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August 25, 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, August 25, 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 risk of death following acute coronary syndromes. The report will be fed Tuesday, August 25, 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, August 25, 2009
Genetic Variation Associated With Poorer Response, Cardiovascular Outcomes With Use of Clopidogrel
CHICAGO—Patients with a certain genetic variation who received the antiplatelet drug clopidogrel had a decreased platelet response to treatment and among those who had percutaneous coronary intervention (procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries) had an increased risk of having a cardiovascular event in the following year than patients who did not have this variant, according to a study in the August 26 issue of JAMA. "Dual antiplatelet therapy, including clopidogrel and aspirin, inhibits platelet function, preventing ischemic events and improving outcomes following acute coronary syndromes [such as heart attack or unstable angina] and percutaneous coronary intervention (PCI)," the authors write as background information in the article. Clopidogrel therapy improves outcomes by inhibiting adenosine diphosphate (ADP; a nucleotide)-stimulated platelet activation. However, variability in response to clopidogrel is well established, with nonresponsiveness related to recurrent ischemic events. Some research has suggested that genetic variations may affect clopidogrel response, specifically the gene variant CYP2C19*2. Alan R. Shuldiner, M.D., of the University of Maryland School of Medicine, Baltimore, and colleagues performed a genome-wide association study of ADP-stimulated platelet aggregation to identify genes associated with variation in clopidogrel response. In the Pharmacogenomics of Antiplatelet Intervention (PAPI) Study (2006-2008), the researchers administered clopidogrel for 7 days to 429 healthy Amish persons and measured platelet response. The population in this study (Old Order Amish) are a relatively homogeneous group in which confounding variables (factors that can influence outcomes), including medication usage and lifestyle, are minimized. A genome-wide association study was performed followed by genotyping the loss-of-function cytochrome P450 (CYP) 2C19*2 variant. Findings in the PAPI Study were extended by examining the relation of CYP2C19*2 genotype to platelet function and cardiovascular outcomes in an independent sample of 227 patients undergoing percutaneous coronary intervention. The researchers found that platelet response to clopidogrel was highly heritable. "Indeed, follow-up genotyping indicated that the loss-of-function CYP2C19*2 variant was associated with clopidogrel response and could account for most of the association signal detected in the initial genome-wide association study. The CYP2C19*2 genotype accounts for approximately 12 percent of the variation in clopidogrel response. With age and sex, approximately 22 percent of the variation in clopidogrel response can be explained. Although substantial and highly significant, the majority of the variation in platelet response to clopidogrel remains unexplained," the authors write. In the sample of clopidogrel-treated patients undergoing PCI, after 1 year of follow-up, carriers of the CYP2C19*2 genotype were more likely (20.9 percent vs. 10.0 percent) to have a cardiovascular ischemic event or death compared with noncarriers. "CYP2C19 genotype may prove useful in helping clinicians choose the most effective antiplatelet therapy and dose for a given individual. Those with the CYP2C19*2 genotype may benefit more from an antiplatelet regimen that does not include clopidogrel, such as the third-generation thienopyridine prasugrel, or ticagrelor and cangrelor. Like clopidogrel, these agents inhibit ADP-stimulated platelet aggregation but are not as dependent on CYP2C19 for activation. Genotype-directed decisions regarding which antiplatelet agent to use in a specific patient may also have an important economic impact if costs of equally efficacious medications differ greatly. Whether CYP2C19*2 carriers may benefit from increased dosing of clopidogrel is not yet known," the author write. "Prospective randomized clinical trials will be necessary to determine the efficacy of CYP2C19 genotype-directed therapy in evidence-based clinical decision making."(JAMA 2009;302[8]:849-858. Available pre-embargo to the media at www.jamamedia.org) Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. Editorial: Tailoring Antiplatelet Therapy Based on Pharmacogenomics
In an accompanying editorial, Deepak L. Bhatt, M.D., M.P.H., of the VA Boston Healthcare System and Brigham and Women's Hospital, Boston, writes that the findings of this study provides important information. "The study by Shuldiner et al moves closer to fulfilling the promise of pharmacogenomic testing in tailoring antiplatelet therapy to the individual patient. Strides toward individualized therapy have already been made in cancer care and human immunodeficiency virus treatment. Antiplatelet therapy seems well suited to a tailored approach, and future investigations should pursue this promising area."(JAMA 2009;302[8]:896-898. Available pre-embargo to the media at www.jamamedia.org) 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, August 25, 2009
Typhoid Fever Cases in U.S. Linked to Foreign Travel
