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February 2, 2010 — Embargoed ContentJAMA 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. JAMA NEWS RELEASES
Complete Table of Contents
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: This week's JAMA Report video is on the association between low levels of serotonin in the brain and the risk of SIDS. The report will be fed Tuesday, February 2, from 9:00 - 9:15 a.m. ET and 2:00 - 2:15 p.m. ET, on Galaxy 28 (C-Band), Transponder 15, downlink frequency: 4000 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, in VNF Provider A. Please look for the JAMA Report tab. 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 3:00 P.M. (CT), Tuesday, February 2, 2010
Reduced Kidney Function and High Levels of Protein in Urine Associated With Increased Risk of Death, Heart Attack and Kidney Failure
CHICAGO—Patients with high levels of proteinuria (protein in urine) in addition to another marker of reduced kidney function had an associated increased risk of all-cause death, heart attack or progression to kidney failure, according to a study in the February 3 issue of JAMA. As many as 26 million Americans have chronic kidney disease (CKD). The current system for determining the stage of CKD is based primarily on the estimated rate of glomerular filtration (eGFR; measure of the kidneys' ability to filter and remove waste products) with lower eGFR associated with higher risk of adverse outcomes. " ...the guidelines have been criticized because they do not incorporate information about the presence and severity of proteinuria an important marker of CKD that is associated with adverse outcomes," the authors write. Brenda R. Hemmelgarn, M.D., Ph.D., of the University of Calgary, Alberta, Canada, and colleagues examined the association between reduced eGFR, proteinuria, and adverse clinical outcomes, including all-cause death, heart attack, and progression to kidney failure. The researchers analyzed data from a province-wide (Alberta) laboratory registry that included eGFR and proteinuria measurements for 2002 to 2007. There were 920,985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment (i.e., dialysis) at the beginning of the study. The researchers found that within each level of eGFR, there was substantial variability in risk with participants who had greater amounts of proteinuria having increased adjusted rates of all 4 adverse outcomes (all-cause death, heart attack, end-stage renal disease, and the doubling of serum creatinine measurement [corresponding to a 50 percent decline in kidney function]). Patients with heavy proteinuria but without overtly abnormal eGFR appeared to have worse clinical outcomes than those with moderately reduced eGFR but without proteinuria. Significant interactions between eGFR and proteinuria were observed for death, initiation of renal replacement, and doubling of serum creatinine.
"These findings are important because current guidelines for the classification and staging of CKD are based on eGFR without explicit consideration of the severity of concomitant proteinuria. In addition, computerized reporting of eGFR (generally without consideration of proteinuria) is increasingly used to assist physicians in identifying patients at high risk of adverse outcomes—or those who might benefit from specialist care. Although our findings do not directly address which patients would benefit from referral to a nephrologist, they do suggest that risk stratification performed in terms of eGFR alone is relatively insensitive to clinically relevant gradients in risk," the authors write. "These findings suggest that future revisions of the classification system for CKD should incorporate information from proteinuria."
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 3:00 P.M. (CT), Tuesday, February 2, 2010
Lower Levels of Serotonin in Brain Tissue Associated with SIDS
CHICAGO—Preliminary research indicates that decreased levels in the brainstem of serotonin (5-hydroxytryptamine [5-HT]; a neurotransmitter involved in several brain functions) and tryptophan hydroxylase (TPH2; an enzyme involved in the synthesis of serotonin) are associated with an increased risk for sudden infant death syndrome (SIDS), according to a study in the February 3 issue of JAMA. SIDS remains the leading cause of postneonatal (from one month to one year after birth) infant death in the United States. It is believed to result from abnormalities in brainstem control of autonomic function and breathing during a critical developmental period. "Abnormalities of serotonin (5-HT) receptor binding in regions of the medulla oblongata [a region in the brainstem] involved in this control have been reported in infants dying from SIDS," the authors write. They suggest these abnormalities may play a role in the inability of an infant to respond to a life-threatening challenge, such as asphyxia, during sleep. Jhodie R. Duncan, Ph.D., of Children's Hospital Boston and Harvard Medical School, and colleagues tested the hypothesis that SIDS is associated with reductions in tissue levels of 5-HT, TPH2 or both. The study included for biochemical analysis 35 infants dying from SIDS, 5 infants with acute death from known causes (controls), and 5 hospitalized infants with chronic hypoxia-ischemia (a reduction in oxygen supply combined with reduced blood flow to the brain). Tissue samples were obtained via autopsy and levels of serotonin and several enzymes, including 5-HT and TPH2, were measured and analyzed. The researchers found that serotonin levels were 26 percent lower in SIDS cases compared with age-adjusted controls in the raphé obscurus and the paragigantocellularis lateralis (PGCL), regions of the brain. In the raphé obscurus, TPH2 levels were 22 percent lower in the SIDS cases compared with controls. Also, 5-HT levels were 55 percent higher in the raphé obscurus and 126 percent higher in the PGCL in the hospitalized group compared with the SIDS group.
