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September 8, 2009JAMA news releases are made available to the public after 3 pm US Central time on the first 4 Tuesdays of each month. The Archives of 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. THIS WEEK'S CONTENTS
JAMA NEWS RELEASES
(Embargoed for Release: 3 p.m. CT Tuesday, September 8, 2009)
JAMA REPORT (VIDEO SCRIPT)
INFORMATION CONTAINED IN THESE NEWS RELEASES IS PROTECTED BY COPYRIGHT. JOURNAL ATTRIBUTION IS REQUIRED. JOURNALISTS CAN NOW ACCESS EMBARGOED JAMA/ARCHIVES STUDIES ON-LINE. Go to www.jamamedia.org for more information and to apply for access. TV Note: PLEASE NOTE, FEED TIMES ARE NOW 15 MINUTES. This week's JAMA Report video is on how alterations in a brain pathway is associated with certain symptoms of ADHD. The report will be fed Tuesday, Sept. 8, from 9:00 - 9:15 a.m. ET and 2:00 - 2:15 p.m. ET, on Galaxy 28 (C-Band), Transponder 19, downlink frequency: 4080 vertical, audio 6.2/6.8. For more information, call 312/464-JAMA. The JAMA Report video is also now available on Pathfire every Tuesday. Please look for the JAMA Report "channel". Save the Date: The Sixth International Congress on Peer Review and Biomedical Publication will be held September 10-12 in Vancouver, Canada. New research will be presented on peer review and. the other processes used to evaluate and disseminate medical information. Program and registration information is included at the end of this email. Please Note: The FOR THE MEDIA website now has a search feature to enable media to find previous JAMA/Archives news releases on specific medical topics. This search feature link is located on the home page at www.jamamedia.org EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, September 8, 2009
Using Measurement of Chemical in Blood May Help Reduce Overuse of Antibiotics for Lower Respiratory Tract Infections
CHICAGO—The use of guidelines for treatment of lower respiratory tract infections such as bronchitis and pneumonia determined by measurements of a chemical in the blood known as procalcitonin resulted in lower rates of antibiotic use and associated adverse effects, and similar rates of adverse outcomes compared to standard guidelines, according to a study in the September 9 issue of JAMA. "Unnecessary antibiotic use importantly contributes to increasing bacterial resistance and increases medical costs and the risks of drug-related adverse events. The most frequent indication for antibiotic prescriptions in the northwestern hemisphere is lower respiratory tract infections (LRTIs),which range in severity from self-limited acute bronchitis to severe acute exacerbation of chronic obstructive pulmonary disease (COPD), and to life-threatening bacterial community-acquired pneumonia (CAP)," the authors write. The researchers add that clinical signs and symptoms are unreliable in distinguishing viral from bacterial LRTI, and that as many as 75 percent of patients with LRTI are treated with antibiotics despite the predominantly viral origin of their infection. An approach that has been suggested to estimate the probability of bacterial origin in LRTI is the measurement of serum procalcitonin (PCT), with evidence from smaller trials suggesting that use of clinical algorithms (a procedure consisting of a sequence of steps to calculate or determine a specific output) based on certain PCT measurements could lead to needed reductions in antibiotic use, according to background information in the article. Levels of this chemical are high in patients with a bacterial infection but low in those with a viral infection. Philipp Schuetz, M.D., of University Hospital Basel, Switzerland, and colleagues conducted a large, multicenter trial to compare use of PCT guidelines with standard guidelines and subsequent antibiotic use. The study, conducted at 6 tertiary care hospitals in Switzerland, included 1,359 patients with mostly severe LRTIs. Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital. The researchers found that "the rate of overall adverse outcomes was similar in the PCT and control groups [15.4 percent vs. 18.9 percent]. The mean [average] duration of antibiotics exposure in the PCT vs. control groups was lower in all patients [5.7 vs. 8.7 days; relative change, -34.8 percent] and in the subgroups of patients with community-acquired pneumonia [n = 925, 7.2 vs. 10.7 days; -32.4 percent], exacerbation of chronic obstructive pulmonary disease [n = 228, 2.5 vs. 5.1 days; -50.4 percent], and acute bronchitis [n = 151, 1.0 vs. 2.8 days; -65.0 percent]. Antibiotic-associated adverse effects were less frequent in the PCT group [19.8 percent vs. 28.1 percent]."