Antimicrobial-Resistant Strains Among U.S. Patients Increasing CHICAGO—Infection with an antimicrobial-resistant strain of typhoid fever among patients in the United States is associated with international travel, especially to the Indian subcontinent (India, Pakistan, and Bangladesh), according to a study in the August 26 issue of JAMA. The study also shows an increase in certain strains of typhoid fever that are resistant to the most commonly used medications for treatment. "Infection with Salmonella ser Typhi causes an estimated 20 million cases of typhoid fever and 200,000 deaths annually worldwide," the authors provide as background information. Typhoid fever is a rare disease in the United States with approximately 300 clinical cases reported each year. Improvements in municipal water and sewage treatments in the U.S. resulted in dramatic declines in the incidence of and deaths from typhoid fever at the beginning of the last century. The majority of the cases in the U.S. are now associated with foreign travel. "Over the last 20 years, emergence of S Typhi strains resistant to antimicrobial agents has complicated treatment of infected patients." In addition, the authors report that "identification of nalidixic acid-resistant S Typhi (NARST) and reports of infection with S Typhi strains resistant to ciprofloxacin from typhoid-endemic areas have generated concern that strains resistant to fluroquinolones may become more prevalent." Michael F. Lynch, M.D., M.P.H., and colleagues from the Centers for Disease Control and Prevention (CDC), Atlanta, reviewed data from 1999 to 2006 for 1,902 persons with typhoid fever who had epidemiologic information submitted to the CDC and 2, 016 S Typhi isolates from public health laboratories sent to the CDC for antimicrobial susceptibility testing. The median (midpoint) age of patients with typhoid fever was 22 years. The authors report that "1,295 (73 percent) were hospitalized and 3 (0.2 percent) died. Foreign travel within 30 days of illness was reported by 1,439 (79 percent). Only 58 travelers (5 percent) had received typhoid vaccine." Together, three countries accounted for more than two-thirds of all travel associated cases of typhoid fever—India (47 percent), Pakistan (10 percent) and Bangladesh (10 percent). Two-thirds of these travelers reported visiting friends and relatives as the primary reason for their travel, followed by tourism (9 percent) and business travel (3 percent), which were reported much less frequently. In addition, "272 (13 percent) of 2,016 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant S Typhi [MDRST]); 758 (38 percent) were resistant to nalidixic acid (nalidixic acid-resistant S Typhi [NARST]) and 734 NARST isolates (97 percent) had decreased susceptibility to ciprofloxacin. The proportion of NARST increased from 19 percent in 1999 to 54 percent in 2006." "Patients with resistant infections were more likely to report travel to the Indian subcontinent: 85 percent of patients infected with MDRST and 94 percent with NARST traveled to the Indian subcontinent, while 44 percent of those with susceptible infections did," the authors write. The authors conclude: "Since most typhoid fever among patients treated in the United States is acquired abroad, ongoing surveillance may also help track global patterns of antimicrobial resistance of S Typhi. Reducing the burden of typhoid fever in the United States will require increased attention to prevention measures by travelers, including improved vaccination coverage among travelers to typhoid-endemic areas," particularly among travelers visiting friends or family in India or its neighbors. "Further reductions in typhoid fever among travelers will depend on increased availability of safe drinking water as well as improved sanitation and food hygiene in typhoid endemic areas, measures that would go a long way toward reducing the global burden of typhoid fever."(JAMA 2009;302[8]:859-865. Available pre-embargo to the media at www.jamamedia.org) Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. Editorial: Addressing the Global Disease Burden of Typhoid Fever
"The article by Lynch and colleagues underscores the importance of travel in the global spread of S Typhi and, in particular, NARST isolates," writes Zulfiqar A. Bhutta, M.B., B.S., Ph.D., of Aga Khan University, Karachi, Pakistan and John Threlfall, B.Sc., Ph.D., of Health Protection Agency Centre for Infections, London, in an accompanying editorial. "The implications of these findings for global strategies for the prevention and control of typhoid are substantial for both developed and developing countries." "Typhoid remains a deadly disease in many developing countries and, as the article by Lynch et al clearly demonstrates, has the potential for worldwide spread, with considerable effects on the global burden of infection with gastrointestinal pathogens. This, coupled with increasing reports of the emergence of multidrug-resistant nontyphoid salmonellas in vulnerable groups in many developing countries, particularly those in Africa and Southeast Asia, with infections often characterized by disease symptoms similar to those of typhoid, clearly illustrates the need for a global strategy of containment of Salmonella infection, linked, if possible, to vaccination and to the rational use of antimicrobial drugs."(JAMA 2009;302[8]:898-899. Available pre-embargo to the media at www.jamamedia.org) 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, August 25, 2009
Hormone Therapy for Prostate Cancer Patients With Certain Heart Conditions Associated With Increased Risk of Death
