To update the case-fatality rate (CFR) associated with invasive aspergillosis according to underlying conditions, site of infection, and antifungal therapy, data were systematically reviewed and pooled from clinical trials, cohort or case-control studies, and case series of >/=10 patients with definite or probable aspergillosis. Subjects were 1941 patients described in studies published after 1995 that provided sufficient outcome data; cases included were identified by MEDLINE and EMBASE searches. The main outcome measure was the CFR. Fifty of 222 studies met the inclusion criteria. The overall CFR was 58%, and the CFR was highest for bone marrow transplant recipients (86.7%) and for patients with central nervous system or disseminated aspergillosis (88.1%). Amphotericin B deoxycholate and lipid formulations of amphotericin B failed to prevent death in one-half to two-thirds of patients. Mortality is high despite improvements in diagnosis and despite the advent of newer formulations of amphotericin B. Underlying patient conditions and the site of infection remain important prognostic factors.

Although the individual components of the metabolic syndrome are clearly associated with increased risk for coronary heart disease (CHD), we wanted to quantify the increased prevalence of CHD among people with metabolic syndrome. The Third National Health and Nutrition Examination Survey (NHANES III) was used to categorize adults over 50 years of age by presence of metabolic syndrome (National Cholesterol Education Program [NCEP] definition) with or without diabetes. Demographic and risk factor information was determined for each group, as well as the proportion of each group meeting specific criteria for metabolic syndrome. The prevalence of CHD for each group was then determined. Metabolic syndrome is very common, with ϳ44% of the U.S. population over 50 years of age meeting the NCEP criteria. In contrast, diabetes without metabolic syndrome is uncommon (13% of those with diabetes). Older Americans over 50 years of age without metabolic syndrome regardless of diabetes status had the lowest CHD prevalence (8.7% without diabetes, 7.5% with diabetes). Compared with those with metabolic syndrome, people with diabetes without metabolic syndrome did not have an increase in CHD prevalence. Those with metabolic syndrome without diabetes had higher CHD prevalence (13.9%), and those with both metabolic syndrome and diabetes had the highest prevalence of CHD (19.2%) compared with those with neither. Metabolic syndrome was a significant univariate predictor of prevalent CHD (OR 2.07, 95% CI 1.66 -2.59). However, blood pressure, HDL cholesterol, and diabetes, but not presence of metabolic syndrome, were significant multivariate predictors of prevalent CHD. The prevalence of CHD markedly increased with the presence of metabolic syndrome. Among people with diabetes, the prevalence of metabolic syndrome was very high, and those with diabetes and metabolic syndrome had the highest prevalence of CHD. Among all individuals with diabetes, prevalence of CHD was increased compared with those with metabolic syndrome without diabetes. However, individuals with diabetes without metabolic syndrome had no greater prevalence of CHD compared with those with neither. Diabetes

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PPROXIMATELY 38% OF POSTmenopausal women in the United States in 1995 used h o r m o n e r e p l a c e m e n t therapy (HRT), estrogen with or without progestin, to treat symptoms of menopause and prevent chronic conditions such as cardiovascular disease and osteoporosis. 1 Although treatment of symptoms of menopause, such as hot flashes and urogenital atrophy, among others, is a common indication for short-term use, potential preventive effects of HRT on long-term health outcomes have become an increasingly important consideration.In 1996, the second US Preventive Services Task Force (USPSTF) determined that there was insufficient evidence to recommend for or against HRT for all women but thought that individual decisions should be based on patient risk factors, an understanding of the probable benefits and harms, and personal preferences. 2 Many studies have been published since these recommendations were released, including the first report from the Women's Health Initiative (WHI), 3 a large randomized primary prevention trial, and the Heart and Estrogen/ progestin Replacement Study (HERS), 4 a secondary prevention trial reporting multiple outcomes. [4][5][6] This review was initiated to aid the current USPSTF in making new recommendations that will be Author Affiliations and Financial Disclosures are listed at the end of this article.