"In conclusion, particularly in countries with higher antibiotic prescription rates than Switzerland, PCT guidance will have substantial clinical and public health implications to reduce antibiotic exposure and associated risks of adverse effects and antibiotic resistance," the authors write.
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. Editorial: Measurement of Serum Procalcitonin — A Step Closer to Tailored Care for Respiratory Infections?
In an accompanying editorial, Donald M. Yealy, M.D., of the University of Pittsburgh School of Medicine, and Michael J. Fine, M.D., M.Sc., of the University of Pittsburgh Medical Center, comment on the findings of this study.
"...Schuetz and colleagues have charted the waters for more tailored management of LRTIs by demonstrating that a PCT-guided decision rule safely diminishes antibiotic use and adverse effects in patients with such illness. In the future, an increasing number of such 'theragnostic' approaches are likely to be possible in which blood samples or tissue specimens can be used to quickly measure microbial fragments, circulating markers of organ stress and system responses, and genetic patterns that predict clinical outcomes, drug effectiveness, or both. PCT-guided care is an initial step toward such a tailored approach that could lead to more appropriate antibiotic therapy for patients with LRTI, while promoting antibiotic stewardship for the entire population."
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org. EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, September 8, 2009
Administering Dopamine to Brain-Dead Kidney Donor May Improve Outcome of Transplant
CHICAGO—Pretreatment of a brain-dead, heart-beating kidney donor with dopamine reduced the need for dialysis for the kidney recipient in the first week after the transplantation, according to a study in the September 9 issue of JAMA. "The majority of kidneys transplanted worldwide are retrieved from deceased heart-beating donors. As a consequence of brain death, the kidney graft is exposed to numerous injurious events prior to transplantation that predispose it to functional impairment after transplantation," according to background information provided by the authors. While limiting organ injury through medical donor management may have an effect on the transplantation outcome, current recommendations are based on limited evidence from observational studies only. Peter Schnuelle, M.D., Ph.D., of the University Medical Centre Mannheim, Germany, and colleagues assessed the effectiveness of donor pretreatment with dopamine by measuring the postoperative incidence of dialyses in kidney transplant recipients who received a kidney graft from a brain-dead donor. The trial included 264 deceased heart-beating donors and 487 subsequent kidney transplants performed at 60 European centers between March 2004 and August 2007, with final follow-up through December 2008. Donors were randomized to receive low-dose dopamine, which was infused for a median (midpoint) of 344 minutes. The researchers found that donor dopamine treatment resulted in a significantly reduced use of dialysis after transplantation. Fewer recipients in the treatment group (24.7 percent) needed multiple dialyses before renal function recovered than did recipients in the nondopamine group (35.4 percent). "Accordingly, when both kidneys of each donor were transplanted, pretreatment of 10 donors prevented the need for multiple dialyses in 2 renal transplant recipients," the researchers write. The data also indicated that multiple dialyses increased the chances of graft failure in the long-term, whereas a single dialysis posttransplant did not. "Dopamine resulted in significant but clinically meaningless increases in the donor's systolic blood pressure and urine production before surgical recovery of the kidneys but had no influence on outcome," the authors note.
"In conclusion, this study shows that pretreatment of the deceased heart-beating donor with low-dose dopamine reduces the need for dialysis in the recipient after kidney transplantation."