CHICAGO—Men with coronary artery disease-induced congestive heart failure or heart attack who receive hormone therapy before or along with radiation therapy for treatment of prostate cancer have an associated increased risk of death, according to a study in the August 26 issue of JAMA. Patients with localized prostate cancer have several options available for treatment, including the use of brachytherapy (treatment in which radioactive seeds are implanted in the prostate), both as monotherapy and in conjunction with external beam radiation therapy, according to background information in the article. Neoadjuvant (treatment that is given before or with the primary treatment) hormonal therapy (HT) is used as a means for prostate gland cytoreduction (decrease in number of cells, as in a tumor) in order to eliminate pubic arch (an arch formed by the pubic bones) interference and improve the ability to perform brachytherapy. Previous research has suggested that "hormonal therapy when added to radiation therapy (RT) for treating unfavorable-risk prostate cancer leads to an increase in survival except possibly in men with moderate to severe comorbidity [co-existing illnesses]. However, it is unknown which comorbid conditions eliminate this survival benefit," the authors write. Akash Nanda, M.D., Ph.D., of Brigham & Women's Hospital-Dana-Farber Cancer Institute, Boston, and colleagues assessed whether neoadjuvant HT use in men with prostate cancer treated with brachytherapy affects the risk of all-cause death of men with known coronary artery disease-induced conditions, including congestive heart failure and heart attack. The study included 5,077 men (median [midpoint] age, 69.5 years) with localized or locally advanced prostate cancer who were treated with or without a median of 4 months of neoadjuvant HT followed by RT between 1997 and 2006 and were followed up until July 2008. During the study period, 419 men died. Of those, 200 had no underlying comorbidity, 176 had one coronary artery disease risk factor, and 43 had a history of known coronary artery disease resulting in congestive heart failure or heart attack. Analyses of the data indicated that "when considering comorbidity groups separately, neoadjuvant HT use was not associated with an increased risk of all-cause mortality in men with no comorbidity (9.6 percent vs. 6.7 percent) or a single coronary artery disease risk factor (10.7 percent vs. 7.0 percent) after median follow-ups of 5.0 years and 4.4 years, respectively," the researchers write. However, for men with coronary artery disease-induced congestive heart failure or heart attack, after a median follow-up of 5.1 years, neoadjuvant HT use was associated with nearly twice the risk of all-cause mortality (26.3 percent vs. 11.2 percent). "It is also important to note that the population of men in whom the use of neoadjuvant HT may be detrimental was limited to 5 percent (256 of 5,077) in this community-based study cohort. This latter point may explain why there has been a survival benefit observed in the major randomized trials comparing HT plus external beam radiation therapy to external beam radiation therapy alone," the authors write. "The clinical significance of this finding is that for men with favorable-risk prostate cancer and a history of congestive heart failure or myocardial infarction who require neoadjuvant HT solely to eliminate pubic arch interference, alternative strategies such as active surveillance or treatment with external beam radiation therapy or prostatectomy should be considered. However, for men with unfavorable-risk prostate cancer who require HT in addition to radiation therapy to take advantage of its survival benefit, appropriate medical evaluation prior to initiation should facilitate clinicians in balancing the relative risks against the benefits of HT use."(JAMA 2009;302[8]:866-873. Available pre-embargo to the media at www.jamamedia.org) 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, August 25, 2009
Risk of Death Following Acute Coronary Syndromes Different For Men, Women; Attributable to Various Factors
CHICAGO—Women may have a slightly higher risk of death than men in the 30 days following an acute coronary syndrome (ACS; such as heart attack or unstable angina), but this difference appears attributable to factors such as severity and type of ACS, clinical differences and angiographic severity according to a study in the August 26 issue of JAMA. "Cardiovascular disease is the leading cause of death in both men and women, accounting for one-third of all deaths. Although several studies have shown an improvement of prognosis in women over time, overall outcomes remain worse for women compared with men, providing a strong rationale for focusing on the study of sex-based differences in the outcome of acute coronary syndromes," according to background information in the article. Previous analyses of the differences in outcomes for men and women following ACS have reported conflicting results. Jeffrey S. Berger, M.D., M.S., of the New York University School of Medicine, New York, and colleagues evaluated the relationship between sex and 30-day mortality following ACS and analyzed factors such as clinical classification at the time of ACS and the severity of angiographic disease. Patients for the study were pooled from a sample of 11 independent, international, randomized ACS clinical trials between 1993 and 2006. Of the 136,247 patients in this analysis, 38,048 (28 percent) were