"In this article we report the presence of lower levels of medullary 5-HT and TPH2 in infants dying from SIDS, pointing to a deficiency, as opposed to an excess, of 5-HT in the pathogenesis of the disorder," the authors write. "We now postulate that SIDS can be viewed as a disorder caused by a defect in 1 or more components of the medullary 5-HT system..."
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 3:00 P.M. (CT), Tuesday, February 2, 2010
Findings Suggest Performing Single Ultrasound To Detect Blood Clot May Be Sufficient for Some Patients
CHICAGO—An analysis of previous studies suggests that for patients with a suspected blood clot in a deep vein of a leg, withholding anticoagulation therapy after a negative whole-leg compression ultrasound is associated with a low risk of developing a blood clot during the subsequent 3 months, suggesting that multiple ultrasounds may not be necessary for some low-risk patients, according to an article in the February 3 issue of JAMA. Compression ultrasound (CUS) is the primary testing procedure used to diagnose proximal deep vein thrombosis (DVT; a blood clot in a deep vein in the thigh or leg), as the method confirms and excludes DVT of the proximal veins (above the knee) but its accuracy for distal vein DVT (below the knee) has been questioned. Up to 25 percent of distal DVTs may move into proximal veins, increasing the risk of pulmonary embolism (blood clot in the veins moving into the lung). "Consequently, practice guidelines recommend serial CUS of the proximal veins 5 to 7 days after an initial negative result to safely exclude clinically suspected DVT. Because only 1 percent to 2 percent of repeat CUS tests detect thrombus propagation, many repeat studies are conducted to detect a small number of DVTs," the authors write. Whole-leg CUS may exclude proximal and distal DVT in a single evaluation and lessen the need for repeat CUS tests, however concerns exist regarding the safety of using a single whole-leg CUS to exclude DVT following an initially negative result, according to background information in the article. Stacy A. Johnson, M.D., of the University of Utah School of Medicine, Salt Lake City, and colleagues conducted a review and meta-analysis of previous studies to examine the risk of venous thromboembolism (blood clots in the deep veins of the legs or in the lungs) in patients with suspected lower-extremity DVT following a single negative whole-leg CUS result for whom anticoagulation was withheld. The authors identified seven studies for the analysis, which included 4,731 patients. An analysis of data indicated that venous thromboembolism or suspected venous thromboembolism-related death occurred in 34 patients (0.7 percent), including 11 patients with distal DVT (32.4 percent), 7 patients with proximal DVT (20.6 percent), 7 patients with nonfatal pulmonary emboli (20.6 percent), and 9 patients (26.5 percent) who died, which may have been related to venous thromboembolism. Use of a model indicated that the combined venous thromboembolism event rate at 3 months was 0.57 percent.
"In summary, withholding anticoagulation following a single negative whole-leg CUS result was associated with a low risk for venous thromboembolism during 3-month follow-up in patients with suspected DVT. Using a single negative whole-leg CUS result as the sole diagnostic modality in patients with high pretest probability of DVT requires further study," 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. Editorial: Evidence-Based Medicine Requires Appropriate Clinical Context
In an accompanying editorial, Robert A. McNutt, M.D., Ph.D., of Rush University Medical Center, Chicago, and Edward H. Livingston, M.D., of the University of Texas Southwestern Medical Center, Dallas, (both are also Contributing Editors, JAMA), comment on the findings of this study. "... based on the meta-analysis by Johnson et al, clinicians may infer that not initiating anticoagulation treatment after a negative CUS result in some surgical or ambulatory patients at low risk of having VTE may be appropriate; however, that inference may not be true for hospitalized patients or those with cancer. Greater detail about individual patient scenarios is necessary to facilitate better application of the study results to individual patients. One helpful approach may be for reports of meta-analyses to include, in detail, the inclusion and exclusion criteria for patients enrolled in the original studies."
"However, summary statements from meta-analyses should not be used to guide patient care. Such conclusions are not helpful when the clinical studies are combined and averaged in a way that reduces the complex world of medical care to overly simple and consequently not clinically useful statistical summaries. ...meta-analysis may have a useful role in synthesizing available evidence, especially, for example, in identifying signals of potential harm that may not be readily apparent in individual studies. However, meta-analyses are most appropriately used to formulate, but not test hypotheses."
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.
JAMA REPORTS
VIDEO: Windows Media | Quicktime
LOWER BRAINSTEM SEROTONIN LEVELS ASSOCIATED WITH SUDDEN INFANT DEATH SYNDROME
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