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org. EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, September 8, 2009
Study Identifies Genetic Variation Associated With Increased Risk of Liver Disease for Patients With Cystic Fibrosis
CHICAGO—A genetic analysis indicates that a certain gene variation in patients with cystic fibrosis may significantly increase their risk of developing severe liver disease, according to a study in the September 9 issue of JAMA. A small fraction (about 3 - 5 percent) of patients with cystic fibrosis (CF) develop severe liver disease characterized by cirrhosis with portal hypertension (CFLD; increase in blood pressure caused by obstruction in the liver). Previous research has suggested that genetic variability that is not associated with the cystic fibrosis transmembrane conductance regulator (CFTR) gene may contribute to the risk for severe liver disease. Jaclyn R. Bartlett, Ph.D., of the University of North Carolina at Chapel Hill, and colleagues examined nine variants in five genes previously studied in CF liver disease to determine the association between non-CFTR genetic variations and CFLD. The initial study compared genetic variations in the candidate genes in persons with CFLD (n = 124) and in control patients without CFLD (n = 843), with a second study testing these findings in different populations of patients with (n = 136) and without (n = 1,088) CFLD. The researchers found that of the 5 genes studied, "only the SERPINA1 Z allele [an alternative form of a gene] was significantly associated with CFLD and portal hypertension. This polymorphism is relatively uncommon in CF [about 2.2 percent of patients with CF are carriers], but the odds ratio for association with severe liver disease is relatively high [about 5 times higher] for the contribution of a genetic modifier to a mendelian [genetic] disorder. Moreover, the estimated population-attributable risk among patients with CF is 6.7 percent. From a clinical perspective, a rare variant with large penetrance (such as the Z allele) may be more useful than a common variant with low penetrance in screening for genetic polymorphisms."
"The identification of the SERPINA1 Z allele as the first marker for the development of severe liver disease in CF illustrates the possibility of identifying CF risk factors early in life, conceptually as a secondary component of neonatal screening after the diagnosis of CF is confirmed," the authors conclude.
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org. EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, September 8, 2009
Alterations in Brain Dopamine Pathway Appears to be Associated With Certain Symptoms of ADHD
CHICAGO—Results from brain scans suggest an association between a reduction in the transmission of dopamine markers with symptoms of inattention for individuals with attention deficit/hyperactivity disorder (ADHD), according to a preliminary study in the September 9 issue of JAMA. ADHD is a childhood psychiatric disorder that frequently persists into adulthood, and is estimated to affect 3 percent to 5 percent of the U.S. adult population, which makes it one of the most prevalent of all psychiatric disorders, according to background information in the article. Previous research has indicated that dopamine (a neurotransmitter essential for the normal functioning of the central nervous system) transmission is disrupted in some pathways of the brain in ADHD. Nora D. Volkow, M.D., of the National Institute on Drug Abuse, Bethesda, Md., and colleagues conducted a study to determine whether there are abnormalities in the mesoaccumbens (site of the dopamine reward pathway in the mid-brain) in patients with ADHD. The researchers produced brain images with positron emission tomography (PET) to measure dopamine synaptic markers (transporters and D2/D3 receptors) in 53 nonmedicated adults with ADHD and 44 healthy controls. Among the findings of the authors: "This study provides evidence in favor of the predicted disruption in the mesoaccumbens dopamine pathway in ADHD. With PET imaging, lower D2/D3 receptor and DAT [dopamine transporters] availability in those with ADHD than in the control group was documented in 2 key brain regions for reward and motivation (accumbens and midbrain)," they write. "The lower than normal D2/D3 receptor and DAT availability in the accumbens and midbrain regions supports the hypothesis of an impairment of the dopamine reward pathway in ADHD."
"Our findings of an association of the mesoaccumbens dopamine pathway with ADHD inattention symptoms may have clinical relevance. This pathway plays a key role in reinforcement-motivation and in learning stimuli-reward associations, and its involvement in ADHD supports the use of interventions to enhance the saliency of school and work tasks to improve performance. Both motivational interventions and contingency management have been shown to improve performance in ADHD patients. Also stimulant medications have been shown to increase the saliency of a cognitive task (motivation, interest) in proportion to the drug-induced dopamine increases in striatum [a region of the brain]," the researchers write.
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org.
JAMA REPORTS
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BRAIN IMAGING GIVES NEW INSIGHT INTO UNDERLYING CAUSE OF ADHD
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