Study Selection: When available, the most recent high-quality systematic review was used to identify relevant articles. This review was then supplemented with a MEDLINE search for more recent articles.Data Extraction: One reviewer abstracted information from the final set of studies into evidence tables, and a second reviewer checked the tables for accuracy. Discrepancies were resolved by consensus.Data Synthesis: For average-risk adults older than 50 years of age, evidence from multiple well-conducted randomized trials supported the effectiveness of fecal occult blood testing in reducing colorectal cancer incidence and mortality rates compared with no screening. Data from well-conducted case-control studies supported the effectiveness of sigmoidoscopy and possibly colonoscopy in reducing colon cancer incidence and mortality rates. A nonrandomized, controlled trial examining colorectal cancer mortality rates and randomized trials examining diagnostic yield supported the use of fecal occult blood testing plus sigmoidoscopy. The effectiveness of barium enema is unclear. Data are insufficient to support a definitive determination of the most effective screening strategy.Conclusions: Colorectal cancer screening reduces death from colorectal cancer and can decrease the incidence of disease through removal of adenomatous polyps. Several available screening options seem to be effective, but the single best screening approach cannot be determined because data are insufficient. T he U.S. Preventive Services Task Force (USPSTF) last considered its recommendations regarding colorectal cancer screening in 1996 (1). At that time, the available evidence included one randomized, controlled trial showing that fecal occult blood testing (FOBT) reduced mortality rates (2); a case-control study showing that persons having sigmoidoscopy were less likely to die of colorectal cancer (3); and one nonrandomized, controlled trial of FOBT combined with rigid sigmoidoscopy that suggested some benefit from the two tests together (4). On the basis of this evidence, the USPSTF recommended screening for colorectal cancer with FOBT, sigmoidoscopy, or both (a grade B recommendation) but did not recommend for or against other means of screening (digital rectal examination, double-contrast barium enema, or colonoscopy) because the available evidence was insufficient. (See the companion article in this issue for a description of the USPSTF classification of recommendations.) The Task Force also recommended that FOBT be performed yearly but did not specify an interval for sigmoidoscopy.Since 1996, important new evidence has emerged regarding the effectiveness of colorectal cancer screening. We performed an updated systematic review to help the USP-STF evaluate new evidence on the effectiveness of different colorectal cancer screening tests as it updated its previous recommendation. We examined the evidence concerning the effectiveness of screening in adults older than 50 years of age who are at average risk for colorectal cancer. The effectiveness,...

is an employee and stock options holder of Merck. Dr Teutsch is an employee and stock options holder of Merck and a stockholder in Johnson & Johnson.

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative, established by the National Office of Public Health Genomics at the Centers for Disease Control and Prevention, supports the development and implementation of a rigorous, evidence-based process for evaluating genetic tests and other genomic applications for clinical and public health practice in the United States. An independent, non-federal EGAPP Working Group (EWG), a multidisciplinary expert panel selects topics, oversees the systematic review of evidence, and makes recommendations based on that evidence. This article describes the EGAPP processes and details the specific methods and approaches used by the EWG.

Background National guidelines disagree on who should be screened for undiagnosed diabetes. No existing diabetes risk score is highly generalizable or widely followed. Objectives To develop a new diabetes screening score and compare it to other available screening instruments (Centers for Disease Control and Prevention, American Diabetes Association (ADA) and U.S. Preventive Services Task Force guidelines; two ADA risk questionnaires; and Rotterdam model) Design Cross-sectional data. Setting National Health and Nutrition Examination Survey (NHANES) 1999–2004 for model development, and NHANES 2005–2006 plus a combined cohort of two community studies, Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS), for validation. Participants U.S. adults ≥20 years old. Measurements A risk scoring algorithm for undiagnosed diabetes, defined as fasting plasma glucose ≥7.0 mmol/L(126 mg/dL) without known diabetes, was developed in the development dataset. Logistic regression was used to determine participant characteristics that were independently associated with undiagnosed diabetes. The new algorithm and other methods were evaluated by standard diagnostic and feasibility measures. Results Age, sex, family history of diabetes, history of hypertension, obesity, and physical activity were associated with undiagnosed diabetes. In NHANES (in ARIC/CHS), the cutpoint of ≥5 selected 30(40)% of persons for diabetes screening and yielded sensitivity of 79(72)%, specificity of 67(62)%, positive predictive value of 10(10)% and likelihood ratio-positive of 2.39(1.89). In contrast, the comparison scores yielded sensitivity of 44–100%, specificity of 10–73%, positive predictive value of 5–8%, and likelihood ratio-positive of 1.11–1.98. Limitations Data during pregnancy were not available. Conclusions This new diabetes screening score, simple and easily implemented, seems to demonstrate improvements upon the existing methods. Future studies are needed to evaluate it in diverse populations in real world settings. Primary Funding Source Clinical and Translational Science Center at Cornell Medical College.