women. There were 102,004 patients (26 percent women) with ST-segment elevation myocardial infarction (STEMI; a certain pattern on an electrocardiogram following a heart attack); 14,466 with non-STEMI (NSTEMI; 29 percent women); and 19,777 with unstable angina (40 percent women). Women were older and had a higher prevalence of hypertension, hyperlipidemia, diabetes and heart failure. Men were more likely to be smokers and had a higher prevalence of prior heart attack and prior coronary artery bypass graft surgery. The researchers found that women had a significantly higher unadjusted 30-day risk of death compared with men (9.6 percent vs. 5.3 percent). But after multivariable adjustment for clinical characteristics and clinical presentation, no significant difference was observed in 30-day mortality. "Perhaps the most striking findings in our analyses relate to the examination of mortality according to type of ACS. We found a significant interaction between sex and type of ACS, such that 30-day mortality risk among women was modestly higher than men only for those patients presenting with STEMI. In patients with NSTEMI and unstable angina, women had a lower adjusted 30-day mortality risk than men. In fact, the strongest finding after full adjustment was lower risk among women with unstable angina," the authors write. The researchers also found that overall, women who underwent catheterization were more likely to have nonobstructive coronary artery disease and less likely to have multivessel disease compared with men. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity. "Our study suggests a better understanding of the observed sex-based differences. Sex-based differences exist in 30-day mortality among patients with ACS and vary depending on clinical presentation. However, these differences are markedly attenuated following adjustment for clinical differences and angiographic data. The attenuation in the difference in mortality suggests that much of the crude differences are explained by these factors. This study further highlights the clinical and angiographic differences among men and women at presentation with ACS. Understanding and considering these differences may lead to better risk stratification and treatment of all patients with ACS," the researchers conclude.(JAMA 2009;302[8]:874-882. Available pre-embargo to the media at www.jamamedia.org) 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, August 25, 2009
Hip Fracture Rates Decline in Canada
CHICAGO—Standardized rates of hip fracture have steadily declined in Canada since 1985, with a more rapid decline between 1996 and 2005 and a more marked decrease among individuals age 55 to 64 years, according to a report in the August 26 issue of JAMA. Osteoporosis is a common bone-thinning disease that predisposes individuals to fractures, according to background information in the article. "Because the prevalence of osteoporosis increases with age, the global burden of osteoporosis is projected to rise markedly over the next few decades as the number of elderly individuals increases," the authors write. "The incidence of hip fractures is an index of osteoporosis burden and the potential impact of preventive efforts in the population." William D. Leslie, M.D., M.Sc., of the University of Manitoba, Winnipeg, Canada, and colleagues analyzed nationwide hospitalization data from the Canadian Institute for Health Information for 1985 to 2005. A total of 570,872 individuals were hospitalized for hip fracture during this time period. Over the 21 years, age-adjusted rates of hip fracture declined 31.8 percent in females and 25 percent in males. The largest percentage decrease was observed among individuals age 55 to 64 years; hip fracture rates decreased by almost one-half in females and about one-third in males in this age range. Detailed analyses identified a more rapid decline beginning around 1996. "For the overall population, the average age-adjusted annual percentage decrease in hip fracture rates was 1.2 percent per year from 1985 to 1996 and 2.4 percent per year from 1996 to 2005," the authors write. "Similar trends have been reported in other countries, including the United States," the authors write. The reasons for the decrease are not clear, they note. The decline began before the widespread availability of bone density testing or pharmacological treatments for osteoporosis, and there is little evidence to suggest that improvements in physical activity, calcium intake, vitamin D status or prevention of falls are responsible. "Overweight and obesity are epidemic in modern societies and may contribute to reduced fracture rates," they write. Although the percentage rates decreased, the absolute number of hip fracture increased over the study period—a phenomenon attributable to the changing age structure of the population, the authors note. "Hip fractures continue to exert major effects on the population, particularly the elderly, and on the health care system, related to the morbidity, costs and mortality from these fractures," they conclude. "Therefore, the decreasing incidence rates are not grounds for complacency toward osteoporosis prevention and treatment."(JAMA 2009;302[8]:883-889. Available pre-embargo to the media at www.jamamedia.org) 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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STUDY INVESTIGATES WHY DEATH RATES DIFFER FOR MEN AND WOMEN FOLLOWING ACUTE CORONARY SYNDROMES
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