0.10 percent in more recent trials," the authors write. "We observed a much higher rate of toxic death (0.63 percent) with the doxorubicin-docetaxel regimen. The higher rate of febrile neutropenia observed with doxorubicin-docetaxel than with doxorubicin-cyclophosphamide in our trial may have induced severe immunosuppression and contributed to the high rate of toxic death, which was 3 times as much as that observed in [another trial], in which 3 of 7 deaths were attributable to sequential docetaxel immunosuppression among 1,584 patients (0.19 percent)."

"In conclusion, this study shows that the doxorubicin-docetaxel combination is associated with an increased risk of severe sepsis and life-threatening complications. Clinicians should be aware of the potential toxicity of the doxorubicin-docetaxel regimen and consider the preventive use of granulocyte colony-stimulating factor (G-CSF) and/or antibiotics (neither of which was recommended at the time of our trial) in both the adjuvant and metastatic settings. At this time the doxorubicin-docetaxel regimen should not be recommended outside of carefully designed clinical trials," the authors conclude.
(JAMA. 2005;293:2367-2371. Available post-embargo at jama.com)

Editor's Note: René Huguenin Cancer Centre was the sponsor of the RAPP-01 trial. This work was also supported in part by Aventis-Oncology France and the Ligue Régionale Contre le Cancer du Département des Yvelines. Aventis-Oncology France supplied the docetaxel.

For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: mediarelations{at}jama-archives.org.

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JAMA REPORTS

VIDEO: Windows Media | Quicktime

INFANT CEREAL LINKED TO INCREASED RISK OF CELIAC DISEASE — AGE OF INTRODUCTION IS CRITICAL FACTOR

VIDEO:
NAT SOT UP FULL FOR :02
Mom feeding baby infant cereal/talking to baby

AUDIO:
"It's good stuff."

VIDEO:
B-ROLL
More mom feeding baby infant cereal
Close-up baby's messy face

AUDIO:
DOCTORS RECOMMEND THAT MOST BABIES START EATING INFANT CEREAL AROUND SIX MONTHS OF AGE. BUT FOR BABIES AT RISK OF CELIAC DISEASE, SIX MONTHS MAY BE TOO LATE.

VIDEO:
SOT/FULL
@ :12
Super: Jill Norris, M.P.H., Ph.D.
Univ. of Colorado Health Sciences Center
Runs :09

AUDIO:
"People with celiac disease have an intolerance to the dietary protein called gluten, which is found in wheat, barley and rye. When they eat foods containing gluten, their immune system reacts by damaging the small intestine."

VIDEO:
B-ROLL
Dr. Norris walking down hall
Dr. Norris with colleague going over data
Mom feeding baby
Baby eating

AUDIO:
DR. JILL NORRIS AND HER COLLEAGUES AT UNIVERSITY OF COLORADO HEALTH SCIENCES CENTER IDENTIFIED 15-HUNDRED BABIES AT RISK OF CELIAC DISEASE. THE BABIES HAD A FAMILY HISTORY OF THE DISEASE OR OF TYPE 1 DIABETES, OR A BLOOD TEST SHOWED THEY WERE PRE-DISPOSED FOR CELIAC DISEASE. THE RESEARCHERS TRACKED THE BABIES AND THEIR EATING HABITS FOR MORE THAN FOUR YEARS.

VIDEO:
SOT/FULL
Jill Norris, M.P.H., Ph.D.
Univ. of Colorado Health Sciences Center
Runs :06

AUDIO:
"We asked the parents to tell us what they introduced in the infant diet and when they introduced it."

VIDEO:
B-ROLL
Baby eating cereal
GFX/JAMA COVER

AUDIO:
IN PARTICULAR, WHEN THE BABIES FIRST ATE CEREALS CONTAINING GLUTEN. THE FINDINGS APPEAR IN JAMA, THE JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION.

VIDEO:
SOT/FULL
Jill Norris, M.P.H., Ph.D.
Univ. of Colorado Health Sciences Center
Runs :11

AUDIO:
"We found that children who were exposed to gluten in the first three months of life had a 5-fold increased risk of celiac disease autoimmunity, compared to children who weren't exposed until 4 to 6 months of age."

VIDEO:
B-ROLL
Baby eating cereal

AUDIO:
AND BABIES WHO STARTED EATING GLUTEN AFTER SIX MONTHS OF AGE WERE ALSO AT INCREASED RISK.

VIDEO:
SOT/FULL
Jill Norris, M.P.H., Ph.D.
Univ. of Colorado Health Sciences Center
Runs :11

AUDIO:
"It's been thought that delaying the introduction of gluten in the infant diet may have a beneficial effect with regarding to preventing celiac disease. However, our study suggests that's not the case."

VIDEO:
B-ROLL
Boys playing basketball
Boys playing basketball with their mother

AUDIO:
EIGHT-YEAR OLD TWINS DAVID AND MICHAEL POOLE HAVE CELIAC DISEASE. THEIR MOM STARTED FEEDING THEM CEREAL CONTAINING GLUTEN WHEN THEY WERE ABOUT EIGHT MONTHS OF AGE. SHE WAS SURPRISED TO HEAR HOW IMPORTANT TIMING MAY BE.

VIDEO:
SOT/FULL
@1:37
Super: Monica Poole
Mother
Runs: 03

AUDIO:
"It's a striking finding."

VIDEO:
B-ROLL
Mom feeding infant
Wheat flour ingredient on cereal box highlighted
Barley cereal

AUDIO:
A FINDING THAT NEW PARENTS CAN CONSIDER AS THEY DECIDE WHEN TO INTRODUCE WHEAT, RYE OR BARLEY CEREALS INTO THEIR BABY'S DIET. THIS IS MAVIS PRALL WITH THE JAMA REPORT.